In September 2020, the FDA published guidance on the assessment of COVID-19 symptoms in clinical trials for drugs and biologics relating to the prevention and treatment of COVID-19, detailing a set of symptom-related questions and recommendations for how the questions should be used. This guidance is intended to remain in effect for the duration of the COVID-19 pandemic, with the plan to revise and replace the guidance within 60 days following the termination of the public health emergency declared by the Department of Health and Human Services.
Here we provide a summary of this guidance and recommendations for implementation in clinical trials
- Assess symptoms with Patient Reported Outcome (PRO) instruments
- Perform assessments at least every 24 hours and at the same time each day
- Use electronic collection systems with reminders and time stamps of completion
- Response scales should include numeric scores with verbal descriptors (such as none, mild, moderate, severe) to avoid misunderstanding
- Include all symptom assessments at each administration, as new symptoms may appear at any time
- Conduct an evaluation of the PRO instrument to document basic comprehensibility and usability before starting the clinical trial
In Table 1 of the guidance document, an example assessment of 14 common COVID-19 symptoms is presented. These symptoms include
- multiple respiratory symptoms
- fever and chills
- muscle or body aches
- nausea, vomiting and diarrhea
- effects on the sense of smell and taste
Sponsors are asked to consider adapting the example assessment as needed for the specific study, including the use of additional COVID-19 related assessments. This would include
- medications used to treat COVID-19 related symptoms
- body temperature
- oxygen saturation
- global impressions related to overall symptom severity
- global impressions regarding return to health and normal activities
The guidance specifically recommends that sponsors consult with the appropriate FDA review division regarding any PRO instruments used for assessing COVID-19 symptoms.
Using COVID-19 Symptom Assessments in Your Clinical Trial
The FDA has provided an important starting point for assessing COVID-19 symptoms. The guidance provided represents the FDA’s “current thinking” and is meant to allow discussion, adaptation and discussion based on the specific study protocol.
It is understood that no two clinical trials are alike. Decisions on what symptoms to assess, assessment frequency, need for translations, development of electronic instruments, usability testing, and cognitive evaluation of new instruments has created many unique challenges in a pandemic world. Sponsors, experts, and technology providers are moving fast to adapt, but always with a firm eye on patient safety. Now more than ever, it is critical to have the right partners in your corner to help navigate the rapidly changing regulatory and healthcare environment during the ongoing public health emergency.
Kenneth G. Faulkner, PhD is the Vice President of eCOA Science at ERT.