By: Dr. Laura Moro – Marin, Kolabtree
Coronavirus disease 2019 (COVID-19) pandemic is undoubtedly having a disruptive effect on health systems and healthcare 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  and several vaccination campaigns have been halted due to the emergence of COVID-19 , which may contribute to the indirect morbidity and mortality.
Clinical research practice 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) . A survey of the American Society of Clinical Oncology 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) . 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 . 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 . 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) .
The US Food and Drug Administration (FDA)  has issued guidance for industry, investigators, and institutional review boards to conduct clinical trials of medical products during the COVID-19 crisis while ensuring the protection of patients and healthcare workers. Similarly, the European Medicines Agency (EMA) has published guidance for sponsors on how to manage clinical trials during the pandemic . This guidance supports certain protocol flexibility regarding policy and procedures to guarantee the integrity of clinical research, including changes in study visits and procedures, data collection, study monitoring, reporting of adverse events, or changes in investigators, site staff, and/or monitors due to COVID-19 illness, travel restrictions or quarantine measures . Medicine agencies across different countries have adopted a variety of measures to ensure the safety and wellbeing of trial subjects during the pandemic, and a guide to assist sponsors to manage clinical trials summarizing several national measures has been published .
Once the main obstacles have been identified −mostly mobility and travel restrictions, lack of adequate technologies and disruptions in supply chains − 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 artificial intelligence 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 machine learning that can offer predictions and forecasts to support decision-making during clinical operations management .
It is clear that the disruptive effect of COVID-19 has shifted the way of conducting clinical trials, pushing towards the digitalization of healthcare and the use of innovative tools and methodologies. Let’s take advantage of this disruption to improve patients’ experience and bring safe, effective and accesible therapies to the market.
- 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 Glob Heal. doi:10.1016/S2214-109X(20)30229-1.
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- World Health Organization (2020) At least 80 million children under one at risk of diseases such as diphtheria, measles and polio as COVID-19 disrupts routine vaccination efforts, warn Gavi, WHO and UNICEF. Available: https://www.who.int/news-room/detail/22-05-2020-at-least-80-million-children-under-one-at-risk-of-diseases-such-as-diphtheria-measles-and-polio-as-covid-19-disrupts-routine-vaccination-efforts-warn-gavi-who-and-unicef. Accessed 5 June 2020.
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- Waterhouse DM, Harvey RD, Hurley P, Levit LA, Kim ES, et al. (2020) Early Impact of COVID-19 on the Conduct of Oncology Clinical Trials and Long-Term Opportunities for Transformation: Findings From an American Society of Clinical Oncology Survey. https://doi.org/101200/OP2000275. doi:10.1200/OP.20.00275.
- Servick K (2020) Clinical trials press on for conditions other than COVID-19. Will the pandemic’s effects sneak into their data? Science. Available: https://www.sciencemag.org/news/2020/05/clinical-trials-press-conditions-other-covid-19-will-pandemic-s-effects-sneak-their. Accessed 5 June 2020.
- Medidata (2020) COVID-19 and Clinical Trials: The Medidata Perspective. Release 5.0. Available: https://www.medidata.com/en/insight/covid-19-and-clinical-trials-the-medidata-perspective/. Accessed 5 June 2020.
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- European Medicines Agency (2020) Guidance on the management of clinical trials during the COVID-19 (coronavirus) pandemic. Available: https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-10/guidanceclinicaltrials_covid19_en.pdf. Accessed 2 June 2020.
- Sarah Morgan, Liz O’Neil, Karin Parks (2020) Impact of COVID-19 on Clinical Trials. Available: https://www.healthwaregroup.com/blog/impact-of-covid-19-on-clinical-trials-609. Accessed 2 June 2020.
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