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. 2020 Jun 2:5:116.
doi: 10.12688/wellcomeopenres.15933.1. eCollection 2020.

Baseline results of a living systematic review for COVID-19 clinical trial registrations

Brittany J Maguire  1   2 , Alistair R D McLean  1   2 , Sumayyah Rashan  1   2 , Emilia Sitsofe Antonio  2 , Jayshree Bagaria  1 , Zineb Bentounsi  3 , Matthew Brack  1   2 , Fiona Caldwell  1 , Verena Ilona Carrara  2   4   5 , Barbara Wanjiru Citarella  1   2 , Prabin Dahal  1   2 , Vitalis Fambombi Feteh  6   7 , Marius H B Guérin  1 , Kalynn Kennon  1   2 , Kathinka Bilton Lahaut  8 , Gerald Jamberi Makuka  9 , Roland Ngu  1   2 , Sopuruchukwu Obiesie  2 , Caitlin Richmond  1   2 , Sauman Singh-Phulgenda  1   2 , Samantha Strudwick  1   2 , Carina S B Tyrrell  10   11 , Austin Schwinn  12 , David King  12 , Paul N Newton  1   2   13 , Ric N Price  2   14   15 , Laura Merson  1   2   16 , Kasia Stepniewska  1   2 , Philippe J Guérin  1   2
Affiliations

Baseline results of a living systematic review for COVID-19 clinical trial registrations

Brittany J Maguire et al. Wellcome Open Res. .

Abstract

Background: Since the coronavirus disease 2019 (COVID-19) outbreak was first reported in December 2019, many independent trials have been planned that aim to answer similar questions. Tools allowing researchers to review studies already underway can facilitate collaboration, cooperation and harmonisation. The Infectious Diseases Data Observatory (IDDO) has undertaken a living systematic review (LSR) to provide an open, accessible and frequently updated resource summarising characteristics of COVID-19 study registrations. Methods: Review of all eligible trial records identified by systematic searches as of 3 April 2020 and initial synthesis of clinical study characteristics were conducted. In partnership with Exaptive, an open access, cloud-based knowledge graph has been created using the results. Results: There were 728 study registrations which met eligibility criteria and were still active. Median (25 th, 75 th percentile) sample size was 130 (60, 400) for all studies and 134 (70, 300) for RCTs. Eight lower middle and low income countries were represented among the planned recruitment sites. Overall 109 pharmacological interventions or advanced therapy medicinal products covering 23 drug categories were studied. Majority (57%, 62/109) of them were planned only in one study arm, either alone or in combination with other interventions. There were 49 distinct combinations studied with 90% (44/49) of them administered in only one or two study arms. The data and interactive platform are available at https://iddo.cognitive.city/. Conclusions: Baseline review highlighted that the majority of investigations in the first three months of the outbreak were small studies with unique treatment arms, likely to be unpowered to provide solid evidence. The continued work of this LSR will allow a more dependable overview of interventions tested, predict the likely strength of evidence generated, allow fast and informative filtering of relevant trials for specific user groups and provide the rapid guidance needed by investigators and funders to avoid duplication of efforts.

Keywords: COVID-19; Living systematic review; SARS2-CoV2; clinical trials; coronavirus; emerging infections.

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Conflict of interest statement

No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. PRISMA Flow Diagram Living Systematic Review Registry Searches for Baseline Results at 3 April 2020.
All de-duplicated records screened, assessment of eligibility, list of included records available as supplementary materials, see Data Availability. a Per protocol search terms of ((COVID-19) OR (coronav*) OR (*CoV-2) OR (nCoV*)) b Search terms as per only publicly available WHO ICTRP registry export of COVID-19 trials, compiled by WHO ICTRP using the terms ((COVID-19) OR (novel coronavirus) OR (2019-ncov)) c Other sources last searched as per protocol up to 31 st March 2020. Abbreviations: WHO ICTRP, World Health Organization International Clinical Trials Registry Platform; ANZCTR, Australia New Zealand Clinical Trials Registry; EUCTR, European Clinical Trials Registry. The latest and previous versions of this figure are available as extended data .
Figure 2.
Figure 2.
( A) Number of studies and ( B) planned sample size by design type. Planned sample size was unknown for two non-randomised (interventional) studies and 1 other study. Each black circle denotes one trial; red box denotes 25 th and 75 th percentiles; vertical white line indicates the median. The latest and previous versions of this figure are available as extended data .
Figure 3.
Figure 3.. Number of registered studies planning to recruit participants in each country.
Note the break in the x axis between 40 and 580. The latest and previous versions of this figure are available as extended data .
Figure 4.
Figure 4.. Number of study arms and planned sample sizes in cohort/non-randomised, and randomised studies.
The number of study arms assessing each of the drug interventions is presented in upper panels. Planned sample size is presented in lower panels. The x-axis ranges are different for bottom panels with discontinuous x-axis at 8,000 for the bottom right panel. The number inside the dots present the number of arms (upper panels) and planned sample size (lower panels). Abbreviations: ATMP = Advanced Therapy Medical Products; RCT = Randomised controlled trial. The latest and previous versions of this figure are available as extended data .
Figure 5.
Figure 5.
( A) Cognitive City showing graph network of intervention and trial from raw WHO ICTRP data. The network is highly disconnected due to the high number of redundant interventions that result from an uncontrolled vocabulary. ( B) Cognitive City showing graph network of intervention and trial using standardised IDDO COVID living systematic review data and ( C) Cognitive City sub-graph of 5b with intervention and trial using standardised data, for any trial with at least 1 pharmacological intervention arm. The network is highly connected due to the controlled intervention vocabulary and ontology. The latest and previous versions of this figure are available as extended data .
See this image and copyright information in PMC

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