Policy makers, researchers, and industry look to the future of orthopaedic clinical trials

The AAOS/ORS Clinical Trials in Orthopaedics Research Symposium concluded with a panel discussion on bridging the gap between policy makers, researchers, and sponsors of clinical trials. Participants included James G. Wright, MD, MPH, FRCSC, cochair of the symposium; Marc F. Swiontkowski, MD, deputy editor of the Journal of Bone and Joint Surgery (JBJS); Joan McGowan, PhD, director of the musculoskeletal diseases branch of the National Institute of Arthritis and Musculoskeletal Diseases (NIAMS); Dan Schultz, MD, director of the Center for Devices and Radiological Health (CDRH) within the U.S. Food and Drug Administration (FDA); Paul Voorhorst, MS, MBA, DePuy Orthopaedics; Kristy L. Weber, MD, chair, AAOS Council on Research, Quality Assessment, and Technology (CORQAT); Christopher Evans, PhD, Orthopaedic Research Society (ORS); and Thomas A. Einhorn, MD, Orthopaedic Research and Education Foundation (OREF). Dr. Wright posed the first question to the panel.

The future of clinical trials
Dr. Wright: Having heard the conversations over the last two days, what should be done differently to sponsor clinical trials?

Dr. Weber: The AAOS is already taking steps to help bridge the gap between policy makers, researchers, and sponsors. For example, we are developing clinical practice guidelines, because we realize that if orthopaedic surgeons don’t take this step, others will do it. We are meeting with NIAMS to identify key gaps in current evidence that may lead to clinical trials. We are in a position to help validate and to disseminate information to our members. Whether the information will change practice is a big question.

Dr. McGowan: I see us moving in the same direction. My colleagues at NIAMS and at the National Institutes of Health (NIH) are very engaged and seeking to develop a better way to identify, prioritize, support, and manage clinical trials. One option is to take advantage of the power of partnerships within the NIH and across the government. This is an option that hasn’t been fully explored, particularly for orthopaedic research.

Dr. Schultz: We need data to make regulatory and public health decisions; we can’t just rely on the strong opinions of individuals for what should happen. Even with data, problems may arise with interpretation and matching data to decisions, but with no information, decision making is totally impossible.

At CDRH, the “total product lifecycle approach” is not just a slogan; it embodies the way we look at the regulation of medical devices. We want to be involved all the way, from the initial applications and decisions on whether to go to market, to understanding how devices work through their life cycles after they’ve been released. If we can improve the way things are studied, we can fine tune our knowledge and provide better information to clinicians and patients.

Dr. Einhorn: Two issues that will change the way I think about clinical trials are the question of equipoise and the importance of research leading to changes in clinical practice. The SPRINT (Study to Prospectively Evaluate Reamed Intramedullary Nails in Tibial Fractures) trial is an example of the latter issue. Not only did we learn a lot, it changed clinical practice. Researchers need to think about how important and how valuable it is to answer a particular question.

The concept of equipoise—being able to recommend randomization to a patient who meets the guidelines for a clinical trial even if I personally think one treatment or another might be better—was not something I had thought about. (For more on equipoise, see “Can you admit not knowing?”) It's hard to divorce yourself from what you think works. I hadn't thought about how much of a bias I have and how that could affect the conduct of research.

Mr. Voorhorst: There’s been a dramatic cultural shift in industry over the past 20 years. Industry wants to gear up the quality of its studies. We share your commitment to improve the health of patients; how we do it differs, but in many areas, we can partner together. Industry can help fund large randomized clinical trials.

What struck home for me is the need for leadership that is dedicated to improving the quality of research and clinical trials.

Another area where we can work together to bridge the gap is on national registries. If they’re going to work, they will require partnerships. Industry is very supportive, especially if the registries can serve as a way to meet the FDA’s postmarket surveillance requirements. We’re very interested and want to make it a win-win situation.

Dr. Evans: I represent the ORS, whose members do the basic research that leads to larger trials and, in particular, clinical trials. The ability to perform that type of translational research depends on the institutional environment. The question is how do we create and nurture such an environment? How can we get clinical and laboratory researchers working together? We need to reinforce the value of research in allocating resources and to amplify NIH dollars with other resources.

Dr. Swiontkowski: Journals such as JBJS will continue to encourage submissions, but will also need to rebalance reports from basic to clinical research. They will also need to be aware of publication bias, particularly if a study has negative, rather than positive, results. We need to encourage the publication of these studies because the information is just as important as the positive studies.

In preparing questions for the Orthopaedic In-Training Exam or board certification exams, question writers need to focus on using Level 1 evidence. I would encourage them to use JBJS as a source of those questions.

I would also encourage all the parties here to consider that a rebalancing of priorities, from basic research to clinical research, is in order. We need to know that what we do works.

Validating outcomes
The next question, from the floor, focused on the need for validated outcome measures.

Dr. Wright: Orthopaedics, as a field, is a leader in developing outcome measurement tools. We have tools to measure outcomes in both the upper and lower extremities, the neck, and the back. In addition, the orthopaedic culture has adopted and accepted validated psychometric work and new measures.

Dr. Swiontkowski: JBJS emphasizes high quality outcome measurement across the full spectrum of clinical research. There are better ways to measure outcomes than have been used in the past, and we are seeing some improvement.

Joint registries
A question on the use of joint registries to serve as an outcome measure for randomized clinical trials after the FDA has approved a device drew the following responses.

Dr. Schultz: We need to be sensitive to the fact that many types of devices exist. Some incorporate incremental changes and do not require randomized clinical trials. We already know that the procedure is meaningful. On the other hand, we need to be aware of when technology crosses the line. It’s impossible to do a randomized clinical trial after a device has been introduced. I believe very strongly that we need to figure out a proper balance on the data that’s required before a device goes to market.

We also need a registry. Most devices are made and used in this country. We cannot rely solely on passive surveillance and voluntary reporting.

Dr. Weber: AAOS is committed to establishing a total joint registry; it’s embarrassing that the United States does not have one. The AAOS has committed $300,000 to support the development of a registry; the details will be worked out over the next 6 months.

Research provides credibility to our message. Evidence-based medicine enables us to say “this does or doesn’t work.” Lobbying and advocacy efforts are not going to stop, but we need to shift the message to the context of patient care.

Mary Ann Porucznik is managing editor of AAOS Now. She can be reached at porucznik@aaos.org