Master program in paediatric clinical pharmacology: Scope, Organization, Training

Transcription

1 Deliverable number D1.6 Master program in paediatric clinical pharmacology: Scope, Organization, Training GRiP Global Research in Paediatrics Network of Excellence HEALTH-F Lead Beneficiaries: INSERM Author(s) E. Jacqz-Aigrain, P. Rossi Revision date 13 July 2014 Diss emination Level Public PU Start date 01/01/2011 Duration 5 years Project Coordinator Dr. Carlo GIAQUINTO Azienda Ospedaliera di Padova (AOPD) Refere nce W P W P1 Joint paedi atri c cli nical pharmacolog y intern ation al training pro gram Refere nce Activity Ta sk De fine the scope, qualification s and training cu rriculums for the majo r groups of profe ssion al exp ert s This project has received funding from the European Union s Seventh Framework Programme for research, technological development and demonstration under grant agreement n

2 Index LIST OF AUTHORS... 3 SUMMARY... 3 SCOPE, ORGANIZATION, TRAINING... 3 METHODOLOGY... 4 COMPETENCIES OR INTENDED LEARNING OUTCOMES... 9 MODULE SCHEDULE AND TIME TABLE MODULE MODULE MODULE MODULE MODULE MODULE MODULE MODULE MODULE MODULE CONCLUSIONS Annex 1: draft Partnership Agreement Annex 2: Description of the centres conducting Paediatric Clinical Pharmacology Research D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 2

3 LIST OF AUTHORS Name Prof Paolo Rossi Prof Evelyne Jacqz-Aigrain Mariangela Lupo Institution Children s Hospital Bambino Gesù (OPBG), Dept of Paediatrics and University of Rome Tor Vergata INSERM and University Paris Diderot G. Benzi Foundation (CVBF-TEDDY 3 rd party) SUMMARY This document is presenting the programme of the GRiP Master. A first programme was developed from the beginning of the GRiP project to October 2013 by the leaders of WP1 (INSERM, HUS, Sickkids and EMC) and shared with the participating Universities in France, the Netherlands, UK and Italy in September In October 2013 an Educational Board Meeting was held in London and a new organization was established. The Master title has changed into Master in Paediatric Medicines Development and Evaluation and OPBG has been appointed as the Coordinating GRiP partner in collaboration with the University of Rome Tor Vergata (OPBG 3 rd party). From November 2013, University of Rome Tor Vergata (IT) has initiated legal procedures and has received approval from the Faculty to establish an International MSc aimed to be recognized as a European Joint Degree with the participation of three other Collaborating Universities (Erasmus Medical Center Rotterdam NL, University Paris Diderot FR, and University of Basel, CH). The joint degree will initiate when the partnership agreement will be signed by all collaborating universities. In the meantime, the Faculty of Medicine at the University of Rome Tor Vergata has approved (prot nr /2014, Dcr nr 1202/2014) the programme to be published on the 1 Sept with activation time (beginning of the educational activities) on the 5 Nov A minimum of 5, with maximum of 20 attendees will be admitted to the programme with admission request before 10 th of October 2014 ( or or ( A list of successful applicants will be published on the above mentioned websites by 20 October SCOPE, ORGANIZATION, TRAINING It is widely known that pharmacological treatment of children poses unique efficacy and safety challenges for children and health professionals in all countries worldwide. The use of off-label drugs is a public health problem world-wide. Indeed, over 50% of children admitted to hospitals in Europe will receive an unlicensed or off-label medicine. Such drug use is associated with increased risks of reduced efficacy as well as medications errors. According to the National Patient Safety Institute, at least 60,000 children suffer from medical errors every year in the US. The largest category of mistakes, involving about 10,000 children and babies, is referred to medication. The heart of the problem remains the absence of clinical trials that examine optimal dosage in children and the absence of formulations adapted to young patients. One strategy to address this is to D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 3

4 adequately educate current and future generations of health professionals to be able to conduct robust paediatric clinical drug trials (1-8). 1. Choonara I. Unlicensed and off-label drug use in children: implications for safety. Expert Opin Drug Saf Mar;2: Frattarelli DA, Galinkin JL, Green TP, Johnson TD, Neville KA, Paul IM, Van Den Anker JN; American Academy of Pediatrics Committee on Drugs. Off-label use of drugs in children. Pediatrics. 2014;133: doi: /peds Epub 2014 Feb Tzimenatos L, Bond GR; Pediatric Therapeutic Error Study Group. Severe injury or death in young children from therapeutic errors: a summary of 238 cases from the American Association of Poison Control Centers. Clin Toxicol (Phila) Apr;47(4): doi: / Crouch BI, Caravati EM, Moltz E. Tenfold therapeutic dosing errors in young children reported to U.S. poison control centers. Am J Health Syst Pharm Jul 15;66(14): doi: / Joseph MP, Craig PJ, Caldwell DP. Clinical trials in children. Br J Clin Pharmacol Dec 10. doi: /bcp [Epub ahead of print] 6. Pansieri C, Bonati M, Choonara I, Jacqz-Aigrain E Neonatal drug trials: Impact of EU and US paediatric regulations. Arch Dis Child (in press). 7. Mahmood I. Dosing in children: a critical review of the pharmacokinetic allometric scaling and modelling approaches in paediatric drug development and clinical settings. Clin Pharmacokinet. 2014; 53: doi: /s Gazarian M. Training pediatric clinical pharmacology and therapeutics specialists of the future: the needs, the reality, and opportunities for international networking. Paediatr Drugs. 2009;11:63-6. The curriculum of the Master s programme on Paediatric Medicines Development and Evaluation has two important aims: 1. To educate the next generation of researchers, paediatricians, physicians and health professionals in paediatric pharmacology and trial design in order to conduct robust paediatric clinical drug trials; 2. To stimulate continuing professional development of practicing physicians and pharmacists to acquire additional competences in all the specific aspects of paediatric pharmacology, drug evaluation, trial design and conduct in the paediatric population as well as the regulatory requirements for the in-label use of medicines in the paediatric ages. The GRiP master programme will deliver an International/Joint Master degree to be recognized by participating universities, within the Bologna process. METHODOLOGY The ten training modules included in the GRiP master palette are organised as a curriculum map which articulates the learning objectives of the module, the enabling competencies, the instructional methods used to achieve the objectives and the assessment methods (how learners will be assessed to determine if they have achieved the objectives). D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 4

5 Each module is organised according to the Bloom s Taxonomy 1,2 in bloom levels, expressing the level of expertise required to achieve each measurable student outcome. The GRiP master programme has been developed following a specific and well defined methodology: A. Identification of the two Key Competencies: Each module is grounded in the following two Key Competencies which have given rise to different learning competencies and that are specific for each master module: a) Design, conduct and assess scientifically robust and ethical paediatric drug studies, taking into account the regulatory framework and the special needs of children; b) Develop and implement a plan for making knowledge users aware of the knowledge generated through a paediatric drug study. B. Identification of the following eight Enabling Competencies, The Enabling Competences describe what students should know or be able to do at the end of the course that they couldn't do before and are the following: 1. Demonstrate an understanding for the need and application of individualized/optimized medicines therapy in paediatric diseases. 2. Demonstrate an understanding of medicines development for a paediatric population. 3. Describe various study designs and their advantages and challenges in relation to paediatric population. 4. Critically appraise existing paediatric medicines studies. 5. Demonstrate an understanding of regulatory environment pertaining to paediatric medicines studies. 6. Develop a study protocol for a paediatric medicines study 7. Conduct a scientifically robust and ethical paediatric medicines study. 8. Develop a report of a paediatric medicines study. C. Listing the learning objectives for each module (Topics to achieve) using Bloom s taxonomy to help determine what level of learning each learning objective is aimed at. objectives articulate the knowledge and skills students acquire at the end of the course and they differ from module to module according to the objective to be achieved. Each learning objective has to be linked to the appropriate enabling competency and has to be: specific, measurable/observable, attainable for target audience within scheduled time and specified conditions; and results-oriented, targeted to the learner and to the desired level of learning. 1 Bloom, B. S.; Engelhart, M. D.; Furst, E. J.; Hill, W. H.; Krathwohl, D. R. (1956). Taxonomy of educational objectives: The classification of educational goals. Handbook I: Cognitive domain. New York: David McKay Company. 2 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 5

6 D. Identification of the appropriate bloom level (1-6) for each learning objective The Bloom s taxonomy was originally created by Benjamin Bloom in 1956 to categorise a continuum of educational objectives and provides a common language for teachers to discuss and exchange learning and assessment methods. Since it is a multi-tiered scale, it will encourage higher-order thought in students by building up from lower-level cognitive skills. The table below defines each cognitive level from higher- to lower-order thinking and lists the Bloom levels of expertise: Level of Expertise Description of Level 1. Knowledge Recall, or recognition of terms, ideas, procedure, theories, etc 2. Comprehension Translate, interpret, extrapolate, but not see full implications or transfer to other situations, closer to literal translation 3. Application Apply abstractions, general principles, or methods to specific concrete situations 4. Analysis Separation of a complex idea into its constituent parts and an understanding of organization and relationship between the parts. Includes realizing the distinction between hypothesis and fact as well as between and extraneous variables 5. Synthesis Creative, mental construction of ideas and concepts from multiple sources to form complex ideas into a new, integrated, and meaningful pattern subject to given constraints 6. Evaluation To make a judgment of ideas or methods using external evidence or self-selected criteria substantiated by observations or informed rationalizations According to the bloom level, the assessment and the instructional methods will vary accordingly. E. Identification of the instructional methods (the way to deliver the didactic s for each learning objective, e.g. lecture, small group discussion, etc.). The instructional methods are chosen by each module Leads to foster student learning towards meeting the objectives and are the means used to teach training s. According to Bloom levels, training contents have been organised at many levels of expertise and have taken different and appropriate forms. Bloom's taxonomy is, infact, a convenient way to describe the degree to which we want our students to understand and use concepts, to demonstrate particular skills, and to have their values, attitudes, and interests affected. D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 6

7 The table 3 below shows some instructional methods for each Bloom level: The first modules have a very low bloom level and present the most common forms of classroom assessment such as multiple choice tests and open questions that are quite adequate for assessing knowledge and comprehension (levels 1 and 2). Progressively, this type of assessment has been increased according to the difficulty of the objective to be achieved and the assessment methods. These latter will allow to assess students knowledge at the higher levels of synthesis and evaluation (levels 5 and 6). F. Identification of assessment methods (the way to assess if students have met the learning objectives, e.g. multiple choice test, case study, etc.) Assessment methods allow the instructor to check the degree to which the students are meeting the learning objectives. While Assessments should reveal how well students have learned what we want them to learn, instructional methods ensures that they learn it. To achieve and high quality education contents, all the module Leads had to bear in mind that the education activities are based on assessment of learning needs, that the employed educational methods are effective and will result in the desired learning outcomes and that the above mentioned three components (learning objectives, assessments and instructional strategies) are aligned. To this aim, all module Leads had to ask themselves the following questions: objectives: What do I want students to know how to do when they leave this course? Assessments: What kinds of tasks will reveal whether students have achieved the learning objectives I have identified? 3 ftp://ftp-fc.sc.egov.usda.gov/nedc/isd/taxonomy.pdf D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 7

8 Instructional strategies: What kinds of activities in and out of class will reinforce my learning objectives and prepare students for assessments? G. Indication of Timing (when the learning objective is taught in terms of weeks) The ten modules, consisting of 100 hours each and corresponding to 4 ECTS, are to be taken in a sequenced manner while work placement [see Annex 2- Description of the centres conducting Paediatric Clinical Pharmacology Research] or research activity, consisting of 18 ECTS (corresponding to 450 hours) are to be organised at the end of the master programme. During this period the student can elaborate some of the aspects of the different modules by applying the knowledge already achieved during the study-period (Bloom level at least 3) and this can comprise of selected learning objectives chosen by the student among those that are highlighted in the curriculum maps. H. Preparation of the didactic s for each s (pre-reading, lectures and postreading) to be recorded and uploaded in the VLE (virtual learning environment). For each learning objective, we have designed one or more topics, consisting of s (e.g. lessons) and a final test: 1. For each (80 minutes): o 20 pre-reading o 20 o 40 post-reading 2. At the end of each topic, students have to test their knowledge through different possibilities that can be for examples: o Final test (case study, report, multiple choice test, quiz with on line answers and final web discussion, etc.) o Participation in webinar and group activity discussion o Preparation of a presentation on all aspects of the topic. Each teacher, dealing with the specific, is requested to: - Prepare one (max 20') video presentation with (PowerPoint presentation) on the selected by glossary of y - Prepare and web links for the pre-reading and postreading (each teacher has to provide didactic to support the individual student s D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 8

9 study before and after the video recorded lesson in particular s for 20 minutes of pre-reading and 40 minutes of post-reading. - Prepare the Educational tests I. Identification of teachers for each The module coordinators have suggested a list of teachers to be involved in each. They have to provide with their short bio and an updated curriculum vitae highlighting their academic work and describing specific teaching experiences. These documents have to be provided to the faculty to show that they possess both the professional and teaching expertise needed to deliver the program. J. Periodic Curriculum maps alignment All the curriculum maps have been revised with the main aim: - to ensure that the curriculum is developed and delivered in the most efficient and effective way in order to set the student up for success; - to ensure that all partners are not subject to duplication of efforts and resources. COMPETENCIES OR INTENDED LEARNING OUTCOMES Promise to students: We will build and deliver a 2-year Masters program that will teach you how to design, conduct and assess scientifically robust and ethical paediatric medicines studies, taking into account the regulatory framework and the special needs of children. By the end of this program, you will be able to do the following 1. Demonstrate an understanding for the need and application of individualized/optimized medicines therapy in paediatric diseases. 2. Demonstrate an understanding of medicines development for a paediatric population. 3. Describe various study designs and their advantages and challenges in relation to paediatric population. 4. Critically appraise existing paediatric medicines studies. 5. Demonstrate an understanding of regulatory environment pertaining to paediatric medicines studies. 6. Develop a study protocol for a paediatric medicines study 7. Conduct a scientifically robust and ethical paediatric medicines study. 8. Develop a report of a paediatric medicines study..as taught in the following program modules X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 9

10 The International/Joint Master programme on Paediatric Medicines Development and Evaluation is based on e-learning modules. Almost all theoretical education is offered in online modules. Students only physically attend the programme during the Fresher s and Re-Fresher s meetings and under their research/work placement training. The Master programme is a twoyears programme with 60 ECTS offered in part time with ten modules to be taken in a sequenced manner (see table below). Module 1 MED 2 DEV 3 REG 4 EXP 5 FOR 6 TRI 7 PPP Module title Introduction to Paediatric Medicines Developmental Pharmacology - Pharmacokinetics Regulatory and ethical issues regarding paediatric medicines research Experimental Drug evaluation in Paediatrics Paediatric Drug Formulations Paediatric Clinical Trial Management Post-licensure paediatric drug evaluation: Pharmacovigilance & Pharmacoepidemiology 8 Pharmacology in pregnancy PREG and in neonates Biomarkers and Innovative 9 BIO tools in paediatric clinical pharmacology 10 VAC Paediatric vaccines SCIENTIFIC RESPONSIBLE COORDINATOR Scientific collaborator(s) PAOLO ROSSI Viviana Moschese Agnes Saint-Raymond EVELYNE JACQZ-AIGRAIN John van Den Anker Saskia de Wildt AGNES SAINT RAYMOND Paolo Tomasi ADRIANA CECI Gerard Pons Paola Baiardi TONY NUNN Catherine Tuleu Mark Turner JOHN VAN DEN ANKER Mark Turner MIRIAM STURKENBOOM Katia Verhamme Sabine Straus Agnes Saint Raymond Jim Slattery EVELYNE JACQZ-AIGRAIN OSCAR DELLA PASQUA Adriana Ceci Paola Baiardi JAN BONHOEFFER Miriam Sturkenboom Coordinating University University of Rome Tor Vergata University Paris Diderot University of Rome Tor Vergata University of Rome Tor Vergata Erasmus University Rotterdam University of Basel Erasmus University Rotterdam University Paris Diderot University of Rome Tor Vergata University of Basel D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 10

11 MODULE SCHEDULE AND TIME TABLE Year 1 44 Fresher week Module 1 Module 2 Holidays Exam Exam 2 Module 3 Module D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 11

12 7 8 9 Exam Exam Module 5 Module Easter Exam Exam Module 7 Module Exam Exam Module 9 Module 10 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 12

13 Exam Exam 03/08/ Year 2 44 Re-fresher week D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 13

14 45 46 Research Training/Work placement Hollidays Research D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 14

15 Easter /08/16 31 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 15

16 MODULE 1 Module 1: Introduction to Paediatric Medicine CURRICULUM MAP for Module At the end of the module the student will be able to: Fresher Meeting Know on Master objective, items, and virtual learning environment Bloom Level (1-6) Topics to achieve 1 Master objective, items, and virtual learning environment Enabling Competency for Masters Program (see below) Instructional 1 Face to face lessons on the occasion of the Fresher Week Assessment Simulation of multiple choice test Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) Week 0 5,6,7 November 2014 Hours 25 Instructional methods Paediatric Epidemiology Describe Paediatric Population: Demography, Prevalence and burden of Diseases and Public health issues in children. 2 Description of paediatric population in the world and the impact of paediatric diseases in Global Health. (A. Tozzi) 1, 2, 4 Pre-reading by recorded presentation with and glossary of y via VLE Multiple choice test via VLE on the topic discussed Week Nov -3 Dec sub topics (3 x 80 min ) Each topic: - Pre-reading 20 - s 20 - Post-reading 40 Meet the Professor 90 min Multiple choice test 30 min D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 16

17 for Module At the end of the module the student will be able to: Describe Evidence Based Medicine criteria and application in paediatrics Principles of genetics and inheritance Discuss major aspects of the genetic and epigenetic impact on the development and expression of disease Growth Describe the dynamic process of growth related to its pharmacokinetics implications Bloom Level (1-6) Topics to achieve 2 The impact of genetics and epigenetics in disease expression (B. Dalla Piccola) 2 Principle of growth mechanism in different paediatric ages (S. Cianfarani, L. Savendal ) Enabling Competency for Masters Program (see below) Instructional Critical Reading s via VLE 1 Pre-reading by recorded presentation with and glossary of y via VLE Critical Reading s via VLE 1, 2, 4 Pre-reading by recorded presentation with and glossary of y via VLE Critical Assessment Multiple choice test via VLE on the topic discussed Multiple choice test via VLE on the topic discussed Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) Week Nov -3 Dec 2014 Week Nov -3 Dec 2014 Hours Instructional methods 6 3 sub topics (3 x 80 min ) Each topic: - Pre-reading 20 - s 20 - Post-reading 40 Meet the Professor 90 min Multiple choice test 30 min 6 3 sub topics (3 x 80 min ) Each topic: - Pre-reading 20 - s 20 - Post-reading 40 Meet the Professor 90 min Multiple choice test 30 min D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 17

18 for Module At the end of the module the student will be able to: Organ Specific Maturational Aspects Define the specificity of paediatric age with particular focus on organ specific maturational aspects, growth and principle of metabolism The neonate and neonatal specific diseases Define the complexity of the neonatal period focusing on therapeutic needs, new trials and evidence needs, and application of Bloom Level (1-6) Topics to achieve 1 The mechanisms of liver, kidney and CNS development with respect of drug metabolism (E. Jacqz-Aigrain) 1 The basic features of the neonatal period (P. Manzoni) Enabling Competency for Masters Program (see below) Instructional Reading s via VLE 1, 2, 4 Pre-reading by recorded presentation with and glossary of y via VLE Critical Reading s via VLE 1, 2, 4 Pre-reading by recorded presentation with and glossary of y via VLE Critical Reading Assessment Multiple choice test via VLE on the topic discussed Multiple choice test via VLE on the topic discussed Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) Week Nov -3 Dec 2014 Week Nov -3 Dec 2014 Hours Instructional methods 6 3 sub topics (3 x 80 min ) Each topic: - Pre-reading 20 - s 20 - Post-reading 40 Meet the Professor 90 min Multiple choice test 30 min 6 3 sub topics (3 x 80 min ) Each topic: - Pre-reading 20 - s 20 - Post-reading 40 Meet the Professor 90 min Multiple choice test 30 min D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 18

19 for Module At the end of the module the student will be able to: individualized/optimized medicines therapy Peculiarity of oncology and hematology diseases in paediatric age Describe Paediatric Oncology and Haematology Diseases focusing on current guidelines, therapeutic needs, new trials and evidence needs, and application of individualized/optimized medicines therapy Peculiarity of immune mediated Bloom Level (1-6) Topics to achieve 2 Therapeutic needs and guidelines identification and explanation related to Paediatric Oncology and Haematology (F. Locatelli, P. Paolucci) 2 Therapeutic needs and guidelines identification Enabling Competency for Masters Program (see below) Instructional s via VLE 1 Pre-reading by recorded presentation with and glossary of y via VLE Critical Reading s via VLE Group activity through a tutored seminar 1 Pre-reading Assessment Individual case solving to be evaluated with respect to therapeutic aspects using an EBM approach and including the application of therapeutic guidelines, followed by forum discussion on raised issues Individual case solving Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) Week Dec Jan 2015 Holidays from December 24th 2014 to Jan 7th 2015 Week 5-10 Hours Instructional methods 10 5 sub topics Each sub topic: Pre-reading 20 s 20 Post-reading 40 Guided case solving applying the guidelines and meet the professor 30 Multiple choice test 50 TOPIC to be EXPANDED DURING WORK PLACEMENT/RESEARCH ACTIVITY 10 5 sub topics Each sub topic: D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 19

20 for Module At the end of the module the student will be able to: diseases and infectious diseases in paediatric age Describe paediatric immune mediated diseases and infectious diseases focusing on current guidelines, therapeutic needs, new trials and evidence needs, and application of individualized/optimized medicines therapy Bloom Level (1-6) Topics to achieve and explanation related to paediatric immune mediated diseases and Infectious Diseases Primary Immunodeficienci es Antibody defects (V.Moschese) Primary Immunodeficienci es Cellular defects (A. Aiuti) Rheumatologic diseases (F. De Benedetti) Bacterial Infections (P.Rossi) Viral Infections (C. Giaquinto) Enabling Competency for Masters Program (see below) Instructional by recorded presentation with and glossary of y via VLE Critical Reading s via VLE Group activity through a tutored seminar Assessment to be evaluated with respect to therapeutic aspects using an EBM approach and including the application of therapeutic guidelines, followed by forum discussion on raised issues Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) 4 Dec Jan 2015 Holidays from December 24th 2014 to Jan 7th 2015 Hours Instructional methods Pre-reading 20 s 20 Post-reading 40 Guided case solving applying the guidelines and meet the professor 30 Multiple choice test 50 TOPIC to be EXPANDED DURING WORK PLACEMENT/RESEARCH ACTIVITY D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 20

21 for Module At the end of the module the student will be able to: Peculiarity of CNS and pain in paediatric age Describe pain mechanism and CNS development focusing on current guidelines, therapeutic needs, new trials and evidence needs, and application of individualized/optimized medicines therapy Bloom Level (1-6) Topics to achieve 2 Therapeutic needs and guidelines identification and explanation related to pain mechanism and CNS development (F. Vigevano, E. M. Mercuri) Enabling Competency for Masters Program (see below) Instructional 1 Pre-reading by recorded presentation with and glossary of y via VLE Critical Reading s via VLE Group activity through a tutored seminar Assessment Individual case solving to be evaluated with respect to therapeutic aspects using an EBM approach and including the application of therapeutic guidelines, followed by forum discussion on raised issues Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) Week Dec Jan 2015 Holidays from December 24th 2014 to Jan 7th 2015 Hours Instructional methods 10 5 sub topics Each sub topic: Pre-reading 20 s 20 Post-reading 40 Guided case solving applying the guidelines and meet the professor 30 Multiple choice test 50 TOPIC to be EXPANDED DURING WORK PLACEMENT/RESEARCH ACTIVITY Peculiarity of metabolic and rare 2 Therapeutic needs and guidelines identification 1 Pre-reading Individual case solving Week sub topics Each sub topic: D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 21

22 for Module At the end of the module the student will be able to: diseases in paediatric age Describe the major content of Paediatric Metabolic and Rare Diseases focusing on current guidelines, therapeutic needs, new trials and evidence needs, and application of individualized/optimized medicines therapy Bloom Level (1-6) Topics to achieve and explanation related Paediatric Metabolic and Rare Diseases (C. Dionisi Vici E. Bertini ) Enabling Competency for Masters Program (see below) Instructional by recorded presentation with and glossary of y via VLE Critical Reading s via VLE Group activity through a tutored seminar Assessment to be evaluated with respect to therapeutic aspects using an EBM approach and including the application of therapeutic guidelines, followed by forum discussion on raised issues Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) 4 Dec Jan 2015 Holidays from December 24th 2014 to Jan 7th 2015 Hours Instructional methods Pre-reading 20 s 20 Post-reading 40 Guided case solving applying the guidelines and meet the professor 30 Multiple choice test 50 TOPIC to be EXPANDED DURING WORK PLACEMENT/RESEARCH ACTIVITY Peculiarity of cardiologic diseases in paediatric age Describe the major 2 Therapeutic needs and guidelines identification and explanation related to Paediatric Cardiology (C. Male, B. Marino Taussig 1 Pre-reading by recorded presentation with Individual case solving to be evaluated with Week Dec sub topics Each sub topic: Pre-reading 20 s 20 Post-reading 40 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 22

23 for Module At the end of the module the student will be able to: content of Paediatric Cardiology focusing on current guidelines, therapeutic needs, new trials and evidence needs, and application of individualized/optimized medicines therapy Bloom Level (1-6) Topics to achieve De Bodonia) Enabling Competency for Masters Program (see below) Instructional and glossary of y via VLE Critical Reading s via VLE Group activity through a tutored seminar Assessment respect to therapeutic aspects using an EBM approach and including the application of therapeutic guidelines, followed by forum discussion on raised issues Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) Jan 2015 Holidays from December 24th 2014 to Jan 7th 2015 Hours Instructional methods Guided case solving applying the guidelines and meet the professor 30 Multiple choice test 50 TOPIC to be EXPANDED DURING WORK PLACEMENT/RESEARCH ACTIVITY D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 23

24 for Module At the end of the module the student will be able to: Peculiarity of respiratory and allergy diseases in paediatric age Describe the major content of Paediatric Respiratory and Allergy Diseases focusing on current guidelines, therapeutic needs, new trials and evidence needs, and application of individualized/optimized medicines therapy Bloom Level (1-6) Topics to achieve 2 Therapeutic needs and guidelines identification and explanation related Paediatric Respiratory and Allergy Diseases (V. Moschese, L. Chini, M. Migdal) Enabling Competency for Masters Program (see below) Instructional 1 Pre-reading by recorded presentation with and glossary of y via VLE Critical Reading s via VLE Group activity through a tutored seminar Assessment Individual case solving to be evaluated with respect to therapeutic aspects using an EBM approach and including the application of therapeutic guidelines, followed by forum discussion on raised issues Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) Week Dec Jan 2015 Holidays from December 24th 2014 to Jan 7th 2015 Hours Instructional methods 10 5 sub topics Each sub topic: Pre-reading 20 s 20 Post-reading 40 Guided case solving applying the guidelines and meet the professor 30 Multiple choice test 50 TOPIC to be EXPANDED DURING WORK PLACEMENT/RESEARCH ACTIVITY Paediatric therapeutics Define the major 1 Therapeutic needs and regulatory aspects explanation related to 1 Face to face lessons on the occasion Multiple choice test via VLE on Week sub topics Each sub topic: Pre-reading 20 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 24

25 for Module At the end of the module the student will be able to: regulatory aspects of paediatric therapeutics including description of off-label use of medicine Bloom Level (1-6) Topics to achieve paediatric therapeutics (A. Saint Raymond, F. Rocchi) Enabling Competency for Masters Program (see below) Instructional of the Fresher Week Pre-reading by recorded presentation with and glossary of y via VLE Assessment the topic discussed Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) 4 Dec Jan 2015 Holidays from December 24th 2014 to Jan 7th 2015 Hours Instructional methods s 20 Post-reading 40 Guided case solving applying the guidelines and meet the professor 30 Multiple choice test 50 TOPIC to be EXPANDED DURING WORK PLACEMENT/RESEARCH ACTIVITY Critical Reading s via VLE D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 25

26 MODULE 2 Module 2: Principles of Pharmacology Developmental Pharmacology CURRICULUM MAP for Module At the end of the module the student will be able to: Bloom Level (1-6) Topics to achieve Enabling Competency for Masters Program Instructional Assessment Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) Fresher Week Know on Master objective, items, and virtual learning environment Introduction to pharmacology Define a drug (different types and names ) List the different drug targets (receptors, channels, enzymes, nucleic acids) Describe drug receptor interaction 1 Master objective, items, and virtual learning environment 1 EJA 1. Molecular pharmacology and overview of drug targets. Mechanism of drug action 1 Face to face lessons on the occasion of the fresher week Introduction to Pharmacology 1, 2 Glossary of definitions Recorded Directed readings of chapters Simulation of multiple choice test Explain parameters of drug action (specificity, selectivity.. Explain dose response curve (Emax, DE50) Describe the impact of agonists, antagonists Quizz with online responses Hours Week 0 Week 1 10 hours Prereading : 3 : 30 min Postreading : 3 Meet the D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 26

27 for Module At the end of the module the student will be able to: Bloom Level (1-6) Topics to achieve Enabling Competency for Masters Program Instructional Assessment Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) and dose effect curves Define agonists and antagonists Describe methods of drug screening and selection, in vitro testing Explain preclinical toxicity studies and developmental studies in animals (including juvenile animal studies) Define PK parameters Compare the pharmacokinetics of different drugs Explain important physiological factors 2. Overview of preclinical 1 drug selection : from the candidate compounds to Samia Mourah drug 1 JVA SW 3. Pharmacokinetic drug disposition (ADME) Impact of age and diseases 4 Pharmacokinetics in practice Parameters and s in Introduction to Pharmacology 1, 2 1, 2, 3 Recorded Glossary of definitions Directed readings of chapters Pre-readings Recorded Directed reading of selected PK articles Discuss published data Provide defintions of all PK parameters and describe changes with age Present and discuss PK studies from the litterature Clinical cases Hours teacher : 2 Multiple choice questions 1 Week 2 Prereading : 3 : 30 min Postreading : 3 Meet the teacher : 2 Multiple choice questions 1 Week 3 Prereading : 3 : 30 min Postreading : 3 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 27

28 for Module At the end of the module the student will be able to: Bloom Level (1-6) Topics to achieve Enabling Competency for Masters Program Instructional Assessment Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) and their development across age ranges Explain the impact of specific diseases (hepatic, renal, infection ) pharmacokinetics : stable isotopes, microdoses, DBS, analytical methods.. Hours Meet the teacher : 2 Multiple choice questions 1 Week 4 Prereading : 3 : 30 min Postreading : 3 Principles of Pharmacodynamics Discuss the methods to measure drug response in children (direct, use of biomarkers, etc ). 2 GLK 5. Principles of Pharmacodynamics 1, 2 Recorded Directed reading of chapters Define end-points Discuss changes in end points with age and reasons by examples and reports : tools for pain, sedation.. Meet the teacher : 2 Multiple choice questions 1 Week 5 Prereading : 3 : 30 min Postreading : 3 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 28

29 for Module At the end of the module the student will be able to: Bloom Level (1-6) Topics to achieve Enabling Competency for Masters Program Instructional Assessment Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) Explain the need for tools adapted to children Learn about the placebo effect Pharmacogenetics Define genotype and phenotype List the important pharmacogenetic examples in paediatrics Understand the impact of age on genotype phenotype concordance Describe epigenetic studues during development Pharmacokinetics and PK/PD Understand the basic principles and use of 2 JSL 2 ZW 6. Principles and tools in pharmacogenomics introduction to epigenetics and to omic tools and techniques 7. Introduction to PK population approaches, PK /PD models and PB / PK models, Principles of bridging 1, 2, 6 1, 2, 6 Pre readings of well documented examples Recorded Directed readings Pre-reading of review articles Recorded Identify and comment on paediatric examples important in therapeutic decision making : CYP2D6 and codeine TPMT and mercaptopurine Review human studies (twins, diseases) illustrating epigenetics Comment of published pediatric PK studies Discuss the need for PK studies in children and the Hours Meet the teacher : 2 Multiple choice questions 1 W6 Prereading : 3 : 30 min Postreading : 3 Meet the teacher : 2 Multiple choice questions 1 W7 Prereading : 3 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 29

30 for Module At the end of the module the student will be able to: Bloom Level (1-6) Topics to achieve Enabling Competency for Masters Program Instructional Assessment Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) modeling and simulation Discuss the PK studies adapted to age Understand the impact of covariates in PK variability Review physiological parameters adapted to age Therapeutic drug monitoring Define therapeutic target range Report on the advantages and limitations of TDM Understand criteria for dosage interpretation and the PK impact of drug interactions 2 Saskia studies 8. Therapeutic drug monitoring Principles Analytical methods.. Specific drugs TDM in developing countries Published PK and PKPD studies 1, 2 Pre-readings (Recorded ) Case studies importance of age groups Discuss the PK/PD studies with the example of antibiotics Define a therapeutic target and give examles of high risk drugs in children Case studies to discuss and Interpret monitoring data in children Hours : 30 min Postreading : 3 Meet the teacher : 2 Multiple choice questions 1 W8 Prereading : 3 : 30 min Postreading : 3 Meet the teacher : 2 Multiple choice questions 1 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 30

31 for Module At the end of the module the student will be able to: Bloom Level (1-6) Topics to achieve Enabling Competency for Masters Program Instructional Assessment Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) Describe the mechanisms of adverse drug reactions, Classification Understand the analysis and report of ADR in clinical trials Have an overview of risk benefit ratio and how to improve drug prescription, evaluation, monitoring, surveillance, initiation of prescriptions 1 FK 2 EJA Tiphaine 9. Introduction to pharmacovigilance 10. Overview of drug evaluation and use in children : the risk benefit ratio and how to improve it Off label-off licence Clinical studies Phases 1-3 Post marketting surveillance Regulatory aspects PIP 1, 2, 6 Directed readings of chapters and paediatric guidelines 1, 2 (5, 7, 8) Pre-readings (Recorded ) And Case studies Multiple choice testing Report on prerequises for drug use in children according to age groups Draft a pharmacokinetic protocol based on known data in adults and select important covariates Hours W9 Prereading : 3 : 30 min Postreading : 3 Meet the teacher : 2 Multiple choice questions 1 W10 Prereading : 3 : 30 min Postreading : 3 Meet the teacher : 2 Multiple choice questions 1 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 31

32 MODULE 3 Module 3: Regulatory and ethical issues regarding paediatric medicines research CURRICULUM MAP Explain the basic ethics principles pertaining to paediatric public health and clinical trials. Unit Lead Instructo r 1. ETHICS Agnes Saint Raymond Agnes Saint Raymond Compet. Bloo m Topic 1, 3, 7 2 Main ethics principles: subject autonomy, beneficence, distributive justice. Main guidelines and legislation for ethical considerations in EU and US. Deliverables from Instructors One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (5, with commented answers) 4) MCQs for final test (5 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (5, with commented answers) Notes on Instructional Material Videopresentati on, Videopresentati on, Assessment by Interim Educational MCQ test Interim Educational MCQ test Stage hrs (student ) Wk 1 1,5 Wk1 2,5 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 32

33 Unit Lead Instructo r Compet. Bloo m Topic Deliverables from Instructors 4) MCQs for final test (5 Q&A) Notes on Instructional Material Assessment by Stage hrs (student ) Agnes Saint Raymond Agnes Saint Raymond Assent and consent. Risk assessment and management (ethics committees, DSMBs, ). One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (5, with commented answers) 4) MCQs for final test (5 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (5, with commented answers) 4) MCQs for final test (5 Q&A) Videopresentati on, Videopresentati on, Interim Educational MCQ test Interim Educational MCQ test Wk1 1,5 Wk1 2,5 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 33

34 Explain the basic regulatory environment pertaining to paediatric clinical trials. Unit 2. PRODUCT LIFE-CYCLE Lead Instructo r Agnes Saint Raymond Agnes Saint Raymond Agnes Saint Raymond Compet. Bloo m Topic General revision of Unit / final assessement 5 2 Introduction into product life-cycle (high level): concept of prepost-marketing authorization. General revision of Unit / final assessement Deliverables from Instructors Prepare final MCQ test from questions obtained from individual topics One (max 15-20') videopresentati on on the topic 2) Relevant final MCQ test (7-15 Q&A) Notes on Instructional Material Assessment by N/A Preparation of a presentation on all aspects of Unit (duration 45', between 25 and 50 ) and/or discussion essay on a specific topic. 2) final MCQ test Videopresentati on, N/A Preparation of a presentation on all aspects of Unit (duration 30', between 15 and 25 Stage hrs (student ) Wk1 4 N/A Wk 1 2,5 Wk1 2 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 34

35 Unit Lead Instructo r Compet. Bloo m Topic Deliverables from Instructors Notes on Instructional Material Assessment by 2) final MCQ test Stage hrs (student ) Explain the basic regulatory environment pertaining to paediatric clinical trials 3. CLINICAL TRIAL LEGISLATION Agnes Saint Raymond Agnes Saint Raymond 5 2 General information on clinical trials (in Europe): naming legislation, difference Directive, Regulation, Medicinal Products definition, role of regulatory agencies, where to find the information. Main legislation (detail what aspects are covered): Regulation 726/2004, 1901/2006 and Directive 2001/20 (under rev), 2001/83 (brief overview) and US legislation. One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (5, with commented answers) 4) MCQs for final test (5 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (5, with commented answers) 4) MCQs for final test (5 Q&A) Videopresentati on, Videopresentati on, Interim Educational MCQ test Interim Educational MCQ test Wk 1 2 Wk 1 2 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 35

36 Unit Lead Instructo r Agnes Saint Raymond Gunter Egger Agnes Saint Raymond Compet. Bloo m Topic Principles and scope of medicinal product application: European Union application National vs EMA and comparison with US Guidelines around the conduct of clinical trials (EMA, ICH). Clinical trial databases (EudraCT, EUCTR, Clinicaltrials.gov, WHO ) General revision of Unit / final assessement Deliverables from Instructors One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (5, with commented answers) 4) MCQs for final test (5 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (5, with commented answers) 4) MCQs for final test (5 Q&A) assembly of final MCQ test (20-30 Q&A) Notes on Instructional Material Videopresentati on, Videopresentati on, Assessment by Interim Educational MCQ test Interim Educational MCQ test N/A Preparation of an essay on the "EU Clinical trial legislation and its impact on Stage hrs (student ) Wk 1 2,5 Wk 1 1,5 Wk 1 3 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 36

37 Explain the different types of Medicinal Products. Unit 4. TYPES OF MEDICINAL PRODUCTS Lead Instructo r Giovanni Lesa Compet. Bloo m Topic 5 2 Regulatory classification of medicinal products: - chemical products (radiopharm, antinsense..) - biological products (nucleic acids, recombinant DNA tech, cellbased, tissuebased, classical biological) - Blood products - Vaccines - Medical devices combined with medicines - Other Deliverables from Instructors One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (5, with commented answers) 4) MCQs for final test (7 Q&A) Notes on Instructional Material Videopresentati on, Assessment by paediatric clinical trials" ( words, English, French, German, Italian allowed) 2) final MCQ test Interim Educational MCQ test Stage Wk 2 2 hrs (student ) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 37

38 Unit Lead Instructo r Giovanni Lesa Giovanni Lesa Compet. Bloo m Topic Special legal basis for authorisation of products, and regulatory impact (generic, hybrid, biosimilar, wellestablished use, traditional herbal and homeopathic products; fixeddose combinations and combination packs) General revision of Unit / final assessement Deliverables from Instructors One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (5, with commented answers) 4) MCQs for final test (7 Q&A) assembly of final MCQ test (14-20 Q&A) Notes on Instructional Material Videopresentati on, Assessment by Interim Educational MCQ test N/A Preparation of a PowerPoint presentation on "Different types of medicinal products and their regulatory consequence s" (15-20, minutes) 2) final MCQ test Stage hrs (student ) Wk2 2 Wk 2 2 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 38

39 Comprehend the need for regulation to achieve public health objectives in negleced populations (orphan diseases, pregnancy, paediatrics, other). Know the mainstays of the orphan and paediatric regulations Unit 5. NEGLECTED POPULATIONS Lead Instructo r Paolo Tomasi Jordi Llinares Compet. Bloo m Topic 1, 2, 5 3 Introduction on neglected populations Orphan diseases (General overview of patients with rare diseases and legislation. Requirements for an orphan designation and timing of application. Incentives: fee reductions, market exclusivity, centralised procedure, protocol assistance.) Deliverables from Instructors One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (5, with commented answers) 4) MCQs for final test (5 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (5, with commented answers) 4) MCQs for final test (5 Q&A) Notes on Instructional Material Videopresentati on, Videopresentati on, Assessment by Interim Educational MCQ test Interim Educational MCQ test Stage hrs (student ) Wk 2 1 Wk 2 2 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 39

40 Unit Lead Instructo r Paolo Tomasi Francesca Cerreta Paolo Tomasi Compet. Bloo m Topic Paediatric Medicines - EU Paediatric Regulation (Why created. and pillars, incl. PDCO, transparency, art. 45 and 46, networks, etc. Incentives) Medicines in pregnancy (use in pregnancy to cover newborns) General revision of Unit / final assessement Deliverables from Instructors One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (7, with commented answers) 4) MCQs for final test (10 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) assembly of final MCQ test (23-25 Q&A) Notes on Instructional Material Videopresentati on, Videopresentati on, Assessment by Interim Educational MCQ test Interim Educational MCQ test N/A Preparation of a presentation on "The EU Paediatric Regulation" Stage hrs (student ) Wk 2 3,5 Wk 2 1 Wk 2 2 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 40

41 Unit Lead Instructo r Compet. Bloo m Topic Deliverables from Instructors Notes on Instructional Material Assessment by (20-25, 45 minutes) 2) final MCQ test Stage hrs (student ) Explain the PIP content, process and lifecycle; describe global regulatory interactions and global developmen t; be able to prepare a PIP for a new medicine 6. THE PAEDIATRIC INVESTIGATIO N PLAN (PIP) Paolo Tomasi Paolo Tomasi 2, 4, 5, 6, 7 3, 4 When is a PIP needed and what is the scope of the PIP (condition/indicatio n) PIP content (pharmaceutical forms and formulations, nonclinical studies, clinical studies) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) Videopresentati on 2) policy on scope of PIP 3) Additional, Videopresentati on, 3) example of a PIP full opinion Interim Educational MCQ test Interim Educational MCQ test Wk Wk D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 41

42 Unit Lead Instructo r Cecile Ollivier Janina Karres Paolo Tomasi Compet. Bloo m Topic Extrapolation, modelling & simulation in paediatric drug development, biomarkers. PIP/waiver application procedure, and PIP life cycle (including modifications). Compliance with the agreed PIP (annual reports, compliance check, penalties). Deliverables from Instructors One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (4, with commented answers) 4) MCQs for final test (4 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant Notes on Instructional Material Videopresentati on, Videopresentati on, Videopresentati on Assessment by Interim Educational MCQ test Interim Educational MCQ test Interim Educational MCQ test Stage hrs (student ) Wk Wk 2 5 3,5 Wk D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 42

43 Unit Lead Instructo r Compet. Bloo m Topic Deliverables from Instructors 3) Educational MCQ (2, with commented answers) 4) MCQs for final test (2 Q&A) Notes on Instructional Material, 3) example of a PIP compliance check report and opinion Assessment by Stage hrs (student ) Cecile Ollivier Irmgard Eichler Regulatory interactions (CHMP, SAWP, orphan medicines). Global paediatric development (interactions with FDA, Japan, Canada, Australia ). One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (2, with commented answers) 4) MCQs for final test (2 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (2, with commented answers) 4) MCQs for final test (2 Q&A) Videopresentati on, Videopresentati on, Interim Educational MCQ test Interim Educational MCQ test Wk Wk D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 43

44 Unit Lead Instructo r Irmgard Eichler Ralph Bax Paolo Tomasi Compet. Bloo m Topic The US legislation (BPCA, PREA, FDASIA ) and the FDA process: difference and commonalities Relevant guidelines and links, expert workshops, outcome analysis. How to prepare a PIP application Deliverables from Instructors One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (4, with commented answers) 4) MCQs for final test (4 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (2, with commented answers) 4) MCQs for final test (2 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant Notes on Instructional Material Videopresentati on, 3) BPCA, PREA, FDASIA legislation Videopresentati on 2) 5-year report to EC 3) IOM analysis of US legislation 4) Additional, Videopresentati on Assessment by Interim Educational MCQ test Interim Educational MCQ test Interim Educational MCQ test Stage hrs (student ) Wk Wk Wk D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 44

45 Unit Lead Instructo r Compet. Bloo m Topic Deliverables from Instructors 3) Educational MCQ (5, with commented answers) 4) MCQs for final test (5 Q&A) Notes on Instructional Material, Assessment by Stage hrs (student ) Explain the general principles of the Scientific Advice procedure for paediatric developmen t issues 7. PAEDIATRIC SCIENTIFIC ADVICE Paolo Tomasi Spiros Vamvakas General revision of Unit / final assessement 5 2 Procedure outline (EMA and national advices, FDA), timing, content of application, benefits selection of product and data for PIP preparation 2) selection of PIP for assessment 3) assembly of final MCQ test (30 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (5, with commented answers) 4) MCQs for final test (5 Q&A) N/A Preparation of a PIP application for a specific product 2) Assessment of a PIP application 3) final MCQ test Videopresentati on, Interim Educational MCQ test Wk 2 5 3,5 Wk 6 2 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 45

46 Unit Lead Instructo r Spiros Vamvakas Spiros Vamvakas Spiros Vamvakas Compet. Bloo m Topic Qualification of novel methodologies for medicine development incl. biomarker qualification procedure: applications to paediatric drug development. HTA joint advice General revision of Unit / final assessement Deliverables from Instructors One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (5, with commented answers) 4) MCQs for final test (5 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (5, with commented answers) 4) MCQs for final test (5 Q&A) assembly of final MCQ test (15 Q&A) Notes on Instructional Material Videopresentati on, Videopresentati on, Assessment by Interim Educational MCQ test Interim Educational MCQ test N/A preparation of a slide presentation on Scientific Advice for paediatric Stage hrs (student ) Wk 6 1 Wk 6 2 Wk 6 3 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 46

47 Unit Lead Instructo r Compet. Bloo m Topic Deliverables from Instructors Notes on Instructional Material Assessment by development ; 2) final MCQ test Stage hrs (student ) Describe the elements required for a paediatric clinical trial application. 8. PAEDIATRIC CLINICAL TRIALS Ralf Herold Gunter Egger 5, 6, 7 3 The new Clinical trial regulation, incl. prerequisites to paediatric trials (e.g. quality, preclinical, PK/PD, adult data) CT authorisation in the Member States where the trial is going to take place One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) Videopresentati on 2) New Clinical Trials regulation 3) Additional, Videopresentati on, Interim Educational MCQ test Interim Educational MCQ test Wk Wk D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 47

48 Unit Lead Instructo r Ralph Herold Gunter Egger Gunter Egger Compet. Bloo m Topic Ethics opinion Application form EudraCT / EuCTR Deliverables from Instructors One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant Notes on Instructional Material Videopresentati on, Videopresentati on 2) application form 3) Additional, Videopresentati on Assessment by Interim Educational MCQ test Interim Educational MCQ test Interim Educational MCQ test Stage hrs (student ) Wk Wk Wk D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 48

49 Unit Lead Instructo r Compet. Bloo m Topic Deliverables from Instructors 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) Notes on Instructional Material, Assessment by Stage hrs (student ) Gunter Egger Gunter Egger Major (significant) amendment Final report/ Publication; Safety reporting- final reporting One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) Videopresentati on, Videopresentati on, Interim Educational MCQ test Interim Educational MCQ test Wk Wk D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 49

50 Explain the marketing authorizatio n application procedure and its most important elements. Unit 9. THE MARKETING AUTHORIZATIO N (MA) Lead Instructo r Giovanni Lesa Gunter Egger Andrea Ecker Compet. Bloo m Topic Inspections (GCP), with paediatricspecific aspects General revision of Unit / final assessement 5 2 Types of MA in the EU Deliverables from Instructors One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) assembly of final MCQ test (24-25 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) Notes on Instructional Material Videopresentati on, N/A Videopresentati on, Assessment by Interim Educational MCQ test final MCQ test Interim Educational MCQ test Stage hrs (student ) Wk Wk Wk D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 50

51 Unit Lead Instructo r Andrea Ecker Andrea Ecker Andrea Ecker Compet. Bloo m Topic MA procedure and scope (mandatory and optional scope, incl. remark on Art. 58 of Regulation 726/2004) Role of the CHMP and the NCAs Application - CTD Deliverables from Instructors One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant Notes on Instructional Material Videopresentati on, Videopresentati on, Videopresentati on Assessment by Interim Educational MCQ test Interim Educational MCQ test Interim Educational MCQ test Stage Wk 9 10 Wk 9 10 Wk 9 10 hrs (student ) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 51

52 Unit Lead Instructo r Compet. Bloo m Topic Deliverables from Instructors 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) Notes on Instructional Material, Assessment by Stage hrs (student ) Paolo Tomasi Benjamin Pelle SmPC (labelling); Indications in the paediatric population. Risk management plans (timing, Content, update), post-authorisation studies One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (3, with commented answers) 4) MCQs for final test (3 Q&A) One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (2, with commented answers) 4) MCQs for final test (2 Q&A) Videopresentati on, Videopresentati on, Interim Educational MCQ test Interim Educational MCQ test Wk 9 10 Wk D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 52

53 Unit 10. Tutoring and Final Assessment Lead Instructo r Giovanni Lesa Andrea Ecker Agnes, Janina, Paolo Compet. Bloo m Topic Types of inspections (can be expected: GMP, GLP, Phvig Insp). General revision of Unit / final assessement Deliverables from Instructors One (max 15-20') videopresentati on on the topic 2) Relevant 3) Educational MCQ (2, with commented answers) 4) MCQs for final test (2 Q&A) assembly of final MCQ test (15-20 Q&A) Notes on Instructional Material Videopresentati on, Assessment by Interim Educational MCQ test N/A preparation of a PowerPoint presentation, 15-25, on the marketing authorisation in the EU 2) final MCQ test If feasible, interview at the end of the module Stage Wk 9 10 Wk 9 10 After completio n of the module hrs (student ) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 53

54 MODULE 4 Module 4: Experimental Drug evaluation in Paediatrics CURRICULUM MAP for Module Fresher Meeting Understand Master objective, items, and virtual learning environmen t Understand ing the need of performing ad hoc paediatric trials in the drug developme ntal process Bloo m Leve l (1-6) Topics to achieve 1 Master objective, items, and virtual learning environmen t 1 1. Paediatric studies and clinical trials supporting medicines marketed for human use (analysis by ATC groups, therapeutic areas, age groups) Enabling Compete ncy Lead Instructo r 1 Adriana Ceci 2,4 Adriana Ceci Instructio nal Face to face lessons on the occasion of the Fresher Week Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Assessme nt by Simulation of multiple choice test Multiple choice test (15') Sub-topic Introduction to the Module 1.1 Overview on paediatric studies and clinical trials with to medicines currently used in children Deliverables from Instructors Prepare F2F lecture with anticipated Q&A and upload MCQ test and answers Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Notes on Instructional Material Videopresenta tion, Timin g Week 0 Week 1 hrs (studen t) 6 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 54

55 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal Assessme nt by Sub-topic Deliverables from Instructors Notes on Instructional Material Timin g hrs (studen t) Marek Migdal Adriana Ceci Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Educationa l MCQ test (15') Multiple choice test (30') 2) Webinar on "Clinical trials involving children" and group activity for web discussion (1 hr) 1.2 Why to perform clinical trials in neonates and pre-terms 1.3 Prioritising paediatric trials to cover the gap 1.4 Webinar on "Clinical trials involving children" (1 hr) Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Prepare one (max 20') videopresenta tion on the 3) Prepare the MCQs final test (30') 4) Prepare the Videopresenta tion, Videopresenta tion, D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 55

56 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal Assessme nt by Sub-topic Deliverables from Instructors webinar and the group activitiy for discussion (1 hr) Notes on Instructional Material Timin g hrs (studen t) Understand ing the need of performing ad hoc paediatric trials in the drug developme ntal process 1 2. Critical issues in developing paediatric trials 2,4 Khazal Paradis Martin Offringa Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Post- Educatio nal test (15') Educatio nal test (15') 2.1 An Industry perspective on challenges to drug development in pediatric population 2.2 ological barriers: how to reduce the risk of Bias Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational Videopresenta tion, Videopresenta tion, Week D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 56

57 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal reading Assessme nt by Sub-topic Deliverables from Instructors test (15') Notes on Instructional Material Timin g hrs (studen t) Martin Offringa Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Preparatio n of a presentati on on all aspects of Unit (duration 30', between 15 and 25 ) 2) Give a brief outline of the main issues and problems in paediatric clinical trials (1 hr) 3) Webinar on "main issues and problems in paediatric clinical trials" 2.3 ological barriers: selection and measurement of meaningful outcomes 2.4. Webinar on "main issues and problems in paediatric clinical trials" Prepare one (max 20') videopresenta tion on the 3) Prepare quiz with on line answers (1 hr) 4) Prepare the webinar and the group activitiy for discussion (1 hr) Videopresenta tion, D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 57

58 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal Assessme nt by Sub-topic Deliverables from Instructors Notes on Instructional Material Timin g hrs (studen t) To be familiar with basic principles of clinical trials in children 2 3. Clinical studies and trials for drug developmen t in human (phase and types definition) 2,3,4 Agnes Saint- Raymond Agnes Saint- Raymond Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) Educationa l test / MCQ test (15') Educationa l test / MCQ test (15') 3.1 tbd Prepare one (max 20') videopresenta tion on the 3) Prepare the educational MCQ test 3.2 tbd Prepare one (max 20') videopresenta tion on the Videopresenta tion, Videopresenta tion, Week 2 6 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 58

59 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal presentatio n, 20'); 3) Postreading Assessme nt by Sub-topic Deliverables from Instructors 3) Prepare the educational MCQ test Notes on Instructional Material Timin g hrs (studen t) To be familiar with basic principles of clinical trials in children 2 4. Details on PK in different age groups: - PK/PD relationship s and phase II dose findings studies Agnes Saint- Raymond 2,3,4 Massimo Cella Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio Final Test /Questions on a case scenario. Write & post answers, commenta ry 1000 words (1 hr) 2) Preparatio n of a presentati on on all aspects of Unit (30') Educationa l test (15') 3.3 tbd Prepare one (max 20') videopresenta tion on the 3) Prepare the final test (1 hr) 4.1 What is the right dose for children? Prepare one (max 20') videopresenta tion on the Videopresenta tion, Videopresenta tion, Week 2-3 6,5 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 59

60 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal n, 20'); 3) Postreading Assessme nt by Sub-topic Deliverables from Instructors 3) Prepare the Educational test (15') Notes on Instructional Material Timin g hrs (studen t) M. Cella, Oscar della Pasqua Oscar Della Pasqua Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Educationa l test (15') Questions around a PK study case. Write & post answers, commenta ry 1000 words (1 hr) 2) Live session, group activity 4.2 Dealing with heterogeneity and uncertainty in PK trials in children 4.3 tbd 4.4 Live session (group activity and web discussion) on a PK study case (1 hr) Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Prepare one (max 20') videopresenta tion on the 3) Prepare the final test (questions around a PK study case) (1 Videopresenta tion, Videopresenta tion, D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 60

61 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal Assessme nt by and web discussion (1 hr) Sub-topic Deliverables from Instructors hr) 4) Prepare the live session and the group activitiy for discussion (1 hr) Notes on Instructional Material Timin g hrs (studen t) To be familiar with basic principles of clinical trials in children 2 5. Principle of modelling, simulation and extrapolatio n 2,3,4 Oscar Della Pasqua, Gérard Pons Oscar Della Pasqua Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Post- Educationa l Test (15') Educationa l Test (15') 5.1 Principle of modelling Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') 5.2 Simulation Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational Videopresenta tion, Videopresenta tion, Week 4 6,5 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 61

62 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal reading Assessme nt by Sub-topic Deliverables from Instructors test (15') Notes on Instructional Material Timin g hrs (studen t) Gérard Pons Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Final test: Multiple choice questions (1 hr) 2) Live session and group activity with a tutor and web discussion (1 hr) 5.3 Extrapolation 5.4 Live session (group activity and web discussion, 1 hr) Prepare one (max 20') videopresenta tion on the 3) Prepare the final test (1 hr) 4) Prepare the live session (group activity and web discussion, 1 hr) Videopresenta tion, D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 62

63 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal Assessme nt by Sub-topic Deliverables from Instructors Notes on Instructional Material Timin g hrs (studen t) To be familiar with basic principles to conduct the paediatric research 2 7. Statistical methods for sample size definition 2,3,4 Paola Baiardi Giovanni Smania Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Educationa l Test (15') Educationa l Test and exercises (15') 7.1 Sample size issues in paediatric trials 7.2 Innovative methodologies for sample size calculation Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Videopresenta tion, Videopresenta tion, Week D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 63

64 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal Assessme nt by Sub-topic Deliverables from Instructors Notes on Instructional Material Timin g hrs (studen t) To be familiar with basic principles to conduct the paediatric research 2 8. Randomisat ion, control in paediatric trials (placebo use, active control and current therapy) and assessment of appropriate endpoints Paola Baiardi 2,3,4 Giuseppe Pontrelli Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Final Test: Multiple choice questions and exercises, simulation (1hr 30') Educationa l test: Prepare a short report listing examples of endpoints to be applied in paediatric trials (30') 7.3 Choice of study design and trial feasibility: methods aimed at reducing sample size 8.1 The appropriate endpoint Prepare one (max 20') videopresenta tion on the 3) Prepare the final test (1 hr 30') Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (30') Videopresenta tion, Videopresenta tion, Week 6 6 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 64

65 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Giuseppe Pontrelli Martin Offringa Instructio nal Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Assessme nt by Educationa l test (15') Final Test: Questions around brief scenarios illustrating the use of placebo, control groups and endpoints 2) Preparatio n of presentati on on all aspects of Sub-topic Deliverables from Instructors 8.2 Biomarkers Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (30') 8.3 Justifiable comparators Prepare one (max 20') videopresenta tion on the 3) Prepare the final Educational test Notes on Instructional Material Videopresenta tion, Videopresenta tion, Timin g hrs (studen t) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 65

66 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal Assessme nt by Unit (15') Sub-topic Deliverables from Instructors Notes on Instructional Material Timin g hrs (studen t) Describe the various approaches to specific paediatric conditions in the paediatric population 3 9. How to perform trials for biological and advanced therapies (gene, tissutal and cellular) 3,4,6 Fabrizio De Benedett i Alessand ro Aiuti Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Educationa l test (15') Educationa l test (15') 9.1 Biologicals Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') 9.2 Gene Therapy Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Videopresenta tion, Videopresenta tion, Week 7 6 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 66

67 for Module Describe the various approaches to specific paediatric conditions in the paediatric population Bloo m Leve l (1-6) Topics to achieve The role of age in the developmen tal process: impact on type and phase of the study Enabling Compete ncy Lead Instructo r Maria Ester Bernardo 2,3,4 (Evelyne Jacqz- Aigrain, John N. van den Anker) Instructio nal Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Assessme nt by Final Test: multiple choice questions and final case study discussion (1 hr 30') Educationa l test (15') / Test with answers posted and commenta ry then online Sub-topic Deliverables from Instructors 9.3 Cell therapy Prepare one (max 20') videopresenta tion on the 3) Prepare the final Educational test and final case study discussion (1hr 30') 10.1 tbd Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Notes on Instructional Material Videopresenta tion, Videopresenta tion, Timin g Week 3 hrs (studen t) 6 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 67

68 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r (Evelyne Jacqz- Aigrain, John N. van den Anker) (Evelyne Jacqz- Aigrain, John N. van den Anker) Instructio nal Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Assessme nt by Educationa l test (15') Test: Discuss the reason why to initiate drug developme nt in children at different phases of drug developme nt in adults 2) Preparatio n of presentati Sub-topic Deliverables from Instructors 10.2 tbd Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') 10.3 tbd Prepare one (max 20') videopresenta tion on the 3) Prepare the final test (1 hr) Notes on Instructional Material Videopresenta tion, Videopresenta tion, Timin g hrs (studen t) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 68

69 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal Assessme nt by on on all aspects of Unit (30') Sub-topic Deliverables from Instructors Notes on Instructional Material Timin g hrs (studen t) To enable trainees to be familiar with a paediatric clinical protocol Prepare a Study protocol: - objectives - experiment al drug - study population - study drugs - trial procedures - randomisati on - statistical analysis - sample size and endpoints - expected results - timing 3,6,7,8 Giovanni Smania Saskia N. de Wildt Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Educationa l test (15') Educationa l test (15') 11.1 Study design features 11.2 Defining questions, rationale, population and inclusion/exclu sion criteria of the study Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Videopresenta tion, Videopresenta tion, Week D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 69

70 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal Assessme nt by Sub-topic Deliverables from Instructors Notes on Instructional Material Timin g hrs (studen t) Saskia N. de Wildt M. Felisi /Arianna G. Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Educationa l test (15') Educationa l test (20') 11.3, endpoints, study population and randomisation procedures 11.4 Trial procedure and Data management Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (20') Videopresenta tion, Videopresenta tion, D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 70

71 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Viviana Giannuzz i 2,3,4 Laura Mangiari ni Instructio nal Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Assessme nt by Educationa l test (20') Educationa l Test (15) Sub-topic 11.5 Protocol amendaments: procedures and authorisation 11.6 Technical specificities of clinical trial in children Deliverables from Instructors Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (20') Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Notes on Instructional Material Videopresenta tion, Videopresenta tion, Timin g Week 5 hrs (studen t) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 71

72 for Module To enable trainees to be familiar with a paediatric clinical protocol Bloo m Leve l (1-6) Topics to achieve Prepare a clinical study report Enabling Compete ncy Lead Instructo r Laura Mangiari ni 3,6,7,8 P. Baiardi Instructio nal Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Assessme nt by Final Test: writing a synopsis for protocol (3 hours) Webinar on the Case study: Deep project (1 hr) Educationa l test (20') Sub-topic 11.7 Recruitment facilities: focus on multinational studies 11.8 Webinar "Deep project: a case study"(1 hr) 12.1 Main features of a Clinical Study Report: ICH Topic E3 Deliverables from Instructors Prepare one (max 20') videopresenta tion on the 3) Prepare the final test (3 hrs) 4) Webinar discussion ( 1 hr) Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Notes on Instructional Material Videopresenta tion, Videopresenta tion, Timin g Week 9 hrs (studen t) 5 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 72

73 for Module How to appraise and use the existing paediatric drug studies Bloo m Leve l (1-6) Topics to achieve How to use data from preclinical and early clinical studies in design clinical trials. Source of data for the existing clinical trials. Enabling Compete ncy Lead Instructo r P. Baiardi 2,3,4,8 Oscar Della Pasqua/ Massimo Cella Instructio nal Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Assessme nt by Final Test: Study report test with answers posted and commenta ry then on line (1 hr) 2) Live session (group activity and web discussion, 1 hr) Educationa l test (15') Sub-topic 12.2 Reporting of randomised controlled trials: the CONSORT (Consolidated Standards of Reporting Trials) statement 12.3 Live session (group activity and web discussion, 1 hr) 13.1 Principles of translational science. Deliverables from Instructors Prepare one (max 20') videopresenta tion on the 3) Prepare the final Educational test (1 hr) 4) Prepare the live session (group activity and web discussion, 1 hr) Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Notes on Instructional Material Videopresenta tion, Videopresenta tion, Timin g Week 9-10 hrs (studen t) 6 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 73

74 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal Assessme nt by Sub-topic Deliverables from Instructors Notes on Instructional Material Timin g hrs (studen t) Massimo Cella Massimo Cella Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Educationa l test (15') Final test: Individual research of the literature and CT data sources electronica lly (1 hr) 2) Preparatio n of 13.2 Modelbased paediatric drug development Advanced techniques in the analysis of paediatric data Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Prepare one (max 20') videopresenta tion on the 3) Prepare the final Educational test (1 hr ) Videopresenta tion, Videopresenta tion, D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 74

75 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal Assessme nt by presentati on on all aspects of Unit (30') Sub-topic Deliverables from Instructors Notes on Instructional Material Timin g hrs (studen t) How to appraise and use the existing paediatric drug studies Observation al studies: benefits and limitations 2,3,4,8 Mariagra zia Felisi /Rachele Giuliani Mariagra zia Felisi /Rachele Giuliani Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Educationa l test (20') Educatio nal test (20') 14.1 Study Design, Precision, and Validity in Observational Studies 14.2 Role of observational studies in evaluating drug efficacy and safety in children Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (20') Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (20') Videopresenta tion, Videopresenta tion, Week 10 7 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 75

76 for Module How to appraise and use the existing paediatric drug studies Bloo m Leve l (1-6) Topics to achieve Health Technology Assessment Enabling Compete ncy Lead Instructo r Mariagra zia Felisi /Rachele Giuliani 2,3,4,8 Fedele Bonifazi Instructio nal Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Assessme nt by Final Test: Evaluate an observatio nal study and discuss it in term of differences from CTs (1 hr) 2) Live session: Problembased case followed by a case study discussion (1 hr 40') Educationa l test (15') Sub-topic 14.3 The lesson learned by the off-label use of medicines Live session (group activity and web discussion, 1 hr 40') 15.1 Introduction to HTA Deliverables from Instructors Prepare one (max 20') videopresenta tion on the 3) Prepare the final Educational test (1 hr ) 4) Prepare the live session (group activity and web discussion, 1 hr 40') Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Notes on Instructional Material Videopresenta tion, Videopresenta tion, Timin g Week 10 hrs (studen t) 7 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 76

77 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal Assessme nt by Sub-topic Deliverables from Instructors Notes on Instructional Material Timin g hrs (studen t) Martin Offringa Fedele Bonifazi Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentatio n, 20'); 3) Postreading Educationa l test (15') Discuss the structure of a SR. Posted on line and comments added by other students (1 hr) 2) Preparatio n of presentati 15.2 Paediatric systematic reviews 15.3 Economic evaluations Live session (group activity and web discussion, 1hr) Prepare one (max 20') videopresenta tion on the 3) Prepare the Educational test (15') Prepare one (max 20') videopresenta tion on the 3) Prepare the final Educational test (1 hr ) 4) Prepare the Videopresenta tion, Videopresenta tion, D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 77

78 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructo r Instructio nal Assessme nt by on on all aspects of Unit (30') 3) Live session (group activity and web discussion (1 hr) Sub-topic Deliverables from Instructors live session (group activity and web discussion, 1 hr) Notes on Instructional Material Timin g hrs (studen t) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 78

79 MODULE 5 Module 5: Paediatric Drug Formulations CURRICULUM MAP Unit Fresher week 1. Introduction Introduction 1. Introduction [10h] Lead Instruc tor Catherin e Tuleu tbc Comp et. 1 and 2 1 and 2 Bloo m Topic 2 1a. Basics of paediatric formulation development. 2 1a. Introduction to paediatric formulation development. Instructiona l method F2F lecture with Q&A Pre-reading [2] Recorded and glossary of y [1] Webinar on Palatable drug products [1] Assessment by MCQ test 1a.Group activity (explore experiences of parents/non parents in the group of e.g. at what age a child can take a tablet ) through a web discussion [1] 1b. Give a brief outline of the main issues in paediatric formulation. Quiz with on Deliverables from Instructors 1. Prepare F2F lecture with anticipated Q&A 2. Prepare and upload MCQ test and answers 1. Prereading list and web links 2. recorded and glossary of y. 3. Webinar on Palatable drug products Jun 2013) 4. Moderate web discussion 5. Formulations Stag e Fresh er week Week 1 hrs (stude nt) 2 6 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 79

80 Unit Lead Instruc tor Comp et. Bloo m Topic Instructiona l method Assessment by line answers. [1] Deliverables from Instructors quiz and answers. Stag e hrs (stude nt) Module tutor 1b.Module orientation and planning, including development of a portfolio of resources. Webinar discussion [1] n/a 1. Webinar discussion Week 1 1 Paediatric Drug delivery appraise and demonstrate the place of the paediatric formulation in achieving compliance/ adherence and concordance with drug therapy 2. Paediatric drug delivery [27h] Module tutor Tony Nunn 1 and 2 1c. Selection of a (innovative) drug delivery system as subject of final assessment Age-adapted dosage forms for children Pre-reading [2] Individual teleconferenc e [1] Pre-reading [3] Recorded [1] Webinar on ageappropriate dosage forms [1] Individual reading [2] n/a Select three different oral dosage forms and compare and contrast their suitability for different age groups - short report handed in on line [3] 1. Individual TC's 1. Prereading list and web links 2. Recorded 3. Webinar on ageappropriate dosage forms by J Breikreutz Nov 2012) 4. Assess short report Week 1 Week D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 80

81 Review 1 Prepare for summative assessment Unit Lead Instruc tor Sara Arenas Sara Arenas Module tutor Comp et. Bloo m Topic 3. Special needs of neonates 4. Drug administration, devices and packaging Review of progress and preparation for final assessment Instructiona l method Pre-reading [3] Recorded [1] 2 x Video [1] Individual reading [2] Pre-reading [2] Recorded [1] Individual reading [2] Individual discussion analysing requirements of final assessment and feedback to student from tutor (informed in week. Assessment by Questions around case scenario with problematic medicine (e.g. phenobarbital). Write & post answers, commentary 1000 words [3] Calculations test [1] and brief scenarios illustrating potential problems with answers posted and commentary then on line [1] Deliverables from Instructors 1. Prereading list and web links 2. Recorded 3. Videos (x 2) 4. Case scenarios and questions 5. Assess answers to questions and short report 1. Prereading list 2. Recorded 3. Calculations test and scenarios 4. moderate commentary 1. Individual TC's Stag e Week 3 Week 4 End of week 4 hrs (stude nt) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 81

82 Paediatric Biopharmaceuticsa ppraise the interaction between biological, physicochemical and pharmaceutical factors that influence drug disposition. Unit 3. Paediatric biopharmace utics [18h] Lead Instruc tor H Batchelo r Jenny Duncan with Catherin e Tuleu Comp et. Bloo m Topic 1, 2, Bioavailability - Pharmaceutical factorsincludinginfluence of food/beverages/age/devel opment 6. Modification of dosage forms Instructiona l method Pre reading [3]Recorded [1]Individual reading [2] Pre-reading [3] Recorded webinar on Modification of Dosage Forms [1] Individual reading [2] Assessment by Prepare a report on patient and dosage form features that may influence rate and extent of absorption from the gut [4] Questions around brief scenarios illustrating common modifications to dosage forms (both manipulation and compounding) and potential problems [1]. Answers posted and commentary then on line [1] Deliverables from Instructors 1. Prereading list2. Recorded (webinar recorded Oct 13)3. Assess reports 1. Prereading list 2. Webinar on Modification of Dosage Forms by D Woods Apr 13) 3. Questions and scenarios 4. moderate commentary Stag e Week 5 Week 6 hrs (stude nt) 10 8 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 82

83 Pharmaceutical safety and risk management appraise pharmaceutical factors that optimises safe and effective treatment Review 2 Prepare for summative assessment Unit 4. Pharmaceutic al safety and risk management [10h] Lead Instruc tor Jenny Duncan with Catherin e Tuleu Module tutor Comp et. Bloo m Topic 1, 2, Formulation problems and safety (to include excipients and medication errors linked to formulations) Review of progress and advanced preparation for final assessment Instructiona l method Pre reading [3] Webinars on -Excipients in neonates [1] Webinar on palatability/ta ste-masking [1] Individual discussion analysing requirements of final assessment and feedback to student from tutor Assessment by 7a. Write a commentary on safety of propylene glycol as an excipient in medicines for babies and infants (1000 words). Posted on line and comments added by other students [3] 7b. Calculations test illustrating medication error issues e.g. 10x overdoses and paracetamol injection with answers posted and commentary then on line [2] n/a Deliverables from Instructors 1. Prereading list 2. Webinar on - Excipients in neonates Jan 2013) 3. Webinar on palatability/ta ste-masking Jun 2013) 4. Calculations test and answers 5. Assess report and comments 1. Individual TC's Stag e Week 7 End of week 7 hrs (stude nt) 10 3 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 83

84 Quality of paediatric medicinal products analyse the requirements of regulation and directives with regards to quality of paediatric medicinal products Summative assessment for the whole moduledemonstrate Unit 5. Quality of paediatric medicinal products [17h] 6. Summative assessment [12h] Lead Instruc tor Piotr Kozarew icz Mandy Wan Catherin e Tuleu Comp et. 1, 2, 4, 5 1, 2, 4, 5 Bloo m Topic 4 8. Quality in relation to PIP (including EMA/ICH/FDA and WHO guidance on paediatric pharmaceutical development) 9. GMP/GCP and Clinical trials (including IMP) Pharmaceutical research and innovative drug delivery Instructiona l method Pre reading [3] Recorded [1] Individual reading [3] Pre reading [3] Recorded [1] Individual reading [3] Directed reading and personal investigation Assessment by Incorporated in module assessment (week 10) with a report taking account of the requirements for a successful quality section of the PIP Scenario (e.g. the early use of co-amoxiclav for at risk children with influenza) around pharmaceutical aspects of clinical trial design on line discussion forum (assessed) [3] Prepare a structured report on a formulation Deliverables from Instructors 1. Prereading list 2. Webinar recorded (Feb 2014) 3. Assess report 1. Prereading list 2. Recorded (Feb 2014) 3. Assess discussion 1. Reading list2. Outline search strategy3. Stag e Week 8 Week 9 Week 10(a nd durin hrs (stude nt) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 84

85 how neonatal and paediatric issues can be taken into account when evaluating an innovative formulation Unit Lead Instruc tor Atieno Ojoo and Helena Lutescia Comp et. Bloo m Topic 11. Special needs of developing countries, including WHO formulation guidance. Instructiona l method of the literature electronically. Assessment by innovation or problematic formulation identified by the student and tutor with identification of pros and cons. The report will draw upon presented in formative assessments and take into account information learnt from topics supporting the learning outcomes of this module. It will include information in note form that would address issues of regulatory importance and will also identify issues to resourcepoor countries.altern ative group work with first group building Deliverables from Instructors Stag e Assess report g week s 1-9) hrs (stude nt) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 85

86 Unit Lead Instruc tor Comp et. Bloo m Topic Instructiona l method Assessment by a case, second group solving the problems with first group assessing the second and feeding back (and vice versa). Deliverables from Instructors Stag e hrs (stude nt) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 86

87 MODULE 6 Module 6: Paediatric Clinical Trial Management CURRICULUM MAP for Module Identify the optimal approach to resourceand risk- management for a clinical trial Reconcile the requirements for ethics and regulatory approvals in multiple jurisdictions Assessment 1 Enabling Competency for Masters Program (see below) Develop a study protocol for a paediatric drug study Demonstrate an understanding of regulatory environment pertaining to paediatric drug studies. Bloom Level (1-6) Instructional 4 Prepare an outline clinical trial management plan (resources and riskmanagement) providing a critical commentary on the options 4 Compare regulatory requirements in the student s home jurisdiction and two others with contrasting perspectives [webased discussions and personal reflection] Timing (When in the module is this learning objective Assessment taught? Is it linked to another learning objective?) See Assessment 1. Week word summary for faculty assessment to be submitted by the end of week 5. Assess a colleague s outline trial plan with Week 3 Assessment of colleague s work by D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 87

88 for Module Interpret the needs of multiple sites as they plan to open a clinical trial and develop individualized trial opening plans for sites. Contrast the needs of multiple sites and prepare individualized close down plans Select the most appropriate ways to engage children, young people and families in a range of clinical trials Enabling Competency for Masters Program (see below) Develop a study protocol for a paediatric drug study Develop a study protocol for a paediatric drug study Build good partnerships with regulatory bodies, pharmaceutical companies, patients, families, industry, patient advocate Bloom Level (1-6) Instructional 5 Use the risk management plan developed in Week 1 to identify strengths and weaknesses of a number trial sites and propose a plan 5 Use the risk management plan developed in Week 1 to identify strengths and weaknesses of a number trial sites and propose a plan 6 Self-directed learning to identify sources of information (searches seeded by Faculty) Assessment critical commentary on key areas and risks for the trial [Formative, feedback predominantly from colleagues with some mediation from Faculty] 1000 word summary and spreadsheet of tasks to be submitted Essay to compare, contrast and evaluate strategies for engagement citing real-world examples. [Summative] to be submitted by the end of Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) end of Week 3. Week 4-5 Week 6 Week 7 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 88

89 for Module Assessment 2 Revision Discriminate between well-performing sites and poorly-performing sites and develop individualized performance management plans for sites. Enabling Competency for Masters Program (see below) organizations and others. (this also maps on to key competency # Use metrics and frameworks to gauge impact of their dissemination and research efforts. Bloom Level (1-6) Instructional Revise for assessment. Contrast different metrics used to monitor clinical trials by a range of Sponsors and networks Assessment week 9. Assess a colleague s trial opening and closing plan with critical commentary on key areas and risks for the trial [Formative, feedback predominantly from colleagues with some mediation from Faculty] 6 Simulated assessment of a clinical trial using data from a real trial. Two hour review of a scenario presented in stages, with the student taking the role of the Sponsor. Short notes answers to a series of questions. Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) Assessment of colleague s work by end of Week 8. Weeks 8 and 9 Week 10 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 89

90 for Module Enabling Competency for Masters Program (see below) Bloom Level (1-6) Instructional Assessment Early questions in the scenario to include proposed risk management plans to mitigate issues that arise and how those plans are adapted. [Summative] Timing (When in the module is this learning objective taught? Is it linked to another learning objective?) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 90

91 MODULE 7 Module 7: Post-licensure paediatric drug evaluation: Pharmacovigilance & Pharmacoepidemiology CURRICULUM MAP learning objective number learning objectives Topic Bloom Topics Teacher timing sequence hours Instructional methods status 1 To recognize the differences between adults and children regarding safety of medicines 1 introduction to learning objective How differences in Pk/PD may lead to safety issues C. Ferrajolo week 1 0,15 prerecorded lecture John van den Anker Week 1 3 pre-read: 1 hour; prerecorded lecture 30'; post-read 1.5 hours 3 2 How off label drug use may lead to safety issues in children Antonio Clavenna Week 1 3 pre-read: 1 hour; prerecorded lecture 30'; post-read 1.5 hours recorded lecture from ICPE (ask approval) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 91

92 learning objective number learning objectives Topic Bloom Topics Teacher timing sequence hours Instructional methods status 4 2 How medication errors may leadt to safety issues in children S. Conroy Week 1 3 pre-read: 1 hour; prerecorded lecture 30'; post-read 1.5 hours recorded lecture from ICPE (ask approval) 5 2 Assessment Week 2 5 self-study & online quiz 6 topic 1 review C. Ferrajolo week 2 1 live session learning objective 1 2 To explain Pediatric Pharmacovigilance Guidelines & Risk management plans from regulatory perspective 1 introduction to learning objective History of adverse drug reactions and subsequent regulations 15,15 Sabine Straus week 3 0,15 prerecorded lecture Sabine Straus week 3 3 pre-read: 1 hour; prerecorded lecture 30'; post-read 1.5 hours D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 92

93 learning objective number learning objectives Topic Bloom Topics Teacher timing sequence hours Instructional methods status 3 2 Explain the pediatric legislation and requirements Agnes St Raymond week 3 0,5 lecture 30' 4 2 Why separate pharmacovigilance guidance for children 5 2 Industry perspective to pediatric regulations in US & EC Sabine Straus week 4 3 pre-read: 1 hour; prerecorded lecture 30'; post-read 1.5 hours C de Luise week 4 3 pre-read: 1 hour; lecture 30'; post-read 1.5 hours recorded lecture from ICPE (ask approval) 6 2 Assessment Week 4 5 self-study & online quizz 7 topic 2 review S. Straus Week 4 1 live session learning objective 2 15,65 3 To explain and understand principles of identifying and 1 introduction to learning objective 3 Katia Verhamme week 5 0,15 prerecorded lecture D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 93

94 learning objective number learning objectives Topic Bloom Topics Teacher timing sequence hours Instructional methods status recognizing adverse events and safety signals 2 2 To explain adverse drug events and reactions 3 3 To be able to detect, recognize and write paediatric adverse events in trials 4 4 To assess paediatric specific causality algorithms and recognize why adult algorithms may not apply 5 4 To apply causality assessment algorithms for paediatric ADEs Katia Verhamme Madlen Gazarian Madlen Gazarian Jan Bonhoeffer / Madlen Gazarian week 5 2 pre-read: 1.5 hours; prerecorded lecture 30' week 5 4,5 Prerecorded lecture 30'; Exercise case study: 4 hours week 5 6,5 pre-read 1 hour; Prerecorded lecture 30'; Exercise critique: 5 hours week 6 10 exercise of classifying case reports D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 94

95 learning objective number learning objectives Topic Bloom Topics Teacher timing sequence hours Instructional methods status 6 4 To explain and apply signal detection methods for spontaneous reports Katia Verhamme / Caitlin Dodd week 6 5,5 Pre-read: 1 hour Prerecorded lecture: 30 minutes; post read 1 hour; exercise 3 hours 7 Assessment 5 self-study & online quizz 8 topic 3 review Katia Verhamme week 7 1 live session learning objective 3 34,65 4 To explain and apply epidemiological measures, principles and study designs 1 introduction to learning objective 4 Miriam Sturkenboom week 8 0,15 prerecorded lecture D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 95

96 learning objective number learning objectives Topic Bloom Topics Teacher timing sequence hours Instructional methods status 2 3 To explain the methods to assess occurrence of disease and principles of pediatric (pharmaco)epidemiology 3 3 To explain epidemiological study designs, measures of association & bias 4 2 Examples of pediatrics studies Miriam Sturkenboom / Yolanda Brauchli Miriam Sturkenboom Miriam Sturkenboom week 8 10 pre-read: 3 hours; 2 prerecorded lectures 30' each; postread: 3 hours; exercises 3 hours week 9 12 Pre-read; 3 hours; prerecorded lecture: 3 hours; postread 6 hours week 9 2 Prerecorded lecture 30'; post-read 1.5 hours 5 4 To critique a pediatric pharmacoepidemiological paper Yolanda Brauchli week 9 6 Exercise 6 hours D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 96

97 learning objective number learning objectives Topic Bloom Topics Teacher timing sequence hours Instructional methods status 6 3 To explain the role of pharmacoepidemiology in pediatric medicines research Madlen Gazarian week 10 3 Pre-read: 2 hours; prerecorded lecture 1 hour 7 2 To understand the need for studies in critically ill patients Saskia de Wildt week 10 0,5 Prerecorded lecture recorded lecture from ICPE (ask approval) 8 Assessment 5 self-study & online quizz 9 Topic 4 review Miriam Sturkenboom week 10 1 learning objective 4 39,65 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 97

98 MODULE 8 Module 1: Pharmacology in pregnancy and in neonates CURRICULUM MAP for Module At the end of the module the student will be able to: Bloom Level (1-6) Topics to achieve Refresher Meeting 1 Master objective, items and virtual learning environment Describe epidemiology data over the world on birth rate, maternal and neonatal diseases, prematurity, risks and outcome (mortality or sequelae), specific medical needs 2 V. Biran 1. Pregnancy and neonates over the world Enabling Competency for Masters Program (see below) Instructional 1 Face to face lessons on the occasion of the fresher week 1 Pre reading Recorded Assessment Simulation of multiple choice tests Group discussions to summarise recent epidemiology data over the world on birth rate, maternal and neonatal diseases, prematurity, risks and outcome (mortality or sequelae), specific medical needschanges in the neonatal population worldwide Timing / hours (When in the module is this learning objective taught? Is it linked to another learning objective?) Week 0 Week 1 : 10h Pre and post reading / learning : 6h 1h Meet the professor 2h Multiple choice 1h D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 98

99 Describe the physiological changes occuring during pregnancy and impact on drug disposition Analyse factors affecting placental drug transfer and methods of quantification (in vivo ex-vivo) 4 Elisa Llurba Magi Farre 2. Maternal physiological changes and pharmacokinetic consequences during pregnancy. Placental transfer 3, 4, Pre-reading of review chapters Recorded Selected publications Summary and documents on selected publications Quizz with online responses Case study to calculate placental drug transfer Week 2 Pre and post reading / learning : 5h 1h Personal work (report) : 2h Meet the professor : 1h Multiple choice :1h Quantify placental drug transfer List of factors associated with PK variability in neonates Describe ante and perinatal maturation of metabolic and renal eliminations Interpret the potential impact of neonatal diseases Discuss the use of modelisation in developmental pharmacokinetics 4 EJA 3. Neonatal drug disposition and effects according to neonatal age groups 1, 2, 4 Pre-readings of review articles Recorded Quizz with online responses on ADME In neonates and impact of age, formulations Group discussions to identify and explain PK differences observed within neonatal groups accoding to drug properties and PK in adults Case study : Calculate PK parameters and comment on dosage adaptation of different drugs Week3 Pre and post reading / learning : 6h 1h Meet the professor 2h Multiple choice 1h D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 99

100 Define teratogenicity and foetotoxicity Recognize the need for preclinical studies Recognize the need for long term safety studies, the methodologies and the difficulties to organize them Describe all issues related to formulations Understand clinical issues related to formulations Illustrate the mechanisms of milk transfer and how to quantify it 2 O.Garcia- Algar 2 S.Ito 4. Drug toxicity during pregnancy Drug toxicity in neonates Including Neonatal effects of drugs administered during pregnancy 5. Specific issues of drug administration in neonates Drug exposure through breastfeeding 1, 2, 4, 5 Pre-readings Recorded Directed readings and litterature review 1,2 Recorded (with short summary of previous knowledge) Directed readings and litterature review Analyse and report on guidelines for teratogenicity and foetotoxicity evaluation Group work : Report on «historical exemples of major teratogens Group work : Report on historical examples of drug toxicity (pregnancy and neonates) Quizz to summarize all specific issues related to formulations in neonates Exercises : drug dilutions and volume of administration in neonates Explain with examples the risks of cutaneous exposure in neonates Week 4 Pre and post reading / learning : 6h 1h Meet the professor 2h Multiple choice 1h Week 5 Pre and post reading / learning : 6h 1h Meet the professor 2h Multiple choice 1h Week 6 Pre and post reading / learning : 6h 1h Meet the professor 2h Multiple choice 1h Discuss the advantages and potential risks of breastfeeding D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 100

101 Analyse the risk/benefit ratio for the mother and the fetus/neonate in selected maternal conditions Differenciate the impact of disease and treatment in pregnancy outcome Understand all regulatory documents / recommendations for drug evaluation in neonates Understand the specificities of Ethics in neonates and the role of patients associations Analyse the context and objectives of drug evaluation and the resulting impact on study design and results 4 E. Llurba R. de la Torre M.Rodriguez F. Cabañas M. Vento Van Den Anker 6. Drug administration and evaluation during pregnancy 1.Maternel conditions 2. Fetal conditions 7. Drug trials in neonates Identification of medical needs, ologies adapted to small numbers Ethical issues 8. Drug evaluation in specific therapeutic areas ( from the evaluation of surfactant in neonates : a case study 1, 2, 4, Recorded 1, 5, 6 1, 2, 5 Selected readings Recorded Directed readings and litterature review Group discussions on the physiopathology of diseases and evaluation of risk / benefit ratio in selected conditions : Epilepsy, Congenital adrenal hyperplasia and hypothyrodism, Alcool, Illicit drugs Group discussions To develop a pharmacokinetic protocol in neonates Group discussions Short reports (1000 words) on selected publications on each topic to summarize data, comment on design and quality, evidence based conclusions Week 7 Pre and post reading / learning : 6h 1h Meet the professor 2h Multiple choice 1h Week 8 Pre and post reading / learning : 4h 1h Personnal work : 2 Meet the professor 2h Multiple choice 1h NSAIDs and the developmental D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 101

102 Analyse the context and objectives of drug evaluation and the resulting impact on study design and results Analyse the context and objectives of drug evaluation and the resulting impact on study design and results 4 Biran EJA Wei JvdAnker kidney 9. Drug evaluation in specific therapeutic areas (2) Developmental pharmacology of analgesics and sedatives in neonatal care. Pain evaluation, Therapeutic use 10. Drug evaluation in specific therapeutic areas (3) Neonatal infections : which studies for a safe administration? 1, 2, 5 1, 2, 5 Recorded Directed readings and litterature review Recorded Directed readings and litterature review Group discussions Short reports (1000 words) on selected publications on each topic to summarize data, comment on design and quality, evidence based conclusions Group discussions Short reports (1000 words) on selected publications on each topic to summarize data, comment on design and quality, eidence based conclusions Week 9 Pre and post reading / learning : 6h 1h Pre and post reading / learning : 6h 1h Meet the professor 2h Personal work : 2hMultiple choice 1h Week10 Pre and post reading / learning : 6h 1h Meet the professor 2h Multiple choice 1h D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 102

103 MODULE 9 Module 9: Biomarkers and Innovative tools in paediatric clinical pharmacology CURRICULUM MAP for Module Fresher Meeting Understan d Master objective, items, and virtual learning environme nt Understan d about innovative approache s for conducting clinical trials in children Bloo m Leve l (1-6) Topics to achieve 1 Master objective, items, and virtual learning environment 4 1. Issues in designing clinical studies in specific paediatric conditions Enabling Compete ncy Lead Instructor 1 Oscar Della Pasqua/ Flora Musuamba Instructio nal Face to face lessons on the occasion of the Fresher Week 1,2,4 M. Cella Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading Assessm ent by Simulatio n of multiple choice test Multiple choice test Sub-topic Introduction to the Module 1.1. Issues in designig studies in paediatrics Deliverable s from Instructors Prepare F2F lecture with anticipated Q&A and upload MCQ test and answers Prepare one (max 20') videopresent ation on the Notes on Instructiona l Material Videopresent ation, weblinks, etc.) Timi ng Week 0 Week 1 hrs (stude nt) 4 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 103

104 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructor Instructio nal (20') Assessm ent by Sub-topic Deliverable s from Instructors Notes on Instructiona l Material Timi ng hrs (stude nt) M. Cella Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading (20') M. Cella Prereading by glossary of y (20'); 2) presentati on, 20'); Multiple choice test Multiple choice test 1.2. Challenges in designing trials in paediatrics 1.3. Regulatory trials (PIP) Prepare one (max 20') videopresent ation on the Prepare one (max 20') videopresent ation on the Videopresent ation, weblinks, etc.) Videopresent ation, weblinks, etc.) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 104

105 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructor Instructio nal 3) Postreading (20') Assessm ent by Sub-topic Deliverable s from Instructors Notes on Instructiona l Material Timi ng hrs (stude nt) M. Cella Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading (20') Multiple choice test and group activity through a web discussion 1.4. Innovative tools: PKPD modelling. Prepare one (max 20') videopresent ation on the 3) Multiple choice test and group activity through a web discussion 4) Meet the Professor Videopresent ation, weblinks, etc.) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 105

106 for Module Understan d about innovative approache s for conducting clinical trials in children Bloo m Leve l (1-6) Topics to achieve 6 2. PK/PD modeling, simulation and application to dose finding in paediatric drug development Enabling Compete ncy Lead Instructor 1,2,3 (Flora Musuamba/G érard Pons) Emmanuelle Comets Instructio nal Prereading by glossary of y (30'); 2) presentati on, 20'); 3) Postreading Prereading by glossary of y (30'); 2) presentati on, 20'); 3) Postreading Assessm ent by Multiple choice test and group activity through a web discussion Multiple choice questions and exercises Sub-topic 1.1. Application of PK/PD modelling and simulation to extrapolation from adult to children 1.2. PK/PD modeling and simulation and application to dose finding Deliverable s from Instructors Prepare one (max 20') videopresent ation on the Prepare one (max 20') videopresent ation on the 3) Multiple choice questions and exercises 4) Meet the Professor Notes on Instructiona l Material Videopresent ation, weblinks, etc.) Videopresent ation, weblinks, etc.) Timi ng Week 1 hrs (stude nt) 4 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 106

107 for Module Understan d about innovative approache s for conducting clinical trials in children Bloo m Leve l (1-6) Topics to achieve 4 3. Application of clinical trial simulations, bridging and extrapolation methods to assessment of drug efficacy and safety in paediatrics Enabling Compete ncy Lead Instructor 2,3,4,7 Terry Sheppard Terry Sheppard Instructio nal Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading Assessm ent by Multiple choice questions and exercises Multiple choice questions and exercises Sub-topic 3.1 Acceptable methods for assessment of drug efficacy in paediatrics 3.2 Acceptable methods for assessment of drug safety in paediatrics Deliverable s from Instructors Prepare one (max 20') videopresent ation on the Prepare one (max 20') videopresent ation on the Notes on Instructiona l Material Videopresent ation, weblinks, etc.) Videopresent ation, weblinks, etc.) Timi ng Week 2 hrs (stude nt) 5 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 107

108 for Module Understan d about innovative approache s for conducting clinical trials in children Bloo m Leve l (1-6) Topics to achieve 6 4. Statistical (innovative) tools to improve study designand to optimize study sample size in paediatrics Enabling Compete ncy Lead Instructor Terry Sheppard Instructio nal Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading 1,3,4 P. Baiardi Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading Assessm ent by Test with answers posted and comment ary then online (1 hr) 2) Meet the Professor Multiple choice questions and exercises Sub-topic 3.3 Acceptable methods for benefit/risks assessment of drug in paediatrics 4.1. adaptive designs and sequential methodologic al approaches to improve study design in paediatrics Deliverable s from Instructors Prepare one (max 20') videopresent ation on the 3) Multiple choice questions and exercises 4) Meet the Professor Prepare one (max 20') videopresent ation on the Notes on Instructiona l Material Videopresent ation, weblinks, etc.) Videopresent ation, weblinks, etc.) Timi ng Week 2 hrs (stude nt) 5 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 108

109 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructor Instructio nal P. Baiardi Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading Eric Belissant Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading Assessm ent by Multiple choice questions and exercises Prepare a short report to evaluate safety and efficacy in specific children conditions 2) Meet the Professor Sub-topic 4.2. Bayesan approach to improve study design in paediatrics 4.2. Sample size computation in optimized trial in paediatrics Deliverable s from Instructors Prepare one (max 20') videopresent ation on the Prepare one (max 20') videopresent ation on the 3) Prepare a short report to evaluate safety and efficacy in specific children conditions Notes on Instructiona l Material Videopresent ation, weblinks, etc.) Videopresent ation, weblinks, etc.) Timi ng hrs (stude nt) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 109

110 for Module Identify the requireme nts and opportuniti es for the use of biomarkers in the evaluation of efficacy and safety in paediatric diseases Bloo m Leve l (1-6) Topics to achieve 4 5. Biomarkers definition and rationale for the implementatio n of a biomarkerguided approach in paediatric drug research Enabling Compete ncy Lead Instructor 2,3,4,7 Oscar Della Pasqua/ Flora Musuamba Oscar Della Pasqua/ Flora Musuamba Instructio nal Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading Assessm ent by Multiple choice questions and exercises Multiple choice questions and exercises Sub-topic 5.1. Use of Biomarkers in drug development 5.2. requirements and opportunities for the use of biomarkers in paediatric drug research Deliverable s from Instructors 4) Meet the Professor Prepare one (max 20') videopresent ation on the Prepare one (max 20') videopresent ation on the Notes on Instructiona l Material Videopresent ation, weblinks, etc.) Videopresent ation, weblinks, etc.) Timi ng Week 3 hrs (stude nt) 6 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 110

111 for Module Identify the requireme nts and opportuniti es for the use of biomarkers in the evaluation of efficacy and safety in Bloo m Leve l (1-6) Topics to achieve 4 6. Biomarkers based on pharmacogene tics and other omics advancement Enabling Compete ncy Lead Instructor Oscar Della Pasqua/ Flora Musuamba 2,3,4,7 Evelyne Jacqz-Agrain Instructio nal Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading Prereading by glossary of y (30'); 2) presentati on, 20'); 3) Post- Assessm ent by Provide an example of biomarker s use for therapeut ic managem ent and for drug developm ent 2) Meet the Professor Case study from literature 2) Meet the Professor Sub-topic 5.3. Challenges for the use of biomarkers in paediatric drug research 6.1. Role of pharmacogen etics in drug development Deliverable s from Instructors Prepare one (max 20') videopresent ation on the 3) Provide an example of biomarkers use for therapeutic management and for drug development 4) Meet the Professor Prepare one (max 20') videopresent ation on the Notes on Instructiona l Material Videopresent ation, weblinks, etc.) Videopresent ation, weblinks, etc.) Timi ng Week 3-4 hrs (stude nt) 5 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 111

112 for Module paediatric diseases Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructor Instructio nal reading Assessm ent by Sub-topic Deliverable s from Instructors Notes on Instructiona l Material Timi ng hrs (stude nt) Identify the requireme nts and opportuniti es for the use of biomarkers in the evaluation 6 7. Predictive vs. prognostic value of biomarkers Evelyne Jacqz-Agrain 2,3,4 Bart LAURIJSSENS Prereading by glossary of y (30'); 2) presentati on, 20'); 3) Postreading Prereading by glossary of y (30'); 2) Case study from literature 2) Meet the Professor Case study from literature 2) Meet the Professor 6.2. Biomarkers based on pharmacogen etics and other omics advancement 7.1. Prognostic biomarkers in drug development Prepare one (max 20') videopresent ation on the 3) Case study from literature 4) Meet the Professor Prepare one (max 20') videopresent ation on the Videopresent ation, weblinks, etc.) Videopresent ation Week 4 5 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 112

113 for Module of efficacy and safety in paediatric diseases Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructor Instructio nal presentati on, 20'); 3) Postreading Assessm ent by Sub-topic Deliverable s from Instructors Notes on Instructiona l Material, weblinks, etc.) Timi ng hrs (stude nt) Identify the requireme nts and opportuniti es for the use of biomarkers in the evaluation 4 8.Biomarkers use to demonstrate pharmacology /efficacy Bart LAURIJSSENS 2,3,4 Bart LAURIJSSENS Prereading by glossary of y (30'); 2) presentati on, 20'); 3) Postreading Prereading by glossary of y (30'); 2) Case study from literature 2) Meet the Professor Case study from literature 2) Meet the Professor 7.2. Predictive biomarkers in drug development 8.1. Biomarkers of drug efficacy (I): Concept and rationale Prepare one (max 20') videopresent ation on the 3) Case study from literature 4) Meet the Professor Prepare one (max 20') videopresent ation on the Videopresent ation, weblinks, etc.) Videopresent ation Week 5 4 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 113

114 for Module of efficacy and safety in paediatric diseases Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructor Instructio nal presentati on, 20'); 3) Postreading Assessm ent by Sub-topic Deliverable s from Instructors Notes on Instructiona l Material, weblinks, etc.) Timi ng hrs (stude nt) Identify the requireme nts and opportuniti es for the use of biomarkers in the 4 9.Biomarkers use to study safety/ toxicity Bart LAURIJSSENS 2,3,4 Stephen McWilliam Prereading by glossary of y (30'); 2) presentati on, 20'); 3) Postreading Prereading by glossary of y (20'); 2) Case study from literature 2) Meet the Professor Case study analysis of a specific age group 2) Meet the 8.1. Biomarkers of drug efficacy (II): examples 9.1. Biomarkers of drug safety (I): Concept and rationale Prepare one (max 20') videopresent ation on the 3) Case study from literature 4) Meet the Professor Prepare one (max 20') videopresent ation on the Videopresent ation, weblinks, etc.) Videopresent ation Week 5 5 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 114

115 for Module evaluation of efficacy and safety in paediatric diseases Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructor Instructio nal presentati on, 20'); 3) Postreading Assessm ent by Professor Sub-topic Deliverable s from Instructors Notes on Instructiona l Material, weblinks, etc.) Timi ng hrs (stude nt) Stephen McWilliam Stephen McWilliam Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentati on, 20'); Case study analysis of a specific age group 2) Meet the Professor Case study analysis of a specific age group 2) Meet the Professor 9.2. Biomarkers of drug safety (II): Concept and rationale 9.3. Biomarkers of drug safety (III): Applications Prepare one (max 20') videopresent ation on the Prepare one (max 20') videopresent ation on the Videopresent ation, weblinks, etc.) Videopresent ation, weblinks, etc.) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 115

116 for Module Demonstra te sound understan ding of the medical decisionmaking process when using biomarkers to infer efficacy and safety of drugs in children Bloo m Leve l (1-6) Topics to achieve 4 10.Surrogate endpoint validation, including examples of successful & failed surrogate endpoints Enabling Compete ncy Lead Instructor Maria Isaac Maria Isaac Instructio nal 3) Postreading Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Post- Assessm ent by Prepare a short report listing example of successful & failed surrogate endpoints 2) Meet the Professor Prepare a short report listing example of successful & failed surrogate endpoints 2) Meet Sub-topic ologic al aspects of surrogate endpoint validation (I) ologic al aspects of surrogate endpoint validation (II) Deliverable s from Instructors 3) Case study analysis of a specific age group 4) Meet the Professor Prepare one (max 20') videopresent ation on the Prepare one (max 20') videopresent ation on the Notes on Instructiona l Material Videopresent ation, weblinks, etc.) Videopresent ation, weblinks, etc.) Timi ng Week 6 hrs (stude nt) 5 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 116

117 for Module Demonstra te sound understan ding of the medical decisionmaking process when using Bloo m Leve l (1-6) Topics to achieve Statistical aspects and the role of meta-analysis as a tool for the biomarkers validation Enabling Compete ncy Lead Instructor Maria Isaac Instructio nal reading Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading 2,3,4 Sarah Walker Prereading by glossary of y (20'); 2) Assessm ent by the Professor Prepare a short report listing example of successful & failed surrogate endpoints 2) Meet the Professor Prepare a short report (1000 words). Posted online and comment s added Sub-topic Surrogate endpoint validation: examples of successful & failed surrogate endpoints Biomarkers validation: role of metaanalysis (I) Deliverable s from Instructors Prepare one (max 20') videopresent ation on the 3) Prepare a short report listing example of successful & failed surrogate endpoints 4) Meet the Professor Prepare one (max 20') videopresent ation on the Notes on Instructiona l Material Videopresent ation, weblinks, etc.) Videopresent ation Timi ng Week 6 hrs (stude nt) 6 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 117

118 for Module biomarkers to infer efficacy and safety of drugs in children Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructor Sarah Walker Sarah Walker Instructio nal presentati on, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Post- Assessm ent by by other students 2) Meet the Professor Prepare a short report (1000 words). Posted online and comment s added by other students 2) Meet the Professor Prepare a short report (1000 words). Posted online and comment s added by other students Sub-topic Biomarkers validation: role of metaanalysis (II) Role of meta-analysis in biomarker validation: Examples Deliverable s from Instructors Prepare one (max 20') videopresent ation on the Prepare one (max 20') videopresent ation on the 3) Prepare a Notes on Instructiona l Material, weblinks, etc.) Videopresent ation, weblinks, etc.) Videopresent ation, weblinks, etc.) Timi ng hrs (stude nt) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 118

119 for Module Demonstra te sound understan ding of the medical decisionmaking process when using biomarkers to infer efficacy and safety of drugs in children Bloo m Leve l (1-6) Topics to achieve Biomarkers applications as basis for the dose rationale, patient selection and stratification in paediatric clinical trials Enabling Compete ncy Lead Instructor 2,3,4 Oscar Della Pasqua/ Flora Musuamba Oscar Della Pasqua/ Flora Musuamba Instructio nal reading Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading (20') Prereading by glossary of y (20'); 2) Assessm ent by 2) Meet the Professor Multiple choice questions and exercises (1 hr) 2) Meet the Professor Multiple choice questions and exercises (1 hr) 2) Meet Sub-topic Biomarkers and dose rationale in paediatric drug development Biomarkers and patient selection in paediatric drug development Deliverable s from Instructors short report (1000 words). Posted online and comments added by other students 4) Meet the Professor Prepare one (max 20') videopresent ation on the Prepare one (max 20') videopresent ation on the Notes on Instructiona l Material Videopresent ation, weblinks, etc.) Videopresent ation Timi ng Week 7 hrs (stude nt) 7 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 119

120 for Module Demonstra te sound understan ding of the medical decisionmaking process when Bloo m Leve l (1-6) Topics to achieve 5 13.Biomarker response for the therapeutic management of paediatric patients Enabling Compete ncy Lead Instructor Oscar Della Pasqua/ Flora Musuamba 2,3 Oscar Della Pasqua/ Flora Musuamba Instructio nal presentati on, 20'); 3) Postreading (20') Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading (20') Prereading by glossary of y (20'); 2) Assessm ent by the Professor Multiple choice questions and exercises (1 hr) 2) Meet the Professor Multiple choice questions and exercises (1 hr) Sub-topic Biomarkers and patient stratification in paediatric drug development Biomarker response for the therapeutic management of paediatric patients: concepts Deliverable s from Instructors Prepare one (max 20') videopresent ation on the 3) Multiple choice questions and exercises (1 hr) 4) Meet the Professor (1 hr) Prepare one (max 20') videopresent ation on the Notes on Instructiona l Material, weblinks, etc.) Videopresent ation, weblinks, etc.) Videopresent ation Timi ng Week 7 hrs (stude nt) 6 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 120

121 for Module using biomarkers to infer efficacy and safety of drugs in children Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructor Instructio nal presentati on, 20'); 3) Postreading Assessm ent by Sub-topic Deliverable s from Instructors Notes on Instructiona l Material, weblinks, etc.) Timi ng hrs (stude nt) Oscar Della Pasqua/ Flora Musuamba Prereading by glossary of y (20'); 2) presentati on, 20'); 3) Postreading Give a brief outline of the biomarker s response for the therapeut ic managem ent of paediatric patients. Quiz with on line answers 2) Meet the Professor Biomarker response for the therapeutic management of paediatric patients: applications Prepare one (max 20') videopresent ation on the 3) Give a brief outline of the biomarkers response for the therapeutic management of paediatric patients. Quiz with on line answers 4) Meet the Professor Videopresent ation, weblinks, etc.) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 121

122 for Module Discuss the opportuniti es to optimise experimen tal protocols (e.g. patient stratificati on), based on analysis and interpretat ion of biomarker response Bloo m Leve l (1-6) Topics to achieve Biomarkerbased trials design Enabling Compete ncy Lead Instructor 2,3 Oscar Della Pasqua/ Flora Musuamba Oscar Della Pasqua/ Flora Musuamba Instructio nal Prereading by glossary of y (30'); 2) presentati on, 20'); 3) Postreading Prereading by glossary of y (30'); 2) presentati on, 20'); 3) Postreading Assessm ent by Multiple choice questions and exercises (1 hr) Multiple choice questions and exercises 2) Meet the Professor Sub-topic Biomarkerbased trials design: concepts Biomarkerbased trials design: Examples Deliverable s from Instructors Prepare one (max 20') videopresent ation on the Prepare one (max 20') videopresent ation on the 3) Multiple choice questions and exercises 4) Meet the Professor Notes on Instructiona l Material Videopresent ation, weblinks, etc.) Videopresent ation, weblinks, etc.) Timi ng Week 7 hrs (stude nt) 5 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 122

123 for Module Discuss the opportuniti es to optimise experimen tal protocols (e.g. patient stratificati on), based on analysis and interpretat ion of biomarker response Bloo m Leve l (1-6) Topics to achieve 5 15.Extrapolati on of drug effects on biomarkers from adults to children Enabling Compete ncy Lead Instructor Instructio nal 2, 3 M. Cella Prereading by glossary of y (30'); 2) presentati on, 20'); 3) Postreading M. Cella Prereading by glossary of y (30'); 2) presentati on, 20'); 3) Postreading Assessm ent by Multiple choice questions Prepare an example of extrapolat ion of drug effects on biomarker s in children 2) Meet the Professor Sub-topic Implementati on of clinical trials uing biomarkers in adults for later extrapolation in children: concepts Implementati on of clinical trials uing biomarkers in adults for later extrapolation in children: Applications Deliverable s from Instructors Prepare one (max 20') videopresent ation on the Prepare one (max 20') videopresent ation on the an example of extrapolation of drug effects on biomarkers in children 4) Meet the Professor Notes on Instructiona l Material Videopresent ation, weblinks, etc.) Videopresent ation, weblinks, etc.) Timi ng week 8 hrs (stude nt) 5 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 123

124 for Module Discuss the opportuniti es to optimise experimen tal protocols (e.g. patient stratificati on), based on analysis and interpretat ion of biomarker response Bloo m Leve l (1-6) Topics to achieve 5 16.Extrapolati on from short to long term effects of intervention based on biomarkers evaluation Enabling Compete ncy Lead Instructor Instructio nal 2,3 M. Cella Prereading by glossary of y (30'); 2) presentati on, 20'); 3) Postreading M. Cella Prereading by glossary of y (30'); 2) presentati on, 20'); 3) Postreading Assessm ent by Multiple choice questions Multiple choice questions 2) Meet the Professor Sub-topic Implementati on of clinical trials uing biomarkers in short term studies for later extrapolation of long term effects: concepts Implementati on of clinical trials uing biomarkers in short term studies for later extrapolation of long term effects: applications Deliverable s from Instructors Prepare one (max 20') videopresent ation on the Prepare one (max 20') videopresent ation on the 3) Multiple choice questions 4) Meet the Professor Notes on Instructiona l Material Videopresent ation, weblinks, etc.) Videopresent ation, weblinks, etc.) Timi ng week 8 hrs (stude nt) 5 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 124

125 for Module Discuss the opportuniti es to optimise experimen tal protocols (e.g. patient stratificati on), based on analysis and interpretat ion of biomarker response Bloo m Leve l (1-6) Topics to achieve Biomarkers and personalised medicines in children: - Proteomics - Metabolomics - Pharmacogeno mics - etc. Enabling Compete ncy Lead Instructor 1,2 Evelyne Jacqz-Agrain Evelyne Jacqz-Agrain Instructio nal Prereading by glossary of y (30');2) presentati on, 20');3) Postreading Prereading by glossary of y (30');2) presentati on, 20');3) Postreading Assessm ent by Multiple choice questions Multiple choice questions Sub-topic Biomarkers and personalised medicines in children: Concepts Biomarkers and personalised medicines in children: Examples Deliverable s from Instructors Prepare one (max 20') videopresent ation on the 3) Multiple choice questions 4) Meet the Professor Prepare one (max 20') videopresent ation on the 3) Multiple choice questions 4) Meet the Professor Notes on Instructiona l Material Videopresent ation, weblinks, etc.) Videopresent ation, weblinks, etc.) Timi ng week 8 hrs (stude nt) 5 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 125

126 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructor Instructio nal Assessm ent by Sub-topic Deliverable s from Instructors Notes on Instructiona l Material Timi ng hrs (stude nt) Outline the opportuniti es of using biomarkers in order to speed up and facilitate the developme ntal process of paediatric drugs Regulatory Requirements for clinical validity of biomarkers 5 Maria Isaac Prereading by glossary of y (30');2) presentati on, 20');3) Postreading Maria Isaac Prereading by glossary of y (30');2) Multiple choice questions Multiple choice questions Regulatory requirements for clinical validity of biomarkers: concepts Regulatory requirements for clinical validity of biomarkers: Examples Prepare one (max 20') videopresent ation on the 3) Multiple choice questions 4) Meet the Professor Prepare one (max 20') videopresent ation on the Videopresent ation, weblinks, etc.) Videopresent ation week 8 5 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 126

127 for Module Outline the opportuniti es of using biomarkers in order to speed up and facilitate the developme ntal process of paediatric drugs Bloo m Leve l (1-6) Topics to achieve Biomarkers use in disease models to predict treatment outcome (safety and efficacy) Enabling Compete ncy Lead Instructor 3 Stephen McWilliam Stephen McWilliam Instructio nal presentati on, 20');3) Postreading Prereading by glossary of y (30');2) presentati on, 20');3) Postreading Prereading by glossary of y (30');2) Assessm ent by Multiple choice questions Multiple choice questions Sub-topic 19. Biomarkers use in disease models to predict treatment outcome (safety and efficacy): Concepts Biomarkers use in disease models to predict treatment outcome (safety and Deliverable s from Instructors 3) Multiple choice questions 4) Meet the Professor Prepare one (max 20') videopresent ation on the 3) Multiple choice questions 4) Meet the Professor Prepare one (max 20') videopresent ation on the Notes on Instructiona l Material, weblinks, etc.) Videopresent ation, weblinks, etc.) Videopresent ation Timi ng week 8 hrs (stude nt) 4 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 127

128 for Module Outline the opportuniti es of using biomarkers in order to speed up and facilitate the developme ntal process of paediatric drugs Bloo m Leve l (1-6) Topics to achieve Scientific advice and qualification procedures for biomarkers: Cases studies Enabling Compete ncy Lead Instructor 3, 5 Efthymios Manolis Efthymios Manolis Instructio nal presentati on, 20');3) Postreading Prereading by glossary of y (30');2) presentati on, 20');3) Postreading Prereading by glossary of y (30');2) Assessm ent by Multiple choice questions Multiple choice questions Sub-topic efficacy): Examples Regulatory qualification of biomarkers: Concepts Regulatory qualification of biomarkers: Examples Deliverable s from Instructors 3) Multiple choice questions 4) Meet the Professor Prepare one (max 20') videopresent ation on the 3) Multiple choice questions 4) Meet the Professor Prepare one (max 20') videopresent ation on the Notes on Instructiona l Material, weblinks, etc.) Videopresent ation, weblinks, etc.) Videopresent ation Timi ng week 8 hrs (stude nt) 4 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 128

129 for Module Bloo m Leve l (1-6) Topics to achieve Enabling Compete ncy Lead Instructor Instructio nal presentati on, 20');3) Postreading Assessm ent by Sub-topic Deliverable s from Instructors 3) Multiple choice questions 4) Meet the Professor Notes on Instructiona l Material, weblinks, etc.) Timi ng hrs (stude nt) D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 129

130 MODULE 10 Module 10: Paediatric vaccines CURRICULUM MAP for Module Bloom Level (1-6) Instructional Assessment Timing Link time hours/week The Program: Paediatric Immunization programs To describe the basic differences between vaccines and other medicines from a 1 program, product, host, and methodological perspective To Outline Milestones in the history of paediatric vaccines and immunization To review the impact of paediatric immunization on disease epidemiology To describe basic ethical considerations of testing and implementing vaccines : Introduction to differences between 1 paediatric vaccines and other medicines Fresher - program, product, host, and week methodological perspectives : History of Vaccines and 1 Immunization - Evolution of immunization concepts Quiz Week 1 - Aims of Immunization programs, eradication and elimination Background Literature Reading 3 1 : Prevention of disease by paediatric vaccines Quiz Week 1 Background Literature Reading 3 : Ethics of testing and implementing Quiz Week 1 Background Literature Reading D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 130

131 for Module Bloom Level (1-6) Instructional Assessment Timing Link time hours/week The Product: Paediatric Vaccines To classify vaccine components and immunization technologies To outline the main characteristics of development and production To outline the elements of vaccine licensure and registration 2 : Vaccine components and immunization technologies 1 Antigens, adjuvants, and excipients Principles of immunization technologies Quiz Week 2 Background Literature Reading 3 2 : Vaccine development and production Quiz Week Background Literature Reading 3 : Regulatory aspects of vaccine licensure and registration Quiz Week 2 1 Background Literature Reading 3 12 The Host: Paediatric Immune response to Vaccines : Mechanisms of primary immune 1 response To distinguish mechanisms of primary 2 - b-cell responses Quiz Week 3 immune response to paediatric vaccines - t-cell responses Background Literature Reading 3 To summarize immunological mechanisms of immune memory, boosting, and duration of immunity To describe key issues of vaccination in special populations 2 2 : Memory, boosting, and duration of immunity Quiz Week 3 Background Literature Reading 3 : Vaccination in special pediatric populations Quiz Week 3 - neonates 1 1 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 131

132 for Module Bloom Level (1-6) Instructional Assessment Timing time Link - immune compromised 1 hours/week Background Literature Reading 6 16 The Outcome: Measuring effects of vaccines in paediatrics : Quantifying intended effects of To describe the differences between effects, 2 Quiz Week 4 1 vaccines efficacy, and effectiveness Background Literature Reading 3 : Immunological correlates of protection 1 Describe immunological correlates of 2 - antibodies as correlate pf protection protection - other measures of protection Quiz Week 4 Background Literature Reading 3 Illustrate measures of efficacy in paediatric clinical trials To describe the statistical considerations of paediatric vaccine trial design 3 2 : Designing Phase I and II prelicensure safety and efficacy trials Quiz Week 4 Background Literature Reading 3 12 : Trial design, recruitment, data analysis Quiz Week 5 1 Background Literature Reading 3 1 To outline a clinical trial protocol for a paediatric vaccine 3 Small group work Case study Week 5 4 To outline an observational study protocol for a paediatric vaccine effectiveness study 4 Individual exercise Case study Week D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 132

133 for Module Bloom Level (1-6) Instructional Assessment Timing Link time hours/week The Outcome: Measuring safety vaccines in paediatrics Identify patterns of vaccine safety issues 2 Describe mechanisms of vaccines causing adverse events To appraise the impact of an adverse event following immunization on a family To describe key issues of measuring vaccine safety in clinical trials To describe approaches to quantifying risk of vaccines post marketing : Prototypes of vaccine safety issues 1 - product safety Quiz Week 6 - program safety Background Literature Reading 3 : How Vaccines Cause Adverse 1 events - mechanisms Quiz Week 6 - assessment Background Literature Reading 3 Writing an Small group work impact 1 statement Week 6 from the Individual reading perspective 1 of a family : Vaccine Safety in paediatric 1 preclinical trials - DSMB Quiz Week 6 - algorithms for case identification and causality assessmemt Background Literature Reading 3 14 : Quantifying risk in paediatric 1 vaccines post licensure Quiz Week 7 - methods - identify data sources D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 133

134 for Module To write a risk management plan for a paediatric vaccine for known and un-known AEFI To contrast vaccine and drug specifics in the Good Pharmacovigilance Practice & new legislation Bloom Level (1-6) Instructional Assessment Timing Link time Background Literature Reading 3 4 Small group work Case study Week Individual exercises Quiz Week 7 1 hours/week To write the safety section of a clinical trial.protocol for a paediatric vaccine 3 Small group work Case study Week 7 4 The Outcome: Public confidence and Risk Communication To discuss the drivers of public confidence in : Drivers of public confidence in 2 vaccines vaccines Quiz Week : Principles of cummicating risk Quiz Week To appraise a public concern and its management 4 Small group work Case study Week 9 2 To devise a risk communication strategy 5 Small group work Case study Week 9 2 To tell a parent /patient about safety issues Online life 5 Simulator (good, bad & ugly) Week 9 2 with a vaccine session 6 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 134

135 CONCLUSIONS As illustrated, the GRiP partners have worked together to develop a Joint Degree in Paediatric Medicines Development and Evaluation. However, since the Partnership Agreement and legal documents up to date are not yet completed by all participating Universities, the GRiP consortium is happy to have received the approval for granting an International Master degree under the leadership of University of Rome Tor Vergata (coordinator Professor Paolo Rossi). The Programme reported above is reflecting the international cooperation and the involvement of all GRiP partners in this first step towards the development of a Joint Degree which is based on equal content. In annex 1 it is reported the final draft of the Partnership Agreement among the four universities. This draft has been elaborated by concerned GRiP partners and then reported in the GRiP Educational Board. Upon approval by the legal offices from the Universities, (expected approval time is spring 2015), a Joint Master Degree in Paediatric Medicines Development and Evaluation will be from fall Annex 2 will be used to contact and describe the centres or workplaces that conduct Paediatric Pharmacology Research and have a research environment adequate to research stages of the GRiP Master. D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training 135

136 Partnership agreement This Partnership Agreement is made by and between the following institutions (herein and after also referred to as Parties or Universities ): Erasmus Medical Center Rotterdam (Erasmus MC), whose administrative offices are at Dokter Molewaterplein GJ Rotterdam, the Netherlands, hereby represented by Dean and vicechairperson of the Board of Directors Jaap Verweij. Erasmus MC is part of the Erasmus University Rotterdam, which will sign the degree. University of Basel, whose administrative offices are at Petersgraben 35/4, CH Basel, Switzerland, hereby represented by its Rector, Professor Antonio Loprieno Université Paris Diderot - Paris 7, whose administrative offices are at 5 rue Thomas-Mann, Paris, France, hereby represented by Christine Clerici, Président de l Université Paris Diderot - Paris 7 University of Rome Tor Vergata, whose administrative offices are at Via Orazio Raimondo 18 Rome, Italy, hereby represented by its Rector, Professor Giuseppe Novelli D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

137 Contents Partnership agreement 1 1 Background Summary of the joint MSc programme 3 2 Purpose of the Agreement 3 3 Definitions 3 4 Validity and Amendments 5 5 The programme Modules and Module Coordinators 5 6 The governing structure The Educational Steering committee (EdS) Invited additional participants Programme Coordinator Educational Administrative office (Admin office) and the Administrative Coordinator8 6.4 The Joint Selection Committee The Joint Examination Committee (Exam Com) The Joint Quality Committee (JQC) The GRiP Quality Advisory Committee 10 7 Obligations of the Parties to the agreement 10 8 Student Administration Application procedures Admission requirements and registration 12 9 Selection procedure Selection criteria Registration and enrolment Students rights and responsibilities Academic progress Exam recognition Joint supervision of the Master thesis Joint Degree Degree Awarding Universities Joint Recognition Signing of the degree Financial Arrangements General financial management during GRiP Costs General financial management after GRiP Costs Programme fees Prevention and safety Intellectual property rights Settlement of disputes Copies and language Liability Signatures 20 Annex I List of GRiP partners 21 Annex II Curriculum 22 D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

138 1 Background In 2010 a consortium of 21 universities and research groups was awarded a grant in the European Framework 7 programme (EC contract nr HEALTH-F ); a list of GRiP partners is included in Annex 1. The consortium initiated the Global Research in Paediatrics (GRiP) network, which is a network of scientists that aims to stimulate and facilitate the development and safe use of medicines in children. GRiP wants to become the leading research network in the field of paediatric clinical pharmacology. The general objective of the GRiP project is to facilitate the development, and promote the availability of medicines for children by reducing the fragmentation of on-going efforts in fields of research. In addition, GRIP aims to create consensus on international standards, methodologies and tools for paediatric research. Part of the GRiP activities is to set up diverse educational offers, including a joint Master programme. The Parties to this Partnership Agreement are participants of the GRiP Network and are responsible for the joint Master programme. The initiation of this programme is funded by the GRiP Network grant, but the programme will need to be self-sustainable when GRiP funding ends. 1.1 Summary of the joint MSc programme The joint Master programme is based on e-learning modules. Almost all theoretical education is offered in online modules. Students only physically attend the programme during the Fresher s meeting and their research training. The Master is a one-year programme of 60 ECTS offered in part-time. It starts off with the Fresher s Meeting (1ECTS). There are ten modules of either 4 ECTS. 19 ECTS are reserved for the research training. The curriculum of the programme is described in Annex 2. 2 Purpose of the Agreement The purpose of this agreement is to agree on the implementation and management of the joint Master programme: the Master of Science programme in Paediatric Medicines Development and Evaluation. The joint programme is initiated to reach one of the objectives of the EU Project GRiP, namely to develop a paediatric clinical pharmacology training programme. The degree shall be jointly awarded by Erasmus University Rotterdam, Université Paris Diderot - Paris 7, University of Basel and the University of Rome Tor Vergata. This agreement shall specify the respective rights and obligations of the Parties with regard to the running of the joint Master programme. 3 Definitions Academic Director Professor representative of each Party, member of the Educational Steering Committee Administrative Coordinator Supports the Programme Coordinator, head of the Educational Administrative Office D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

139 Coordinating University University of Rome Tor Vergata Educational Administrative office (Admin office) Located at the University of Rome Tor Vergata, coordinates the administration and prepares all necessary reports and documents concerning the joint Master programme. Educational Steering Committee (EdS) Consists of the four Academic Directors, each representing their Party, overseeing the joint Master programme and organisation and collaboration among the Parties. Enrolment Registering the student on the roll of one of the Parties in order for that University to fully manage individual students academic careers (i.e. study programme, mobility, results). GRiP Quality Advisory Committee Established in the GRiP project, is involved in the quality assessment for all GRiP educational programmes. Provides suggestions to the EdS to improve them. Joint Degree Joint diploma - an international diploma which is recognized by all Parties. Degrees shall be jointly awarded by Erasmus University Rotterdam, Université Paris Diderot - Paris 7, University of Basel and the University of Rome Tor Vergata. Joint Master Examination Committee (Exam Com) The Exam Com collects local grades and local decisions regarding students results. Joint programme Study programme, which has been jointly developed by all the Parties, where students have access to the facilities and expertise of all Parties. Modules and courses completed during the mobility period are automatically recognized. Joint Quality Committee (JQC) Is responsible for the quality enhancement of the programme. Joint Selection Committee Reviews applications, decides on ranking of applications, decides on study track. Module Coordinator Person responsible for the correct delivery of a Module. Parties The Universities signing this Agreement having the responsibility for the execution of a joint degree diploma. Programme Coordinator The Academic Director, who represents the Coordinating University: The University of Tor Vergata. Chairperson of the Educational Steering Committee. Supported by the Administrative Coordinator.. Registration Entering student data in the institution s student database in order to provide the student with a student ID, give access to facilities such as library, electronic learning platform, etc., and to provide them with a transcript. Third party location A location for the execution of the thesis, which is not one of the Parties or a GRiP partner. To be approved by the Joint Quality Committee. Tuition fee The Parties agree to one joint tuition fee for the degree programme. They agree to a fee waiver from the individual universities. The D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

140 4 Validity and Amendments students pay the tuition fee to the University of Tor Vergata, which distributes the money to the Parties. This Partnership Agreement shall come into force on the day of signature of the undersigning Party. The Parties commit to offering the MSc programme until 2020, provided that the programme is financially sustainable. The sustainability of the programme will be guaranteed by the GRiP funding until the end of the GRiP Project itself. The Agreement shall be reviewed by the EdS every other academic year. The EdS has to agree upon proposals for amendments to the Agreement. Amendments to this Agreement shall be made only by written supplementary addenda signed on behalf of each of the Parties by a person, who is able to represent and commit the university, according to their regulations. 5 The programme The Parties have agreed to provide a joint Master programme: The MSc programme Paediatric Medicines Development and Evaluation: a 60 ECTS programme, consisting of ten modules of in total 40 ECTS, a research training period (19 ECTS) and a Fresher s Meeting (1 ECTS). The joint programme is studied part-time and spread over two years, with a maximum registration period of four years. The programme is aimed at medical professionals. The programme is developed jointly between the Parties. The Parties are responsible for producing the Programme-contents, in collaboration with external institutions, professors and experts. The Parties hereby agree to the joint curriculum, which is detailed in Annex 2. Material changes to the curriculum and other aspects of the programme (like mobility) are only allowed after prior written approval of the EdS (in accordance with the regulations of the Parties), without detriment to students already enrolled. 5.1 Modules and Module Coordinators The Parties together offer ten modules with the programme. A module consists of lectures, online discussions, interaction with the teachers and assessments. Each module is worth 4 ECTS and is equivalent to 100 hours of work, both self-study and teaching. A Module Coordinator is a representative of one of the Parties. He/she is responsible for the proper delivery of the module. The Module Coordinator is obliged to ensure the quality of the module. This includes providing tutors during the runtime of the module and input from external teachers who are not employed by one of the Parties. When a lack of quality is identified, either by the Module Coordinator, the JQC or one of the involved staff members, the Module Coordinator is responsible for implementing improvements in cooperation with the teaching staff. Should an external teacher not D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

141 provide teaching according to the quality expected for the modules, the Module Coordinator may replace the teacher. Should an external teacher discontinue their contribution to the module, the Module Coordinator is responsible for finding a replacement. 6 The governing structure The following Committees are set up for proper execution of the programme. 6.1 The Educational Steering committee (EdS) The EdS is responsible for overseeing the delivery and management of the joint Master programme in Paediatric Medicines Development and Evaluation. It is responsible for the organisation of the partnership, for collaboration among the four Parties and for ensuring compliance with the provisions of the programme. Members in the EdS are: One voting representative from each of the Parties, the Academic Director; One non-voting member from the GRiP Educational Board during the duration-time of the GRiP Project; One non-voting member of the GRiP project management team and/or Educational Administrative representative during the duration-time of the GRiP Project; One non-voting representative of the Educational Administrative Office, the Administrative Coordinator. The Programme Coordinator is the Chair person. The EdS shall meet at least once a year to define and update all organizational aspects of the joint programme. Meetings can be organized via telephone or video conference or as face-to-face meeting. The decisions of the EdS are taken by a simple majority vote with one vote per Party. The Academic Director of a Party can be replaced by a person authorized by that Party. The Chairperson has the deciding vote in the case of an equal vote. It is possible to request voting in writing by to the Programme Coordinator no later than one week after the voting was requested, when a consultation with the Party is required. The Academic Directors ensure that decisions that are made by the EdS have the consent of their Parties if it is needed. The EdS is responsible for: Supporting the Programme Coordinator in managing the programme; Evaluating the Programme Coordinator; Providing overall project management policy; Appointing the Joint Selection Committee, Joint Quality Committee, Joint Examination Committee at the suggestion of the Parties to this agreement; Establishing ad hoc committees and their composition; Setting the amount of the tuition fees; Deciding on the distribution of the fee income and of other contributions among the Parties; Deciding which costs made on behalf of the programme can be claimed and which costs cannot be claimed, see also chapter 13; Engaging with the GRiP Quality Advisory Committee without undue delay to ensure that the quality criteria set forth by the GRiP project are considered; D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

142 Ensuring quality assurance of the joint programme, by deciding on the proposals of the Joint Quality Committee; Deciding on the proposals of the GRiP Quality Advisory Committee; Reviewing admission criteria annually and making necessary changes; Defining the student quotas for the programme; Agreeing on any changes in the selection procedure and methods; Making applications for additional funding (including Erasmus+); Deciding on the evolution of the Partnership (including Partnership decisions); Agreeing (in accordance with the regulations of the Parties) on the adaptation and update of the joint curriculum to recent developments Invited additional participants Additional participants can be invited to the EdS meeting upon requests by the EdS members and when the agenda requires such attendance. 6.2 Programme Coordinator The Academic Director of the University of Rome Tor Vergata is the Programme Coordinator for the joint programme. He/She will act as the Chairperson of the Educational Steering Committee and will oversee the administrative, legal and financial matters of the Partnership and the joint Master programme. The Programme Coordinator shall report to the Parties in such a way that these have full insight into the administrative, legal and financial matters. The Programme Coordinator, assisted by the Educational Administrative office and the Administrative Coordinator, shall undertake to: Take all the steps necessary to prepare for, perform and correctly manage the programme set out in this Agreement and annexes; Chair all meetings of the EdS; Formulate proposals on any issue to be decided on by the EdS; Collaborate with the Joint Selection Committee and oversee the admission procedure; Evaluate whether all Parties fulfil all their requirements. If the performance of one of the Parties to this Agreement is unsatisfactory, the Programme Coordinator shall summon the Party that does not perform in accordance with the agreement to comply with the agreement within a reasonable period of time. In case the Party that is in breach with the agreement does not remedy the failure within the aforementioned reasonable period, the Programme Coordinator is entitled to propose to the EdS to end the cooperation with the defaulting Party; Notify and provide the Parties with any proposals for amendments made to this Agreement; Issue warnings and, if necessary, sanctions for students misbehaviour. Sanctions must be ratified by the university involved and the EdS; Report to the EdS on the yearly income; Manage the Financial Reserve. The Programme Coordinator will report yearly to the EdS on the Financial Reserve. Decisions regarding the spending of the Financial Reserve are made by the EdS. When the applications to the joint Master programme have been processed by the Joint Selection Committee, the Programme Coordinator is responsible for the communication to the applicants and sends out a letter of admission on behalf of the Partnership, as well D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

143 as letters of refusal and information about waiting list. All selected students will be send an official letter of admission and a Letter of invitation to the Fresher s meeting. A letter of support may be send if a student needs one for the visa procedure. 6.3 Educational Administrative office (Admin office) and the Administrative Coordinator The Admin Office is located at the University of Rome Tor Vergata. The Parties shall each appoint one member of staff to serve as the local administrative contact person. In collaboration with the administrative contact person in each Party, the Admin office shall coordinate the administration and prepare all necessary reports and documents concerning the joint Master programme. The Admin office is acting under the responsibility of the Programme Coordinator and serves as a central hub to maintain communication across the Parties as well as communication to all programme stakeholders, using website, meetings, memos, presentation etc. as tools for communication. Within the joint Master programme in Paediatric Medicines Development and Evaluation, the office shall: Assist the Programme Coordinator; Serve as the contact point for administrators for the joint Master programme; Assist the Parties in the organization of face-to-face meetings in the Fresher s Meeting; Prepare Administrative documents for the joint Master programme (including agreements, amendments, certificates etc) to be signed by the four Parties; Send the Parties to this agreement copies of the Agreements together with annexes and any other official document concerning the project; Assist the Joint Examination Committee with administration (follow up of students performance, assessment); Assist with dissemination of the joint Master programme (prepare for brochures, catalogues, update on the website etc.); Follow-up on financial arrangements referred to in this Partnership Agreement; During the theoretical period, when student take the modules on the VLE, offer student guidance and counselling to all students. This may be done by personnel of the University of Tor Vergata outside of the Admin Office; Support the Joint Selection Committee with the processing of the applications. 6.4 The Joint Selection Committee The Joint Selection Committee consists of one academic representative from each of the Parties. The Committee members are nominated by their universities and appointed by the EdS. The Chairperson is chosen among the members of the committee. Any meeting can be organized via telephone or video conference or as face-to-face meeting. The Committee shall review all applications to the joint Master programme in Paediatric Medicines Development and Evaluation following the student eligibility and selection criteria as outlined in chapter 9.1. These may be modified by the EdS. D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

144 The Joint Selection Committee makes an overall ranking between applicants. It does so by majority of votes. The Joint Selection Committee also assigns a Research Supervising University to each student. Students are provided with a list of places where the research training can take place. They discuss a research topic with a potential supervisor based on the descriptions of topics at the location (four Research Supervising Universities and the other GRiP partners). After the first three Modules all students indicate their Research Supervising University ps. The Joint Selection Committee assigns a Research Supervising University, based on the ranking of preferred Research Supervising Universities by each individual student and the availability of places at each University. The Committee reports its decisions to the EdS. The EdS will have the final decision on the student enrolment and the distribution of students among the Parties. 6.5 The Joint Examination Committee (Exam Com) The Exam Com consists of one representative from each of the Parties. The Chairperson is chosen among the members of the committee. The voting can be done at the meetings or in writing by to the Chairperson no later than one week after the voting was requested. The representative in the Exam Com is responsible for the grades according to regulations and laws of their university. The Exam Com collects local grades and local decisions regarding students results. The Committee is responsible for determining whether a student has met the requirements of all Universities and of the Partnership and can be awarded the Joint Master Degree. The Exam Com shall ensure that the assessment process is conducted and in accordance with each University s local rules. The Exam Com reports yearly on its activities to the EdS. An annual Exam Committee meeting will be held in each year and results of each student communicated to the Parties. Voting has to be unanimous. The Exam Com s tasks shall include: To define and update the Teaching and Examination Regulations; To receive the Module assessment results from the Module coordinators; To consider the assessment results achieved by the students; To confirm progression from Year 1 to Year 2 of the programme. The Exam Com is responsible for The final calculation on students results and their graduation; The students grading lists; The granting of exemptions to individual students from part of the programme on the grounds of knowledge or skills gained within or outside higher education. The Committee has the power to deviate from the Teaching and Examination Rules and Regulations in individual cases (e.g. a longer validity of assessment results or exemptions in the curriculum). D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

145 6.6 The Joint Quality Committee (JQC) The Joint Quality Committee consists of one representative from each of the Parties. The Chairperson is chosen among the members of the committee. Any meeting can be organized via telephone or video conference or as face-to-face meeting. The decisions of the JQC are taken by a simple majority vote with one vote per Party. The voting can be done at the meetings of the JQC or in writing by to the Chairperson no later than one week after the voting was requested. The representative of a Party can be replaced by a person authorized by that Party. The Chairperson has the deciding vote in the case of an equal vote. The tasks of the Joint Quality Committee are to: Evaluate the curriculum, the contents of the modules, the quality of the teaching, and the practical organisation of the study programme based on evaluation forms completed by students and staff. The JQC will devise a process for quality monitoring that involves all learning content to the student. Relevant elements are content, clarity, consistency and agreement with academic standards. The JQC offers a forum to all teaching staff members involved to discuss the contents of all modules; Decide on requests from students to write their thesis at a third party location that is not a GRiP partner; Share policy documents; Discuss local practices and Report to the EdS on recommendations for adaptations to the joint Master programme or curriculum or for new policy. 6.7 The GRiP Quality Advisory Committee The GRiP Quality Advisory Committee is part of the FP7-funded GRiP consortium. As GRiP is the initiator of the joint Master programme, it is involved in the quality assessment for the programme until the end of the GRiP project unless otherwise agreed within the EdS. The GRiP Quality Advisory Committee can provide suggestions to improve the programme; it will advise on educational topics, course content, educational competencies and the joint Master programme implementation. These recommendations will be made to the EdS, which will have to approve the recommendations before their implementations. 7 Obligations of the Parties to the agreement Each Party appoints a representative on the EdS, the Academic Director. By signing this Partnership Agreement, the Universities agree that their representative is able to make decisions on behalf of the university. Each Academic Director can request to delay the vote by 21 calendar days to consult with its institution or to produce documents that may affect the decision. The Academic Director will ensure that the organisation of teaching and the students facilities at their university are in line with the decisions taken by the EdS. They will support the Programme Coordinator in carrying out his/her duties. They shall cooperate and communicate with each other on a regular basis and will do so immediately when D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

146 requested by the Programme Coordinator. It is agreed that correspondence shall be the standard means of communication within the Partnership. All Parties to this agreement shall: Nominate one member from its staff to represent the Party in the Joint Quality Committee; Nominate one member from its staff to represent the Party in the Joint Selection Committee; Nominate one member from its staff to represent the Party in the Exam Com; Communicate to the Programme Coordinator any information or document required by the latter that is necessary for the management of the programme, including addresses to be used for any communication related to the programme; Be responsible for all information communicated to the Programme Coordinator, including details of costs claimed; Report to the Programme Coordinator on the progress of the students, the number of credits obtained and the marks. The communication will be undertaken by the administrative contacts of each Party through the transcript of records released in English. Each university is able to access information about all students; Take all the steps necessary to prepare for, perform and correctly manage the joint Master programme set out in this contract and its annexes (especially the course and research descriptions); Have and maintain an excellent academic quality in the joint Master programme, sufficient experience and teaching capacity to fulfil their role in the Partnership; Recognise the ECTS earned at the different universities within the Partnership and at recognised third party locations; Assist the other Parties with the process of obtaining national accreditation or other national or institutional requirements to guarantee institutional or national approval and authorisation for the joint programme; Accept the responsibility to organise the face-to-face meeting during the Fresher s Meeting at least once every four years; During the research training period, offer student guidance and counselling to all students for whom the Party acts as a Research Supervising University; Notify the Admin Office immediately if a student is no longer able to follow the agreed study track in the specified time or a total withdrawal situation occurs; Communicate all data of their students to the Admin Office, even though the universities store student data according to the respective rules of each University. Notify promptly any delay in performance or any event that may impact the joint Masters programme to the EdS; Inform the EdS of information received from third parties as regards the joint Master programme; Act at all times in good faith and in a manner that reflects the good name, goodwill and reputation of the other Parties to this agreement and in accordance with scientific and academic ethics; Participate in a cooperative manner at the meetings of the different bodies under this Partnership Agreement. It is understood that GRiP third parties or GRiP beneficiaries other than the Parties to this Partnership Agreement, will participate in teaching sessions in the programme. However, the four Parties to the underlying Partnership Agreement are ultimately responsible for the quality of teaching and exams. D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

147 8 Student Administration 8.1 Application procedures Each year the EdS decides on the maximum number of students to be accepted into the programme. Places are allocated according to the ranking of preferred Research Supervising Universities by each individual student and the resources. The Parties agree to accept at least five students per year for the research training. The maximum capacity of students to be accepted at each Party, as decided by that Party, will be published annually on the website of the joint Master programme. After taking the first three Modules the student indicates at which of the Parties they wish to be placed. They can give three ps. The selection procedure is done by the Joint Selection Committee as described in chapter 6.4. Application deadline: April 15 th each year Selection procedure: scheduled to be finalised June 10 at the latest. Start of the programme: September (NB: the first cohort will start in November 2014, the second cohort will start in September 2015) 8.2 Admission requirements and registration A student wishing to join the joint Master programme in Paediatric Medicines Development and Evaluation will register for the programme for the upcoming year. Students can also register to study one or more modules only; in that case only a certificate of completion or participation will be awarded for each module. Details on the required documents for registering will be provided in the application form. 9 Selection procedure 9.1 Selection criteria Minimum requirements to enter the Master are A university education of at least 240 ECTS with corresponding degrees or certificates; English proficiency corresponding to o a minimum IELTS (International English Testing System) score of 6.5 (minimum score subsection: 6.0); or o a minimum TOEFL (Test of English as a Foreign Language) scores of: 575 for the paper based test (minimum score subsection: 57); 90 for the internet based test (minimum score subsection: 22); Computer literacy ability. The Joint Selection Committee will select the students on the basis of their Relevant academic background; Convincing letter of motivation; D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

148 Quality of the letters; Work experience and professional qualifications (if applicable); Results of any interviews (if applicable); candidates may be asked to attend an interview either in person, by Skype, by video-teleconference or by telephone. All individuals are selected and treated based on their relative merits and abilities. The joint Master programme shall be open to anyone regardless of age, class, religious believes, disability, ethnic origin, gender, marital status, nationality, or sexual orientation. 9.2 Registration and enrolment Students of the programme shall be enrolled with the University of Tor Vergata when: They have paid the first instalment of the annual Master degree fee; They have provided proof that they have initiated the necessary visa and permit procedures if needed for the research project period(s) and/or the Fresher s Meeting; They have provided proof of insurance policy to cover medical expenses, maternity, illness or death, transportation back to the applicant home country in case of a serious accident, as well as to cover any consequences of civil liability. 10 Students rights and responsibilities Each of the Parties undertakes to provide information to the students enrolled and/or registered at their university with regard to preparation for the programme, obtaining visas, orientation, language support and study counselling. The Partnership does not financially sponsor student visas, health insurance, accommodation or language courses. Living and travel expenses, other costs related to academic facilities delivered by external bodies and other costs related to the management of the individual academic files will be charged directly to the students. The students must be in compliance with the regulations of social welfare of the country in which they execute their research training period. For each student, the EdS representative of the university concerned will appoint a tutor, whom the student may consult for advice or assistance during their study programme, also including during the e-learning modules. The staff members of the Parties engage themselves in helping students with incoming procedures such as finding accommodation and ensuring that students have access to language courses, libraries and to the services offered by the respective International Offices. During the research training, each Research Supervising University will provide a student card to the student. The students rights and responsibilities are the same as those valid for any other student at the institution where the student is studying at the specific moment. Teaching and Examination Regulations The Teaching and Examination Regulations (TER) of the joint Master programme deal with the common aspects of the programme. All matters not discussed in the TER, are dealt with in its annexes: the local teaching and examination regulations. The TER includes descriptions of the intended learning outcomes, admission procedures, structure of the programme, grading and the tuition fee. The local regulations cover the procedures D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

149 regarding Masters thesis defence, examinations and examination results, and re-sits of courses and elective courses. 11 Academic progress 11.1 Exam recognition All Parties agree to operate along the principle of mutual recognition of exam results, ECTS awarding and each other s rules and regulations. At the end of each semester, students results will be communicated from the Parties to the Joint Examination Committee including grades. The Joint Examination Committee assumes the responsibility to summarize the results of all Parties and publishes (for internal use only) by the end of the second semester of each academic year, the following information: progress, retakes of exams, number of degrees awarded Joint supervision of the Master thesis The Master thesis will be undertaken, under the supervision of academic staff member(s) of the Research Supervising University, who are qualified for supervision of MSc students according to local regulations. The thesis can be prepared at the premises of one of the Research Supervising Universities or one of the GRiP partners or at another third party location. The student who wishes to write their thesis at a third party location has to get approval of their thesis location from the Joint Quality Committee. Supervision by the Research Supervising University is always required. The Research Supervising University will offer a Student Agreement to the student supervised by the University. The Student Agreement will include the rights and duties of the student, Research Supervising University supervisor and, if applicable, the GRiP or third party supervisor. The topic of the thesis must be agreed according to the local rules of the Research Supervising University, and will be evaluated according to local procedures and regulations of the Research Supervising University. The Master thesis must be written in English and presented orally in English. If needed, a video-conference connection can be allowed. Grading of the thesis will be according to the same grading system as is used in the VLE. The Master thesis is graded by the student s supervisor and a second examiner from another of the Parties within the partnership. If the grade differs by more than one grade point or if the supervisor or second examiner gives a fail grade, they have to discuss the grading and come to an agreement. D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

150 12 Joint Degree 12.1 Degree Awarding Universities The following Parties have agreed to grant a Joint Degree to successful students: Erasmus University Rotterdam University of Basel Université Paris Diderot - Paris 7 University of Rome Tor Vergata 12.2 Joint Recognition Upon successful completion of the part-time joint Master, the students will be awarded a Master of Science (MSc) degree in Paediatric Medicines Development and Evaluation, recognized by all countries of the Parties. The degree is called: Master of Science in Paediatric Medicines Development and Evaluation. The local titles are: In Italy: Master In the Netherlands: no Dutch translation In In Switzerland: no Swiss translation If the students have studied only part of the programme, a certificate for participation in the respective module(s) will be issued in English. The degrees and the certificates will be awarded in accordance with the study regulations of each participating country of the Module Coordinator. All degrees and certificates will be issued in English Signing of the degree The Joint Degree will be issued by the Admin Office. At each of the Parties, the Joint Degree will be signed by the person who is indicated by the national law or regulations of that university. In the Netherlands: the chairperson of the Joint Examination Committee. In Switzerland: the Rector In France: the Education Officer of the Regional Education Authority and the President of University In Italy: the Rector? The Master degree can only be signed if a student has earned 60 ECTS credits or more and has paid all tuition fees. Diploma supplement The Exam Com will issue a Joint Diploma Supplement (JDS) to secure degree transparency. The Joint Diploma Supplement will be signed by the chairman of the Joint Examination Committee. D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

151 13 Financial Arrangements The Parties understand the benefits of an internationalization profile. The Parties are committed to use their existing institutional resources to create and maintain the joint Master programme General financial management during GRiP During the runtime of the GRiP project, the GRiP Network will pay for the online management database and for maintaining and implementing the administrative and management tasks of the joint programme in collaboration with the Parties. After the runtime of the GRiP project, these costs will be borne by the Partnership. The fee income and any other funding generated by the programme will constitute funding of the joint Master programme and a) shall be used to cover its costs; and b) may not have the purpose or effect of producing a profit for the Parties, unless after the termination of the GRiP project. The tuition fees to be paid by the students are collected by the University of Tor Vergata. The University of Tor Vergata reserves 26% of the tuition fees for overhead. If incomes from the fees exceed the full programme cost, the difference will be transferred to the Financial Reserve. The Financial Reserve is a fund at the disposition of the EdS. Every year the remaining Financial Reserve funds will be used for the advertising of the joint Master programme, and/or cover any losses of previous years, and/or development of new courses, unless it is agreed differently. The financial arrangement will be reviewed by the Parties on an annual basis, as part of the general annual assessment by the EdS Costs Each Party to this agreement agrees to keep a full financial record and documentation for all transactions relating to funds distributed under this contract and to make all requested financial documentation for audit and/or reporting purposes within a maximum of thirty days of the request, unless a shorter time is requested by the EC/the auditor. If a Party to this agreement wishes to claim costs for s made on behalf of the Partnership, it should first contact the Programme Coordinator. After permission of the Programme Coordinator, the Party concerned may claim the costs with the Programme Coordinator. The following costs can be The following costs cannot be claimed and are to be borne by the Party who made the cost: D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

152 @ 13.2 General financial management after GRiP The tuition fees to be paid by the students are collected by the Programme Coordinator. The Programme Coordinator is required by the University of Tor Vergata to reserve 26% of the tuition fees for overhead. The Programme Coordinator reserves of the tuition fee for management costs. The remaining sum will be divided among the Parties: % for the Module Coordinators based on the ECTS of their modules; % for the supervision of the thesis; % for local management costs Costs Each Party agrees to keep a full financial record and documentation for all transactions relating to funds distributed under this Agreement and to make all requested financial documentation for audit and/or reporting purposes within a maximum of thirty days of the request, unless a shorter time is requested by the auditor. If a Party to this agreement wishes to claim costs for s made on behalf of the Partnership, it should first contact the Programme Coordinator. After permission of the Programme Coordinator, the Party concerned may claim the costs with the Programme Coordinator. The following costs can be The following costs cannot be claimed and are to be borne by the Party who made the cost: Costs for travel to and from meetings; Costs for teleconferences, Skype and other long distance meetings Programme fees The Parties agree to one joint tuition fee for the degree programme. They agree to a fee waiver from the individual universities. The Partnership agrees that students who are citizens of EU member states or EEA countries will be charged the tuition fee of 4,000 per programme. Those citizens of non- EU/EEA-states will be charged the tuition fee of 8,000 per programme. The fee will be paid in two instalments per year: before November 1 st and May 1 st. The students with a previous degree or with a current registration as MSc or PhD student at any of the four Parties will get a discount of the annual fee. The fees will be reviewed on an annual basis, without detriment to registered students. The EdS shall propose tuition fees and discount rates. Any changes to the fees as well as to any discount rate must be agreed by all four universities. These tuition fees include the following services: Enrolment in all the teaching units and modules delivered by the four Parties and access to related educational resources for the duration of the registration on those modules; Participation in the Fresher s meeting; D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

153 Free access to library, document centres and related services at the Research Supervising University; Examination, diploma and certificate. The fees do not include costs relating to accommodation, food, international travel or travel on site. Fees other than tuition fees, such as re-examination, late registration, may be payable by students in addition to the tuition fee. In addition to the tuition fees, a health insurance is compulsory for accepted students. The purchase of a third party liability insurance is also highly recommended and should be purchased individually. 14 Prevention and safety The Parties shall supply all involved students and staff with detailed information about the specific risks existing in the work environment in which they will be carrying out their functions. The Parties will also provide the necessary documentation concerning prevention and emergency safety measures in conformity with the legislative norms and regulations in force in the country of the host University. 15 Intellectual property rights All intellectual property rights and know-how owned by or licensed to one of the Parties to this Agreement prior to and after the date of this Agreement is and shall remain the property of that specific Party. Module and module content is owned by who developed the module. The developers of a module are entitled to use that module outside the Paediatric Medicines Development and Evaluation Programme. The other Parties need permission of the developer to use the module outside the programme. Nothing in this Agreement shall be deemed to constitute or imply the granting of any license or other right to the Parties under this agreement under any industrial or intellectual property right. All data and results resulting from the research performed by the student during the research training period shall be the property of the university where the research is performed and the Parties therefore agree that this university shall be the sole owner of all related intellectual property rights. 16 Settlement of disputes In case of appeal against joint academic decisions or procedural irregularities, it is the Programme Coordinator, who is the recipient of such communication and is responsible for further communication and follow-up of legal rights and obligations. In case of appeal against local academic decisions or local procedural irregularities, it is the local university, who is the recipient of such communication and is responsible for further communication and follow-up of legal rights and obligations. The differentiation between local and joint student issues is made in the joint Teaching and Examination Regulations (chapter 10). D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

154 This agreement shall be in every respect understood and operated as an Agreement made in compliance with the respective national laws of the Parties. In particular, this Agreement shall be governed by all laws and regulations applicable to university education. The Parties shall make all reasonable efforts to settle disputes arising from or in connection with this Agreement in an amicable way. Any disputes that remain unsolved shall be heard exclusively by the competent court in Brussels, Belgium. 17 Copies and language 18 Liability This Agreement has been written and signed in four original copies in English and each is equally valid. English will be the working language between the Parties. Each Party shall be independently responsible for the performance of any part of its tasks under this Agreement. No one Party shall be liable towards any other Party for any and all damage incurred in relation to the agreement and the performance of the joint Master programme. Each Party shall arrange insurance cover for any and all liability and/or damages suffered in relation to the agreement and/or the performance of the programme. D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

155 19 Signatures Authorised to sign on behalf of Erasmus University Rotterdam, the Netherlands (EUR): Dean and vice-chairperson of the Erasmus University Medical Center Rotterdam, Professor Jaap Verweij Date Authorised to sign on behalf of University of Basel: Rector, Professor Antonio Loprieno Date Authorised to sign on behalf of Université Paris Diderot - Paris 7: Christine Clerici, Président de l Université Paris Diderot - Paris 7 Date Authorised to sign on behalf of University of Rome Tor Vergata : Rector, Professor Giuseppe Novelli Date D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

156 Annex I List of GRiP partners Academic Medical Center, the Netherlands Azienda Ospedaliera di Padova, Italy Basque Foundation for Health Research and Innovation, Spain Brighton Collaboration Foundation, United Kingdom Consorzio per le Valutazioni Biologiche e Farmacologiche, Italy Dutch Genetic Alliance - VSOP-EGAN, the Netherlands European Medicines Agency, United Kingdom Erasmus University Medical Center Rotterdam, the Netherlands Institut National de la Santé et de la Recherche Médicale, France Instytut Pomnik Centrum Zdrowia Dziecka, Poland Joint Authority for the Hospital District of Helsinki and Uusimaa (HUS), Finland Leiden University, the Netherlands National Center for Child Health and Development, Japan National Institute of Child Health and Human Development, United States of America Ospedale Pediatrico Bambino Gesù, Italy PENTA Foundation, Italy Saint Georges Hospital Medical School, United Kingdom SickKids, Canada University College London, School of Pharmacy UCL, United Kingdom University of Liverpool, United Kingdom University of Liverpool - Medicines for Children Research Network, United Kingdom World Health Organisation D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

157 Annex II Curriculum Here the GRiP Master doc will be added, in a shortened version. D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 1

158 Annex 2 - Description of the centres conducting Paediatric Clinical Pharmacology Research The present document will be used to contact and describe the centres or workplaces that conduct Paediatric Pharmacology Research and have a research environment adapted to research stages of the GRiP Master. They include 3 categories of workplaces : 1. Paediatric Pharmacology Research Center (academic center or pharmaceutical industry) 2. Regulatory Agency Research Center 3. Clinical Paediatric Center / Clinical Paediatric Department The corresponding research workplaces will be accredited for the GRiP Master after validation by the Master Scientific Committee Name Paolo Rossi Evelyne Jacqz-Aigrain John van Den Anker Kathryn Parker Agnes Saint Raymond Institution University of Rome Tor Vergata / OPBG - Italy Inserm - France EMC The Nederlands SickKids Toronto- Canada EMA - UK D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 2

159 Presentation of the GRiP program GRiP (Global Research in Paediatrics) is an EU FP7 project with the overall objective to enhance the availability of medicines for children in Europe and in the USA. Within GRiP, the partners reached the successful development of a joint paediatric clinical pharmacology training programme, including a Master programme. The master entitled Paediatric Medicines Research is organised by four universities in Europe, namely : Erasmus University Rotterdam University of Basel University Paris Diderot University of Rome Tor Vergata, in order to ensure the continuing professional development of practicing physicians and pharmacists to order to acquire additional competences in all the specific aspects of paediatric pharmacology, drug evaluation, trial design and conduct in the paediatric population and also to ensure the cultivation of researchers, paediatricians, physicians and health professionals with expertise in paediatric pharmacology. The structure of the master consists of ten modules with 100 hours each, corresponding to 4 ECTS. Work placement or research activity with 18 ECTS, with 2 ECTS used for elaborating a Master-thesis and Fresher s meeting. The work placement or research activity is organized in workplaces or centres in agreement with the national coordinator or contact of GRiP and validation by the Joint Selection Committee. Detailed presentation of the center is required and the applicant has to provide the questionnaire corresponding to the department or structure where the stage takes place : Paediatric pharmacology department ( Research unit with paediatric pharmacology programmes ( Research department in Pharmaceutical Industry ( Pharmacy within paediatric activity ( Paediatric department with experience in drug evaluation (3) National Medical Agencies (2) Regulatory department n Pharmaceutical Industry ( Additional work place D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 2

160 Description of the accredited research workplaces for the GRiP Master 1. Paediatric Pharmacology Research Center (i.e. academic research units or industry research units) Country Center Address Department in which the research will be conducted Head of department (taking responsibility of the student) - Name - Title - Specialty Areas of research / Expertise Is Paediatric research the unique / predominant research activity of the center (Y/N) Clinical research activities (trial design, patients inclusion, trial management, data analysis, network activities Clinical research facilities (responsible or )(CRU, CIC..) Laboratory facilities (responsible or ) Paediatric tools ( preclinical studies, drug analysis, pharmacometrics, pharmacogenetics, pharmacoepidemiology, statistics ) Description of the research team - nb of confirmed researchers / experts - health professionals involved in laboratory work collaboration with health professionals involved in clinical trial D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 2

161 conduct (nurses, research technicians ) Paediatric pharmacology training - nb of PhD students trained in the past 3 years -number of staff who have received formal education (courses, mentors) on how to supervise students -Do members of the research team have access to formal education (courses, mentors) on how to supervise students? Publications in the past three years - total - nb in Paediatric journals - nb in Pharmacology / paediatric Pharmacology journals What other characteristics of your site make it an optimal place to educate students? Please explain. D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 2

162 2. Regulatory Research Departments (i.e. EMA and national regulatory agencies, EU Research departments, Industry departments, Research Institutions ) Country Regulatory Agency Address Department in which the research will be conducted Head of department (taking responsibility of the student)- Name - Title - Specialty Areas of Expertise and Evaluation Activities Is Paediatric evaluation the unique / predominant activity of the center (Y/N) Clinical trial activities (trial design, patients inclusion, trial management, data analysis, network activities) Paediatric data : preclinical studies Pediatric data : pharmacometrics, pharmacogenetics, pharmacoepidemiology, statistics Modelling Simulation Paediatric data : paediatric forms and formulations assessment Description of the evaluation team - nb of confirmed experts - other EU Agencies - International partners for paediatrics - link with families or patients organisations Peadiatric pharmacology training D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 2

163 - nb of Masters students trained in the past 3 years Publications in the past three years - total - nb in Pediatric journals - nb in other journals (but to paeds) What other characteristics of your site make it an optimal place to educate students? Please explain. D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 2

164 3. Clinical Paediatric Center / Clinical Paediatric Department (with paediatric medical activities) Country Address Department in which the research will be conducted Head of department (taking responsibility of the student)- Name - Title - Specialty Clinical activity : pediatric subspecialty Other paediatric subspecialty / activities - radiology : Y/N - explorations Y/N Staff trained in clinical research in the department : - paediatrician (Y/N) - pharmacist (Y/N) - nurses (Y/N) Participation to drug trials (Y/N) Type of trial activities (phases) Clinical trial activities (trial design, patients inclusion, trial management, data analysis, network activities) - link with families or patients organisations Paediatric pharmacology training - nb of Masters students trained in the past 3 years Publications in the past three years - Publications in the past three years - total D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 2

165 - nb in Paediatric journals - nb in other journals (but to paeds) What other characteristics of your site make it an optimal place to educate students? Please explain. D1.6 - Master program in Paediatric Clinical Pharmacology: Scope, Organization, Training Annex 2