Standard of prevention: a qualitative study of principal investigators’ perspectives Bridget Haire

Methods Participants identified through clinical trial data bases and key publications Contacted by Invited to participate in survey, interview or both (only interview data presented here) Semi-structured interviews predominantly by phone Coded using spontaneous and predetermined codes Analysed thematically

Results No consensus

Guidelines UNAIDS 2007 “state of the art” HPTN 2009 Effective, achievable accessible

We need to concentrate on the thing we want to measure and peel back from offering everything - P1

What we have created is a massive gap between the real world and clinical trials. – P1

The more you provide to the control arm, the more difficult it becomes scientifically then, to come up with a reliable result in terms of the impact of the intervention itself… and that might then deny the intervention to very large numbers of people and communities in the future. – P2

We wanted to be able to show that our intervention for HIV prevention added to the benefit of existing care… above and beyond everything else that we know how to do. P3

I think that we should not use placebos if we know that they are inferior to something else… …I don’t think you have to provide something that is not feasible. But I think that most things that we are talking about are feasible…it’s just a matter of lowering the price and raising the funds to make these things available…P3

It’s a fine line between the importance and the impetus and the imperative for your research question, versus all the other things that we can potentially help to improve [conditions for participants]…. That’s where things get varied between lighter and darker shades of grey, for some people, and for some people it becomes black and white issues. P4

It’s a genuinely difficult issue, as to what stage placebo controlled trials become inappropriate or unethical or both …. And indeed even when we do have sufficient evidence, is it only when the product is licensed and available that a placebo controlled trial would become unethical, or is the mere fact that the evidence is there, sufficient to make further trials inappropriate? P5

Study Effect size (CI) Medical male circumcision (MMC) ( Orange Farm, Rakai, Kisumu) 57% (42, 68) Prime-boost HIV Vaccine (Thai RV144) 31% (1, 51) Efficacy 0% % TDF/FTC oral-PrEP in MSM (iPrEx, Grant et al 2010) 44% (15, 63) 1% tenofovir gel (Caprisa 004, Karim et al.) 39% (6, 60) Slide:Robin Shattoch Plenary IAS Rome 2011 Immediate ART for positive Partners (HPTN052) 96% (82, 99)* TDF/FTC oral-PrEP in heterosexuals ( TDF2, CDC) TDF oral-PrEP in serodiscordant Partner (Partners PrEP) 63% (22, 83)* TDF/FTC oral-PrEP in serodiscordant Partner (Partners PrEP) 62% (34, 78)* 73% (49, 85)* New biomedical intervention strategies

Your ethics committee says you can’t have a placebo controlled study, and your regulator says that’s the only study we will licence the products on. So what do you do? P8

Equipoise: a state of uncertainty, or more specifically of having no reason to prefer one intervention over another.

We introduced circumcision before WHO and we were criticised because we went before anyone, because we thought the nature of the data was overwhelming. P10

With male circumcision, it took Uganda longer than Kenya for example, to adopt the national policy. Until they really did adopt the policy … we were limited in our ability to actually make it available. P11

I think where we get into ambiguity is … let’s say a new intervention has shown some level of effectiveness, but clearly isn’t imminently available in the communities where we’re doing our studies, and may never be – to what extent should that then become part of your prevention package as it were. And I think that can be quite difficult. p4

Conclusion No theoretical consensus Moral ambiguity Gaps in research ethics theory

Thank you to the participants