Democratising the design and delivery of large-scale randomised, controlled clinical trials in primary care: A personal view

Abstract

Background

Rapid identification of effective treatments for use in the community during a pandemic is vital for the well-being of individuals and the sustainability of healthcare systems and society. Furthermore, identifying treatments that do not work reduces research wastage, spares people unnecessary side effects, rationalises the cost of purchasing and stockpiling medication, and reduces inappropriate medication use. Nevertheless, only a small minority of therapeutic trials for SARS-CoV-2 infections have been in primary care: most opened too late, struggled to recruit, and few produced actionable results. Participation in research is often limited by where one lives or receives health care, and trial participants may not represent those for whom the treatments are intended.

Innovative trials

The ALIC4E, PRINCIPLE and the ongoing PANORAMIC trial have randomised over 40,500 people with COVID-19. This personal view describes how these trials have innovated in: trial design (by using novel adaptive platform designs); trial delivery (by complementing traditional site-based recruitment (‘the patient comes to the research’) with mechanisms to enable sick, infectious people to participate without having to leave home (‘taking research to the people’), and by addressing the ‘inverse research participation law,’ which highlights disproportionate barriers faced by those who have the most to contribute, and benefit from, research, and; in transforming the evidence base by evaluating nine medicines to support guidelines and care decisions world-wide for COVID-19 and contribute to antimicrobial stewardship.

Conclusion

The PRINCIPLE and PANORAMIC trials represent models of innovation and inclusivity, and exemplify the potential of primary care to lead the way in addressing pressing global health challenges.

KEY MESSAGES

• Adaptive platform trials can efficiently evaluate several treatments in parallel and sequentially

• ‘Taking research to people’ can democratise participation by enabling sick, contagious people to contribute from home, country-wide

• The PRINCIPLE and PANORAMIC Trials innovated in trial design and delivery to produce evidence on nine treatments for COVID-19 in the community

Keywords:

• General practice/family medicine
• general
• epidemiology
• treatment/intervention research
• experimental designs

Acknowledgements

I wrote this article from a personal viewpoint based on an invited lecture at WONCA Europe 2023. I acknowledge the European Union for funding and the ALIC4E trial as part of the Platform foR European Preparedness Against (Re-)emerging Epidemics (PREPARE), and the UK National Institute for Health and Care Research in funding and supporting the implementation of the PRINCIPLE and PANORAMIC trials, and thank all the participants, health care and research professionals that made these studies possible. I am grateful to the following people who commented and helped improve this manuscript: Haroon Ahmed, Julie Allen, Judith Breuer, Sophie Betteridge, Daniel Butler, Andrew Carson-Stevens, Johanna Cook, Lucy Cureton, Melissa Dobson, Mark Dolman, Jienchi Dorward, Philip Evans, Nick Francis, Oghenekome A Gbinigie, Victoria Harris, Nigel D Hart, Gail Hayward, F.D. Richard Hobbs, Jane Holmes, Kerenza Hood, Bhautesh Jani, Saye Khoo, Charlotte Latimer Bell, Mona Koshkouei, Paul Little, David M Lowe, Mark Lown, Michael McKenna, Bernadette Mundy, Jonathan S Nguyen-Van-Tam, May Ee Png, Emma Ogburn, Mahendra G Patel, Stavros Petrou, Najib M Rahman, Duncan B Richards, Heather Rutter, Jared Robinson, Benjamin R Saville, Joseph F Standing, Nicholas P B Thomas, Oliver Van Hecke, Ly-Mee Yu.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

UK National Institute for Health and Care Research.