Who paid for the research, who managed it?
A research project in Kenya, 2002-6, recruited men willing to be circumcised, then on a random basis assigned half to an intervention group to be circumcised first and half to a control group to remain intact (uncircumcised) until the end of the study. The study team followed and retested all men at scheduled visits over as long as 2 years.
The study was funded by the US government and approved by committees at the Universities of Illinois, Washington, and Manitoba, Research Triangle Institute, and Kenyatta National Hospital.[1,2]
Did the research clinic give 4 men HIV?
The trial found four men with new HIV infections one month after circumcision (tests found no HIV in blood collected at the beginning of the study). Three of the four men reported no sexual activity during the month. Among circumcised men, HIV incidence at the rate of 3.8% per year during the first month after circumcision (calculated from 4 infections in one month in 1,268 circumcised men) exceeded average annual incidence of less than 1% during the remainder of the trial. Possible paths for HIV transmission during circumcision include contaminated skin-piercing instruments and contaminated multidose vials of local anesthetic.
Not reporting, not investigating
The US government regulates research on human subjects funded by the government, whether the human subjects are in the US or in another country (for example, Kenya). (Quote from US regulations, p 105 of reference , the regulations apply to: “…research conducted, supported, or otherwise subject to regulation by the federal government outside the United States.”) The US government’s Office of Human Research Protection (previously called the Office for Protection from Research Risks) is responsible to enforce the regulations.[3,4] According to regulations, the research team should report unanticipated problems that may have been caused by research procedures to the committees (institutional review boards) at their university or other institution that are responsible to monitor the research. These committees should investigate reported unanticipated problems and — if they appear to have been related to the research — report them to the US Office of Human Research Protection.
The study’s published account of adverse events does not recognize or include these apparently non-sexual HIV infections shortly after circumcision as adverse events. There is no indication the study team, university committees monitoring the research, or the Office for Human Research Protections of the US government considered these infections to be unanticipated problems to be reported and investigated.
Failure to investigate unanticipated problems may have left participants receiving circumcisions and other procedures from the study with unknown and avoidable risks. Moreover, investigations of these and other unanticipated problems during research could advance understanding of HIV transmission in generalized epidemics and support more effective prevention information and initiatives.
1. Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet 2007; 369: 643-656. Available at: https://www.ncbi.nlm.nih.gov/pubmed/17321310 (accessed 30 October 2018).
2. ClinicalTrials.gov. Male circumcision and HIV rates in Kenya, last updated 28 May 2008. Available at: http://clinicaltrials.gov/ct2/show/NCT00059371?term=NCT00059371&rank=1 (accessed 30 October 2018).
3. Office for Human Research Protections (OHRP) Guidance on reviewing and reporting unanticipated problems involving risks to subjects or others and adverse events, 17 January 15 2007. Available at: https://www.hhs.gov/ohrp/sites/default/files/ohrp/policy/advevntguid.pdf (accessed 30 October 2018).
4. Office for Human Research Protections (OHRP) Guidance on reviewing and reporting unanticipated problems involving risks to subjects or others and adverse events, 17 January 15 2007. Available at: https://www.hhs.gov/ohrp/sites/default/files/ohrp/policy/advevntguid.pdf (accessed 30 October 2018).
5. Gisselquist D. HIV infections as unanticipated problems during medical research in Africa. Account Research 2009; 16: 199- 217. Abstract available at: https://www.ncbi.nlm.nih.gov/pubmed/20183161 (accessed 30 October 2018).