L'impatto di COVID-19 sugli studi clinici: sfide e opportunità

In questo articolo scrittore medico freelance per Kolabtree Laura Moro-Martin, MSc, PhD, discusses the impact of COVID-19 on studi clinici. 

Coronavirus disease 2019 (COVID-19) pandemic is undoubtedly having a disruptive effect on health systems and assistenza sanitaria 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.

Pratica di ricerca clinica 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 Oncologia 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) degli Stati Uniti [9] ha pubblicato una guida per l'industria, gli sperimentatori e le commissioni di revisione istituzionale per condurre studi clinici di prodotti medici durante la crisi della COVID-19, garantendo la protezione dei pazienti e degli operatori sanitari. Allo stesso modo, l'Agenzia europea per i medicinali (EMA) ha pubblicato una guida per gli sponsor su come gestire gli studi clinici durante la pandemia [10]. Questa guida sostiene una certa flessibilità dei protocolli per quanto riguarda la politica e le procedure per garantire l'integrità della ricerca clinica, compresi i cambiamenti nelle visite e nelle procedure dello studio, la raccolta dei dati, il monitoraggio dello studio, la segnalazione degli eventi avversi, o i cambiamenti negli investigatori, nel personale del sito e/o nei monitor a causa della malattia COVID-19, delle restrizioni di viaggio o delle misure di quarantena [11]. Le agenzie mediche di diversi paesi hanno adottato una varietà di misure per garantire la sicurezza e il benessere dei soggetti dello studio durante la pandemia, ed è stata pubblicata una guida per assistere gli sponsor nella gestione degli studi clinici che riassume diverse misure nazionali [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 intelligenza artificiale 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 apprendimento automatico that can offer predictions and forecasts to support decision-making during clinical operations management [15].

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 accessible therapies to the market.

Bibliografia

1. Roberton T, Carter ED, Chou VB, Stegmuller AR, Jackson BD, et al. (2020) Prime stime degli effetti indiretti della pandemia COVID-19 sulla mortalità materna e infantile nei paesi a basso e medio reddito: uno studio di modellazione. Lancet Glob 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.
3. Lazzerini M, Barbi E, Apicella A, Marchetti F, Cardinale F, et al. (2020) Ritardo nell'accesso o nella fornitura di cure in Italia per paura di COVID-19. Lancet Child Adolesc Heal 4: e10-e11. doi:10.1016/S2352-4642(20)30108-5.
4. Organizzazione Mondiale della Sanità (2020) Almeno 80 milioni di bambini sotto l'anno a rischio di malattie come la difterite, il morbillo e la poliomielite perché il COVID-19 interrompe gli sforzi di vaccinazione di routine, avvertono Gavi, OMS e UNICEF. Disponibile qui. Accesso al 5 giugno 2020.
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) Challenges in Early Phase Clinical Trials for Childhood Cancer During the COVID-19 Pandemic: 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.
6. 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.
7. Servick K (2020) Gli studi clinici proseguono per condizioni diverse dalla COVID-19. Gli effetti della pandemia si insinueranno nei loro dati? Scienza. Disponibile qui. Accesso al 5 giugno 2020.
8. Medidata (2020) COVID-19 e le sperimentazioni cliniche: La prospettiva di Medidata. Versione 5.0. Disponibile qui. Accesso al 5 giugno 2020.
9. US Food and Drug Administration (2020) FDA Guidance on Conduct of Clinical Trials of Medical Products (Guida della FDA sulla conduzione di sperimentazioni cliniche di prodotti medici durante la COVID-19). Salute pubblica Emergency Guidance for Industry, Investigators, and Institutional Review Boards. Available qui. Accesso al 5 giugno 2020.
10. Agenzia europea per i medicinali (2020) Guida alla gestione delle sperimentazioni cliniche durante la pandemia di COVID-19 (coronavirus). Disponibile qui. Accesso 2 giugno 2020.
11. Sarah Morgan, Liz O'Neil, Karin Parks (2020) Impact of COVID-19 on Clinical Trials. Disponibile qui. Accesso 2 giugno 2020.
12. DLA Piper (2020) Una guida alla gestione degli studi clinici durante la pandemia di COVID-19. Disponibile qui. Accesso al 5 giugno 2020.
13. Fareed Melhem (2020) The Global Impact of COVID-19 on Clinical Trials and the Way Forward | Technology Networks. Disponibile qui. Accesso al 5 giugno 2020.
14. ICON plc (2020) Minimizzare l'impatto di COVID-19 sugli studi clinici con servizi clinici a domicilio. Disponibile qui. Accesso al 5 giugno 2020.
15. Ben van der Schaaf, Thomas Unger, Michael Eiden, Ben Enejo, Craig Wylie, Tom Teixeira RE (2020) Gestione degli studi clinici durante COVID-19 e oltre. Disponibile qui. Accesso 2 giugno 2020.