The Pharmacy Special Interest Group The Institute of Clinical Research

Transcription

1 The Pharmacy Special Interest Group The Institute of Clinical Research

2 To be internationally recognised as the premier organisation for clinical research respected as a key influencer, promoting knowledge and understanding by engaging the healthcare community and the general public. The Institute of Clinical Research info@icr-global.org Telephone: Facsimile: Disclaimer: The opinions expressed in this publication are those of the subcommittee, and not necessarily those of The Institute of Clinical Research All rights reserved. No parts of this book may be reproduced by any means or transmitted, or translated into machine language without written permission of the publisher. ISBN-13: Designed by Stretton Graphics

3 Conference: Annual Spring Conference and Exhibition Forums/seminars: free to members Special Interest and Steering Groups: provide important and up to date information on clinical research Education: further education leading to formal qualifications Training: covering all aspects of clinical research elearning: a practical and flexible way to study CRfocus: your journal, free 11 times a year Information Services: helpline, resource centre, online resources and international news bulletins Website: access to members only section ICR Publishing: wide range of books and monographs on clinical research topics The Institute of Clinical Research Institute House, Boston Drive, Bourne End, Buckinghamshire SL8 5YS, UK Tel: info@icr-global.org raising standards sharing knowledge developing professionals

4 Acknowledgement Grateful thanks are extended to members of the Pharmacy Special Interest Group past and present. To be a Pharmacy Professional iv

5 Contents Acknowledgement iv Introduction The Pharmacist in a Phase I Unit What are Phase I clinical trials?... 3 What is the role of a Pharmacist in a Phase I unit? Education and Training Opportunities... 4 Qualifications and Experience... 4 Desirable Skills... 4 The NHS Hospital Pharmacy Clinical Trials Co-ordinator.. 6 The role of the Pharmacy Clinical Trials Co-ordinator... 6 Qualifications, Experience and Skills... 7 Essential Skills... 7 The Pharmacist working in Research and Development... 8 Role and Function IMP management... 8 Regulatory affairs... 8 Pharmacovigilance... 8 Inspection preparation and GCP audit of pharmacy department. 8 Qualifications and Essential Skills... 9 A Pharmacist as a Research Ethics Committee member.. 10 Introduction Role and Function Education and Training Qualifications and Experience Skills To be a Pharmacy Professional v

6 Clinical Supplies Pharmacist/Pharmacy Technician in the Pharmaceutical Industry Role and Function Education and Training Opportunities Qualifications and Experience Essential Skills Organisations and websites useful to pharmacy professionals in clinical research Glossary and useful definitions References To be a Pharmacy Professional vi

7 Introduction After two to three years of broad based general pharmacy experience a pharmacist or pharmacy technician may choose to go into a number of more specialised fields, one of these is clinical research. Some of the advantages of going into clinical research for a pharmacy professional are: an opportunity to work independently using all of the skills they have gained, and be responsible for a finite service and their own entity work to protect patients and the public be at the forefront of drug development develop protocols, SOPs and policies be involved in problem solving and regulation implementation be part of multi-disciplinary team working with many people outside the pharmacy profession. The diversity of opportunities available to pharmacy professionals within clinical research means that it is possible to move into a variety of roles including positions within research networks, governance, regulatory affairs and training. Other career options include working as a CRA or within the MHRA Inspection team to name a few. The Pharmacy Special Interest Group at the Institute of Clinical Research comprises of both pharmacists and pharmacy technicians, mainly from the hospital pharmacy service, but membership is open to anyone with a pharmacy related career within the pharmaceutical industry or an academic research institution. Since it was established in 1998 the aim of the group has been to raise the profile of pharmacy personnel working in clinical research, to develop training programmes and a support network specifically for pharmacy related issues and promote closer co-operation between pharmacy and other professional groups working in clinical research. In addition to compiling this publication, the group has published practice guidance for pharmacy personnel working in clinical research, a guide to pharmacy related SOPs and developed a template for a Clinical Trials Policy for safe handling of Investigational Medicinal Products (IMPs) in NHS hospitals which can be used to support To be a Pharmacy Professional 1

8 Pharmacy Clinical Trials units in obtaining formal approval from their Trust for the activities they will undertake. This booklet is aimed at those seeking a career as pharmacy professionals working in clinical research. It discusses the work of the pharmacy professional working in the UK. To be a Pharmacy Professional 2

9 The Pharmacist in a Phase I Unit What are Phase I clinical trials? A Phase I trial includes the initial introduction of an investigational medicinal product (IMP) into humans. These studies are closely monitored and usually conducted in healthy volunteer subjects, however they may be conducted in patients where the nature of the compound dictates that it is unethical for administration to healthy volunteers, for example cytotoxic drugs. These studies are designed to determine the safety and pharmacologic actions of the drug in humans. Many sponsor companies outsource some or all aspects of a Phase I clinical trial to a CRO. What is the role of a Pharmacist in a Phase I unit? The role of a pharmacist within a Phase I is to manage all aspects relating to the IMP. This includes receipt of bulk items, manufacturing, dispensing, accountability, reconciliation, returns and destruction. All activities conducted within the pharmacy must comply with the requirements of Good Manufacturing Practice (GMP) and Good Clinical Practice (GCP). But what does this mean? In practice, this means leading the pharmacy to adopt a common sense approach, to ensure the right dose of the right drug gets to the right person in a timely and appropriate way. Phase I units are subject to a high number of audits/inspections from sponsor companies and the MHRA. Auditors/Inspectors are looking for evidence that the pharmacy staff are qualified in training and education to manage the trial. They will also look for quality systems in order to gain confidence that pharmacy staff are in control. It is therefore critical for the pharmacist to review work practices regularly and change them if they are not working effectively. There s no such thing as a typical day but some of the activities the pharmacist will be involved in include: Liaising with prospective clients to define the needs for a new study Reviewing clinical protocols Manufacturing subject specific doses of a wide range of dosage forms Training other members of the clinical team including investigators and nurses. To be a Pharmacy Professional 3

10 Education and Training Opportunities With the increasing amount of new clinical trial legislation, Phase I Units will provide many opportunities for pharmacy staff to attend training courses. Statutory Instrument (S.I) 2004/ came into effect on the 1st May 2004 and implemented the provisions laid out in the Clinical Trial Directive 2001/20/EC 2. Some pharmacists became what is known as a Transitional Qualified Person (QP). Such individuals, in addition to other responsibilities, are responsible for ensuring that each batch of IMP produced complies with GMP. The window to become a Transitional QP has now closed. Those who wish to be registered as QPs must do so via the permanent provisions. This requires the demonstration of qualifications, knowledge and experience relevant to their proposed area of activity. This will include membership of an appropriate professional body such as the Institute of Biology, the Royal Society of Chemistry or the Royal Pharmaceutical Society of Great Britain. (The Joint Professional Bodies) An oral assessment is used to confirm competency to act as a QP in the candidates chosen area before recognition by the MHRA as the named individual to act as a QP on a manufacturers authorisation is possible. Qualifications and Experience Under GCP, the responsibility for the management of the IMP can be delegated from an investigator/institution to a pharmacist or other appropriate individual (such as a pharmacy technician) who is under the supervision of the investigator/institution. Most clinical trial pharmacy technicians and pharmacists are likely to come from the hospital sector. Experience would not necessarily be in clinical trials as employers are more interested in pharmacists or pharmacy technicians who are methodical and logical in their approach. Attention to detail is critical by the very nature of working with experimental compounds. Desirable Skills The ability to challenge current practices to ensure they are robust To understand and implement new rules and regulations Strong organisation and communication skills. To be a Pharmacy Professional 4

11 Roles in this area are typically advertised through specialist recruitment agencies or the Pharmaceutical Journal. They are also advertised in Clinical Research focus (CRf), the journal of the Institute of Clinical Research. To be a Pharmacy Professional 5

12 The NHS Hospital Pharmacy Clinical Trials Co-ordinator The role of the Pharmacy Clinical Trials Co-ordinator The role of the Pharmacy Clinical Trials Co-ordinator in an NHS hospital is to manage the pharmacy aspects of clinical trials, including investigational medicinal product (IMP) management, which should be delegated to the pharmacy department by the trial investigator. IMP management includes receipt, storage, dispensing, returns and full accountability which must be conducted in compliance with the protocol and the Medicines for Human Use (Clinical Trials) Amendment Regulations In order to manage IMPs to the required standards the co-ordinator will perform the following tasks for each trial: Review the trial protocol Liaise with the sponsor, investigator and research team Set-up and manage a pharmacy file Approve/design trial paperwork (e.g. prescriptions, drug accountability) Review packaging and labelling to ensure regulatory and hospital standards are met Provide protocol specific training and produce written instructions for pharmacy staff on how to handle the IMP, perform code-breaks etc. Ensure appropriate storage conditions and carry out stock inventories and expiry date checks Counsel patients on the correct use of the IMP Meet regularly with monitors for commercial studies and liaise with the investigator and the research team for non-commercial studies. As each clinical trial is unique with varying complexity, each trial will be dealt with on an individual basis. The role of the co-ordinator will often vary between commercial trials (i.e. sponsored by the pharmaceutical industry) and non-commercial trials, usually with the latter requiring more input. Non-commercial trials may require the co-ordinator to perform additional duties such as advising on protocol design and clinical trial authorisation (CTA) application or sourcing IMPs. To be a Pharmacy Professional 6

13 The co-ordinator s role also extends to dealing with the financial aspects of clinical trials for pharmacy, training pharmacy staff in GCP and IMP management in order to delegate appropriate duties, producing standard operation procedures (SOPs) for the conduct of trials in the pharmacy department and preparing for audits and inspections. There will inevitably be some overlap between the trial co-ordinator s role and that of the pharmacist working in research and development, depending on the configuration of the pharmacy clinical trials service within individual Trusts. Qualifications, Experience and Skills In the NHS Hospital setting, a member of pharmacy staff must be designated to take responsibility for the pharmacy clinical trials service. This may be a pharmacist registered with the Royal Pharmaceutical Society of Great Britain (RPSGB) or a pharmacy technician holding a minimum of NVQ 3 in pharmacy services or equivalent qualification. Therefore, the role of the Pharmacy Clinical Trials Co-ordinator may be undertaken by a pharmacist or pharmacy technician. There must be a designated pharmacist who takes ultimate professional responsibility for the pharmacy clinical trials service (e.g. Chief Pharmacist). The Pharmacy Clinical Trials Co-ordinator must have a thorough working knowledge of clinical trials legislation, research governance and Good Clinical Practice (GCP). Updates or training in GCP should occur at regular intervals (currently a time has not been specified) and assumes particular importance if there are changes in legislation or guidelines. Essential Skills Organisational skills Methodical and accurate Excellent communication and interpersonal skills Problem solving IT skills Confidentiality. Roles in this area are usually advertised in the Pharmaceutical Journal or on the NHS Jobs website ( To be a Pharmacy Professional 7

14 The Pharmacist working in Research and Development Role and Function There will inevitably be some overlap between the R&D pharmacist s role and that of the Clinical Trials Co-ordinator, depending on the configuration of the pharmacy clinical trials service within individual Trusts. IMP management Follow the RPSGB guidelines 4 for clinical trials services and ensuring that the pharmaceutical aspects of a clinical trial are managed in pharmacy in accordance with the clinical trials regulations and the NHS research governance framework. Regulatory affairs This involves helping investigators with applications to the MHRA for clinical trials authorisation, sourcing IMPs and supplies, advising on IMP aspects of investigator led clinical trials, and writing sections in the protocol regarding pharmacovigilance and the IMP. The role also involves liaising with the MHRA regarding any outstanding information required before final approval is granted. Pharmacovigilance This requires involvement in reviewing safety reports, annual safety reports and advising on pharmacovigilance systems including reporting SUSARs to the MHRA in accordance with the expedited reporting timelines. Inspection preparation and GCP audit of pharmacy department The R&D pharmacist will liaise with the pharmacy department(s) during preparations for inspections and may be the main point of contact for the inspectors during the inspection process. To be a Pharmacy Professional 8

15 It may involve working for the UKCRN (UK Clinical Research Networks) or an NHS R&D Trust. Qualifications and Essential Skills BSc Pharmacy, MRPharmS Training specific to GCP in pharmacy and clinical trials design and research methodology Excellent communication skills and organisational skills A thorough knowledge of the clinical trials regulations and relevant guidance to research in the NHS. Roles in this area are usually advertised in the Pharmaceutical Journal or on the NHS Jobs website ( To be a Pharmacy Professional 9

16 A Pharmacist as a Research Ethics Committee member Introduction Research Ethics Committees (RECs) are independent advisory bodies convened to protect research participants and to facilitate ethical research. Members of a REC include lay and expert members with a broad range of experience and expertise. Vacancies are advertised locally by the Strategic Health Authority and appointment follows an interview usually with the Chair and Vice Chair of the committee. Recognised RECs are recognised by the United Kingdom Ethics Committee Authority (UKECA) for the review of clinical trials of investigational medicinal products (CTIMPs), and apart from Type 1 Independent Ethics Committees, can also review non-ctimp research. Type 1 RECs recognised for review of Phase I Clinical Trials of Investigational Medicinal Products (CTIMPs) in healthy volunteers only. Type 2 RECs recognised for review of Clinical Trials of Investigational Medicinal Products (other than Phase I trials in healthy volunteers) taking place within a single domain, i.e. the area covered by a Strategic Health Authority (England), a Health Board (Scotland), a regional office of the NHS Wales Department or the whole of Northern Ireland. Type 3 RECs recognised for review of Clinical Trials of Investigational Medicinal Products (other than Phase I trials in healthy volunteers) taking place in more than one domain anywhere in the UK. Authorised RECs may only review non CTIMP research. Role and Function The pharmacist s role is more appropriate to the remit of Recognised RECs. This is unpaid and, although voluntary, may form part of the wider role of a clinical trials or R&D pharmacist. It is recognised that there may a perceived conflict of interest where a pharmacist advising an ethics committee also has responsibility for IMP management in that study. To be a Pharmacy Professional 10

17 This should be formally declared and recorded in the committee meeting minutes. Most committees meet once a month to review up to 10 new studies. Information for review includes the NRES application form, study protocol, investigator s brochure, CTA application form, patient information, GP or participant letters, patient diary cards, questionnaires and any posters or adverts to aid recruitment. Peer review of the proposed protocol or grant applications may also be provided. There is a large amount of prior reading, representing a considerable time commitment often in the pharmacist s own time. In addition to considering the health, safety and welfare of potential trial participants, the pharmacist is required to provide an expert opinion on the pharmaceutical aspects of CTIMPs undergoing ethical review. This includes study design and methodology, choice of IMP and comparator, blinding issues, formulation, administration, contraindications, side effects and interactions of the IMPs. Education and Training New REC members should attend induction training within the first six months of membership. This may be provided locally but there are several national introductory courses for ethics committee members. Regular training is a requirement of membership and pharmacists should attend at least one training day per year or be able to demonstrate that they have done six hours of self directed learning per year. Courses are plentiful and topics covered are varied so it isn t difficult to find training that is interesting and relevant to the type of research reviewed by the REC. Training is usually funded, but NHS pharmacists often have difficulty in securing time off to attend training courses. Qualifications and Experience As an expert member of a recognised REC, pharmacists must be currently registered with the RPSGB and have experience relating to the conduct of CTIMPs. To be a Pharmacy Professional 11

18 A working knowledge of the current legislation relating to clinical trials, and experience of the interpretation of published research papers (critical appraisal skills) is also valuable. Skills An ability to absorb large amounts of complex information in a reasonable time Good written and verbal communication Close attention to detail. To be a Pharmacy Professional 12

19 Clinical Supplies Pharmacist/Pharmacy Technician in the Pharmaceutical Industry Role and Function The Clinical Supplies Pharmacist s or Pharmacy Technician s responsibility within the sponsor company (or contract supplier) is to manage the supply chain (manufacture, packaging and distribution) for IMPs to ensure they are available for shipment in time for planned study start and that they meet the requirements of Good Manufacturing Practice (GMP) for IMPs and Good Clinical Practice (GCP) where applicable. The preparation of IMPs is typically more complex than the manufacture, packaging and distribution of commercial pharmaceutical products. The basic requirement for quality of the product is the same but the process is often more complex because products are still under development; clinical requirements tend to change frequently and every job tends to be a one-off. Additionally there is the requirement to ensure IMPs are blinded. A complex logistical exercise is what makes the job so interesting and challenging. There are a variety of roles that a pharmacist or pharmacy technician can be involved in: - Manufacture of dosage forms (e.g. tablets, ampoules, inhalers) Packaging and labelling of the dosage forms (blinded and randomised, in multiple languages) Project co-ordination; liaising with clinical departments (or sponsors in the case of contract suppliers) to define their requirements for future studies Contractor management; where a pharmaceutical company has outsourced its manufacturing, packaging or distribution of IMPs Education and Training Opportunities Pharmaceutical companies and contract suppliers mostly provide on-the-job training or may have a structured internal training programme. There are some external training courses available but there To be a Pharmacy Professional 13

20 is no substitute for practical, hands-on experience. It may be possible to register as a QP(IMP), see page 4. Qualifications and Experience Unlike other pharmacy roles, there isn t a legal requirement for a person managing clinical supplies within a pharmaceutical company to be a member of the RPSGB. However the skills and experience that a pharmacist or pharmacy technician gains from other more traditional pharmacy roles (hospital or community) are a good basis for transition to a role in clinical supplies. Additionally it s an ideal role for a non-eu pharmacist to achieve recognition for their qualification without the need to become a member of the RPSGB. It is also not uncommon to find people from other scientific disciplines working in clinical supplies. Essential Skills Organisational and time management skills Methodical and meticulous nature with attention to detail Communication and interpersonal skills Flexibility and versatility IT skills Influencing skills. Roles in this area are typically advertised in the Pharmaceutical Journal or through recruitment agencies. To be a Pharmacy Professional 14

21 Organisations and websites useful to pharmacy professionals in clinical research ABPI Association of the British Pharmaceutical Industry BARQA British Association of Research Quality Assurance CSDG Clinical Supplies Discussion Group Department of Health Department of Health and Medical Research Council Clinical Trials Tool Kit EMEA The European Medicines Evaluation Agency European Commission - Enterprise and Industry DG - Pharmaceuticals ICR Institute of Clinical Research MRC Medical Research Council MHRA Medicines and Healthcare Products Regulatory Agency NCRN National Cancer Research Network NHS R&D Department of Health Research and Development and guidance/researchanddevelopment/fs/en NRES National Research Ethics Service To be a Pharmacy Professional 15

22 Research and Development Forum RPSGB Royal Pharmaceutical Society of Great Britain UKCRN United Kingdom Clinical Research Network http/ To be a Pharmacy Professional 16

23 Glossary and useful definitions (IMP) Accountability Maintenance of records that adequately document IMP delivery to trial site, inventory at site, use by each trial subject and return to sponsor or alternative disposition of unused product. Active Control An active, rather than a placebo treatment allocated to a group of subjects to act as a reference for comparison with the trial drug. Adverse drug reaction (ADR) In the pre-approval clinical experience with a new medicinal product or its new usages, particularly as the therapeutic dose(s) may not be established: all noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions. The phrase responses to a medicinal product means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e. the relationship cannot be ruled out. Regarding marketed medicinal products: a response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases or for modification of physiological function (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting). Adverse event (AE) Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting). Archiving Controlled, long term retention and retrieval of trial documentation. To be a Pharmacy Professional 17

24 Audit A systematic and independent examination of trial related activities and documents to determine whether the evaluated trial related activities were conducted, and the data were recorded, analyzed and accurately reported according to the protocol, sponsor s standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s). Blinding/masking A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s). Single-blinding usually refers to the subject(s) being unaware, and double-blinding usually refers to the subject(s), investigator(s), monitor, and, in some cases, data analyst(s) being unaware of the treatment assignment(s). Case report form (CRF) A printed, optical, or electronic document designed to record all of the protocol required information to be reported to the sponsor on each trial subject. Centre(or site) The location(s) where trial related activities are conducted, trials may take place at a single or multiple sites. Clinical research Clinical research is the design, management, conduct and reporting of an evaluation of the impact of a therapeutic intervention. Clinical research aims to specifically answer a question about treating a disease through human participation, records based trials, clinical samples or in technology development for clinical use. It conducts the research, within the confines of current legislation and medical ethics, according to good clinical practice. Human participation: trials which require the intervention to be tested using direct contact with human participants (clinical trial). Records based trials: require access to personal data on health or lifestyle without direct contact (health economic trials or health services research). Clinical samples: trials which involve laboratory trials on human material. Technology development for clinical use: instrument development for diagnostic or surgical use or new techniques. To be a Pharmacy Professional 18

25 Clinical research associate(cra) Professional carrying out activities which may include investigational site selection, set up, initiation, monitoring and close out. Involvement in the operational aspects of all phases of clinical development is possible. Clinical trial administrator (CTA) Someone who administers, maintains and co-ordinates the logistical aspects of clinical trials according to Good Clinical Practice and relevant SOPs and acts as a pivotal point of contact for the clinical trial team. Clinical trial of an investigational medicinal product (CTIMP) Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product(s), and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy. The terms clinical trial and clinical study are synonymous. Clinical trial authorisation (CTA) The process for obtaining regulatory approval for a study which fall within the requirements of the EU clinical trials directive 2001/20/EC. Commercially sponsored trial A trial in which sponsor responsibilities are delegated to a company or organisation with a commercial interest in the investigational medicinal product. Comparator product An investigational or marketed product or placebo used as a reference in a clinical trial. Comparator trial A trial in which subjects are allocated to more than one alternative active treatment for comparative purposes. Competent authority Is responsible for implementation of the provisions of EU clinical trials directive 2001/20/EC. In the UK this is the licensing authority which acts through the Medicines and Healthcare Products Regulatory Agency (MHRA). To be a Pharmacy Professional 19

26 Competitor drug An alternative treatment used for the same indication as that proposed for the trial drug and therefore a competitor for market share. Contract (clinical) research organisation (CRO) A person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or more of a sponsor s trial-related duties and functions. Cross over trial A trial in which subjects receive one treatment followed by another, the treatments often being separated by a washout period when the subjects receive no treatment or placebo. Data management All procedures for handling and processing data collected during a trial. Double blind A system to ensure that the treatment allocated is unknown to both the investigator and the subject. Entry criteria Rules to ensure that suitable subjects are selected for entry into a trial. Inclusion criteria describe subjects who are suitable in terms of age, sex, disease. Exclusion criteria describe subjects who should not be selected, so as to avoid various health risks and to maximise the validity of the trial results. Essential documents Documents which individually and collectively permit evaluation of the conduct of a study and the quality of the data produced. Good clinical practice (GCP) A standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial subjects are protected. To be a Pharmacy Professional 20

27 Good manufacturing practice (GMP) That part of quality assurance which ensures that medicinal products are consistently produced and controlled to the quality standards appropriate for their intended use and as required by the Marketing Authorisation or product specification. GMP provides a model on which to base a documented quality system and describes the practical activities and the controls which must be in place in order to manufacture medicinal products which comply with their specification and are safe for use. International Conference on Harmonisation (ICH) GCP Guideline The ICH GCP guideline was developed to provide a unified standard for the European Union, Japan and United States, as well as those of Australia, Canada, the Nordic countries and the World Health Organisation (WHO). The principles form the basis of the GCP directive 2005/EC/28 5 and are incorporated in the amended regulations Indication The condition or disease for which a licensed or trial treatment is to be used. Informed consent A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject s decision to participate. Informed consent is documented by means of a written, signed and dated informed consent form. Inspection The act by a regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authority(ies) to be related to the clinical trial and that may be located at the site of the trial, at the sponsor s and/or contract research organisation s (CRO s) facilities, or at other establishments deemed appropriate by the regulatory authority(ies). Institute of Clinical Research (ICR) Premier organisation for clinical research respected as a key influencer, promoting knowledge and understanding by engaging the healthcare community and the general public. To be a Pharmacy Professional 21

28 Investigational medicinal product A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use. Principal Investigator (PI) or Chief Investigator (CI) A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator. If the trial is conducted at more than one site in any one country, the person with primary responsibility for the investigator related conduct of the study in that country may be called the chief investigator. Investigator brochure A compilation of the clinical and nonclinical data on the investigational product(s) which is relevant to the study of the investigational product(s) in human subjects. Investigational Medicinal Product Manufacturing Authorisation (MA(IMP)) An authorisation granted by the licensing authority to permit manufacture, assembly or import of IMPs in accordance with the conditions specified in the IMP manufacturing authorisation (MA(IMP)). Medicines and Healthcare Products Regulatory Agency (MHRA) The government agency which is responsible for ensuring that medicines and medical devices work and are acceptably safe. Monitoring The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s). Multicentre Trial A clinical trial conducted according to a single protocol but at more than one site, and therefore, carried out by more than one investigator. To be a Pharmacy Professional 22

29 National Research Ethics Service (NRES) The National Research Ethics Service works with colleagues in the UK to maintain a UK-wide system of ethical review that protects the safety, dignity and well being of research participants, whilst facilitating and promoting ethical research within the NHS. Non commercially sponsored trial A trial in which sponsor responsibilities are delegated to an individual, institution or organisation with no commercial interest in the investigational medicinal product. Non interventional trial A study of one or more medicincal products which have a marketing authorisation, where the following conditions are met: the products are prescribed in the usual manner in accordance with the terms of that authorisation the assignment of any patient involved in the study to a particular therapeutic strategy is not decided in advance by a protocol but falls within current practice the decision to prescribe a particular medicinal product is clearly separated from the decision to include the patient in the study no diagnostic or monitoring procedures are applied to the patients included in the study, other than those which are ordinarily applied in the course of the particular therapeutic strategy in question epidemiological methods are to be used for the analysis of the data arising from the study. Parallel trial A trial in which two or more separate groups of subjects are used to compare two or more treatments, each group receiving a different single treatment, usually by random allocation. Pharmacovigilance in clinical research The collection, monitoring, research, assessment and evaluation of information from investigators and trial subjects on the adverse events of IMPs with a view to identifying information on potential new hazards and preventing harm to trial subjects. To be a Pharmacy Professional 23

30 Phase of trials Clinical trials are conducted in phases. The trials at each phase have a different purpose and help scientists answer different questions: In Phase I trials, researchers test an experimental drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range and identify side effects. In Phase II trials, the experimental study drug or treatment is given to a larger group of people ( ) to see if it is effective and to further evaluate its safety. In Phase III trials, the experimental study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments and collect information that will allow the experimental drug or treatment to be used safely. Phase IV trials, post marketing studies delineate additional information including the benefits, optimal use and adverse events associated with the licensed medicine. Pivotal trial A trial conducted to GCP Guidelines and providing crucial efficacy and safety data to Regulatory Authorities. Placebo An inactive substance, usually formulated to be identical to the trial treatment, used to provide reference data, which controls psychosomatic effects and designed to minimise investigator and/or subject bias towards a treatment. Protocol A document that describes the objective(s), design, methodology, statistical considerations, and organisation of a trial. The protocol usually also gives the background and rationale for the trial, but these could be provided in other protocol referenced documents. Protocol amendment written description of a change(s) to or formal clarification of a protocol. To be a Pharmacy Professional 24

31 Qualified person (QP (IMP)) A person who by qualification and experience, can, to the satisfaction of the Regulatory Authority, certify the quality of production batches of IMPs. They are responsible for the quality systems in place to ensure compliance with GMP and will have a broad knowledge of pharmaceutical development and the clinical trials process. Quality Assurance All those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented (recorded) and reported in compliance with Good Clinical Practice (GCP) and the applicable regulatory requirement(s). Quality Control (QC) The operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of the trialrelated activities have been fulfilled. Randomisation The process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce bias. Research ethics committee Works with colleagues in the UK to maintain a UK-wide system of ethical review that protects the safety, dignity and well being of research participants. A recognised REC is legally recognised by the United Kingdom Ethics Committee Authority (UKECA) to give an ethical opinion on a clinical trial of an investigational medicinal product to be undertaken anywhere in the UK. An authorised REC is established under Governance Arrangements for Research Ethics Committees (GAfREC) but is not recognised by UKECA for the review of clinical trials of investigational medicinal products. Research governance The broad range of regulations, principles and standards of good practice that exist to achieve and continuously improve research quality across all aspects of healthcare in the UK and worldwide. To be a Pharmacy Professional 25

32 Royal Pharmaceutical Society of Great Britain (RPSGB) The professional and regulatory body for pharmacists in England, Scotland and Wales. It also regulates pharmacy technicians on a voluntary basis, which is expected to become statutory under anticipated legislation. Safety/tolerability An assessment of adverse events, serious events or toxicity associated with a treatment. Shelf life The period for which a product is confirmed as being fit for its purpose. Single blind A system to ensure that the treatment allocated is unknown to the subject. In this case the investigator does know which treatment the subject is taking. Source data verification Verifying that all information in original records and certified copies of original records of clinical findings, observations or other activities in a clinical trial are accurately reported in the Case Report Form (CRF). Sponsor An individual, company, institution or organisation which takes responsibility for the initiation, management and/or financing of a clinical trial. Standard operating procedure (SOP) Detailed, written instructions to achieve uniformity of the performance of a specific function. Suspected Serious adverse event/reaction (SAE/SSAR) An untoward occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity or consists of a congenital anomaly or birth defect. To be a Pharmacy Professional 26

33 Suspected unexpected serious adverse reaction (SUSAR) A suspected serious adverse reaction which is unexpected, meaning that the nature or severity are not consistent with the applicable product information, e.g. Investigator Brochure for an unapproved investigational product, or package insert/summary of product characteristics (SPC) for an approved product. United Kingdom Clinical Research Networks (UKCRN) Established to develop and strengthen NHS infrastructure to support the delivery of clinical research in the UK. Dedicated networks co-ordinate and support research in cancer, dementias and neurogenerative diseases, diabetes, medicines for children, mental health, primary care and stroke. Functions include developing a high quality research portfolio, offering a regulatory and governance advice service, supporting the work of clinical trials units and working closely with organisations responsible for funding research. To be a Pharmacy Professional 27

34 References 1 Medicines for Human Use (Clinical Trials) Regulation SI 2004 (No. 1031), HMSO, Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Official Journal of the European Communities L121/ The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006,Statutory Instrument 2006 No Practice guidance on pharmacy services for clinical trials, RPSGB/ ICR, June 2005 Available from: clinicaltrialsguid.pdf [Accessed 10 Oct. 2007] 5 Commission Directive 2005/EC/28 of 8th April 2005 laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products. Official journal of the European Union L91/13-19 To be a Pharmacy Professional 28

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36 The Institute of Clinical Research Tel: Fax: Web: