Sponsors of drugs being developed to treat or prevent COVID-19 should strive to enroll populations at greatest risk in their trials, including older adults, ethnic and racial minorities, children and pregnant/lactating women, the agency advises in a straight-to-final guidance.

The 19-page guidance, which focuses primarily on trials for COVID-19 treatments, pertains to phase 2 and 3 trials and focuses on trial populations, trial design, efficacy endpoints, safety considerations and statistical considerations. It does not cover long COVID-19 treatments, preventative vaccines or convalescent plasma.

“Although the COVID-19 public health emergency has expired, SARS-CoV-2 continues to circulate, and COVID-19 remains a serious health risk for some individuals,” says the guidance, which takes effect immediately.

“Age is one of the strongest risk factors for severe COVID-19 outcomes,” the guidance says. “To the fullest extent possible, older adults, including individuals 75 years of age and older, should be represented in relevant clinical trials.” The agency also encourages trials conducted in nursing homes or other eldercare facilities.

In addition, the FDA reiterated the importance of enrolling diverse study populations and notes that this latest guidance can be used to inform COVID-19 drug development for children and pregnant/lactating patients.

“There is a need to generate clinical trial data to inform the use of drugs in these populations,” the guidance says.

The guidance lists examples of important clinical outcome measures in COVID-19 treatment trials. These include:

• All-cause mortality;
• Respiratory failure (need for mechanical ventilation, extracorporeal membrane oxygenation, noninvasive positive pressure ventilation or high-flow nasal cannula oxygen delivery);
• Need for invasive mechanical ventilation;
• Need for hospitalization;
• Objective measures of sustained improvement (return to room air or baseline oxygen requirement);
• Sustained symptom alleviation or resolution; and
• Clinical status using an ordinal scale that uses multiple clinical outcomes of interest ordered by clinical importance.

The guidance additionally recommends using an independent, external data monitoring committee “to ensure subject safety and trial integrity” in COVID-19 treatment trials.

For trials of preventive drugs, the FDA recommends using as the primary endpoint the occurrence of laboratory-confirmed COVID-19 infection, with or without symptoms, or COVID-19 with symptoms. When possible, both of these endpoints should be assessed.

The guidance also includes three appendices that provide examples of baseline categorizations for COVID-19 infection, drug resistance analysis plan considerations and advice on characterizing how drugs impact viral shedding and immune responses.

Although the FDA issued the guidance without a comment period, the agency will accept public comments at any time.

Read the guidance here.