Examining the challenges and solutions to the implementation of trials in resource-limited settings: Limited Resource Trials.

Well-conducted clinical research trials that address questions relevant in resource limited settings (RLS), like the study examined here, are of critical importance in the fight against AIDS.1 Nevirapine (NVP) is a drug commonly used in RLS to prevent mother to child transmission (pMTCT). For many mothers, its use in pMTCT leads to later emergence of resistance to NVP, which is also standard of care for first line treatment in many RL S. Study A5207 sought to identify interventions to reduce NVP resistance. However, rapid implementation of such time-sensitive multi-site studies is challenging.2, 3, 5 Ensuring cross-site standardization and expeditiously implementing clinical research in RLS remains encumbered by inadequate infrastructure (e.g., need for appropriate space, training, and major equipment) and overburdened health systems.1, 2, 6, 8 Most often laboratory, pharmacy, clinical, and regulatory areas in RLS bring about start-up challenges. Laboratories play a critical role in the conduct of therapeutic clinical trials. They ensure not only the continuity of research data, but also quality of care and safety of participants on study.6 The Centers for Disease Control and Prevention (CDC) released a report in 2004 indicating the importance of and need for laboratory capacity building to support HIV/AIDS care programs in RLS.6 Although the report centered on laboratory services that were needed for the President's Emergency Plan for AIDS Relief, in which half the sites in this study have participated, CDC's findings suggested that laboratory capacity building in RLS is fraught with significant challenges needing to be addressed. Clinical research pharmacies play an equally important role in the research process. Research pharmacies are responsible for dispensing study drug, counseling research participants, conducting pill counts, and ensuring security and destruction of the study drug. When study product is dispensed outside the research area, careful attention to details around storage and administration is needed. Research conducted in hospitals also poses challenges. Hospitals in RLS often lack appropriate areas for storing study medications that require refrigeration. Clinical and pharmacy areas are frequently set up with open air ventilation, making it a challenge to find secure storage that is temperature controlled. Dependable power sources are needed for equipment and for alarm systems necessary to monitor temperature and provide security. To ensure the protection of human research participants and the quality of data collected for the study, an institutional review board (IRB) or ethics committee (EC) must approve the protocol document and the site-specific informed consent.7 The IRB should have appropriate representation from the medical community and from the community under study,7 which aids in the effort to ensure research is guided by ethical principles derived from the Common Rule. The AIDS Clinical Trials Group (ACTG) Network Operations Center works with scientists around the globe to develop and implement protocols that address questions relevant to people living with HIV and AIDS. The network began its first large international trial in 2004, the same year that the study A5207, “3 ART Strategies to Reduce NVP-Resistant HIV after Intrapartum Single Dose NVP,” was released to sites. The A5207 study was designed to evaluate the effectiveness of three different antiretroviral strategies toward prevention of NVP resistance in mothers who received single-dose NVP at the onset of active labor. Pregnant women 13 years and older were enrolled. The A5207 sample size was 420 mother/infant pairs, 70 in each of three arms. The A5207 study was funded through the Division of AIDS (DAIDS) at the National Institute of Allergy and Infectious Diseases (NIAID). The International Program and Laboratory Coordination Groups at ACTG Operations Center closely supported the development of sites and their laboratories for preparedness of studies such as A5207. Despite high levels of support, the last site opened the A5207 study in March 2009.