How achievable are COVID-19 clinical trial recruitment targets? A UK observational cohort study and trials registry analysis

Nick G Cunniffe; Simon J Gunter; Michael Brown; Sarah W Burge; Clare Coyle; Anthony De Soyza; Tom Dymond; Hanif Esmail; Darrel P Francis; Jacqui Galloway; James B Galloway; Effrossyni Gkrania-Klotsas; Jane Greenaway; George Katritsis; Prapa Kanagaratnam; Martin D Knolle; Kelly Leonard; Zoe C McIntyre; Ben Prudon; Tommy Rampling; Mili Estee Torok; Ben Warne; Mark Yates; Nicholas J Matheson; Li Su; Sofia Villar; Grant D Stewart; Mark Toshner

doi:10.1136/bmjopen-2020-044566

How achievable are COVID-19 clinical trial recruitment targets? A UK observational cohort study and trials registry analysis

BMJ Open. 2020 Oct 5;10(10):e044566. doi: 10.1136/bmjopen-2020-044566.

Authors

Nick G Cunniffe^#¹, Simon J Gunter^#², Michael Brown³, Sarah W Burge⁴, Clare Coyle⁵, Anthony De Soyza⁶, Tom Dymond⁷, Hanif Esmail^{8

9

10}, Darrel P Francis¹¹, Jacqui Galloway¹², James B Galloway¹³, Effrossyni Gkrania-Klotsas¹⁴, Jane Greenaway¹⁵, George Katritsis¹⁶, Prapa Kanagaratnam¹⁷, Martin D Knolle¹², Kelly Leonard¹⁸, Zoe C McIntyre¹⁹, Ben Prudon²⁰, Tommy Rampling²¹, Mili Estee Torok²², Ben Warne²³, Mark Yates¹³, Nicholas J Matheson^{14

23

24

25}, Li Su²⁶, Sofia Villar²⁶, Grant D Stewart^#^{4

27}, Mark Toshner^#^{28

29}

Affiliations

¹ Department of Clinical Neurosciences, Cambridge University, Cambridge, UK.
² Harvard Medical School, Harvard University, Boston, Massachusetts, USA.
³ Division of Infection, University College London Hospital NHS Trust, London, UK.
⁴ Cancer Research UK Urological Malignancies Programme, Department of Oncology, University of Cambridge, Cambridge, UK.
⁵ Department of Cardiology, Hammersmith Hospitals NHS Trust, London, UK.
⁶ Respiratory Medicine, Freeman Hospital, Newcastle upon Tyne, UK.
⁷ Department of Infection and Inflammation Research, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
⁸ Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, UK.
⁹ MRC Clinical Trials Unit, University College London, London, UK.
¹⁰ Institute for Global Health, University College London, London, United Kingdom.
¹¹ Faculty of Medicine, National Heart & Lung Institute, Imperial College London, London, UK.
¹² Department of Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
¹³ Centre for Rheumatic Diseases, Kings College London, London, UK.
¹⁴ Department of Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
¹⁵ Research and Development, North Tees Hospital, Stockton-on-Tees, UK.
¹⁶ National Heart and Lung Institute, Imperial College London, London, UK.
¹⁷ Department of Cardiology, St Marys Hospital, Imperial College Healthcare NHS Trust, London, UK.
¹⁸ Cambridge Urology Translational Research and Clinical Trials Department, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
¹⁹ School of Clinical Medicine, Office for Translational Research, University of Cambridge, Cambridge, UK.
²⁰ Department of Respiratory Medicine, North Tees Hospital, Stockton-on-Tees, UK.
²¹ Division of Pathology, University College London Hospital NHS Trust, London, United Kingdom.
²² University of Cambridge, Cambridge, UK.
²³ Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.
²⁴ NHS Blood and Transplant, Cambridge, UK.
²⁵ Department of Medicine, University of Cambridge, Cambridge, UK.
²⁶ MRC Biostatistics Unit, University of Cambridge School of Clinical Medicine, Cambridge Institute of Public Health, Cambridge, United Kingdom.
²⁷ Department of Surgery, University of Cambridge, Cambridge, UK.
²⁸ Department of Medicine, University of Cambridge, Cambridge, UK [email protected].
²⁹ NIHR Respiratory Translational Research Collaboration, Cambridge, UK.

^# Contributed equally.

Abstract

Objectives: To analyse enrolment to interventional trials during the first wave of the COVID-19 pandemic in England and describe the barriers to successful recruitment in the circumstance of a further wave or future pandemics.

Design: We analysed registered interventional COVID-19 trial data and concurrently did a prospective observational study of hospitalised patients with COVID-19 who were being assessed for eligibility to one of the RECOVERY, C19-ACS or SIMPLE trials.

Setting: Interventional COVID-19 trial data were analysed from the clinicaltrials.gov and International Standard Randomized Controlled Trial Number databases on 12 July 2020. The patient cohort was taken from five centres in a respiratory National Institute for Health Research network. Population and modelling data were taken from published reports from the UK government and Medical Research Council Biostatistics Unit.

Participants: 2082 consecutive admitted patients with laboratory-confirmed SARS-CoV-2 infection from 27 March 2020 were included.

Main outcome measures: Proportions enrolled, and reasons for exclusion from the aforementioned trials. Comparisons of trial recruitment targets with estimated feasible recruitment numbers.

Results: Analysis of trial registration data for COVID-19 treatment studies enrolling in England showed that by 12 July 2020, 29 142 participants were needed. In the observational study, 430 (20.7%) proceeded to randomisation. 82 (3.9%) declined participation, 699 (33.6%) were excluded on clinical grounds, 363 (17.4%) were medically fit for discharge and 153 (7.3%) were receiving palliative care. With 111 037 people hospitalised with COVID-19 in England by 12 July 2020, we determine that 22 985 people were potentially suitable for trial enrolment. We estimate a UK hospitalisation rate of 2.38%, and that another 1.25 million infections would be required to meet recruitment targets of ongoing trials.

Conclusions: Feasible recruitment rates, study design and proliferation of trials can limit the number, and size, that will successfully complete recruitment. We consider that fewer, more appropriately designed trials, prioritising cooperation between centres would maximise productivity in a further wave.

Keywords: COVID-19; clinical trials; infectious diseases.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Betacoronavirus / isolation & purification
Biomedical Research* / organization & administration
Biomedical Research* / statistics & numerical data
COVID-19
Coronavirus Infections* / epidemiology
Coronavirus Infections* / therapy
Eligibility Determination
Female
Health Services Accessibility / statistics & numerical data
Hospitalization / statistics & numerical data
Humans
Male
Middle Aged
Pandemics*
Patient Selection*
Pneumonia, Viral* / epidemiology
Pneumonia, Viral* / therapy
Prospective Studies
Randomized Controlled Trials as Topic* / methods
Randomized Controlled Trials as Topic* / statistics & numerical data
Registries / statistics & numerical data
SARS-CoV-2
United Kingdom

Abstract

Publication types

MeSH terms

Grants and funding