key: cord-0995162-84t4841p
authors: de Paula, Bruno H R; Araújo, Indiara; Bandeira, Lívia; Barreto, Nathália M P B; Doherty, Gary J
title: Recommendations from national regulatory agencies for ongoing cancer trials during the COVID-19 pandemic
date: 2020-04-08
journal: Lancet Oncol
DOI: 10.1016/s1470-2045(20)30226-6
sha: c4cdc0ac92810cecaaf623205c19c7ed5086f10b
doc_id: 995162
cord_uid: 84t4841p

nan

Clinical research has transformed cancer care and is often integrated seamlessly into routine oncology clinics, offering eligible patients additional treatment options or lines of therapy. Typically, and particularly for diseases with poor prognoses or when trials entail biomarker-directed personalised treatment, clinical trial enrolment can be preferred (by both doctors and patients) over standard care. 1 However, many barriers already preclude patients' participation in clinical trials, with only a small proportion enrolled in interventional trials. 2 The coronavirus disease 2019 (COVID-19) pandemic presents an additional major barrier to patients' enrolment and ongoing participation in clinical trials. Institutions are adapting their oncology practice, considering alternative treat ment strategies to appropriately balance risks and benefits, despite the absolute individual risk increases from COVID-19 for patients being currently unknown. 3 The US Food and Drug Administration (FDA) and other international bodies have released guidance for sponsors and study sites to ensure the safety of trial participants while maintaining compliance with Good Clinical Practice and minimising risks to study integrity. This guidance is summarised in the panel. [4] [5] [6] [7] [8] [9] [10] Although this guidance is very welcome and helpful, specific considerations must be made for each trial, in view of the wide variety of study types, relative complexities, and perceived risks and benefits. Many study sites and sponsors have already stopped study enrolment, and it is not clear when these studies will reopen because of the probable prolonged effects of the COVID-19 pandemic. For patients on study treatment, the difficult decision to stop or carry on with the investigational medical product or other study treatments should be discussed between Recommendations from national regulatory agencies for ongoing cancer trials during the COVID-19 pandemic the Birmingham Environment for Academic Research local Cloud. 10 UKCCMP delivers meaningful real-time data to all UK cancer centres and clinicians to allow more personalised approaches to individual patient care and inform clinical decision making. This initiative will improve cancer care in the UK and beyond at this time of unprecedented global turmoil and reliance on health-care resources.

We declare no other competing interests. We thank the oncologists, acute physicians, and health-care staff working tirelessly on the frontlines of the COVID-19 pandemic. The UK Coronavirus Monitoring Project team donated time and resources to support the project. The project was initially funded through the donation of time and resources from the supporters and advocates of the project. 8 • Sponsors and PIs should collaborate to decide which study visits can be done remotely (eg, by telephone) and which can be delayed or cancelled, applying a risk-based approach (including a study amendment) when necessary • Patients can be transferred to another study centre should this be necessary to provide continuous treatment • New trials shall not begin • The sponsor should consider closing a study centre, and how to do so safely, if it is not possible for the centre to continue their involvement, and the BDA should be informed about how this is done • A risk assessment should be undertaken to ascertain if patients' recruitment should be suspended

March 20, 2020) 9 • Always ascertain the infection and quarantine status of the participant and their household by telephone • Exchange patient's physical follow-up visits with telephone calls when possible, and provide patients with appropriate personal protective equipment when study visits are required (Continues on next page) sponsors and study sites, but most importantly between the investigator and patient. Substantial uncertainty remains about which interven tions or treatments might increase the risk for con tracting COVID-19 or for COVID-19-related morbidity or mortality. Presumably, immuno suppressive regimens and drugs with a higher risk for drug-related lung injury present the biggest risk to patients. Careful consideration of additional COVID-19associated risks of continuing these agents should be balanced against the potential issues with stopping or delaying treatment that might extend life, help with or delay symptoms, or reduce the risk for disease-related complications.

We encourage all sponsors and regulatory authorities to permit rational changes to study assessments and interventions that allow individualisation of these complex decisions, putting the patient first while continuing to optimise safety and endpoint assessment. We hope that risk mitigation and easing of previously inflexible rules, which will put the patient at the centre of clinical research, will continue long into the future. GJD 10 • Specific national legislation and guidance must be taken into account • Sponsors should consider a risk assessment to modify ongoing trials and consider measures such as converting physical visits to remote visits, postponing or cancelling visits, halting or suspending recruitment to trials, and closing trial sites • Consider transfer of participants to alternative study sites, and doing study assessments (eg, laboratory tests and imaging) at other centres, when necessary, to ensure participant safety

• Submit a substantial amendment application if changes are likely to affect the safety or wellbeing of the participants or the scientific value of the trial • Risk assessments by the sponsor should be ongoing and documented • Implement measures that prioritise patient's safety and data validity • When consent needs to be reobtained from patients for studies, visits to centres solely for documentation of consent should be avoided; consent can be obtained using other means (eg, verbally over the telephone or by videocall with email confirmation)

Report of the WHO-China joint mission on coronavirus disease 2019 (COVID-19). Geneva: World Health Organization

Coronavirus COVID-19 global cases by the

Cancer in numbers. Macmillan Cancer Support

Clinical characteristics of coronavirus disease 2019 in China

Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

SARS-CoV-2 transmission in patients with cancer at a tertiary care hospital in Wuhan, China

Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China

What should medical oncologists know about COVID-19? European Society for Medical Oncology

CaStLeS (Compute and Storage for the Life Sciences): a collection of compute and storage resources for supporting research at the University of Birmingham. Birmingham: Birmingham Environment for Academic Research

COVID-19=coronavirus disease 2019. FDA=Food and Drug Administration. IRB=institutional review board. IEC=independent ethics committee. IMP=investigational medicinal product. NoMA=Norwegian Medicines Agency. PI=principal investigator. MHRA=Medicines and Healthcare products Regulatory Agency. BDA=Bulgarian Drug Agency. Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust

and Division of Cardiology, Hospital Pró-Cardiaco

Facilitating access to new therapeutic options through clinical trials: the vision of a regulator to reconcile innovation and safety

Systematic review and meta-analysis of the magnitude of structural, clinical, and physician and patient barriers to cancer clinical trial participation

The treatment of patients with cancer and containment of COVID-19: experiences from Italy

FDA guidance on conduct of clinical trials of medical products during COVID-19 pandemic: guidance for industry, investigators, and institutional review boards

Lineamientos investigación clínica coronavirus (COVID-19)

Management of clinical trials in relation to COVID-19

Managing clinical trials during coronavirus (COVID-19): how investigators and sponsors should manage clinical trials during COVID-19

Recommendations to COVID-19 clinical trial sponsors