commenter explains that current would have to be applied across the
brain to induce seizures, FDA notes that the biochemical pathways that
contribute to seizures are not well understood. As such and given the
dearth of research on the effects of ESDs, FDA continues to regard
seizures as a possible additional risk, but we agree that this is not a
well-established risk. Since we weighed the evidence in part according
to its source and the degree of support in the scientific literature,
we did not accord this information significant weight, and it does not
significantly affect our evaluation of the benefit-risk profile of ESDs
for SIB or AB.
    With regard to the evidence of the risk of heart palpitations, FDA
believes the evidence is somewhat stronger but acknowledges the risk
also has not been well studied. The commenter describes the manner in
which electrodes would have to be placed on the skin in order to cause
palpitations as a direct result of electric current flowing through the
heart. He states that, because ESD electrodes are not arranged in that
way, individuals subject to ESDs should not experience palpitations. In
contrast, an individual who was subject to ESDs and an expert in this
field have opined that the use of one model of ESD, a GED, presents a
risk of heart palpitations to the patient (Ref. 15 at 63; Ref. 41,
attachment 2).
    We note that people who manifest SIB or AB may have conditions or
take medications that increase their predisposition for palpitations;
however, the relationship between such a predisposition and the risk of
this harm from the application of ESDs is speculative. As with the
potential additional risk of seizures, the reports are anecdotal, so we
did not accord them significant weight, and they do not significantly
affect our evaluation of the benefit-risk profile.
    (Comment 25) One comment objects to FDA's reliance on JRC's policy
document listing possible collateral effects of ESDs because this
document was created in response to a requirement from the NYSED
through Corrective Action Requests to include a discussion of the
collateral effects of aversive interventions in its policies, and there
is no evidence ESDs caused any of these collateral effects.
    (Response) FDA disagrees. The discussion of possible AEs that JRC
included in its documents is consistent with the literature and NYSED's
reports. It is also consistent with information identified by and
submitted to FDA by individuals formerly at JRC and their parents.
Specifically, NYSED received reports of AEs, which NYSED refers to as
collateral effects, from the use of these devices, such as increases in
aggression and increases in escape behaviors or emotional reactions.
Also included were ``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),'' (see Ref. 22).
    In addition, based on its site visit, the NYSED criticized JRC for
inadequate monitoring for AEs, which partially precipitated the
Corrective Action Requests. Without adequate monitoring, JRC's
statement is not persuasive when it says that ``no evidence'' shows the
use of ESDs caused the ``collateral effects.'' Adequate monitoring is
necessary to instill confidence in such claims. Given the reasons NYSED
required the statements, the consistency with the literature and
anecdotal reports, and the fact that JRC ultimately included the
statements in its documents, we continue to regard this information as
evidence of risks.
    (Comment 26) A comment questions the validity of FDA's concerns
regarding AEs and underreporting because the commenter asserts it can
confidently state that no treatment with an ESD has ever resulted in a
patient death or serious injury. The comment argues that FDA's position
on AEs is speculative and not backed by data and that underreporting
would pertain to other alternative treatments for SIB or AB.
    (Response) FDA disagrees. As discussed in the proposed rule, FDA
believes that the scientific literature suffers from various
limitations and has likely underreported AEs associated with ESDs for a
number of reasons (see 81 FR 24386 at 24935). 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, including injuries. Although FDA did not identify
death as a risk of ESD use, we have reason to doubt the commenter's
confidence about the lack of serious injuries related to ESD use.
    For example, JRC provided no data regarding AEs in the resident
summaries it submitted, and the submission includes no information to
assess whether AEs were systematically planned for, tracked, or
documented in any of the clinical data. A qualified clinician should
have inquired about AEs with open-ended questioning at predefined times
after each use of the GED; there is no indication this occurred.
Therefore, these data are inconclusive regarding whether AEs occurred.
As we stated in the proposed rule, 66 patient case histories spanning a
23-year period did not report any AEs, which is highly unusual over
such a long time. For instance, FDA expected to read about a known case
of skin damage in these histories; however, there is no mention of that
event. This may be because none of these case histories included
systematically defined methods for short- or long-term AE monitoring.
    In the Massachusetts hearing, JRC submitted only one paper about
adverse effects of ESD use (Ref. 7). The paper acknowledges that few
studies have systematically investigated adverse effects, and it does
not include a statistical analysis because it did not collect enough
data. Dr. McCracken testified that in the literature about the use of
ESDs, ``there has been almost no attempt to identify or examine side
effects'' (Ref. 14, day 9 at 604). He then stated that ``concerns me.
In every other field of investigation of medical treatment, this would
be considered--we go to great pains to capture all of those types of
side effects'' (id., referring to ``reactions such as fear, panic,
vigilance, regression, attempts to avoid the shock. Basically
heightened anxiety, traumatic-like symptoms.''). These support FDA's
position.
    There may also be an underreporting bias due to impairments with
provider recognition, which is related to the difficulties individuals
would have communicating or otherwise demonstrating to providers AEs
including injuries (see 81 FR 24386 at 24398). SIB and AB are exhibited
at disproportionately high rates by people with intellectual or
developmental disabilities. Notably, many such people have difficulty
communicating because of such disabilities. This difficulty is part of
what makes these individuals members of a vulnerable population.
Although some individuals were able to offer their opinions to FDA at
the Panel Meeting, through interviews, and in the docket, most
individuals at JRC currently subject to ESDs who have reported IQ
scores, have scores that indicate their intellectual impairments are
profound, severe, or moderate. This indicates that those individuals at
JRC are, to varying degrees, vulnerable due to difficulty
communicating. Thus, FDA cannot conclude that communicative individuals
are representative (with respect to their communicative abilities) of
other individuals subject to ESDs.
    The bulk of the articles describe case reports or series, employing
only retrospective reviews of clinical experience, not prospective
studies. Because such retrospective reviews do not systematically plan
for the identification of AEs in advance, their assessment of such has
limited value. In contrast, prospective studies that include plans to
observe and record AEs from the outset generally provide greater
confidence in their assessment of AEs. 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. Most of this dated research did not adhere to modern standards
for AE monitoring.
    Although a ban does not require proof of harm, evidence of actual
harm helps inform the analysis, so FDA extensively reviewed the
available data and information for AEs associated with the use of ESDs.
FDA relied on that data and information to understand specific risks
and dangers that ESDs present to individuals' health (see 81 FR 24386
at 24393). FDA considered data and information from one prospective
case-control study and one retrospective chart review of 60 subjects
that reported AEs. Note that the case-control study did not
systematically assess AEs. These references reported:
     The emergence or intensification of self-restraint;
     low-intensity SIB that eventually resulted in tissue
damage;
     temporary skin discoloration that cleared up in a few
minutes or days; and
     ``collateral behavior'' not reported as AEs, including
emotional behaviors, tensing of the body, and attempts to grab or
remove the device.
    In addition, FDA considered 25 case reports or series encompassing
66 subjects that included an assessment of AE occurrences. These
references reported:
     Symptom substitution, including head-snapping, and
possible symptom substitution, including increased incontinence;
     escape behavior;
     possible hostility and retaliation;
     anticipatory fear and avoidance upon observing the
experimenter's initial movements to deliver a shock, immediately
developing fear of the device itself, and fear (phobic response) of
buzzing sounds;
     aggression, including accounts of surrogate retaliation,
self-aggression, lesser aggressive action, aggression fantasies,
threats and warnings;
     development of episodic bursts of SIB and aggression
toward others;
     crying, increases in crying, cries of pain, whimpering;
     shivering;
     statements that the shocks were painful and grimacing;
     panic;

     extreme anxiety (consisting of screaming, crying, attack,
and escape attempts);
     freezing (generalized behavior suppression) including an
observation of pseudocatatonic sitdown;
     initial increase in self-mutilative behavior and
emotionality;
     decrease in happiness or contentment and increased
dependency;
     slight local tremor in the thigh due to the shock;
     arc burns to the skin;
     lesion or bruise on the skin that resolved in 1 week and
slightly reddened areas;
     flinching;
     perspiration; and
     demonstrating other undesirable behaviors, including
smearing feces, spitting, stamping feet, swearing and using racial
epithets, making obscene gestures, rolling eyes, and imitating others.
    A later submission of 68 case reports revealed three subjects for
whom AEs were noted; however, FDA is aware of at least one AE (skin
burning) that did not appear in that set of reports (Ref. 5 at 69; Ref.
15 at 135-36). These documents reported:
     Urinary retention;
     arm pain;
     seizure;
     injured foot;
     angioma (an abnormal growth) below the ribs that did not
need treatment;
     lipoma on arm; and
     cloudy urine specimen.

These AEs occurred while the residents were subject to an ESD, but the
reports do not describe an evaluation of whether the ESDs caused or
related to the AEs. Note that FDA is not identifying all of these as
risks of ESDs for SIB or AB.
    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.
    Because of the likely underreporting of AEs in the literature, FDA
carefully considered the risks identified through other sources, which
provide further support for the risks reported in the literature. These
sources beyond the scientific literature indicate that ESDs are
associated with additional risks such as suicidality, chronic stress,
neuropathy, and injuries from falling (see 81 FR 24386 at 24399).
Although JRC has only publicly acknowledged the risks of pain and
erythema, its own documents provide evidence that aversive
interventions such as ESDs are associated with several other risks,
including nightmares, flashbacks of panic and rage, hypervigilance,
insensitivity to fatigue or pain, changes in sleep patterns, loss of
interest, difficulty concentrating, and withdrawal from usual activity
(see 81 FR 24386 at 24398).
    With regard to underreporting AEs pertaining to other treatments,
the comment specifically refers only to pharmacotherapy. However, the
studies conducted for approval of the drugs provide a better baseline
to understand their risks than that available for ESDs, and the studies
supplement our understanding from spontaneous postmarket reports of
AEs. As a result, the possibility that the pharmacotherapy poses risks
additional to those that have been reported is much less of a concern
in FDA's consideration of state-of-the-art treatment for SIB or AB than
is the likelihood of underreporting of AEs associated with ESDs in
FDA's consideration of ESD risks. For example, to obtain drug approval
for the pharmacotherapies used in relation to SIB and AB or the
underlying conditions, the sponsors conducted Phase I clinical trials
that included neurotypical individuals to assess the safety profiles of
the drugs, meaning the subjects of the study were generally better able
to communicate AEs than the individuals on whom ESDs for SIB or AB have
been used. Further, such trials assessed AEs according to prospectively
determined protocols. In the Phase II and Phase III trials, AEs were
also systematically monitored in the intended-use population. Thus, in
the case of pharmacotherapy used for SIB or AB, the safety of the drugs
has been studied in formal trials that provide a much better
understanding of their risks than the much more limited data that exist
for ESDs.
    In contrast, the safety of ESDs has not been equivalently studied.
This is not to suggest that a finding of substantial equivalence to an
existing device type must rely on adequate and well-controlled studies
as if the sponsor sought new drug approval. Rather, it indicates to FDA
that the safety profile for pharmacotherapy used in relation to SIB and
AB or the underlying conditions is better understood than the safety
profile of ESDs for SIB or AB, in particular that AEs are better
understood. The data and analysis for such pharmacotherapies are more
robust because the available data and information for ESDs suffer from
various limitations discussed throughout this rulemaking, whereas the
clinical studies for these drugs do not. As such, the pharmacotherapy
premarket data provide a more complete understanding of risks, reducing
any concern regarding underreporting of AEs.
    The commenter agrees that other state-of-the-art approaches such as
positive behavioral treatments pose little to no risk. As discussed in
the comment responses regarding the state of the art, the only risk
that FDA found to be associated with positive behavioral treatments is
the potential risk of ``extinction bursts,'' an upsurge of the actual
undesirable behavior, which is easily recognized and quickly mitigated
by competent therapists.
    (Comment 27) Quoting from Ref. 42 and Ref. 16, a comment states
that ``most published accounts report few, if any, side effects from
treatment'' and that ``overall, there was little to suggest the
development of adverse side-effects.'' The comment argues that positive
side effects are most often observed, including relief from other
symptoms. The comment also argues that scientific research ``does not
have a shelf life.''
    (Response) FDA disagrees with the characterization of the published
accounts as well as the implication that previous scientific research
cannot be understood in a different way over time. FDA considered the
cited references in their entirety at the proposed rule stage,
including in the context of ethics and treatment options prevailing at
the time the research was conducted. We note that this comment relies
on research from earlier decades; both references date back to 1975,
well before the development of less-invasive behavioral treatments.
After considering these references in light of then-prevailing ethics
and conceptions of harm, FDA is not persuaded that these references
speak to modern standards of care regarding ``positive side effects.''
    As to ``adverse side effects,'' we believe that these and other
early studies underreported AEs for various reasons discussed in the
proposed rule and other comment responses, were subject to lower peer-
review standards for observation and reporting relative to modern
standards, and did not have the benefit of recent decades of research
into the treatment of SIB and AB. As a result, the articles quoted by
the commenter have various weaknesses that undermine the commenter's
position.
    First, Ref. 42 notes that in its literature review ``only two
articles [Refs. 40 and 43] consider in any detail the problems
associated with aversion in self-injurious behavior or in the severely
retarded.'' Further, ``even those accounts which have been included
vary considerably in the adequacy of the information given; particular

deficiencies being the lack of adequate clinical data about the subject
or the results of previous treatment and the short duration and
variability in methods of recording of baseline observations, bearing
in mind that self-injurious behavior tends to fluctuate in intensity
over time'' (Ref. 42). The article also notes the importance of the
concomitant positive behavioral program in producing positive side
effects. Finally, the article concludes: ``an answer to the problems
associated with aversion will not reach any rapid solution and it is
therefore essential that treated cases are properly documented and
reported'' (Ref. 42). Thus, the commenter's reliance on this article as
support for its position that ESDs cause ``few, if any, side effects''
is not persuasive.
    Similarly, the authors of Ref. 16 conclude that ``the work with
this technique is still at a preliminary stage and the apparatus is not
yet sufficiently trouble-free to warrant its use outside research
settings.'' Thus, the commenter's reliance on this article as support
for the statement that there is ``little to suggest the development of
adverse side-effects'' is also unpersuasive.
    Other literature submitted by the commenter supports FDA's findings
of risks. For example, Ref. 39 reports risks from other studies of
elicited and operant aggression, other emotional responses (e.g.,
crying), decreases in appropriate behavior (``generalized response
suppression''), escape from or avoidance of the punishing agent or
situation, and caregivers' misuse of punishment (see also Ref. 44).
Further, according to Ref. 39, aggression and emotional responses may
be more likely to occur when the individual is exposed to unavoidable
and intense aversive stimulation. Ref. 36 reports the risk of
untargeted positive behavior being modified by the device. Ref. 40
includes negative reaction to authority figures, the increase in
behaviors undergoing treatment, prolonged treatment potential,
production of undesirable emotional states, behavioral rigidity,
general disruption of cognitive processes, production of neurotic
syndrome, suppression effects not specific to responses punished, and
chronic emotional maladjustment. (See also Response 19 discussing
pseudocatatonic states and generalized behavior suppression.) Ref. 45
discusses the risks of an unreliable apparatus, including inappropriate
intensity of shock, inconsistent delivery of shock, inappropriate delay
of shock, or inappropriately prolonged shocks. Ref. 46 enumerates 19
negative side effects. Another article submitted by the commenter
acknowledged that few studies have systematically investigated side
effects of skin shock (Ref. 47). The few studies reporting the
potential benefits of the devices that were published in more recent
years similarly did not systematically report AEs or include safety
outcome measures (see Ref. 47).
    Recent testimony from the Massachusetts hearing corroborates that
AEs are understudied (Ref. 14, day 9 at 604 (McCracken)) and that
certain risks are underreported and undertreated in people with
developmental and intellectual disabilities (Ref. 14, day 26 at 1519-20
(Miner)). Other testimony indicates that shocks are rarely used because
of negative side effects, for example, avoidance, emotional responses,
and perpetuation effects (see Ref. 14, exhibit 494 (Spiegler 2014)).
Similarly, JRC's own documents state that side effects (i.e., risks)
can include emotional reactions, aggressiveness, escape from or
avoidance of the punishment situation, increased unwanted behaviors,
and self-perpetuation of punishment (Ref. 38), as well as exacerbation
of violent behaviors (Ref. 48).
    Keeping the foregoing in mind, the quotations of Refs. 42 and 16
indicating that published accounts report few, if any, negative side
effects do not fairly characterize the decades of research since 1975.
In the intervening decades, clinicians have expanded what they consider
to be negative side effects and have made significant advances in the
ability to diagnose and classify negative psychological effects. For
example, pain is itself a harm, yet earlier studies did not view the
pain as a harm.
    As we have explained, providers' and researchers' concerns about
intentionally inflicting such conditions upon a vulnerable patient
population led to advancements in behavioral therapy (see 81 FR 24386
at 24404). In fact, Ref. 42 advocated for active research to establish
``alternative forms of treatment'' because he recognized the ethical
concerns presented by this treatment, particularly in a patient
population that cannot give consent (Ref. 42). In the case of using
ESDs for SIB or AB, the ethics of using restrictive interventions on
such a population contributed to the evolution of treatments and of
understanding their attendant risks.
    While empirical findings may not have a ``shelf life,'' the
understanding of the completeness and implications of those findings
may change as science evolves, which it has with respect to assessment
of risks for ESDs. Based on such evolution, for example, because the
decades-old references did not consider pain, anxiety, or other such
sequelae as harms--nor did researchers systematically monitor for AEs
according to current standards--FDA continues to regard such references
as poor indicators for the occurrence of AEs.
    (Comment 28) A comment disputes FDA's position regarding AE
underreporting due to communication difficulties on the part of
intellectually and developmentally disabled individuals by arguing that
individuals subject to ESDs ``many times'' demonstrate improved
communication, and that communication can be through nonverbal means,
assisted by augmentative communication devices such as a picture board.
    (Response) Although FDA acknowledges that some of these individuals
may demonstrate improved communication and that communication can be
through nonverbal means, this does not change FDA's view that many
individuals manifesting SIB or AB would have difficulty communicating
AEs and injuries, verbally or otherwise, and that this likely results
in underreporting of AEs. Behavioral interventions typically include
elements intended to improve communication skills; this does not mean
that all or most individuals will be able to adequately communicate
AEs.
    We also note that, although augmentative communication devices may
assist staff in communicating with nonverbal individuals, this is
nevertheless evidence that those individuals have difficulty
communicating. The comment does not explain or give examples of how
these devices compensate for difficulties communicating AEs and
injuries, nor does the comment present evidence contradicting the
likelihood of atypical pain expression. FDA maintains that many
individuals who present with SIB or AB would have difficulty
communicating or otherwise demonstrating AEs and injuries and the Panel
agreed (see Ref. 15 at 54, 155, 355).
    (Comment 29) One comment questions FDA's claim of researcher bias,
and it notes that in some ``N-equals-1'' studies, the researcher is
blinded, which eliminates the researcher's bias.
    (Response) FDA discussed numerous reasons in the proposed rule that
researcher bias and author conflicts of interest may have influenced
study results and conclusions, for example with respect to
underreporting of adverse events, 81 FR 24386 at 24395,

and regarding poor study design, 81 FR 24386 at 24400 to 24401, and
this comment does not address any of them. Instead, it points to the
testimony of one of its experts regarding some blinded N-equals-1
studies, a study design that combines information from single-subject
trials. We note that no N-equals-1 studies have been conducted on the
use of ESDs for SIB or AB. Thus, although some study designs may reduce
or eliminate researcher bias, this observation does not reflect the
state of research into ESDs used for SIB or AB, and FDA is not revising
our views regarding bias or the reduced weight we have given biased
evidence.
    (Comment 30) A comment asserts that JRC uses extensive measures to
ensure ESDs are applied only to refractory patients, for example,
evaluating each patient with a functional behavioral assessment (FBA)
performed by a JRC clinician; first attempting PBS approaches;
exhausting all other options; and obtaining a prior court order with
the involvement of multiple parties. In the commenter's view, FDA fails
to discuss and consider these measures in the assessment of risks.
    (Response) FDA disagrees with the comment's rationale on several
points. First, FDA did consider these measures. However, as we
explained in the proposed rule, no clinical criteria identify
refractory patients, and no rigorous or systematically collected data
distinguish a refractory subpopulation that does not respond to other
available treatments (81 FR 24386 at 24406). Similarly, members of the
Panel unanimously concluded that such a subpopulation seems to exist
but is very difficult to define (81 FR 24386 at 24406). Thus, as we
explained, although evidence indicates that a very small subpopulation
of refractory individuals may exist, that subpopulation is difficult if
not impossible to define (81 FR 24386 at 24412). We are not persuaded
that JRC has successfully defined a refractory subpopulation by
exhausting a selected list of options, and this undercuts the certainty
in JRC's claim that its patients are uniquely refractory.
    Regarding exhaustion of options, we also explained that the
available evidence casts doubt on whether JRC in fact applies the
devices as a last resort after adequately attempting all other
measures, and the evidence shows that some patients JRC had considered
to be refractory were transitioned successfully to other treatments (81
FR 24386 at 24412). As we describe in more detail in Responses 39 and
44 to 46, additional data and information cast further doubt on the
adequacy of JRC's attempts at alternative treatments. In other words,
this undermines claims that ESD use can be limited to a truly
refractory subpopulation.
    More importantly, these measures to limit use of the device to a
specific subpopulation in no way reduce or eliminate the risks posed by
ESDs, and the commenter does not argue they do. Even if the measures
were effective, they would merely limit the number of vulnerable
individuals exposed to the risks; those individuals would still be
exposed to the same risks as they would be in the absence of such
measures. Rather than showing risk mitigation, the commenter's
statements about limiting the exposed population provide support for
the severity of the risks: If as the commenter claims, the devices are
low risk, such measures would not be needed. Thus, the use of such
measures fails to reduce the risks even as the reliance on such
measures tends to confirm the severity of the risks.
    Even if the risks could be limited to a very small subpopulation,
this would not alter FDA's determinations that the risks are
substantial and unreasonable. This is because, as discussed in the
comments regarding effects, effectiveness has not been established in
any population of patients exhibiting SIB or AB. Further, as discussed
in the comments regarding the state of the art, positive behavioral
approaches, sometimes alongside pharmacotherapy, have generally been
successful even in the most difficult cases. However small this patient
population may be, these vulnerable individuals, like all individuals,
are entitled to the public health protections provided in the FD&C Act.

D. Effects of ESDs on SIB and AB

    (Comment 31) A comment states that FDA acknowledges ESDs have been
shown to reduce SIB and AB.
    (Response) In the proposed rule, FDA acknowledged that ESDs may
cause the immediate interruption of SIB or AB (81 FR 24386 at 24387) if
the shock is applied while the SIB or AB is occurring. We also
explained that some evidence suggests ESDs reduce SIB and AB in some
individuals, but this evidence cannot be generalized because the
studies suffer from serious limitations such as weak design, small
size, confounding factors, outdated standards for study conduct, and
study-specific methodological limitations (81 FR 24386 at 24400). We
are also concerned about potential bias in some of the evidence of
effectiveness related to lack of peer review and conflicts of interest
(81 FR 24386 at 24401). Other evidence shows that ESDs are completely
ineffective for certain individuals. For these reasons, FDA concluded
that the evidence is sufficient to show that ESDs may interrupt
behaviors when a shock is applied, but the evidence is otherwise
inconclusive and does not establish that ESDs improve the underlying
condition or condition individuals to achieve durable reduction of SIB
or AB for a clinically meaningful period of time (81 FR 24386 at 24399
to 24403).
    (Comment 32) One comment interprets FDA's statement in the proposed
rule that, ``the possibility that some patients are refractory [to
other treatments] does not necessarily mean that ESDs would be an
effective treatment'' to mean that FDA believes ESDs should be banned
because they are not effective for every individual with SIB or AB.
    (Response) FDA disagrees. The statement referred to in the comment
only makes the point that the fact that one treatment does not work for
a patient or group of patients does not mean that a different treatment
will work. FDA understands that devices are not always effective for
every individual with the condition the device is intended to treat;
this is not a reason that FDA is banning ESDs.
    (Comment 33) A comment argues that, although there are no
randomized controlled clinical studies of ESDs for SIB or AB, the
available data, including over 100 published peer-reviewed articles,
among other sources, amply provide evidence of the safety and efficacy
of ESDs for SIB or AB. The comment provides a table summarizing 162
references discussing the use of skin shock.
    (Response) FDA disagrees. As the comment acknowledges, these data
have been provided to FDA and reviewed by the Agency, and FDA has also
reviewed all of the additional information provided by commenters. We
weighed the evidence according to factors that we explained in the
proposed rule (see 81 FR 24386 at 24393). Where FDA has reconsidered
the interpretation or significance of specific sources or claims in
response to comments on the proposed rule, we have explained the
reevaluation and how it affects the analysis in the appropriate section
of this final rule. For example, based on additional data and
information, we believe the proposed rule understated the harm of pain
(see Response 13), and we no longer consider affection-seeking a risk
of ESDs (see Response 16(c)). In other cases, we have elaborated on the
significance of certain statements identified in the available
information,

for example with respect to the potential risk of seizures (see
Response 24).
    FDA's review of the references cited by the commenter, along with
the corresponding comments, does not change our conclusion that, beyond
the ability of ESDs to cause immediate interruption of the behavior at
the time of shock, the evidence is otherwise inconclusive with regard
to the benefits and effectiveness of ESDs for SIB or AB. We continue to
conclude that the evidence does not establish that ESDs improve the
underlying disorder of which SIB or AB is a symptom, or successfully
achieve a durable reduction of SIB or AB for clinically meaningful
periods of time by conditioning individuals' behavior.
    FDA previously reviewed 44 of the 162 references highlighted by the
comment, which we discussed in the Executive Summary for the Panel
Meeting and the proposed rule (see 81 FR 24386 at 24393). There were
few comments regarding ESD effectiveness with respect to the references
previously discussed by FDA, and FDA continues to view these as we did
at the proposed rule stage. Note that one reference appeared twice,
meaning the total of summarized references is 161. The references that
FDA had not previously reviewed are:
     19 case reports, 10 of which (involving 17 total subjects)
provide some information regarding durability of effects;
     10 literature reviews, all of which summarize literature
that FDA has already reviewed;
     41 references with limited or no discussion of ESDs,
including opinion pieces and miscellaneous documents that do not
directly bear on ESD risks or effects--these have limited relevance to
this rulemaking;
     38 reports on treating conditions other than SIB or AB--
these also have limited relevance to this rulemaking; and
     9 unpublished presentations or other documents that the
commenter did not provide and FDA could not locate, including two
written by JRC's former director-founder that are no longer available
on JRC's website.

We focused our review of these references on the 64 references (45
discussed in the proposed rule and 19 cited in comments) that discuss
patient data from clinical studies on ESDs for SIB or AB. With the
exception of the one case-control study discussed in the proposed rule
(see 81 FR 24386 at 24393, discussing Ref. 17), all of the other
studies are case reports or literature reviews pulling from these case
reports.
    The case reports show immediate interruption of target behaviors at
the time of shock application. One study on subjects with Lesch-Nyhan
syndrome exhibiting SIB and AB shows no effectiveness whatsoever (Ref.
49), and a few report ultimate failure after a period of apparent
success. However, all of the other case reports appear to demonstrate
immediate interruption of the behavior at the time of shock
application. FDA continues to conclude that the evidence shows that ESD
shocks generally cause immediate interruption of the behavior that is
occurring when the shock is delivered, provided the individual has not
adapted to the shock, which has been shown to occur for some
individuals.
    More critical to the evaluation of the effectiveness of ESDs for
SIB or AB is their ability to achieve durable effects by aversively
conditioning behavior. A durable effect is one where an individual
develops a conditioned response, so the target behavior, along with the
frequency of shocks, is significantly reduced over a clinically
meaningful period of time, either while the individual continues to
wear the ESD or after the ESD is removed. Half of the references, 32 of
64, include at least some information regarding durability of ESD
effects.\7\ Several of these references report cases where there was
some short period of reduction in target behaviors followed by failure.
Most report a reduction in the target behavior ranging from a few
months up to several years, particularly with continued (less frequent)
ESD use. However, conditioned reduction of SIB or AB over clinically
meaningful periods of time is much more difficult to demonstrate than
immediate interruption of behaviors because, for example, data
regarding such are more vulnerable to the errors that well-designed and
controlled studies are intended to minimize. Establishing durable
conditioning demands well-conducted clinical studies and data spanning
longer periods. For example, an individual may undergo several
different behavior modification techniques over a period of time, and
it is more difficult to draw conclusions regarding the effectiveness of
ESDs from a study that does not control for such confounding factors
than from a study that did control for them. As a result of such
weaknesses and limitations, as described in the paragraphs that follow,
the limited data that currently exist for ESDs for SIB or AB are
inadequate to establish durable conditioning.
---------------------------------------------------------------------------

    \7\ We had not previously discussed 10 of these references in
the proposed rule or Panel Executive Summary, Refs. 50-59.
---------------------------------------------------------------------------

    As the comment recognizes, there are no randomized controlled
clinical studies of ESDs for SIB or AB; there are only case reports
and, as discussed in the proposed rule, one prospective case-control
study on 16 subjects, 8 in the device group and 8 in the control group
(see Ref. 17). The comment acknowledges this study has an extremely
small sample size. The results of the case-control study are further
limited because the study was not randomized or blinded, and it used an
unvalidated surrogate endpoint (decrease in mechanical restraint). Case
reports are, by definition, extremely small in size; the ones regarding
ESDs for SIB or AB typically include fewer than five subjects, and
often only a single subject. They have no control group, blinding, or
randomization, do not test statistical significance, and the results
are unlikely to be generalizable across subjects.
    The particular case reports cited in the comment suffer from
various other shortcomings that limit the ability to draw conclusions
from their results regarding the effectiveness of ESDs for SIB or AB.
Perhaps most importantly, many subjects were given concomitant
treatments such as positive reinforcement or time-outs; therefore, it
is unclear how much, if anything, the use of ESDs contributed to the
observed reductions in SIB or AB. Many other case studies lacked
sufficient detail to determine whether concomitant treatments were
given. Other information important to assessing ESD effectiveness was
often missing, such as details regarding the subjects and their
particular forms of SIB or AB, baseline behavior measurements, device
output and electrode locations, and shock administration protocols.
    Further, most of the studies were conducted several decades ago and
do not conform to current study conduct, reporting, or peer-review
publication standards. Results were sometimes reported anecdotally and
were not always recorded by a trained investigator, which raises
questions regarding their reliability. Most studies lacked predefined,
clinically meaningful endpoints, and typically study sessions and
followup were of inadequate duration to assess effectiveness for a
clinically meaningful time period or generalizability to the subjects'
everyday environment. As a result of these limitations, the data are
inadequate to draw any scientific conclusions regarding the durability
of ESD effects on SIB and AB.

    (Comment 34) A comment notes that a literature review discussed in
the proposed rule states, ``basic findings suggest that relatively
intense punishers may be associated with successful long-term
outcomes'' (Ref. 60). The comment asserts this demonstrates that
aversives are effective and durable.
    (Response) FDA disagrees. As discussed in the proposed rule, even
though the cited article opines that research findings suggest
sufficiently intense punishers such as ESDs may be associated with
long-term success, it cautions that such findings suffer from various
limitations, and the authors conclude that ``[u]ntil additional
research on long-term maintenance is conducted, practitioners and
caregivers should not assume punishment will remain effective over the
long run.'' (81 FR 24386 at 24399, citing Ref. 60). The article
explains that most of the time periods evaluated in the literature on
punishment are brief, which may limit their applicability to treatment
outcomes in clinical settings, and these studies have shown
inconsistent outcomes in maintaining a reduction in target behavior
(see, e.g., Refs. 19, 20, 61 to 64). According to this article,
conclusions about applied findings on maintenance of effect are
difficult to draw for a number of reasons, including that relapse cases
are less likely to be submitted or accepted for publication than
successful ones. Thus, the reference does not demonstrate that
aversives such as ESDs achieve durable reduction of SIB or AB for a
clinically meaningful period of time. Rather, the article questions
their effectiveness, and ultimately concludes that current knowledge is
insufficient to support clinical application.
    (Comment 35) A comment states that FDA badly mischaracterized a
reference, Ref. 65, in the proposed rule, and that the findings in the
reference contradict claims that ESDs cannot be successful unless
continuously applied.
    (Response) FDA disagrees. Providing only an excerpt from the
article's abstract in support of its assertion, the comment
misrepresents the findings of this article, which does not purport to
study the effects of punishers, much less reach any conclusions
regarding ESD effectiveness. Rather, the authors studied the ability to
terminate the use of punishment-based procedures--described as
``multiple, `aversive' treatments'' that ``were discontinued
abruptly''--in favor of less invasive alternatives, specifically
multielement positive interventions. The article explained, ``The
question posed was how do adults with developmental disabilities and
seriously challenging behaviors respond in the long-term when they are
no longer exposed to negative and highly invasive procedures?''
    Interventions that included contingent electric shock from ESDs
were used for each subject prior to the positive interventions studied
by the authors. The article acknowledges, ``[i]t is possible, of course
that the prior invasive [restrictive] treatment contributed to the
long-term outcomes presented in this report,'' but concludes that its
``results are encouraging in demonstrating that punishment-based
approaches can be terminated, alternative strategies can be
substituted, and through a clinically responsive system of monitoring
and decision-making, behavioral adjustment can be supported without
having to resort to invasive forms of treatment'' (Ref. 65). In sum,
the authors were not validating the initial use of punishers or
evaluating their long-term effectiveness but rather studying the
ability of multielement positive interventions (i.e., state-of-the-art
approaches) to supplant punishment procedures, finding encouraging
results that behavioral adjustment can be supported without invasive
forms of treatment.
    (Comment 36) One comment states that a reference cited in the
proposed rule, Ref. 66, included ``surprising findings'' on the use of
shock ``pertaining to `the immediate increase in socially directed
behavior, such as eye-to-eye contact and physical contact, as well as
the simultaneous decrease in a large variety of inappropriate
behaviors, such as whining, fussing, and facial grimacing . . .' '' The
comment asserts that FDA selectively used information from this article
for our own purposes.
    (Response) FDA disagrees. FDA referred to this article in the
proposed rule for several reasons, including: To support some of the
risks posed by ESDs; to support the occurrence of adaptation, wherein a
patient grows accustomed to a particular level of shock and no longer
responds; and to support the ability of ESDs to immediately interrupt
behavior occurring at the time of shock. The cited article studied
short-term treatment and reported some immediate benefits from the use
of ESDs for SIB or AB, as stated in the proposed rule. However,
regarding longer-term followup, it states: ``Although the immediate
`side-effects' of punishment point in a desirable direction, one should
be less optimistic about long-term behavioral change under certain
conditions. We can supply few data which exceed a couple of months'
followup, and in the case of only two children have we had the
opportunity to conduct follow-ups for as much as 1 year, while the
suppression of self-destruction was being maintained.'' This is
consistent with FDA's determination that the data suggesting durable
effectiveness of ESDs are generally weak, and the reference's statement
is also consistent with the commenter's criticism (elsewhere in its
comments) of this reference's ``extremely small sample size'' of three
subjects.
    It is also important to note that this article was published in
1969, so as explained elsewhere, we believe that it suffers from
outdated methodology, such as a lack of systematic observation and
reporting of AEs. Thus, the article's characterization of ``side
effects'' as pointing in a ``desirable direction'' must be considered
in this light. FDA considered the entire reference with regard to both
benefits and risks and continues to regard the reference as we did for
the proposed rule.
    (Comment 37) A comment asserts that FDA's claims that Dr. Israel's
2008 and 2010 papers (Refs. 47 and 67) were not peer reviewed, and that
they failed to disclose Dr. Israel's affiliation with JRC, are
incorrect. The comment states that the copy of the 2008 review posted
by FDA includes an apparent printing error that omitted the references
to Dr. Israel's disclosure.
    (Response) FDA acknowledges the apparent printing error in the
omission of Dr. Israel's disclosure in the 2008 paper. Thus, other
readers may have been adequately notified of any potential bias.
However, as we explained in the proposed rule, FDA was aware of the
affiliation and took into account the possible conflicts of interest,
which stem from the facts that Dr. Israel was the founder of JRC and,
at the time his papers were published, was on the journal's editorial
board and thus part of the reviewing and approving body (for his own
papers). As such, this printing error does not affect our conclusion
with respect to Dr. Israel's potential bias. As we stated in the
proposed rule, possible conflicts of interest do not, on their own,
invalidate results. However, we continue to view Dr. Israel as a
potentially biased source and weigh this evidence accordingly.
    With regard to peer review, the commenter simply asserts without
explanation that the papers were peer reviewed. However, as we
explained in the proposed rule, we determined that the publications
(both 2008 and 2010) were not peer reviewed because the articles were
only reviewed by the journal's editorial board rather than an
independent expert whose sole role was

to verify accuracy and validity (see 81 FR 24386 at 24401).
    (Comment 38) One comment asserts that all of JRC's residents'
harmful and dangerous behaviors decreased substantially as a result of
treatment with the GED device, as evidenced in JRC's resident case
reports, behavior tracking charts, and analyses from the past 16 years.
The comment asserts this data set is extraordinarily robust because the
individuals reside at JRC and are continuously monitored. The comment
also asserts this data and information demonstrate the effectiveness of
ESDs for SIB or AB for refractory patients.
    (Response) FDA disagrees that this is a robust data set, and this
information does not change FDA's assessment of the effects of ESDs for
SIB or AB. The case reports and other information submitted by JRC
about its residents on whom ESDs have been used appear to indicate that
their SIB and AB decreased substantially once they began wearing the
GED and remained at low levels for years. However, as explained in the
paragraphs that follow, this information suffers from several serious
methodological limitations that prevent FDA from drawing any scientific
conclusions regarding ESD effectiveness based on it. For example, these
are resident records, not study data, and they also suffer from the
same limitations that generally apply to the case studies discussed in
the literature. In addition, the manner in which the information was
collected and documented undermines its reliability.
    In particular, these resident records are anecdotal and do not
amount to study data. The information was collected by JRC, which did
not take measures to minimize the impact of subjectivity and potential
bias. Important measures that its employees did not take include having
an investigational plan and study protocol, running an analysis to
demonstrate scientific soundness, validating methodology and endpoints,
and selecting qualified investigators. JRC also failed to implement
features designed to minimize confounding factors and other types of
bias, such as a control group, blinding, and randomization, the
importance of which are discussed in the proposed rule and in the
responses to other comments. These records also suffer from the
limitations that apply to extremely small studies. Although in 2016 JRC
submitted case summaries for 68 residents (and has applied the devices
to close to 300 individuals over the years, including about 51 then
subject to the devices), we consider these data to be 68 individual
resident summaries, not a single study including all residents, because
the records do not show, for example, that conditions were controlled
across individuals or subgroups of individuals.
    Further, confounding factors and uncontrolled conditions make it
very difficult to attribute JRC's observed improvements in behavior to
the GED device or draw any conclusions about its effects. For example,
according to these records, most of the individuals on GEDs received
concurrent treatment with various forms of behavioral therapy,
including positive behavioral programming and various differential
reinforcement programs, counseling, and functional communication
training. Without adequately controlling for, or adequately documenting
the formulation, application, and effects of the other behavioral
intervention components, it is difficult if not impossible to
differentiate effects of the GED from effects of behavioral treatments.
Additionally, these records indicate that JRC targeted different
behaviors during different time periods. As a result, many of the
tracking charts show highly variable behavior, in some instances
showing some target behaviors decreasing for an individual while other
target behaviors did not decrease for that individual, and thus shocks
continue to be applied. This makes it difficult to assess overall ESD
effectiveness.
    Where data represent a relatively small number of individuals,
detailed, systematic observations are critical to reducing uncertainty
regarding results. Yet the information submitted by JRC fails to
include important details regarding how the data were collected and
recorded. This creates considerable uncertainty as to its significance
and reliability and prevents us from drawing clinically meaningful
conclusions regarding the benefits of the GED from the limited data
provided in the case summaries. For example, the information lacks key
details regarding the time at which the device was applied, the
specific behaviors targeted, behaviors that occurred prior to
administration of shocks, criteria for counting behaviors, the number
of electrodes and their location on the body, which ESD model was used,
frequency and duration of data collection, who determined a behavior to
be SIB or AB, who recorded the count data, and the medical training (if
any) or qualifications of those recording data to evaluate the
residents. The information submitted to FDA suggests that JRC often
applied multiple devices at once to single individuals, but the
submissions do not explain why this was necessary or how the number of
devices was determined; the submissions only provide gross detail, for
example, that shocks were indicated for ``health-dangerous behavior.''
Finally, the charts include little information regarding the
individuals and their behaviors before and after ESD use, making it
difficult to draw conclusions regarding how the devices affected the
target behaviors.
    (Comment 39) A comment argues that the ESD shock is applied to help
residents identify their dangerous behaviors for purposes of reducing
the frequency of that behavior. As residents learn to identify and
control their dangerous behaviors, the number of shocks delivered
decreases. The comment asserts that, for a significant portion of JRC
residents, the duration of effects from ESDs for SIB or AB is lasting
as demonstrated by the numerous residents who have been transitioned or
``faded'' off of the GED and no longer manifest SIB or AB.
    (Response) Although ESDs may interrupt behaviors occurring at the
time of shock, FDA has not seen adequate evidence demonstrating that
ESD shocks produce a conditioned response. Additionally, although the
ability of ESDs to condition individuals not to engage in SIB or AB
after removing the device is part of the evaluation of ESD
effectiveness, fading itself is not demonstrative of effectiveness.
Fading of the GED is an indication of JRC's decision to reduce or cease
use of the device for an individual, and submissions from JRC do not
establish that it makes such decisions consistently, much less that it
adequately establishes that the device caused changes in behavior.
Further, SIB and AB can exceed pre-baseline levels once an ESD is
removed, as has been observed in the literature. This is partly why, as
discussed in the previous comment response, FDA disagrees that the
resident data submitted by JRC demonstrate a durable effect for ESDs
for SIB or AB.
    With respect to individuals transitioned off of the GED, only a
small percentage of individuals at JRC have been completely faded off
of the GED. According to the records submitted by JRC for the 68
residents on whom ESDs have been used, only 13 (19 percent) have been
completely faded, and the duration of ESD use prior to fading ranges
from 3.5 to 23 years. According to the summary information for the 189
residents on whom ESDs have been used since 2000, which is even less
detailed than the 68 resident records, only 58 (31 percent) had been

completely faded off of the GED device at least 2 weeks before
discharge from JRC.
    Further, JRC provided no information regarding clinical protocols,
treatment plans, or behavior frequencies for individuals after they
left JRC. At the Massachusetts hearing, Dr. Blenkush stated that JRC
has not systematically collected follow-up data on individuals after
they leave JRC (Ref. 14, day 37 at 81). FDA is not suggesting JRC
necessarily must collect followup data; however, such data are
important to understanding the effects of ESDs. Based on the scant
information provided, FDA is unable to determine, for example, whether
behaviors worsened after leaving JRC or whether other non-aversive
treatments are responsible for any successes. Overall, it is difficult
if not impossible to evaluate the effects of ESDs, much less draw any
conclusions regarding ESD effectiveness, from the fading data provided
by JRC for the GED, without: (1) A standardized clinical assessment
protocol (e.g., specific behaviors targeted, criteria for counting
behaviors, frequency and duration of data collection, who determined a
behavior to be SIB or AB, who recorded the data, and the medical
training or qualifications to evaluate patients of those recording
data); (2) controlling for or adequately documenting the formulation,
application, and effects of the other behavioral intervention
components that were applied according to JRC's data; and (3) well-
documented followup to determine whether behaviors worsened after ESD
use discontinued at JRC or after leaving JRC.
    The claim that these devices produce durable conditioning is
further undermined by the fact that, as evidenced in the resident
records submitted by JRC, the device has been used on many individuals
for years and even decades. As Dr. Iwata explained during the Panel
Meeting:

[M]y understanding of the way this whole process works is that
within a given range in terms of interventions that we use, some are
effective and some are not, and if they're not effective, you go on
to something else. Now, electrical stimulation is designed to be
very effective very quickly, which means that the individual should
not experience very many stimulations, which means that very few
people should habituate to the stimulus. And if they do, it's not
really habituation; that is, they haven't adapted to it. It's simply
ineffective, and you would move on rather than to step up the
voltage, so to speak. To use an analogy, a small amount of lemon
juice on the tongue might be another aversive event, but if that
doesn't work, we don't put acid on the tongue.

(Ref. 15 at 142). Regardless of whether adaptation is the correct
characterization, even JRC has acknowledged that its strongest ESD
sometimes loses any effects it may have had in reducing target
behaviors, necessitating the use of an alternative method to modify
behaviors program instead of an ESD. Dr. Blenkush highlighted ``a very
comprehensive alternative behavior program'' at JRC that was ``very
effective'' after adaptation to the GED-4 even for patients engaging in
SIB that could result in serious injury to themselves (Ref. 15 at 148).
    (Comment 40) One comment states some Panel members recognized ESDs
as potentially appropriate for certain patients and asserts that FDA
has ignored the comments of several Panel members that there is
evidence to demonstrate that ESDs for SIB or AB have beneficial
effects, particularly in the refractory population treated at JRC.
    (Response) FDA agrees that some Panel members opined that ESDs
provide benefits for some patients but disagrees that we ignored these
comments in the proposed rule and disagrees that Panel members opined
that the benefits would be more likely to occur in JRC's patients. As
explained in the proposed rule, approximately half of the Panel agreed
that there was a benefit, but they qualified their answers by
explaining that the evidence showed a benefit from the interruption and
immediate cessation of the behavior and noted the weaknesses in the
evidence (81 FR 24386 at 24401). Regarding refractory individuals
residing at JRC, when asked specifically about the subpopulation for
whom any benefits might manifest, most panelists stated that they could
not define that subpopulation. Further, as noted in Responses 13, 32,
and 43, being refractory to other treatments does not mean ESDs will be
effective. However, overall, the Panel recommended to FDA that the
Agency ban ESDs for SIB or AB, with the members taking into
consideration potential benefits and risks of the devices, including
use of the device in a refractory population. Accordingly, the Panel's
overall evaluation of ESD effectiveness is consistent with FDA's.
    (Comment 41) One comment says that expert testimony from the
Massachusetts hearing supports JRC's argument that the GED is effective
for the population on whom it is used at JRC.
    (Response) FDA agrees that some of the expert witnesses at the
Massachusetts hearing testified about the beneficial effects from the
GED for SIB or AB at JRC. For example, Dr. Susan Shnidman, a clinician,
testified that she observed improvements in the behaviors of many JRC
residents after beginning treatment with the GED, and Dr. Philip
Levendusky, another clinician, acknowledged in his testimony that there
are many examples where the GED had a positive impact on a JRC
resident. Further, clinicians Dr. Mikkelsen stated, and Dr. Zarcone
confirmed, that in many cases there was rapid deceleration in SIB after
the use of the GED, with the problematic behaviors decreasing from
hundreds per day to zero in a very short period of time.
    While expert testimony regarding observed benefits of the GED in
many individuals at JRC is certainly relevant to this rulemaking, and
FDA has taken this information into account in our decision-making,
much more important is the issue of durable, clinically meaningful,
effectiveness of ESDs for SIB or AB. On this more scientifically
complex issue, the expert testimony from the Massachusetts hearing
generally cuts in the opposite direction and is consistent with FDA's
assessment that the evidence is insufficient to establish behavioral
conditioning or durable effectiveness.
    For example, although Dr. Mikkelsen testified that the GED can
suppress the behavior and that he has seen some residents' behaviors
respond to the GED, he also testified that, based on JRC's spreadsheets
regarding efficacy, the GED ``doesn't have any statistically lasting
effect'' and that he does not believe the GED ``actually changes the
behavior in any lasting way'' (Ref. 14, day 7 at 196). Dr. Geller
testified, ``[t]he 168 articles represent a small number of cases that
have extremely mixed results. . .The studies fail to show whether or
not [contingent skin shock] is effective, if the outcome means that the
individual could live a life without the self-injurious behaviors or
would have aggression without shock'' (see Ref. 14, day 21 at 49-60).
Dr. McCracken testified regarding the design weaknesses and inadequate
duration of observation of the majority of studies on ESDs for SIB,
which are particularly detrimental due to the fact that SIB ``waxes and
wanes over time''; one ``could mistakenly attribute those changes to
the treatment if you don't have a comparison group'' (Ref. 14, day 9 at
152). Dr. McCracken summarized that, ``the use of painful electric
shock lacks what any professional group would deem an adequate and well
supported evidence base'' (Ref. 14, day 9 at 85-86), and that he would
never use

shock even if no other treatment worked (see also Ref. 14, day 9 at
149-50, 160).
    Further, according to hearing testimony and an exhibit from Dr.
Geller, for nearly half of the 87 JRC residents with GEDs between 2000
and 2014, the ``peak 12-month period'' during which they received the
most GED shocks was after their first year using a GED at JRC. Based on
Dr. Geller's analysis of JRC data, the average time to peak
applications was 2.7 years, and in some cases the peak was not reached
until they had been receiving GED shocks for 8 years or longer. Dr.
Blenkush of JRC criticized this analysis insofar as it did not include
pre-2000 data; however, JRC did not provide this GED application
frequency data to FDA. According to this hearing testimony and exhibit,
JRC's own data show that for many individuals, the frequency of GED
shocks and hence, the frequency of SIB and AB, increased rather than
decreased for some period of time after GED use began; for many
individuals, the peak 12-month period was many months, and for some
individuals, many years, after GED use began. This casts additional
doubt on JRC's assertions that the GED very quickly decreases SIB and
AB and produces a lasting conditioning effect, as well as on the
ability of ESDs to achieve durable conditioning generally.

E. State of the Art for the Treatment of SIB and AB

    (Comment 42) A comment asserts that PBS is not a state-of-the-art
treatment for individuals exhibiting SIB and AB, arguing that PBS is
not formally defined by any authoritative professional body and that it
has no professional credential or license. However, the comment also
states that ESDs must be used in conjunction with positive approaches.
    (Response) FDA disagrees that the lack of PBS-specific professional
credentialing or licensing means it is not a state-of-the-art treatment
for SIB or AB. As explained in the preamble to the proposed rule, and
as FDA continues to maintain, state-of-the-art treatment for
individuals exhibiting SIB and AB generally relies on multielement
positive interventions such as PBS (81 FR 24386 at 24403-10; see also
section I.A.). The comment cites the hearing testimony of Dr. Zarcone,
a psychologist and board-certified behavior analyst, to show that there
is no educational degree or licensing for PBS. However, elsewhere in
her testimony, Dr. Zarcone states that the use of PBS is generally
accepted practice for the treatment of individuals who have
intellectual and developmental disabilities and severe behavior
problems (Ref. 14, day 13 at 98).
    As we recognized in the proposed rule, multielement positive
methods such as PBS or dialectical behavioral therapy (DBT) span
several categories of intervention for a wide variety of purposes
(Refs. 68 and 69). Likewise, the term ``positive'' can apply to many
different treatment modalities (Refs. 9 and 70). This does not,
however, mean that positive approaches are vague or ill-defined. To the
contrary, a large body of scholarship as well as broad institutional
support informs the use of multielement positive approaches like PBS.
    To take PBS as an example, as we explained in the proposed rule,
the Association for Positive Behavior Supports has adopted specific
standards of practice for the elements that comprise PBS (Ref. 12).
Multielement positive interventions that rely on FBAs, such as PBS, are
described in academic journals, books, graduate training programs, and
professional organization publications (Ref. 12). Likewise, other
positive-only models such as DBT are well-defined and formally
described (see Refs. 71 and 72). Although the comment here states that
PBS is not formally defined, it elsewhere refers to techniques of PBS
as a discrete subset of ABA techniques in which JRC employees have
experience. Furthermore, the comment characterizes one provider, Dr.
Zarcone, as a national expert on PBS, recognizing that PBS is a
distinct, defined treatment approach for SIB and AB. We note that no
professional organization publishes standards of practice for the use
of ESDs, and no journals, graduate programs, or professional
organizations focus on the skills necessary to use contingent electric
shock (see Ref. 12).
    Comments from healthcare providers who have experience treating
patients with SIB and AB explain that state-of-the-art positive
behavioral interventions are even more advanced and effective than the
methods that FDA described in the proposed rule (e.g., PBS). FDA
agrees. For example, in one form of functional behavior assessment
referred to as ``analog functional analysis,'' clinicians identify the
antecedents and consequences that maintain problem behaviors by
experimentally replicating the events or conditions thought to trigger,
incentivize, or reinforce the behavior, then develop a behavior plan
based on modifying these antecedents and consequences (Ref. 73).
According to Dr. Zarcone, analog functional analysis is the most
rigorous and precise level of FBA, and it is now considered to be the
``gold standard'' in the field of applied behavior analysis for
individuals with severe problem behaviors (see Ref. 14, day 13 at 66-
67, 71-72, 80). This is demonstrated by the exponential increase in the
number of research studies relating to analog functional analysis in
recent years: While there were only a handful of such studies before
1985, there were approximately 250 in the 1990s and almost 1,000
between 2001 and 2010 (Refs. 74 and 75).
    The comment asserting that PBS is not a state-of-the-art treatment
for SIB or AB concedes that state-of-the-art treatments available to
patients with SIB and AB include, among other options, positive
behavior therapy, and that, ``PBS therapy is almost always the first
line therapy in the treatment of numerous disorders, including AB and
SIB, due to its limited risk profile.'' The comment goes further,
stating that ESDs ``must always be used in conjunction with positive
behavioral programming as part of a comprehensive care protocol
individualized for the patient.'' These statements contradict the
comment's assertion that approaches such as PBS are not within the
state of the art.
    In analyzing the state of the art in a device ban, the Agency
assesses the risks of the device being banned relative to the risks of
other treatments used in current medical practice for the same
purposes. Positive behavioral treatment techniques have a very low risk
profile, and FDA did not receive any comments suggesting otherwise.
Even this comment concedes PBS is ``low risk.'' The only risk that FDA
found to be associated with positive behavioral treatments is one posed
by ``extinction,'' a common component of behavioral plans (see 81 FR
24386 at 24405). Extinction exhibits the potential risk of ``extinction
bursts,'' an upsurge of the actual undesirable behavior, particularly
manifested in the early stages of the intervention. If this upsurge in
behavior poses a danger to the individual or others, then an extinction
paradigm may not be a feasible option. The behavioral therapist would
have to use a different treatment plan component to accomplish the same
objective. However, extinction bursts would be easily recognized and
quickly mitigated by competent therapists. With respect to SIB and AB,
positive behavioral treatment alternatives present much lower risks
than ESDs, supporting the conclusion that the risks posed by ESDs are
unreasonable.
    (Comment 43) Some comments argue ESDs are necessary options because
positive-only behavioral approaches such as PBS are ineffective for
certain patients, citing literature indicating that

PBS is not always effective for every patient in every situation, and
pointing out that the Panel agreed that treatment options other than
ESDs would not be adequate for all patients. One comment asserts that
FDA has erroneously clung to the notion that the effectiveness of PBS
to treat SIB and AB is an absolute and that FDA was not forthright in
the proposed rule because we treated PBS as though it has been
universally recognized as effective.
    (Response) FDA disagrees. Citing most of the same literature cited
by the commenter, we acknowledged in the proposed rule that positive
behavioral approaches may not always be completely successful for all
patients, either used alone or in conjunction with pharmacological
treatment or other non-ESD treatment options. We also acknowledged that
the Panel agreed that positive behavioral approaches alone are not
adequate for all individuals who exhibit SIB or AB (81 FR 24386 at
24405 to 24406). Further, we explained that not all providers follow a
positive-only behavioral treatment model such as PBS (81 FR 24386 at
24405, citing Refs. 10 and 76). For example, we discussed the sources
cited by the commenter that showed success in 52 percent and 60 percent
of patients where positive behavioral approaches were attempted and
concluded that positive behavioral therapy may sometimes need to be
supplemented with pharmacotherapy or other non-ESD treatment options
(81 FR 24386 at 24405 to 24406). Thus, FDA has not portrayed PBS
effectiveness as an absolute or universally recognized panacea.
However, the literature does indicate PBS is successful for many
individuals who exhibit SIB or AB and that substantial progress in non-
aversive approaches for the treatment of SIB and AB has been evident in
the literature for at least 20 years. More recent literature
corroborates FDA's position; for example, a recent meta-analysis of
case studies in individuals with autism or developmental disabilities
and SIB found that 77 percent of subjects had a positive outcome from
behavioral interventions for SIB (Ref. 77).
    The commenter asserts far more research is needed regarding the
efficacy of PBS for SIB and AB, quoting from a literature review that
FDA cited in the proposed rule. The review states: ``in recent years, a
number of questions have been raised regarding PBS, including questions
regarding the efficacy of using an exclusively positive approach to
support people with seriously challenging behavior'' (Ref. 8). Although
this article states that further research is needed to validate the
findings of the studies conducted, the article goes on to say its
review of 12 published studies concludes that ``the results for
literally hundreds of individuals who received services in different
countries around the world appear to support the conclusion that the
(multi-element PBS) model is effective. Specifically, PBS appears to be
beneficial for the most severe problems (as well as less severe
problems), for high-rate behaviour (as well as low-rate behaviour), and
for behaviour problems exhibited by people who live in institutional
settings (as well as for people who live in the community'' (Ref. 8).
FDA agrees more clinical research on PBS would be helpful, but this
does not undermine the benefits and general success of PBS that have
been shown thus far.
    Two sources cited by the commenter that we did not discuss in the
proposed rule provide further evidence that state-of-the-art behavioral
techniques and psychotropic medications are not always completely
effective for all individuals who exhibit SIB or AB, and that further
research would be helpful (Refs. 78 and 79). Notably, one of them
concludes that outcome measures ``suggest a high degree of
effectiveness'' for behavioral interventions for self-injury (Ref. 79,
noting that treatment failures may be underreported). This echoes our
explanation in the proposed rule (81 FR 24386 at 24403 to 24410):
Although PBS and multielement positive approaches may not be completely
effective for every patient, the literature and the experience of
experts in the field indicate that these are generally successful,
sometimes alongside pharmacotherapy. This is true regardless of the
severity of the behavior targeted, there has been substantial progress
in non-aversive treatments for SIB and AB, and the success rate for
such interventions continues to improve. (See, e.g., Refs. 2, 10, 12,
68, and 80 to 88).
    As discussed in the previous comment response, comments on the
proposed rule from healthcare providers and experts not affiliated with
JRC indicate that positive behavioral interventions are more advanced
and effective than described in the proposed rule, and, most
importantly, such interventions are very low risk. Based on FDA's
expertise, experience, and knowledge of the literature, we agree with
the findings of Dr. McCracken, who testified that the majority of this
patient population can be successfully treated using a combination of
positive behavior supports and pharmacotherapy, without the use of ESDs
(Ref. 14, day 9 at 148; day 10 at 107-08).
    Lastly, even though there are some patients for whom positive
behavioral approaches may not be completely successful, that does not
mean ESDs are effective for those patients. As one Panel member stated,
the fact that other ``therapies are not completely successful or don't
work on all patients does not mean, therefore, that electrical aversive
stimulation is indicated.'' See section V.D. for a discussion of ESD
effectiveness.
    (Comment 44) One comment supports its arguments regarding the
ineffectiveness of non-ESD treatment options for certain individuals by
asserting that, for the individuals on whom ESDs have been used at JRC,
all other behavioral and pharmacological treatment options were
attempted and failed.
    (Response) FDA has reason to doubt that pharmacological and
positive behavioral treatment options were adequately attempted for the
individuals on whom ESDs have been used at JRC based on the available
data and information from JRC. JRC submitted resident summaries to FDA
for 68 individuals at JRC in 2016 on whom ESDs had been used. Of those
68 summaries, only 9 (13 percent) indicate a formal functional
assessment was conducted by JRC, and the summaries indicate that 5
other individuals underwent prior assessments at other facilities. JRC
also submitted related case conference reports to FDA for 54 of those
68 individuals. Those reports indicate that only 19 individuals (35
percent of 54, 28 percent of 68) had either past or ongoing functional
assessments. Therefore, based on the available data and information,
only a fraction of individuals at JRC subject to ESDs appear to have
undergone functional behavioral assessments.
    Further, the resident summaries and conference reports provided to
FDA by JRC provide little to no detail regarding the functional
assessments that had been conducted. For example, information regarding
assessment instruments, granular results, and reassessment results is
nonexistent, and in many cases, they do not identify the function of
the behavior. Thus, for the minority of individuals who have undergone
a documented assessment, the lack of any detail makes it difficult to
identify the functions of the target behaviors, corroborate that the
assessments met accepted standards, or even that the individuals were
periodically reassessed.
    In his hearing testimony, JRC's Director of Research, Dr. Blenkush,
not only acknowledged that JRC does not perform functional analyses but

recognized that outside observers would question why they have not.
(Ref. 14, day 38 at 174). This is consistent with what we explained in
the proposed rule: At least some parents who withdrew their children
from JRC did not report any activity that would indicate the
development of prevention or antecedent strategies, and some reported
that facilities their children attended prior to JRC had not attempted
such strategies or even conducted FBAs.
    As we explained in the proposed rule, a functional behavioral
assessment is critical to developing a successful multi-element
positive intervention or other empirically derived, individualized
behavioral interventions (81 FR 24386 at 24403 to 24404). Failure to
conduct a functional behavioral assessment and do so adequately may
actually lead to harm because the resulting plan may inadvertently
reinforce and consequently increase the problem behavior (Ref. 12).
Similarly, inadequately performed functional assessments could reduce
the effectiveness of the resulting behavioral intervention (Brown
report). The failure to conduct an assessment or re-assessment
properly, or even at all, is tantamount to a failure to attempt multi-
element positive interventions (e.g., PBS) or other interventions that
utilize such assessments.
    Further, the resident summaries JRC submitted include diagnoses but
do not include any information regarding how primary diagnoses were
made, such as what clinical tests or scales were used, or any other
information regarding past medical history. Dr. McCracken testified
that methods of diagnosing individuals at JRC are outdated, and that
its staff ``puts very little effort'' into properly diagnosing
individuals; ``the [JRC] clinicians adopted a kind of cut-and-paste
mentality from the prior evaluations and appear to not feel the need to
more carefully assign and evaluate the presence of these overlapping
terms in an effort to understand their clients more deeply.'' FDA
agrees that JRC's diagnoses lack thoroughness and careful assessment
based on our review of the summaries JRC submitted in its comment. Dr.
McCracken further testified, and FDA agrees, that without a proper
diagnosis, it is difficult for clinicians to develop an appropriate
treatment plan (see Ref. 14, day 9 at 99-101, 104, 107-09, 116-17). As
with any medical condition, improper diagnosis, treatment, and lack of
access to specialty care limits positive outcomes. A proper diagnosis
can greatly increase the chances of beneficial treatment; for example,
when comorbid conditions are correctly diagnosed, they can be
successfully treated with psychotherapies, behavioral therapies, and
pharmacotherapies that are individualized to the patient's needs.
    With regard to the use of positive interventions prior to ESD use,
whether at JRC or before an individual was brought to JRC, the
available data and information lack critical details necessary to
assess whether these treatments were adequately or appropriately
administered. For example, the documents do not provide detail on what
specific therapies were attempted, how long they were tried, or what
the effects were. We cannot determine from the JRC resident charts and
summaries which, if any, treatments were tried prior to placement at
JRC. Critically, the documents do not provide enough information to
determine whether the interventions were appropriately targeting
behaviors, which is necessary to understand whether the interventions
failed, and if so, why they failed.
    More importantly, these omissions also prevent evaluating whether
the use of ESDs caused or contributed to different outcomes. The
reasons provided for placement at JRC include not only unsuccessful
treatment at previous facilities, but also aging out of previous
facilities, rejection by previous facilities, and inability of parents
to handle behaviors at home. For some cases, no reason is provided. Dr.
Shnidman, a psychologist who wrote reports justifying the use of GEDs
on JRC residents as part of the State court approval process, testified
that in almost every case, she recommended that the GED was the most
effective, least restrictive treatment, yet she was not aware whether
JRC tried to use positive interventions or whether positive
interventions were effective (see Ref. 14, day 12 at 156, 217).
Similarly, Dr. Fox testified that he never saw an individual at JRC for
whom an adequate workup had been conducted to establish that a GED was
the most effective, least restrictive treatment (see Ref. 14, day 40 at
39).
    The JRC resident summaries and the hearing testimony and exhibits
that JRC submitted in its comments also cast doubt on JRC's assertions
that pharmacological alternatives were adequately attempted prior to
GED use on individuals. For example, the resident summaries excluded
information on dosage, regimen (e.g., how many, how often, and for what
duration), and both positive and negative effects. In certain
instances, the summaries indicate that maximum therapeutic doses were
not attempted. Dr. Mikkelsen testified that many of the medication
trials he looked at closely ``were inadequate or, you know, the person
may only have been on it for two weeks at a low dose and it's listed as
all these medications didn't work'' (Ref. 14, day 7 at 156). Dr. Geller
testified that, based on the charts he reviewed for individuals weaned
off medication and put on the GED, individuals did not have sufficient
trials of psychopharmacology (see Ref. 14, day 21 at 66).
    JRC documents indicate that JRC generally opposes the use of
pharmacological treatments and makes little effort to attempt their use
before or after prescribing the GED for an individual. For example,
JRC's Policy on Psychotropic Medication states, ``it is JRC's policy to
avoid, or at least minimize the use of psychotropic medication'' and
explains that, for individuals on psychotropic medication prior to
enrollment at JRC, a psychiatrist will be consulted to consider the
benefits of psychotropic medication removal (Ref. 14, exhibit 718). Dr.
Joseph, JRC's sole consulting psychopharmacologist, recommends
medication removal in response to almost every JRC referral (Ref. 14,
day 40 at 136-37). Once psychotropic medications are eliminated, the
individual is typically discharged from Dr. Joseph's care, and no
psychiatrist follows the individual thereafter. In the words of Dr.
Geller, Dr. Joseph ``sees his task as removing people from all their
psychiatric medications and then ending his contact with them'' (Ref.
14, day 21 at 66). Of the 64 individuals with a treatment plan
including ESD use as of June 2015, 7 had no record of any
psychopharmacological consultations, 50 had not had
psychopharmacological evaluations for over 5 years; of these 50, 37 had
not had psychopharmacological evaluations for over 10 years, and 8 had
not had psychopharmacological evaluations for over 20 years (Ref. 14,
day 21 at 6-9, referring to impounded exhibit 662).
    Other comments and testimony indicate that non-ESD alternatives
have been or likely would be successful for individuals on whom ESDs
have been used at JRC. Several comments from healthcare providers
explain that patients with severe SIB or AB at JRC present behaviors
that are challenging to treat. However, such behaviors are no more
challenging to treat than those exhibited by patients with similar
conditions who are successfully treated across the country without the
use of ESDs. This is supported by fact and expert witnesses in the
hearing testimony cited by JRC, who testified

that individuals with the most challenging SIB and AB have been
successfully treated without the use of skin shock at various
institutions across the country. (See, e.g., Ref. 14, day 4 at 42-43
(Simons); day 7 at 49, 60-61, 181 (Mikkelson); day 9 at 39-40, 160
(McCracken); day 13 at 11-12, 138 (Zarcone); day 14 at 24, 28
(Thaler).)
    For example, Dr. McCracken, a clinician who treats individuals with
developmental disabilities who engage in SIB and AB, testified that his
clinic has been successful in treating the vast majority of individuals
and has been able to help everyone, at least to some degree, without
using skin shock (Ref. 14, day 10 at 107-08). Dr. Alfred Bacotti,
another clinician, testified that in his 30 years as a psychologist
treating patients, including some with SIB and AB as severe as those
exhibited by JRC residents, he never used skin shock (Ref. 14 at 212).
Perhaps most tellingly, Dr. Chris White, a licensed psychologist with
over 30 years of experience in the field of behavioral therapies who
runs a facility to which many individuals formerly on ESDs at JRC were
transferred, testified at a Massachusetts DDS hearing in 2011 that his
facility has been able to successfully serve these individuals without
the use of aversives by taking a combined-treatment approach,
emphasizing positive interventions. (See Ref. 14, exhibit 455, at 142-
43, for a partial transcript of the July 2001 hearing.)
    (Comment 45) Behavioral therapists comment that state-of-the-art
treatments such as PBS can prevent the recurrence of SIB and AB because
they address the underlying causes of SIB and AB and the communicative
needs of patients, unlike ESDs.
    (Response) FDA agrees that state-of-the-art interventions such as
PBS are generally successful because, unlike ESDs, they address the
underlying causes of SIB and AB. As we explained in the proposed rule,
one goal of state-of-the-art approaches such as PBS is to teach new
behaviors that proactively displace undesirable behaviors (SIB and AB)
by teaching individuals to express themselves with behavioral
substitutions that will not cause harm to themselves or others (Refs.
87 and 89). For example, functional communication training, as one
element of an intervention, examines the communicative intent of the
problem behaviors (what the individual is trying to communicate or
obtain from others), and then focuses on teaching the individual a
functionally equivalent, but non-problematic, behavior (Ref. 12). There
has been a shift toward prevention in recent years (e.g., structured
environment and schedule, support services at school), and prevention
of SIB and AB is considered the best practice, particularly for those
with intellectual and developmental disabilities (Refs. 77 and 90).
    In contrast, as these comments point out, the use of ESDs does not
teach a person new skills or replacement behaviors, does not mitigate
the underlying cause, and cannot achieve behavioral conditioning for
some patients who have conditions that impair their ability to
understand consequences and react by changing their behaviors (Ref. 8).
Even Dr. Blenkush of JRC stated that providers there can reduce the use
of ESDs through skill training or other procedures and that even people
whom JRC thought could not be faded off of ESDs responded to these
treatments (Ref. 15 at 148). These are some of the reasons that the
field of ABA as a whole moved away from intrusive physical aversive
conditioning techniques such as ESDs two decades ago (Ref. 9, reprinted
from 1990, and Ref. 91).
    (Comment 46) Some parents of individuals at JRC who exhibit SIB or
AB comment that ESDs have been the only treatment capable of reducing
their family member's behaviors. They argue that a ban on ESDs for SIB
or AB would force them to resort to ineffective and risky therapies
such as restraints and medication. Another comment states that FDA has
dismissed such parents' views on the basis that a very small minority
claimed they were coerced or misled.
    (Response) FDA has not dismissed the views of these parents but
rather has given their input careful consideration. As we stated in the
proposed rule, FDA has no reason to doubt these parents' best
intentions, the sincerity of their belief that an ESD is the best or
perhaps only option for their loved one, or that they have tried
alternatives without success. Whether they were opposed to or in favor
of a ban, FDA considered each parent's comments and submissions for the
Panel Meeting, as well as their comments submitted to the public docket
for this rule. As explained in the proposed rule, we did not consider
these parents' reports as scientific evidence relating to the use of
the devices. Rather, FDA used these parents' reports to help inform our
understanding of parents' and patients' experiences and knowledge
regarding the risks and benefits of ESDs and the state of the art.
    As explained in the proposed rule, FDA has reason to question the
information provided to family members by JRC. We explained how some of
the parents' reported experiences contradicted assertions that the
devices were only used as a last resort and indicated that other
treatment strategies were not adequately attempted, in which case it is
not known whether they would have been successful. In the proposed
rule, we referred to parents' reports that, for some of their children,
schools did not attempt all treatment options. For example, some
schools did not use a functional behavioral assessment to develop
prevention or antecedent strategies, strategies that are hallmarks of
state-of-the-art interventions (81 FR 24386 at 21409). Ref. 92 also
stated that once the family members were at JRC, none of the parents
reported the development of prevention or antecedent strategies. None
of the comments on the proposed rule cause us to view these reports
differently. Taken together, these parents' reports indicate that non-
ESD interventions based on functional behavioral assessments that seek
to prevent target behaviors were not adequately attempted for these
individuals. As we acknowledged in the proposed rule, we understand
that these reports are only from certain parents who volunteered to
share negative experiences, and we cannot conclude that these reported
experiences were shared by others or are generally representative of
families' experiences at JRC.
    As with the parents of individuals at JRC, we have no reason to
doubt the sincerity of the parents who removed their children from JRC.
As one researcher noted, these individuals and their families ``have
likely traveled a rough path'' (Ref. 12). For these individuals, ESDs
were not in fact applied as a last resort, and their parents reported
feelings of coercion from JRC (Ref. 92). It thus appears that at least
some parents felt pressured to agree to the use of ESDs, and for at
least some individuals, alternative treatments were not exhausted.
    One comment asserts these viewpoints are hearsay and criticizes FDA
for relying on them while elsewhere rejecting articles supporting ESD
effectiveness because they are not deemed adequately controlled
studies. This criticism is without merit. In fact, FDA's views
regarding the exhaustion of behavioral and pharmacological treatment
options are informed primarily by the scientific literature regarding
state-of-the-art treatments for SIB and AB, expert views on these
issues, and the records provided by JRC regarding individual treatment
prior to ESD use, which suffer from serious limitations, as discussed
in Responses

38 and 44. FDA also considered the views and experiences of parents; as
they relate to the current state of medical practice and alternative
treatment attempts, the reports from parents who oppose the use of ESDs
are consistent with the data and information we considered and
explained in the proposed rule as well as the records JRC provided
regarding its residents. Further, the vast majority of parents who
commented on the state of the art opposed the use of ESDs.
    Again, evidence of failures of treatments other than ESDs is not
evidence that ESDs safely or successfully treat patients. Programs
across the nation successfully treat SIB and AB without ESDs. While
some parents may sincerely believe in the necessity of ESDs and
undoubtedly face serious difficulties in selecting treatment, their
information may be incomplete, and alternatives may not have been
adequately attempted.
    (Comment 47) Hundreds of parents of individuals who exhibit SIB or
AB comment that positive-only approaches work even for the most severe
manifestations of SIB or AB. Some describe a need to be supportive of
individuals, contrasting support with the physically punitive nature of
ESDs.
    (Response) These comments are consistent with FDA's finding that
the state of the art for the treatment of SIB or AB relies on
multielement positive methods, especially PBS, sometimes in conjunction
with pharmacological treatments. ``Positive'' can apply to many
different treatment modalities, but it does not include aversive
interventions such as contingent skin shock (Refs. 9 and 70). State-of-
the-art, multielement, positive interventions such as PBS rely on
functional behavior assessments to design a treatment plan for
individual patients.
    Clinicians ordinarily try multiple positive treatment interventions
if the initial treatment is not successful. Indeed, if a given
intervention does not reduce or eliminate an unwanted behavior, a
clinician would adjust the treatment on an empirical basis. As one
expert in PBS explained, the assessment of behaviors and design of
interventions is an iterative process, and continual adjustment of
positive interventions will serve the patient better than substituting
elements with the use of ESDs (Ref. 82). FDA believes that what these
parents describe in their comments mirrors the state of the art for the
treatment of SIB or AB. Multielement positive interventions are
designed to support the individual by teaching skills and replacement
behaviors, and such interventions can achieve durable success in
community and home settings (Refs. 12, 87, and 88).
    (Comment 48) Comments assert that punishment generally, contingent
shock, and the use of ESDs are state-of-the-art treatment options for
patients with SIB and AB (along with PBS, pharmacotherapy, and
restraint).
    (Response) To ban a device under section 516 of the FD&C Act, FDA
must find that it presents substantial deception or an unreasonable and
substantial risk of illness or injury. As we explained in the preamble
to the proposed rule, 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 (81 FR 24386 at 24386 to 24388).
    The purpose of the analysis of the state of the art is to assess
the risks and benefits of alternatives used in current medical practice
to treat a particular patient population and to compare those to the
risks and benefits of the device that is the subject of the ban, not to
determine whether the device that is the subject of the ban is part of
the state of the art. For these reasons, whether punishment, contingent
shock, or ESDs are within the standard of care or state of the art is
not an issue in this rulemaking. However, the state of current
technical and scientific knowledge and medical practice with regard to
the use of punishment generally and ESDs in particular on patients
exhibiting SIB and AB may still bear some indirect relevance to the
risk-benefit profile of ESDs as compared to alternative treatments.
    As we explained in the proposed rule, punishment techniques include
a broad range of consequences (81 FR 24386 at 24405 to 22406). On one
end of the spectrum, some are highly restrictive and/or painful, such
as the use of ESDs or food deprivation, while, on the other end, some
are less or non-intrusive, such as using ``time-outs.'' Given such a
broad range, FDA did not attempt to define all possible punishment
techniques relative to the state of the art.
    During the hearing, Dr. Zarcone testified that she uses punishment
techniques such as time-outs, holds, and facial screening. However, she
said that she distinguishes her techniques from those that cause pain
such as the use of ESDs (Ref. 14, day 15 at 31-41). Her techniques are
less intrusive, and in her view, teach the individual something about
the behavior and are effective. Such techniques can be compatible with
PBS. In contrast, painful punishments, including aversive
interventions, are not compatible (Ref. 14, day 13 at 103-04). One
textbook explains that electric shock can be replaced with ``more
acceptable aversive outcomes'' such as a squirt of lemon juice or a
reprimand (Ref. 59 at 56-79). Similarly, Dr. Daniel Bagner, a clinician
and professor, testified that he does not teach parents to use painful
punishment such as electric shocks or spanking, and that such
techniques are not part of any evidence-based treatment (Ref. 14, day
11 at 81).
    While punishment-based techniques may appear in textbooks that
provide an overview of treatments for completeness, such references
often caveat the use of punishment-based techniques as less beneficial
than others. As we stated in the proposed rule, a 2008 survey of the
members of the Association for Behavior Analysis found that providers
generally view punishment procedures as having more negative side
effects and being less successful than other reinforcement procedures
(Ref. 76). The study of punishment to treat SIB and AB peaked in the
1980s and has been declining steadily ever since (Ref. 93).
    Regarding ESDs, as we explained in the proposed rule, researchers
have long raised ethical concerns about purposefully subjecting
patients to the harms caused by physically aversive stimuli (see, e.g.,
Refs. 9, 60, 66, 71, and 88). Review of the current scientific
literature confirms that, in recent decades, medical practice has
shifted away from restrictive physical aversive conditioning techniques
such as ESDs and toward treating patients with SIB and AB with
positive-based behavioral interventions (see, e.g., Refs. 9, 10, and
91; see also 81 FR 24386 at 24405). Indeed, of the 57 total published
studies on the effectiveness of contingent skin shock, only 10 such
studies have been published in the past 20 years, and only 1 in the
past decade. Although a few ABA textbooks (one of which is authored by
a JRC Board member) mention contingent skin shock as an available
technique, they also emphasize the highly limited use of ESDs due to
negative side effects and

ethical and humanitarian objections (Ref. 94). FDA acknowledges that a
number of States do not prohibit the use of ESDs for SIB or AB on their
residents, and some States reimburse individuals for the use of ESDs on
their residents in certain circumstances. However, according to a 2015
survey conducted by NASDDDS, 37 of the 45 States that responded
reported that aversive interventions are disallowed for treatment of
people with intellectual or developmental disabilities, and none of the
other eight States included ESDs as permissible aversives. With regard
to the GED specifically, Dr. McCracken testified that no valid evidence
supports the use of the GED and that its use is unethical (Ref. 14, day
9 at 79, 85-86, 160).
    Perhaps most revealingly, as JRC acknowledges in its comments, JRC
is currently the only facility in the country that uses ESDs for SIB or
AB, and it uses ESDs on individuals from only 12 States.
    (Comment 49) A comment questions FDA's reliance on expert reports
for the proposed rule because the experts are vocal advocates for PBS
and vocal critics against the use of ESDs. The comment argues that FDA
sought to bolster a particular point of view with biased advocates
rather than seek information in a more neutral way, and that FDA did
not similarly defer to the opinions of experts affiliated with the
manufacturer.
    (Response) FDA disagrees. Although two of the three outside experts
from whom FDA solicited reports oppose the use of ESDs and support the
ban, the third, Dr. Smith, opposes the ban and instead argues in his
report for allowing their continued use with new regulatory
restrictions. In the proposed rule, we made clear these reports are
``solicited opinions.'' The fact that we found the views of some
experts more compelling than others does not mean we deferred to some
and dismissed others. Rather, given their expertise and experience, we
considered the opinions of all three experts in our analysis of the
risks and benefits of ESDs and alternative treatments, similar to our
consideration of the expert views of the Panel members. In evaluating
these views, we took into account any potential biases, similar to our
review of the literature. FDA made these solicited opinions and the
transcript of the Panel Meeting publicly available in the docket for
the proposed rule, so commenters had an opportunity to examine and
respond to them.
    (Comment 50) One comment asserts that there are no pharmacologic
treatments specifically approved for treatment of SIB and AB; thus, no
drug has been proven effective for such uses, such uses are off-label,
and no drug should be considered a state-of-the-art treatment for SIB
or AB. The comment further asserts that pharmacotherapy is ineffective
for some patients and has severe risks.
    (Response) FDA disagrees with the assertions that state-of-the-art
treatments for SIB or AB do not include pharmacotherapy, and that there
are no pharmacologic treatments specifically approved for the treatment
of SIB or AB.
    It is important to understand that SIB and AB are not disorders
themselves but rather symptoms associated with various underlying
conditions. In clinical practice, SIB and AB are referred to as
transdiagnostic symptoms because they can be associated with numerous,
sometimes comorbid conditions and are not specific to a particular
diagnosis. Examples of disorders in which patients may exhibit SIB and
AB include, but are not limited to:
     Psychiatric disorders, which have a relatively high
prevalence of SIB and AB, for example, attention deficit hyperactivity
disorder (ADHD), mood disorders, psychotic disorders, PTSD, eating
disorders, anxiety disorders, adjustment disorders, and substance use
disorders;
     neurodevelopmental disorders (NDDs) and genetic disorders,
which also have a relatively high prevalence of SIB and AB, for
example, ASD (the definition of which was recently broadened in the
DSM-5), stereotypic movement disorder, intellectual disability, Lesch-
Nyhan Syndrome, fragile X syndrome, Angelman Syndrome, and fetal
alcohol syndrome (FAS); and
     medical diagnoses, for example, traumatic brain injury,
cerebral palsy, and sleep disorders.
    The comment incorrectly minimizes the importance of proper
diagnosis and treatment of underlying causes of SIB and AB. Treatment
of moderate to severe SIB and AB is complex and should be tailored to
the individual needs of each patient; treating the underlying condition
often improves SIB and AB symptoms. Therefore, state-of-the-art
treatment for SIB and AB begins with a proper diagnosis, obtained using
a comprehensive psychiatric and medical examination by a board-
certified specialist (e.g., psychiatrist) in consultation with other
professionals, such as psychologists, pediatricians or internists, and
neurologists (Ref. 95). In recent years, advancements in psychiatric
research and clinical care have improved our understanding of
psychiatric diagnosis and treatment, particularly in individuals with
intellectual and developmental disabilities. This has facilitated the
use of pharmacological treatments that reduce SIB and AB, whether the
drug products target SIB or AB symptoms directly, regardless of the
underlying condition, or by more indirectly reducing SIB and AB by
improving the underlying condition.
    The prevalence of SIB in NDD is high, as high as 50 percent in ASD
(Ref. 96), a population representing a subset of all patients with SIB
and AB. Two drugs are approved for treating irritability associated
with ASD, one of which specifically includes SIB and AB among its
approved indications. Specifically, RISPERDAL (risperidone) is FDA-
approved for the treatment of ``irritability associated with autistic
disorder, including symptoms of aggression towards others, deliberate
self-injuriousness, temper tantrums, and quickly changing moods,''
(emphasis added).\8\ As described in the proposed rule, ABILIFY
(aripiprazole), has also been approved by FDA for the treatment of
irritability associated with autistic disorder in children. As
explained in the FDA-approved labeling for ABILIFY, ``The efficacy of
ABILIFY (aripiprazole) in the treatment of irritability associated with
autistic disorder was established in two 8-week, placebo-controlled
trials in pediatric patients (6 to 17 years of age) who met the DSM-IV
criteria for autistic disorder and demonstrated behaviors such as
tantrums, aggression, self-injurious behavior, or a combination of
these problems,'' (emphasis added).\9\ Both ABILIFY (aripiprazole) and
RISPERDAL (risperidone) met their primary efficacy endpoint by
demonstrating statistically significant changes in score on the
Aberrant Behavior Checklist--Irritability scale (ABC-I), which is one
of the most commonly used scales to measure SIB and AB in drug
development programs. Thus, the comment is incorrect that no drugs have
been proven effective for SIB and AB in any population.
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    \8\ Labeling available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020272s082,020588s070,021444s056lbl.pdf.
    \9\ Labeling available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021436s043,021713s034,021729s026,021866s028lbl.pdf.
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    To date, most of the randomized clinical trials completed for the
treatment of SIB and AB have been conducted in youth with developmental
disabilities such as ASD (see Ref. 77 for review). In clinical
practice, results from these clinical trials for the treatment of SIB
and AB in ASD inform state-of-the-

art pharmacotherapy for SIB and AB treatment across diagnoses because
SIB and AB are considered transdiagnostic symptoms. Therefore,
clinicians consider data related to treatment of SIB and AB in ASD when
determining whether to prescribe drugs for the treatment of SIB and AB
in other psychiatric, genetic, medical and neurodevelopmental disorders
in children and adults.
    The comment recognizes that ``pharmacotherapy may be effective in
controlling the behaviors of certain patients.'' The comment's main
concern seems to be that, ``pharmacotherapy is not uniformly
effective,'' or that ``these types of drugs are not effective for all
persons that exhibit aggressive and SIB behavior.'' FDA agrees that
risperidone and aripiprazole are not uniformly effective for the
treatment of SIB and AB in all patients. However, this does not
undermine FDA's conclusion that the literature indicates that positive
behavioral interventions, sometimes alongside pharmacotherapy, are
generally successful for the treatment of SIB and AB, regardless of the
severity of the behavior targeted.
    The comment highlights the side effects that drugs used to treat
SIB and AB can cause, some of which can be severe. For example, as FDA
pointed out in the proposed rule, the most common adverse reactions
observed in the trials conducted for approval of RISPERDAL and ABILIFY
were sedation, increased appetite, fatigue, constipation, vomiting, and
drooling. Other less common serious adverse reactions with the use of
risperidone or aripiprazole may include neuroleptic malignant syndrome,
gynecomastia, galactorrhea, metabolic changes, and tardive dyskinesia
(note, valbenazine (INGREZZA) and deutetrabenazine (AUSTEDO) have been
approved for the treatment of tardive dyskinesia). FDA acknowledges the
significance of the risks posed by pharmacotherapy, but assesses them
together with their proven benefits. FDA determined that the benefits
outweigh the risks in the population for which they are intended when
we approved these drugs for irritability associated with ASD based on
well-controlled clinical studies.
    Further, drugs that have not been approved for treatment of SIB and
AB and thus have not been found safe and effective for this use may
nonetheless be part of state-of-the-art treatment for SIB and AB, which
has a specific meaning in the context of a device ban. As we explained
in the preamble to the proposed rule, and maintain now, 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 (81 FR 24386 at 24388). Elsewhere in its comments, the
commenter recognizes that state-of-the-art treatment for this patient
population can include pharmacotherapy, among other options, and
asserts that a wide range of pharmacological interventions have been
used to treat patients with SIB and AB, including mood stabilizers,
antidepressants, and antipsychotics.
    A systematic review was recently completed of randomized, placebo-
controlled studies that measured the effect of pharmacologic treatments
on reduction of aggressive behaviors and irritability, measured using
the ABC-I change from baseline score in children with ASD (Ref. 97).
Ref. 97 reports improvement on ABC-I scores for numerous drugs,
including risperidone (Cohen's d = 0.9), aripiprazole (d = 0.8),
clonidine (Cohen's d = 0.6), methylphenidate (d = 0.6), venlafaxine (d
= 0.4), naltrexone (d = 0.35), and valproate (d = 0.3). Ref. 97
illustrates that several drugs in addition to risperidone and
aripiprazole have evidence-based support suggesting that they can
improve symptoms of SIB and AB in ASD. As noted above, only risperidone
and aripiprazole have FDA approval for the treatment of irritability in
ASD.
    In evaluating the state of the art for purposes of determining
whether to ban ESDs, FDA considered the available information regarding
risks of these drugs used for SIB and AB, as well as the available
information regarding their benefits in treating SIB and AB symptoms.
The general risks of risperidone, aripiprazole, clonidine (an alpha-
agonist), and methylphenidate (a stimulant) are described elsewhere in
this comment response. Common adverse reactions associated with
serotonin-norepinephrine reuptake inhibitors (SNRIs) such as
venlafaxine include headache, insomnia, diarrhea, vomiting, decreased
appetite, hyperactivity, irritability, sexual dysfunction, muscle pain,
and change in weight; mania, abnormal heart rhythm, and suicidal
ideation and behavior can also occur. Valproate has FDA-approved
indications in adults related to bipolar disorder, seizures, and
migraine headaches. Common side effects include somnolence, dyspepsia,
nausea, vomiting, diarrhea, dizziness, and pain. Serious adverse
reactions can occur, including hepatoxicity, fetal malformations,
multiorgan hypersensitivity reactions, and thrombocytopenia. Naltrexone
is an opioid antagonist approved for the treatment of addiction and is
associated with dyspepsia, diarrhea, nervousness, sleep problems,
muscle pain and can cause liver injury and allergic pneumonia.
    As stated previously, other drugs may improve SIB and AB symptoms
by treating the underlying disorder for which they are approved. Thus,
in considering the state-of-the-art treatment for SIB and AB, FDA also
considered these treatments of underlying disorders. For example,
children who are impulsive with aggressive outbursts may have moderate
to severe ADHD. FDA-approved medications can treat symptoms of ADHD,
including impulsivity, and therefore may also reduce associated SIB and
AB symptoms. FDA-approved medications for ADHD include stimulant and
non-stimulant medications. Stimulants include amphetamine and
methylphenidate drugs. Common adverse reactions with stimulant use
include decreased appetite, trouble falling asleep, irritability,
headaches, and stomachaches. Reduction in growth rate, sadness,
irritability, tics, abuse, dependence, and elevation in blood pressures
and heart rate can also occur. Sudden death, stroke, and myocardial
infarction have been reported in otherwise healthy adults and in youth
with heart problems taking stimulants. Non-stimulants with FDA-approval
for ADHD include atomoxetine and alpha-agonists. Adverse reactions to
non-stimulant medications include tiredness, insomnia, stomachaches,
headaches, and nausea; hepatitis and suicidal thoughts can also occur.
Thus, these drugs are not without risks, although in approving them,
FDA determined that their risks are outweighed by their benefits in
treating ADHD.
    Accurate diagnosis is especially important for mood disorders
because choosing the wrong class of medications for treatment may
worsen SIB or AB symptoms. For example, individuals who have bipolar
disorder can be misdiagnosed with depression, especially children and
adolescents. This is important because prescribing antidepressant
medications to patients with bipolar disorder may induce or worsen
symptoms of mania, which may include symptoms of irritability and
impulsivity, both of which can be associated with SIB or AB.
Medications approved to treat bipolar disorder include atypical
antipsychotics, anticonvulsants, and lithium salts. Risks associated
with these medications include but are not limited to sedation,

metabolic changes, rash, and other cardiovascular, endocrine,
hematopoietic, and neurological adverse reactions. Neuroleptic
malignant syndrome, extrapyramidal symptoms, tardive dyskinesia, and
gynecomastia/galactorrhea can also occur.
    Some congenital and genetic disorders are also associated with SIB
and AB symptoms. Advancements in understanding genetic and prenatal
exposure-related causes for intellectual and developmental disabilities
have improved diagnosis and management of these conditions, for example
through genetic testing. This is important because some genetic
disorders have treatments, some of which are pharmacological, that can
improve the underlying condition and may also improve associated
behavioral problems such as SIB and AB. For example, psychiatric and
behavioral symptoms associated with phenylketonuria (PKU) can improve
with diet or medications such as pegvaliase-pqpz, which received FDA
approval for the treatment of PKU in 2018 (Ref. 98). The most common
adverse reactions occurring in at least 15 percent of patients taking
pegvaliase-pqpz were injection site reactions, arthralgia,
hypersensitivity reactions, headache, pruritus, nausea, and dizziness.
    Finally, we now recognize that individuals with NDDs, intellectual
disabilities, and other developmental disabilities can have comorbid
psychiatric conditions that benefit from treatment. For example,
treatment of comorbid depression, anxiety, ADHD, psychosis, or bipolar
disorder, can improve symptoms such as irritability, psychomotor
agitation, impulsivity, and worthlessness, which, in turn, can
attenuate associated SIB and AB symptoms. As Dr. McCracken testified at
the Massachusetts hearing, psychiatrists now recognize that
developmentally disabled individuals are at high risk for a variety of
psychological disorders and it is generally accepted medical practice
to treat co-morbid disorders in individuals who exhibit challenging
behaviors (Ref. 14, day 9 at 93). Patients and healthcare providers
have numerous medication options to treat comorbid psychiatric
diagnoses and the associated symptoms, as described earlier in this
comment response.

F. Labeling and Correcting or Eliminating Risks

    (Comment 51) Some comments argue that the risks associated with
ESDs for SIB or AB can be corrected or eliminated through labeling and
other controls, such as the labeling and process JRC currently uses
prior to using ESDs on an individual.
    (Response) FDA disagrees. FDA considered all available data and
information, and we have determined that labeling or a change in
labeling cannot correct or eliminate the unreasonable and substantial
risk of illness or injury. Regardless of how the device is labeled, the
individual subject to it will receive shocks intended to be painful and
will continue to be subject to the physical and psychological risks we
have described in this rulemaking. No manner of labeling will correct
or eliminate these risks, so the device will continue to present the
same unreasonable and substantial risk of illness or injury. The
commenter does not offer any alternative except to limit the number of
vulnerable individuals subject to the unreasonable and substantial
risk.
    The Panel members who opined that the banning standard is met (a
majority of the Panel) were asked whether labeling could correct or
eliminate the risk of illness or injury posed by ESDs and all concluded
that labeling could not correct or eliminate the dangers associated
with ESDs. As we explain in Responses 14 and 18, factors outside of the
user's control, including the psychological state of the individual
subject to the device, can play a significant role in how an individual
perceives any given shock or series of shocks. Further, especially for
those with intellectual or developmental disabilities, the individual
may not communicate or be able to communicate information for the
device user to change the manner in which the device is used to correct
or eliminate the risks. Because these factors are outside of the user's
control or are difficult to ascertain or predict, labeling that
corrects or eliminates the risks of ESDs for SIB or AB cannot be
written.
    The only labeling suggestion the commenter offers regards labeling
the device for use only in individuals refractory to other treatments,
which is how JRC's GED devices are currently labeled. As explained in
comment Response 30, if such a subpopulation does exist, it is very
difficult to define. Even if such a subpopulation could be identified,
specifying this limitation in the labeling would not correct or
eliminate the risks for those individuals. Further, as discussed in the
comment responses regarding effects, no subpopulation has been
identified in which ESDs are more likely to be effective, and thus the
risks of ESDs would still outweigh the benefits. Similarly, as
recognized by the Panel members who were asked, limiting the
indications to a subpopulation of individuals who engage in life-
threatening behaviors would not mitigate the risks for those
individuals, and there is no evidence that the device is effective in
such a subpopulation. Accordingly, limiting the use of the device to a
narrower population through labeling would also not correct or
eliminate the risks.
    (Comment 52) A comment argues that general ``treatment resistant''
language adequately defines the population for whom ECT devices are
intended, which is precisely the population on whom JRC uses ESDs, and
which language could be used in ESD labeling to limit the device's use
to individuals who are refractory to all behavior controls except ESDs.
    (Response) FDA acknowledges that there is language regarding
treatment resistance that does not precisely define a refractory
subpopulation in the labeling for certain other devices that have
different intended uses and different intended patient populations.
However, FDA's position is not that imprecise descriptions of a
refractory patient population are necessarily inadequate but rather
that, in the case of ESDs used for SIB or AB, labeling stating that the
device should only be used in a refractory subpopulation would not
correct or eliminate the unreasonable and substantial risk of illness
or injury to that population. This is because in the case of ESDs, the
available data and information do not establish that the devices are
effective for treating SIB or AB in people who are refractory to other
approaches. Thus, given that the serious risks posed by ESDs for SIB or
AB apply to refractory patients just as they do to others, the risks of
this device outweigh its benefits regardless of whether other options
may have been attempted, and labeling limiting its use to a refractory
population would in no way change this. In contrast, for ECT, the
available data associated with its use, including in treatment
resistant patients, was of better quality and provided a reasonable
assurance of safety and effectiveness.
    Further, for ECT there are better-defined hierarchies of treatment
options prior to use of ECT, based on data demonstrating instances
where other appropriate treatment options were tried and failed. For
example, the APA has issued recommendations for determining when the
use of ECT may be appropriate (Ref. 99), as has the National Institute
for Health and Clinical Excellence in the United Kingdom (Ref. 100).
Thus, the use of ``treatment resistant'' language for ECT, in light of
the data and the formal,

evidence-based practice guidelines, reflects a much clearer consensus
than is available for the use of ESDs for SIB or AB. As discussed in
earlier comment responses, it is difficult to define a refractory
population for ESDs for SIB or AB, JRC has not established that its
residents on whom ESDs are used are refractory to other treatments, and
the evidence shows that state-of-the-art alternatives have generally
been successful even for the most difficult cases. Accordingly, ECT is
distinguishable and FDA's determination remains that labeling or a
change in labeling cannot correct or eliminate the substantial and
unreasonable risks of illness or injury of ESDs used for SIB or AB.
    (Comment 53) A comment argues that an expert believes labeling can
be developed to minimize the risks of ESDs. The comment refers to an
expert whose opinion FDA solicited regarding this ban.
    (Response) FDA disagrees. Dr. Smith proposed certain restrictions,
but none of these address labeling.

G. Legal Issues

    (Comment 54) One commenter suggests that the evidentiary standard
for banning a device is a ``preponderance of evidence,'' meaning that
there must be proof of harm and not just theoretical risk. The
commenter bases this on a statement in the proposed glove powder ban
that the preponderance of evidence suggests that use of an alternative
reduces the incidence of certain harms (81 FR 15173, 15179, March 22,
2016).\10\
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    \10\ Available at https://www.federalregister.gov/documents/2016/03/22/2016-06360/banned-devices-proposal-to-ban-powdered-surgeons-gloves-powdered-patient-examination-gloves-and.
---------------------------------------------------------------------------

    (Response) FDA disagrees. As Congress explained in the legislative
history of section 516 of the FD&C Act, and as FDA stated in the
preamble to its banning regulations at 21 CFR part 895 and in the
preambles to the proposed rules to ban ESDs and glove powder, 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 29214 at
29215; 81 FR 15173 at 15176; 81 FR 24386 at 24392. The proposed rule to
ban glove powder does not state otherwise. The statement cited by the
commenter does not address the standard for a device ban, nor does it
imply that actual harm is required to meet the standard; it simply
states that the evidence relevant to that proceeding indicated that
using alternatives would more likely than not result in lower frequency
of certain harms relative to glove powder.
    (Comment 55) One commenter claims that FDA arbitrarily and
capriciously discounted JRC patient data in the proposed rule and
instead relied on data that are anecdotal and that were carefully