THE VANISHING FDA ORTHO PANEL MEETING (Orthopedics This Week)
In the last few years the ortho panel meeting has gone radio silent.
In 2010 there were nine panel meetings, in 2017 there were only two. In 2018 and 2019 there was not a single premarket approval application (PMA) advisory panel meeting.
We asked the FDA why there were no meetings. More radio silence.
What Do Ortho Panel Meeting Do?
For presenters, sponsoring companies and, indeed, the entire orthopedic community of physicians and companies, the ortho panel meeting is a fascinating process.
Companies submitting their PMAs spend months choreographing every word and speaker. FDA staffers look for the weakest link in the company’s proposal and panel members prepare to perform in front of the public, their peers and industry.
The day of the meeting is like walking into a wedding. In the first couple of rows on the right sit FDA staffers. You’ll know them by their youth, full heads of hair and color in their clothing.
In the front couple of rows on the left sit company representatives and their bevy of staffers and expert consultants. You’ll know them by their maturity, gray or balding heads and conservative clothing.
At the altar sit the wise ones. Listening to the presentations, asking questions and challenging presenters and each other over scientific details and nuances.
Over the next two days there will be public presentations by the sponsoring company, FDA staffers and members of the public. Every speaker will give their reasons why this particular device should or should not be deemed safe and effective.
Lives Changed, Fortunes Won and Lost
At the end of the second day lives will be changed and fortunes will be decided as panel members from prestigious teaching hospitals, clinics and universities vote on whether they will give their support to the FDA for commercializing a new device.
During breaks, panel members are sequestered and under strict orders to speak to no one about any of the presentations. Company presenters retreat to their suite to evaluate what they’ve heard and prepare for the next round. Everybody else spreads out over the Hilton in Gaithersburg, Virginia, and gets into mosh pits of conjecture, second-guessing and predicting how Dr. X on the right-hand side of the panel tables will vote.
It’s a cauldron of science, politics, business policy and media schmoozing. It’s a place where government, business, the public and scientists meet to figure out the latest measure of safety and effectiveness.
So why have there been no meetings?
Are there fewer first-of-kind devices? Is the FDA staff more comfortable in analyzing and regulating these devices? Is the risk of an unpredictable panel meeting too great for both parties?
Former Chief of the Orthopedic Devices Branch at the Food and Drug Administration, Glenn Stiegman, says based on the devices he’s recently seen approved by the FDA, the answer to those questions is—all of the above.
The Rare and Possibly Endangered First-of-Kind PMA
First, says Stiegman, now SVP of Clinical and Regulatory Affairs at MCRA, LLC (Musculoskeletal Clinical Regulatory Advisors), since 2016, there have been nine original PMAs approved under the Orthopedic Advisory Committee. “Four of these PMAs were hyaluronic acid knee injections (i.e., not first-of-kind), one was a ceramic-on-ceramic hip (i.e., not first of kind), one was a cervical total disc replacement (i.e., not first-of-kind), one was an unconstrained total ankle replacement (i.e., not first-of-kind), but two approved PMAs were first-of-kind devices (i.e., Barricaid Anular Closure Device, Cartiva Synthetic Cartilage Implant).”
Both of these devices went to the Advisory Panel.
With such a small sample size, Stiegman added it seems that there are not as many first-of-kind PMAs.
“Why is that?” Stiegman asks rhetorically. What has happened over the course of the last few years to drive innovation down?
It costs a lot of time and money.
“Getting a device to market takes an enormous amount of time and capital. If the device is a first-of-kind, it takes time, money, and the effort can be exponential. “In my experience, the preclinical testing program can take several years, especially if there are animal studies, and the clinical study can take up to 4 years for enrollment and follow-up.
“Finally, the PMA, itself, can take anywhere from 12-18 months. To bring a new Class III device from concept to market, a company could easily spend 8-10 years before having their PMA approved.”
What was happening 8-10 years ago?
Stiegman says the Great Recession of 2007-2009, “greatly impacted the influx of financial support from investors, which in turn slows down research and development, which ultimately affects bringing anything that requires almost a decade of testing to market.
“At MCRA, we saw a slowdown in pre-submissions, IDEs [investigational device exemption], and, in general, companies attempting to get new first-of-kind devices to market.
“In addition, companies that were in process of getting these devices to market, put holds on their clinical study and PMA plans. Many of the smaller companies did not have the ability to test their device using expensive animal studies or run lengthy IDE studies during that time period. Innovation seemed to stop for years after the Great Recession, thus having a butterfly effect on the frequency of Advisory Panels today.”
New Approaches Undercut Panel’s Relevance
The second reason for fewer panel meetings, says Stiegman, is that over the course of the past 10 years the need for consulting the panel has lessened as the FDA has “embraced creative statistical plans, the use of alternative controls, have exercised different methods of analyzing new materials, and have been more transparent with understanding the various treatments and/or patient populations.”
In the past, Stiegman says these would all be reasons to bring a device in front of the Advisory Panel for feedback.
“In addition, over the course of this time, FDA has pushed the Real-World Data Initiative, have formalized the de novo 510(k) pathway, increased their scrutiny of materials, and have had general panel meetings and workshops about groups of devices or general topics.
“At the end of the day, these mechanisms allow the FDA to bypass those Advisory Panels that are scrutinizing a single device.”
Unpredictability
The final reason for fewer panel meetings, according to Stiegman, is that organizing a panel is not only a lot of work and costly for the FDA, it can also be risky. “FDA will bring a device to panel to seek specific questions to be answered, in addition, to the safety, effectiveness, and risk/benefit questions. There is a risk of the panel not addressing FDA’s device specific questions, which brought this device to panel in the first place.”
Stiegman has prepared for Advisory Panels on both the FDA side and the company side. “It is a long and arduous task to prepare for a panel meeting.”
In general, Stiegman says companies often do not want to bring their device to a panel because of the unpredictable nature of panels and their discussions.
The FDA also has other options.
“In an already short-staffed and busy review team, FDA may want to look at other options to get their questions answered instead of a public Advisory Panel such as Panel Homework Assignment.”
“Scientifically and clinically, FDA and review team have to weigh the value of the panel input on any questions, how panel’s input would affect their overall decision, and ultimately, the overall benefit compared to the risks associated with preparing a panel.
“In some cases, where a device may have a safety concern or may not have met their success criteria, FDA may use a panel to justify an approval or justify a disapproval. However, in many cases, these scenarios have precedent, where the safety and effectiveness can be determined using the totality of information for similar devices, as well as, the benefit risk profile being evident.”
In general, the decision of FDA to take a device to an Advisory Panel, according to Stiegman, is complex and sometimes difficult given the number of factors with no true straight-forward formula to help in this decision.
“The combination of all three of these scenarios culminate into Advisory Panels seemingly looking like a dying breed.”
Innovation Renaissance?
However, Stiegman and his team at MCRA have seen a turn in innovation, with new technologies, materials, and patient treatments being discussed with the FDA.
The team is seeing more and more devices that represent a “first-of-kind device, and FDA wants to be careful that they understand the ramification of their approvals, as to not set a damaging precedent with how an innovative class of devices is regulated. There a sense of hope that the excitement and intrigue of Advisory Panels will once again return to a Gaithersburg Hilton near you.”
If Stiegman is right, we should all be getting out our good clothes and get ready for another Happening. The post-Great Recession innovations should be exciting.