Editorial: The Current Use of Biologics and Cellular Therapies in Orthopaedics: Are We Going Down the Right Path?

The problem of biologics, cellular therapies, and stem cells as therapeutic entities—and we choose the term “problem” after due consideration—has been addressed at a number of levels already: Thoughtful editorials [3, 15], consensus statements with which we generally agree [4, 11], and even actions by state licensing boards for unprofessional conduct [7, 8].

But the main unresolved issue is that stem cells and related products are a USD 10 billion industry [1] even though the only stem-cell-based products that are FDA-approved for use in the United States consist of blood-forming stem cells (hematopoietic progenitor cells) derived from cord blood. In light of that, one must surmise that a large part of this growing industry consists of off-label uses, and many of the indications in common use seem somewhat farfetched and lack evidence to support them [3, 5], while others seem to be practice patterns that fly in the face of it [12, 14]. And there are some indications where biologics and cellular therapies show genuine promise, such as diabetes [13] and Alzheimer’s dementia, but even for these, substantive questions remain, including some basic concerns about safety, efficacy, cell sourcing and delivery, host response, and mechanism of action [6]. There is only one way to work this problem, and that is money. More on where that should come from and how it should be deployed in a moment.

We hit pause on that only to discuss the issue of opportunity cost, because as relevant as this is to stem cells, it applies equally to the life cycle of any new set of ideas in practice.

In general, people thrive on novelty. And if the problem we’re fixing is of little consequence, like a kitchen spill, why not try the ShamWow®? It’s cheap, the ads for it are fun, and it’s probably no worse than anything else. In the same way, we look for the latest and newest forms of treatment, hoping that the just-released remedy with the special formula will be the one to cure our problems and ease our pains. We do this as patients, and we do it as physicians.

But musculoskeletal disease, and the resulting pain and loss of function, are not kitchen spills. And the time, effort, and money spent on nostrums of no value are not just worthless—their loss represents a serious opportunity cost, since every dollar spent on junk science is a dollar not spent on worthwhile research. The NIH will fund about USD 400 million this year on grants addressing arthritis in all forms—a tidy sum, but one that represents 1% of total NIH funding [16]. When 20% of the population experiences arthritis and other serious musculoskeletal diseases, and resources are not available for well-designed research, it’s not surprising that patients (and providers) will look anywhere for relief.

In the past, this approach has not worked well for our patients. The list of failed treatments for common musculoskeletal diseases is a long and sad one, from neutraceuticals to chelation therapy, and diets from alfalfa to zinc [10]. And orthopaedic surgeons have not been careful stewards of clinical evidence—we continue to use viscosupplementation, despite the paucity of good evidence [2], and we continue to use arthroscopic knee surgery in patients who should not have it, according to a large number of randomized trials and convincing meta-analyses [9]. It would be nice, after all this, to get it right vis-à-vis stem cells and related treatments.

It appears that government sanctions, editorial sermons, and statements from specialty groups have not arrested the many dubious practice patterns we’ve all seen; that being so, we are left uncertain about which (if any) biologics and cellular therapies are effective. To resolve this uncertainty, we must return to money, where it might come from, and how best to spend it. In our view, it is time for agencies such as the NIH to focus on funding research that looks specifically at use of these therapies in clinical practice. As valuable as bench research can be, it cannot address the immediacy the of current need, which has patients paying astonishing amounts of money (and taking yet-unquantified risk) for treatments that are of no benefit. We suggest that national agencies emphasize and promote the use of fast-track funding opportunities to underwrite well-designed, hypothesis-driven, and peer-reviewed clinical grants that involve biologics and cell therapies for regeneration of musculoskeletal tissues. The funding requirement to answer these questions may be large, but it is a small fraction of the amount of money patients and the healthcare system spends on treatments of dubious value. The faster we get the answers to the many questions we all have about these treatments, the less our healthcare system—and our patients—will pay in terms of this opportunity cost.

Programs we think might be especially appropriate to develop fast-track funding processes for regenerative musculoskeletal treatments might include those offered by the NIH through its Small Business Innovation Research/Small Business Technology Transfer program, where applicants can obtain simultaneous funding for proof of concept and development of promising work. Recently, the Department of Defense placed substantial resources into its Armed Forces Institute of Regenerative Medicine, a program focused on developing advanced treatment options for severely wounded soldiers, sailors, and airmen; this has developed into a multi-center consortium with a specific focus on the wounded warrior. The Concept to Clinic: Commercializing Innovation Program, a partnership between the NIH and the Wallace Coulter Foundation, is another example where national agencies can and do provide valuable resources. These efforts are laudable, but ought to be expanded. Relevant agencies might include foundations (such as the Arthritis Foundation, Arthritis National Research Foundation, and Orthopaedic Research and Education Foundation), government agencies including the NIH (in particular the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute of Allergy and Infectious Diseases and others), and the Agency for Healthcare Research and Quality. Pharmaceutical and implant companies should fund such studies as well. They have a vested interest in the performance of their new therapies in comparison to current established ones.

In return for improved access to funding, funding agencies should insist on consistent terminology, and identify what’s being done and compare well-designed studies to establish safety, efficacy and cost-effective care. The orthopaedic community can help regulators, policy makers, and patients understand what is scientifically valid and what is nonsense. Providers everywhere need to realize that what any of us does, to some degree, reflects on all of us. Physicians are scientists first. When we see advertisements that promote unsubstantiated treatments and make outrageous claims, physicians should work with state medical boards and regulatory authorities to stop those providers who are crossing the line into quackery, and ensure that patients are not harmed by them.