COVID19 Expected to Impact Clinical Trials and Slow Down Drug Development

One of the long-term effects of the ongoing COVID19 pandemic is a slowing down of global drug development, leading to less approved therapeutic agents in the coming years. This is the conclusion based on a recent survey by Clinical Research IO, an eSource solution for clinical research sites.

The impact of COVID19 on clinical research and the operations of clinical trial sites will vary based on many factors, including the nature of the disease being studied, the trial design, and in what regions the study is being conducted. [1]

In a viewpoint published online in the March 25, 2020 edition of the Journal of the American Medical Association (JAMA), Mary M. McDermott, M.D., at the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, and the current Deputy Editor of JAMA, and Anne B. Newman, MD, MPH, at the Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, write how mitigation efforts may interfere with clinical trials.

They note that “…mitigation efforts include self-isolation and avoiding health care centers where symptomatic patients congregate for medical care and where randomized trials are typically conducted. [These ..] efforts interfere with all aspects of a successful clinical trial, [including] efficient accrual and randomization, intervention adherence and delivery, and outcome collection.” [2]

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To address concerns, earlier this month, the U.S. Food and Drug Administration (FDA) outlined a number of key considerations to guarantee the safety of trial participants, while maintaining compliance with good clinical practice, and minimizing the risks to the integrity of the clinical study being conducted. The FDA’s guidance aligns with the approaches announced by other international regulatory authorities, such as the United Kingdom’s Medicines and Healthcare Products Regulatory Authority (MHRA), the European Commission and the European Medicines Agency (EMA).[1]

Significant interruptions
The survey shows that investigators conducting clinical trials on a wide range of diseases are experiencing significant interruptions in their trials due to the ongoing pandemic.

Twentyfour percent of investigators being interviewed reported that they have stopped enrolling new patients due to patient safety concerns. From the remaining 76% of investigators, nearly half, or 37%, indicated they are considering halting new patient enrollment.

The interruptions of clinical trials are not only seen within oncology and hematology but are noticed in all therapeutic areas.

“We noticed a significant slowdown in patient recruitment at the beginning of March,” said Elena A Christofides, MD, FACE, owner and principal investigator of Endocrinology Associates.

“We then decided that it was in the best interest of public safety to halt all further enrollment,” she added.

This slowdown has been further exacerbated by the recent spate of shelter-in-place orders imposed by states and municipalities.

“Due to COVID-19 restrictions in health care, clinical trial activity has largely come to a halt,” noted Marcus Stone, Ph.D., Chief Executive Officer of The Spine Institute of Louisiana Foundation.

“This will lead to a significant slowdown in new drug and device development,” Stone further noted.

“New treatments that could have come out in, say, 2022 now might come out in 2023. So, this COVID19 crisis could have a significant long-term effect on health care in general.”

Major challenges
Even for trial sites that are continuing to enroll, significant challenges remain.

Challenges may arise, for example, from quarantines, site closures, travel limitations, interruptions to the supply chain for the investigational product, or other considerations if site personnel or trial subjects become infected with SARS-CoV-2, the virus that causes COVID19. These challenges may lead to difficulties in conducting clinical trials and may require protocol modifications or unavoidable protocol deviations.

To minimize the effect of these deviations, the FDA, like most regulatory bodies, allows these changes to be implemented without approval from the institutional review board (IRB) or independent ethics committee before filing an amendment to the investigational new drug (IND) or investigational device exemption (IDE) application if the changes are designed to “minimize or eliminate immediate hazards or to protect life and the well-being of research participants.”

In their guidance document, the EMA states: “The situation is evolving, and pragmatic actions may be required to deal with the challenges of conducting research, and in ensuring the rights, safety and wellbeing of participants.”

Patient retention
The survey indicated that sites are reporting a 9% decrease in patient retention. This means that nearly one in ten enrolled subjects may be withdrawing from their studies. In addition, 63% of trial sites reported that they have prohibited on-site monitoring by pharmaceutical sponsors, inhibiting the ability of sponsors to perform effective oversight.

“This is one of the second-order casualties of the COVID19-crisis,” said Harvard-trained lawyer and former management consultant Raymond Nomizu, Chief Executive Officer of EO of Clinical Research IO.

“When we look back five years from now, I fully expect to see a drop in the number of breakthrough new medications being approved – a drop you can directly tie to this crisis,” Nomizu concluded.

The survey was conducted March 19-23, 2020 and included 73 clinical trial research sites across a range of therapeutic indications.

Reference
[1] Coronavirus (COVID-19) Update: FDA Issues Guidance for Conducting Clinical Trials. [FDA News release]
[2] McDermott MM, Newman AB. Preserving Clinical Trial Integrity During the Coronavirus Pandemic. JAMA. Published online March 25, 2020. doi:10.1001/jama.2020.4689

A version of this article was first published in Onco’Zine of March 26, 2020