On June 6, the U.S. Food and Drug Administration (FDA) issued a draft guidance on improving the diversity of patient populations in clinical trials. Public comments are expected through August 6, 2019.
“Over the past few decades, FDA policy initiatives have focused on promoting enrollment practices that lead to clinical trials better reflecting the population most likely to use the drug if the drug is approved, primarily through broadening eligibility criteria,” the agency said.
The guidance tends to focus on getting sponsor companies to include more historically underserved populations in clinical trials, including women, the elderly and minorities. It Inclusion and exclusion criteria are important in how a clinical trial is designed—companies don’t just grab random people off the street and ask them if they want to take a new drug, after all. But, the agency notes, many patients are “excluded from trials without strong clinical or scientific justification.”
The guidance points out that eligibility criteria often exclude patients to protect the patients. “For example, patients with decreased renal function or certain concomitant illnesses are often excluded because of concerns that they may be more susceptible to the adverse effects of an investigational drug because it is metabolized by the kidney or interacts with other medications the patient takes.”
And patients with multiple diseases or who are on other medications are often excluded because of how they might affect the investigational compound’s safety or effectiveness. Pregnant women, obviously, are typically excluded because of concerns over how the drugs might affect the fetus.
From a scientific perspective, patients on multiple drugs or with multiple other diseases are often excluded because of what the agency calls “noise” in the safety data meaning it complicates the interpretation of the analysis. “Medically complex patients often have adverse clinical events that are related to their underlying conditions, which may make it difficult to determine whether the adverse event is related to the investigational drug, to the medical condition, or to a concomitant treatment.”
The concern, of course, is that a drug may get approved on a narrow patient population’s response to the drug, but then be given after approval to a much broader patient group with much more variations in weight, age, gender, race, or other illness and organ dysfunction.
The 18-page draft guidance makes numerous recommendations on how to increase diversity in clinical trials. These recommendations include enrichment, inclusive trial practices and design, and methodological ways to bring in a wider range of patient populations.
“It may be possible in some cases to have the development program include specific studies in higher risk populations conducted at sites with expertise in working with such participants,” the guidance states, adding that consent forms should clearly state if these participants will be at increased risk.
It also addressed expanded access as an option. Expanded access is typically granted to treat, monitor or diagnose a patient’s illness, often under a compassionate-use rationale, but the FDA says that, “In certain limited circumstances, data from expanded access use may inform clinical development.”
The FDA also took into account and provides a separate group of recommendations for rare disease clinical trials, stating, “Because rare disease often affect small, geographically dispersed patient populations with disease-related travel limitations, special efforts may be necessary to enroll and retain these participants to ensure that a broad spectrum of the patient population is represented.”