Repositioning the Bar: More Africans can now volunteer in clinical trials
AGHAN DANIEL

Africans wishing to volunteer in clinical trials for drugs and vaccines against emerging infectious diseases, including AIDS, TB and malaria, will now have an easier time meeting the set health criteria, as they will no longer be judged against Western standards, or ‘reference ranges. These new ranges will also help clinicians to better monitor the health of trial volunteers and define adverse events in trials.

‘Reference range’ is the medical term for the limits in readings of such medical tests as haemoglobin levels, white blood cell and CD4 cell counts, within which a person’s health is considered sound. At the AIDS Vaccine Conference in Seattle, USA in August, final results from a series of reference range studies for East Africans and Zambians were unveiled.

The studies that evaluated the reference range values, conducted by the International AIDS Vaccine Initiative (IAVI), U.S. Centers for Disease Control and Prevention (CDC) and the U.S. Military HIV Research Program (USMHRP), looked at the health of the kidneys, liver, blood and immune systems of about 5,500 healthy HIV-negative volunteers from Kenya, Uganda, Rwanda and Zambia. These countries, which are some of the hardest hit by the epidemic, play a crucial role in the testing of AIDS vaccine candidates that could help to stop the spread of AIDS.

Compared with similar populations in the West, the researchers found that healthy, HIV-negative adults in the African countries generally had lower levels of lymphocytes, neutrophils (a common type of white blood cells that protects the body against infection), and red blood cells. They also had higher levels of eosinophils (the white blood cells that fight off parasitic infections). Some sex-based differences were seen, as is the case with populations in the West.

The reference ranges for a host of medical indicators have been established based on studies on Caucasian populations living in North America and Europe. Although scientists realize that differences in these ranges based on geographic and environmental factors do exist, only limited information on what constitutes a healthy African adult have been published to date. As a result, the criteria for healthy African adults have not been formally established, and these “Western” ranges continue to be used in Africa.

The characterization of these African reference ranges is good news for trial physicians in Africa, and for trial volunteers too. “Localized ranges will help change the recruitment paradigm for clinical trials, by localizing the standards by which volunteers are assessed,” says Anatoli Kamali, an epidemiologist with the Medical Research Council/Uganda Virus Research Institute and the Protocol Chair of the IAVI-sponsored study of 2,400 individuals. In practical terms this means that more volunteers will be eligible to enroll in clinical trials, speeding up the recruitment process. “Improving participation in AIDS vaccine trials is the first step in ultimately reaching our goal of ending the AIDS crisis,” says Pat Fast, Executive Director of Medical Affairs at the study’s sponsoring organization, the International AIDS Vaccine Initiative (IAVI).

By applying local reference ranges in a USMHRP trial in Uganda already the rate of volunteers denied entry in studies has fallen – from 58% to 23%.

Local norms will also allow researchers to more accurately evaluate the health of volunteers throughout vaccine or drug clinical trials, says Mark de Souza, Director, International Laboratory Program, USMHRP.

A likely cause for the differences between African and Western reference ranges is the environment; people in Africa encounter different parasites and pathogens—and more of them—and their blood and organs respond accordingly. Differences in nutrition or genetic background may also play a role.
MESHA Features Service