FDA advisory committee did not recommend de novo classification for meniscus implant
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Key takeaways:
- Panelists had concerns about implant failure rate, the quality of evidence presented and issues with the study design.
- Panelists recommended that post-market studies keep record of implants that are replaced.
The Orthopaedic and Rehabilitation Devices Panel of the Medical Devices Advisory Committee of the FDA did not recommend de novo classification for an artificial meniscus implant.
The panel voted 6-2 with one abstention that the probable benefits of the artificial meniscus implant (NUsurface Meniscus Implant, Active Implants LLC) did not outweigh the probable risks.
Mercury trial
The de novo application included a prospective, randomized, multicenter superiority clinical trial (Mercury) that compared the NUsurface to nonsurgical treatment, including multimodal therapies, such as injections with corticosteroids or hyaluronic acid, prescription or nonprescription NSAIDs, physical therapy or bracing. According to the executive summary, the primary composite endpoint of the Mercury trial included the following:
- a 20-point improvement or more in the KOOS overall score;
- a 20-point improvement or more in KOOS pain considered independently;
- confirmation of the position and condition of the NUsurface device on MRI; and
- absence of a protocol-defined secondary surgical intervention that qualified as an automatic failure of the study, defined as patients who had surgery to remove the device with or without replacement for any reason and control group patients who underwent any surgical procedure on the medial compartment of the index knee.
Researchers also used two MRI criteria to identify a subpopulation of patients with improved outcomes and a lower incidence of second surgeries compared with the total Mercury population.
At 24-month follow-up, results showed that the NUsurface implant was statistically superior to the nonsurgical control group in the primary composite endpoint that combined safety and effectiveness outcomes. Researchers also found that the NUsurface implant was statistically superior to the nonsurgical control group in the primary composite endpoint in the subpopulation. However, researchers noted the subpopulation of patients who received the NUsurface implant had 50% fewer secondary surgical interventions vs. the total Mercury population, increasing the overall study success rate from 44.8% to 51.4%. Based on these results, the sponsor limited the indications for use to the subpopulation in the de novo submission.
Panel responses
When reviewing submitted data, panelists voiced concerns about the failure rate of the NUsurface implant, the quality of evidence presented and issues with the study design.
“I had concerns about the highly selected nature of the patients involved,” Paul A. Manner, MD, temporary voting member and professor in the department of orthopedics and sports medicine at the University of Washington School of Medicine, said. “I also had concerns about the highly selected nature of the surgeons involved, but my concern here was, even in the best of circumstances, the efficacy demonstrated by this device was not acceptable in terms of the risk that potentially would be taken. I think it would be a virtual certainty that the effectiveness would be far lower in the real world.”
Col. Melvin D. Helgeson, MD, FAOA, FAAO, temporary voting member and director for surgery at Walter Reed National Military Medical Center, said that data initially presented in the Mercury trial were the most relevant and that the modified Mercury subset data were difficult to interpret.
Similarly, Scott R. Evans, PhD, temporary voting member and professor and founding chair of the department of biostatistics and bioinformatics at George Washington University, said the different success criteria for the different study arms and the inconsistencies in the way the automatic study failure was evaluated in the two groups made the comparative analysis challenging to interpret.
Concerns with labeling
Panelists also said that they did not agree with the labeling of the NUsurface implant.
“Being asked to vote on the suggested label was what was difficult,” Shelby D. Reed, PhD, RPh, temporary voting member and director and co-founder of the Preference Evaluation Research Group at the Duke Clinical Research Institute and Duke University Medical Center, said. “I think it’s too broad. Including people with mild pain and with mild functional limitations really gave me pause.”
Although most of the panelists said that a change in the label would not affect their vote, Amy M. Cizik, PhD, MPH, said that she believed a change in labeling would help.
“I would like to have seen more functional data presented and, again, the data that was presented and the indication currently as it’s worded to me did not link well,” Cizik, temporary voting member at affiliate research assistant professor in the department of orthopedics at the University of Utah School of Medicine, said.
Post-market studies
Despite these concerns, several panelists said they believed that the benefits of the NUsurface implant did outweigh the risks.
“I do believe that there is a met need and few options for people in this situation,” Reed said. “I considered voting yes because, although the benefit isn’t as great as I would want it to be and I had a lot of shared concerns with regard to the analysis and the different definitions, the risk was primarily on reoperation, which people seemed to tolerate before moving on to arthroplasty, which is just a delay in the inevitable. So, that risk didn’t seem to be as large for me.”
John S. Kirkpatrick, MD, temporary voting member and chief of the section on orthopedic surgery at the Orlando Veterans Administration Medical Center, said that the sponsor should consider performing post-market studies.
“The easiest [post-market study] that I can think of is keeping record of any implants that are replaced, because I think that’s something that they should be able to be tracking.” Kirkpatrick said. “Otherwise, there might be some other tracking to make sure that they’re capturing the other types of failures.”
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Orthopaedic and Rehabilitation Devices panel of the Medical Devices Advisory Committee meeting announcement. https://www.fda.gov/advisory-committees/advisory-committee-calendar/april-20-2023-orthopaedic-and-rehabilitation-devices-panel-medical-devices-advisory-committee#event-materials. Published April 18, 2023. Accessed April 20, 2023.
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