3. Study design and review

The features of a global health emergency, identified in section 1, pose a number of major challenges for both the design, and then the review, of research proposals. Throughout the process of prioritising, designing, and reviewing a particular study, decisions may have to be made within very tight timeframes in the knowledge that delay in moving forward also carries risk: decisions, for example, as to what constitutes an acceptable balance of risk and potential benefit, in a context of considerable scientific uncertainty. The contextual risks (both physical and non-physical) to which populations are exposed, and which may affect consideration of balance of risks and benefits of study participation, may also not be well understood, especially by non-local researchers and reviewers. These include risks of stigma associated with local attitudes to disease or research, or inadvertent loss of confidentiality through the very fact of research participation. Importantly, the risk of exclusion from research may also be overlooked, especially where studies offer access to potential benefits (financial or non-financial) that are otherwise unavailable to the population (see also section 5).

The 2014-16 Ebola outbreak in West Africa brought to the fore debates about the ethical acceptability of novel trial designs. These include:

  • ‘cluster’ randomised trials, where it is groups or clusters (such as health centres or villages), rather than individuals, that are randomly assigned to an intervention;
  • ‘stepped wedge’ designs, where an intervention is allocated sequentially to study participants or to clusters (as, for example, in the 2015 Ebola ring vaccination trial where the clusters of contacts of infected persons were randomly assigned to immediate or delayed vaccination);
  • ‘adaptive’ designs in which allocation to study arms (or indeed the study arms themselves) changes throughout the study in response to emerging results.

An expert panel convened by WHO also approved the “monitored emergency use of unregistered and experimental interventions”: that is, the use of such interventions outside the framework of any kind of clinical trial. Despite considerable work in this area in the intervening time, there remains a lack of consensus as to the circumstances in which particular designs are acceptable, or indeed whether this can be determined without reference to the specific context for which they are proposed.

Global health emergencies also pose unique challenges to the functioning of research ethics committees, particularly where these are already under-resourced and / or disrupted by the nature of the emergency. In addition to the pressure of responding flexibly and within tight timescales, research ethics committees may also be faced with sudden increases in the number of protocols being presented for review, and trial designs that are unfamiliar to committee members. Proposed approaches such as ‘pre-approval’ or ‘pre-review’ of aspects of protocols as part of emergency planning, and joint multi-country review committees, might help respond to capacity concerns, but bring their own risks of loss of local ownership and trust.

Read more: study design and review

Questions 6–10

6. In your view, in what ways, if at all, should decisions about study design and acceptable risk be affected by the fact that the research will be taking place in a global health emergency? On what basis would you justify any variation?

7. In what ways, if at all, could it be morally justifiable to change the ‘standard’ ethical and regulatory review processes to respond to the time pressures inherent in a global health emergency?

8. If any differences in approach to study design or review can be justified because of the features of a global health emergency, would safeguards, such as an independent declaration that ‘emergency’ criteria have been met, be necessary?

9. When choosing a study design, is it ever justifiable to prioritise a design that will maximise knowledge and hence scope for benefit for future generations, over a design that maximises the possibility of benefit for people affected by the current emergency; or could this never be justified? On what ethical basis would you justify such a choice?

10. Are there any specific kinds of research or innovation that, in your view, raise distinct ethical questions and / or might demand differential ethical treatment?

Proceed to section 4: making decisions about participation in research

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