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

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.

Figure 1

The proliferation of global clinical trials in response to COVID-19. (A) Cumulative number of enrolling studies registered with clinicaltrials.gov or International Standard Randomized Controlled Trial Number until 12 July 2020, subdivided by those testing drugs for COVID-19 treatment and prevention. (B) Cumulative number of participants required to meet recruitment targets for registered clinical trials. (C) Geographical distribution of COVID-19 clinical trials.

Figure 2

Feasibility of achieving target recruitment in England for COVID-19 interventional studies. (A) Cumulative number of enrolling studies in England registered with clinicaltrials.gov or International Standard Randomized Controlled Trial Number until 12 July 2020, subdivided by those testing drugs for COVID-19 treatment and prevention. (B) Cumulative number of participants required to meet recruitment targets for registered COVID-19 treatment trials until 12 July 2020, and predicted number of patients who would have been eligible for randomisation (grey shaded area represents point-wise 95% confidence band for the predictive cumulative number of eligible patients using the lower and upper value of 95% CI for the recruitment rate estimate with continuity correction). The reduction in the infection rate in England means that the recruitment target at 12 July is unlikely to be reached unless there is a second wave; further illustrated by extending hospitalisation data to 5 August 2020.