L'impact de COVID-19 sur les essais cliniques : défis et opportunités

Dans cet article rédacteur médical indépendant pour Kolabtree Laura Moro-Martin, MSc, PhD, discusses the impact of COVID-19 on les essais cliniques. 

Coronavirus disease 2019 (COVID-19) pandemic is undoubtedly having a disruptive effect on health systems and soins de santé delivery worldwide. The overwhelm of health systems in many countries is predicted to cause a concerning increase in both direct mortality from COVID-19 and indirect mortality from other conditions [1,2]. For example, emergency visits have been substantially reduced [3] and several vaccination campaigns have been halted due to the emergence of COVID-19 [4], which may contribute to the indirect morbidity and mortality.

Pratique de la recherche clinique is no exception, with the pandemic causing tremendous disruptions on ongoing clinical trials. This is particularly relevant for trials not directly dealing with COVID-19 prevention or treatment, and those requiring participants access to clinical sites. A Spanish study on early phase trials for paediatric cancer reported personnel shortages, difficulties in enrolling patients (up to 75% reduction of the expected enrolment and 50% of ongoing trials interrupting recruitment), problems for treatment continuity, and delays in trial assessments (with monitoring activities postponed in 73% of cases) [5]. A survey of the American Society of Clinical Oncologie on 32 clinical trial cancer programs identified numerous challenges, including difficulties in enrolment (60% of respondents declared halted enrolment and/or screening) and protocol adherence, decreased patient visits (60% of respondents), staffing limitations, and narrow availability of ancillary services (50% of respondents) [6]. For patients with cancer or other serious conditions, participation in a clinical trial could be an essential part of treatment that cannot be stopped. 

Other challenges reported as a consequence of the pandemic include interactions with sponsors and CROs about modifying trial procedures, and protocol modifications and/or deviations −either intentional or unintentional− with unknown effects over scientific integrity, interpretation, and conclusions of the trials [6]. Some authors have warned about the possibility that forced changes introduced in clinical trials by the pandemic −such as decreased follow-up visits, participants’ poorer mental or physical health, or even infection with the novel coronavirus− may interfere with the results of the treatment’s risks and benefits [7]. Besides, the impact of COVID-19 on clinical trials is uneven depending on the therapeutic area. One report found declines in participant enrolment ranging from 34% for respiratory diseases up to 80% for endocrine diseases, with intermediate percentages for other therapeutic areas (47% for infectious diseases, 48% for oncology, 64% for dermatology, 68% for neurological diseases, and 70% for cardiovascular diseases) [8].

La Food and Drug Administration (FDA) des États-Unis [9] a publié des conseils à l'intention de l'industrie, des enquêteurs et des comités d'examen institutionnels pour mener des essais cliniques de produits médicaux pendant la crise du COVID-19 tout en assurant la protection des patients et des travailleurs de la santé. De même, l'Agence européenne des médicaments (EMA) a publié des conseils à l'intention des promoteurs sur la manière de gérer les essais cliniques pendant la pandémie [10]. Ces conseils soutiennent une certaine flexibilité du protocole en ce qui concerne la politique et les procédures visant à garantir l'intégrité de la recherche clinique, y compris les changements dans les visites et les procédures de l'étude, la collecte de données, le suivi de l'étude, le signalement des événements indésirables, ou les changements d'investigateurs, de personnel du site et/ou de moniteurs en raison de la maladie COVID-19, des restrictions de voyage ou des mesures de quarantaine [11]. Les agences médicales de différents pays ont adopté une variété de mesures pour assurer la sécurité et le bien-être des sujets d'essai pendant la pandémie, et un guide pour aider les promoteurs à gérer les essais cliniques résumant plusieurs mesures nationales a été publié [12]. 

Once the main obstacles have been identified −mostly mobility and travel restrictions, lack of adequate technologies and disruptions in supply chains [8]− COVID-19 may be seen as an opportunity to ‘rethink’ clinical trials. Some of the solutions proposed to overcome these challenges [13,14] include moving clinical sites to countries and regions less impacted by COVID-19, virtualization of several aspects of the trial (such as remote consent, remote randomization, and remote data capture and reporting), use of technology to closely monitor patient volume and drug supply to minimize disruptions, creation of synthetic control arms from historical trial data combined with intelligence artificielle algorithms, or offering in-home clinical services. In particular, technology innovation can provide new tools to guarantee the continuity and success of clinical studies during the pandemics. An example of this innovation is a risk-based predictive analytical approach powered by apprentissage machine that can offer predictions and forecasts to support decision-making during clinical operations management [15].

Il est clair que l'effet disruptif de COVID-19 a bouleversé la manière de mener les essais cliniques, poussant à la numérisation des soins de santé et à l'utilisation d'outils et de méthodologies innovants. Profitons de cette perturbation pour améliorer l'expérience des patients et mettre sur le marché des thérapies sûres, efficaces et accessibles.

Bibliographie

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