2 - Before and during the trial

The two principal approaches to improving the protections of human participants in international clinical trials are:

Ethics committees

The protocol must be submitted to an ethics committee in both the country where the trial is conducted, and the country of the sponsor. This procedure safeguards trial subjects in those settings where the existence and know how of ethics committees are incomplete but also offers input from local committees that may be aware of cultural barriers, economic constraints, health hazards and other factors that may elude members of international ethics boards.
In cases where local committees are not formed, the sponsor must address a third party (i.e. the WHO, international aid organizations etc.) and provide funds to help to build this capacity in a way that will ensure the independence of the committee from the sponsor;
The local ethics committee must be independent from the investigator and from the sponsor, and the roster of their members specifying professional skills and affiliations be made public;
People living with HIV/AIDS must be represented in both ethics committees evaluating the trial;
Research proposals submitted to ethics review committees should conform to the standard request from investigators in high income countries. Hence, all protocols should provide a clear explanation of study aims, methods, risks and benefits, and other treatment options. Presented protocols should also include an explanation of how the new interventions, that will be proven effective by the research conducted in the community will become available to some or all the host country population beyond the research participants themselves (cf below);

Involvement of organizations of people living with HIV/AIDS

In the setting of vulnerable communities the significant involvement of community representatives and advocates, allowing them to supply meaningful input, is an indispensable safeguard of research subjects.

By meaningful involvement it is intended that community representatives are individuals actively working for the HIV community, possessing basic scientific skills, and endorsed by the latter or by local NGOs, rather than being individuals selected by sponsors solely on the basis of HIV status, or of belonging to a known risk group.

Whenever such community representation is unavailable it is the responsibility of the sponsor to involve patient groups from high income countries providing them with resources to allow training and mentoring of their colleagues creating, whenever possible Community Advisory Boards (CABs) equipped by the knowledge necessary to express judgement on clinical trials in their countries. By meaningful input it is intended that such representatives be given access to research protocols in time to influence the design and ethics requirements, and in particular:

The protocol must also be submitted to the local CABs that will work in parallel to the local ethics committees.
The informed consent sheet must be written and/or revised in collaboration with these representatives;
Regular information should be given to these representatives about enrolment, the march of the trial, any unexpected outcome or adverse events, trial conclusion, and so on.

Informed consent for participation in the study

Informed consent sheets should be realised with the aid of local community and healthcare professionals to guarantee their readability and understanding, or the ability to be administered to individuals unable to read. Each informed consent sheet should contain clear and truthful explanations of the following:

The benefit/risk ratio for each trial participant, including the risk of adverse events, viral resistance, and limitations of future options.
Eventual treatment options available to potential participants.
Clear instructions regarding treatment management, adherence, and non medical factors able to interfere with treatment success, i.e. nutrition, life style factors etc.
A clear commitment regarding continuation of treatment and care beyond study termination.
A clear statement regarding the voluntary nature of the trial. This last is of particular importance when dealing with groups who have an impaired freedom of choice (i.e. prisoners, migrants, refugees etc.). When proposing a trial to such populations every effort must be made to dissuade local researchers from pressuring patients into participation.

Treatment during the trial

The Helsinki declaration recommends that participants in clinical trials should receive the best proven therapy. Neither the Helsinki declaration nor the CIOMS (Council for international Organizations of Medical Sciences) guidelines refer to restrictions in any circumstances. [2] Therefore, during the trial, the patients must receive nothing less the best proven therapy or the experimental drug / combination. Placebo is not acceptable where a treatment has proven been proven effective in the past, and hence new treatments must be compared to those already available. [3] lf a new treatment becomes available in the course of the study, the protocol must be revised and treatment arms adapted accordingly.

Expenses

The sponsor must pay for every expense related to participation in the study, including the provision of drugs to treat opportunistic infections, the best diagnostics. Sponsors must also ensure that patients receive the best possible environmental and nutritional conditions during the trial.