Abstract
Introduction
The COVID-19 pandemic impacted the operationalisation of non-COVID-19 clinical trials globally, particularly site and participant recruitment and trial success/stoppage. Trials which anticipate recruitment challenges may embed methods such as the QuinteT Recruitment Intervention (QRI) to help identify and understand the sources of challenges. Such interventions can help shed light on pandemic-related challenges. This paper reports our experience of the impact of the COVID-19 pandemic on conducting clinical trials with an embedded QRI, highlighting how the QRI aided in identifying challenges and potential solutions, particularly related to the site set-up and participant recruitment.
Main body
We report on 13 UK clinical trials which included a QRI. Information is from QRI data and researchers’ experience and reflections. In most trials, recruitment was lower than even the lowest anticipated rates. The flexibility of the QRI facilitated rapid data collection to understand and document, and in some instances respond to, operational challenges. Challenges were mostly logistical, pandemic-related and beyond the control of the site or central trial teams. Specifically: disrupted and variable site opening timelines —often due to local research and development (R&D) delays— shortages of staff to recruit patients; fewer eligible patients or limited access to patients; and intervention-related factors. Almost all trials were affected by pandemic-related staffing issues including redeployment, prioritisation of COVID-19 care and research, and COVID-19-related staff illness and absence. Trials of elective procedures were particularly impacted by the pandemic, which caused changes to care/recruitment pathways, deprioritisation of services, reduced clinical and surgical capacity and longer waiting lists. Attempted solutions included extra engagement with staff and R&D departments, trial protocol changes (primarily moving online) and seeking additional resourcing.
Conclusion
We have highlighted wide-ranging, extensive and consistent pandemic-related challenges faced by UK clinical trials, which the QRI helped to identify and, in some cases, address. Many challenges were insurmountable at individual trials or trials unit level. This overview highlights the need to streamline trial regulatory processes, address staffing crises, improve recognition of NHS research staff and for clearer, more nuanced central guidance on the prioritisation of studies and how to deal with the backlog. Pre-emptively embedding qualitative work and stakeholder consultation into trials with anticipated difficulties, moving some processes online, and flexible trial protocols may improve the resilience of trials in the current challenging context.
Background
The COVID-19 pandemic has impacted clinical trials, particularly site opening, trial activation and participant recruitment. Although UK pandemic-related restrictions stopped in February 2022, the impact of the pandemic is ongoing and COVID-19 infections are still present. In the UK, the onset of the pandemic resulted in a rapid large-scale reorganisation of research staff, research infrastructures and research priorities [1]. Internationally, activation for trials (excluding trials of COVID-19 treatments/vaccines) was 57% of that expected pre-pandemic [Success of embedded QRI Many of the pandemic-related challenges identified were logistical barriers which also limited the QRIs' ability to explore hidden challenges to recruitment [37]. However, having the QRI integrated at trial design facilitated rapid data collection to understand and document the challenges. Using interviews with the study staff and analysis of screening data, the QRI was able to provide detailed data on barriers and challenges, which may inform decisions about prioritisation in trial portfolios. QRIs rapidly adapted, and many added opportunities for engagement with staff (RNs, principal investigators (PIs), recruiters) to identify emerging challenges. This engagement included study/site staff meetings (to update trial teams on adaptations to trial procedures/recruitment/clinical updates, energise local research teams and troubleshoot site issues), staff training on identifying and discussing the study with potential participants, webinars, newsletters, prize incentives and meetings with RNs. In five trials (trials 2, 6, 7, 11, 13), the QRI adapted to start staff training before sites opened. Some QRIs introduced new methods of data collection, e.g. collecting data on issues from recruiters by email or survey. Although many challenges were beyond the control of trial teams/units, some trials attempted to mitigate challenges, often in response to QRI findings. This was through extra engagement opportunities for staff and R&D departments, amended study protocols and requests for additional resourcing. The staff engagement and training integral to the QRI demonstrates the benefits of consultation with and involvement of stakeholders (in assessing both the potential impact of the pandemic and possible solutions) in successfully maintaining trials during the pandemic [38]. Wider engagement beyond the study team and patients may also be beneficial, including with funders, collaborating research centres and health systems [38]. Protocol changes included primary outcome timing reflecting delays to surgery (trial 11), switching to online patient contact, e.g. online/postal consent and/or data collection, removing extra visits and medication by post. Many changes are likely to be sustained, in particular, moving towards digitisation [39, 40]. Other positive changes were staff adaptability, improved teamwork and innovations to interventions [38]. Some studies suggest electronic/online recruitment and consent may improve recruitment rates [41], trial diversity [42] and efficiency [43], even during pandemic lockdowns [44], although possibly result in lower conversion rates than offline strategies [41]. Online/remote study meetings, e.g. site initiation visits, are beneficial (better attendance, lower costs, can be more frequent) and unlikely to impair setup times, screening, recruitment or data collection [45]. Online recruitment may widen existing digital inequalities [46] but conversely may help to recruit underserved groups [47]. Online data collection is potentially more acceptable to participants, even for clinical measures [43]. Many of the pandemic-related challenges were exacerbated by inflexible trial protocols unable to adapt to using digital methods. Protocols using pragmatic trial designs and a variety of recruitment options may have helped [48]. The POWER study is a good example of a redesigned and successfully recruiting trial where the comparator was switched prior to site opening from surgery to waiting list to accommodate anticipated recruitment challenges resulting from pandemic-related delays to surgery [49]. Some sites sought additional resourcing, e.g. requesting recruitment extensions from funders, recruiting new staff or promoting the NIHR Associate Principal Investigators’ scheme (a 6-month in-work training opportunity for healthcare practitioners starting their research journey) to enable study workload pressures on site clinicians/research staff to be alleviated [50]. This overview of 13 clinical trials has demonstrated the range of ways the pandemic has impacted on recruitment of trial participants and sites. We have shown that an embedded qualitative intervention (in this case the QRI), opportunities to engage with trial teams, moving online and flexible trial protocols are beneficial in mitigating pandemic-related challenges. This highlights the value of trials likely to face difficulties embedding qualitative work and stakeholder consultation around challenges faced and possible solutions, for both pandemic and non-pandemic-related reasons. Although some of the issues identified, particularly the lack of patients, are likely to improve with the lifting of pandemic-related restrictions, the site/trial set-up disruption, capacity and staffing issues are ongoing and urgently need to be addressed. The multi-site studies reviewed highlight the wide variation in study set-up times and ongoing disruption to set-up, mainly attributed to R&D. Studies exploring whether this is pandemic-related are warranted. Kolstoe and Carpenter highlight that although the new HRA (Health Research Authority) process recommends local R&D offices only address local capacity and capability issues, hospital sites often create new local processes, causing delays [51]. The system is improving [52]; however, further suggestions include deadlines on the R&D process, researcher access to data on local R&D performance, and fewer forms to complete [24, 53, 54]. There are opportunities to improve the system’s efficiency especially in these times of innovation and increased connectivity [55]. These changes may help to speed up and standardise the site set-up process [24, 54] and bring down timescales for study set-up in the UK in line with other countries [5]. Although unusual, the RECOVERY trial has shown how it is possible to rapidly set up a UK clinical trial if processes are streamlined and centralised [56]. The Department of Health and Social Care (DHSC) stated in September 2022 that they are ‘working closely with the NHS R&D community to identify ways to support them in tackling the current situation’ [23]. The UK government’s 2021 plan for delivering NHS clinical research now covers five areas including making the process streamlined, efficient and innovative, enabling through using data and digital tools, and a sustainable and supported research delivery workforce [57]. However, there is clearly a need to increase R&D capacity. One suggestion to address the capacity issues of RNs and ‘crisis’ in the clinical trial staff recruitment/retention, is more opportunities for recognition of RNs’ skills and experiences and validation/progression support via a nationally accredited scheme similar to the NIHR associate PI scheme. We also support Mitchell et al.’s recommendations for greater recognition of the role of the clinical trial manager, improving the role via flexible working and longer contracts, and making efforts to attract people to the role [30]. The DHSC is working on a ‘cross-sector research workforce plan’, including additional investment in the research workforce from 2024 [23], which may help in the longer term. That the pandemic differentially affected certain clinical areas and types of interventions may lead to a disparity in available treatments between clinical areas, for example, in neuro-oncology it is anticipated that the availability of new, potentially life-extending treatments has been reduced due to the premature closure of clinical trials in this area [58]. The use of routine health care for research and analysis, and embedding research in NHS practice, can help overcome barriers and is an important focus for both the government and NHS [27], included in the UK government’s 2021 plan for clinical research in the NHS following the pandemic [57]. Resourcing is needed to help clinical staff and hospital management embed trials in their settings [20]. Hillman provides the example of COVID-19 studies where every single COVID-19 patient was considered for enrolment, with great success [5]. Research needs to be integrated into staff roles, with protected research time [5]. In early 2022, the NHS acknowledged the challenges facing the NHS research portfolio, including staffing, and made plans to ‘take firm action on studies that are struggling to deliver’ [59], with the Reset programme in September 2022 confirming the closure of studies not feasible within current resources [23]. Guidance on the prioritisation of studies to consider for closure is however vague and largely based on crude recruitment figures rather than factors such as the priority of the research question or health condition or analysis of the specific barriers and how effectively these could be overcome. Many challenges were insurmountable at individual study, or even trials unit level, yet there has been a paucity of clear guidance from central bodies on how to overcome them. As long as new trials continue to be considered for funding, the backlog of research will not be cleared. Strategic decision-making is needed on priorities for UK NHS clinical research and how this translates to a local R&D level. The NIHR states that it is ‘vital’ that new studies continue to open [23], but this appears unrealistic unless moves are made to streamline the regulatory process, increase R&D capacity and trial staffing, and give greater recognition to NHS staff’s contribution to research. Embedding qualitative interventions into trials provides the opportunity to quickly identify and help address recruitment challenges. Such interventions may improve a trial’s resilience when facing the challenges to recruitment identified in this paper.Solutions implemented
Recommendations
Conclusions
This analysis of 13 trials has highlighted the range of ways the pandemic continues to impact the success of UK clinical trials. Pandemic-related challenges included staffing issues, local R&D-related disruption to sites opening, prioritisation of healthcare and difficulty accessing patients. Many of these were insurmountable at individual study, or even trials unit level, highlighting the need for central action on the staffing/capacity crises in research and R&D and the ever-increasing NHS trial portfolio, and clear guidance on prioritisation of studies.
The QRI was able to adapt to understand, document and, in some instances respond to, challenges and provide data potentially useful in prioritisation exercises within trial portfolios. Trials, especially those likely to face difficulties, should consider the value of embedding methods to address recruitment difficulties, using stakeholder consultation, routine data, online tools and flexible pragmatic protocols.
Availability of data and materials
Not applicable.
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Acknowledgements
We are grateful to the trial study teams and CIs from Best-BRA, CARE, DISCUS, Hand-2, Inspire, NightLife, OPTIMA, Prepare for Kidney Care, PRoCuRe, PURSUIT, SMALL, STRATA and Sunflower for giving us permission to report on their trial in this paper.
Funding
All the trials reported in this paper were funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. All the authors of this paper are funded by the trials they worked on; however, no additional funding was provided for this paper.
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All authors collected and analysed the data for the QRI in at least one of the trials included. All authors contributed to the paper and read and approved the final version.
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Lorenc, A., Rooshenas, L., Conefrey, C. et al. Non-COVID-19 UK clinical trials and the COVID-19 pandemic: impact, challenges and possible solutions. Trials 24, 424 (2023). https://doi.org/10.1186/s13063-023-07414-w
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DOI: https://doi.org/10.1186/s13063-023-07414-w