FDA: Use Alternate Strategies to Include Data From “Interesting” Patients in Clinical Trials 
[Posted on: Thursday, August 23, 2018]

The enrollment criteria for most clinical trials exclude older or pediatric patients, patients with organ disfunctions, pregnant and lactating women, and patients with multiple chronic conditions. An FDA report released this week summarizes how data from such patient populations can be collected to support inclusion of these populations on the product labels.
Sponsors are reluctant to include all patient populations in clinical trials that may add “noise” to the data hence most clinical testing programs are designed to collected supportive data in “sanitized” well-defined populations. The excluded patients however represent a medically “interesting” population where the drug may behave very differently from the patients included in the clinical trials. The regulators must walk the delicate balance between the scientific desire to include “interesting” patient populations, while not forcing measures that could make development programs untenable for the manufacturers. To review how this balance can be achieved, FDA held a public workshop in April of this year and invited representatives from all stakeholders to discuss the challenges and opportunities in improving eligibility criteria for clinical trials and alternative methods to get data where conventional methods won’t do. The report from the workshop released this week highlights key suggestions to improve inclusion and exclusion criteria and use expanded access programs, open-label long-term safety studies, and pharmacokinetic studies aimed to evaluate the new drug in excluded populations. The inclusion and exclusion criteria should be adequately justified based on prevention of harm to patients rather than just copy-pasting criteria from other trials. For example, age-based exclusion is rarely appropriate. Sponsors should consult with qualified physicians to evaluate each inclusion and exclusion criteria for a given trial population. Important safety and efficacy data can be collected from open-label studies, studies in adolescents and children, early pediatric inclusion protocols, and pharmacokinetic modeling and simulation to bridge data between different population groups. Broad patient population following by subset analysis and adaptive trials are other promising tools available to sponsors. In addition, data from patients not eligible to participate in clinical trials can also come from expanded access programs. Patients may also get access to investigational drugs through the Right-To-Try mechanism and provide data that can be used to support or warn the use of the investigational products in other populations. The report is an excellent primer on the current challenges and options available to collect data from “interesting” populations. Historically, sponsors and FDA have relied on post-market data to understand how a new product behaves in populations not included in clinical trials. Now, FDA is pushing to get as much information during pre-approval process about the same populations. This report should be a great step in that direction.