Martha Murray, MD, FAAOS, FAOA, professor of orthopaedic surgery at Harvard Medical School and a sports medicine surgeon at Boston Children’s Hospital, has worked for the past 15 years to develop an alternative treatment for ACL tears. Her research ultimately led to the FDA’s recent granting of de novo approval for the Bridge-Enhanced® ACL Repair (BEAR®) Implant for the treatment of ACL tears. The BEAR Implant is the only medical technology to demonstrate healing of a torn ACL, which differs from the long-held approach to perform an ACL reconstruction with a graft of tendon. The BEAR Implant was found to be noninferior to autograft ACL reconstruction in patients aged 14 to 35 years and demonstrated faster recovery of muscle strength, higher patient satisfaction, and better Knee Injury and Osteoarthritis Outcome Score measures of pain and symptoms. Julie Balch Samora, MD, PhD, MPH, FAAOS, FAOA, interviewed Dr. Murray about her work in developing this technology.
Dr. Samora: I am intrigued with the origin of this idea and would like to know why you have spent so much time developing an alternative approach (ACL repair) to an already good option (ACL reconstruction)?
Dr. Murray: From the first time I heard about the treatment of ACL injuries using a graft, I wondered why the ACL wouldn’t heal like so many other tissues in the body. I wanted to see if we could make the ACL heal the way other tissues do.
Can you discuss how you take a kernel of an idea from animal trials to human trials to FDA approval?
We started with examining the injured tissues (pathology), and then we looked at how the cells behaved in a petri dish. Once we understood some of the basic biology there, we moved into relevant animal models to improve the implant and surgical technique. Once we had good results in the preclinical studies, we contacted the FDA to see what we would need to do to move to clinical trials. The FDA assigned us a review panel, and they provided guidance on how to demonstrate enough evidence of safety and efficacy of the implant in a preclinical model to justify a clinical trial. The FDA also gave guidance on how to design a pivotal clinical trial that could serve as the basis for FDA approval via the 510(k) de novo pathway.
You founded Miach Orthopaedics Inc. Can you discuss the process of creating a biotechnology company and when it’s appropriate to “make that leap”?
It comes down to what skill sets you have and what the project needs. We had the skill sets for doing preclinical studies and clinical trials, as well as small-scale manufacturing. We did not have the skill set for upscaling the manufacturing process or for sales and distribution. When it appeared that those were going to be important next steps in getting the technology to patients, we started a company that could bring in people with those skill sets to take it that next step.
I’m presuming you’ve had as many “failures” as you’ve had successes in this demanding process. Can you describe how you work through such failures, such as experiments that didn’t go as planned or grant and manuscript rejections? What advice might you give to young surgeon-scientists when they come up against such obstacles?
Everyone experiences failures and rejections. I think our project has had more than most. I would suggest giving yourself a few days to be miserable and then seeing what you can learn from the failure (there is always something) and move on. Having great collaborators and a resilient team really helps in those tough times, too.
Can you provide a bit of background on your relationship with the NFL Players Association (NFLPA) (and the National Institutes of Health [NIH])?
The NFLPA funded an initiative at Harvard Medical School (the Football Players Health Study), and our BEAR project was one of the first funded under that initiative. Since those early days, the NFLPA has funded both clinical trials of the BEAR technology. We have found the NFLPA to be a terrific partner and supporter throughout this translational process. The NIH has also been an invaluable source of funding and expertise. The vast majority of the preclinical work was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the grant reviews often contained very valuable and salient advice.
What does your typical workweek look like? How do you navigate both your scientific career and surgical demands?
For the first 15 years of my career, I spent 50 percent of my time in the lab and 50 percent in the clinic/OR. The key to that was to have good support people in both spaces—physician assistants in the clinic/OR and research fellows in the lab. About 18 months ago, I left my clinical practice and began devoting 100 percent of my time to research.
Do you have any words of advice for someone considering a career as a surgeon-scientist?
Do it. I can’t think of a more rewarding career. Make sure you have enough time devoted to science if you want to make it a career—two days a week at minimum. Find good collaborators who are excellent scientists and can help you grow. Find good research fellows who can manage the lab when you are in the clinic/OR. Find good partners and clinical providers who can take care of routine patient questions and issues when you are in the lab. Set aside two- to three-hour blocks on your research days for grant writing, data analysis, and manuscript preparation. Don’t let email steal your day. Assign an hour midday and at the end of the day to deal with it; otherwise, shut it off.
Julie Balch Samora, MD, PhD, MPH, FAAOS, FAOA, is associate medical director for quality at Nationwide Children’s Hospital in Columbus, Ohio, and deputy editor of AAOS Now. She can be reached at firstname.lastname@example.org.