Understanding Trial Approval

How does an AIDS vaccine trial gain official approval and community support?

OFFICIAL APPROVAL

Before an AIDS vaccine is tested in people, review committees from the countries and institutions involved in the research must approve the trial. This official review process is designed to ensure that trials are conducted ethically. A simple definition of ethical research is that it upholds the safety, human rights and well-being of the volunteers involved in the trial. Review committees also provide guidelines for trial staff, and monitor the trial once it has begun. This review process is not unique to AIDS vaccines. It is part of all ethical research projects involving humans.

Who is involved in the official approval process?

All developed countries and a growing number of developing countries have official 'regulatory' committees that are trained in evaluating research proposals. These committees are made up of scientists, ethicists, community members and other experts who are independent from the trial sponsors and investigators. They provide an unbiased evaluation of the study proposal.

The names and composition of these review committees vary from country to country. However, in general there is an ethical review committee (ERC) and/or an institutional review board (IRB), and a scientific review committee. The main concerns of the IRB or ERC are the safety and human rights of trial participants and the ethical conduct of the trial. The scientific committee ensures that the trial is asking legitimate scientific questions and that the study is well designed to answer these questions. A few countries like Uganda and South Africa have AIDS vaccine committees that have been created specifically to review AIDS vaccine trials. All of these committees follow internationally agreedupon guidelines such as the Declaration of Helsinki, which gives a detailed definition of the requirements for ethical research. These guidelines create uniform ethical and scientific standards for all trials with human participants, wherever they take place.

However, just because a trial has been approved in one country it does not mean that it will be approved in another. A 'multisite' trial that is being conducted in more than one country must be reviewed and approved independently by each country.

What trial materials are reviewed?

All of these committees review the trial 'protocol', a detailed document that defines exactly how the trial will be carried out. A trial protocol contains in-depth information on every aspect of the trial such as the vaccine candidate that will be tested, the goals and design of the study, standards for including or excluding volunteers, the number of visits that volunteers will be asked to make to the trial site, the procedures to be done at each visit, the type of information that will be collected and how it will be analyzed.

ERCs and IRBs assess other trial documents too. These include advertisements that may be used to recruit volunteers and the forms and plans for obtaining 'informed consent', a crucial part of ethical research. Informed consent is an agreement signed by all volunteers that indicates their understanding of the purpose and goals of the trial; what will be done during the trial and for how long; the risks and benefits of participation; and their rights and responsibilities as research volunteers. ERCs and IRBs look at all available information about the vaccine candidate and the potential risks of trial participation to be certain that all of this information is provided to volunteers in ways that they can readily understand. They also review documents such as brochures, videos and short quizzes that may be used in the informed consent process.

These committees also consider the package of benefits that will be offered to volunteers during the trial and compensation such as travel costs to and from the trial site. They ensure that the benefits are fair but do not have an inappropriate or 'undue' influence on a volunteers' decision to participate.

When can a trial begin?

All of these committees have the opportunity to review the protocol, make suggestions, and recommend or require changes. Trial sponsors make required changes to the protocol or other documents and re-submit them. A trial can only begin after all of the committees have given their approval.

What happens once a trial has started?

After an AIDS vaccine trial begins, ERCs, IRBs and other groups receive regular updates that allow them to determine whether the trial is safe and ethical and that trial sponsors are fulfilling their obligations to participants. These committees also have the power to stop the trial if there are any concerns for safety or if the trial is not being conducted ethically.

BUILDING COMMUNITY SUPPORT

For a trial to be successful it is also important for trial site investigators and sponsors to inform and obtain general support from the countries and communities that will be involved in the research. (The agencies and scientists who have designed and funded the trial [the sponsors] are often separate from the clinics and staff [the investigators] who will conduct the trial.)

Site investigators often conduct meetings with community leaders and people who might volunteer for the trial. These consultations are not part of the formal approval process but they help to ensure that communities have accurate information and that their concerns are addressed. Sponsors may make changes to the trial protocol so that it reflects community input.

Trial sponsors frequently meet with political leaders, national AIDS organizations and other partners to build national and local support for AIDS vaccine research.

Many sites also establish community advisory boards (CABs). For AIDS vaccine trials these are usually committees composed of community representatives such as religious leaders, teachers, journalists, and people living with HIV and AIDS. CABs have a variety of duties that may include informed consent documents and educational materials, monitoring trials, and helping to inform and educate the rest of the community.