Book 5: Clinical trial phases

As all clinical phases of vaccine development have their own particular scientific requirements and ethical challenges, the choice of study populations for each trial phase should be justified in advance in scientific and ethical terms in all cases, regardless of where the study population is found. Generally, early clinical phases of HIV vaccine research should be conducted in communities that are less vulnerable to harm or exploitation, usually within the sponsor country. However, South Africa may choose, for valid scientific and public health reasons, to conduct any phase within its own populations, if scientific infrastructure and ethical safeguards can be ensured.

8.1 Initial stages in a vaccine development programme entail research in laboratories and the use of animals.

8.1.1 The transition from this pre-clinical phase to a phase I clinical trial, in which testing involves the administration of the candidate vaccine to human participants to assess safety and immunogenicity, is a time when risks may not yet be well defined.

8.1.2 Specific infrastructures are often required in order to ensure the safety and care of research participants at these early stages.

8.1.3 For these reasons, the first administration of a candidate HIV vaccine in humans should generally be conducted in less vulnerable research populations, usually in the country of the sponsor.

8.2 South Africa, however, may choose to conduct phases I/II and/or III (large-scale trials to assess efficacy) among its own populations, in cluding those that are relatively vulnerable to risk, after appropriate scientific, ethical and community consultation, for the following reasons:

8.2.1 The experimental HIV vaccine is directed primarily towards a viral strain that does not exist in the sponsor country but does exist in South Africa. Conducting phase I/II trials may be the only way to determine whether safety and immunogenicity are acceptable in the South African population, prior to conducting a phase III trial;

8.2.2 The level of HIV risk in the population is so high, and the gravity of HIV/AIDS so severe that South Africa is willing to test an HIV vaccine concept that is not being tested in another country;

8.2.3 Furthermore, if phase I and II trials are hosted in South Africa prior to phase III trials being initiated, this may result in important capacity building experiences (see Point 3) and opportunities to investigate important scientific questions.

8.3 A South African vaccine development programme that entails conducting some, most or all of its trial components in South Africa, or in communities that are relatively vulnerable to harm or exploitation, is ethically justified if:

8.3.1 The vaccine development programme is necessary for and responsive to the health needs and priorities of South Africa;

8.3.2 The vaccine is anticipated to be effective against a strain of HIV that is an important public health problem in South Africa;

8.3.3 Scientific and ethical review capability, and administrative and health infrastructure in South Africa are adequate to ensure the successful conduct of the proposed research;

8.3.4 Research ethics committee members, community representatives, investigators and policy makers in South Africa have determined that participants will be adequately protected from harm or exploitation; and

8.3.5 All other conditions for ethical justification, as set forth in this document, are satisfied.

8.4 In cases where it is decided to carry out phase I or phase II trials first in South Africa, due consideration should be given to conducting such trials simultaneously in the country of the sponsor, where this is practical and ethical.

8.5 Careful scientific and ethical consideration should be given to whether phase I and II trials that have been performed in a sponsor country should be repeated in the South African community in which phase III trials are to be conducted.