ity does not obviate the need for it. Experience with the NIMH Collaborative HIV/STD Prevention Trial shows that a trial of this complexity is feasible (Personal communication, D. Celentano, co-principle investigator on NIMH trial, Johns Hopkins University, August 11, 2006).
In approaching such a multi-national and multi-faceted study, critical ethical issues must be anticipated and essential safeguards put in place. Such a trial could be designed in a highly ethical manner consistent with local values. If undertaken, such a study would require extensive and closely coordinated planning and scrupulous attention to the ethical underpinnings. While the details of establishing such assurances and safeguards depend on the specific protocol(s), the basic principles for protecting human rights would apply. Below we outline some of these parameters.
The principles and strategies for ethical safeguards are well identified and can ensure the rights of research participants, as guaranteed under the Declaration of Helsinki and elaborated in the Belmont Accords. All such research must safeguard against exploitation of individuals and communities. Individuals should be afforded the benefits of enhanced treatments (the principle of beneficence), and receive only complementary pre-specified approaches or combinations of approaches whose comparative advantages remain uncertain (the principle of equipoise). Participation in research must be fully informed and freely given according to international and local norms for the particular methodologies being employed, and without repercussion or coercion (respect for dignity and autonomy). Community access to participation should be widely available (distributive justice). For example, extensive promotion of the study would allow as many communities as possible to be considered for participation.
The evaluations would be most informative if conducted in high-risk countries that are initiating programs to protect against HIV among IDUs, given that the evidence base is largely drawn from developed countries. However, the contributions of various components of a comprehensive program are also unknown in countries with more extensive existing HIV prevention programs for IDUs. Thus, communities in these countries might also participate in the trial, furthering the distributive justice of the study.
As noted, a stepped-wedge design would guard against ethical concerns about withholding effective therapies because all communities would eventually receive the interventions. A “no treatment” or “minimal treatment” control arm would be inappropriate. Rather, control communities should have a substantial prevention program equaling or exceeding that already available in the study sites. For example, in evaluating the effectiveness of a needle and syringe exchange component, investigators might provide a basic package of services such as voluntary HIV counseling and testing to promote behavioral change, education on needle disinfection, and referrals to health services and drug treatment in both the control and experimental