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

References

• World Health Organisation. Strengthening clinical trials to provide high-quality evidence on health interventions and to improve research quality and coordination: seventy-Fifth World Health Assembly, 2022. [cited 2023 August 4]. Available from: https://apps.who.int/gb/ebwha/pdf_files/WHA75/A75_R8-en.pdf.
   Google Scholar
• Hart JT. The inverse care law. Lancet. 1971;1(7696):1–11. doi: 10.1016/s0140-6736(71)92410-x.
   PubMed Web of Science ®Google Scholar
• Bambra C. Pandemic inequalities: emerging infectious diseases and health equity. Int J Equity Health. 2022;21(1):6. doi: 10.1186/s12939-021-01611-2.
   PubMed Web of Science ®Google Scholar
• Office for National Statistics. Deaths involving COVID-19 by local area and socioeconomic deprivation: deaths occurring between 1 March and 31 July 2020. 2023. [cited August, 4, 2023]. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/bulletins/deathsinvolvingcovid19bylocalareasanddeprivation/deathsoccurringbetween1marchand31july2020.).
   Google Scholar
• The Health Foundation. Life expectancy and healthy life expectancy at birth by deprivation. 6 January 2023. [cited August, 4, 2023]. Available from: https://www.health.org.uk/evidence-hub/health-inequalities/life-expectancy-and-healthy-life-expectancy-at-birth-by-deprivation#:∼:text=In%20Wales%2C%20women%20living%20in,slightly%20smaller%2C%20at%2016.9%20years.
   Google Scholar
• Park JJH, Mogg R, Smith GE, et al. How COVID-19 has fundamentally changed clinical research in global health. Lancet Glob Health. 2021;9(5):e711–e20. doi: 10.1016/S2214-109X(20)30542-8.
   PubMed Web of Science ®Google Scholar
• Nile SH, Nile A, Qiu J, et al. COVID-19: pathogenesis, cytokine storm and therapeutic potential of interferons. Cytokine Growth Factor Rev. 2020;53:66–70. doi: 10.1016/j.cytogfr.2020.05.002.
   PubMed Web of Science ®Google Scholar
• Nelson D, Moore JE, Millar BC, et al. Antimicrobial properties of native ulster macrofungi (mushrooms and toadstools) to clinical pathogens. Ulster Med J. 2019;88(2):130–132.
   PubMedGoogle Scholar
• Stott NC, West RR. Randomised controlled trial of antibiotics in patients with cough and purulent sputum. Br Med J. 1976;2(6035):556–559. doi: 10.1136/bmj.2.6035.556.
   PubMedGoogle Scholar
• Anthierens S, Tonkin-Crine S, Cals JW, et al. Clinicians’ views and experiences of interventions to enhance the quality of antibiotic prescribing for acute respiratory tract infections. J Gen Intern Med. 2015;30(4):408–416. doi: 10.1007/s11606-014-3076-6.
   PubMed Web of Science ®Google Scholar
• Little P, Stuart B, Moore M, et al. Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial. Lancet Infect Dis. 2013;13(2):123–129. doi: 10.1016/S1473-3099(12)70300-6.
   PubMed Web of Science ®Google Scholar
• Goossens H, Derde L, Horby P, et al. The European clinical research response to optimise treatment of patients with COVID-19: lessons learned, future perspective, and recommendations. Lancet Infect Dis. 2022;22(5):e153–e8. doi: 10.1016/S1473-3099(21)00705-2.
   PubMed Web of Science ®Google Scholar
• Butler CC, Connor JT, Lewis RJ, et al. Answering patient-centred questions efficiently: response-adaptive platform trials in primary care. Br J Gen Pract. 2018;68(671):294–295. doi: 10.3399/bjgp18X696569.
   PubMed Web of Science ®Google Scholar
• Butler CC, Coenen S, Saville BR, et al. A trial like ALIC(4)E: why design a platform, response-adaptive, open, randomised controlled trial of antivirals for influenza-like illness? ERJ Open Res. 2018;4(2):00046-2018. doi: 10.1183/23120541.00046-2018.
   PubMedGoogle Scholar
• Butler CC, van der Velden AW, Bongard E, et al. Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial. Lancet. 2020;395(10217):42–52. doi: 10.1016/S0140-6736(19)32982-4.
   PubMed Web of Science ®Google Scholar
• Park JJH, Harari O, Dron L, et al. An overview of platform trials with a checklist for clinical readers. J Clin Epidemiol. 2020;125:1–8. doi: 10.1016/j.jclinepi.2020.04.025.
   PubMed Web of Science ®Google Scholar
• Hayward G, Butler CC, Yu LM, et al. Platform randomised trial of INterventions against COVID-19 in older peoPLE (PRINCIPLE): protocol for a randomised, controlled, open-label, adaptive platform, trial of community treatment of COVID-19 syndromic illness in people at higher risk. BMJ Open. 2021;11(6):e046799. doi: 10.1136/bmjopen-2020-046799.
   PubMedGoogle Scholar
• Gobat N, Butler CC, Mollison J, et al. What the public think about participation in medical research during an influenza pandemic: an international cross-sectional survey. Public Health. 2019;177:80–94. doi: 10.1016/j.puhe.2019.07.005.
   PubMed Web of Science ®Google Scholar
• Ford I, Norrie J. Pragmatic trials. N Engl J Med. 2016;375(5):454–463. doi: 10.1056/NEJMra1510059.
   PubMed Web of Science ®Google Scholar
• Zuidgeest MGP, Welsing PMJ, van Thiel G, et al. Series: pragmatic trials and real-world evidence: paper 5. Usual care and real life comparators. J Clin Epidemiol. 2017;90:92–98. doi: 10.1016/j.jclinepi.2017.07.001.
   PubMed Web of Science ®Google Scholar
• Anand R, Norrie J, Bradley JM, et al. Fool’s gold? Why blinded trials are not always best. BMJ. 2020;368:l6228. doi: 10.1136/bmj.l6228.
   PubMedGoogle Scholar
• Moustgaard H, Clayton GL, Jones HE, et al. Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study. BMJ. 2020;368:l6802. doi: 10.1136/bmj.l6802.
   PubMed Web of Science ®Google Scholar
• Little P, Gould C, Williamson I, et al. Reattendance and complications in a randomised trial of prescribing strategies for sore throat: the medicalising effect of prescribing antibiotics. BMJ. 1997;315(7104):350–352. doi: 10.1136/bmj.315.7104.350.
   PubMedGoogle Scholar
• Jefferson T, Jones M, Doshi P, et al. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ. 2014;348(2):g2545–g2545. doi: 10.1136/bmj.g2545.
   PubMedGoogle Scholar
• Dobson J, Whitley RJ, Pocock S, et al. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet. 2015;385(9979):1729–1737. doi: 10.1016/S0140-6736(14)62449-1.
   PubMed Web of Science ®Google Scholar
• Yu LM, Bafadhel M, Dorward J, et al. Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet. 2021;398(10303):843–855. doi: 10.1016/S0140-6736(21)01744-X.
   PubMed Web of Science ®Google Scholar
• Butler CC, Yu LM, Dorward J, et al. Doxycycline for community treatment of suspected COVID-19 in people at high risk of adverse outcomes in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet Respir Med. 2021;9(9):1010–1020. doi: 10.1016/S2213-2600(21)00310-6.
   PubMed Web of Science ®Google Scholar
• Principle Trial Collaborative Group. Azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical course in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet. 2021;397(10279):1063–1074.
   PubMed Web of Science ®Google Scholar
• Dorward J, Yu LM, Hayward G, et al. Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial. Br J Gen Pract. 2022;72(720):e446–e55. doi: 10.3399/BJGP.2022.0083.
   PubMedGoogle Scholar
• Thorpe KE, Zwarenstein M, Oxman AD, et al. A pragmatic-explanatory continuum indicator summary (PRECIS): a tool to help trial designers. J Clin Epidemiol. 2009;62(5):464–475. doi: 10.1016/j.jclinepi.2008.12.011.
   PubMed Web of Science ®Google Scholar
• Jacobson LD, Edwards AG, Granier SK, et al. Evidence-based medicine and general practice. Br J Gen Pract. 1997;47(420):449–452.
   PubMed Web of Science ®Google Scholar
• Cake C, Ogburn E, Pinches H, et al. Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments. Trials. 2022;23(1):62. doi: 10.1186/s13063-021-05965-4.
   PubMed Web of Science ®Google Scholar
• de Lusignan S, Joy M, Sherlock M, et al. PRINCIPLE trial demonstrates scope for in-pandemic improvement in primary care antibiotic stewardship: a retrospective sentinel network cohort study. BJGP Open. 2021;0087:1–11. doi: 10.3399/BJGPO.2021.0087.
   Google Scholar
• COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. 2021. [cited August, 4, 2023]. Available from: https://www.covid19treatmentguidelines.nih.gov/.
   Google Scholar
• World Health Organisation. Therapeutics and COVID-19: living guideline. July, 14, 2023. cited August, 6, 2023]. Available from: https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.4.
   Google Scholar
• Tardif JC, Bouabdallaoui N, L'Allier PL, et al. Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial. Lancet Respir Med. 2021;9(8):924–932. doi: 10.1016/S2213-2600(21)00222-8.
   PubMed Web of Science ®Google Scholar
• Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for oral treatment of covid-19 in nonhospitalized patients. N Engl J Med. 2022;386(6):509–520. doi: 10.1056/NEJMoa2116044.
   PubMed Web of Science ®Google Scholar
• Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with covid-19. N Engl J Med. 2022;386(15):1397–1408. doi: 10.1056/NEJMoa2118542.
   PubMed Web of Science ®Google Scholar
• Gbinigie O, Ogburn E, Allen J, et al. Platform adaptive trial of novel antivirals for early treatment of COVID-19 in the community (PANORAMIC): protocol for a randomised, controlled, open-label, adaptive platform trial of community novel antiviral treatment of COVID-19 in people at increased risk of more severe disease. BMJ Open. 2023;13(8):e069176. doi: 10.1136/bmjopen-2022-069176.
   PubMedGoogle Scholar
• Butler CC, Hobbs FDR, Gbinigie OA, et al. Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet. 2023;401(10373):281–293. doi: 10.1016/S0140-6736(22)02597-1.
   PubMed Web of Science ®Google Scholar
• Patel MG, Dorward J, Yu LM, et al. Inclusion and diversity in the PRINCIPLE trial. Lancet. 2021;397(10291):2251–2252. doi: 10.1016/S0140-6736(21)00945-4.
   PubMed Web of Science ®Google Scholar