Humanitarian Device Exemptions (HDEs)

“What’s in a name? That which we call a rose by any other name would smell as sweet.” – Romeo and Juliet, Act II, Scene II, Shakespeare

Considerable confusion seems to stem from the fact that the US Food and Drug Administration (FDA) has approved Deep Brain Stimulation (DBS) for some conditions under a Humanitarian Device Exemption (HDE). The confusion is further heightened by the FDA’s recommendation of Institutional Review Board’s (IRB) approval of protocols to use DBS under the HDE. Current HDE approved conditions are primary dystonia, as well as Obsessive Compulsive Disorder (OCD). There is a notion that the use of DBS under a HDE is not “legitimate”, compared to devices approved under the typical Pre-Market Approval (PMA) or the device equivalence under a 510(k) rule. This notion of illegitimacy is heightened by the recommendation of IRB involvement. Needless to say, this confusion can be exploited by unscrupulous insurers to deny coverage for HDE approved indications (although it is interesting that in conversations, some insurers also reserve the right to deny coverage even for FDA approved indications). The fact of the matter is that an HDE approval is every bit as legitimate as if it had another name, such as a PMA or 510(k).

An HDE approval is based on the anticipated need, typically less than 4000 patients in any given year. Note, the criteria of safety and efficacy are not the issue. The FDA’s awarding of a HDE status is at tacit acceptance of the safety and efficacy. Thus, an indication of receiving an HDE approval is not experimental or investigational. From the FDA website, (

“To obtain approval for an HDE, an humanitarian device exemption (HDE) application is submitted to FDA. An HDE is similar in both form and content to a premarket approval (PMA) application, but is exempt from the effectiveness requirements of a PMA. An HDE application is not required to contain the results of scientifically valid clinical investigations demonstrating that the device is effective for its intended purpose. The application, however, must contain sufficient information for FDA to determine that the device does not pose an unreasonable or significant risk of illness or injury [italics added], and that the probable benefit to health outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment [italics added]. Additionally, the applicant must demonstrate that no comparable devices are available to treat or diagnose the disease or condition, and that they could not otherwise bring the device to market.”

The question is why involve the IRB? In fact, imposing this responsibility is contrary to the Belmont Report that was the basis for establishing IRBs ( In their deliberations, the authors of the Belmont Report were confronted with having to distinguish the difference between research and innovative, but accepted therapies. The Belmont Report reserved the label of research as those human studies that were intended to increase the general knowledge while those that were considered innovative were specifically directed to the best medical care of the individual. This distinction was important and follows from the Kantian ethics that every individual is an end unto themselves and not a means to an end for others. Research is directed to the potential benefit of future patients as its conduct cannot assure the participating research patient of benefit. Further, the research patient is exposed to the consequences of the researcher’s inherent conflict of interest in wanting to help future patients, versus their obligation to the patient asked to participate in research.

Requiring an IRB to rule on the use of an HDE approved device changes the role of the IRB and interjects the IRB into the care of individual patients. It is not unreasonable to argue that IRBs, generally, are not equipped to do so. Also, IRBs may be very reluctant to provide an open-ended approval but rather limit the number of patients that can be provided the therapy. The effect could be a cap, at least until some renewal, on the number of patients offered the therapy.

The interesting question is what force does the FDA requirement of IRB approval have? For example, a surgeon may decide to offer the therapy as an “off-label use” which has long been recognized as the privilege of the physician, provided certain requirements are met. Typically these requirements are that the off-label use not be used for research (particularly when asking for FDA approval). The perverse effect is that surgeons may face no restrictions in offering DBS for patients with secondary dystonia as an off-label use and yet face hurtles to providing DBS to patients with primary dystonia. Further, the same DBS systems that are used for patients with Parkinson’s disease are used in DBS for dystonia and so access to the DBS system is relatively unencumbered.

The situation is different for OCD where the DBS lead typically used (such as the Medtronic 3391 lead) is not readily available for any other indication. The manufacturer may require documented proof of IRB approval before providing the DBS lead. Perhaps this is meant to impose an inventory control allowing documentation that the number of cases of DBS for primary dystonia does not exceed the limits for an HDE. The question is what would stop a physician from using a more readily available DBS lead for OCD DBS?

If a surgeon wishes to pursue IRB approval for the use of a device for an HDE approved indication, the surgeon can enlist the help of the IRB in seeking prior authorization from insurers. One can ask IRBs providing approval to provide a letter explaining the role of the IRB in this process. The physician can ask the IRB to specifically note that their involvement does not mean that the indication is either experimental or investigational. Also, it may be good practice to explain to the patient or the patient’s representative about the nature of HDE approvals. However, the physician who mistakes the HDE label as some epistemic criticism, meaning that the evidence in support of the HDE is somehow less legitimate, will do his or her patient a disservice.