• Clinical trials
• HIV Infection and AIDS
• Research Ethics
• Research on Special Populations
• Drugs and Drug Industry

In many countries around the world, people who inject drugs remain at high risk of HIV acquisition not because effective forms of prevention are unknown, nor because they find effective prevention undesirable, but because those in charge, mainly politicians but also bureaucrats, find evidence-based practice politically unacceptable. The evidence for preventive efficacy of harm reduction strategies, most prominently needle and syringe programmes (sometimes called ‘needle exchange programmes’) but also treatment programmes such as opiate substitution, is irrefutable.1 However, political responses to drug use issues are varied and complex, so the will to implement appropriate harm reduction programmes in the interests of public health remains lacking in too many jurisdictions. As a consequence, the discussion of how best, in the context of research, to reduce HIV incidence in populations of people who inject drugs but are not offered comprehensive access to known prevention strategies is—tragically—an important one.

Dawson et al2 focus on access to sterile injecting equipment and recognise that this should remain the ‘default’ standard of prevention for HIV prevention trials involving people for whom injecting drug use is the primary risk factor for HIV acquisition. ‘Standard of prevention’ means the background or minimal HIV risk reduction interventions offered to all participants in a trial, regardless of what other investigational interventions they are assigned to receive. The standard of prevention concept is grounded in the ethical principle of beneficence—that researchers and sponsors are obliged to maximise benefits and minimise risks to participants in research studies.3

In view of the ongoing HIV transmission through the practice of drug injecting in settings where best practice harm reduction is not available for political reasons, Dawson et al argue that there is a case for considering whether it could be ethically permissible to conduct research without meeting its basic components and particularly the provision of sterile injecting equipment. At this point, they depart from the ethical guidance provided by the UNAIDS Ethical Considerations in Biomedical HIV Prevention Trials, which stipulates that if this basic provision is not met the trial should not go ahead.3 They consider circumstances under which such research could be justified via a set of seven criteria (A–G) that need to be met if such research is to proceed. In this commentary, we in turn will examine and evaluate their criteria.

• A. The study must fill an evidence gap that could be used to improve healthcare and services in one or more host countries, even if … implementation [is] … uncertain in the short term.

This criterion echoes ethical guidance stipulating that research with vulnerable populations needs to be responsive to the needs of the population and address a scientifically important question.4 However, it is considerably weaker than the ‘reasonable availability’ criterion that usually accompanies this guidance, in that it leaves the possibility open as to whether the improvement will actually take place. While this is pragmatic—ensuring post-trial access to effective interventions is complex and results can be unpredictable5—it ratchets down the expectation of the research outcome being beneficial to the population. Uncertainty as to whether the research will produce any population-level programmatic outcome that includes local trial populations may be viewed as a reflection of the political contexts in which research takes place, but it also raises questions of opportunity cost and potential exploitation.

• B. Community consultation with PWID and advocacy organisations should take place before the trial and should inform study design, procedures and dissemination …

Genuine and robust community collaboration is critical to the ethical permissibility of research with vulnerable populations, and particularly so when it fails ‘standard of prevention’ guidelines. Dawson et al recognise the importance of community acceptability in this criterion, but do not explicitly assign a decision-making role to the community that includes the power to veto unacceptable research. Without this explicit power, given the vastly different power relationships between researchers and people who inject drugs, especially those living under political regimes that disallow standard of care in research studies, it is difficult to see consultation as being sufficiently meaningful. A case in point, in their discussion of the Bangkok Tenofovir Study—a study involving people who inject drugs that did not supply sterile injecting equipment6—the authors note the opposition of ‘some’ local advocacy groups. The concerns raised by these advocates were portrayed as an example of how community consultation should occur earlier in the process and include input on trial design rather than recognising it as an instance of the interests of trial sponsors and researchers prevailing over those of communities.

• C. … Risk mitigation procedures [should be] in place to ensure that the research does not exacerbate the conditions of criminalisation, stigma and violence.

Dawson et al have provided evidence that shows how this can work in practice to reduce these very real risks. Accordingly, this criterion is justified and feasible.

• D. … Potential risks of research interventions should be counterbalanced by direct benefits.

Given the social marginalisation of people who inject drugs, Dawson et al make a sound argument that provision of direct benefits to participants is necessary to balance the potential risks of research participation.

• E. The standard of prevention must be established at the highest feasibly and safely deliverable at the site; sterile injecting equipment must be a basic ethical requirement.

Read in the context of the article, the authors are not arguing here that research should never occur in the absence of sterile injecting equipment. Rather, they are proposing that sterile injecting equipment is the expected standard, and any deviation from it needs to be strongly supported by the community, have favourable risk–benefit analysis and only be considered if all other ethical requirements are met.

• The final two criteria require that research teams contribute to advancing policy discussion in host countries, collaborate with local advocacy and community based PWID groups (F), and support and contribute to global advocacy for evidence based standards of care and treatment and human rights protections for PWID (G).

These are substantial demands to make of researchers, and perhaps reflect an inference of behalf of Dawson et al that deviation from the sterile equipment standard would only be made by researchers who are politically adept, highly experienced, with demonstrated personal committed to advocating for improving the health for people who inject drugs. That said, it is difficult to imagine how these criteria would work in practice. How would ethical review committees assess this capacity prospectively? Would evaluation of the advocacy be instituted, and if so, who would be responsible for monitoring the advocacy activity? Would it be funded, and if so, by whom?

In conclusion, Dawson et al have constructed a nuanced argument in favour of the ethical permissibility of research with people who inject drugs that does not meet ‘standard of prevention’ guidance, providing that the research meets other articulated ethical criteria. While the criteria they have proposed are generally well justified, they place too great an emphasis on the advocacy of the researchers and too little on the voices of advocates in the communities that they seek to research. The test of an empowered community collaboration is whether the community's voice is respected when it says no.