Ethically designing research to inform multidimensional, rapidly evolving policy decisions: Lessons learned from the PROMISE HIV Perinatal Prevention Trial

1. Curtis, LH, Dember, LM, Vazquez, MA, et al. Addressing guideline and policy changes during pragmatic clinical trials. Clin Trials 2019; 16(4): 431–437.
Google Scholar | SAGE Journals | ISI2. Cohen, MS, McCauley, M, Sugarman, J. The ethical odyssey in testing HIV treatment as prevention. Clin Trials 2012; 9(3): 340–347.
Google Scholar | SAGE Journals | ISI3. London, AJ . The moral foundations of equipoise and its role in international research. Am J Bioethics 2006; 6(4): 48–51.
Google Scholar | Crossref | Medline4. Miller, FG, Joffe, S. Equipoise and the dilemma of randomized clinical trials. N Engl J Med; 364(5): 476–480.
Google Scholar | Crossref | Medline5. London, AJ . Responsiveness to host community health needs. In: Emanuel, EJ, Crouch, R, Grady, C, et al. (eds) Oxford textbook of clinical research ethics. Oxford: Oxford University Press, 2008, pp. 737–746.
Google Scholar6. Shah, S, Wolitz, R, Emanuel, E. Refocusing the responsiveness requirement. Bioethics 2013; 27(3): 151–159.
Google Scholar | Crossref | Medline7. Wertheimer, A . The social value requirement reconsidered. Bioethics 2015; 29(5): 301–308.
Google Scholar | Crossref | Medline8. Wendler, D, Rid, A. In defense of a social value requirement for clinical research. Bioethics 2017; 31(2): 77–86.
Google Scholar | Crossref | Medline9. Lurie, P, Wolfe, SM. Unethical trials of interventions to reduce perinatal transmission of the human immunodeficiency virus in developing countries. N Engl J Med 1997; 337: 853–856.
Google Scholar | Crossref | Medline | ISI10. Angell, M . The ethics of clinical research in the third world. N Engl J Med 1997; 337: 847–849.
Google Scholar | Crossref | Medline | ISI11. Philpott, S, Heise, L, McGrory, E, et al. The challenge of defining standards of prevention in HIV prevention trials. J Med Ethics 2011; 37(4): 244–248.
Google Scholar | Crossref | Medline12. Haire, B, Folayan, MO, Hankins, C, et al. Ethical considerations in determining standard of prevention packages for HIV prevention trials: examining PrEP. Dev World Bioeth 2013; 13(2): 87–94.
Google Scholar | Crossref | Medline13. Dawson, L, Zwerski, S. Clinical trial design for HIV prevention research: determining standards of prevention. Bioethics 2015; 29(5): 316–323.
Google Scholar | Crossref | Medline14. Holt, N . Opinion: the murky world of medical ethics: why are researchers still denying some study participants potentially life-saving therapies? The Scientist, 7 August 2014, https://www.the-scientist.com/news-opinion/opinion-the-murky-world-of-medical-ethics-37035
Google Scholar15. Fowler, MG, Qin, M, Fiscus, SA, et al. Benefits and risks of antiretroviral therapy for perinatal HIV prevention. N Engl J Med 2016; 375(18): 1726–1737.
Google Scholar | Crossref | Medline16. World Health Organization . Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants: recommendations for a public health approach. Geneva, 2010, http://whqlibdoc.who.int/publications/2010/9789241599818_eng.pdf?ua=1
Google Scholar17. Duval, G, Shah, SK. When does evidence from clinical trials influence health policy? A qualitative study of officials in nine African countries of the factors behind the HIV policy decision to adopt Option B+. Evid Pol 2020; 16(1): 123–144.
Google Scholar | Crossref18. Hayden, EC . HIV trial attacked. Nature, 7 June 2014, http://www.nature.com/news/hiv-trial-attacked-1.15421
Google Scholar19. Ammann, AJ . Optimal versus suboptimal treatment for HIV-infected pregnant women and HIV-exposed infants in clinical research studies. J Acquir Immune Defic Syndr 2009; 51(5): 509–512.
Google Scholar | Crossref | Medline20. Schouten, EJ, Jahn, A, Midiani, D, et al. Prevention of mother-to-child transmission of HIV and the health-related millennium development goals: time for a public health approach. Lancet 2011; 378(9787): 16–22.
Google Scholar | Crossref21. World Health Organization . Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants. Geneva: World Health Organization, 2004.
Google Scholar22. Wendler, D, Emanuel, EJ, Lie, RK. The standard of care debate: can research in developing countries be both ethical and responsive to those countries’ health needs? Am J Public Health 2004; 94(6): 923–928.
Google Scholar | Crossref | Medline23. Biesma, RG, Brugha, R, Harmer, A, et al. The effects of global health initiatives on country health systems: a review of the evidence from HIV/AIDS control. Health Policy Plan 2009; 24(4): 239–252.
Google Scholar | Crossref | Medline24. PROMISE Study . ClinicalTrials.govIdentifier:NCT01061151. https://clinicaltrials.gov/ct2/show/NCT01061151?term=Fowler&cond=Hiv&draw=2&rank=1
Google Scholar25. Ahmed, S, Kim, MH, Abrams, EJ. Risks and benefits of lifelong antiretroviral treatment for pregnant and breastfeeding women: a review of the evidence for the Option B+ approach. Curr Opin HIV AIDS 2013; 8(5): 474–489.
Google Scholar | Crossref | Medline26. Cohen, MS, Chen, YQ, McCauley, M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011; 365(6): 493–505.
Google Scholar | Crossref | Medline | ISI27. World Health Organization HIV/AIDS Programme . Use of antiretroviral drugs for treating pregnant women and preventing HIV infections in infants, http://www.who.int/hiv/PMTCT_update.pdf (accessed April 2012).
Google Scholar28. Coustoudis, A, Goga, A, Desmond, C, et al. Is option B+ the best choice? Lancet 2013; 381(9863): 269–271.
Google Scholar | Crossref | Medline29. Joffe, S, Babiker, A, Ellenberg, SS, et al. Data and safety monitoring of COVID-19 vaccine clinical trials. J Infect Dis. Epub ahead of print 19 May 2021. DOI: 10.1093/infdis/jiab263.
Google Scholar | Crossref | Medline30. World Medical Association. Declaration of Helsinki 2013, Guideline 33, https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/
Google Scholar31. Council for the International Organizations of Medical Sciences (CIOMS). International ethical guidelines for health-related research involving humans, guideline 5 (2016), https://cioms.ch/wp-content/uploads/2017/01/WEB-CIOMS-EthicalGuidelines.pdf
Google Scholar32. Rid, A . Judging the social value of health-related research: current debate and open questions. Persp Biol Med 2020; 63(2): 293–312.
Google Scholar | Crossref | Medline33. Currier, JS, Britto, P, Hoffman, RM, et al. Randomized trial of stopping or continuing ART among postpartum women with pre-ART CD4 >400 cells/mm3. PLoS ONE 2017; 12: e0176009.
Google Scholar | Crossref | Medline34. Van Delden, JJM, van der Graaf, R. Revised CIOMS international ethical guidelines for health-related research involving humans. JAMA 2017; 317(2): 135–136.
Google Scholar | Crossref | Medline35. Wolitz, R, Emanuel, E, Shah, S. Rethinking the responsiveness requirement for international research. Lancet 2009; 374(9692): 847–849.
Google Scholar | Crossref | Medline36. Nayak, R, Shah, SK. Should social value obligations be local or global? Bioethics 2017; 31(2): 115–127.
Google Scholar | Crossref37. Ganguli Mitra, A, Dove, E, Laurie, G, et al. Reconfiguring social value in health research through the lens of liminality. Bioethics 2017; 31(2): 116–127.
Google Scholar | Crossref | Medline38. World Health Organization HIV/AIDS Programme . Use of antiretroviral drugs for treating pregnant women and preventing HIV infections in infants, 2012. http://www.who.int/hiv/PMTCT_update.pdf
Google Scholar39. Flynn, PM, Taha, TE, Cababasay, M, et al. Prevention of HIV—1 transmission through breastfeeding: efficacy and safety of maternal antiretroviral therapy versus infant nevirapine prophylaxis for duration of breastfeeding in HIV—1 infected women with high CD4 cell count (IMPAACT PROMISE)—a randomized, open-label clinical trial. J Acquir Immune Defic Syndr 2018; 77: 383–392.
Google Scholar40. Stranix, L . Impact of tenofovir-containing triple antiretroviral therapy (ART) on bone mineral density in HIV-infected breastfeeding women in sub-Saharan Africa. Oral presentation at the 8th International Workshop on HIV Pediatrics. Durban, South Africa. . https://www.impaactnetwork.org/sites/default/files/2020-12/P1084s_Stranix_maternalDXA_PdsWksp2016.pdf.
Google Scholar41. WHO . Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV, 2015, http://www.who.int/hiv/pub/guidelines/earlyrelease-arv/en/
Google Scholar42. INSIGHT START Study Group . Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med 2015; 373: 795–807.
Google Scholar | Crossref | Medline | ISI43. Wenner, DM . The social value of knowledge and the responsiveness requirement for international research. Bioethics 2017; 31(2): 97–104.
Google Scholar | Crossref | Medline44. London, AJ . Social value, clinical equipoise, and research in a public health emergency. Bioethics 2019; 33(3): 326–334.
Google Scholar | Crossref | Medline45. London, AJ . Learning health systems, clinical equipoise and the ethics of response adaptive randomisation. J Med Eth 2018; 44(6): 409–415.
Google Scholar | Crossref | Medline46. Bateman, C . Much ado over the new South African PMTCT guidelines. S Afr Med J 2013; 103(4): 218–221.
Google Scholar | Crossref | Medline47. Dobrow, MJ, Goel, V, Upshur, RJ. Evidence-based health policy: context and utilization. Soc Sci Med 2004; 58: 207–217.
Google Scholar | Crossref | Medline | ISI48. Kimmelman, J, London, AJ. The structure of clinical translation: efficiency, information, and ethics. Hastings Center Rep 2015; 45(2): 27–39.
Google Scholar | Crossref | Medline49. Eckstein, L, Rid, A, Kamuya, D, et al. The essential role of DSMBs in ensuring the ethics of global vaccine trials to address COVID-19. Clin Infect Dis 2021; 2021: ciab239.
Google Scholar50. Sydes, MR, Spiegelhalter, DJ, Altman, DG, et al. Systematic qualitative review of the literature on data monitoring committees for randomized controlled trials. Clin Trials 2004; 1: 60–79.
Google Scholar | SAGE Journals51. Eckstein, L . Building a more connected DSMB: better integrating ethics review and safety monitoring. Account Res 2015; 22(2): 81–105.
Google Scholar | Crossref | Medline52. Lavery, JV, Singer, PA, Ridzon, R, et al. In global health research, is it legitimate to stop clinical trials early on account of their opportunity costs? PLoS Med 2009; 6(6): e1000071.
Google Scholar | Crossref | Medline

Comments (0)

No login
gif