Clinical trials in sub-Saharan Africa and established standards of care: a systematic review of HIV, tuberculosis, and malaria trials.

Abstract

The minimum standard of care required for participants in clinical trials conducted in resource-poor settings is a matter of controversy; international documents offer contradictory guidance. To determine whether recently published trials conducted in sub-Saharan Africa met standards of care consistent with best current clinical standards for human immunodeficiency virus (HIV) treatment, tuberculosis treatment, and malaria prevention. Trials published during or after January 1998 that were indexed at the time of the MEDLINE and Cochrane Controlled Trials Register Search (November 20, 2003). All randomized clinical trials that were conducted in sub-Saharan Africa in 3 clinical domains: HIV disease, tuberculosis treatment, and malaria prophylaxis. To establish criteria for best current standards of care, evidence from the literature and published guidelines accepted for well-resourced settings were analyzed; the actual care offered in the trial was then compared with these standards. A total of 128 eligible articles described data from 73 different randomized clinical trials. Only 12 trials (16%) provided care that met guidelines to both intervention and control patients. Only 1 of the 34 trials that enrolled patients with HIV disease provided antiretroviral treatment that conformed to guidelines. Conversely, all tuberculosis treatment trials (n = 13, including 3 for HIV-infected patients) provided tuberculosis therapy that conformed to guidelines. Twenty-one (72%) of 29 malaria prophylaxis trials tested interventions that met guidelines, but only 3 (10%) used any active prophylactic intervention in the control group. Of the 59 trials (81%) that reported on the process of ethical review, all were reviewed by a host African institution and 64% were additionally reviewed by an institution in a developed country. Rates of adherence to established clinical guidelines of care in randomized clinical trials of HIV treatment, tuberculosis treatment, and malaria prophylaxis varied considerably between disease categories. In determining clinical standards for trials in sub-Saharan Africa, researchers and ethics committees appear to take the local level of care into account.