[Federal Register Volume 87, Number 135 (Friday, July 15, 2022)]
[Notices]
[Pages 42465-42468]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-15112]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality


Supplemental Evidence and Data Request on ADHD Diagnosis and 
Treatment in Children and Adolescents

AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS.

ACTION: Request for Supplemental Evidence and Data Submissions.

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SUMMARY: The Agency for Healthcare Research and Quality (AHRQ) is 
seeking scientific information submissions from the public. Scientific 
information is being solicited to inform our review on ADHD Diagnosis 
and Treatment in Children and Adolescents, which is currently being 
conducted by the AHRQ's Evidence-based Practice Centers (EPC) Program. 
Access to published and unpublished pertinent scientific information 
will improve the quality of this review.

DATES: Submission Deadline on or before August 15, 2022.

ADDRESSES: 
    Email submissions: <a href="/cdn-cgi/l/email-protection#d0b5a0b390b1b8a2a1feb8b8a3feb7bfa6"><span class="__cf_email__" data-cfemail="bcd9ccdffcddd4cecd92d4d4cf92dbd3ca">[email protected]</span></a>.
    Print submissions:
    Mailing Address: Center for Evidence and Practice Improvement, 
Agency for Healthcare Research and Quality, ATTN: EPC SEADs 
Coordinator, 5600 Fishers Lane, Mail Stop 06E53A, Rockville, MD 20857.
    Shipping Address (FedEx, UPS, etc.): Center for Evidence and 
Practice Improvement, Agency for Healthcare Research and Quality, ATTN: 
EPC SEADs Coordinator, 5600 Fishers Lane, Mail Stop 06E77D, Rockville, 
MD 20857.

FOR FURTHER INFORMATION CONTACT: Jenae Benns, Telephone: 301-427-1496 
or Email: <a href="/cdn-cgi/l/email-protection#0e6b7e6d4e6f667c7f2066667d20696178"><span class="__cf_email__" data-cfemail="2c495c4f6c4d445e5d0244445f024b435a">[email protected]</span></a>.

SUPPLEMENTARY INFORMATION: The Agency for Healthcare Research and 
Quality has commissioned the Evidence-based Practice Center (EPC) 
Program to complete a review of the evidence for ADHD Diagnosis and 
Treatment in Children and Adolescents. AHRQ is conducting this 
systematic review pursuant to Section 902 of the Public Health Service 
Act, 42 U.S.C. 299a.
    The EPC Program is dedicated to identifying as many studies as 
possible that are relevant to the questions for each of its reviews. In 
order to do so, we are supplementing the usual manual and electronic 
database searches of the literature by requesting information from the 
public (e.g., details of studies conducted). We are looking for studies 
that report on ADHD Diagnosis and Treatment in Children and 
Adolescents, including those that describe adverse events. The entire 
research protocol is available online at: https://effectivehealthcare.ahrq.gov/products/attention-deficit-hyperactivity-disorder/protocol.
    This is to notify the public that the EPC Program would find the 
following information on ADHD Diagnosis and Treatment in Children and 
Adolescents helpful:
    [ssquf] A list of completed studies that your organization has 
sponsored for this indication. In the list, please indicate whether 
results are available on ClinicalTrials.gov along with the 
ClinicalTrials.gov trial number.
    [ssquf] For completed studies that do not have results on 
ClinicalTrials.gov, a summary, including the following elements: study 
number, study period, design, methodology, indication and diagnosis, 
proper use instructions, inclusion and exclusion criteria, primary and 
secondary outcomes, baseline characteristics, number of patients 
screened/eligible/enrolled/lost to follow-up/withdrawn/analyzed, 
effectiveness/efficacy, and safety results.
    [ssquf] A list of ongoing studies that your organization has 
sponsored for this indication. In the list, please provide the 
ClinicalTrials.gov trial number or, if the trial is not registered, the 
protocol for the study including a study number, the study period, 
design, methodology, indication and diagnosis, proper use instructions, 
inclusion and exclusion criteria, and primary and secondary outcomes.
    [ssquf] Description of whether the above studies constitute ALL 
Phase II and above clinical trials sponsored by your organization for 
this indication and an index outlining the relevant information in each 
submitted file.
    Your contribution is very beneficial to the Program. Materials 
submitted must be publicly available or able to be made public. 
Materials that are considered confidential; marketing materials; study 
types not included in the review; or information on indications not 
included in the review cannot be used by the EPC Program. This is a 
voluntary request for information, and all costs for complying with 
this request must be borne by the submitter.

[[Page 42466]]

    The draft of this review will be posted on AHRQ's EPC Program 
website and available for public comment for a period of 4 weeks. If 
you would like to be notified when the draft is posted, please sign up 
for the email list at: https://www.effectivehealthcare.ahrq.gov/email-updates.
    The systematic review will answer the following questions. This 
information is provided as background. AHRQ is not requesting that the 
public provide answers to these questions.

Key Questions (KQ)

    KQ1: For the diagnosis of ADHD:
    <bullet> What is the comparative diagnostic accuracy of approaches 
that can be used in the primary care practice setting or by specialists 
to diagnose ADHD among individuals younger than 7 years of age?
    <bullet> What is the comparative diagnostic accuracy of EEG, 
imaging, or approaches assessing executive function that can be used in 
the primary care practice setting or by specialists to diagnose ADHD 
among individuals aged 7 through 17?
    <bullet> For both populations, how does the comparative diagnostic 
accuracy of these approaches vary by clinical setting, including 
primary care or specialty clinic, or patient subgroup, including age, 
sex, or other risk factors associated with ADHD?
    <bullet> What are the adverse effects associated with being labeled 
correctly or incorrectly as having ADHD?
    KQ2: What are the comparative safety and effectiveness of 
pharmacologic and/or nonpharmacologic treatments of ADHD in improving 
outcomes associated with ADHD?
    <bullet> How do these outcomes vary by presentation (inattentive, 
hyperactive/impulsive, and combined) or other comorbid conditions?
    <bullet> What is the risk of diversion of pharmacologic treatment?
    KQ 3: What are the comparative safety and effectiveness of 
different empirical monitoring strategies to evaluate the effectiveness 
of treatment in improving ADHD symptoms or other long-term outcomes?

                 PICOTS (Populations, Interventions, Comparators, Outcomes, Timing, and Setting)
----------------------------------------------------------------------------------------------------------------
          PICOTS element                     Inclusion criteria                      Exclusion criteria
----------------------------------------------------------------------------------------------------------------
Population.......................  KQ 1 (diagnosis): Individuals birth     KQ 1, KQ 2: Individuals 18 years of
                                    through 17 years of age without the     age or older unless findings are
                                    diagnosis of ADHD.                      reported separately for individuals
                                   KQ 2 (treatment): Individuals birth      18 years and under, or if the mean
                                    through 17 years of age with a          patient age plus the standard
                                    diagnosis of ADHD.                      deviation is not greater than 21
                                   KQ 3 (monitoring): Individuals birth     years of age.
                                    through 17 years of age who have       KQ 3: For long-term studies, the age
                                    previously begun treatment for ADHD.    of the individuals may be greater
                                                                            than 17, but these studies are only
                                                                            considered for inclusion if the age
                                                                            at enrollment in the study was 18
                                                                            years or younger, and administrative
                                                                            claims data used for diagnosis of
                                                                            ADHD.
Interventions....................  KQ 1 (diagnosis): Any standard ADHD     KQ 1: Validation studies or diagnosis
                                    diagnostic strategy, including          conducted using a non-validated
                                    clinician interview, standardized       instrument.
                                    instrument (e.g., Vanderbilt scales,   KQ 2: Studies comparing pharmacologic
                                    Conner scales, SNAP-IV rating score),   agents approved by the FDA for the
                                    neuropsychological test measures        treatment of ADHD that have
                                    (e.g., working memory, processing       enrollment of fewer than 100
                                    speed, continuous performance tasks)    patients with ADHD, or less than 6
                                    for individuals under 7 years of age.   months of follow-up.
                                    The use of EEG-based systems,
                                    imaging, or assessment of executive
                                    function for the diagnosis of ADHD in
                                    individuals through 17 years.
                                   KQ 2 (treatment): Any pharmacologic or
                                    nonpharmacologic treatment of ADHD,
                                    alone or in combination:
                                   <bullet> Pharmacologic treatments       .....................................
                                    considered are brand name and generic
                                    formulations of FDA-approved
                                    stimulants (methylphenidate,
                                    amphetamine) and non-stimulants
                                    (norepinephrine reuptake inhibitors,
                                    alpha agonists) and other suggested
                                    treatments, including
                                    methylphenidate, dexmethylphenidate,
                                    dextroamphetamine, lisdexamfetamine,
                                    mixed amphetamine salts, amphetamine,
                                    tricyclic antidepressants,
                                    desipramine, nortriptyline, selective
                                    norepinephrine reuptake inhibitors,
                                    atomoxetine, alpha-2 agonists,
                                    clonidine, guanfacine, dopamine
                                    reuptake inhibitors, modafinil,
                                    armodafinil, norepinephrine-dopamine
                                    reuptake inhibitors, bupropion,
                                    serotonin-norepinephrine reuptake
                                    inhibitors, duloxetine, serotonin-
                                    norepinephrine-dopamine reuptake
                                    inhibitors, venlafaxine, monoamine
                                    oxidase type B inhibitors,
                                    selegiline, N-methyl-D-aspartate
                                    receptor antagonists, amantadine,
                                    memantine.

[[Page 42467]]

 
                                   <bullet> Nonpharmacologic therapies     .....................................
                                    considered include psychosocial
                                    interventions, behavioral
                                    interventions, cognitive behavioral
                                    therapy, digital gamified cognitive
                                    therapies, EndeavorRx, play therapy,
                                    play-based interventions, mindfulness-
                                    based therapies, school
                                    interventions, cognitive training
                                    therapies, biofeedback or
                                    neurofeedback, parent behavior
                                    training, dietary supplements (e.g.,
                                    omega-3 fatty acids, vitamins, herbal
                                    supplements, probiotics), homeopathy,
                                    acupuncture, elimination diets,
                                    vision training, exercise,
                                    chiropractic treatment, peer
                                    interventions, and Monarch external
                                    trigeminal nerve stimulation (eTNS)
                                    system.
                                   KQ 3 (monitoring): Follow-up visits in  .....................................
                                    primary care using various methods
                                    and frequencies (monthly to annually)
                                    for monitoring, independent of
                                    treatment, including the selection of
                                    scales/validated tools for monitoring
                                    of ADHD severity and treatment
                                    response along with forms of remote
                                    monitoring or telehealth strategies.
Comparators......................  KQ 1 (diagnosis): Confirmation of       KQ 1: Comparison to diagnosis with a
                                    diagnosis by a specialist (gold         non-validated instrument.
                                    standard), such as a psychologist,
                                    psychiatrist or other care provider
                                    using a well-validated and reliable
                                    process of confirming the diagnosis
                                    of ADHD according to the DSM-5.
                                   KQ 2 (treatment): Specific treatments   KQ 2: Comparisons to other patient
                                    compared with other treatments as       groups rather than treatments.
                                    described above or to no treatment.
                                   KQ 3 (monitoring): Follow-up compared   .....................................
                                    with differing frequencies of follow-
                                    up or different settings of follow-up
                                    for monitoring strategies; no
                                    restrictions for long-term outcomes.
Outcomes.........................  KQ 1 (diagnosis):                       .....................................
                                   <bullet> Accuracy of diagnostic         .....................................
                                    strategy, as measured by: diagnostic
                                    concordance of primary care provider
                                    with specialist, inter-rater
                                    reliability, internal consistency,
                                    test-retest, sensitivity,
                                    specificity, area under the curve,
                                    positive predictive value, negative
                                    predictive value, false positives,
                                    false negatives.
                                   <bullet> Risk of misdiagnosis, missed   .....................................
                                    condition that can appear as ADHD
                                    Labeling is any measure of stigma
                                    following diagnosis comparing those
                                    with and without ADHD.
                                   <bullet> Costs.                         .....................................
                                   KQ 2 (treatment):                       .....................................
                                   <bullet> Intermediate outcomes:         .....................................
                                   [cir] Changes on standardized symptom   .....................................
                                    scores, including narrow-band focused
                                    instruments (Vanderbilt rating
                                    scales, ADHD Rating Scales such as
                                    the Strength and Weaknesses of
                                    Attention-Deficit/Hyperactivity
                                    Disorder Symptoms [SWAN]) and broad-
                                    band scales (Child Behavior Checklist
                                    and Teacher Report Form, Behavior
                                    Assessment System for Children,
                                    Conners' Rating Scales-Revised,
                                    Conners' 3 Parent, Conners' 3
                                    Teacher).
                                   [cir] Progress toward patient-          .....................................
                                    identified goals.
                                   [cir] Executive functioning measure     .....................................
                                    changes.
                                   [cir] Functional impairment (assessed   .....................................
                                    using the Clinical Global Impressions
                                    [CGI] scale of the Impairment Rating
                                    Scale [IRS]).
                                   [cir] Acceptability of treatment.       .....................................
                                   <bullet> Final outcomes:                .....................................
                                   [cir] Academic performance (Academic    .....................................
                                    Performance Rating Scale Academic
                                    Competency Evaluation Scale (ACES),
                                    school grades, grade retention/not
                                    being promoted, Vanderbilt Teacher
                                    Form Academic Performance Subscale,
                                    standardized achievement tests (WIAT,
                                    WJ, WRAT).

[[Page 42468]]

 
                                   [cir] Workforce participation, quality  .....................................
                                    of peer relationships, divorce/
                                    relationship status, motor vehicle
                                    collisions or other accidents, motor
                                    vehicle violations, risk-taking
                                    behaviors, incarceration or other
                                    interactions with the legal system
                                    (juvenile detention, probation, court-
                                    mandated interventions, need for
                                    residential placement).
                                   [cir] Obesity, tobacco use, substance   .....................................
                                    abuse, mood disorders, depression or
                                    anxiety, self-injurious non-suicidal
                                    behavior, suicide (attempted or
                                    completed), suicidal ideation,
                                    mortality.
                                   [cir] Potential adverse effects of      .....................................
                                    treatment, including changes in
                                    appetite, growth suppression, weight
                                    decrease, sleep disturbance,
                                    gastrointestinal symptoms, elevated
                                    blood pressure, increased heart rate,
                                    risk of sudden cardiac death, cardiac
                                    arrhythmias, conduction
                                    abnormalities, chemical leukoderma;
                                    priapism, tics or other movement
                                    disorders, hallucination, aggression,
                                    behavior changes, personality change,
                                    loss of spontaneity, number of
                                    adverse events.
                                   [cir] Overtreatment, diversion and      .....................................
                                    misuse of pharmacotherapy, parental
                                    stress, time demands/opportunity
                                    cost.
                                   KQ 3 (monitoring):                      .....................................
                                   <bullet> Changes in treatment or dose.  .....................................
                                   <bullet> Adverse effects of treatment.  .....................................
                                   <bullet> Changes in intermediate and    .....................................
                                    final outcomes.
Timing...........................  KQ 1 (diagnosis):                       .....................................
                                   <bullet> For assessment of diagnostic   .....................................
                                    accuracy: diagnostic follow-up must
                                    be within 4 months of the initial
                                    evaluation and must be completed
                                    before treatment is initiated.
                                   <bullet> For labeling: any time after   .....................................
                                    the ADHD diagnosis.
                                   KQ 2 (treatment) and KQ 3               .....................................
                                    (monitoring): Any.
Setting..........................  KQ 1 (diagnosis): Primary or specialty  .....................................
                                    care settings.
                                   KQ 2 (treatment) and KQ 3
                                    (monitoring): Any (including remote
                                    monitoring and telehealth).
Study Design.....................  <bullet> Original data.                 Editorials, nonsystematic reviews,
                                   KQ 1-3: Randomized controlled trials     letters, case series, case reports,
                                    (RCTs).                                 abstract-only, pre-post studies.
                                   KQ 1 (diagnosis): For diagnostic         Because studies with fewer than 20
                                    accuracy, observational studies,        subjects are often pilot studies or
                                    including cross-sectional studies,      studies of lower quality, these are
                                    are eligible if they include patients   excluded. Given the research volume
                                    with diagnostic uncertainty and         on pharmacologic treatment the
                                    direct comparison of diagnosis in       sample size limit for non-RCTs is
                                    primary care to diagnosis by a          100 participants, representing
                                    specialist.                             population study sizes that could
                                   KQ 1 (diagnosis) and KQ 2 (treatment):   substantially impact the assessment
                                    controlled clinical trials and          of the existing evidence base.
                                    prospective and retrospective           Systematic reviews are not eligible
                                    observational studies with              for inclusion but will be retained.
                                    comparator; sample size:
                                   <bullet> >=20 participants.
                                   <bullet> >=100 participants for
                                    studies comparing two or more
                                    pharmacologic treatments.
                                   KQ 3 (monitoring): no study size
                                    restriction.
Other limiters...................  <bullet> English-language               Non-English language and abbreviated
                                    publications.                           publications (abstracts, letters).
                                   <bullet> KQ 1 and KQ 2: Published in
                                    or after 2016 and not included in the
                                    prior AHRQ report on ADHD; in
                                    addition, we will use studies
                                    included in meta-analyses in the
                                    prior report for cumulative meta-
                                    analyses.
                                   <bullet> KQ 3: Monitoring strategies    .....................................
                                    and long-term effects have no
                                    publication year restriction.
                                   <bullet> Journal manuscripts and trial
                                    record data with results.
----------------------------------------------------------------------------------------------------------------
Note: FDA: Food and Drug Administration, KQ: Key Question.


    Dated: July 11, 2022.
Marquita Cullom,
Associate Director.
[FR Doc. 2022-15112 Filed 7-14-22; 8:45 am]
BILLING CODE 4160-90-P


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