I’m Dr. Diana Zuckerman, president of the National Center for Health Research. Our center is a nonprofit think tank that scrutinizes the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products. My expertise is based on post-doc training in epidemiology and public health, and as a faculty member and researcher at Vassar, Yale, and Harvard. I’ve also worked at HHS, the U.S. Congress, and the White House.
FDA requires evidence that devices are reasonably safe and reasonably effective, defined as having benefits that outweigh the risks for most patients. So, how do MDUFA performance goals and other funded activities ensure those criteria are met?
MDUFA has provided the financial support FDA needed to improve the timeliness of reviews and increase FDA staff availability for meetings with industry. User fees were created because federal appropriations were not sufficient for the essential work of the FDA. Unfortunately, patients are not included at the table when MDUFA negotiations and decisions take place, and as a result, most patient-centered outcomes are not the focus.
- Performance data are currently based on speed. Those standards are usually met.
- However, performance data should also be based on other patient-centered outcomes
- MDUFA does NOT address many issues that are most important to patients that we work with
- MDUFA should help patients make informed choices, which is limited when FDA staff don’t required 510(k) clearance based on evidence of safety or effectiveness and almost never require clinical trials
- MDUFA should support greater scrutiny of De Novo and PMA decisions, which usually are based on case studies or clinical trials, but often lack diversity and often have no comparison groups to control for a placebo effect
- Are user fees sufficient to support more thorough scrutiny by FDA staff? PMA fees are much, much lower than PDUFA fees, even for the largest companies (such as J & J) And 510(k) fees are miniscule, and can’t support careful scrutiny
Since a picture is worth 1000 words, here are a few photos of devices that were cleared for market as substantially equivalent.
The first is a DePuy spinal system, which you can see is very different from its predicate. They added or modified parts, and the new complex systems were not tested prior to clearance.
This slide shows Diathermy devices for pain. The photo on the left shows that the device is so large that the patient is inside the device. So how is that substantially equivalent to the device on the right that is small enough to put on top of the knee or elbow?
This slide asks the question: Is FDA comparing apples and oranges in their 510(k) process? Actually, apples and oranges are much more similar than most predicates are to the newly cleared devices, because apples and oranges are both fruit, they are round, about the same size, and nutritious with some of the same vitamins. That’s much more similar than many of the devices that are cleared under MDUFA funding.
How can MDUFA improve?
- When good data are lacking prior to clearance, De Novo, or PMA decisions, post-market surveillance is especially important.
- But device user fees are inadequate to support excellent post-market surveillance
- MDUFA could be used to ensure that clinical studies are large enough and long-term enough
- Staff could use MDUFA resources to determine if there are solid safety and effectiveness data for male and female patients of different ages and race/ethnicity. Diversity is too often lacking in device clinical trials.
- MDUFA funds could be used to increase staff who review DTC ads and other promotional activities
This slide is upsetting. It shows a 2-year old whose face has swollen because of the off label use of Infuse bone cement. Infuse is a device whose label specifically says use in children is dangerous, so why did the company sell it to a children’s hospital? And what did FDA do about it?
FDA put information on their website that lists the risks, but instead of calling the product Infuse, they call it “Certain recombinant proteins and synthetic peptides…. that may be used as bone graft substitutes.” MDUFA could and should be used to provide better warnings to doctors, patients, and parents about dangerous off label uses.
- MDUFA should support FDA staff to develop patient and provider materials to explain off label risks and target off-label uses that are known to be ineffective or unsafe.
- FDA should use MDUFA funding to determine if detailing activities, DTC ads, or ads to doctors directly or indirectly promote inappropriate off label use
- Prior to allowing devices on the market, MDUFA should provide support for FDA staff to create Patient Booklets, Informed Consent Checklists, and other patient materials.
- MDUFA should also support comprehensive postmarket surveillance
- MDUFA should support FDA “Dear Doctor” letters, warnings to patients when risks are discovered
My last slide focuses on the need to increase user fees to support post-market surveillance
- Enforce clinical trial requirements
- Use them to evaluate data from adverse event reports, registries, and other real world data, which can supplement not replace controlled clinical trials
In summary, the term “performance goals” is a misnomer because MDUFA performance standards are currently based only on speed and industry access to FDA staff. Performance standards should also be based on patient-centered outcomes, such fewer symptoms, improved quality of life, and overall survival; short-term and long-term safety and side effects; and clearly defined warnings and contraindications.
MDUFA user fees should support FDA scientific and decision-making staff to meet upon request with consumer & public health advocates and patient advocates who are concerned about safety and effectiveness standards in general as well as specific products, and not just with industry. This is essential at all stages of the pre-market and post-market process, and these advocates should represent all patients and consumers, not just those recruited by industry and organizations funded by industry.
User fees should also be used to improve inspections. This has become an even more important issue in 2020 because FDA inspections have been reduced and delayed due to the pandemic.
As I noted previously, 2 key concerns are:
#1 Patient and Consumer Advocates should be at the table during MDUFA negotiations between industry and the FDA. We appreciate meetings like this one today, as well as briefings after the closed door meetings, but those do not replace being at the table.
#2 MDUFA fees should be increased to generously support post-market surveillance and enforcement of post-market study requirements.
In summary, MDUFA performance goals need to be more patient-centered by including specific metrics pertaining to safety and effectiveness, both pre-market and post-market, and improving patients and consumer advocates’ access to meet with FDA decision-making officials. That will help provide the safeguards that patients and consumers deserve.