Research and analysis

Ethical integration of research in public health emergencies: preparation, response and recovery

Published 17 April 2025

Executive summary

This report by the Ethox Centre at the University of Oxford was commissioned by UKHSA in order to identify the key ethical considerations that arise when integrating research in public health emergency response strategies; and to provide practical recommendations for future emergency preparedness, response, and recovery. It is based on a rapid literature review, building on earlier substantial work in this area, and on input from an expert roundtable and external reviewers. While much of the recent literature focuses on infectious disease outbreaks, the broad conclusions are also applicable to other forms of emergency response.

We argue that there is a strong ethical obligation in emergencies to seek to improve the existing evidence base for interventions and reduce uncertainty through high quality research, using both quantitative and qualitative methods. This obligation applies equally to pharmaceutical and non-pharmaceutical interventions, and is particularly compelling if such interventions are mandated. Other forms of evidence generation, including public health surveillance, policy evaluation, modelling and market research, also have a part to play in emergency response. Careful attention, however, must be paid to identifying the most appropriate form of evidence generation for the required purpose, and to ensuring that the choice can be ethically justified. While the challenging context of an emergency may lead to the need to act initially on partial evidence and expert opinion, this reinforces the importance of an ongoing commitment to evidence generation, and of upholding key ethical requirements including respect for participant or citizen welfare, scientific rigour, and transparency whatever the methodology selected.

While there may be occasions when research is not feasible, at least on a temporary basis, claims that this is the case must be carefully scrutinised, in light of the serious opportunity costs of failing to improve the evidence base for emergency response in a rigorous manner. Crucially, much can, and should, be done to support and enable research in advance of the emergency, as part of adequately-funded emergency preparedness. The related need to strengthen existing systems of evaluation of the implementation and impact of policy interventions has already been reiterated (1).

Responsibilities that arise for policy-makers include:

• support for emergency preparedness encompassing
  • facilitative regulatory and ethical pathways that can support rapid and effective research relevant to a new emergency and that help minimise impact on the emergency response effort
  • sustainable support for, and enablement of, the infrastructure required to conduct that research, including multi-institution research platforms, priority-setting mechanisms, community engagement plans, and data sharing arrangements
• a minimum commitment to ensuring that evidence is generated during or after policy implementation, and that well-designed studies begin as soon as possible after the start of the emergency, addressing evidence gaps that have been prioritised in a transparent and accountable manner
• transparency with respect to how emerging evidence has been incorporated into decisions (including decisions not to act), and what underlying values have steered policy and operational choices
• support for ongoing research in inter-emergency periods to help maximise public benefit from emergency research, including commitment to involving members of the public, along with data experts, in developing trustworthy systems for data access and use (a core element of emergency preparedness)
• commitment to an ongoing cycle of learning during and between public health emergencies, including rigorous processes to identify the impact of policies, assess their effect on inequalities, and respond to negative unintended consequences
• recognition of the role of real time social science and ethics research in understanding and guiding the response to public health emergencies, and in helping support trustworthy approaches in which the public can have confidence

Chapter 1. Background

Approach

This report builds on existing work on the ethical conduct of research in emergencies (2, 3, 4). It draws on a rapid review of academic and grey literature published since 2019, in order to explore systematically how the experience of the coronavirus (COVID-19) pandemic might have challenged existing thinking, and to evaluate the ethical feasibility (indeed the ethical imperative) of incorporating research into health emergency response strategies. The material found through the rapid review was supplemented by additional relevant literature identified by the authors. The initial analysis of this literature, and the implications for policy and practice in the UK, was discussed and refined at an expert roundtable meeting and through external review of a draft report.

Further details of the methodology, and of those contributing to the roundtable meeting and external review, are set out in the Annexe.

Rapid literature review

The main themes that emerged in the reviewed literature included:

• the essential nature of diverse forms of research in emergency response
• the need for prioritisation and collaboration
• challenges around study design and methodology
• the role of the ethics and regulatory environment
• the complex interconnections between research and public health surveillance

Inevitably, much of the recent literature focused narrowly on COVID-19 and epidemic response, but many of the broad themes are also applicable to other forms of public health emergency. While the literature review itself centred on evidence-generation activities that would be classified formally as ‘research’ and subject to the norms of research governance, the discussion of the implications for UK policy has been extended in this report to include other forms of evidence generation such as policy evaluation. (A further review would, however, be required in order to explore more systematically the extent to which the ethical aspects of other forms of evidence generation in emergencies have been considered in the literature.)

Essential nature of research

The 2011 ‘UK pandemic influenza strategy’ describes research as “particularly vital at the onset of a pandemic to improve the understanding of the health and wider impacts of a new virus and to inform the response to the pandemic” (5). More recently, research has been categorised as “ethically obligatory” on the basis of its importance in disturbing equipoise and removing uncertainty (6); and as an “ethical duty” for professionals that is in the best interests of patients (7). (Equipoise is a situation in which there is uncertainty among relevant experts about which is the most effective course of action. Disturbing equipoise refers to the potential value of research in ‘disturbing’ the balance of evidence in favour of the different alternatives in such a way that the experts come to see the uncertainty as resolved).

Expanding the range of those traditionally understood to have ethical responsibilities, the Nuffield Council on Bioethics argued that all those with influence over the research agenda, including research funders, governments and journals, should be considered “duty-bearers” with respect to the conduct of research during emergencies (4). It was further suggested in the first year of the COVID-19 pandemic that there was a “moral imperative for technology and telecoms companies to share their data in a proportionate, ethical and privacy-preserving manner” both to support research and inform public health interventions (8, 9). Matching the breadth of institutions and individuals identified as bearing moral responsibilities with respect to research, it is argued that any consideration of the scope of research and development should also include the role of upstream or facilitative activities such as “global research platforms, research priority setting, community engagement, data sharing, funding, and associated regulatory and ethical pathways” (10). Policy decisions, including the establishment of major programmes such as the UK COVID-19 Test and Trace programme and decisions whether and when to lift social restrictions, with or without particular mitigations, should be evaluated “as robustly as possible as a default” (11). (An evaluation of Test and Trace was commissioned in 2022 (12)).

The argument that research is essential in order to “reduce uncertainty and enable caregivers, health systems, and policy-makers to better address individual and public health” is qualified by London and Kimmelmann by reference to 5 conditions which, it is argued, must be met if research is to be aligned with the public interest and thereby fulfil its “moral mission” (13). These are:

• importance – to the emergency response: addressing key gaps in evidence
• rigorous design – able to detect clinically meaningful effects (both positive and negative)
• analytical integrity – with designs pre-specified in protocols and prospectively registered
• prompt and complete reporting
• feasibility – with a credible prospect of reaching their recruitment target

Different emphases emerged in the literature with respect to the forms of research for which such a moral claim might be made. In addition to research on pharmaceutical and non-pharmaceutical interventions (6), authors highlighted the value of biospecimen research in increasing knowledge on viral infectivity, immune response and effect of treatments (14); qualitative research to understand the experiences and needs of different parts of the population, with a particular focus on more vulnerable or marginalised communities (15, 16); and research on the impact of public measures, including on people’s mental health (17). The importance of not neglecting ongoing research on pre-existing health issues was also reiterated (18).

Prioritisation and selection

The criteria for socially responsible research set out by London and Kimmelman above highlight the need for clear criteria for prioritising research proposals, accompanied by transparent and accountable procedures, particularly given the risks of more valuable research proposals being crowded out by those offering less prospect of benefit.

For interventional clinical studies, criteria such as “clinical relevance” and a “sufficiently high probability of success” were put forward to provide at least a short-term guide to prioritisation (19). In the context of the wider public health response, it was argued that there is strong justification for “prioritizing research of known vulnerable populations such as children and minority groups” (16). The use of an equity matrix was proposed to help guide research on the full spectrum of health inequities and their sources and interactions (20). The importance of ensuring that “populations from a variety of socioeconomic, gendered, and racialised backgrounds” are included in studies, and that data is disaggregated accordingly, was reiterated, in order to help identify differences in experience or response (20).

At the institutional level, it was suggested by Meyer and colleagues that a structured approach to prioritising and approving studies should be followed (21). The following should be considered, in order:

• threshold criteria relating to social value, scientific validity, feasibility and collaboration or consolidation
• institutional capacity assessment, considering whether the institution has the ability to support all studies that meet the threshold criteria
• if not, prioritisation by reference to both study specific criteria (including promising intervention and robust design) and portfolio criteria (including diversity of patient population likely to benefit and disease stage)
• studies to proceed in order of prioritisation, but continually be assessed against new opportunities

While it was recognised that the clinical response to the demands of the COVID-19 pandemic, and related research, should take priority, the importance of seeking to continue research into other urgent health needs (adapted and streamlined to the extent possible) was reiterated (22). It was also argued that any concerns about the impact of non-COVID research on scarce resources (for example, on use of acute care) should be “carefully estimated and put into perspective to prevent the shutdown of an integral part of healthcare for no apparent reason” (18).

Collaboration and devolution

Responsibilities to collaborate were identified at multiple levels. It was noted that global pandemics require a global response, indicating, for example, the role of the World Health Organization (WHO) in co-ordinating research and access to resulting interventions (10) and the importance of standardised forms of data collection that allow for data to be shared, aggregated and interpreted on a global basis (23). However, such global collaboration should be guided by the principle of subsidiarity: major funders should avoid establishing parallel R&D initiatives that risk competing with local health resources, and instead support the capacity of local- and national-level research initiatives, accompanied by meaningful community engagement and accountable to local oversight mechanisms (10). Participatory approaches were noted as enhancing the likelihood of ensuring research responds to local needs, priorities and knowledge, as well as enabling local populations to regain a degree of control, and promoting engagement with service providers (17).

Recognising that research in non-emergency times is often pursued on a less co-ordinated basis than suggested here, it is argued that robust leadership is required from regulators, health authorities and major funding bodies to promote this collaborative approach, for example through identifying priority studies, fostering collaboration among research centres, and using public briefings to raise awareness of ongoing recruitment to trials (13). Similar proposals are put forward (in the specific context of Spain) for a national pandemic plan, supported by a scientific advisory board, with national centres, networks and platforms working in a co-ordinated manner (24). The success of the RECOVERY trial illustrated the value of research platforms across multiple institutions, and the importance of establishing such infrastructure in advance of future emergencies (25, 26).

At the level of individual clinicians, it is argued that they should avoid off-label use of unvalidated interventions, and instead seek out opportunities to join existing studies (13).

Study designs

The argument that “crises are no excuse for lowering scientific standards” is put forward strongly, illustrated by examples of how low-quality and underpowered research strategies have failed to produce useful results, undermined the ability of better-designed studies to recruit sufficient participants, or led to the promulgation of ineffective treatments (13, 25). Rigorous design and analytical integrity, including prospective registration of studies, is essential if researchers are to fulfil their social responsibilities (13). Methodological decisions associated with compromised research standards include “using smaller sample sizes, employing unvalidated surrogate end points, disregarding randomisation, using partial evidence, and altering prespecified research organization and design” (23). While recognising the challenges facing individual clinicians, it is argued that the decision to limit access to unvalidated medical interventions other than through research (avoiding off-label use, for example) can be justified (27, 13). Lessons learned from the UK Events Research Programme (integral to the re-opening of major public events in England after the first COVID-19 lockdown) included the need for greater scrutiny of the trade-off between “acting immediately to meet policy demands with some compromises on study design versus having a short delay to strengthen the study”, and the need, where justified, for scientists to pushback more robustly on questions of design (11).

Adaptive platform trials using master protocols can test multiple interventions within the same trial, permit timely adaptations as new information emerges, and enable easy transition into clinical practice (13, 28). Streamlined ‘point of care’ trials, designed to integrate smoothly with existing care systems, allow for the recruitment of larger samples of participants and hence for the identification of smaller effect sizes, while not detracting from urgent patient care (29); examples such as RECOVERY played a central role in COVID-19 response (30). Decentralised trials may also be particularly suitable for pandemic conditions, although the need for careful checks and balances around physical safety, privacy, consent and participant wellbeing are noted (31, 32). Challenge studies may play a role (with some concerns about acceptable levels of risk), but it is noted that they are not necessarily the ‘quick win’ they are often assumed to be, given the long lead-in times involved in developing the challenge strain of the virus (33, 25).

Natural experiments may be considered in cases where randomisation is deemed impossible, but should meet additional scientific and ethical criteria: ensuring data collection can be justified as adding value; where possible ensuring relevant hypotheses are in place; if time allows seeking ethics review even if not formally required; and willingness to intervene if evidence of serious harm is uncovered (34). Qualitative studies are noted to be pivotal to pandemic response, for example by generating evidence to inform tailored, culturally appropriate approaches to COVID-19; while moving to online methods of data collection is feasible it requires “thoughtful, reflexive, and deliberative approaches in order to identify and mitigate potential and dynamically evolving risks” (15).

When considering acceptable degrees of risk, there may be a conflict between safety and generalisability, for example if recruiting younger participants who may not be typical of those most at risk (35, 36). It is also important to separate out the risks of a trial intervention from the baseline risk from the disease itself (37).

Ethical and regulatory environment

A strong plea is made to take account of the “upstream structures and mechanisms that govern and facilitate research and development”, and which can play an important normative role through promoting strong and fair governance, supporting broad research collaborations, and fostering multiple levels of trust (10). The team involved in the RECOVERY trial, for example, argues for a “more coordinated, competent and timely approach to getting the approvals needed to set up multi-centre clinical studies” and the need to “embed simple clinical trials at scale within the NHS” as practical examples of such an enabling environment (30). In addition to standard oversight and regulatory requirements, the “development of a framework for R&D that addresses the importance of community engagement and transparency will play a key role in building trust” at micro, meso and macro levels, involving actors such as local and national politicians as well as those more directly involved in research (10). In the UK, the Health Research Authority (HRA) played a leading role in promoting public involvement and engagement in research planning and design (which had dropped off dramatically at the beginning of the pandemic) by developing a “UK COVID-19 public involvement matching service” to enable researchers to access public involvement support (38).

As far as standard ethical requirements and oversight are concerned, it is emphasised that these should not be lessened in light of the emergency context; rather, heightened attention needs to be paid to ethical principles (7, 39), with particular attention to the needs and interests of disadvantaged communities (14). The development of ‘master’ or ‘umbrella’ protocols with input from regulatory and ethics review bodies in advance of a future pandemic is an important part of emergency preparedness for a wide range of research (5, 25, 40, 41); as is the development of procedures for rapid ethics review in emergencies (42, 43).

There was general consensus that the emergency context does not alter the need to meet the ‘gold standard’ of consent for research participation: voluntary and ongoing informed consent, given by legally competent individuals or authorised third parties (39). In some cases, deferred consent may be permissible where a person is unable to consent at the time, for example because of the severity of their condition (19, 14). This should be understood as seeking consent for ongoing use of data since retrospective consent for an intervention itself is meaningless (37).

Strong emphasis was placed on the importance of good communication between participants and researchers (17, 31) and on the importance of taking extra care with regard to privacy because of the emergency context or remote setting (15, 32). The need for particular attention to consent practices was noted for challenge studies (36), and in trials being conducted remotely (32).

Sharing and using data for multiple purposes

‘Research’ and ‘public health’ practices such as public health surveillance are commonly conceptualised as distinct activities and subject to different governance arrangements (44), particularly with respect to the need for individual patient or participant consent for the use of data, and requirement for independent ethical review. These distinctions can contribute to uncertainties about the ethical acceptability of sharing data between these different forms of evidence generation during emergencies.

The idea of a ‘bright-line’ distinction between research and public health surveillance is increasingly challenged, especially where the intended uses of patient-identifiable information may look very similar from the perspective of the patient/participant concerned, and the need for greater alertness to the ethical considerations inherent in surveillance has been emphasised (4, 45). While one common distinction between research and public health practice relates to publication, for example, data collected for surveillance under public health governance frameworks may in fact be published not only via public health agencies but also in academic journals where requirements for ethics review and other oversight mechanisms may be waived for public health data (for example 46, 47).

The technologies used in public health surveillance have also developed rapidly in recent years. Surveillance traditionally used relatively simple data (for example, regarding the number of people seeking healthcare with syndromes such as influenza-like illness), sometimes combined with summary data on the results of diagnostic tests such as polymerase chain reaction (PCR). Recent developments include the use of pathogen genomic sequencing, wider use of rapid antigen tests and serological measures, and the use of mobile devices for data collection and/or monitoring of mobile phones to determine patterns of human movement (48, 49). In future epidemics with novel pathogens, it is likely that metagenomic sequencing may be used, which would involve ‘pathogen agnostic’ genetic testing from samples from individuals, or from communities via waste-water testing, with the goal of identifying a new pathogen sooner than current technologies would allow. Among other things, the use of pathogen genomic data, especially in combination with other types of data, allows very detailed mapping of the transmission of infection between individuals. The benefits of such methods therefore need to be weighed against other considerations including infringements of individual privacy.

While ethical concerns often centre on the use specifically of health data, a review of digital technologies in the public health response to COVID-19 illustrated the scope for using novel sources of non-health data such as social media posts, web searches, location data and crowd-sourced data in both surveillance and research (8). Aggregated location data collected by smartphones, for example, was used for surveillance purposes to monitor real-time population flows and identify potential hotspots; it could also be used to research the effectiveness of particular public health interventions such as travel restrictions. The controversial use of digital contact-tracing apps illustrated both the importance of research in evaluating their accuracy and effectiveness, and the importance of public confidence in the governance systems underlying such data use, if they were to be effective (8, 50, 51).

Greater co-operation and transparency is called for in making both public and private data sets more accessible for different purposes (with appropriate protections for privacy and security): for example by governments making data sets, such as epidemiological data, available in downloadable form for research (8). The importance of standardised approaches to data collection is similarly reiterated in the context of routine health data and research, with a call for core data sets to be “agreed upon and included in routinely-collected health records” in order to facilitate research (25).

These multiple and intersecting uses of both health and non-health data, along with the scope for emergency powers to extend the normally-permissible scope of data-sharing between official bodies, raise important questions of consent and control, governance and future trust, as summarised by Budd and others:

“There is concern that emergency measures set precedent and may remain in place beyond the emergency, which will lead to the ongoing collection of information about private citizens with no emergency-related purpose. All systems will need to be ‘proofed’ against invasions of privacy and will need to comply with appropriate legal, ethical and clinical governance. Data can be shared under a legal contract for a well-defined purpose and time, with requirements for independent audit to ensure data is not used for purposes outside of the pandemic. Dynamic consent processes could also allow users to share their data, and privacy-preserving technologies, such as differential privacy and homomorphic encryption, could ensure that access is possible only for specific purposes and is available in a tamper-proof manner to allow auditing.” (8)

The issue of the continuing use of new data-sharing permissions, originally authorised through emergency measures, has been subject to scrutiny by the National Data Guardian, who co-commissioned 3 citizens’ juries to explore public views on data sharing during and after the emergency phases of COVID-19 (52). Members of the public taking part in the citizens’ juries were generally in favour of emergency data-sharing initiatives continuing as long as they were useful. However, the governance of such initiatives was thought to be very important, with most jurors in favour of an independent body of experts and lay people (not politicians or research institutions) making decisions about permissible forms of data sharing and usage.

Focus for this report

Drawing on this rapid literature review, and on subsequent discussion at an expert roundtable, we have focused our analysis first on the ethical aspects of whether and when to conduct research during public health emergencies (Chapter 2), and then on ethical considerations relevant to how that research and/or other forms of evidence generation should be conducted (Chapter 3). Conclusions are set out in Chapter 4.

Chapter 2. Ethical considerations in whether and when to conduct research

Is there an ethical imperative to integrate research into a public health emergency response?

Much of the focus of ethical deliberation in the past has been on the question of whether it is possible to conduct research ethically at all during an emergency: exploring, for example, concerns that research may hinder essential emergency response activities, and that prospective participants are not in a position to provide meaningful consent. As a result, detailed guidance has been issued by, among others, the WHO (2), the Nuffield Council on Bioethics (4), and Research for Health in Humanitarian Crises (3) on how research in such challenging circumstances can meet ethical standards. However, the question of whether there is an ethical imperative to integrate research in public health emergency response – in other words whether it is unethical to fail to conduct research – has been the subject of less consideration.

The ethical costs of not doing research in connection with emergency responses are substantial. In the context of a novel threat, such as that posed by COVID-19, the greatest cost is that simply not enough is known about the benefits and harms of possible interventions; the relative effectiveness of different approaches; or the differential impact of particular approaches on different groups within a population. Well-designed studies help save lives and minimise suffering, reduce the risk that resources are wasted on ineffective or even harmful interventions, and support equitable policy decisions. They also take into account the needs of future generations, by enhancing the likelihood that the response to future pandemics can be informed by a more secure evidence base, and in some cases that lessons learned from the emergency can help improve health or healthcare in non-emergency contexts.

The imperative to obtain robust evidence in such circumstances is already well recognised in the context of pharmaceutical interventions, including diagnostics, treatments and vaccines. This was evidenced from the beginning of the COVID-19 pandemic in the strong support from the government, the NHS, and the wider public for initiatives such as the RECOVERY trial: closely embedded within clinical practice and able rapidly to recruit large number of patients and produce equally rapid results that saved many lives (25, 53, 28).

However, the same approach has not routinely been taken to non-pharmaceutical interventions (NPIs), including the effects (both positive and negative) of lockdowns, school closures, restrictions on people living in care homes, quarantine and masking. While attempts were made to embed systematic evaluation in the re-opening of major public events, thereby informing policy, and standard operating procedures within the test and trace programme drew on learnings across multiple sites and were regularly revised (for example 54), it has been argued that this approach remained the exception rather than the rule (11). The lack of research or systematic evaluation in some policy areas was problematic not only in the lack of evidence to inform ongoing policy as to the effectiveness of the various interventions imposed (whether singly or in combination), and whether and when they should be lifted. It was also critical with respect to how these policy choices were affecting different parts of the population unevenly, with often disproportionate burden experienced by those already most disadvantaged (55). The absence of adequate research evidence can also operate as an exacerbating factor in social and political divisions over interventions such as mask mandates, and undermine trust in public policy decisions (56).

These opportunity costs are a key consideration in determining the nature and scope of ethical responsibilities to undertake research. A decision not to act is as much a policy choice as a decision to take action; and it is far from the case that the ethically ‘safer’ option is necessarily not to conduct research. In the context both of new threats, and of existing threats where past failure to conduct research has resulted in an inadequate evidence base, we argue that there is an ethical obligation to seek to improve that evidence base and reduce uncertainty through high quality research. This presumption is strengthened when it relates to interventions that are imposed on populations, rather than simply offered or recommended.

The ethical imperative to enable high quality research extends beyond those immediately engaged in the research enterprise (research teams, research institutions, research funders, healthcare systems) to a wide range of policy stakeholders, whose decisions and choices influence the practical feasibility of conducting research.

Complementary and competing obligations

It is important to recognise that this obligation to improve the evidence base for emergency response may arise in the context of competing obligations, not least in terms of the demands of the immediate emergency response and the ability of the health, social care and public health system to provide urgently-needed care. We suggest that the 5 criteria that London and Kimmerman specify for research to be in the public interest (which are closely mirrored by the threshold criteria identified by Meyer and others) provide a structured way of analysing the strength of the ethical argument for research in specific contexts, identifying both complementary and competing obligations. Below we expand on 3 of these criteria (importance, reporting obligations and feasibility), drawing on contributions from the round-table. The remaining 2 criteria of rigorous design and analytical integrity are addressed in Chapter 3.

Importance of research

The importance of a proposed research project lies at the heart of any claim that there is an ethical imperative to conduct it. In considering the importance of research in the context of a particular emergency, it will be necessary to consider separately:

• the nature of the research question (is it addressing key evidence gaps, including the issues that those affected by the emergency consider most important?)
• the purpose for which any research data will be used (how will the results feed into public policy or clinical decision-making? How will it help calibrate policy to respond effectively to differential impacts either of the emergency itself or the measures taken to combat it?)
• who is likely to benefit from that research (is it for the wider public good? How does it address the needs of those who are disproportionately affected by the emergency and address existing health disparities?)

Strong arguments were made in the literature covered by the rapid literature review for the importance of prioritisation mechanisms at both local and national level, reflecting the value of the proposed research to the emergency response. Such mechanisms are particularly important given the inevitable constraints on the number of research projects that will be feasible during an emergency, including in terms of time, money, and the capacity of the ethics review, regulatory and healthcare systems. In addition to avoiding duplication of effort (which may additionally result in failure to recruit sufficient participants because of competition between research projects), prioritisation systems need to address questions of equity, with due attention given to research proposals that contribute to understanding of the scope for differential impact on particular population groups. This reinforces the need to take into account the potential value of diverse forms of research, including operational field-based research, impact data, and public experience and opinion data, all of which are crucial to influence decision-making at appropriately local levels. Ethics research and reflection similarly plays an important role, for example with respect to innovative technologies such as digital contact tracing, and the exceptional imposition of mandatory measures.

Reporting obligations and transparency

As London and Kimmerman argue, there is a heightened responsibility in emergencies on researchers to ensure that their results (negative as well as positive) are made promptly available, in an accessible form that enables their integration into decision-making processes (13). Indeed, in July 2020, the HRA published its #MakeItPublic strategy, which made the case for transparency and openness in health and social care research, whether during emergency or non-emergency times (57). This responsibility also applies to those who have commissioned research, to help ensure maximum public benefit from the data obtained. The absence of such a commitment would undermine the ethical justification of research as necessary to improve the evidence base for emergency response. Given the inherent tension between early reporting of potentially important results and quality assurance processes, clarity is required about the status of any findings: for example when these are published as a preprint or via organisational websites in advance of peer review.

A complementary responsibility lies on decision-makers, and those responsible for the wider policy-making environment, to ensure that research evidence is properly integrated – and seen to be integrated – into decision-making processes. It is important to recognise not only how evidence may often be interpreted in multiple ways, but also how values, as well as facts, steer policy: even if facts are clear (unlikely in an evolving emergency), a decision about how, for example, to prioritise the needs of older and younger people when these come into conflict, is not one that research alone can resolve (58).

Transparency is therefore crucial on the part of decision-makers with respect to how they have (or have not) incorporated emerging evidence into their decisions, and what underlying values have steered policy choices.

Public communication about how decisions are made, and how these may be affected by a changing evidence base or shifting values, will be particularly important in maintaining the level of public trust in the government’s approach to the emergency. This need for transparency and accountability continues once the emergency is over: accountability mechanisms that provide a route to review the effectiveness and consequences of emergency research can provide assurance that research was indeed ethically conducted, thereby enhancing the trustworthiness of future research.

Feasibility of research

It is self-evident that any obligation to conduct research can only arise if such research is feasible: whether in the sense of being practically possible in the circumstances, or in the sense of being justifiable in the light of competing obligations. Given the opportunity costs of not doing research, it is also crucial that feasibility concerns are not used as an excuse to limit research where they can reasonably be resolved. Collaboration – at local, national and global levels, within the research sector, and across different government departments – is an essential component in enhancing feasibility, not least in learning from, and building on, knowledge from other countries. Devolution to the appropriately local level, working within existing systems rather than creating new initiatives, and working closely with communities, will help address concerns about feasibility and ensure relevance to local needs (10, 17). Effective co-ordination and linkages between such local initiatives may be required to ensure adequate statistical power (1).

The practical and moral requirements of feasibility highlight the importance of looking at responsibilities of different stakeholders over various time-frames. In considering what research is feasible to undertake, it is essential to distinguish between the immediate acute phase of an emergency (when a new threat emerges, both at the start of an emergency, and potentially again at later stages) and the longer-term. There may be a need to make immediate policy decisions, for example on the imposition of NPIs to limit exposure and tranmission, and waiting for research evidence before acting may not be feasible. However, as COVID-19 illustrated, public health emergencies may extend over many months, even years, and the justification of immediate urgency will rapidly lose its force. As a minimum, as Barosa and others (6) argue, there must be a plan to generate and collect evidence during or after policy implementation, and to begin well-designed trials as soon as possible.

The challenges of initiating research in the immediate onset of an emergency highlight the crucial role that emergency preparedness can play in enabling the rapid ethical generation of evidence (both clinical and non-clinical) in the emergency itself (4).

Public policy-makers have a responsibility in inter-emergency periods to support the development of research systems able to pivot rapidly and effectively to conduct research relevant to a new emergency.

As indicated by Katz and others, these essential upstream systems include “research platforms, research priority setting, community engagement, data sharing, funding, and associated regulatory and ethical pathways” (10). It is extremely difficult to set up these essential elements of research infrastructure from scratch during an emergency, and hence both adequate investment and longterm commitment is required as part of emergency planning. This includes looking closely at how research can be made less onerous (for example through close integration with standard healthcare processes, using pragmatic trial designs), and on the role of ‘master’ protocols that allow for pre-emergency regulatory and ethical input, hence enabling rapid turn around at the start of an emergency. Effective horizon-scanning will also help inform policy alertness to the possible nature of future risks.

Knowledge of public input into research development and the role of independent ethical review have both been found to play an important role in public perceptions of the acceptability of research, a further key component of feasibility (59).

Chapter 3. Ethical considerations in how research is conducted

Selecting research methodologies

Research in emergencies almost always takes place in “radically non-ideal circumstances”, in complex, urgent and time-pressured contexts (4). The analyses reviewed in our rapid literature review reiterated how these circumstances do not reduce the ‘standard’ ethical requirements for research: indeed heightened attention may be required, with particular attention paid to impacts on disadvantaged communities who may be disproportionately impacted. This leads to important questions regarding how research should be conducted during emergencies, especially research regarding the public health responses to an epidemic. In this first section of Chapter 3 we focus on formal research methodologies, while in the section that follows we consider other forms of evidence generation and use of data, including public health surveillance and policy evaluation.

There are several reasons why research methodology should be especially rigorous in emergency contexts. First, in widespread epidemics or major disasters, very large populations are affected – in a pandemic, the entire global population is at risk of infection. Second, epidemic emergencies often involve pathogens with a high risk of significant illness or death among at least some of the people infected. Third, epidemic emergencies caused by novel pathogens involve significant uncertainty, for example regarding which treatments, vaccines, or non-pharmaceutical interventions work and how safe or effective each intervention is likely to be. An important goal of research is reducing these uncertainties and therefore guiding clinicians or policymakers towards interventions with the most favourable balance of benefits over harms. Poor quality research, even if subsequently retracted, can exercise harmful influence on policy making (60, 61). Fourth, health interventions are often mandated during emergencies. There is a stronger ethical rationale for high quality research to determine the likely benefits and harms of interventions that are mandated, rather than merely recommended or simply authorised for use, because individuals and populations are required by public health agencies to comply with these measures (62).

Emergencies are also contexts in which experts and members of the public may disagree about the appropriate use of health interventions (whether pharmaceutical or non-pharmaceutical), in part because there may be significant uncertainty about their potential benefits or harms (63). A lack of high quality research can entrench disagreements (64), because different groups (of experts or members of the public) can appeal to different low quality studies producing divergent conclusions that support the differing views of each group. High quality research, in contrast can contribute to resolving such disagreements by providing stronger evidence to support continuing or ceasing specific interventions or policies used in epidemic response.

As explored in the previous chapter, the conduct of successful, ethically acceptable, and scientifically valid studies during emergencies requires significant pre-existing infrastructure and expertise, as well as appropriate mechanisms for trial governance and community engagement. Leading scientists have highlighted the need both for “strategic and long-term investment to significantly deliver on stated policy commitments around pandemic preparedness” and for further progress on “cultivating an enabling environment” in order to enhance the UK’s ability to conduct effective and ethical research in future emergencies (30).

Use of randomised controlled trials

In the face of the challenges posed by emergencies, some research methodologies may be particularly well suited to providing timely, reliable results in order to guide clinicans and policymakers during the emergency. Randomised controlled trials (RCTs) are widely considered to be the gold standard in clinical trials. Such trials are designed to measure efficacy – that is, whether an intervention is likely to cause an effect of a certain size under controlled conditions. Compared with observational research, RCTs, if well designed, can increase the likelihood that the observed effects (beneficial or harmful) are truly associated with the intervention (drug, vaccine, or non-pharmaceutical) rather than caused by other factors or random chance. Although poorly designed RCTs, such as those with low analytical integrity, may be less informative than less rigorous research designs such as observational studies, a well-designed RCT will typically be more reliable than a well-designed observational study addressing a similar research question.

There have also been recent innovations in RCT design,to produce faster and more pragmatic outcomes in public health emergencies. First, factorial designs permit the testing of multiple interventions within one trial (including 2 or more interventions in combination), using a relatively small sample size. Second, multi-centre adaptive platform designs allow the testing of multiple interventions (for example, drugs or vaccines) in different settings, with the potential to add new interventions to the trial as these become available or remove interventions from testing if they are shown to be ineffective or rendered obsolete (for example when new formulations of a drug or vaccine are developed), and update the standard of care as the trial progresses. Third, cluster randomisation allows groups of people to be randomized to an intervention or control, whereas standard RCTs typically randomized individuals. Such designs can be scientifically appropriate where interventions such as public health measures are used with groups (for example, as residents of a geographic location) rather than individuals, and where outcomes (such as transmission of infection) are measured at the group level.

These innovations in trial design may be pragmatic, permitting the use of an RCT design where traditional RCTs may be infeasible. Such designs may also have implications for the ethical acceptability of a given trial. For example, factorial designs may be attractive not only because more interventions (including combinations of interventions) can be tested in a shorter time. If the interventions being tested are likely to have a better balance of benefits and harms than placebo, more participants will receive benefits as a result of participation. Adaptive platform trials can be ethically advantageous because adaptation ideally results in fewer participants receiving interventions that are known to be ineffective or harmful (based on preliminary results from the platform trial and/or results from other trials), and ensure that results are more timely by updating the list of interventions used in the trial over time. Cluster randomisation can be ethically advantageous where individual randomisation is not acceptable to the local population and/or where it is important to measure the effect of an intervention but infeasible to measure this effect at the individual level.

Other approaches

Yet RCTs are not the only useful study design in public health emergencies. Other types of quantitative and qualitative research, including observational studies, social science research, and ethics research, will often also play essential roles in emergency responses. Such types of research may complement the role of RCTs in measuring efficacy: for example by providing supplemental data on effectiveness (how well an intervention works in real-world conditions); understanding how interventions are viewed and used by community members; or analysing the conditions under which it would be ethical to use an intervention with a given set of benefits and harms.

In any case, standard RCT designs may be difficult to conduct in certain emergency settings, or may be unsuited to the particular research question. Other similar designs possess some of the methodological advantages of standard RCTs and may be more feasible in certain circumstances. For example, where government agencies adopt different public health responses to similar epidemics, but such responses are not randomised, a natural experiment study design may allow the use of de facto controls. This occurs when one jurisdiction adopts a specific policy (the intervention) not used by a second jurisdiction (the control) but where the public health responses are otherwise similar. An example was the use of curfews in certain jurisdictions (but not others) in Germany during the COVID-19 pandemic. This natural experiment suggested that curfews had minimal additional effects on transmission of the virus beyond other measures implemented at the same time (65).

Similar considerations apply to clinical practice. In emergencies, some physicians and patients may experiment with medical therapies (for example using unproven or off-licence treatments) outside of research settings. Such experimental use of therapies may produce net benefits compared to the standard of care; however, the rigorous assessment of benefits and harms arguably requires controlled research rather than observational data on the results of variations in clinical practice. Where such experimental use of medical therapy occurs outside of standard research designs, data collection should nevertheless be as rigorous as possible in order to provide at least some evidence of benefits and harms (66). Such data may help to support either the initiation of formal research regarding a promising experimental therapy or the discontinuation of a clearly harmful practice.

The evidence from COVID-19 of differential impact on different parts of the UK population (55) highlights the importance of all studies, regardless of the methodological approach taken, being inclusive by design: both in terms of proactively ensuring diverse representation across study participation, and in terms of analysing and reporting results in ways that enable differential impact (for example, by sex or gender or by ethnicity) to be identified and acted upon (67).

Using data: research, public health surveillance and other forms of evidence generation

Public health surveillance versus public health research

Public health surveillance involves the collection of data about individuals and their health conditions with the primary goal of informing public health interventions in the local or national context. A secondary goal of surveillance is to produce generalisable knowledge that might inform, for example, further scientific work on a given health problem, interventions in other contexts, and/or future public health interventions. In this respect, surveillance is similar to public health research, where the primary goal is to produce knowledge about public health problems, and there is often a secondary goal to inform interventions for these problems (although typically on a longer timescale than public health surveillance).

As noted earlier, there is often no ‘bright line’ distinction between research and public health surveillance – both activities often involve identical activities from the perspective of the person whose data is being used. However, in practice, ethics and governance approaches in these 2 areas differ significantly. Research typically requires the informed consent of participants as well as prospective review by an ethics committee, and there are many safeguards in place to facilitate the ethical conduct of research.

At the international level, the World Health Organization produced ethical guidelines on public health surveillance in 2017 (68). Among other topics, these guidelines set out requirements regarding the rationale for surveillance, appropriate data collection and sharing, and the application of relevant ethical principles including transparency, harm minimisation, and justice. Yet, in practice, governance mechanisms for public health surveillance are less well-developed than those for research, and unlike researchers, few public health agencies are able to draw on timely ethics advice during an emergency (69).

Further, as identified in the rapid review in Chapter 1, the technology used in surveillance has changed rapidly in recent years, including much wider use of pathogen genomics as part of routine surveillance and emergency responses. Technological developments often have major implications for the ethics of surveillance, as well as for research.

The area of public health surveillance, and its overlap with research, is therefore an area requiring significant additional activity to prepare public health agencies for an ethical response to future public health emergencies. This is likely to require further public and expert consultation regarding appropriate governance mechanisms for surveillance, the development of mechanisms within health agencies to improve the ethical conduct of surveillance, as well as work on the ethical use of novel technologies in this context.

Other data collection activities

Public health emergencies also involve the collection of data relevant to the emergency response as part of activities that are neither research nor surveillance. Such activities might include real time policy evaluation via the collection of data on how well an intervention is used in the real world (70). These activities differ from research in several ways (see Table 1). For example, evaluating an intervention that is part of current policy typically does not involve a control arm or comparisons to where the intervention is not being used. While some policy evaluations are part of implementation research (where standard research ethics requirements apply), in other circumstances it may be appropriate to collect data to evaluate current policies without formal research ethics oversight.

These data collection activities may nevertheless be improved through similar governance mechanisms as those that are applied to research. For example, the details of policy evaluations, especially for policies that are likely to have major health impacts or are mandated, should ideally be transparently available to the public (much like the ethical requirement for research trial designs to be deposited in publicly available trial registries). Data collection should also be as rigorous as possible and designed to minimise bias; for example, policy evaluations should not only collect data about the benefits of current policy but also any relevant harms.

The question of whether it is appropriate to adopt formal research methodologies and governance should always be kept under review. It will be particularly appropriate to adopt formal research methodologies (including registration of the study protocol before the start date, ethical review, and publications of results) when policy proposals are contentious and/or where there is significant disagreement between experts as to most appropriate ways of balancing public health and other interests (71, 72).

Table 1. Public health research compared with surveillance and policy evaluation

	Primary goal	Secondary goal	Human participants	Ethics review	Consent for use of data	Example questions
Public health research	Generalisable knowledge	Inform policy	Yes	Yes	Yes	What are the characteristics of a novel pathogen? What is the efficacy of public health interventions?
Public health surveillance	Inform policy	Generalisable knowledge	Yes	No	No	What is the local incidence of an infectious disease?
Policy evaluation	Inform policy	Generalisable knowledge [note 1]	Yes	No	No	How is an intervention being used in practice?

Note 1: if shared outside the organisation.

Demonstrating trustworthiness

Given the importance of learning from health emergencies in ways that have the potential to inform robust and evidence-based preparations for future emergencies, we suggest that there are ethical obligations for a range of actors – researchers, funders, public health institutions – to contribute to the creation of resources to support research between pandemics, build on what has been learned, and ensure the greatest public benefit from the research that has been conducted during the recent emergency.

To achieve the scale and efficiency required for high quality research, this may require increased capacity for the systematic storage and appropriate sharing of data and samples in ways that will require coordination and collaboration between institutions and researchers who may have competing commitments and interests. Achieving this will require leadership and policy coordination. It will also require governance arrangements that secure the confidence of those who have provided the samples and data, and a willingness to engage in public dialogue to make the case for the value of such data linkage use, and take on board public concerns and expectations as to when and how such use can be acceptable.

One of the important responsibilities of those who establish and oversee such resources and inter-pandemic research preparation is thus to do so in a way that enables and justifies sustainable and appropriate public trust and confidence in research in general, and in the storage and use of personal data in particular. As indicated in the findings of the citizens’ juries co-commissioned by the National Data Guardian, an important element of demonstrating such trustworthiness is likely to be openness on the part of policy-makers and research institutions to public engagement and input into governance arrangements, including public involvement in access decisions (52, 73). Such assurances will be particularly important where research involves commercial, as well as academic and public partners.

Chapter 4. Conclusions

In the context both of new threats, and of existing threats where past failure to conduct research has resulted in an inadequate evidence base, we argue that there is an ethical obligation to seek to improve that evidence base and reduce uncertainty through high quality research. That obligation extends beyond those immediately engaged in the research enterprise to a wide range of policy stakeholders, whose decisions and choices influence the practical feasibility of conducting research. Where other forms of evidence generation, such as policy evaluation or market research, are the most appropriate ways of generating evidence, these should be guided by equivalent ethical standards to promote respect for participant or citizen welfare, scientific rigour, and transparency.

Responsibilities that arise for policy-makers include:

• support for emergency preparedness encompassing
  • facilitative regulatory and ethical pathways that can support rapid and effective research relevant to a new emergency and that help minimise impact on the emergency response effort
  • sustainable support for, and enablement of, the infrastructure required to conduct that research, including multi-institution research platforms, priority-setting mechanisms, community engagement plans, and data sharing arrangements
• a minimum commitment to ensuring that evidence is generated during or after policy implementation, and that well-designed studies begin as soon as possible after the start of the emergency, addressing evidence gaps that have been prioritised in a transparent and accountable manner
• transparency with respect to how emerging evidence has been incorporated into decisions (including decisions not to act), and what underlying values have steered policy and operational choices
• support for ongoing research in inter-emergency periods to help maximise public benefit from emergency research, including commitment to involving members of the public, along with data experts, in developing trustworthy systems for data access and use
• commitment to an ongoing cycle of learning during and between public health emergencies, including rigorous processes to identify the impact of policies, assess their effect on inequalities, and respond to negative unintended consequences

Finally, we highlight the importance of considering how ethics and social science expertise can be better embedded in decision-making systems, including in the design and prioritisation of research. We emphasise that the role of experts in this space is not to take decisions directly but rather to provide an ‘evidence landscape’ and ethical tools to support decision-makers in managing the evolving evidence and ethical conflicts that characterise public health emergencies (74). In the fast-moving climate of a public health emergency, and in the context of competing obligations, timely ethics support and advice (supported by rigorous research on infectious disease and emergency ethics) has a key role to play in the public sphere.

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Annexe. Methodology

This report builds on existing work on the ethical conduct of research in emergencies (2, 3, 4). It draws on a rapid review of academic and grey literature published since 2019, in order to explore systematically how the experience of the coronavirus (COVID-19) pandemic might have challenged existing thinking, and to evaluate the ethical feasibility of incorporating research into health emergency response strategies. The material found through the rapid review was supplemented by additional relevant literature identified by the authors. The initial analysis of this literature, and the implications for policy and practice in the UK, was discussed and refined at an expert roundtable meeting and through external review of a draft report.

Rapid literature review

The aims of the rapid literature review, conducted by Thomas Henning, were to identify and summarise key recent academic papers on 3 topics:

1. Ethical obligations to conduct research on responses to pandemics.
2. Disagreements about appropriate research methodologies.
3. Ethical aspects of public health surveillance.

In the light of timing constraints, this was undertaken as a narrative review, not an exhaustive or full systematic review. Databases used were:

• Pubmed, using the search strategy research ethic* AND (“emergency” OR crisis OR pandemic OR urgent), and
• Google Scholar, using the search strategy research ethic* AND (“emergency” OR crisis OR pandemic OR urgent) AND (medic* OR health)
• Google, using the advanced search function and the same strategy as Google Scholar

Inclusion and exclusion criteria

Included

Papers (original articles, reviews, and commentaries) from 2019 to present, in English, on ethical aspects of research on responses to pandemics or infectious disease health emergencies, including “lessons learned” type papers on what went well or badly regarding research during COVID-19, and papers on practical ethics, such as social science studies on the experiences of participants and research teams in relevant research.

Excluded

Papers not relevant to UK context; papers on research conducted during emergencies but not studying emergency responses; papers on non-infectious disease emergencies or disasters and so on; conference abstracts.

The abstracts of 1,731 papers retrieved from PubMed, the first 250 papers appearing on the Google Scholar search, and the first 250 results from the Google search were screened for relevance, and 35 papers identified for fuller consideration. The subsequent detailed analysis of themes was supplemented by additional papers identified by the authors and by attendees at the roundtable.

Roundtable meeting

The roundtable was convened on Friday 22 March 2024 (at the UKHSA’s office in London and virtually) to discuss and strengthen emerging findings from the rapid literature review and initial analysis. The discussion was structured around the 3 topics covered by the review, listed above. Emerging themes and associated questions, derived from the initial analysis, were circulated to attendees in advance.

Attendance list

• Mike Parker, University of Oxford (in person – chair)
• Alex Broadbent, Durham University (remote)
• Kirsty Edwards, HRA (remote)
• Tom Fowler, UKHSA (in person)
• Nina Gobat, WHO (remote)
• Patricia Kingori, University of Oxford (in person)
• Heidi Larson, LSHTM (remote)
• Richard Pebody, UKHSA (remote)
• Amanda Rojek, University of Oxford (in person)
• Julian Sheather, MSF (in person)
• Sariyu Shoge, UKHSA (in person)
• Mehrunisha Suleman, University of Oxford (first hour – remote)
• Zeb Jamrozik (consultant, in person)
• Katharine Wright (consultant, in person)
• Thomas Henning (research assistant, in person)

External review

All attendees at the roundtable meeting were invited to review the initial draft report, which was subsequently revised. The authors are very grateful for the constructive review comments received.