Improving oversight of innovative medical interventions in Texas, USA

In April 2012, the Texas (USA) Medical Board adopted new rules governing physicians’ use of investigational agents – primarily medical interventions not approved by the US FDA – in patient care. These new rules, which appear to be inspired by Governor Rick Perry’s experience with a stem cell-based intervention (SCBI) last year [1], are designed to allow physicians a “reasonable and responsible degree of latitude in the kinds of therapies they offer their patients” (See 22 TAC §§198.1–198.3 for the text of the rules, available online at [101]).

To offer this latitude, the rules outline a set of conditions under which physicians can offer certain unproven medical interventions to their patients – presumably on a fee-for-service basis. These conditions include the requirement that the proposed use of investigational agents is either included in a study approved by the FDA/NIH or has been approved by an institutional review board (IRB).

The rules also require that the administration of investigational agents, such as SCBIs, be part of a systematic and competently designed program to evaluate their efficacy and safety. Requirements for these evaluations include informed consent of all participants, the provision to all participants of a written description of the goals of the study, including the distinction between the goals of the clinical research study and the goals, risks and benefits of the treatment, and written disclosure to participants if the use of placebos are involved.

Physicians must also provide data on the safety and efficacy of these investigational agents as well as the names and contact information of any individual who received the investigational agents to the Texas Medical Board upon request. The rules do not provide any guidance as to why or when the Texas Medical Board might request this information, nor do they provide for any other reporting of the results of the required systematic evaluations.

Although these rules are not specific to SCBIs, they seem to have been developed, at least in part, in response to Governor Perry’s July 2011 experience with a SCBI [2], and most of the attention surrounding their passage has focused on their implications for the clinical translation of stem cell science [3–6]. The rules do explicitly indicate that the use of stem cells in humans should be considered investigational unless they are used in a FDA-approved protocol or have been previously approved by the FDA. To the extent that these rules affect stem cell research, they should be considered in a broader context of excitement about the translation of stem cell research into therapies and concerns about growing numbers of clinicians marketing and patients receiving unproven SCBIs around the world [7–11]. These unproven SCBIs raise concerns both about risks to individual patients and to the broader field of stem cell research [12].

Presumably, the Texas Medical Board adopted these guidelines in the hope that they would offer useful protection to patients considering unproven medical interventions, and guidance to physicians considering offering such investigational agents to their patients. These are noble goals and the possibility exists that the new rules will rein in some physicians who are already offering unproven medical interventions to their patients in Texas. As currently written, however, the rules have several important shortcomings and may, unfortunately, offer protection to unscrupulous providers taking advantage of their patients rather than protecting patients from such providers.

Among the improvements the Texas Medical Board should consider when it revises these rules, are more clearly defining the types of investigational agents they are designed to cover. Indeed, the current rules appear to contradict themselves. First, by excluding human cell- and tissue-based products that fall under two key sections of the Public Health Service Act from the definition of investigational agents, many SCBIs are apparently removed from the rules’ remit. Later, however, the rules state, without qualification, that the use of stem cells in humans should be considered investigational. This contradiction and the broader ambiguity in what the rules are intended to cover are problematic for patients and providers (including those treating patients with non-FDA approved but standard-of-care approaches) and clarity regarding the intended reach of these rules would be a substantial step forward. Different types of stem cells raise different issues and, as part of this clarification, the board might be wise to consider a more nuanced oversight approach reflecting these differences.

A major flaw in the current rules is that they appear to permit IRB approval to substitute for FDA approval. The rules should be revised to make it clear that IRBs cannot fill this role for any medical intervention for which the FDA would require premarket approval. Rather, the rules should allow IRB approval only for that subset of investigational agents that fall outside the scope of the FDA regulation or for which the FDA would not require premarket approval. In this way, the Texas Medical Board’s rules would toughen rather than weaken oversight and improve protections for patients.

Given the controversy and ongoing litigation [13] over the appropriate scope of FDA regulation for SCBIs (particularly using autologous adult stem cells), firms isolating, banking, and/or distributing stem cells for use as investigational agents and/or physicians treating patients with these cells should be required to verify in advance with the FDA that premarket clearance is not required. This step would help protect patients from providers attempting to bypass FDA oversight and offer clarity to firms and physicians developing new medical interventions.

The uncertainty surrounding the reporting of evaluations of investigational agents is also problematic. As recognized by the growth and increasingly mandated use of clinical trial registries [14], the public good is served when the outcomes of clinical research are widely and publicly shared. Yet, dissemination of systematic outcome data is often not in the interest of purveyors of unproven medical interventions, particularly when such dissemination would highlight the lack of efficacy of their approach and threaten their business. Indeed, some unscrupulous providers might prefer their interventions remain ‘investigational’ indefinitely. If the Texas Medical Board is serious about protecting patients, they should address this conflict. To do so, the board will need to ensure that the evaluations of investigational agents conducted under these rules are rigorously designed and implemented. In addition, they will also need to either mandate full and timely reporting of results of these evaluations or use their existing authority to acquire and publish sufficient data for external assessment of these investigational medical interventions.

Balancing medical innovation with patient safety is a challenging task, made more so in the context of stem cell science by the number of unscrupulous providers playing on the hype surrounding stem cells to prey on desperate patients. Given the observation that unproven SCBIs have been offered to patients in Texas [1,5] and uncertainty about the FDA’s authority to oversee certain types of SCBIs, the justification for the Texas Medical Board’s rules is sound. As written, however, the rules are problematic and provide ample opportunities for abuse. The Texas Medical Board should promptly revise them to ensure they strengthen rather than weaken patient protection and make it more difficult rather than less difficult for unscrupulous providers to call Texas home.