FDA Struggles to Balance Early Access Demands with Need for Valid Test Information

Still smarting from charges of inaction and confusion that delayed the availability of much-needed diagnostics to detect patients infected with the coronavirus (COVID-19), FDA officials are rolling out guidance and support for researchers striving to assess potential treatments for the deadly virus, both existing therapies and new drugs and vaccines that warrant clinical testing. 

The agency’s leadership seeks to regain credibility by objecting to premature optimism about the effectiveness of unproven therapies and to offset calls from politicians and struggling clinicians seeking access to treatments offering any signs of effectiveness. 

FDA commissioner Stephen Hahn only recently moved to moderate exaggerated claims from President Trump, along with strong hopes from some health care providers, that long-used malaria treatments chloroquine and hydroxychloroquine may be effective against the new virus. Some very preliminary data from France fanned optimistic predictions, and doctors who lacked alternative therapies for a rising volume of sick patients began a run on the drugs, despite warnings of potentially serious side effects for some individuals. This initiated shortages of the typically available medicines, which are critical for treating lupus and rheumatoid arthritis. 

Hahn issued a statement last week noting that without evidence that chloroquine products are effective against COVID-19, “we risk treating patients with a product that might not work” instead of more appropriate treatments. He supported efforts by manufacturers to ramp up production to ensure ample supplies if clinical data is promising.  

FDA is also working with biopharma companies to process the hundreds of requests being filed for individual emergency-use access to still unproven therapies, while also facilitating data collection through randomized controlled clinical trials. The challenges in supporting expanded access programs parallel to gold-standard clinical studies became clear. For instance, when Gilead announced this week that it would suspend providing its experimental drug remdesivir via compassionate use-which requires each patient request for treatment to be evaluated individually-that task became impossible, with hundreds of requests overwhelming its treatment access system for this potential Ebola treatment, which may be effective against COVID-19. 

Demonstrating flexibility

Meanwhile, FDA is rolling out a range of guidance documents and policies to provide flexibility for manufacturers facing added challenges in meeting various regulatory requirements. New guidance related to COVID-19 do not follow the usual comment-and-revision process, but instead go into effect immediately. One recent advisory, for example, aims to ensure that patients will continue to access vital medicines provided through risk evaluation and mitigation strategies (REMS) by permitting pharma companies to waive lab tests and imaging studies normally required, but likely to increase the risk of COVID-19 infection and add to the burdens on health care systems during the pandemic.

Additionally, FDA updated a previous guidance to support flexibility for all regulated firms to delay reporting certain adverse events because of personnel disruptions and other problems affecting food and drug companies during the pandemic. The agency similarly outlined flexibility for biopharma companies looking to halt or modify ongoing clinical trials in response to difficulties in carrying out tests or enrolling. And the Center for Biologics Evaluation and Research (CBER) revised lot release activities, informing manufacturers to stop providing samples or lot release protocols in physical form, but to instead submit such information to the agency electronically and to anticipate final release notifications from CBER via email. 

Regulatory modifications, along with an emphasis on the importance of scientific evidence regarding drug and vaccine safety and efficacy, is critical for FDA to maintain public confidence in the agency’s ability to speed needed treatments to patients based on sound evidence that the product may benefit patients. Too often, FDA critics cite delays and missteps as evidence that government regulators merely hinder individuals from making personal decisions on treatment options. Yet, uninformed actions can lead to harmful effects that endanger public health and delay development of effective care strategies. Such actions also open the door for unscrupulous entities to promote unproven and often dangerous tests and treatments to the public. Strong leadership that can deflect and address erroneous and unscientific responses to the COVID-19 pandemic is needed now more than ever.