How Do Patients With Multiple Sclerosis Perceive the U.S. Drug Approval Process?

Many patients with multiple sclerosis (MS) do not believe the U.S. Food and Administration (FDA) balances the benefits and risks of investigational drugs before approving them, according to a nationwide survey led by Cleveland Clinic researchers. Half the survey respondents did not believe that approval of a disease-modifying therapy (DMT) meant that the benefits outweighed the risks, and respondents’ opinions appeared to differ by whether they had tried the agents.

“The most important finding from this study is that greater education is needed for people who are living with MS about the FDA approval process because there appear to be misunderstandings about what it means when a drug is approved,” says the study’s lead author, Paul J. Ford, PhD, Director of the NeuroEthics Program at Cleveland Clinic.

Essentials of the survey design

The study report, published online in Neurology Clinical Practice, details findings of a web-based survey of 3,533 patients with MS conducted in March and April 2016. The survey was administered via invitation to participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry and also via the National Multiple Sclerosis Society website. It was connected with a larger research project concerning risk tolerance in MS directed by Robert Fox, MD, Vice Chair for Research in Cleveland Clinic’s Neurological Institute.

Survey respondents had lived with MS a median of 16 years. Their mean age was 55.2 years, 78% were female and 92% were white.

Overall, 88.8% of those surveyed had ever used a DMT. Compared with these respondents, those who had never used a DMT were older (mean age, 58.9 vs. 54.7 years), more likely to be male (32.2% vs 20.6%) and less likely to ever have had a clinical relapse (68.2% vs 83.4%) (P < 0.001 for all comparisons).

The survey was designed to explore patients’ perceptions in four areas:

• The meaning of FDA drug approval, for which eight options were provided. Respondents were able to choose as many as they believed applied.
• The importance of certain factors in FDA’s decision to approve. Respondents were asked to indicate whether each of six factors should play a big role, a small role or no role in drug approval.
• Who best represents the views of people living with MS during the review discussion. Each of seven stakeholder groups were to be graded on a scale from “not well at all” to “extremely well.”
• Degree of comfort with uncertainty about the long-term safety effects of a new drug, to be rated from “not comfortable at all” to “extremely comfortable.”

Top-line findings

Almost all respondents believed that overall benefits, risks of serious side effects and whether benefits outweigh risks were important factors to FDA drug approval, with no difference by DMT use. Most also felt that improvement in quality of life was an important factor, but this was deemed important by a significantly larger share of DMT never-users.

Over two-thirds said that approval meant that a DMT had been tested in MS, provided a benefit in the disease and could now be used for treatment. “Only 6% of overall respondents said that FDA approval didn’t mean anything — what we call skeptics about the FDA — but a larger percentage (14%) of those who had never tried DMTs fell into this group,” notes Dr. Ford. “That indicates we may need different types of engagement with patients with MS to help them feel more included. Even if someone does not choose a DMT, we still want them to believe that the drug review process is meaningful.”

Nearly 80% of respondents felt that people with MS who were included in a clinical trial of a specific DMT could represent them well during the approval process. Other groups perceived as representing patients extremely well were doctors who treat patients with MS (45.6%), researchers who conducted the trial (40.7%) and patient advocacy groups (26.7%).

“We were surprised that 25% of the survey population thought that drug company representatives could represent them extremely or somewhat well,” says Dr. Ford. “Too often, we discount industry as a voice for patients, but a significant share of respondents may feel that the FDA is keeping companies from making drugs available that could help them.”

A majority of respondents were either not very comfortable (36.4%) or not at all comfortable (22.1%) with the uncertainty about long-term safety of new MS drugs upon their approval.

Recommendations moving forward

The researchers conclude that perceptions of the FDA approval process vary according to patients’ personal values as well as by whether or not they had tried DMTs. Their recommendations for addressing gaps in patient understanding identified in the survey include:

• Inviting participants in clinical trials to provide direct representation during the FDA review process, including both responders and nonresponders to therapy
• Ensuring that representatives in the review process are selected by neutral parties without financial or professional conflicts of interest
• Involving patient advocacy organizations to better educate patients about the approval process and the FDA’s mission