Téa Gremi1, Éric Ginesy2, Didier Payen3, Jean-Yves Lefrant4, Benoît Marin5. 1. EA 2992 IMAGINE, pôle anesthésie-réanimation douleur urgence, CHU de Nîmes, université Montpellier, Nîmes, France. Electronic address: gremi.tea@gmail.com. 2. Inspection générale des affaires sociales, Paris, France. 3. UMR Inserm 1160, UFR de médecine de l'université Paris 7, Paris, France. 4. EA 2992 IMAGINE, pôle anesthésie-réanimation douleur urgence, CHU de Nîmes, université Montpellier, Nîmes, France. 5. Direction générale de la santé, ministère des Solidarités et de la Santé, Paris, France.
The COVID-19 outbreak triggered a huge international research effort, a key factor to fight the pandemic. In this context, and to allow a rapid start of research projects, the French Ministry of Health decided to initiate a fast-track process for approval of prospective research protocols in humans by the National Ethics Committee (NEC) [1]. The present letter reports the worldwide registration of human research clinical studies on COVID-19, with a specific focus on French specificities.
Worldwide studies recording
All clinical studies in the field of COVID-19 recorded on the national registries between May 15th and 20th (search terms: COVID-19 or SARS-CoV-2) were carefully identified [2]. They were classified into study type, i.e, interventional (“expanded access” studies were considered as interventional) or observational, recruitment status (recruiting, not yet recruiting, or completed), and country (countries with < 10 studies were grouped in “others”).
French studies recording
In France, all prospective clinical studies must be approved by one of the 39 NECs before the first inclusion. These studies are divided into three different categories according to the risk/benefit ratio for the patient (category 1: randomised controlled trials [RCT], category 2: interventional; category 3: observational). During the COVID-19 outbreak, all NECs maintained their assessment of submitted studies (non-COVID-19 studies: one meeting per month). Some volunteer NECs were assessing the COVID-19 studies daily leading to decrease the time between submission and first assessment < 5 days [3].
Results
On May 20th, 2255 clinical studies about COVID-19 were registered in 18 national registries (1319 [58%] interventional, 899 [40%] observational, 37 not classified). Fig. 1
shows the number of studies registered per country; 1289 (57%) studies are still recruiting and 138 were declared completed (6%). USA, China and France performed more than half of the studies worldwide (1202 studies [53%]).
Fig. 1
Type and status of COVID-19 studies worldwide. NA: these studies could not be assessed as observational or interventional.
Type and status of COVID-19 studies worldwide. NA: these studies could not be assessed as observational or interventional.In France, 1269 studies were submitted to NEC between February 4th and May 16th. Among them, 376 (30%) were focused on COVID-19: 96 (26%) RCTs; 134 (36%) interventional and 146 (39%) observational. On May 16th, 273 (72%) of those COVID-19 studies were approved, 27 (7%) were refused, 72 (19%) were pending, 2 (0.5%) were dealing with exceptions to consent requirement in case of a change in the purpose of a sample of collection of elements and products of the human body and 6 (1.5%) were deemed to be out of the scope of NEC.Overall, between March 16th and April 15th, the median time to obtain a decision was 6 days (interquartile [IQR] [5-8]) (Fig. 2
). This pattern was 8 days (IQR [6-13]) for randomised controlled trials (n = 43). It was similar to the time to obtain an approval by the French National Competent Authority for drugs and medical devices (“Agence nationale de sécurité du médicament et des produits de santé”), which is also mandatory for category 1 clinical research (interventional with higher risk level) [4].
Fig. 2
Times (median with IQ to final decision for COVID-19 and non-COVID-19 studies [before and after March 15th]).
Times (median with IQ to final decision for COVID-19 and non-COVID-19 studies [before and after March 15th]).Outside the fast-track process, the median time to the final approval by the NEC for non-COVID-19 studies decreased from 77 days (IQR [51-104]) (n = 277) between February 15th and March 15th, to 66 days (IQR [44-112]) between March 15th and April 15th (n = 259) (Fig. 2). Hence, the fast-track process for COVID-19 did not lead to downgraded times of instruction of non-COVID-19 studies.This report shows that the COVID-19 outbreak stimulated clinical research projects, mainly in countries with a high incidence of COVID-19. The specific French process for NECs evaluation greatly improved the speed of decision-making and encouraged the initiation of COVID-19 clinical studies. This is probably a specific effect of the fast-track process for COVID-19 projects in the context of the national monitoring efforts requested by the Prime Minister in 2018 in order to prepare French NEC to the new European regulation on drugs and medical devices [5].Certain limitations should be pointed out. First, the retrospective observational studies not requiring national registration are missed by this survey. secondly, the study registration cannot guarantee a close correlation with the publishing rate. Indeed, the fortunate drastic reduction in COVID-19 cases admitted in hospital question the ability to obtain completion of the sample size and the publication of relevant studies.
Disclosure of interest
The authors declare that they have no competing interest.
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