Keywords

2.1 Introduction

Generally speaking, research prioritization is the process of determining which research topics or approaches should be considered a priority for approval, funding and staffing, and it allows for the reasoned allocation of scarce resources (Etti et al. 2021). Priority-setting is an important and common challenge for institutions, governments and funders, as there are always limitations on capacities and resources for research. It is, however, a heightened consideration in epidemics and pandemics, given the increased need for relevant research findings to address pandemic health needs, and the multiple adverse ways that epidemics and emergencies can impact the capacity to conduct research. Whether at the international level or the local level, the idea of research prioritization calls for attention to factors such as which research topics should be prioritized and on what grounds, the ethically significant considerations that should inform prioritization, existing frameworks to guide prioritization decisions, and the risks and burdens that may be associated with prioritizing or de-prioritizing research. A prioritization exercise may also give clarity on whether and when it may be appropriate to prioritize research over the provision of health care during pandemics.

2.2 The Role of Research Prioritization in Epidemics

Epidemics are disruptive of normal life, at the level of both the individual and the community, and research also gets interrupted. Particular challenges that arise in epidemics and which influence priority-setting for research, include resource shortages, especially in acute crises; uncertainty over what type of knowledge will be most useful in addressing the epidemic (clinical, epidemiological, virological, social science or economic data for instance); and the implications of neglecting non-emergency research. In addition, epidemics often give rise to new priorities in medical, scientific or social research, especially if they involve new pathogens or variants. This may cause competition between long-standing and emerging research priorities. For example, as resources get re-allocated to addressing a pandemic, there is a risk that important on-going research and disease-control interventions for illnesses that kill more people than the pandemic does – such as malaria in tropical regions – will be suspended (Weiss et al. 2021). During times where some research institutions suspended all non-COVID-19 research activities, concerns may arise that important research areas that were deprioritized may continue to be perceived as no longer as important as the pandemic abates. The potential neglect of non-pandemic research may cause professional rivalry among researchers and have inequitable impacts on capacities to conduct research and on career progression. Furthermore, in the context of epidemics, an important question arises about whether and when it is justifiable for resources to be spent on research rather than on the delivery of health care. Addressing these challenges is difficult and can be frustrating. It makes priority-setting more complex and demanding of time, energy, critical thinking and resources than it otherwise would be. Research prioritization activities need to balance conflicting priorities and create clarity on these issues.

Although research prioritization during a pandemic may be informed by “the most pressing questions for clinicians and public health professionals” and may involve determining which research is likely going to be of the greatest health benefit to the relevant populations (Etti et al. 2021), other value-based approaches may play equally significant roles. A priority-setting exercise which draws on the views of a broad range of persons involved in addressing the epidemic, can help in the identification and ranking of the main questions surrounding the epidemic, and assist funding organizations and national governments to decide which research should be conducted first and why. In contrast, if research prioritization activities are not undertaken and aligned during pandemics, a number of challenges can arise. In the absence of priorities, scarce resources, including funds, research personnel, facilities, equipment and time, may be used ineffectively in research which is irrelevant or insignificant in the face of the bigger aim of addressing health burdens in pandemics or epidemics. Fragmented approaches may result in a lack of focus on important research areas and poor coverage of key research topics in epidemics.

Epidemics tend to be sudden, unexpected and uncertain – and usually funding is not readily available to address the urgent questions they raise. Furthermore, time is important – understood not only in terms of the time it takes to do good research, but also in terms of the time health workers may have to spend on research, given their clinical care responsibilities. In that context, it is very important to ensure that there is an appropriate decision-making process to help make informed decisions about how scarce resources are to be used for maximum effect. Finally, when a resource-allocation process is administered locally or nationally, it can help identify local research priorities which are likely to promote effective problem-solving in affected communities (Etti et al. 2021). Within countries undergoing pandemics, there are likely to be multiple explicit and implicit priority-setting exercises undertaken at different organizational levels, all of which have some influence. In such contexts, aligning or streamlining research priorities may be important.

2.3 What Considerations Should Inform Research Prioritization?

Setting priorities for research involves considering questions about which kinds of research ought to be supported or conducted in emergency situations. In determining which research is likely going to be of the greatest health benefit to the relevant populations, on the one hand there may be uncertainty about what type of knowledge would be most valuable to address the emergency, and on the other there are assumptions about the relative utility of some types of research over others. The need to prioritize specific research themes related to the epidemic may generate controversies on what is a more significant priority: clinical research versus epidemiology; people’s social behaviour versus pathogen mutations; public health versus the economic impact of the epidemic. For instance, there may be a focus on health science research rather than research in the humanities, even though the latter may be equally important for the design of interventions that are widely supported by the people who need to adopt those interventions. Concerns have arisen, for example, that the initial absence of social science research during the West African Ebola outbreak played a role in the design of interventions that were not broadly supported. The absence of local support for the way the interventions had been designed resulted in the continuation of traditional burial practices, and avoidance of clinical care facilities, which contributed to further spread of the epidemic. Social scientists’ engagement with the socio-cultural aspects of the epidemic played a role in building a response that contributed to the end of the epidemic, and a key lesson learned was that “understanding social dynamics is essential to designing robust interventions and should be a priority in public health and emergency planning” (Wilkinson et al. 2017). Case 2.1 in this chapter provides an example of a social science study which researchers thought might play an important role in understanding how pandemic burdens are experienced by families of patients with severe COVID-19, and inform the design of protocols for support.

In determining which research has the greatest likelihood of reducing epidemic health burdens in relevant populations, both the nature and distribution of such burdens is a key consideration. Epidemics and pandemics tend to disproportionately affect the most disadvantaged and vulnerable people in society, highlighting the importance of using theoretical approaches that take account of their struggles, not approaches that keep these struggles from view (Nussbaum 2009). Pratt and Hyder (2016) recommend the use of concepts that best reflect moral commitments to perform research focused on reducing health inequalities or systematic disadvantage more broadly, which would lead to the prioritization of research with outcomes that are likely to advance the interests of people who are more disadvantaged and would thus have the greatest potential to increase health equity (Nussbaum 2009; Barsdorf and Millum 2017). Certain types of intervention and forms of research are more likely to benefit those whose overall lives and health situations reflect the worst possible disadvantages, and not just those who will be faced with temporary difficulties at the time of research (Barsdorf and Millum 2017). These considerations demonstrate the importance of evaluating not just which research approaches have the greatest potential public health benefit, but also the likelihood that they will help reduce unjust health disparities and address the most pressing health needs of vulnerable and disadvantaged groups (Pratt et al. 2018).

2.4 Research Prioritization in Practice

When developing robust, inclusive and accountable priority-setting exercises in epidemics, the challenges and tensions outlined above emphasize the importance of carefully thinking about which ethical concepts and values should inform priority-setting, how such decisions should be made, who should be involved, and what interests should be represented. The World Health Organization has developed a three-step process for research prioritization in emergency and disaster-management situations, with each step outlining what actions need to be taken by researchers in such situations (Nasser et al. 2021). The first step involves forming a leadership team, understanding context and collecting necessary data, identifying and engaging with stakeholders, and collecting background information. The second step is to identify research options, decide on what criteria to use to prioritize them, and rank the research options. The third step involves actions after the priority-setting exercise, namely conducting the prioritized research projects, implementing their findings, evaluating the impact of those findings, reporting and publishing the priority-setting exercise, evaluating the process and outcome of the exercise, and feeding the results back to inform future exercises (Nasser et al. 2021). The evaluation and feedback are especially important for informing future prioritization.

Another source of guidance for research priority setting exercises has been developed by the Johns Hopkins COVID-19 Clinical Research Coordinating Committee (CCRCC 2021). These guidelines articulate the overarching principles that should be considered when conducting COVID-19 research. They include the following: scientific and ethical soundness, potential to be informative, minimal risks and burdens, safety and effectiveness, the needs of those affected by COVID-19, room for changes in priorities during the pandemic, and transparency to stakeholders. Case 2.2 demonstrates some of the competing considerations that can arise in such exercises, as an example of research which is prioritized not because the treatment is necessarily anticipated to be effective (given limited evidence and low credibility), but because, problematically, it is being widely prescribed or accessed despite the absence of an appropriate evidence base. In this example a proposed study has the potential to be informative in terms of an anticipated lack of evidence about amantadine’s value in treating COVID, but arguably there is no scientific foundation that would typically justify research into the drug’s safety and efficacy for such off-label use.

In order to streamline the process and to increase the consistency in priority-setting exercises, Viergever et al. (2010) developed a checklist that incorporates nine common elements of good practice in research priority setting intended to “assist researchers and policymakers in effectively targeting research that has the greatest potential public health benefit”. These common elements are context, inclusiveness, information-gathering, planning for implementation, criteria, methods for deciding on priorities, use of a comprehensive approach, transparency and evaluation” (Mador et al. 2016; Viergever et al. 2010). The checklist explains what needs to be clarified in order to establish the context for which priorities are set; it reviews available approaches to health research priority setting; it discusses stakeholder participation and information-gathering; it sets out options for use of criteria and different methods for deciding upon priorities; and it emphasizes the importance of well-planned implementation, evaluation and transparency (Viergever et al. 2010).

The importance of ensuring that priority-setting is appropriately informed and responsive to the context, rather than being a one-size-fits-all or other externally imposed approach, is clear. In the COVID-19 pandemic, the COVID-19 Clinical Research Coalition has been established to, among other things, support the “development of locally identified, context-specific research priorities” (Norton et al. 2021). Case 2.3 is an example of where local knowledge – in this case about the widespread use of traditional medicines to alleviate symptoms of COVID-19 – can inform potential national research priorities.

In low-income settings, such as those found in many parts of Africa, past research experiences in previous epidemics may inform research priority setting. At the Africa Centres for Disease Control, a task force for COVID-19 has worked with experts to identify six key priority areas. These are: epidemiology and surveillance of COVID-19; development of diagnostics; clinical characterization of cases; drug and vaccine clinical trials; investigation of the impact of COVID-19 on the health systems; and social science and policy research ACDC (2021). We can see these research priority areas are broad and may not be easy to fund. The team engaged experts from various research institutes in the six research areas and proposed “a limited number of actionable policy statements”. The recommendations from the experts provided further details on each research priority area for ease of understanding and implementation, providing a useful example of how some of the procedural considerations outlined above have been met in practice.

2.5 Challenges in Research Priority Setting

Research-prioritization exercises are not straightforward, and they may be controversial. For instance, in some settings, challenges may emerge which may complicate the research. A first and important challenge relating to research priority setting exercises is that they necessarily risk curtailing academic freedom, especially if some research is de-prioritized (Khumalo et al. 2020). Since epidemics cannot usually be accurately predicted, they take place in contexts where researchers are already engaged in other research activities. New priorities may deprioritize current research and constrain researchers’ freedom to engage in a subject they are passionate about and would like to develop to a conclusion.

A second, related, challenge is that research priority setting during an epidemic invariably introduces questions about whether research that is on-going should be de-escalated or stopped. An example is Case 2.4, in which researchers had to postpone research on sexual assault in order to prioritize COVID-19 prevention and infection control. Research can be de-escalated or stopped not just because of priority-setting exercises, but also because the risk–benefit profile has been so altered by the pandemic that it is no longer justifiable to undertake the study. Concerns arise especially on research projects which, if stopped or de-escalated, may lead to highly compromised, or altogether unhelpful, results. A few hypothetical responses may suffice. One response is to perceive research and other academic engagements as dispensable luxuries so that we focus only on epidemic-focused research. Another response is to undertake all the research for which resources are available, but establish a dedicated team looking into nothing but the pandemic. A third response is to de-escalate on-going research to give priority to the epidemic, especially in resource-scarce contexts. This could be combined with a policy that allows for some non-pandemic research to be continued, provided that a request is made and approved by an ethics committee and the relevant institutions. Research that is long-standing – for instance, cohort studies – or where the pausing of research activities constitutes a risk for those involved – for instance, clinical trials that require regular follow-up and where the trial drug cannot simply or easily be replaced with standard clinical care – could then be continued without interruption.

A third challenge relating to research priority setting activities relates to their implementation in practice. If priority-setting activities are not accompanied by a plan for implementation or a broad commitment by the research community (including funders) to consider taking the priorities into account, then the exercise is meaningless. For instance, one study conducted in South Africa concluded that “under one-third of the themes of priority questions developed in the KZN [Kwa-Zulu Natal] research prioritization process were reflected in subsequent research projects. Thus, many areas of health and healthcare considered as priorities remain under-researched” (Khumalo et al. 2020).

The case studies in this chapter highlight how some of the challenges discussed above have manifested in practice. Case 2.1 asks what priority should be placed on conducting qualitative research into the experiences of family members of severely ill and dying COVID-19 patients while isolation measures prohibit in-person visits, and how such research should be conducted. Cases 2.2 and 2.3 demonstrate how research prioritization measures may need to be responsive to widespread use of traditional medicine and off-label use of medications to treat COVID-19, despite the lack of evidence about their efficacy in this context. Cases 2.4 and 2.5 illustrate the issues that research teams may face as research priorities are re-evaluated in pandemics. Case 2.4 prompts reflection on the questions research teams may need to consider when determining whether to completely redesign proposed research in response to the logistical challenges posed by the pandemic and evolving pandemic research priorities. In Case 2.5 questions arise about continuing recruitment into oncology trials in public hospitals, as infection-control measures and anticipated constraints on capacities to provide health care prompt a re-revaluation of research priorities.