On Patient Safety: Regenerative Medicine—The Hype Amplifies Safety Concerns

In early April of this year, New York state Attorney General Letitia James announced a lawsuit against a stem cell clinic for performing unproven procedures on patients with varied medical conditions including orthopaedic injuries. In a statement, Ms. James noted that “misleading vulnerable consumers who are desperate to find a treatment for serious and painful medical conditions is unacceptable, unlawful, and immoral” [1]. Such procedures can also be unsafe.

Although stem cell and other regenerative medicine clinics generally operate on the fringes of medical care both in the United States and other parts of the world [6], the demand for regenerative treatments like stem cell injections is real and some healthcare providers are willing to peddle unproven results to the public. Indeed, treatment claims for regenerative medicine often run far ahead of any sort of good quality medical evidence. For example, in an online interview sponsored by Washington state’s Swedish Hospital, a clinic physician claimed of his regenerative medicine program: “We can treat really any tendon or any joint. It’s particularly effective at tendons” [12].

Such statements are worrisome considering that most regenerative therapies have not been evaluated for either efficacy or safety concerns for the vast majority of human joints and tendons.

It is our professional duty to protect our patients from deliberate misinformation. Surgeons, specialty societies, and the government each have specific and important roles to play in combatting the available misinformation on this topic in the interest of keeping patients with potentially disabling musculoskeletal conditions safe.

Weak Evidence

I believe that the evidence in favor of these treatments is weak. The authors of a systematic review of stem cell injections in patients with knee osteoarthritis concluded that they could not recommend stem cell therapy [9]. Additionally, researchers using MRI mapping of knee cartilage showed no significant changes as a result of the stem cell injections [14]. In fact, results from a randomized controlled trial of platelet-rich matrix in rotator cuff repair suggested its use may have had a negative effect on healing [13].

Although a recent sham-controlled randomized controlled trial of platelet-rich plasma (PRP) did show positive results [7], many studies question both the efficacy of PRP and the data supporting its use. For instance, the largest meta-analysis of PRP to date found the available evidence to be of “very low quality due to inconsistency, imprecision, and risk of bias” [4].

According to the meta-analysis, most studies examining regenerative therapies lack sufficient documentation and have methodological inadequacies including poor patient allocation and blinding, incomplete outcome data, and selective reporting, in which complications were downplayed or omitted entirely [4]. Studies that downplay or do not even mention complications of an intervention are more akin to cheerleading or sales pitches than medical evidence, and we cannot rely upon them to ensure patient safety.

Aggressive Marketing Campaigns

Despite these concerns, orthopaedic surgeons and their patients have to deal with aggressive marketing of regenerative medicine. Currently, there are more than 40 commercial systems in operation that concentrate whole blood into PRP [5]. And although direct-to-consumer marketing of stem cell therapies has been called “downright dangerous” [3], I expect these campaigns to increase in size and scope. In fact, I’ve seen marketing materials that prop up a company’s own procedures by questioning the safety and evidence behind traditional orthopaedic surgery. For example, an online article featured on the Regenexx® (Des Moines, IA, USA) website notes, “Approximately 70% of orthopedic surgeries can be completely avoided with a Regenexx procedure. This orthopedic healthcare innovation is less costly, less invasive, and less risky than traditional orthopedic surgery” [11].

Pushing Back

Federal regulators must become more actively involved in the regulation of regenerative therapies. The FDA recently stated that once they are reinserted into the body “stem cell products can create unique and serious risks” [17]. Considering this statement, the FDA should immediately end its period of enforcement discretion for regenerative medicine providers and subject providers who use regenerative medical treatments on their patients to the same approval and regulatory requirements imposed on other drug and device manufacturers. Such a step would end the current “wild-west” era of these therapies and increase our patients’ safety.

Individual surgeons can be drawn to regenerative therapies by the lure of hassle-free insurance reimbursements. However, we should both avoid these therapies at present and strongly discourage referrals to regenerative clinics. Charges at such clinics can be as high as USD 17,000 [15]—a cost of the same order of magnitude as that of our most effective and resource intensive procedures such as total joint replacement. With their unknown safety profile and questionable efficacy, I believe it is wrong to subject our patients to these kinds of procedures, particularly at these kinds of prices.

Finally, and most importantly, our professional societies, such as the American Academy of Orthopaedic Surgeons (AAOS), must offer protections for our patients against potentially harmful and misleading advertising. Currently, our academy’s Professional Compliance Program works well to protect our members from inaccurate information or misleading statements in the course of malpractice litigation. It is well past time to afford our patients these same protections. According to one study of marketing material, only 6% of stem cell clinics—including those run by physicians—acknowledge risks specific to the treatments they offer [8]. A further study of Canadian clinics found that almost all of them minimize safety concerns [16].

Professional societies, including the AAOS, should hold members to the same standards for impartial and complete information in our marketing as we do when we testify against other orthopaedic surgeons. As an AAOS member, I’ve read of numerous disciplinary actions for violating the standards expected for expert testimony, but I’ve never seen even one for violating standards for advertising. It is time to take our Standard of Professionalism in Advertising [2] every bit as seriously as we take professional standards when one of our members is at risk during a lawsuit. These standards should require advertising to adhere to the same evidentiary requirements, and the AAOS should publish the procedures for physicians, the general public, and consumer advocacy organizations to lodge a complaint.

At present, I recommend a continued skeptical view of regenerative therapies. Let us steer patients interested in such treatments toward clinical trials while waiting for long-term data to emerge (or not) documenting both its safety and efficacy before we begin to make it a routine component of our treatment armamentarium [10, 18]. Let us push the FDA to immediately regulate regenerative providers and make the AAOS a leading voice in combatting incomplete or deceptive marketing.