Applied Clinical Trials
The need for new therapies to treat coronavirus patients has prompted an onslaught of advisories from FDA clarifying how sponsors should assess and implement changes necessary to fit this new reality.
The imperative to accelerate the development of new therapies to treat patients infected by the COVID-19 virus has prompted a steady wave of new advisories from FDA on strategies for modifying practices for treating and tracking patients in clinical trials. The pandemic has required changes in how study participants receive test therapies, undergo evaluation for treatment effects, and report results to investigators. FDA seeks to clarify how sponsors should assess and implement changes necessary to fit this new reality.
One recent guidance explains ways to consider and manage changes in statistical methods for quantifying uncertainty generated by the pandemic. The document issued June 17, 2020 outlines how sponsors should update statistical analysis plans when changes are needed due to smaller sample sizes, early stoppage of trials, supply disruptions in test products, treatment discontinuation, or modifications in endpoints, and includes a list of data to consider when such revisions are needed.
FDA also has issued numerous updates to an overarching guidance published in March 2020 that responds to a long list of questions on how sponsors and researchers can modify clinical trials to adjust effectively to healthcare realities. Recent additions address the use of alternative laboratory or imaging centers and implementing video conferencing in ongoing studies. FDA has updated information on how and when sponsors should report serious adverse events related to a trial, particularly for infections with the COVID-19 virus.
In early June, FDA also clarified accepted changes to informed consent practices to facilitate the use of e-signatures and remote assessments during the pandemic. This guidance specifies that FDA’s COVID MyStudies App is an acceptable electronic method for obtaining patient consent, and that a stylus- or finger-drawn electronic signature on a document may be an acceptable alternative where e-signature systems are not available. And to help Institutional Review Boards (IRBs) deal with a rising number of individual patient expanded access requests for investigational drugs and biologics to treat COVID-19, FDA advises IRBs to establish policies that permit one member of a Board to review and approve such requests. The agency outlines what key information might be needed to assure appropriate consideration of patient risks and benefits by a single-member review, such as patient history, previous treatment, known risks of the drug, plan for administration and discontinuation in the case of adverse events. [See here.]
FDA officials expect that one result of the coronavirus pandemic will be a continuation of the current accelerated and more efficient process for developing and issuing guidance documents. In the recent months, agency staff has devised a much more streamlined process for guidance development due to pressures to address R&D issues quickly, observed Peter Marks, director of the Center for Biologics Evaluation and Research (CBER), at the June virtual annual meeting of the Drug Information Association (DIA). In considering likely changes in clinical research from the pandemic, Marks noted that the agency is moving away from what in the past has been a “challenging and somewhat tortured” process, where it often took two or three years of deliberations to develop a guidance-producing a document that was “often outdated by the time it is published.” Now FDA staff irons “out our differences quickly,” Marks commented, enabling a shorter process that often produces fresher and more useful advisories.
These and other policy changes may form a basis for more streamlined and efficient clinical trial operations in the future, according to both regulators and sponsors. More remote monitoring of patients, telemedicine visits to check study effects, direct-to-patient delivery of test therapies, and expanded use of real world evidence to monitor patients following trial closure are slated to become more institutionalized in clinical research design and oversight in the U.S. and abroad.