A new viewpoint article from Harvard Medical School, published in the journal JAMA Pediatrics, discusses the hesitancy to include children in coronavirus disease 2019 (COVID-19) clinical trials, potentially diminishing their therapeutic options in the long run.
A recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of an ongoing COVID-19 pandemic, has raised extraordinary challenges to the society as a whole. While the vaccine solution is still not in sight, only stringent epidemiological measures can curb the spread of the disease.
But there is also a need for an effective drug to mitigate a potential second wave of infection. Consequently, clinical trials of several new and repurposed drugs/treatments for COVID-19 are being designed rapidly or even enrolling patients already.
Nonetheless, only a handful of trials are currently open to including children. Between February 1 and May 7, 2020, a total of 745 interventional clinical trials on COVID-19 were registered on ClinicalTrials.gov, which is a database of publicly and privately funded clinical studies conducted globally. Of those, only 69 (or 9.3 percent) were open to patients younger than 18 years of age.
"In the absence of pediatric data available at the time of regulatory approval, children may be exposed to ineffective dosing or possibly unsafe treatments," caution viewpoint authors from Boston Children's Hospital and Harvard Medical School in Boston, Massachusetts.
Do children even need COVID-19 treatment?
Although early reports describe a milder clinical course of COVID-19 in children, emerging epidemiological data suggest that the disease can be severe in certain pediatric populations – emphasizing the public health need for the meticulous study of potential COVID-19 treatments in children.
For example, the risks SARS-CoV-2 infection and severe COVID-19 may be increased in children who are immunocompromised, who receive immunosuppressive drugs, those with malignant disease, or those with preexisting lung or respiratory conditions (including the use of e-cigarettes and vaping).
And enrolling children in clinical trials during outbreaks is not exactly a novelty. Between one quarter and one-third of the study population in two trials conducted by the U.S. National Institutes of Health (NIH) during the Ebola virus disease were children. Moreover, one of the drugs included in those trials was remdesivir, which is now intensely studied for COVID-19.
"The pandemic has revealed substantial health disparities, and it is critical that COVID-19 studies enroll participants from underrepresented communities across the lifespan", say viewpoint authors.
Tectonic changes in pediatric research
The underrepresentation of children in clinical trials was addressed by legislators in the United States and European Union during the past decade, with subsequent regulatory and statutory changes. The introduced policies basically changed the landscape of pediatric research endeavors.
In the U.S., pediatric studies are now mandated by the Food and Drug Administration (FDA) for new drugs, biologics, but also new drug indications. In the European Union, studies on children are required by the Pediatric Regulation with a six-month extension of patent protection upon completing all such studies.
"These policies have led to substantial changes in the pediatric research enterprise, including the completion of hundreds of pediatric studies," emphasize viewpoint authors. "Regulators, public health agencies, and trial investigators and sponsors should act to ensure the clinical study of COVID-19 in children and the availability of pediatric labeling data on market entry of new products", they add.
Closing the evidence gap
"The exclusion of children from COVID-19 clinical trials is a tremendous lost opportunity to generate timely knowledge to guide treatment of pediatric populations", say study authors. "Without adequate studies, if any COVID-19 therapies successfully obtain regulatory approval, clinicians would need to prescribe them for children off label", they add.
Even now, when discovering new therapies for COVID-19 is a pressing and timely issue, obtaining high-quality evidence to guide the treatment of children is feasible – e.g., by expanding existing studies and conducting parallel pediatric, adaptive designed clinical trials.
In the past decade, research infrastructure, policies, and regulations were all improved in order to close the evidence gap in the usage of new drugs in children. This should serve as the basis for the urgent advocacy to include pediatric patients in ongoing and planned COVID-19 clinical trials, the viewpoint concludes.