Author Affiliations: Institute for Clinical Research and Health Policy Studies (Dr Kent and Mr Kupelnick) and Division of Geographic Medicine and Infectious Diseases (Dr Mwamburi), Department of Medicine, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Mass; Africa Centre for Health and Population Studies, Mtubatuba, South Africa (Dr Bennish); and Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece (Dr Ioannidis).
Context 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.
Objective 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.
Data Sources Trials published during or after January 1998 that were indexed at the
time of the MEDLINE and Cochrane Controlled Trials Register Search (November
Study Selection All randomized clinical trials that were conducted in sub-Saharan Africa
in 3 clinical domains: HIV disease, tuberculosis treatment, and malaria prophylaxis.
Data Extraction 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
Data Synthesis 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.
Conclusions 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.
Kent DM, Mwamburi DM, Bennish ML, Kupelnick B, Ioannidis JPA. Clinical Trials in Sub-Saharan Africa and Established Standards of CareA Systematic Review of HIV, Tuberculosis, and Malaria Trials. JAMA. 2004;292(2):237-242. doi:10.1001/jama.292.2.237