HIV This Week

Morin SF, Morfit S, Maiorana A, Aramrattana A, Goicochea P, Mutsambi JM, Robbins JL, Richards TA. Building community partnerships: case studies of Community Advisory Boards at research sites in Peru, Zimbabwe, and Thailand. Clin Trials. 2008;5(2):147-56.

Differences in resources, knowledge, and infrastructure between countries initiating and countries hosting HIV prevention research trials frequently yield ethical dilemmas. Community Advisory Boards have emerged as one strategy for establishing partnerships between researchers and host communities to promote community consultation in socially sensitive research. Morin and co-authors undertook to understand the evolution of Community Advisory Boards and community partnerships at international research sites conducting HIV prevention trials. Three research sites of the HIV Prevention Trials Network (HPTN) were selected to include geographical representation and diverse populations at risk for HIV exposure - Lima, Peru; Chitungwiza, Zimbabwe; and Chiang Mai, Thailand. Data collection included review of secondary data, including academic publications and site-specific progress reports; observations at the research sites; face-to-face interviews with Community Advisory Boards members, research staff, and other key informants; and focus groups with study participants. Rapid assessment techniques were used for data analysis. The authors found that two of the three Community Advisory Boards developed new strategies for community representation in response to new studies. All three Community Advisory Boards expanded their original function and became advocates for broader community interests beyond HIV prevention. The participation and input of community representatives, in response to critical incidents that occurred at the sites over the past five years, helped to solidify partnerships between researchers and communities. In terms of limitations the authors point out that Rapid Assessment is an exploratory methodology designed to provide an understanding of a situation based on the integration of multiple data sources, collected within a short period of time, without a formal examination of transcribed and coded data. Case studies, as a method, are meant to draw out what can be learned from a single case but are not, in the scientific sense, generalizable. They conclude that in developing countries, Community Advisory Boards can be dynamic entities that enhance the HIV research process, assist in responding to issues involving research ethics, and prepare communities for HIV research.

Editors´note: This assessment of changes in community advisory board conduct and roles over a five year period found that at each site a conflict or challenge arose in which the views and assistance of community advisory board members became not only valuable to the research team but also important for the future success of the research. These conflicts or challenges generated substantial interactions of mutual benefit as issues were debated which led to a more genuine partnership. Community advisory boards clearly can be dynamic entities striving to better represent and advocate for the communities.

Djomand G, Metch B, Zorrilla CD, Donastorg Y, Casapia M, Villafana T, Pape J, Figueroa P, Hansen M, Buchbinder S, Beyrer C; for the 903 Protocol Team. The HVTN Protocol 903 Vaccine Preparedness Study: Lessons Learned in Preparation for HIV Vaccine Efficacy Trials. J Acquir Immune Defic Syndr. 2008;48(1):82-9 2008

Successful recruitment and retention of HIV-uninfected at-risk participants are essential for HIV vaccine efficacy trials. A multicountry vaccine preparedness study was started in 2003 to assess enrolment and retention of HIV-negative high-risk participants, and to assess their willingness to participate in future vaccine efficacy trials. HIV-negative high-risk adults were recruited in the Caribbean, in Southern Africa, and in Latin America, and were followed for 1 year. Participants included men who have sex with men, heterosexual men and women, and female sex workers. History of sexually transmitted infections and sexual risk behaviours were recorded with HIV testing at 0, 6, and 12 months, and willingness to participate in future vaccine trials was recorded at 0 and 12 months. Recruitment, retention, and willingness to participate in future trials were excellent at 3 of the 6 sites, with consistent declines in risk behaviours across cohorts over time. Although not powered to measure seroincidence, HIV seroincidence rates per 100 person-years (95% confidence interval [CI]) were as follows: 2.3 (95% CI: 0.3 to 8.2) in Botswana, 0.5 (95% CI: 0 to 2.9) in the Dominican Republic, and 3.1 (95% CI: 1.1 to 6.8 ) in Peru. The HIV Vaccine Trials Network 903 study helped to develop clinical trial site capacity, with a focus on recruitment and retention of high-risk women in the Americas, and improved network and site expertise about large-scale HIV vaccine efficacy trials.

Editors´note: Finding populations with sufficient risk for HIV infection to support the seroincidence demands of trials is a start but they must also have high rates of retention for there to be adequate power to confirm or refute the study’s hypothesis. Even participating in a study to assess enrolment, retention, and HIV incidence can lead to declines in risk behaviour and HIV incidence, above those already happening in the overall general population. Such a positive effect of being studied is sometimes called the Hawthorne Effect.

Hughes S, L Cuffe R, Lieftucht A, Garrett Nichols W. Informing the selection of futility stopping thresholds: case study from a late-phase clinical trial. Pharm Stat. 2008 Mar 27 [Epub ahead of print]

In an environment where (i) potential risks to subjects participating in clinical studies need to be managed carefully, (ii) trial costs are increasing, and (iii) there are limited research resources available, it is necessary to prioritize research projects and sometimes re-prioritize if early indications suggest that a trial has low probability of success. Futility designs allow this reprioritization to take place. This paper reviews a number of possible futility methods available and presents a case study from a late-phase study of an HIV therapeutic, which utilized conditional power-based stopping thresholds. The two most challenging aspects of incorporating a futility interim analysis into a trial design are the selection of optimal stopping thresholds and the timing of the analysis, both of which require the balancing of various risks. The paper outlines a number of graphical aids that proved useful in explaining the statistical risks involved to the study team. Further, the paper outlines a decision analysis undertaken which combined expectations of drug performance with conditional power calculations in order to produce probabilities of different interim and final outcomes, and which ultimately led to the selection of the final stopping thresholds.

Editors´note: Early indications that a trial has low probability of success - with success defined as confirming or refuting the trial hypothesis - can lead to the stopping of a trial for futility. Although this saves resources, stopping a trial prior to its conclusion because its key endpoints will not be met makes it impossible to determine whether results for secondary endpoints would have generated useful hypotheses for future investigation. It is important to decide up front what the stopping rules will be with respect to all endpoints and understand the consequences and anticipate them.