FDA Encourages More Patient Input to Inform Reported Outcomes

Kendall A. Marcus, MD, Director of the Division of Dermatology and Dental Products with the Center for Drug Evaluation and Research at the U.S. Food and Drug Administration

Kendall A. Marcus, MD, Director of the Division of Dermatology and Dental Products with the Center for Drug Evaluation and Research at the U.S. Food and Drug Administration

In real estate it’s location, location, location. In clinical trials? Try patient, patient, patient.

“Early patient input is critical on the road to patient-focused outcome treatment,” Kendall A. Marcus, MD, director of the Division of Dermatology and Dental Products with the Center for Drug Evaluation and Research at the U.S. Food and Drug Administration, told attendees at the International Dermatology Outcome Measures (IDEOM) 2018 Annual Meeting on May 4 in Washington, D.C. “How do we bridge patient input into patient-focused clinical trial endpoints? It is not a simple process.”

Marcus used her session, “Patient Reported Outcomes (PRO) Evaluation and Labeling of Claims,” to make the case for working closely with patients in the quest to produce meaningful PROs. It begins with definitions of terms, she said.

For example, to make the case for a clinical benefit from a treatment, the research must address how long a patient lives or how a patient feels or functions in daily life due to the treatment. It can be demonstrated as either “a comparative advantage in treatment of the disease or condition, or a comprehensive reduction in a treatment-related toxicity.”

Marcus also outlined the good measurement principles necessary to emerge with useful PROs:

  • Is the instrument reliable?
  • Does the instrument measure what it is supposed to measure?
  • Is the instrument sensitive to detecting change over time?
  • Did a subset of questions drive the result?
  • What does a score improvement of X-points mean?
  • If there are multiple concepts/domains being measured, do they overlap?
  • Does the instrument measure what is important to the patient?
  • Is the instrument appropriate for use in the study population?

“All of these characteristics of PRO instruments are important, and can impact the quality of the data in all of the other parameters,” Marcus said. Another factor: The availability of cultural adaptation, particularly when clinical trials are being conducted in multiple countries or multiple areas of the country with diverse cultural challenges, she said.

Marcus also advised attendees to be on the alert for a lack of variability in PROs, saying, “If all of your patients are reporting high scores, it’s going to be difficult to detect meaningful change when they’re all on this severe end or there’s a ceiling effect.”

Looking at the issue from another perspective, Kristina Callis Duffin, MD, MS, associate professor of dermatology with the University of Utah, said setting the measures in clinical trials demands a deep dive that weights patient and physician input equally.

Turning to a recent psoriasis trial she was involved in, Duffin noted that “there was no consensus” regarding measures and terms to help conduct the trial.  On the positive side, after a rigorous round of survey questions, the research team found much more overlap between terminology than expected. That made it easier to group requested outcomes into a few buckets enveloping what started out as a very long list, she said.

Marcus acknowledged that brand of challenge. “Are you measuring the same concept with different questions, such that a single concept is going to drive the results of your PRO instrument? At times, the item is found not to correlate with the concept that it is intended to measure,” she warned. “Particularly with the concepts of stinging, burning, and pain, there is some question as to whether [these terms are] measuring the same concept or those are all distinct concepts that patients have the ability to distinguish between.”

Also making the case for heavy patient involvement, Alice Gottlieb, MD, PhD, founder and president of IDEOM, applauded practitioners, saying, “clinical trials are key to approval and promotion.”

Author: Michael Causey