International Seminar on HIV Vaccine Research: Ethical and Regulatory Issues
Brasília, Brazil
October 4 - 5, 2006
Final Report
Brazilian National STD and AIDS Program, Ministry of Health
World Health Organization
Pan-American Health Organization
International AIDS Vaccine Initiative
Summary
List of abbreviations 3
Executive Summary 4
Introduction 5
1. International context and cooperation 7
2. The ethical review process in Brazil 9
3. The regulatory review process in Brazil 11
4. The National HIV/AIDS Policy 12
5. Ethics and access 14
Conclusions 15
Proposals and recommendations 16
Relevant links 18
List of Abbreviations
ANVISA – Agência Nacional de Vigilância Sanitária (Brazil’s national regulatory authority)
ARV – Antiretroviral
CAB – Community Advisory Board
CEP – Comite de Ética em Pesquisa (Brazil’s local research ethics committees/ institutional review boards)
CONEP – Comissão Nacional de Ética em Pesquisa (Brazil’s National Ethics Committee)
CTNBio – Comissão Técnica Nacional de Biossegurança (Brazil’s Technical Commission on Biosafety)
IAVI – International AIDS Vaccine Initiative
IBSA - India-Brazil-South Africa
MCT – Ministry of Science and Technology
MF – Ministry of Finance
MRE – Ministry of Foreign Relations
NIH – National Institutes of Health (U.S)
NGO – Non-governmental organization
PLHA – People living with HIV and AIDS
PN-DST/AIDS-SVS-MS – Programa Nacional de DST e HIV/Aids da Secretaria de Vigilância em Saúde (National STD and AIDS Program – Secretary of Sanitary Surveillance of the Ministry of Health)
SISNEP – Sistema Nacional de Informação sobre Ética emPesquisa (National System on Ethics in Research)
SUS – Sistema Único de Saúde (Brazilian Unified Health System)
UNAIDS – The Joint United Nations Programme on HIV/AIDS
Executive Summary
The International Seminar on “HIV Vaccine Research: Ethical and Regulatory Issues” took place on October 4 and 5, 2006 in Brasília, Brazil. The event brought together approximately 100 people, creating an unforeseen opportunity of exchange among ethical and regulatory agencies, policy makers, the scientific community, civil society and international organizations.
One of the key aspects highlighted during the event was the need for enhanced ethical and regulatory processes, as well as for expanded communication between the ethical and regulatory agencies and the scientific community involved in HIV vaccine clinical trials.
The acknowledgement of the importance of HIV vaccines, considering the significant impact that even a partially effective vaccine could have on controlling the pandemic, was a starting point for the discussions throughout the seminar. It was stressed at the meeting that such an impact will only be possible through an active scientific effort focused on answering key research questions in the shortest possible timeframe. Participants emphasized that in order to achieve this goal it will be critical to immediately ensure expedited ethical and regulatory review processes for HIV vaccine trial protocols, while at the same time ensuring the quality of the processes. This would further strengthen all research-related activities as well as relevant international collaborations.
Regarding international collaborative trials, some intrinsic challenges were considered, such as: efficient coordination and management mechanisms for trials happening simultaneously in several countries; compliance to international timeframes; development of national research capacity, product development and innovation, among others. All of these challenges require larger integration between the government, the scientific community, and the ethical and regulatory authorities in the country. It is also necessary to continue educating agencies and investigators about the overall process and to clarify the specific roles of each of the agencies involved and the researchers’ obligations in submitting protocols.
Having an appropriate legal framework and established regulatory bodies, such as the National Agency of Sanitary Surveillance (ANVISA), The National Ethics Review Committee (CONEP) and the National Technical Committee on Biosafety (CTNBio), has been important for conducting adequate HIV vaccine studies in Brazil.
However, several challenges were pointed out at this seminar, among them the inadequate institutional structure of the ethical and regulatory agencies, their limited funding, and above all the lack of appropriate communication pathways between the agencies and the investigators, which makes swift solutions to the identified problems impossible.
It was emphasized that CONEP’s current administrative structure and resources are not adequate to handle the ever-growing demands of the HIV/AIDS research field in the country, including HIV vaccine research.
ANVISA informed the group that it is reassessing its current institutional capabilities, and considering swifter mechanisms for reviewing HIV vaccine candidates to be tested in Brazil.
Also mentioned were both legal and institutional problems that have become obstacles to an expeditious review processes by CTNBio, the committee responsible for reviewing the biosafety aspects of all research involving genetically modified products.
A few proposals and recommendations were put forth with the intention of better defining roles and establishing commitments among the several stakeholders taking part in the event. One of the recommendations referred to the need for increased dialogue between agencies, government, researchers and civil society organizations. Another recommendation highlighted the need for more clarity about the regulatory process for everyone involved (including compliance to deadlines, the order of submission to the diverse agencies, and basic criteria for the preparation of applications).
Reinforcing CONEP’s administrative capacity was discussed as being a critically necessary measure, considering its importance in the approval and monitoring of clinical trials. It was also mentioned how the connections between CONEP and the CEPs need to be expanded and updated in order to further decentralize the ethical review process.
Additionally, participants discussed the need to reinforce ANVISA’s technical capacities for the review of experimental products through partnerships with other regulatory agencies and international institutions.
Finally, the group conceded that it is crucial to strengthen international partnerships according to scientific priorities for HIV vaccine development and national public policies on HIV/AIDS.
Introduction
The AIDS pandemic represents an unprecedented public health challenge. And as such, it requires a comprehensive response, which should prioritize prevention of new infections as well as care for those who have already been infected. In this scenario, research of new technologies, both for the prevention and treatment of AIDS, represents an essential strategy for the sustainability of the global response to the pandemic, aiming to introduce new and improved tools in the fight against it. A future HIV vaccine will be one of the most promising interventions to help control the pandemic, and its development is seen as an international priority by governments, health professionals and activists alike.
However, the complexities of the HIV vaccine research field are still significant and overcoming them depends on a global effort to accelerate research through international scientific collaboration, multi-sector communication and the quest for innovative solutions. Due to its established scientific capacity, as well as a comprehensive commitment to the fight against the epidemic, Brazil plays a pivotal role in the development of an HIV vaccine, and has been actively taking part in research efforts in this field for over a decade.
The International Seminar “HIV Vaccine Research: Ethical and Regulatory Issues,” sponsored by the Brazilian National STD and AIDS Program (PN-DST/AIDS-DST/AIDS-SVS-MS), WHO/UNAIDS and IAVI, represents a strategic opportunity to further strengthen Brazil’s role in HIV vaccine research.. The event has created a unique forum to discuss the national research scenario, having at its core the need for synergy among the several agencies and officials involved in the regulatory processes required for the development, manufacture and access to HIV vaccines. The seminar provided opportunities for exchange and partnering among those agencies and officials, taking into consideration both national and international dynamics.
The discussions concerned both ethical and regulatory agencies not only in relation to their current role in the review and approval of trial protocols, but also in the future licensing process for a product proven to be effective. For both purposes, it is paramount that Brazil relies on a high-quality, efficient system.
Acknowledging the positive aspects and advances of the Brazilian ethical and regulatory review systems–which include an unequivocal commitment to the protection of trial volunteers, as well as of the Brazilian population as a whole–the Seminar sought to identify the fundamental challenges identified through the national experience with HIV vaccine research and formulate propositions that could potentially contribute to and strengthen the Brazilian system.
Having this as a goal, the Seminar (1) emphasized both global and national contexts in which research efforts take place, considering the current scientific challenges as well as the history of national involvement in this field. (2) Provided a comprehensive description of the ethical and regulatory processes currently underway in the country. (3) Included a detailed description of the research being conducted in Brazil. (4) Promoted the debate about policies and incentives for health research innovation, and (5) Created the opportunity for the exchange of international experiences, covering perspectives from developed and developing countries.
The core discussion points at the meeting included: (1) The need to consider Brazilian regulatory processes in the context of an international cooperation and of an intensified research agenda. (2) The debate on ethical and regulatory review processes based on recent experiences and their impact on research. (3) The need for more clarity and integration in some aspects of the review process. (4) The need to strengthen technical and administrative capacities at the agencies/bodies that are responsible for ethical and regulatory reviews. (5) The improvement of communication pathways among the regulatory agencies and investigators.
The country must establish clear policies regarding Brazil’s participation in international HIV vaccine research networks and multilateral initiatives. As it applies to regulatory, ethical and legal aspects, these policies must take into account different legal frameworks, ensuring that Brazilian research legislations are followed, and that the time needed for the approval process in the country does not jeopardize the launch of protocols that must follow the same pace as other participating countries.
In 25 years of the HIV epidemic’s history in Brazil, a collective response has been built through several types of exchanges and partnerships between the government and other actors such as NGOs, universities, corporations, religious institutions, and international agencies, among others. These relations have been built on three main pillars: Firstly, the interdependence between prevention, care/treatment, and human rights efforts–a triangular foundation based on the principles of the SUS (Unified Health System) and on values that have emerged from the history of the epidemic. Secondly, understanding the universal access to antiretroviral treatment as a human right. Last, but certainly not least, the involvement of PLHA and more vulnerable populations with the Brazilian response to the epidemic. These three pillars describe the foundation for the national response to the epidemic, which is synergistic with the international HIV/AIDS scenario. The Seminar, keeping up with this historical reference, promoted debate among diverse social instances, and kept the Brazilian population’s public health needs in a context of respect for human rights at the core of the discussion.
This document is a record of the main topics that were addressed during the Seminar, including the relationships between national regulatory agencies, investigators, government, civil society, and foreign organizations. It provides a summary of the core issues that will guide the future agenda of the participating stakeholders, as well as the coordination between them. It also aims to highlight the issues and proposals that were featured in the debate.
1- International context and cooperation
According to UNAIDS data, approximately 39.5 million people are currently living with AIDS throughout the world (2006); 95% of them live in developing countries; 44% are women. Over 50% are young people between 15 and 24 years old, and over 5% are children under 15 years old. A vaccine continues to be the most promising option for ending the pandemic, attracting researchers and significant investments to the field.
The Seminar included several international groups who are currently dedicated to HIV vaccine research–involved in both scientific activities and on preparedness work to ensure an enabling environment for research, which includes a wide range of political initiatives, training, consultation and global coordination.
Among the many organizations working in this field, the WHO/UNAIDS Vaccine Initiative and IAVI are both well-known for their work in facilitating the international dialogue on vaccine research, and contributing to the building of national and global partnerships that aim to expand the support network and the capacity for participation in trials, especially in developing countries.
The governments of the USA and France, groups linked to the European Union, and public-private partnerships, such as IAVI, have invested considerably in the construction of clinical research networks in areas that are most vulnerable to the epidemic in order to conduct HIV vaccine trials there. South-South cooperation initiatives such as the IBSA Program (India-Brazil-South Africa) have also embraced this topic as a priority and are seeking to broaden the cooperation among the countries involved.
Private foundations, such as the Bill and Melinda Gates Foundation, and international scientific initiatives, such as the Global HIV Vaccine Enterprise, have recently reaffirmed their commitment to vaccine research, establishing partnerships to expand activities in the field and strengthen international capacity for basic and clinical research.
Although the investments from the pharmaceutical industry are considered to be below what would be ideal–given their experience in developing innovative products and the resources that are available to them–a few companies, such as Merck and GlaxoSmithKline have relevant programs in this area.
The combined result of these initiatives is an expanding field of research for HIV vaccines, with a growing number of products being tested, investigators from around the world who are involved, and protocols currently in motion. Today, vaccine research involves 23 countries from North and South, with dozens of trials that are currently in phases I, II and III. Despite the unquestionable scientific obstacles remaining, there are reasons for optimism in light of recent, more promising results. The international community is observing closely the trials that are currently being conducted, in which key issues for the future of vaccine research are being considered.
The growth that can be seen in the field has prompted new pathways for dialogue and cooperation. In Brazil, the Federal Government, investigators and civil society organizations have multiple connections–both formal and informal–to some of the international agencies mentioned above, which were represented at the Seminar. During the event it was possible to undertake a comprehensive discussion of these international cooperation mechanisms, including their vital role for advancing research, as well as the inherent challenges and risks involved in any international collaboration.