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. 2022 Jun;9(1):e001226.
doi: 10.1136/bmjresp-2022-001226.

Large scale clinical trials: lessons from the COVID-19 pandemic

Alex R Horsley  1 , Laurence Pearmain  2   3 , Sean Knight  2   4 , Nick Schindler  5   6 , Ran Wang  2 , Miriam Bennett  2 , Rebecca C Robey  2 , Jane C Davies  7 , Ratko Djukanović  8 , Liam G Heaney  9 , Tracy Hussell  10 , Stefan J Marciniak  11   12 , Lorcan P McGarvey  13 , Joanna Porter  14   15 , Tom Wilkinson  16 , Chris Brightling  17 , Ling-Pei Ho  18   19
Affiliations

Large scale clinical trials: lessons from the COVID-19 pandemic

Alex R Horsley et al. BMJ Open Respir Res. 2022 Jun.

Abstract

Background: The COVID-19 pandemic has presented substantial new challenges to clinical and research teams. Our objective was to analyse the experience of investigators and research delivery staff regarding the research response to COVID-19 in order to identify these challenges as well as solutions for future pandemic planning.

Methods: We conducted a survey of diverse research staff involved in delivery of COVID-19 clinical trials across the UK. This was delivered online across centres linked to the NIHR Respiratory Translational Research Collaboration. Responses were analysed using a formal thematic analysis approach to identify common themes and recommendations.

Results: 83 survey participants from ten teaching hospitals provided 922 individual question responses. Respondents were involved in a range of research delivery roles but the largest cohort (60%) was study investigators. A wide range of research experiences were captured, including early and late phase trials. Responses were coded into overarching themes. Among common observations, complex protocols without adaptation to a pandemic were noted to have hampered recruitment. Recommendations included the need to develop and test pandemic-specific protocols, and make use of innovations in information technology. Research competition needs to be avoided and drug selection processes should be explicitly transparent.

Conclusions: Delivery of clinical trials, particularly earlier phase trials, in a pandemic clinical environment is highly challenging, and was reactive rather than anticipatory. Future pandemic studies should be designed and tested in advance, making use of pragmatic study designs as far as possible and planning for integration between early and later phase trials and regulatory frameworks.

Keywords: COVID-19; respiratory infection; viral infection.

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Conflict of interest statement

Competing interests: ARH, JD, RD, LGH, TH, SJM, LPM, JP, TW, CEB and LPH are all supported by their respective NIHR Respiratory Biomedical Research Centres. Separate to this work: ARH reports grants from JP Moulton Charity, CF Trust, CF Foundation, MRC and UKRI and personal fees from Vertex Pharmaceuticals and Mylan Pharmaceuticals. JD reports grants from CF Trust, CF Foundation, CF Ireland, EPSRC and personal fees Vertex Pharmaceuticals, Boehringer-Ingelheim, Eloxx, Algipharma, Abbvie, Arcturus, Enterprise Therapeutics. RD reports grants from ERS, Teva, GSK, Novartis, Sanofi, Chiesi and personal fees from Synairgen, Sanofi-Genzyme, Galapagos, GSK, AstraZeneca and Airways Vista, and personal shares in Synairgen. LGH reports grants from MRC, including with multiple industrial partners, and personal fees from Astra Zeneca, Novartis, Roche/Genentech, GlaxoSmithKline, Chiesi, Teva, Theravance and Vectura. SM reports grants from BLF, MRC, June Hancock Mesothelioma Research, Alpha-1 Foundation, and Myrolitis Trust. JP reports grants from UKRI, LifeArc and MRC. TW reports grants from UKRI, Synairgen, AZ, UCB, Bergenbio and personal fees from Synairgen and Valneva. CEB reports fees to his institution from AZ, GSK, Novartis, Chiesi, BI, Genentech, Roche, Sanofi, Regeneron, Mologics, 4DPharma, Synairgen, Merck.

Figures

Figure 1
Figure 1
Timeline of first wave of COVID-19 pandemic, showing total UK daily hospital admissions. Source: coronavirus.data.gov.uk/details/healthcare.
Figure 2
Figure 2
Thematic domains presented for review are shown in dark blue boxes, including the three subdivisions of domain 3. Response themes that contributed to these domains are shown in lighter blue, including subthemes that fed into these. Where themes contributed significantly to more than one domain this is also indicated. IT, information technology; MHRA, Medicines and Healthcare Products Regulatory Agency; R&D, Research and Development department. UPH, Urgent Public Health group.
See this image and copyright information in PMC

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