Impact case study database

It is widely reported that 85% of health research is wasted because ‘ it asks the wrong questions, is badly designed, not published or poorly reported’ ( The Lancet, 2009, 374(9683): 86-89). Research ethics committees (RECs) review research proposals and give an opinion about whether the research is ethical. Reviews by RECs normally occur after funding has been granted and protocols have been developed, but prior to study recruitment and data gathering. Failure to achieve a “favourable ethics opinion” can prevent a study progressing. This makes ethics committees a key gatekeeper of research, with the opportunity to influence research conduct so as to reduce research waste and enhance transparency. National Health Service (NHS) RECs consider and approve the ethical acceptability of research involving NHS staff and/or patients, as well as other health-related research. There are more than 60 NHS RECs across the UK and they review around 6,000 project applications each year. The Health Research Authority (HRA), an arm’s-length body situated in England’s Department of Health, takes a leading and coordinating role for managing RECs throughout the UK. The HRA’s mission is to promote and protect the interests of patients, harmonise and streamline regulation, and promote transparency in health and social care research.

4.1. Enhancing the transparency of research in the United Kingdom

Research transparency is central to ethical research practice. Health and social care research studies should be registered and the results made public, so that participants are protected from unnecessary studies, use of research funding is maximised and the greatest public benefit is delivered. Non-publication of research is the main cause of research waste (50%). Kolstoe’s research on reporting bias and non-registration of clinical trials has led to government policy change, specifically a significant extension of the mandate and role of the UK Health Research Authority in relation to monitoring clinical trials transparency. Following the primary publication ( R1), the topic of whether RECs should police reporting bias featured in a BMJ “Head to Head” debate ( https://www.bmj.com/content/356/bmj.j1501, 27/03/2017). Subsequently, Kolstoe submitted written ( S1) and oral evidence ( S2) to the 2017 House of Commons Science and Technology Select Committee (STSC) inquiry on research integrity. This evidence:

1. identified reporting bias as a research integrity issue;

2. highlighted a case where non publication of clinical trials results had led to significant wasted public expenditure (GBP424,000,000 spent on Tamiflu, based on incomplete evidence);

3. proposed that the Health Research Authority was best placed to support research ethics committees in monitoring publications arising from projects and ensuring clinical trials transparency.

In view of this evidence, the STSC considered the issue of clinical trials transparency to be so significant for public health that it recommended it be considered separately and an additional report, ‘ Research integrity: clinical trials transparency’ was published in October 2018 ( S3). This report repeatedly referenced Kolstoe’s research alongside recommendations that the HRA establish a national audit programme, modelled on Kolstoe’s work. The HRA was also instructed to publish information on trials that have received ethical approval but are not registered in a publicly accessible register, and introduce a system of sanctions to drive improvements in clinical trials transparency.

In February 2019 and coinciding with the publication of R2, the HRA established the Research Transparency Strategy Group, with Kolstoe as a member. Following drafting and public consultation, the HRA approved the HRA ‘ Make it Public’ Transparency Strategy, which was published in July 2020 ( S4). The HRA ‘ Make it Public’ Strategy extended the role of the HRA in relation to monitoring clinical trials transparency and directly addressed the Science and Technology Committee recommendations by committing the HRA to:

• assume responsibility for registering clinical trials on behalf of the sponsor, using data that provided for study approval;

• require the submission of a final report within 12 months of study completion; and

• use information in the final report to measure research transparency and take action in cases of non-compliance.

As such, the ‘Make it Public’ Strategy ‘ extends the role of the HRA in relation to monitoring clinical trials transparency and represents a significant advance in our ability to support high-quality health and social care research and to promote the interests of patients and the public’ ( S5).

The HRA also published their commitment to conduct ongoing audits of clinical trials registration, using the method developed by Kolstoe, to monitor legal and policy compliance ( S6). Additionally, in response to the results of R3, the HRA have incorporated data access arrangements into a revision of their ethics review form for Research Databases ( S5).

4.2. Improving the consistency and efficiency of NHS ethics committees

In response to the findings from R4, the Director of Approvals Service at the HRA halted the Shared Ethical Debate (ShED) consistency exercises in 2019, and reinstated them in a new format in 2020, with a new focus on using the exercise as a learning opportunity and encouraging members to explore decision-making ( S5), following suggestions published in R4.

4.3. Enhancing the capability and efficiency of research in the UK Ministry of Defence

The Ministry of Defence Research Ethics Committee (MODREC) ensures that all research involving human participants undertaken, funded or sponsored by MOD meets nationally and internationally accepted ethical standards. It is recognised by the United Kingdom Ethics Committee Authority (UKECA) to review clinical trials of investigational medicinal products involving subjects who are UK Armed Forces personnel recruited in a military setting, as well as Phase 1 trials in healthy volunteers conducted by the MOD. It is also recognised as an Appropriate Body under the Mental Capacity Act 2005 for review of research involving UK Armed Forces personnel who are unable to consent for themselves (commonly research in emergency/battlefield situations).

On the basis of his research and experience of NHS RECs , Kolstoe was appointed chair of the MODREC in 2016, and was tasked by the Surgeon General with an evidence based modernisation of the committee, with the goal of streamlining research governance and approvals within the MOD ( G4). Kolstoe rapidly identified a gap in the MOD’s research governance arrangements in relation to the legal requirements for ethics review and, subsequently, represented the MOD in negotiations with the UKECA. These negotiations ensured that the MOD was able to continue to review and approve studies falling under the Clinical Trials Regulations 2004, Mental Capacity Act 2005 and Human Tissue Act 2004. Without this intervention, the MOD would have not been authorised to approve and conduct these types of research and the disruption to high profile and time-sensitive research would have been significant. For example, in 2014 the MOD directed GBP20,000,000 to a five-year, physiological research programme to understand the health effects of combat roles on men and women. This delivered significant changes within the British Army: data from the ‘Women in Ground Close Combat’ research team underpinned the Defence Secretary’s decision to open Ground Close Combat (GCC) roles to women in July 2016, and new role-related, rather than gender- or age-specific, Physical Employment Standards for GCC roles were introduced in April 2019. Any lapse in the ability of the MOD to conduct research with human participants would have jeopardised this, and other, research programmes of national significance.

The agreement brokered by Kolstoe required the subsequent harmonisation of the MOD human research governance policy (JSP536) with two national policies: the ‘UK Policy Framework on Health and Social Care Research’ and ‘Governance Arrangements for Research Ethics Committees’. A contract was awarded to the University of Portsmouth to complete this critical work ( G5, S7), and the new policy was published in December 2019 ( S8). The revised MOD policy was introduced in January 2020 and provided a Proportionate Review Service which allows for research proposals that present ‘no material ethical issues’ to be reviewed and approved via an executive sub-committee. ‘This revision has hugely improved and clarified the MODREC application process for researchers’ ( S7). As a result, the MODREC approval process has become more streamlined and the average time for MODREC project approval has reduced by 35%, from 32 days to 21 days. In addition, the capacity of the committee to review studies has increased by 40% ( S9) with no additional cost. As the annual governance budget is ~GBP350,000, this could be considered as a GBP140,000 efficiency saving for the department in 2020 alone, compared to the previous three years.