Ongoing non-industry-sponsored COVID-19 clinical trials in the first trimester of the pandemic: significant differences between the European and the USA approaches

ABSTRACT

Background

The different features between non-industry-sponsored medicine trials conducted in Europe and the USA to treat COVID-19 patients registered in the first trimester of the pandemic are unknown.

Methods

A search was conducted on four databases looking for ongoing medicine randomized controlled trials (RCTs) and non-RCTs registered current through April 25, 2020. All trials assessing medicines on prophylaxis, special populations, assessing non-medicines and convalescent plasma, were excluded. Of each trial, medicines assessed, design, sample size, registration date, study start and study completion dates, and type of patients were registered.

Results

106 trials were identified, 62 in Europe and 46 in the USA ─with two conducted in both regions. In Europe, 90% were on hospitalized patients, and 70% in the USA (p<0.01). Mean of the estimated time to completion were 7.8 and 13.6 (p<0.001) months for European and USA trials . Multicenter trials were more frequent in Europe (63%) than in the USA (41%) (p=0.031). Masked RCTs were more frequently run in the USA than in Europe (p<0.001). RCTs on hospitalized patients were more commonly conducted in Europe (91%) than in the USA (65%) (p<0.01).

Conclusions

Features of early registered COVID-19 RCTs with medicines in Europe and America had remarkable differences.

KEYWORDS:

• ClinicalTrials.gov
• coronavirus
• Covid-19
• randomized controlled trials
• treatment
• medicines

Article highlights

• Many clinical trials on COVID-19 were registered in the first trimester after the first cases were described in Europe and the USA on the second half of January 2020. Although several studies have described the main characteristics of trials conducted all over the world, there was no information available on the similarities and differences of trials conducted in different regions that assessed medicines on the treatment of COVID-19 patients.

• A search was conducted looking for clinical trials conducted in the five largest European countries (France, Germany, Italy, Spain and the UK) and the USA that were registered during the first trimester of the pandemic (i.e., up to April 25, 2020)

• There were 106 different trials identified, 62 to be conducted in Europe and 46 in the USA, with 2 conducted in both regions. There were 88 randomized controlled trials, 53 in Europe and 37 in the USA; and 18 single-arm trials, 9 in each region.

• Europe registered a significantly higher percentage of trials in hospitalized patients than the USA, and with a significantly shorter estimated completion time. Multicenter trials were significantly more common in Europe. The median number of participants was similar in both regions (Europe, 200; USA, 164)

• The USA registered a significantly higher percentage of masked randomized controlled trials. Europe registered a significantly higher percentage of randomized controlled trials on hospitalized patients than the USA. Most were 2-arm trials in both regions. There were 10 (7 in Europe) randomized controlled trials with no control (standard of care) arm.

• The trials to be conducted in Europe and the USA were aiming to assess 38 and 29 medicines, respectively. The most common assessed medicines were hydroxychloroquine, azithromycin, and tocilizumab involved in 28, 14, and 12 trials.

• Twenty-one and 12 medicines were going to be evaluated in trials to be run only in Europe and the USA, respectively.

Acknowledgments

The author would like to thank Ignacio Mahillo-Fernández PhD (Health Research Institute-Fundación Jiménez Díaz, University Hospital, Universidad Autónoma de Madrid, Madrid, Spain) for conducting the statistical analyses.

Data sharing

All data is included in the article and as Supplementary online material-1 (main characteristics of all trials included in the analysis) and 2 (timetable: date of the first registration of the trials).

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.