Latin American Network For Clinical Research in Tuberculosis

Transcription

1 TECHNICAL MEETING: Latin American Network For Clinical Research in Tuberculosis Lima, Peru February 22 24, 2006 FINAL REPORT ORGANIZATION: Dirección General de Salud de las Personas Ministry of Health, Peru, National Health Strategy for the Control and Prevention of Tuberculosis Program in Infectious Disease and Social Change, Harvard Medical School, Boston, USA Socios En Salud Sucursal Peru /Partners In Health SPONSORS: Dirección General de Salud de las Personas Ministry of Health, Peru, National Health Strategy for the Control and Prevention of Tuberculosis Program in Infectious Disease and Social Change, Harvard Medical School, Boston, USA Socios En Salud Sucursal Peru / Partners In Health International Consortium for Trials of Chemotherapeutic Agents in Tuberculosis (INTERTB), St. George s University of London, London, UK TECHNICAL SUPPORT: Pan American Health Organization (PAHO) / World Health Organization (WHO) US Agency for International Development (USAID) FUNDING: Global Alliance for TB Drug Development; USAID/Vigía (Lima, Peru); Program in Infectious Disease and Social Change, Harvard Medical School, Boston, USA Pittsfield Anti-tuberculosis Association; David Rockefeller Center for Latin American Studies, Harvard University; Socios En Salud; ESKE S.R.L. (Lima, Peru) 1

2 1. Introduction Meeting objectives Report of Round Tables Specific conclusions of work in groups Conclusions Group Conclusions Group Conclusions Group Final speeches Appendix a. Speakers.. 11 b. Participants addresses. 12 c. List of participants in Groups. 14 d. Steering Committee.. 15 e. Agenda

3 1. INTRODUCTION Tuberculosis remains an important public-health problem in Latin American countries. The present situation is complicated by the presence of multidrugresistant TB (MDR), co-infection with HIV, and also by a series of organizational and financial problems. Efforts to develop solutions to these problems are hampered by a lack of evidence. This lack of information affects the ability of policymakers and national program staff to develop the most efficient, effective, and highest-quality care for patients who suffer from TB. Research is a powerful tool for the improvement of TB care; through research, we can increase the amount and quality of information available to decisionmakers to improve the management of TB. The term research here is used broadly to include, operational, epidemiologic, and clinical research. The Latin American Network for Clinical Research in Tuberculosis (RLIT) has as its objective the pursuit of clinical research that will enhance prevention and treatment strategies, which will improve outcomes and reduce morbidity and mortality caused by all forms of TB. Uncertainties about new treatment regimens and new drugs limit advances in disease control.. Although there are at least five new agents in the drugdevelopment pipeline, there is currently a shortage of sites prepared to implement clinical trials in TB. Thus the first meeting in Cali, Colombia, in 2005 was convened, with the intention of forming a Latin American research network; it concluded with the hope that answers to many pending questions could be found through multi-center studies. In this way, the RLIT serves the larger public-health community by advancing the readiness of Latin American sites for trials of new agents. Only wiith the involvement of existing clinical trial networks, and groups involved in the science and finance of new drug discovery and testing, can groups like the RLIT hope to be successful. The goal of the second meeting of this group, held in Lima, Peru in February 2006, was to review in depth the research methods specific to controlled clinical trials by examining current studies. In addition, the group was to identify 2-3 multi-center studies to be implemented in the region, and elaborate a staged, collaborative work plan for each of these studies, which would include preparing a complete protocol and securing funding. Through this meeting and other efforts of the RLIT, we hope to prepare new sites in 3

4 Latin America to participate in Phase II and Phase III clinical trials of new antituberculosis agents in the near future. Finally, we note that the countries of Latin America that have committed to this network are prepared to collaborate to achieve their core, common mission of developing alternative solutions to problems that are common in the countries forming the network. This powerful, shared commitment and collaborative approach will enhance the impact of clinical trials and other forms of clinical research in tuberculosis. 2. MEETING OBJECTIVES A. To implement a Latin American network for applied, multi-site tuberculosis research. B. To develop participant capacity in methods and designs of, state-of-the art tuberculosis research. C. To identify 2-3 multi-center trials/ studies to be implemented in the region. D. To elaborate a work plan for each these studies, which includes securing funding and preparing a complete protocol. 4

5 The meeting was designed with a combination of plenary sessions and round tables (see agenda below in appendix e). During the plenary sessions, participants learned about ongoing or recently completed tuberculosis research studies, research networks, and funding sources and policy initiatives, which could support the development of more sites ready to conduct trials and trials themselves. During the round tables, participants had the opportunity discuss in more depth existing studies and apply lessons learned from these studies to discussions of future work to be undertaken by the network. Below we summarize the round table discussions. 3. REPORT OF ROUND TABLE Round table on efficacy and tolerability studies: A. Proposal to create a Latin American Network to conduct Clinical Trials. Creation of a national network: The group concluded that each country wishing to participate in the Latin American Network (RLIT) should begin by creating a National Network. In this forum, the questions of scientific interest and the reality of the research environment of each country can be discussed. The advantages of having a National Network are the following: Each country can mobilize political will and develop an inventory of its own resources. The national network can serve as a decision-making body (e.g., regarding participation in a proposed multi-site study). B. Costs and benefits of participation in a clinical trial. Generally the clinical trials have a budget for their execution. The agencies that handle the funds know that the country needs resources to employ more people, to improve its laboratory, to make changes to the program on a national level, so that the patients can receive directly observed therapy (conventional clinical trial protocol is for all medication to be delivered under direct supervision). Benefits will accrue to study subjects as well as to hospital centers where the study is being carried out. This will enhance the training for staff, and 5

6 quality of care provided over the longer term; thus, indirectly more users of the systems will benefit It is important to emphasize that clinical trials and research require specialized training beyond the routine work of the National Tuberculosis Program. Colleagues from Brazil noted the necessity of substantial training (with nurses, doctors, and patients) to create the culture of clinical trials, prior to enrolment of the first patient. The RLIT should accommodate other professionals with interest in research other than clinical trials of new drugs; examples mentioned included studies of novel diagnostic and monitoring methods. The group underscored the importance of ethics committees, which comprise community members, who protect the interests of study subjects. The involvement of ethics committees ensures that the study is reviewed in all its aspects, which in turn would increase the confidence of the patients in the trial. The research experience, which each country brings to the table, is important to consider. Countries that have already participated in multicenter studies even though they may not necessarily have been clinical trials--have already demonstrated their ability to work collaboratively, with good communication and an ability to manage bacteriologic samples according to study protocols. In this presentation Dr. Villarino refers to Dr. Ann Ginsberg who earlier had explained the Global Alliance for TB Drug Development (GATB). The TB Alliance is leading the process to accelerate the discovery and development of new, faster and better novel drugs to fight TB. Round Table on Early Bactericidal Activity Studies: The group read the EBA protocol and appreciate the importance of these studies in advancing anti-tuberculosis drug development. All participants manifested interest in participating in EBA studies. They note the importance of specifiying criteria for inclusion or exclusion of patients. The only site in the region that has carried out an EBA test is Vitoria, Brazil. Brazil presented its experience, offering the possibility of advising the countries that are going to participate. An EBA study of high-dose RIF, in at least one other site hopes to participate, will allow us to demonstrate the benefits of such an 6

7 experience. This extension could permit additional technical support to be available throughout the region. Appropriate biosafety conditions must be in place in hospitals or laboratories for participation in such studies. For these multi-center studies it is important to consider including not only countries of high prevalence of the disease but also countries of low prevalence. 4. SPECIFIC CONCLUSIONS OF WORK IN GROUPS Although originally it was planned to divide into groups that would develop clinical and operational research separately, through the course of the discussion, all groups saw the need to include operational research to a certain extent. Group 1: MDR TB clinical trials and operational research (Dr. Montoro) The following fundamental points were discussed: Causes and consequences of default of MDR-TB treatment were identified as an important issue to be researched. For this the following studies were considered: A follow-up study of patients after defaulting from MDR-TB treatment. It has been observed that in many cases patients that abandon treatment remain bacteriologically negative. A study to document the delays both prior to appropriate treatment and until cure is achieved. Group members identified as important the introduction of methods for rapid diagnosis of MDR-TB. In particular, participants proposed the following concepts for research on MDR-TB treatment, for further development; they should be developed into full concept papers in the next four months and presented at the next meeting to be held in Brazil. a. The current duration of treatment is often extended due to a perceived delay in receiving final culture results. Participants proposed documenting the time lapsed between various steps in treatment (e.g., between the last sample collected for culture and the end of treatment) 7

8 b. Frequency and timing of adverse events of anti-tuberculosis agents received during treatment for MDR-TB. These are perceived to influence abandonment by patients. Group 2: Operational Research (Dr. Orejel) This group identified factors associated with failure of Category I therapy as their top research priority. They proposed that the next step to further develop this concept should be a literature review, which includes not only biologic risk factors, but also social and anthropological factors. Group 3: Clinical Trials (Dr. Goldberg) Discussing the topic of research in clinical trials, a Central American network spontaneously formed between El Salvador, Honduras and Costa Rica with the intention of involving also Guatemala, Panama and Nicaragua. Thus it would be organized like a Central American studies group within the RLIT. 8

9 The members of this group expressed their enthusiasm about becoming involved and participating effectively. They explained their interest in choosing among the ideas that were already proposals for protocols. In particular two studies were considered: Use of rifampin in high doses. (Recognizing the technical challenges in this case, it could be possible to begin with a simpler trial.) This protocol is currently under revision for financing, and a decision is expected in May of Currently three countries are included in the trial. Other interested countries are invited to contact INTERTB with questions about the protocol, the qualification of participating countries, and about trainings for participants. Also, as Ann Ginsberg mentioned earlier, other countries are encouraged to contact Global Alliance for TB Drug Development, for these same reasons. The GATB has a contractor evaluating site readiness around the world; interested groups should let Dr. Ginsberg know. Predictors of relapse after Category I therapy. Idea presented by Amina Jindani. Main writer is Carlos Alvarado from Honduras; Reynaldo Dietze from Brazil will advise in writing the protocol. Next steps There are existing examples of research networks, such as Amazon Malaria Initiative and TBTC. The RLIT will adapt approaches used by many of these other networks to achieve its objectives. 1. Members of all groups endorsed the following steps for development of ideas discussed at the meeting into protocols: Write concept papers. a. Finish the concept papers for the PAHO meeting in Argentina in May Present the concept paper in Argentina in May Present the concept paper to RLIT for revision, and so that the consortium decides whether to continue with the development of the protocol or not. b. If approved, develop and implement the protocol. The consortium will assign a committee for the writing of the protocol to ensuring that participants with a diversity of background experiences are represented (laboratory, clinical work, statistics). The plan is to finish the protocol for the meeting in Brazil in March of Develop a strategic plan 9

10 3. Form a steering committee (see appendix d for appointed members of the committee) 4. Develop a mission statement 5. Develop by laws 6. Produce a web page 5. FINAL SPEECHES Final Speech of Dr. Amina Jindani Dr. Jindani spoke of her two dreams: to eradicate TB and to construct a Latin American Research Network. Her speech concluded with an explanation of Dr. Reynaldo Dietze from Brazil about the planning of the RLIT meeting to be held during the course of the next year in his country. She maintained that nothing would be possible without the organization of a network. The case of Amazon Malaria Initiative, as presented by Dr. Jaime Chang, has been immensely successful and is a good example to follow. The two meetings so far have been of much progress and help. The final idea is to keep contributing to the progress so that the dreams can become reality. 10

11 Final speech of Dr. César Bonilla This is part of a very slow process. We will not be able to obtain immediate results. Doubts exist, and some questions exist to which we must respond. This Latin American Network is an alternative response. representatives of all these countries to spread the Network and the potential benefits that this can bring. He concluded by expressing thanks to all the people who, in one form or another, have helped to make this happen. He urged a commitment from all 6. APPENDIX a. SPEAKERS Dr. César Bonilla Asalde. National Coordinator, National Strategy for the Prevention and Control of TB MINSA. Dr. Marcos Burgos. Assistant Professor, University of New Mexico, School of Medicine. Department of Internal medicine, Division of Infectious Diseases, Albuquerque, New Mexico. Dr. Jaime Chang. USAID, Peru. Dr. Reynaldo Dietze. UFES, Brazil. Dr. Beatriz Ferro. Investigator and leader of the Mycobacterium Laboratory at CIDEIM, Cali Colombia. María Freire. Global Alliance for TB Drug Development, USA. Ann Ginsberg. Global Alliance for TB Drug Development, USA. Dr. Stefan Goldberg. Medical Officer; CDC NCHSTP, Division of TB Elimination; Clinical and Health Systems Research Branch. Dr. David Hadad. Universidade Federal do Espírito Santo (UFES), Brasil. Tom Harrison. INTERTB, UK. Dr. Amina Jindani. Honorary Senior Lecturer; St. George s Hospital Medical School; University of London. 11

12 Dr. Carole Mitnick. Instructor, Department of Social Medicine, Harvard Medical School; Boston, MA, USA. Dr. Ernesto Montoro. Chief of the National Laboratory of Reference and Research in Tuberculosis and Mycobacterium. Institute of Tropical Medicine, Pedro Kourí IPK. Dr. Hildegard Piñeros. CIDEIM, Colombia. Nina Schwalbe. Global Alliance for TB Drug Development, USA. Dr. Elsa Villarino. Team leader: TB Trials Consortium (TBTC); Clinical and Health Systems Research Branch; Division of Tuberculosis Elimination; National Center for HIV, STD, and TB Prevention; Center for Disease Control and Prevention. Dr. Martín Yagui. Socios En Salud, Peru. b. PARTICIPANTS ADDRESSES Name From address Amalia Rodríguez De Paz El Salvador Amina Jindani UK Ana Jiménez Solís Costa Rica Ann Ginsberg USA Aurora Rodríguez Cabrera Dominican Republic Beatriz Ferro Ramos Colombia Carlos Alvarado Gálvez Honduras Carlos Velásquez Rondon Peru Carlton Evans USA Carmen Suárez Nole Peru Carole Mitnick USA Claudia Montero Valencia Brazil Daniel Palazuelos Mexico Daniel Yumpo Castañeda Peru David Hadad Jamil Brazil Deccy Santana Mendoza Ecuador Elsa Villarino USA Ernesto Montoro Cardoso Cuba 12

13 Felícita Palacios Cuentas Peru Germán Henostroza Alayza Peru Héctor Jave Castillo Peru Héctor Palomino Guzmán Peru Hildegard Piñeros Heilbron Colombia Hugo Cornejo Espinoza Peru Irene Gonzáles Peru Ivonne Rosa Orejel Juárez Mexico Jorge Camacho Molina Ecuador Eduardo Gotuzzo Herencia Peru José Yamanija Kanashiro Peru Juan Carlos Jara Rodríguez Paraguay Juan Carlos Millán Peru Julio Garay Ramos El Salvador Julio Torres Chang Peru Lita Alarcón Julca Peru Lucina Gutiérrez Mexico Marcos Burgos USA Marcus Conde Barreto Brazil Maria Delgado San Román Peru Maria O Hara García Peru ohara03@yahoo.es Maricela Curisinche Rojas Peru mcurisinche@yahoo.es Nilda Trejo Maguina Peru nildavictoria@yahoo.com Nina Schwalbe USA nina.schwalbe@tballiance.org Omar Gonzáles Escalante Peru omargonzales@hotmail.com Oscar Chang Neyra Peru jachang@usaid.gov Oscar Niño de Guzmán Peru osquinigu@yahoo.es Oswaldo Videira Paredes Peru mdvideira@yahoo.es Rafael Durand Concha Peru rdurand_ses@pih.org Reynaldo Dietze Brazil rdietze@ndi.ufes.br Scott Franzblau USA sgf@uic.edu 13

14 Stefan Goldberg USA Thomas Stephen Harrison UK Vilma Águila Rivera Peru Zaida Yadon Argentina c. LIST OF PARTICIPANTS IN GROUPS: Group MDR TB Final condition of treatment abandonments Julio Torres Chang Nilda Trejo Maguiña Maricela Curisinche Rojas Irene Gonzáles Apercana Diagnostic delay Mireya Palacios Cuentas Carlos Velásquez Rondón Carmen Suárez N Vilma Águila Rivera Ernesto Montoro Group Operational Research Hugo Cornejo Espinoza Peru Oswaldo Videira Paredes Juan Carlos Jara Rodríguez Rosa Ivonne Orejel Juárez Lucina Gutiérrez Deccy Santana Mendoza Aurora Rodríguez Germán Henostroza Alayza Oscar Niño de Guzmán Velarde Maria O Hara García Group Clinical Trials Rafael Durand Reynaldo Dietze Carlos Alvarado Gálvez Amalia Rodríguez De Paz Julio Garay Ramos El Salvador Omar Gonzáles Escalante Daniel Yumpo Castañeda Tom Harrison Marcos Burgos Hildegard Piñeros Beatriz Ferro Ramos 14

15 Ana María Jiménez Solís Claudia Montero Amina Jindani Stefan Goldberg d. STEERING COMMITTEE Dr. Cesar Bonilla (MINSA-Peru) Dr. Amina Jindani Dr. Reynaldo Dietze CIDEIM (Beatriz Ferro) SES/PIH/HMS OPS Dr. Carlos Alvarado Dr. José C. Yamanija (Secretary) Consultants/Advisors: Dr. Ernesto Montoro (IPK) Dr. Jaime Chang (USAID) Dr. Stefan Goldberg (CDC) Dr. Elsa Villarino (CDC) Dr. Marcos Burgos e. AGENDA TECHNICAL MEETING: LATIN AMERICAN NETWORK FOR CLINICAL TUBERCULOSIS RESEARCH Lima, February 22-24, 2006 TARGET AUDIENCE: This conference was designed for: Directors of Tuberculosis Control Programs of Latin American countries. Persons with experience or interest in tuberculosis research. Proposed participants: 2-3 participants (the Director of the TB Program and 1-2 prospective researcher[s]) from each Latin American country with an elevated TB burden; as well as other health professionals from metropolitan Lima and from the Peruvian National Strategy for the Prevention and Control of TB. METHODOLOGY: The conference included individual work (completing surveys, reviewing study protocols) plenary presentations, discussions, and round tables. LOCATION: Hotel El Condado Alcanfores 464- Miraflores - Lima Telephone (511)

16 Fax (511) CERTIFICATION: By the end of the conference, each participant was committed to complete specific tasks from the work plan of one or more of the four studies. During the meeting or prior to arrival at the meeting, each participating country was expected to have completed two surveys and reviewed background materials. TECHNICAL MEETING: LATIN AMERICAN NETWORK FOR CLINICAL TUBERCULOSIS RESEARCH Lima, Peru, February 22, Day 1 Introduction & Overview: Phase II Trials Morning Moderator: Maria Freire, GATB, USA 8:00 Registration 8:45 Welcome & Introduction to Network Cesar Bonilla, NTP, Peru 9:15 10:00 Process of developing, testing, and gaining approval for a new agent or for a new indication for an existing agent Elements required to introduce new drug Elements required for new indication for existing drug Benefits of multi-site work High-dose RIF trial: EBA Phase IIB Phase III Ann Ginsberg, GATB, USA Amina Jindani, INTERTB, UK 10:45 Coffee break 11:15 12:00 TBTC Study 27 & 28: Evaluation of the activity and tolerability of moxifloxacin Considerations for lab preparation of studies using quantitative culture (EBA, SSCC) Stefan Goldberg, CDC, USA Beatriz Ferro, CIDEIM, Colombia 12:30 Discussion 1:00 Lunch Afternoon 2:15 Round Table: Session I: Early bactericidal activity Moderator: Cesar Bonilla Facilitators: Beatriz Ferro, CIDEIM, Colombia; Ernesto Montoro, Instituto Pedro Kouri, Cuba; Tom 16

17 Efficacy & tolerability Harrison, INTERTB, UK Stefan Goldberg; Elsa Villarino, CDC, USA; Amina Jindani 3:45 Coffee break 4:15 Report on Round Table: Session I 5:00 Survey Instructions Hildegard Piñeros, CIDEIM, Colombia 5:30 Adjourn, Day 1 Lima, Peru, February 23, Day 2 Phase III trials & other considerations Morning Moderator: Tom Harrison 8:30 Complete or update surveys 10:00 GATB Development Initiative Ann Ginsberg 10:30 Coffee break 11:00 11:30 12:00 Phase III trial considerations and examples: Interpreting results from Phase II trials to design Phase III High-dose rifapentine in HIV coinfected OFLOTUB: gatifloxacin in a regimen shortening trial Elsa Villarino Amina Jindani Carole Mitnick (for Tom Kanyok) 12:45 Lunch Afternoon 2:00 Round Table: Session II: Phase III trial issues: methods, sample size and recruitment, willingness to participate Moderator: David Haddad, Brazil Facilitators: Elsa Villarino, Amina Jindani, Maria Freire, Stefan Goldberg 3:15 Report on Round Table Session II 3:45 Coffee Break 4:15 4:45 MDR-TB trials: prophylaxis, first-line, salvage therapy Discussion of funding sources and challenges Carole Mitnick, HMS, USA Nina Schwalbe, GATB, USA 5:30 Adjourn, Day 2 17

18 Lima, Peru, February 24, Day 3 Experience with Other Research Models & Future Planning Morning 8:30 Multi-site operational research: advantages and considerations Moderator: José Carlos Yamanija Kanashiro, Socios En Salud, Peru Carole Mitnick 9:00 Rapid diagnostics: operational research Martin Yagui, Socios En Salud, Peru 9:30 Amazon Malaria Initiative: A successful model for a research network Jaime Chang, USAID, Peru 10:00 Coffee Break 10:30 11:00 11:15 Presentation of results of surveys re: priority research areas Group assignments for discussion of future plans Round Table: Session III: (future development, priorities, action plan re development, support, training, role assignment, etc.) OR projects Clinical trials Oswaldo Jave, MINSA, Peru; Hildegard Piñeros Oswaldo Jave Martin Yagui, Oswaldo Jave, Jaime Chang Amina Jindani, David Haddad, Elsa Villarino, Ann Ginsberg 1:00 Lunch Afternoon Moderator: Marcos Burgos, University of New Mexico, USA 2:15 Report on Round Table: Session III 3:15 Next steps: Meeting in Brazil Collaboration with other groups Other Reynaldo Dietze, UFES, Brazil Marcos Burgos 4:00 Adjourn, Day 3 Cesar Bonilla 4:30 Reception & photo If you have any questions or would like updated information please write to the following addresses: mailto: vhuayta_ses@pih.org mailto: jcyamanija_ses@pih.org 18