Table 1

 International guidance and standard of care—key issues

National Bioethics Advisory Commission10Council for International Organisations of Medical Sciences7Declaration of Helsinki11UNAIDS: Ethical Considerations in HIV preventive vaccine research12Nuffield Council on Bioethics13
RCT, randomised controlled trial; SOC, standard of health care.
Adequate SOC v “undue inducement” “Reasonable to conclude that providing medical care to participants iswarranted, appropriate, and proper” (Chapter 3: 47)Warns against over-large payments that could be undue inducement to participate (Guideline 10)Silent“Care should be taken [not to] … unduly influence freedom of choice in participation” (Guidance point 10)Dividing line is fine between inducement and benefit (Paragraph 44)
Researchers should indicate how they would minimise therapeuticmisconception(Recommendation 3.10)
Protecting vulnerable populations The US Government should not sponsoror conduct trials that do not ata minimum provide … a minimumof risk to participants … and… equal regard for all participants (Recommendation 1.1)In populations with limited resources, researchers must make every effort toensure interventions will be madeavailable (Guideline 10)Particular needs of the economicallyand medically disadvantaged must berecognised (Paragraph 8)Limited availability of care and treatment can increase risk and harm to participants(Guidance point 7: 23)Developing country participants more vulnerable to exploitation because of limited access to basic health care, lack of knowledge about research, cultural differences (Paragraph 11)
… a vulnerable population should not be the focus of research unless the potential benefits of the research will accrue to that group after the trial (Chapter 1: 7)If [vulnerable persons] participate, means of protecting rights and welfare must be strictly applied (Guideline 13)
Universal v best locally available care An RCT must provide “establishedeffective treatment” in controlarm whether or not available in host country(Recommendation 2.2)In RCTs, subjects should generally receivean “established, effective intervention”(Guideline 11)In RCTs, must provide “best current SOC” (Paragraph 29)Need to achieve equity in care andtreatment globally; minimum is best proven locally (Guidance point 16: 42–3)In RCTs there is a strong case for current standard local treatment (Paragraph 36)
Capacity building for SOC Potential problems exist maintaining SOC established during a trial … sponsors could undertake training of personnel, maintenance of equipment post-trial; ultimate goal is to improve welfare of those in host country (Section 5: 77)Sponsors are ethically obliged to ensure availability of services to make intervention reasonably available (Guideline 21)Every participant in trial should be assured access to the best proven methods identified by study(Paragraph 30). This implies building capacity though not explicitly mentionedSponsors should contribute to health care capacity-building integrated into community infrastructure (Guidance point 16: 42–3)The ethical obligation to provide improved care when trial over and by whom is unclear (Paragraph 17)
Treatment of research related injury Adequate care and compensation for injuries directly sustained during research must be provided (Recommendation 1.1)“Sponsors obliged to ensure treatment for subjects who suffer injury as consequence of research interventions”(Guideline 21)SilentSponsors need to ensure care andtreatment for those who become HIV+(Guidance point 16)“Provision of care for seroconverters may be a function of what is locally available” (Paragraph 54)
Community participation Researchers/sponsors should involve community throughout trial design and implementation (Recommendation 2.3)Important to involve community members in decisions around benefit/risk,informed consent, responsiveness to health needs (Guidance 1, 10)SilentComprehensive care and treatment package should be developed by community (Guidance point 5, 16)Silent
Pre-trial agreements Whenever possible, preceding start of research, agreements should benegotiated to makebenefits/intervention available to host country after research is completed (Recommendation 4.3)Sponsor obligations should be clarifiedbefore research begins(Guidance 21)SilentPlans to make vaccines, other knowledgeand care available should be developedat initial stages (Guidance point 2, 16)Researchers can demand pre-trial discussions with pharmaceutical companies (Paragraph 57, 64)