COVID-19が臨床試験に与える影響：課題と機会

この記事では フリーランスのメディカルライター for Kolabtree ローラ・モロ・マーティン, MSc, PhD, discusses the impact of COVID-19 on 臨床試験. 

Coronavirus disease 2019 (COVID-19) pandemic is undoubtedly having a disruptive effect on health systems and ヘルスケア 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.

臨床研究の実践 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 腫瘍学 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].

米国食品医薬品局（FDA）[9]は，COVID-19危機の際に，患者や医療従事者の保護を確保しながら医療製品の臨床試験を実施するために，企業，治験責任医師，施設審査委員会向けのガイダンスを発表しました．同様に，欧州医薬品庁（EMA）も，スポンサー向けにパンデミック時の臨床試験の管理方法に関するガイダンスを発表しています[10]．このガイダンスでは、臨床研究の完全性を保証するための方針と手順に関して、プロトコールの柔軟性をサポートしています。これには、COVID-19の病気、渡航制限、検疫措置などによる、試験の見学や手順、データ収集、試験のモニタリング、有害事象の報告、治験責任医師、施設スタッフ、モニターの変更などが含まれています[11]。各国の医療機関では、パンデミック時に被験者の安全と健康を確保するための様々な対策を採用しており、いくつかの国の対策をまとめた治験依頼者の臨床試験管理を支援するガイドが発表されています[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 人工知能 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 機械学習 that can offer predictions and forecasts to support decision-making during clinical operations management [15].

COVID-19の破壊的な効果により、臨床試験の実施方法が変化し、医療のデジタル化や革新的なツールや方法論の使用が推進されていることは明らかです。この混乱を利用して、患者さんの体験を向上させ、安全で効果的かつ利用しやすい治療法を市場に提供していきましょう」と述べています。

参考文献

1. Roberton T, Carter ED, Chou VB, Stegmuller AR, Jackson BD, et al. (2020) Early estimates of the indirect effects of the COVID-19 pandemic on maternal and child mortality in low-income and middle-income countries: a modelling study.Lancet Global Heal. doi:10.1016/S2214-109X(20)30229-1.
2. Hogan AB, Jewell B, Sherrard-Smith E, Vesga J, Watson OJ, et al. (2020) Report 19: The Potential Impact of the COVID-19 Epidemic on HIV, TB and Malaria in Low and Middle-Income Countries.Imperial College of London.
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5. Rubio-San-Simon A, Verdú-Amorós J, Hladun R, Ribelles AJ, Molero M, Guerra-García P, Pérez-Martínez A, Castañeda A, Cañete A, Rojas Td, Moreno L BF (2020) COVID-19パンデミック時の小児がんに対する初期段階の臨床試験の課題。A Report From the New Agents Group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP).Clin Transl Oncol:1–7. doi:10.1007/S12094-020-02399-3.
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