Banned Devices; Proposal To Ban Electrical Stimulation Devices Used To Treat Self-Injurious or Aggressive Behavior
Federal Register, Volume 81 Issue 79 (Monday, April 25, 2016)
Federal Register Volume 81, Number 79 (Monday, April 25, 2016)
Proposed Rules
Pages 24385-24418
From the Federal Register Online via the Government Publishing Office www.gpo.gov
FR Doc No: 2016-09433
Page 24385
Vol. 81
Monday,
No. 79
April 25, 2016
Part VI
Department of Health and Human Services
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Food and Drug Administration
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21 CFR Parts 882 and 895
Banned Devices; Proposal To Ban Electrical Stimulation Devices Used To Treat Self-Injurious or Aggressive Behavior; Proposed Rule
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 882 and 895
Docket No. FDA-2016-N-1111
Banned Devices; Proposal To Ban Electrical Stimulation Devices Used To Treat Self-Injurious or Aggressive Behavior
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA or we) is proposing to ban electrical stimulation devices used to treat aggressive or self-
injurious behavior. FDA has determined that these devices present an unreasonable and substantial risk of illness or injury that cannot be corrected or eliminated by labeling. FDA is proposing to include in this ban both new devices and devices already in distribution and use.
DATES: Submit either electronic or written comments on the proposed rule by May 25, 2016.
ADDRESSES: You may submit comments as follows:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: http://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to http://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on http://www.regulations.gov.
If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
Mail/Hand delivery/Courier (for written/paper submissions): Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Division of Dockets Management, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No. FDA-2016-N-1111 for ``Proposal to Ban Electrical Stimulation Devices Used To Treat Self-Injurious or Aggressive Behavior.'' Received comments will be placed in the docket and, except for those submitted as ``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.
Confidential Submissions--To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states ``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on http://www.regulations.gov. Submit both copies to the Division of Dockets Management. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as ``confidential.'' Any information marked as ``confidential'' will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the ``Search'' box and follow the prompts and/or go to the Division of Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Rebecca Nipper, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 1540, Silver Spring, MD 20993-0002, 301-796-6527.
SUPPLEMENTARY INFORMATION:
Executive Summary
Purpose of the Proposed Rule
FDA is proposing to ban electrical stimulation devices (ESDs) used for self-injurious or aggressive behavior. ESDs are devices that apply a noxious electrical stimulus to a person's skin upon the occurrence of a target behavior in an attempt to condition the individual over time to reduce or cease the behavior. Self-injurious behaviors (SIB) and aggressive behaviors (AB) frequently manifest in the same individual, and people with intellectual or developmental disabilities exhibit these behaviors at disproportionately high rates. Notably, many such people have difficulty communicating and cannot make their own treatment decisions because of such disabilities, meaning many people who exhibit SIB or AB are among a vulnerable population. SIB commonly include: Head-banging, hand-biting, excessive scratching, and picking of the skin. However, SIB can be more extreme and result in bleeding, protruding, and broken bones; blindness from eye-gouging or poking; other permanent tissue damage; or injuries from swallowing dangerous objects or substances. AB involve repeated physical assaults and can be a danger to the individual, others, or property. In our proposed rule, like much of the scientific literature, we discuss SIB and AB in tandem.
ESDs are intended to reduce SIB and AB according to the principle of aversive conditioning. Aversive conditioning pairs a noxious stimulus with a target behavior such that the individual begins to associate the noxious stimulus with the behavior, with the intended result being that the individual ceases engaging in the behavior and, over time, becomes conditioned not to manifest the target behavior. A noxious stimulus is one that is uncomfortable or painful; the noxious stimulus delivered by an ESD is an
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electric shock to the skin. Some ESDs are intended for other purposes, such as smoking cessation; however, the proposed ban includes only those devices intended to reduce or eliminate SIB or AB. ESDs are not used in electroconvulsive therapy, sometimes called electroshock therapy or ECT, which is unrelated to this proposed rulemaking.
The effects of the shock are both psychological (including suffering) and physical (including pain), each having a complex relationship with the electrical parameters of the shock. As a result, the subjective experience of the person receiving the shock can be difficult to predict. Physical reactions roughly correlate with the peak current of the shock delivered by the ESD. However, various other factors such as sweat, electrode placement, recent history of shocks, and body chemistry can physically affect the sensation. As a result, the intensity or pain of a particular set of shock parameters can vary greatly from patient to patient and from shock to shock. Possible adverse psychological reactions are even more loosely correlated with shock intensity in that the shock need not exceed certain physical thresholds. Rather, the shock need only be subjectively stressful enough to cause trauma or suffering. Trauma becomes more likely, for example, when the recipient does not have control over the shock or has developed a fear of future shocks, neither of which is an electrical parameter of the shock.
Whenever FDA finds, on the basis of all available data and information, that a device presents substantial deception or an unreasonable and substantial risk of illness or injury, and that such deception or risk cannot be, or has not been, corrected or eliminated by labeling or by a change in labeling, FDA may initiate a proceeding to ban the device. In making such a finding, FDA weighs the benefits against the risks posed by the device and considers the risks relative to the state of the art. With respect to ESDs for SIB and AB, FDA has weighed these factors based on consideration of information from a variety of sources, including the scientific literature, opinions from experts (including an advisory panel meeting), information from and actions of State agencies, information from the affected manufacturer, information from patients and their family members, and information from other stakeholders.
FDA has determined that ESDs for SIB or AB present a number of psychological and physical risks: Depression, fear, escape and avoidance behaviors, panic, aggression, substitution of other behaviors (e.g., freezing and catatonic sit-down), worsening of underlying symptoms (e.g., increased frequency or bursts of self-injury), pain, burns, tissue damage, and errant shocks from device misapplication or failure. Based on literature for implantable cardioverter defibrillators, FDA has determined that ESDs present the risks of posttraumatic stress or acute stress disorders, shock stress reaction, and learned helplessness. That literature provides additional support for the risks of depression, anxiety, fear, and pain. Experts in the field of behavioral science, State agencies that regulate the use of ESDs, the sole current manufacturer and user of ESDs, and individuals who were subject to ESDs corroborate most of these findings, and they attest to additional risks.
Our search of the scientific literature revealed a number of studies showing that ESDs result in the immediate interruption of the target behavior upon shock, and some of the literature also suggested varying degrees of durable conditioning. However, the studies in the literature suffer from serious limitations, including weak study design, small size, and adherence to outdated standards for study conduct and reporting. The conclusions of several of the studies are undermined by study-specific methodological limitations, lack of peer review, and author conflicts of interest. There is also evidence that the shocks are completely ineffectual for certain individuals.
FDA weighed the benefits against the risks. FDA recognizes that ESDs can cause the immediate interruption of self-injurious or aggressive behavior, but the evidence is otherwise inconclusive and does not establish that ESDs improve the underlying disability or successfully condition individuals to achieve durable long-term reduction of SIB or AB. The short-term effect of behavior interruption is outweighed by the numerous short- and long-term risks. For many individuals who exhibit SIB or AB, these risks are magnified by their inability to adequately communicate the harms they experience to their health care providers. Even if immediate cessation is achieved, without durable conditioning the target behavior will recur over time and necessitate ongoing shocks to cause immediate cessation, magnifying the risks. For some patients, the shocks are wholly ineffective and can lead to progressively stronger shocks with the same result. Thus the degree to which the risks outweigh the benefits increases over time.
When considering the reasonableness of the risk of illness or injury posed by a device in a banning proceeding, FDA also considers the state of the art. Notably, the use of aversive conditioning in general, and ESDs in particular, has been on the decline for decades; only one facility in the United States still uses ESDs for SIB and AB. This decline is due in part to scientific advances that have yielded new insights into the organic causes and external (environmental or social) triggers of SIB and AB, allowing the field to move beyond intrusive punishment techniques such as aversive conditioning with ESDs. Moreover, punishment techniques (which include the use of ESDs) are highly context-sensitive, so the same technique may lose effectiveness simply by changing rooms or providers. The evolution of the state of the art responded to this limitation by emphasizing skills acquisition and individual choice. The evolution is also due in part to the ethical concerns tied to the risks posed by devices such as ESDs, especially regarding the application of pain to a vulnerable patient population.
In light of scientific advances, out of concern for ethical treatment, and in an attempt to create generalizable interventions that work in community settings, behavioral scientists have developed safer, successful treatments. The development of the functional behavioral assessment, a formalized tool to analyze and determine triggering conditions, has allowed providers to formulate and implement plans based on positive techniques. As a result, multi-element positive interventions (e.g., paradigms such as positive behavior support or dialectical behavioral therapy) have become state-of-the-art treatments for SIB and AB. Such interventions achieve success through environmental modification and an emphasis on teaching appropriate skills. Behavioral intervention providers may also recommend pharmacotherapy (the use of medications) as an adjunct or supplemental method of treatment. Positive-only approaches are generally successful even for challenging SIB and AB, in both clinical and community settings. The scientific community has long since recognized that addressing the underlying causes of SIB or AB, rather than suppressing it with painful shocks, not only avoids the risks posed by ESDs, but can achieve durable, long-term benefits.
Based on all available data and information, FDA has determined that the risk of illness or injury posed by ESDs for SIB and AB is substantial and
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unreasonable and that labeling or a change in labeling cannot correct or eliminate the unreasonable and substantial risk of illness or injury. The purpose of this proposed rule is to seek comments on these determinations as well as seek comments on FDA's proposal to ban ESDs used for SIB or AB and comments on any other associated issues.
Legal Authority
The FD&C Act authorizes FDA to ban a device intended for human use by regulation if it finds, on the basis of all available data and information, that such a device presents substantial deception or an unreasonable and substantial risk of illness or injury. A banned device is adulterated except to the extent it is being studied pursuant to an investigational device exemption. This proposed rule is also issued under the authority to issue regulations for the efficient enforcement of the FD&C Act.
In determining whether a deception or risk of illness or injury is ``substantial,'' FDA will consider whether the risk posed by the continued marketing of the device, or continued marketing of the device as presently labeled, is important, material, or significant in relation to the benefit to the public health from its continued marketing. Although FDA's device banning regulations do not define ``unreasonable risk,'' FDA previously explained that, with respect to ``unreasonable risk,'' we will conduct a careful analysis of risks associated with the use of the device relative to the state of the art and the potential hazard to patients and users. The state of the art with respect to this proposed rule is the state of current technical and scientific knowledge and medical practice with regard to the treatment of patients exhibiting self-injurious and aggressive behavior.
Thus, in determining whether a device presents an ``unreasonable and substantial risk of illness or injury,'' FDA analyzes the risks and the benefits the device poses to individuals, comparing those risks and benefits to the risks and benefits posed by alternative treatments being used in current medical practice. Actual proof of illness or injury is not required; FDA need only find that a device presents the requisite degree of risk on the basis of all available data and information.
Whenever FDA finds, on the basis of all available data and information, that the device presents substantial deception or an unreasonable and substantial risk of illness or injury, and that such deception or risk cannot be, or has not been, corrected or eliminated by labeling or by a change in labeling, FDA may initiate a proceeding to ban the device.
Summary of the Major Provisions of the Proposed Rule
If this proposed rule is finalized as proposed, the ban would include devices that apply a noxious electrical stimulus to a person's skin to reduce or cease aggressive or self-injurious behavior. The proposed ban would apply to devices already in commercial distribution and devices already sold to the ultimate user, as well as devices sold or commercially distributed in the future. A banned device is an adulterated device, subject to enforcement action. The ban may not, however, prevent further study of such devices pursuant to an investigational device exemption.
Costs and Benefits of the Proposed Rule
FDA is proposing to ban ESDs for the purpose of treating self-
injurious or aggressive behavior. Because we lack sufficient information to quantify the benefits, we include a qualitative description of some potential benefits of the proposed rule. We expect that the rule would directly affect only one entity. In addition to the incremental costs this entity would incur to comply with the requirements of the proposed rule, there would be potential transfer payments of between $11.5 million and $15 million annually either within the affected entity or between entities. The present value of total costs over 10 years ranges from $0 million to $60.1 million at a 3 percent discount rate, and ranges from $0 million to $51.4 million at a 7 percent discount rate. Annualized costs range from $0 million to $6.8 million at a 3 percent discount rate and range from $0 million to $6.8 million at a 7 percent discount rate.
Table of Abbreviations and Acronyms
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Abbreviation or acronym What it means
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AB................................ Aggressive Behavior.
ABA............................... Applied Behavior Analysis.
AE................................ Adverse Event.
DBT............................... Dialectical Behavioral Therapy.
DDS............................... (Massachusetts) Department of
Developmental Services.
DEEC.............................. (Massachusetts) Department of Early
Education and Care.
EA................................ Environmental Assessment.
ESD............................... Electrical Stimulation Device.
FD&C Act.......................... Federal Food, Drug, and Cosmetic
Act.
FONSI............................. Finding of No Significant Impact.
GED............................... Graduated Electronic Decelerator.
ICD............................... Implantable Cardioverter
Defibrillator.
JRC............................... Judge Rotenberg Educational Center,
Inc.
NASDDDS........................... National Association of State
Directors of Developmental
Disability Services.
NYSED............................. New York State Education Department.
PBS............................... Positive Behavioral Support.
PTSD.............................. Post-traumatic Stress Disorder.
SIB............................... Self-Injurious Behavior.
SIBIS............................. Self-Injurious Behavior Inhibiting
System.
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Table of Contents
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Background
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Introduction
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What are SIB and AB, and how do they affect patients?
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What are ESDs and how do they affect SIB and AB?
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How has FDA regulated ESDs in the past?
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Scope of the Ban
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Legal Authority
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Evaluation of Data and Information Regarding ESDs
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Risks of Illness or Injury Posed by ESDs
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Effect on Targeted Behavior
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State of the Art
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Determination That ESDs for SIB and AB Present an Unreasonable and Substantial Risk of Illness or Injury
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Labeling
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Application of Ban to Devices in Distribution and Use
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Proposed Effective Date
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Analysis of Environmental Impact
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Economic Analysis of Impacts
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Introduction
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Summary of Costs and Benefits
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Paperwork Reduction Act
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Federalism
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References
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Background
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Introduction
Electrical stimulation devices (ESDs) for self-injurious behavior (SIB) or aggressive behavior (AB) are devices that apply a noxious electrical stimulus (a shock) to a person's skin to reduce or cease such behaviors. Although FDA cleared a few of these devices more than 20 years ago, due to scientific advances and ethical concerns tied to the risks of ESDs, state-of-the-art medical practice has evolved away from their use and toward various positive behavioral treatments, sometimes combined with pharmacological treatments. Only one facility in the United States has manufactured these devices or used them on individuals in recent years. As a result of this evolution in treatment over the past several decades, the available data and information on the risks and benefits of ESDs are limited.
Although the available data and information show that some individuals subject to ESDs exhibit an immediate reduction or cessation of the targeted behavior, the available evidence has not established a durable long-term conditioning effect or an overall-favorable benefit-
risk profile for ESDs for SIB and AB. No randomized, controlled clinical trials have been conducted, and the studies that have been conducted are generally small and suffer from various limitations, including the use of concomitant treatments over long periods that make it difficult to determine the cause of any behavioral changes. The medical literature shows that ESDs present risks of a number of psychological harms including depression, posttraumatic stress disorder (PTSD), anxiety, fear, panic, substitution of other negative behaviors, worsening of underlying symptoms, and learned helplessness (becoming unable or unwilling to respond in any way to the ESD); and the devices present the physical risks of pain, skin burns, and tissue damage.
Because the medical literature likely underreports adverse events (AEs), risks identified through other sources, such as from experts in the field, State agencies that regulate ESD use, and records from the only firm that has recently manufactured and is currently using ESDs for SIB and AB demand closer consideration. As discussed in section II.A, these sources further support the risks reported in the literature and indicate that ESDs have been associated with additional risks such as suicidality, chronic stress, acute stress disorder, neuropathy, withdrawal, nightmares, flashbacks of panic and rage, hypervigilance, insensitivity to fatigue or pain, changes in sleep patterns, loss of interest, difficulty concentrating, and injuries from falling. In contrast to the state of the art for the treatment of SIB and AB, the risks of ESDs are unreasonable.
As discussed later in this document, FDA has determined that ESDs present a substantial and unreasonable risk of illness or injury and that the risks cannot be corrected or eliminated by labeling. Thus, FDA has decided to ban these devices under section 516 of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 360f). The proposed rule applies to devices already in distribution and use, as well as to future sales of these devices.
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What are SIB and AB, and how do they affect patients?
SIB and AB are among the most striking and devastating conditions associated with intellectual and developmental disabilities (Ref. 1). Individuals with such disabilities may exhibit destructive behavior that falls within two major categories, self-injury and aggression toward others or property. The most common forms of self-injury include head-banging, hand-biting, excessive scratching, and picking of the skin. The most extreme cases of persons with serious self-injurious behavior afflict an estimated 25,000 or more individuals in the United States (Ref. 2). These more extreme behaviors usually involve repeated, self-inflicted, non-accidental injuries producing, for example: (1) Bleeding, protruding, and broken bones; (2) eye gouging or poking leading to blindness; (3) other permanent tissue damage; and (4) swallowing dangerous substances or objects. (For a more detailed technical discussion, see Ref. 3.)
Persons who exhibit SIB also frequently demonstrate aggression, the other major category of destructive behavior. Aggressive behaviors encompass a wide range of behaviors, which are generally defined by conduct that, due to its intensity or frequency, presents an imminent danger to the person who demonstrates it, to other people, or to property (see, e.g., Ref. 4 for a discussion of aggression in autistic children). Aggressive behaviors that involve repeated physical assaults are dangerous particularly for caregivers and family. Beyond the potential for obvious physical injury, SIB and AB can be very distressing for parents and caregivers (Ref. 5), severely limit the patient's participation in community activities, and lead to placement of the patient in a more restrictive living environment (Ref. 6). Accordingly, intervention is necessary for the safety of the individual engaging in the aggressive behavior, for those against whom the aggression is directed, and for the protection of property.
The majority of published studies on SIB include aggression either as part of the description of the clinical spectrum of the behavior or as an inclusion criterion for the clinical study. Accordingly, this proposed rule addresses self-injury and aggression in tandem as SIB and AB. Destructive behavior in both major categories--aggression and self-
injury--are often present in individuals with intellectual or developmental disabilities. Examples of those disabilities include, but are not limited to: Autism spectrum disorder, Cornelia de Lange syndrome, Down syndrome, Fragile X syndrome, hereditary sensory neuropathy, Lesch-Nyhan syndrome, Rett syndrome, and Tourette syndrome. Those disabilities may also include visual impairment, severe intellectual impairment, and a variety of cognitive and psychiatric disorders.
Estimates of the prevalence of SIB in individuals with intellectual or developmental disabilities range from 2.6 percent to 40 percent (Ref. 7), or 2 to 23 percent in community samples (Ref. 8). More recently, one analysis found a prevalence of SIB in a clinical population of children with developmental disabilities at 32 percent, suggesting that the actual prevalence may be at the high end of earlier estimates (Ref. 9). Estimates of the prevalence of AB in individuals with intellectual or developmental disabilities range as high as 52 percent, though 10 percent is more commonly reported (Ref. 8). Thus, by conservative estimates, counting only individuals who have intellectual or developmental disabilities (and not all people who manifest SIB or AB), at least 330,000 people in the United States manifest SIB, AB, or both; less conservative estimates are much higher (see Refs. 3 and 8).\1\
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\1\ An estimated 1 to 3 percent of individuals in the United States have an intellectual or developmental disability (Ref. 8). Given a U.S. population of 330 million, at least 3.3 million people would have such a disability; 10 percent of 3.3 million is 330,000, and 2 percent of 3.3 million is 66,000. If there is no overlap, the total would be 396,000 people. These numbers are based on the lowest bounds reported in Ref. 8. Using the same source and method, the highest bound would yield an estimate of about 7.4 million people.
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What are ESDs and how do they affect SIB and AB?
As stated, ESDs apply a noxious electrical stimulus (a shock) to a person's skin upon the occurrence of a target behavior in an attempt to reduce or cease the behavior. As such, ESDs are a type of aversive conditioning device (``aversive''). ESDs apply shocks to the skin. ESDs are not used in ECT, sometimes called electroshock therapy, which is unrelated to this rulemaking. The electrical shock from an ESD is intended to interrupt the undesirable behavior and result in its quick cessation. Repeatedly pairing the shock with the unwanted behavior is intended to cause individuals to associate the two and thereby induce them to decrease the frequency of the behavior or stop it altogether. In order to achieve the intended results, the shock must be applied during the behavior (for cessation and decrease) or immediately afterward (for decrease). ESDs are intended to affect behavior in two ways: By interrupting the target behavior as an immediate response to the stimulus and, over time, through a conditioned reduction in the target behavior.
The main components of ESDs are an electrical stimulus generation module, electrodes, and a trigger switch. Either a remote monitor module or an automatic mechanism can trigger the electric shock to the individual. Typically, the patient carries the stimulus generation module, which applies an electrical current (the shock) to the individual's skin via electrodes. When a remote monitor is used, an observer determines when to apply an electrical shock to the patient and triggers a shock from a specific stimulus generation module via a radiofrequency signal. Alternatively, a sensor can detect certain unwanted behaviors and automatically activate the generation module. For example, an accelerometer attached to the head could detect head-
banging and, when the behavior is severe enough, trigger an electrical shock.
Although several factors specific to the patient affect shock perception, the key device output characteristics that most affect shock perception include: Electric current, voltage, skin resistance (or load), pulse width, shock duration, output frequency and waveform, electrode characteristics (e.g., size, location, design, or material), and the number and frequency of shocks delivered. For the purposes of this proposed rule, a stronger shock is one for which at least one of those parameters is adjusted to increase the intensity or sensation.
Electric current, measured in milliamperes (mA) for ESDs, is the primary variable for determining the effects of an electric shock that passes through the body. To determine the current output of a device designed to deliver a constant voltage, the voltage is divided by the electric resistance, measured in ohms (Omega), the relationship described by Ohm's Law. A lower resistance for a given voltage results in higher current; the skin's conducting resistance can vary between 1 kOmega and 100 kOmega (Refs. 10 and 11). Sweat and blood are excellent conductors and therefore lower the conducting resistance, which increases the current and the intensity of the stimulus.
The sensory nerves respond to the current as a function of its strength and duration. A stronger current will elicit a response with a shorter pulse width, and a weaker current will need a longer pulse width to elicit the same response. The pulse width (or pulse duration) is the length of time a pulse of current is applied to the skin, measured in milliseconds for ESDs. Longer pulse durations have been shown to increase the intensity or unpleasantness of the sensation in healthy subjects (Refs. 12-14).
The characteristics of the electrodes that deliver the shock to the skin also affect the perception of the shock. The amount of current delivered per unit area of an electrode is referred to as the current density. A higher current density has been found to correspond with a more intense or unpleasant feeling (Refs. 15 and 16). One study has shown that smaller electrodes deliver painful shocks that are described as sharp, cutting, or lacerating. Larger electrodes for the same current are associated with pain that was pinching, pressing, or gnawing (Ref. 16). A related measure, power density, is found by multiplying the current and the voltage and relating the product to surface area; it is expressed as watts per unit area. Both current and power densities correlate with the risk of burns; a higher current or power density increases the risk. The risk of burns also increases when the current itself is direct current; all FDA-cleared ESDs utilize alternating current (AC) rather than direct current (DC).
Electrodes additionally affect pain sensation in that placement on locations with a higher density of sensory nerves will result in more pain. For that reason, the hands, feet, genitals, underarms, torso, neck, and face will be particularly sensitive to shocks. Repeated shocks to the same location will also alter the perception, increasing intensity or pain (Refs. 17-19). The exact mechanism behind this change is unclear, but one hypothesis holds that the changing sensation may result from changes in the skin's electrical resistance (Ref. 19). Others have hypothesized that repeated stimulation depletes endorphins, which are chemicals that affect pain sensation (Ref. 17).
Finally, with regard to key device output parameters, some authors have attempted to relate physiological responses, sensations and muscle contraction for example, to electric current (e.g., Refs. 10, 11, and 20). The Judge Rotenberg Educational Center, Inc. (JRC), the only entity of which FDA is aware that has recently manufactured ESDs and that currently uses ESDs, has submitted a similar comparison (Ref. 21). However, comparisons based solely upon the electric current oversimplify the relationship because they do not account for other key parameters, nor do they account for intersubject variability in perception. (See, for example, Refs. 11, 17, 18, and 22-25). Such comparisons also do not account for the recipient's psychological state (Refs. 18, 22, and 23), which can affect the response to shocks. Furthermore, the relationships between current and response as reported by these authors (Refs. 10, 11, and 20) are more relevant in a setting where a body part comes into direct contact with a 60-Hz AC electrical source (e.g., a current from a wall outlet), with the current passing through the chest. In contrast, ESDs provide localized stimulation to the skin through an electrode interface. Thus, although the amount of current may suggest a type of response (e.g., tingling, pain, or involuntary muscle contraction), predictions based on such thresholds are subject to considerable uncertainty.
These key device output parameters affect the experience of the shock primarily in terms of physiological responses (see Ref. 3 for a more technical discussion). As explained in more detail in section II.A.1, a stimulus need not be physically intense to trigger an adverse psychological reaction. Thus, although lower peak current or shorter pulse duration corresponds with lower physical intensity, neither necessarily corresponds with a less-adverse psychological response. Table 1 summarizes the device output characteristics of ESDs for SIB or AB
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that have been cleared by FDA or are currently in use. Note that FDA has cleared 510(k)s for ESDs for SIB or AB from other manufacturers besides JRC.
Table 1--Device Output Characteristics
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Device name Average current Max current Max voltage Pulse width Shock duration Frequency Power density
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Whistle Stop 1............... ................ 10 mA at 20 200 V........... 1-2 ms.......... 0.5-12 s....... 10 Hz.......... 0.02 W/cm. 2
kOmega.
SIBIS........................ 3.5 mA at 20 10 mA........... 200 V........... 6.2 ms.......... 0.1-0.2 s...... 80 Hz.......... 0.16 W/cm. 2
kOmega.
GED, GED-3A 2................ 12 mA at 5 29.4 mA at 5 150 V........... 3.125 ms........ 2 s............ 80 Hz.......... 1.01 W/cm. 2
kOmega. kOmega.
GED-4 2...................... 42 mA at 5 90 mA........... ................ 3.125 ms........ 2 s............ 80 Hz.......... ...............
kOmega.
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\1\ The 510(k) did not include enough information for FDA to determine the average current of the device (as indicated by blank field).
\2\ The GED-3A and GED-4 have not been cleared or approved by FDA, and we do not have information about all device characteristics (as indicated by
blank fields).
Again, individual patient variability makes comparison across devices--and even individual shock applications--difficult. Some people are generally highly sensitive to current, experiencing involuntary muscle contraction from static electric shocks. On the other end of the spectrum, some individuals can draw a large static electric spark and hardly perceive it, much less experience a muscle spasm. Studies of subjects without intellectual or developmental disabilities have demonstrated a large range of intersubject variability for equally applied shocks. For example, one study found that the range of pain thresholds was 3.9 to 11.6 mA (Ref. 11), while another found the range was 0.45 to 2.4 mA (Ref. 25). Such articles often did not include key output characteristics, such as pulse width and frequency or electrode size and placement, further confounding attempts to compare or apply the findings. In light of variability and methodological limitations underlying the reported current-response relationships, physiological responses, including pain perception, are difficult to predict accurately, especially based solely on the current.
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How has FDA regulated ESDs in the past?
In 1979, FDA classified aversive conditioning devices as class II (see Sec. 882.5235 (21 CFR 882.5235)), which was consistent with the recommendation of the Neurological Device Classification Panel of the Medical Device Advisory Committee in 1978. Such devices may or may not use electric shocks to administer a ``noxious stimulus to a patient to modify undesirable behavioral characteristics'' (Sec. 882.5235). Thus, ESDs intended to treat SIB and AB are within the aversive conditioning device classification regulation. The proposed rule for classifying aversives, including ESDs, focused on the risks of: (1) Worsened psychological conditions, (2) errant electric shocks, and (3) the harmful or lethal nature of excess electric current or its inappropriate application (43 FR 55705, November 28, 1978). At the time, FDA and the panelists believed that performance standards could adequately assure the safety and effectiveness of aversives. We received no comments from the public on the proposed rule, and we issued the final rule classifying aversives as proposed at Sec. 882.5235 (44 FR 51726 at 51765, September 4, 1979).
FDA has cleared four devices for the treatment of SIB as substantially equivalent to the ones initially placed into class II, 510(k) notification numbers and clearance dates in parentheses:
Stimulator Sonic Control, ``Whistle Stop'' (K760166; July 20, 1976);
Self-Injurious Behavior Inhibiting System, ``SIBIS'' (K853178; February 28, 1986);
SIBIS Remote Actuator (K871158; May 29, 1987); and
Graduated Electronic Decelerator, ``GED'' (K911820; December 5, 1994).
A prescription is required for each, meaning that Federal law restricts the sale of these aversives to professionals licensed according to State requirements or those acting pursuant to a licensed professionals orders (see 21 CFR 801.109).
As part of the evaluation of the premarket notifications, i.e., the 510(k) submissions, FDA reviewed the average current (the amount of electricity) and power density of the shocks (the wattage applied to a given area of skin), among other things. Average current and power density are important parameters in determining the likelihood and severity of a potential physical injury from a shock. The cleared ESDs include warnings never to place electrodes on the head or chest, or in such a way that current would flow through the chest because this could cause ventricular fibrillation (a dangerous irregularity in the heartbeat).
We are aware of only one manufacturer, JRC, that has recently manufactured ESDs and that currently uses ESDs, including devices that we have not previously cleared. JRC uses these devices because it is also a residential facility, and its employees apply the devices to individuals there. In 2000, FDA incorrectly notified JRC that it qualified for exemption from registration and 510(k) requirements under 21 CFR 807.65(d). Once FDA recognized its error, FDA sent JRC an Untitled Letter on May 23, 2011, and a Warning Letter on December 6, 2012, for violations related to the lack of FDA clearance or approval for the modified GED devices.\2\
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\2\ The Warning Letter is available on the Internet at http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm331291.htm.
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FDA now has a better understanding of the risks and benefits presented by these devices than it did 36 years ago when these devices were classified, and, as discussed later in sections II.A and II.B, the state of the art for the treatment of SIB and AB has progressed significantly over that time period. As a result, FDA now believes that the risk of illness or injury from the use of ESDs for the treatment of SIB and AB is unreasonable and substantial.
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Scope of the Ban
The ban would apply to devices that apply a noxious electrical stimulus to a person's skin to reduce or stop aggressive or self-
injurious behavior. (See section I.B for a discussion of the relevant behaviors; see also Ref. 3 for a more technical discussion of the scientific literature regarding these behaviors.) To FDA's knowledge, the only such devices that are currently in use are two models of the GED device (the GED-3A and GED-4), neither of which has been cleared or approved by the Agency.
The ban would not apply to ESDs used to create aversions to other conditions or habits, such as smoking. Although other ESDs have parallels in
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treatment strategy and method, those devices address very different conditions in very different patient populations. Smoking-cessation devices differ with respect to whether patients have control over the shocks--and what level of control they have--as well as how the electric shock affects the target behavior and underlying conditions. These differing types of ESDs thus present different benefit-risk profiles.
Importantly, individuals who manifest SIB or AB typically have additional vulnerabilities that relate directly to the risks of the treatment method. For example, individuals with intellectual or developmental disabilities who manifest SIB or AB, and who have difficulty communicating pain or other harms that may be caused by ESDs would bear a higher risk of injury from the shock than smokers who choose to use an ESD to help quit smoking. Those smokers, if without intellectual or developmental disabilities, can immediately communicate pain to the device's controller or remove the device themselves. They can communicate symptoms of other harms that may be caused by ESDs, such as PTSD, to their health care provider, which may lead to discontinuation of the device's use. Communication challenges in patients who suffer from SIB and AB are discussed in the literature, were raised by the advisory panel, and are reviewed in more detail in section II.A.
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Legal Authority
Section 516 of the FD&C Act authorizes FDA to ban a device intended for human use by regulation if it finds, on the basis of all available data and information, that such a device ``presents substantial deception or an unreasonable and substantial risk of illness or injury'' (21 U.S.C. 360f(a)(1)). A banned device is adulterated under section 501(g) of the FD&C Act (21 U.S.C. 351(g)), except to the extent it is being studied pursuant to an investigational device exemption under section 520(g) of the FD&C Act (21 U.S.C. 360j(g)). This proposed rule is also issued under the authority of section 701(a) of the FD&C Act (21 U.S.C. 371(a)), which provides authority to issue regulations for the efficient enforcement of the FD&C Act.
In determining whether a deception or risk of illness or injury is ``substantial,'' FDA will consider whether the risk posed by the continued marketing of the device, or continued marketing of the device as presently labeled, is important, material, or significant in relation to the benefit to the public health from its continued marketing (see Sec. 895.21(a)(1) (21 CFR 895.21(a)(1))). Although FDA's device banning regulations do not define ``unreasonable risk,'' in the preamble to the final rule promulgating 21 CFR part 895, FDA explained that, with respect to ``unreasonable risk,'' it ``will conduct a careful analysis of risks associated with the use of the device relative to the state of the art and the potential hazard to patients and users'' (44 FR 29214 at 29215, May 18, 1979; Ref. 25a). The state of the art with respect to this proposed rule is the state of current technical and scientific knowledge and medical practice with regard to the treatment of patients exhibiting self-injurious and aggressive behavior.
Thus, in determining whether a device presents an ``unreasonable and substantial risk of illness or injury,'' FDA analyzes the risks and the benefits the device poses to individuals, comparing those risks and benefits to the risks and benefits posed by alternative treatments being used in current medical practice. Actual proof of illness or injury is not required; FDA need only find that a device presents the requisite degree of risk on the basis of all available data and information (H. Rep. 94-853 at 19; 44 FR 28214 at 29215).
Whenever FDA finds, on the basis of all available data and information, that the device presents substantial deception or an unreasonable and substantial risk of illness or injury, and that such deception or risk cannot be, or has not been, corrected or eliminated by labeling or by a change in labeling, FDA may initiate a proceeding to ban the device (see Sec. 895.20). If FDA determines that the risk can be corrected through labeling, FDA will notify the responsible person of the required labeling or change in labeling necessary to eliminate or correct such risk (see Sec. 895.25).
Section 895.21(d) requires this proposed rule to briefly summarize:
The Agency's findings regarding substantial deception or an unreasonable and substantial risk of illness or injury;
the reasons why FDA initiated the proceeding;
the evaluation of the data and information FDA obtained under provisions (other than section 516) of the FD&C Act, as well as information submitted by the device manufacturer, distributer, or importer, or any other interested party;
the consultation with the classification panel;
the determination that labeling, or a change in labeling, cannot correct or eliminate the deception or risk;
the determination of whether, and the reasons why, the ban should apply to devices already in commercial distribution, sold to ultimate users, or both; and
any other data and information that FDA believes are pertinent to the proceeding.
We have grouped some of these together within broader categories and addressed them in the following order:
Evaluation of data and information regarding ESDs, including data and information FDA obtained under provisions other than section 516 of the FD&C Act, information submitted by the device manufacturer and other interested parties, the consultation with the classification panel, and other data and information that FDA believes are pertinent to the proceeding, with respect to risks, benefits, and the state of the art;
the reasons FDA initiated the proceeding and FDA's determination that ESDs for SIB and AB present an unreasonable and substantial risk of illness or injury (FDA has not made a finding regarding substantial deception);
FDA's determination that labeling, or a change in labeling, cannot correct or eliminate the risk; and
FDA's determination that the ban applies to devices already in commercial distribution and sold to ultimate users, and the reasons for this determination.
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Evaluation of Data and Information Regarding ESDs
In considering whether to ban ESDs, FDA first conducted an extensive, systematic literature review to assess the benefits and risks associated with ESDs as well as the state of the art of treatment of patients exhibiting SIB and AB. In the literature review, as explained earlier, SIB and AB were considered in tandem, and these conditions presented in individuals with intellectual and developmental disabilities, such as autism spectrum disorder, Down syndrome, Tourette syndrome, as well as other cognitive or psychiatric disorders and severe intellectual impairment (including a broad range of intellectual measures). The studies encompassed both children and adults. (For more technical details, see Ref. 3.)
FDA next convened a meeting of the Neurological Devices Panel of the Medical Devices Advisory Committee (``the Panel'') on April 24, 2014 (``the Panel Meeting''), in an open public forum, to discuss issues related to FDA's consideration of a ban on ESDs for SIB and AB (see 79 FR 17155, March 27, 2014; Ref. 26). Although FDA is not
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required to hold a panel meeting before banning a device, FDA decided to do so in the interest of gathering as much data and information as possible, from experts in relevant medical fields as well as all interested stakeholders, before proposing this significant regulatory action. Eighteen panelists with expertise in both pediatric and adult patients represented the following biomedical specialties: Psychology, psychiatry, neurology, neurosurgery, bioethics, and statistics, as well as representatives for patients, industry, and consumers (Ref. 27). FDA provided a presentation that described the banning standard, the regulatory history of aversive conditioning devices, alternative treatments, and a summary of the benefits and risks of ESDs, including a comprehensive, systematic literature review based on the information available at that time (Refs. 3 and 28). After the Panel Meeting, we reviewed all 294 comments from 281 unique commenters submitted to the public docket created for the Panel Meeting (Docket No. FDA-2014-N-
0238).
FDA considered all available data and information from a wide variety of sources, including from the categories listed in this document. In weighing each piece of evidence, FDA took into account its quality, such as the level of scientific rigor supporting it, the objectivity of its source, its recency, and any limitations that might weaken its value. Thus, for example, we generally gave much more weight to the results of a study reported in a peer-reviewed journal than we did to non-peer-reviewed papers.
The scientific literature. FDA considered published scientific sources to understand SIB and AB as well as the risks and benefits of ESDs and the state of the art for the treatment of challenging behaviors. However, several limitations influenced the conclusions drawn from the literature, including the likely underreporting of AEs, reporting biases, and various methodological weaknesses.
Information and opinions from experts, including those expressed by the panelists at the Panel Meeting, as well as those expressed in individual expert reports obtained by FDA from Drs. Tristram Smith, Gary LaVigna, and Fredda Brown. Each of these experts has experience in the field of behavioral psychology, particularly with individuals who manifest SIB or AB. Drs. LaVigna and Brown have expertise regarding the state of the art for treatment of SIB and AB and the development of positive behavioral treatment plans for patients, including for transition away from ESDs and other aversive strategies. FDA obtained reports from these experts to supplement our understanding of the risks and benefits of ESDs and the state of the art for the treatment of SIB and AB.
Information from State agencies and State actions on ESDs. FDA has considered information regarding the use of ESDs for SIB and AB from agencies in Massachusetts and New York. These agencies possess substantial information on ESDs for SIB and AB because the overwhelming majority of patients--nearly 75 percent--on whom ESDs are used are from these two States. According to information provided by JRC in its comments, 60 of the 82 individuals enrolled at JRC as of April 2014 on whom GED devices were used are from these two States. FDA also considered a comment from the Executive Director of the National Association of State Directors of Developmental Disabilities Services (NASDDDS), which was supportive of a ban, and various State legal actions related to the use of ESDs for SIB and AB.
Information from the affected manufacturer/residential facility. In addition to presenting information at the Panel Meeting and responding to questions from Panel members, JRC has made several submissions to the Panel Meeting docket, as has a former JRC clinician.
Information from patients and their family members. Three individuals formerly on ESDs at JRC and family members of four such individuals currently at JRC spoke against a ban at the Panel Meeting. Two associations of family members of such individuals submitted comments opposing a ban (one of the comments included 32 letters from family members). Two individuals formerly on ESDs at JRC spoke in favor of a ban at the Panel Meeting, and one other individual submitted a comment in favor of a ban. In 2013 and 2014, FDA clinicians interviewed three individuals formerly on ESDs at JRC by phone (one of whom spoke in favor of a ban at the Panel Meeting).
Information from other stakeholders, including other government entities, disability rights groups, and members of the public. In addition to NASDDDS and a JRC parents group, referenced earlier, 15 other organizations concerned with the treatment and the rights of individuals with disabilities spoke at the Panel Meeting, all of which supported a ban. Twenty-two disability rights organizations submitted written comments to the Panel Meeting docket, one of which was signed by 23 disability rights groups. Nine of these organizations were among the 15 represented at the Panel Meeting. All of these comments support the ban. FDA also received a comment from the U.S. Department of Justice Civil Rights Division supportive of a ban, and we considered information from the National Council on Disability, the National Institutes of Health, and the United Nations Special Rapporteur on Torture.
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Risks of Illness or Injury Posed by ESDs
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Scientific Literature
FDA conducted an extensive, systematic review of the medical literature for harms, i.e., AEs, associated with ESDs to understand specific risks and dangers that ESDs present to individuals' health. As previously discussed, the focus of the analysis in considering a ban is on risks and does not require proof of actual harm, but evidence of actual harms helps inform the analysis. One prospective case-control study and one retrospective chart review of 60 patients reported AEs (Refs. 29 and 30, respectively). Additionally, 26 case reports or series encompassing 66 subjects included an assessment of AE occurrences. Ten other case reports or series did not assess AEs, and 6 articles, encompassing 11 subjects in total, noted that the researchers did not observe AEs in their subject population. (See table 4 in Ref. 3 for a summary of articles reviewed for adverse events.) We identified the following AEs in the literature.
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Psychological risks. The risks of psychological harm are less tightly linked to the electrical parameters of an ESD shock than are physical risks (section I.C discussed shock parameters and how they relate to the physical response). For example, when the recipient does not have control over the shocks and has previously received multiple such shocks, psychological trauma such as an anxiety or panic reaction can result even when the strength is relatively modest (Ref. 31). In this example, the shock does not necessarily need to be stronger to increase the risk of psychological trauma; it need only recur. Similarly, the shock need not be painful; it need only be psychologically stressful.
Further, a series of less traumatic events can cause the development of stress disorders such as PTSD. The underlying trauma need not be a single, discrete event, although a single trauma can lead to PTSD (Ref. 32; see also Ref.
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31, discussing research on stressors prior to the 2013 update of the Diagnostics and Statistical Manual of Mental Disorders). Shocks that may be tolerable on their own could, in series, amount to a traumatic experience leading to a stress disorder. (See Ref. 33 discussing impaired cue-reversal independent of level of trauma.) In turn, such disorders can leave an individual susceptible to future traumas such as anxiety reactions that can be triggered by a relatively weak stimulus. For example, a provider reaching for an ESD remote control can trigger an anxiety response in individuals wearing ESDs, even without a shock. Thus, although a shock may need to surpass a minimum subjective threshold to be harmful (e.g., the shock needs to be sufficiently stressful to the recipient), that subjective minimum (what is sufficiently stressful) does not correspond with a particular objective minimum (shock parameters).
Several articles reported aversion, fear, and anxiety in response to ESDs. One article states that ESDs may initially evoke fear, panic, and even aggression responses (Ref. 34). For the most part, researchers have interpreted these events as anticipatory responses prior to or upon stimulus application. In addition to reports of panic and bouts of aggression, others have reported events such as screaming, crying, or shivering upon device application; grimacing; flinching; perspiring; and escape behavior (Refs. 34-43). One article reported a temporary aversion to the experimenter (Ref. 36). Such fear, anxiety, or panic reactions are additionally concerning because when they cause the individual to sweat, they would lead to electrical conductivity changes across the skin that increase the intensity of the electric shock.
Other articles report substitution of behaviors--negative or collateral--that span a range of severity. One author speculated that, in institutional settings, ``the probability that a replacement behavior will be undesirable is quite high'' (Ref. 44). Some patients ``froze by refraining from showing any sort of behavior'' (Ref. 34). Similarly, others reported a ``pseudocatatonic sit-down,'' i.e., muscular freezing or melting (Ref. 45). One study described temporary tensing of the body and noted attempts to remove the device or grab the transmitter during treatment (Ref. 30). Some patients resorted to hostility and retaliation (Ref. 46), including surrogate retaliation, threats, and warnings (Ref. 45). In some patients, another undesirable behavior known as self-restraint, where patients attempt to physically restrain themselves, for example, with their clothing, emerged or intensified (Refs. 29 and 47). Others exhibited lesser self-injury and aggression, non-injurious pinching, emotional behaviors, and napkin-
tearing. (See also Refs. 30 and 43.) In some cases, crying increased (Ref. 48). One study reported that, as measured by rating scales of dependency, affection-seeking increased repeatedly during treatment (Ref. 42).
Temporary or long-term increases in symptoms have also been attributed to ESDs in the literature. One article reported increases in emotionality and the frequency of self-injury, as well as post-
treatment incontinence (Ref. 49). Another observed increasing episodic ``bursts'' of self-injury, eventually reaching the point that extended treatment with the ESD became impossible to maintain (Ref. 50).
Some ESDs have been used for conditions other than SIB and AB, e.g., obsessions or compulsions, according to the same principle of aversive conditioning. FDA believes that reports of AEs from these alternative uses are informative regarding the risks of ESDs for SIB and AB because individuals with ESDs for other conditions generally do not have the same patient vulnerabilities that often accompany SIB and AB. As discussed in sections II.A.2 and A.3, these vulnerabilities generally increase the risk of harm from ESDs for individuals who manifest SIB or AB, so any harms from ESDs for other uses would be at least as likely, if not more so, to cause harm to many patients exhibiting SIB or AB.
One article on the effects of shock on five subjects to reduce obsessions and compulsions reported that one subject demonstrated anxiety and psychotic delusions (Ref. 51). One case-control study on ESDs used to treat alcohol dependence in 12 subjects found that symptoms of experimental repression, such as headaches, restlessness, and mild dysphoria, were common and appeared usually within 3 or 4 days of the treatment (Ref. 52). Another researcher performed a prospective study of ESDs used for smoking cessation in 14 subjects. The author reported that seven subjects exhibited mild transient depression (Ref. 53). FDA acknowledges that confounding factors potentially contributed to these AEs.
Since ESDs are aversive conditioning devices, FDA also considered AEs associated with aversive conditioning more generally. We identified 12 review articles examining AEs associated with punishment or aversive conditioning. Many of the reviews acknowledge the possibility of negative emotional reactions associated with punishment in general, such as fear or avoidance (Refs. 54-59) and anxiety and depression (Ref. 54). Some reviews, similar to the findings specific to ESDs, noted AEs that include retaliation, increased aggression, or substitution of one injurious behavior for another (Refs. 54 and 57-
60).
FDA believes that the risks posed by another type of device that delivers a shock to the patient are instructive. Specifically, a comparison to implantable cardioverter defibrillator (ICD) devices further supports the potential for certain psychological risks in patients receiving shocks from ESDs for SIB and AB. While the strength and purposes of the shock differ significantly between ICDs and ESDs, the psychological risks posed by ESDs do not necessarily depend on the strength of the shock, as discussed earlier, and FDA does not believe the different purposes of the shocks undermine the comparison for the following reasons. Treatment with either of these devices entails several similar characteristics that support a comparison, including the lack of patient control over the shocks, the application of multiple shocks, and the startling or unpleasant nature of the shocks. We found that fear of future shocks, in particular, is a trauma that is shared for both the ICD and ESD populations, unlike other trauma experiences in which subsequent trauma (repetition of the experience) is unlikely, indicating that ongoing application worsens the harm (Ref. 61).
The following risks have been reported in the literature for ICDs: The development of PTSD, acute stress disorder, a shock stress reaction (a temporary condition), learned helplessness, depression, and anxiety (Refs. 61-63). A contributing factor in the development of these harms in patients with an ICD may be that treatment with an ICD may act as a constant reminder of the underlying life-threatening disease condition (Ref. 64). A 2011 report observed that ``the available research literature can only provide a limited view of whether ICD shock or the potentially life-threatening arrhythmic condition is the primary driver of a PTSD presentation'' (Ref. 61). However, Sears and Conti report that ``shock is the major distinguishing factor between patients with ICDs and general cardiac patient populations'' (Ref. 63), meaning that the presence of an ICD, rather than the underlying cardiac condition, increases the psychological risks. Other authors have reported that ICD shocks may cause distress either from the associated pain, skeletal muscle contraction, and nerve
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stimulation or merely from fear of shocks (Ref. 62).
Because of the similar characteristics of the shocks delivered by ICDs and ESDs, and because the identified risks may be attributable to the ICD shock itself, as opposed to the fear of a life-threatening condition, the risks of development of PTSD or a shock stress reaction, learned helplessness, depression, or anxiety may also exist when shocks are applied by ESDs in patients with SIB or AB. FDA notes that due to the drastically different intended uses, patient populations, benefit-
risk profiles, and state of the art for these devices, FDA is not considering banning ICDs.
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Physical risks. Research shows that shock strength and other device characteristics play a role in shaping the physical response to ESDs, such as whether the patient receives burns or experiences pain (see section I.C). We note that the lack of complete information regarding shock characteristics in much of the literature can make it difficult to determine to which ESDs these findings are applicable.
The literature contains many reports of tissue damage or burns from ESDs. Reports of skin damage ranged from burns to bruises to slightly reddened or discolored areas. In all such reports, the effects were temporary (Refs. 29, 30, 39, 41, 50, and 65).
Given that ESDs achieve their intended effects by causing an aversion with an electric shock, it is not surprising that researchers have reported experiencing or observing pain upon ESD application to themselves or their patients. For example, one experimenter stated that he definitely felt pain when he applied the ESD to himself. He described it like a dentist drilling on an un-anesthetized tooth, but the pain terminated when the shock ended (Ref. 36). Another report observed pain upon stimulation by the ESD (Ref. 35), and another observed a tremor in the thigh (Ref. 36). Although ESDs are intended to apply an aversive stimulus, and any pain that results from ESDs may cause an aversive reaction, pain is nonetheless a harm that should be considered in our analysis of risks posed by the device.
Finally, two articles reported misapplication or device failure (Refs. 39 and 65). In such cases, there is a risk that any of the harms discussed in this section may occur but without any possibility of benefit.
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Likely Underreporting of AEs
The Agency's analysis indicates that the medical literature suffers from some significant limitations and has likely underreported AEs associated with ESDs for a number of reasons. Perhaps most importantly, the devices have been studied only on a very small number of subjects, many of whom would have difficulty communicating or otherwise demonstrating AEs and injuries. The bulk of the articles describe case reports or series, employing only retrospective reviews of clinical experience, not prospective studies. Further, most of the research articles were published in the 1960s and 1970s, before significant advances in the ability to diagnose and classify psychological AEs such as PTSD. The dated nature of most of the research also means it did not adhere to modern standards for AE monitoring. Simply put, researchers likely did not report AEs because they had not planned to study them separately. None of the articles on the application of ESDs described an attempt to assess AEs systematically, and many articles did not state whether the authors attempted to assess AEs at all. Finally, researcher bias also may have contributed to underreporting of AEs.
As noted, the literature review suggests some subjects' difficulty with reporting AEs due to the subjects' disability likely hindered any assessment of AEs, particularly psychological AEs. Since SIB and AB often present in individuals with cognitive, intellectual, or psychiatric conditions, SIB and AB affect many individuals with diminished communication abilities. Patients who exhibit SIB or AB may not offer--or providers may not recognize--feedback indicating injuries from misfires or other erroneous applications of ESDs. For example, conditions such as an autism spectrum disorder may impair expressions of pain (see Ref. 66 for a discussion of pain sensitivity and expression in autistic individuals). In such a case, an AE could go unrecognized because the provider does not understand the individual's response, if any.
Worse, some individuals' impaired ability to communicate, express themselves, or associate cause and effect, coupled with the difficulty providers may have in distinguishing underlying symptoms from negative effects of ESDs, compounds the dangers posed by these devices. This is because individuals' impairments with communication or stimulus association may prevent the individuals and their health care providers from mitigating or avoiding both physical and especially psychological harms. (See section II.C.1 for a discussion of interventions that do not rely on stimulus association.) In such circumstances, ESDs are riskier than for other patients on whom ESDs are used.
For the reports of AEs that do exist, many of those researchers published during the 1960s and 1970s, an era when conceptions of disease and how a person's physiology may affect or cause disease, i.e., pathophysiology, differed significantly from current medical science, particularly psychiatric pathophysiology. As a result, those researchers may have interpreted pathological processes differently. For instance, they may not have recognized certain currently accepted disease processes like acute and posttraumatic stress. Some researchers did not report pain or discomfort as AEs since they were considered the ESDs' intended result and indicators of effectiveness. (See, e.g., Refs. 44 and 57). In short, because science has advanced since much of the AE reporting, FDA believes existing AE reports in the literature are likely not comprehensive by current scientific and clinical reporting standards.
The Agency's analysis also suggests the possibility of bias against reporting AEs. As previously noted, the majority of articles did not define a systematic method for assessing AEs. In one review, the authors concluded that there was no evidence associating AEs with ESDs (Ref. 67). However, the authors went on to opine, ``in light of the intrusive nature of shock treatment, it is puzzling that so few negative side effects have been reported. In interpreting the existing literature, we might be wise to consider the possibility that some investigators have been predisposed to see only the positive side effects.'' Similarly, the reports of treatment relapse in the literature may not reflect the actual prevalence in clinical settings because such cases are less likely to be submitted or accepted for publication (Ref. 59).
Potential bias against AE reporting might also have influenced the authors of the article that included the largest group of individuals (60) subject to ESD application in its retrospective review. The review noted only one negative side effect, ``temporary discoloration of the skin that cleared up in a few minutes or days'' (Ref. 30). However,''temporary emotional behaviors, a temporary tensing of the body, or attempts to remove the device or grab the transmitter noted during treatment were classified as 'immediate collateral behavior' and were not considered adverse events'' (Ref. 30). The lead author of this article, Dr. Matthew Israel, may also have been biased in his roles as founder of JRC and Chief Executive
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Officer of JRC at the time he co-wrote the article.
In light of the foregoing, FDA believes that researchers, by current clinical and peer-review standards, likely underreported AEs. Many patients on whom ESDs have been used have limited ability to express themselves. Some earlier studies considered certain reactions that we would now consider to be AEs as mere responses or even treatment requirements. Even current researchers may classify AEs as unwanted side effects that then go unreported. For example, of the 66 patient case histories spanning 1991 through 2014 that FDA received from JRC, none reported any AEs, which is highly unusual for so many patients over such a long time (though individual exposure periods varied). Nor did any of these case histories include systematically defined methods for short- or long-term AE monitoring. Thus, even the more recent studies may still reflect outmoded standards. Significantly, because much of the relevant literature was published many years ago, it does not benefit from recent advancements in psychiatric pathophysiology that have expanded researchers' ability to identify and record AEs. In light of the foregoing, we conclude that realized risks and dangers to individuals' health from ESDs are likely greater than reported in the medical literature. As a result, the risks posed by ESDs reported by other sources, discussed in the following sections, warrant careful consideration.
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Information and Opinions From Experts
FDA presented the following dangers to individuals' health related to the use of ESDs at the Panel Meeting: Negative emotional reactions or behaviors, including aggression; burns and other tissue damage; anxiety; acute stress, or PTSD; fear and aversion or avoidance; pain or discomfort; depression and possible suicidality; psychosis; and neurological symptoms and injury. The panelists generally opined that the list was incomplete, and in some cases, too vague and in need of clarification (see Ref. 68).\3\
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\3\ Unless otherwise noted, all references to statements and opinions expressed at the Panel Meeting are taken from Ref. 68.
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One panelist noted peripheral nerve injury as a possible side effect and was surprised JRC had not reported severe depression, especially since ``producing pain in people who have no control over the pain'' is ``a perfect paradigm for the learned helpless,'' and learned helplessness is used in drug studies ``because it produces in animals something analogous to depression and it can be used to test antidepressants.''
Another panelist stated that cardiac effects, renal effects, muscle damage, and neurological symptoms, such as neuropathy, could be happening at low levels but go unreported because there has not been a systematic look at these types of potential injury over the last 40-50 years.
Other panelists recommended specific additions and refinements to the list of risks and dangers, including: Equipment malfunction; long-
term effects of pain; delineation of range of pain; trauma from falls; mistrust of providers; learned helplessness; chronic stress; generalized behavioral suppression; small, repetitive damage of other tissues; cognitive impairment; neuropathy; ventricular fibrillation if the electrodes are placed transthoracically; neuropsychiatric symptoms; and emotional sequelae.
Several Panel members echoed the concerns discussed earlier regarding the likelihood of underreporting of AEs. For example, one Panel member pointed out that the populations treated with ESDs are very vulnerable and may not be able to self-report AEs. Panelists also indicated that because clinicians have little understanding of the breadth and the range of pain experienced by ESD patients, clinicians may mistakenly attribute adverse effects to the patients' cognitive, intellectual, or psychiatric conditions rather than to the device. Some panelists observed that many of the risks and dangers of ESDs resemble co-morbidities in the individuals subject to treatment; as a result, adverse effects of the device would be difficult to distinguish from symptoms of the disability. This could result in AEs being misperceived as underlying symptoms, the likelihood of which is supported by the lack of systematic evaluation of AEs in the literature discussed in section II.A.2. Panel members similarly expressed concerns about communication and diagnosis difficulties exacerbating the harms experienced by patients on whom ESDs are used.
In his expert report, Dr. Smith explains that ESDs for SIB or AB ``necessarily involve inflicting pain on a person with an intellectual or developmental disability,'' and notes the risks of fear and agitation observed in one study. Dr. Smith details several limitations to the studies on ESDs in the literature, including the failure of any of the studies to have a prespecified, systematic plan for monitoring AEs, which may have resulted in underreporting of AEs. He also discusses the possibility that the publication process may also introduce a bias against reporting AEs in the retrospective single-
patient studies relied on by many researchers of ESDs. This is because, according to Dr. Smith, when studying only one patient, researchers tend to emphasize data that epitomize experimental control rather than an average response to the device (Ref. 8). Further, researchers generally tend to publish clear-cut results rather than less-clear outcomes (Ref. 8). Although he notes that the ``overall strength of evidence is low'' with respect to both benefit and harm, Dr. Smith concludes that ``existing evidence shows that aversive conditioning with electric shock can be safe and effective in at least some cases, but that it can also be misapplied, risking severe, negative consequences'' (Ref. 8).
A comment submitted by the Disability Law Center includes a 2014 expert affidavit from Dr. James Eason, a university instructor of biomedical engineering with a Ph.D. in biomedical engineering and a B.S. in electrical engineering who has particular expertise on ICDs (Ref. 69, attachment 2). Dr. Eason opines on the potential hazards posed by three ESDs: The SIBIS (cleared by FDA in 1986), the GED-1 (cleared by FDA in 1994), and the GED-4 (not FDA cleared or approved). Focusing on peak current, based on his views on the relationship between certain electrical stimulus parameters and pain, Dr. Easton compares the SIBIS (4.1 mA), GED-1 (30 mA), and GED-4 (90 mA), with an electrical fence (4 mA), a dog training collar (2-4 mA), and a cattle prod (10 mA), respectively.
Dr. Eason opines that, when applied to non-sensitive locations such as the arm or leg, the SIBIS shock falls below the range usually considered painful; the GED-1 shock falls within the range of pain thresholds, meaning some would find it painful and some may not; and the GED-4 shock would be painful or extremely painful to anyone. According to Dr. Eason, when the electrodes are placed on sensitive parts of the body, such as hands, feet, underarms, torso, or neck, all three ESDs are capable of inflicting extreme pain on anyone. Dr. Eason explains that sweating, which may be caused by stress or anxiety about receiving a shock, lowers skin resistance, which in turn may lower one's pain threshold, and that one's pain threshold may also be lowered by repeated shocks. He further concludes all three devices are capable of producing tissue damage due to strong muscle contractions, and all are capable of causing superficial skin burns under certain circumstances.
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Dr. Eason also concludes that the ESDs ``are likely to induce an immediate increase in physiological stress ranging from mild to severe. Further, the long-term effects of receiving numerous painful and uncontrollable shocks will be an increased risk for developing ASD or PTSD.'' His conclusion is based partly on observations of people who have ICDs, which have been shown to induce psychological trauma, including PTSD, as discussed in section II.A.1. Finally, Dr. Eason believes the GED-4 presents a risk of heart palpitations, long-term psychological disorders, and neurological effects.
Dr. Eason's expert opinion is consistent with other available data and information demonstrating that ESDs can be painful, particularly when placed on sensitive areas, and that physiological and psychological factors contribute to the experience of pain. However, as explained in section I.C, because an individual's experience of pain varies significantly based on many factors, pain predictions based on peak current are subject to considerable uncertainty. As such, although higher peak currents correspond to greater risks of physical illness or injury, the peak current is but one factor in an individual's experience. Similarly, pain is but one risk of physical harm that ESDs pose. The devices pose serious risks of other short- and long-term psychological and physical harms, as discussed in the literature and at the Panel Meeting.
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Information From State Agencies and State Actions on ESDs
FDA reviewed complaints regarding ESD use made to the Massachusetts Disabled Persons Protection Committee (DPPC) from August 30, 1993, to July 28, 2013. Of 53 complaints, DPPC screened out 18 as not meeting complaint criteria; DPPC found 22 more were unsubstantiated. The remaining 13 complaints described the following AEs: Burns or tissue injury (6 reports), inappropriate device use (3 reports), negative emotional reactions (3 reports), and PTSD (1 report).
In 2007, the Massachusetts Department of Early Education and Care (DEEC) conducted an investigation of JRC's Stoughton Residence, where GED devices were used on individuals living there (Ref. 70). According to the Investigation Report, an individual reported waking up because his roommate was screaming; his roommate had been asleep but was shocked by a GED, waking him and causing him to scream. JRC staff reported that ``the skin was off of the area'' of the leg where GED shocks had been applied, that the GED was removed from the leg ``because the area on was too bad to keep the device,'' and either the individual who received the shocks or the staff (it is not clear who) believed a stage two ulcer was in the area where skin was missing (Ref. 70).
In 2006, the New York State Education Department (NYSED) conducted an onsite review of JRC's behavior intervention programs, with purposes including identification of any health and safety issues relating to JRC's use of aversive interventions (Ref. 71). The review was conducted by NYSED staff and three behavioral psychologists serving as independent consultants. It included a review of school policies, student records, observations of school and education programs, and interviews with staff and randomly selected individuals living at JRC. The reviewers witnessed staff rotating GED electrodes on individuals' bodies at regular intervals to ``prevent burns that may result from repeated application of the shock to the same contact point'' (Ref. 71).
During interviews, individuals reported ``pervasive fears and anxieties related to the interventions used at JRC,'' which include other interventions in addition to the GED devices. Although not reported as relating specifically to GED use, one patient stated she felt depressed and fearful, that her greatest fear was having to stay at JRC past her 21st birthday, and that she thought about killing herself every day. The review notes various other potential negative effects that may result from aversive behavioral strategies, such as depression, social withdrawal, aggression, and worsening of PTSD symptoms in individuals diagnosed with PTSD, though it did not report any specific instances of these adverse effects related to GED use.
NYSED also submitted a comment to the 2014 Panel Meeting docket stating that it has received reports of collateral effects from the use of these devices, such as increases in aggression and increases in escape behaviors or emotional reactions. NYSED states it has received ``numerous reports of students who have incurred physical injuries (burns, reddened marks on their skin) as a result of being shocked and for whom parents and students themselves have reported short-term and long-term trauma effects as a result of use of such devices or watching other students being shocked (e.g., loss of hair, loss of appetite, suicidal ideation).'' NYSED believes it is well established that stress and trauma impair brain functioning. According to NYSED, one student explained, ``I am scared and sometimes I feel like my life is in danger. There are days when I am scared to even say a word to anyone. I am afraid to wake up because I never know what is going to happen to me. I think I should not have to live in fear and be scared . . . I get so depressed here I wish my life by fast'' (Ref. 72).
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Information From the Affected Manufacturer/Residential Facility
JRC acknowledges the risk of physical harms to the skin, that ``in rare cases, mild erythema of the skin may result'' that disappears within an hour to a few days, ``less than 1% of applications result in
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