Chaos and waste

Since spring 2020, experts in health policy and use of medicines have been surprised by the large volume of clinical trials assessing treatments for covid-19 and have been concerned by the poor quality of many of these trials (1). As of late March 2020, clinical trial registries included 201 trials, evaluating 92 products, including drugs and plasma from patients who had recovered from covid-19. One-third of the trials had no clinical endpoint, about half of them planned to include fewer than 100 patients, and two-thirds were not blinded. In other words, there was a high risk that many of the trials would not provide any information that was actually useful in practice (1). As of late June 2020, more than 1000 trials were registered, about 40% of which involved fewer than 100 patients (2,3). Analysts talk about "disorganization", "chaos" and "huge financial resources wasted" (a)(2,4).

Most of the conclusive results have been provided by two trials, which compared a range of treatments in thousands of patients. These were the "Recovery" trial in the United Kingdom and the "Solidarity" trial sponsored by the World Health Organization (WHO) (b)(2).This observation points to the need for better coordination of research efforts, to facilitate the initiation of comparative trials which are of the appropriate size to yield decisive and rapid results, rather than a multiplicity of small flawed trials (1-4).

Hydroxychloroquine: misplaced enthusiasm

In late June 2020, more than 100 trials of hydroxychloroquine were underway, planned to include a total of more than 100 000 patients (2,3).Yet, by that time, the Recovery and Solidarity trials had already shown that this drug was not effective in treating severe forms of covid-19 (2).This multitude of trials on hydroxychloroquine is all the more regrettable since the French study which had sparked worldwide enthusiasm for the drug combines several disqualifying methodological biases (5,6).

These resources – of time, money and patients willing to take part in a trial – would have been better employed in evaluating strategies that received far less attention, including personal protective measures or "lockdowns", which continue to be the subject of much controversy (7).

©Prescrire 1 June 2021

Notes:
a- This frenzy led to preprints which were to a greater or lesser extent sloppy and biased, and sometimes retracted due to obvious errors, such as the study based on medical record data provided by the Surgisphere Corporation (ref 8).
b- The European trial "Discovery", coordinated by France, was meant to include 3200 patients from several European countries, but as of mid-September 2020, only 916 patients had been recruited, including only 30 or so outside France. As of 5 January 2021, its results had still not been published (refs 5,9).

Selected references from Prescrire's literature search
1- Mehta HB et al. "Characteristic of registered clinical trials assessing treatment for COVID-19: a cross-sectional analysis" BMJ Open 2020; 10: e039978: 9 pages.
2- Herper M and Riglin E "Data show panic and disorganization dominate the study of Covid-19 drugs" Stat 6 July 2020: 7 pages.
3- Kouzy R et al. "Characteristics of the multiplicity of randomized clinical trials for coronavirus disease 2019 launched during the pandemic" JAMA Netw Open 2020; 3 (7): e2015100: 4 pages.
4-Tikkinen KAO et al. "COVID-19 clinical trials: learning from exceptions in the research chaos" Nat Med 22 September 2020: 2 pages.
5- Bik E "Thoughts on the Gautret et al. paper about hydroxychloroquine and azithromycin treatment of COVID-19 infections". science integritydigest.com accessed 16 October 2020: 9 pages.
6- Prescrire Editorial Staff "News update - Covid-19 and drug trials: what to make of the initial results?" 23 March 2020.
7- Michie S and West R "Behavioural, environmental, social, and systems interventions against covid-19" BMJ Open 2020; 370: m2982: 2 pages.
8- Mehra MR et al. "Retraction - Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis" Lancet 2020; 395: 1820.
9- "Covid-19: l'essai Discovery va évaluer de nouveaux traitements dès les prochaines semaines (Florence Ader)" Dépêche APMnews 15 September 2020: 2 pages.

Source: "Waste in covid-19 clinical trials" Prescrire International 2020; 29 (227): 164. Free

Download the full article