Scientific Information Request on Treatment-Resistant Depression: A Narrative and Systematic Review of Definitions and Methods in Clinical Research Studies, 10015-10018 [2017-02622]
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Federal Register / Vol. 82, No. 26 / Thursday, February 9, 2017 / Notices
Agenda items for these meetings are
subject to change as priorities dictate.
Sharon B. Arnold,
Acting Director.
[FR Doc. 2017–02624 Filed 2–8–17; 8:45 am]
BILLING CODE 4160–90–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Patient Safety Organizations:
Voluntary Relinquishment From the
Fresenius Medical Care PSO, LLC
Agency for Healthcare Research
and Quality (AHRQ), Department of
Health and Human Services (HHS).
ACTION: Notice of delisting.
AGENCY:
The Patient Safety and
Quality Improvement Act of 2005, 42
U.S.C. 299b–21 to b–26, (Patient Safety
Act) and the related Patient Safety and
Quality Improvement Final Rule, 42
CFR part 3 (Patient Safety Rule),
published in the Federal Register on
November 21, 2008, 73 FR 70732–
70814, establish a framework by which
hospitals, doctors, and other health care
providers may voluntarily report
information to Patient Safety
Organizations (PSOs), on a privileged
and confidential basis, for the
aggregation and analysis of patient
safety events. The Patient Safety Rule
authorizes AHRQ, on behalf of the
Secretary of HHS, to list as a PSO an
entity that attests that it meets the
statutory and regulatory requirements
for listing. A PSO can be ‘‘delisted’’ by
the Secretary if it is found to no longer
meet the requirements of the Patient
Safety Act and Patient Safety Rule,
when a PSO chooses to voluntarily
relinquish its status as a PSO for any
reason, or when a PSO’s listing expires.
AHRQ has accepted a notification of
voluntary relinquishment from the
Fresenius Medical Care PSO, LLC of its
status as a PSO, and has delisted the
PSO accordingly. The Fresenius
Medical Care PSO, LLC submitted this
request for voluntary relinquishment
after receiving a Notice of Preliminary
Finding of Deficiency.
DATES: The directories for both listed
and delisted PSOs are ongoing and
reviewed weekly by AHRQ. The
delisting was effective at 12:00 Midnight
ET (2400) on January 6, 2017.
ADDRESSES: Both directories can be
accessed electronically at the following
HHS Web site: https://
www.pso.ahrq.gov/listed.
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Eileen Hogan, Center for Quality
Improvement and Patient Safety, AHRQ,
5600 Fishers Lane, Room 06N94B,
Rockville, MD 20857; Telephone (toll
free): (866) 403–3697; Telephone (local):
(301) 427–1111; TTY (toll free): (866)
438–7231; TTY (local): (301) 427–1130;
Email: pso@ahrq.hhs.gov.
SUPPLEMENTARY INFORMATION:
Background
Agency for Healthcare Research and
Quality
SUMMARY:
FOR FURTHER INFORMATION CONTACT:
The Patient Safety Act authorizes the
listing of PSOs, which are entities or
component organizations whose
mission and primary activity are to
conduct activities to improve patient
safety and the quality of health care
delivery.
HHS issued the Patient Safety Rule to
implement the Patient Safety Act.
AHRQ administers the provisions of the
Patient Safety Act and Patient Safety
Rule relating to the listing and operation
of PSOs. The Patient Safety Rule
authorizes AHRQ to list as a PSO an
entity that attests that it meets the
statutory and regulatory requirements
for listing. A PSO can be ‘‘delisted’’ if
it is found to no longer meet the
requirements of the Patient Safety Act
and Patient Safety Rule, when a PSO
chooses to voluntarily relinquish its
status as a PSO for any reason, or when
a PSO’s listing expires. Section 3.108(d)
of the Patient Safety Rule requires
AHRQ to provide public notice when it
removes an organization from the list of
federally approved PSOs.
AHRQ has accepted a notification
from the Fresenius Medical Care PSO,
LLC, a component entity of Fresenius
Medical Holdings, Inc., PSO number
P0081, to voluntarily relinquish its
status as a PSO. Accordingly, the
Fresenius Medical Care PSO, LLC was
delisted effective at 12:00 Midnight ET
(2400) on January 6, 2017. AHRQ notes
that the Fresenius Medical Care PSO,
LLC submitted this request for voluntary
relinquishment following receipt of the
Notice of Preliminary Finding of
Deficiency sent to the PSO on December
12, 2016.
Fresenius Medical Care PSO, LLC has
patient safety work product (PSWP) in
its possession. The PSO will meet the
requirements of section 3.108(c)(2)(i) of
the Patient Safety Rule regarding
notification to providers that have
reported to the PSO. In addition,
according to sections 3.108(c)(2)(ii) and
3.108(b)(3) of the Patient Safety Rule
regarding disposition of PSWP, the PSO
has 90 days from the effective date of
delisting and revocation to complete the
disposition of PSWP that is currently in
the PSO’s possession.
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More information on PSOs can be
obtained through AHRQ’s PSO Web site
at https://www.pso.ahrq.gov.
Sharon B. Arnold,
Acting Director.
[FR Doc. 2017–02623 Filed 2–8–17; 8:45 am]
BILLING CODE 4160–90–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Agency for Healthcare Research and
Quality
Scientific Information Request on
Treatment-Resistant Depression: A
Narrative and Systematic Review of
Definitions and Methods in Clinical
Research Studies
Agency for Healthcare Research
and Quality (AHRQ), HHS.
ACTION: Request for Scientific
Information Submissions.
AGENCY:
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 of
Treatment-Resistant Depression: A
Narrative and Systematic Review of
Definitions and Methods in Clinical
Research Studies, 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. AHRQ is conducting this
systematic review pursuant to Section
902(a) of the Public Health Service Act,
42 U.S.C. 299a(a).
DATES: Submission Deadline on or
before March 13, 2017.
ADDRESSES: Email submissions:
SEADS@epc-src.org.
Print submissions:
Mailing Address: Portland VA
Research Foundation, Scientific
Resource Center, ATTN: Scientific
Information Packet Coordinator, P.O.
Box 69539, Portland, OR 97239.
Shipping Address (FedEx, UPS, etc.):
Portland VA Research Foundation,
Scientific Resource Center, ATTN:
Scientific Information Packet
Coordinator, 3710 SW U.S. Veterans
Hospital Road, Mail Code: R&D 71,
Portland, OR 97239.
FOR FURTHER INFORMATION CONTACT:
Ryan McKenna, Telephone: 503–220–
8262 ext. 51723 or Email: SIPS@epcsrc.org.
SUMMARY:
The
Agency for Healthcare Research and
Quality has commissioned the
SUPPLEMENTARY INFORMATION:
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Federal Register / Vol. 82, No. 26 / Thursday, February 9, 2017 / Notices
Evidence-based Practice Centers (EPC)
Program to complete a review of the
evidence for Treatment-Resistant
Depression: A Narrative and Systematic
Review of Definitions and Methods in
Clinical Research Studies.
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 Treatment-Resistant
Depression: A Narrative and Systematic
Review of Definitions and Methods in
Clinical Research Studies, including
those that describe adverse events. The
entire research protocol, including the
key questions, is also available online
at: https://www.ahrq.gov/sites/default/
files/wysiwyg/research/findings/ta/
topicrefinement/trdepressionprotocol.pdf
This is to notify the public that the
EPC Program would find the following
information on Treatment-Resistant
Depression (TRD): A Narrative and
Systematic Review of Definitions and
Methods in Clinical Research Studies
helpful:
D 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.
D For completed studies that do not
have results on ClinicalTrials.gov,
please provide 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.
D 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.
D 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.
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Your contribution is very beneficial to
the EPC Program. The contents of all
submissions will be made available to
the public upon request. Materials
submitted must be publicly available or
can 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.
The draft of this review will be posted
on AHRQ’s EPC Program Web site 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://subscriptions.ahrq.gov/accounts/
USAHRQ/subscriber/new?topic_
id=USAHRQ_18.
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. The entire
research protocol, is available online at:
https://www.ahrq.gov/sites/default/files/
wysiwyg/research/findings/ta/
topicrefinement/trdepressionprotocol.pdf
The Key Questions
Narrative Review Questions: Based on
a literature search for consensus
statements, guidelines, materials from
the U.S. Food and Drug Administration
(FDA), the U.S. National Institutes of
Health (NIH), and the U.S. Substance
Abuse and Mental Health Services
Administration (SAMHSA); systematic
reviews; and on a review of UpToDate,
an evidence-based, peer reviewed
clinical information source, we will
address the key questions (Key
Questions [KQs] 1 through 5, with their
subquestions) listed below. In addition,
we will use information from the
Medicare Evidence Development and
Coverage Advisory Committee
(MEDCAC) panel meeting on April 27,
2016, to augment our reporting on TRD
definitions, study design issues, and the
related topics. The specific issues are:
KQ 1. What definitions of TRD are
found in this literature? What
consensus, if any, exists about the best
definition(s) for this condition?
KQ 2. What methods do investigators
use to diagnose this condition in
clinical research? What consensus, if
any, exists about the best measure(s) to
use? Does the setting of the medical visit
influence the choices that investigators
make about the diagnostic tool they use?
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KQ 3. What measures have been
developed to determine the success and
failure of treatment in clinical research
studies of TRD?
I. What consensus, if any, exists about
the best measure(s) to investigate
treatments for TRD? What are the
main points of agreement about
such measures?
II. Are these measures physicianreported or patient-reported?
III. What are the psychometric
properties of these measures? Is the
minimum significant clinical
difference defined for these
measures?
IV. Compare and contrast these
measures in how they describe:
A. Change in depression scores as
measured by depression scales
B. Change in depressive
symptomatology (e.g., sleep
disorders, fatigue, weight change,
cognition)
C. Change in measures of anhedonia
D. Change in measures of functional
capacity (e.g., physical functioning,
ability to care for self)
E. Change in measures of quality of
life
F. Change in measures of suicide
ideation
G. Change in suicide attempts
H. Other
KQ 4. What types of research designs
are used to study TRD?
I. What consensus, if any, exists about
the type of study design that best
minimizes bias and the placebo
effect in this field?
II. If no consensus exists about study
designs to accomplish these goals,
what are the trends in study designs
for assessing interventions for TRD?
Do these trends reflect long-lasting
(e.g., traditional) designs or shortlived, evolving, or newly emerging
designs?
III. What consensus, if any, exists about
the appropriate length of a trial?
KQ 5. What are the risk factors for
TRD?
Systematic Review Questions: From a
systematic literature search for
individual studies on TRD. We will
address the KQs 6 through 11 with their
subquestions as listed below.
KQ 6. What variables were considered
for TRD patients in these studies?
Specify at least the factors listed below.
I. Patient Characteristics:
A. Age
B. Type of depressive episode
(unipolar, bipolar, psychotic,
atypical, other)
C. Number of depression relapses and
time to relapse
D. Psychiatric comorbidities
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E. Medical comorbidities (e.g.,
diabetes, cardiac disease, renal
disease, dementia and other
cognitive abnormalities)
F. Suicidal ideation
G. Suicide attempts
H. Duration of symptoms
I. Screening tools used to make the
diagnosis
J. Diagnostic tools to confirm the
diagnosis
II. Prior Treatments:
A. The number, duration, dosage, or
classes of antidepressants attempted
for each trial of therapy
B. The number of failed trials of
adequate therapy
C. The number of prior treatment
trials that patients did not tolerate
D. The use of augmentation and
combination pharmacological
therapies for each attempted
treatment trial
E. The use of electroconvulsive
therapy
F. The use of psychotherapy
III. Diagnostic characteristics
A. The use of structured versus
unstructured diagnostic
assessments
B. Scores on standardized and
validated depression rating
instruments
C. Setting in which the diagnosis was
made (i.e., primary care,
generalized psychiatric setting,
specialty psychiatric setting, other)
KQ 7. How do these inclusion criteria
compare or contrast with the
definition(s) of TRD noted in the
Narrative Questions?
KQ 8. What were primary
characteristics of included studies?
I. What was the main design of each
included study (e.g., randomized
controlled trial with blinding;
interrupted time series; use of
placebo, wait-list, or sham
procedure)?
II. Were run-in or wash-out periods (or
both) used in included studies? If
so, how long were they?
III. How long was each included study?
KQ 9. How were included studies
designed to account for the risk factors
for TRD (see Narrative Question #5)? If
the following characteristics are not
noted above as risk factors, how did
included studies account for at least the
following: Age, sex, race, socioeconomic
status, duration of symptoms, disease
severity, co-existing medical and
psychiatric conditions, and placebo
effect?
KQ 10. What are relationships
between risk factors and various results
of included studies?
I. Using regression analysis or other
statistical techniques, determine
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whether the risk factors for
Narrative Review Question #5 and
Systematic Review Question # 9 can
be correlated with study results
(i.e., the magnitude of treatment
effects)?
II. What is the influence of placebo
response on the magnitude of
treatment effects for different types
of interventions?
III. Does study duration moderate the
influence of placebo response?
KQ 11. What variables or information
did included studies report?
Specifically:
I. What measures are used to define end
points in these TRD trials?
II. In addition to the measures noted for
Narrative Review Question #3, did
these studies record:
A. Adherence to treatment
B. Attrition from care
C. Changes in patient-selected factors
of importance (i.e., outcome
measures identified by patient as
important)
D. Changes in employment or
disability status
E. Changes in use of medical
resources (e.g., hospitalizations,
emergency room or physician visits)
F. Time to relapse
Any nonpharmacologic device or
procedure tested as a treatment for TRD
as a primary therapy or as augmentation
to an existing primary therapy and
identified as a TRD option by a
consensus statement, guideline, the
MEDCAC panel, or systematic review
(e.g., ECT, repetitive transcranial
magnetic stimulation, vagus nerve
stimulation, deep brain stimulation,
cranial electrotherapy stimulation).
Any nonpharmacologic intervention
tested as a treatment for TRD as a
primary therapy or as augmentation to
an existing primary therapy and
identified as a TRD option by a
consensus statement, guideline, the
MEDCAC panel, or systematic review.
I. Complementary and alternative
medication therapies
II. Psychotherapy
III. Exercise
PICOTS (Populations, Interventions,
Comparators, Outcomes, Time Frames,
Settings)
Mental health outcomes identified in
previous depression comparative
effectiveness review work as either
critical or important for decision
making:
I. Benefits that are reported as primary
endpoints (or outcomes) for a trial.
Such outcomes could include:
Reduction in suicidal ideation or
suicide attempts
A. Quality of life
B. Response to treatment
C. Remission
D. Change in depressive severity
E. Functional capacity (physical and
cognitive functioning measured by
validated scales)
F. Speed of remission
G. Speed of response
H. Intervention durability (rates or
counts of recurrence of a depressive
episode for those who have
remitted)
II. Adverse events from the intervention
identified as either critical or
important for decision making.
Serious adverse events per FDA
definition (rates or counts)
A. Overall adverse events (rates or
counts)
B. Treatment discontinuations
attributed to adverse events (rates or
counts)
Population(s)
All adults (>18 years old) identified as
having a depressive episode (including
major depressive disorder [MDD] and
bipolar disorder) who have not
responded to treatment(s). The
depressive episode must be part of a
major depressive disorder or a bipolar
disorder. Studies of people without a
primary diagnosis of major depressive
disorder or bipolar disorder, or without
evidence of treatment nonresponse, will
be excluded.
Interventions
Any pharmacologic intervention
tested as a treatment for TRD as a
primary therapy or as an augmentation
agent to an existing primary therapy.
I. Antidepressants (e.g., selective
serotonin reuptake inhibitors,
serotonin-norepinephrine reuptake
inhibitors, tricyclic antidepressants,
monoamine oxidase inhibitors
atypical agents)
II. Atypical antipsychotics
III. Anticonvulsants
IV. Mood stabilizers
V. Psychostimulants
VI. Agents approved by the FDA for
other indications but tested in TRD
populations (e.g., ketamine,
levothyroxine [T3], clonidine)
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Comparators
All comparative studies with a
concurrent control group or a control
group from an interrupted time-series
study. These designs exclude pre/post
studies that did not conduct interrupted
time-series analyses.
Outcomes
Time Frames
I. Any study duration.
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Settings
I. All settings.
Our population of interest is adults 18
years of age or older with depression
who have not responded to treatment(s).
The depressive illness can be part of
either major depressive disorder or a
bipolar disorder, but one of these
diagnoses must be a primary diagnosis.
For example, schizophrenia with a
secondary diagnosis of MDD, or
dysthymia, would not be eligible for this
report. If a study involves both eligible
and ineligible patients and does not
report data separately, that whole study
will be excluded. Populations with no
evidence of treatment nonresponse (e.g.,
a study in which the absence of
treatment response is not part of the
selection criteria) will not be eligible.
Eligible interventions include those
that have both been tested as a treatment
targeting TRD in adults and been
identified by guidelines, consensus
statements, the MEDCAC panel, or
systematic reviews as alternatives for
TRD treatment. These criteria ensure
consideration of interventions with a
minimum threshold amount of data
addressing its effectiveness in TRD
populations. Comparison groups
include concurrent control groups (e.g.,
active, sham, or placebo) and a control
group from an interrupted time series.
We will require outcomes to have
been identified previously as the most
meaningful to depression management
decision making. In our earlier
comparative effectiveness work on
depression, we asked our Technical
Expert Panel and Key Informants to rank
the relative importance of these
outcomes following a process proposed
by the GRADE Working Group.30 We
used SurveyMonkey© for an
anonymous ranking of the relative
importance of outcomes. Participants
used a 9-point Likert scale to rank
outcomes into three categories: (1)
Critical for decision making, (2)
important but not critical for decision
making, and (3) of low importance for
decision making. They identified six
outcomes as critical and five as
important, and they supported the
inclusion of an additional depressive
outcome (change in depressive severity).
For one of the adverse events outcomes,
serious adverse events, we will use the
FDA definition and will consider
physical, psychological, and cognitive
events. We will require relevant studies
for the current project to report on at
least 1 of these 12 outcomes.
All study durations and all settings
are eligible. Pre/post studies that do not
use interrupted time series analyses will
be excluded, because potential
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confounding from multiple sources
renders questionable the ability of these
study designs to support causal
inferences. We will include Englishlanguage articles and exclude studies
that are not published fully in English.
Sharon B. Arnold,
Acting Director.
[FR Doc. 2017–02622 Filed 2–8–17; 8:45 am]
BILLING CODE 4160–90–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Health Resources and Services
Administration
National Vaccine Injury Compensation
Program; List of Petitions Received
Health Resources and Services
Administration (HRSA), Department of
Health and Human Services (HHS).
ACTION: Notice.
AGENCY:
HRSA is publishing this
notice of petitions received under the
National Vaccine Injury Compensation
Program (the Program), as required by
the Public Health Service (PHS) Act, as
amended. While the Secretary of HHS
(the Secretary) is named as the
respondent in all proceedings brought
by the filing of petitions for
compensation under the Program, the
United States Court of Federal Claims is
charged by statute with responsibility
for considering and acting upon the
petitions.
SUMMARY:
For
information about requirements for
filing petitions, and the Program in
general, contact the Clerk, United States
Court of Federal Claims, 717 Madison
Place NW., Washington, DC 20005,
(202) 357–6400. For information on
HRSA’s role in the Program, contact the
Director, National Vaccine Injury
Compensation Program, 5600 Fishers
Lane, Room 08N146B, Rockville, MD
20857; (301) 443–6593, or visit our Web
site at: https://www.hrsa.gov/
vaccinecompensation/.
SUPPLEMENTARY INFORMATION: The
Program provides a system of no-fault
compensation for certain individuals
who have been injured by specified
childhood vaccines. Subtitle 2 of Title
XXI of the PHS Act, 42 U.S.C. 300aa–
10 et seq., provides that those seeking
compensation are to file a petition with
the U.S. Court of Federal Claims and to
serve a copy of the petition on the
Secretary, who is named as the
respondent in each proceeding. The
Secretary has delegated this
responsibility under the Program to
FOR FURTHER INFORMATION CONTACT:
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HRSA. The Court is directed by statute
to appoint special masters who take
evidence, conduct hearings as
appropriate, and make initial decisions
as to eligibility for, and amount of,
compensation.
A petition may be filed with respect
to injuries, disabilities, illnesses,
conditions, and deaths resulting from
vaccines described in the Vaccine Injury
Table (the Table) set forth at 42 CFR
100.3. This Table lists for each covered
childhood vaccine the conditions that
may lead to compensation and, for each
condition, the time period for
occurrence of the first symptom or
manifestation of onset or of significant
aggravation after vaccine
administration. Compensation may also
be awarded for conditions not listed in
the Table and for conditions that are
manifested outside the time periods
specified in the Table, but only if the
petitioner shows that the condition was
caused by one of the listed vaccines.
Section 2112(b)(2) of the PHS Act, 42
U.S.C. 300aa–12(b)(2), requires that
‘‘[w]ithin 30 days after the Secretary
receives service of any petition filed
under section 2111 the Secretary shall
publish notice of such petition in the
Federal Register.’’ Set forth below is a
list of petitions received by HRSA on
December 1, 2016, through December
31, 2016. This list provides the name of
petitioner, city and state of vaccination
(if unknown then city and state of
person or attorney filing claim), and
case number. In cases where the Court
has redacted the name of a petitioner
and/or the case number, the list reflects
such redaction.
Section 2112(b)(2) also provides that
the special master ‘‘shall afford all
interested persons an opportunity to
submit relevant, written information’’
relating to the following:
1. The existence of evidence ‘‘that there
is not a preponderance of the
evidence that the illness, disability,
injury, condition, or death
described in the petition is due to
factors unrelated to the
administration of the vaccine
described in the petition,’’ and
2. Any allegation in a petition that the
petitioner either:
a. ‘‘[S]ustained, or had significantly
aggravated, any illness, disability,
injury, or condition not set forth in
the Vaccine Injury Table but which
was caused by’’ one of the vaccines
referred to in the Table, or
b. ‘‘[S]ustained, or had significantly
aggravated, any illness, disability,
injury, or condition set forth in the
Vaccine Injury Table the first
symptom or manifestation of the
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]]>Agencies
[Federal Register Volume 82, Number 26 (Thursday, February 9, 2017)]
[Notices]
[Pages 10015-10018]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-02622]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Agency for Healthcare Research and Quality
Scientific Information Request on Treatment-Resistant Depression:
A Narrative and Systematic Review of Definitions and Methods in
Clinical Research Studies
AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS.
ACTION: Request for Scientific Information Submissions.
-----------------------------------------------------------------------
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 of Treatment-
Resistant Depression: A Narrative and Systematic Review of Definitions
and Methods in Clinical Research Studies, 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. AHRQ is conducting this
systematic review pursuant to Section 902(a) of the Public Health
Service Act, 42 U.S.C. 299a(a).
DATES: Submission Deadline on or before March 13, 2017.
ADDRESSES: Email submissions: src.org">SEADS@epc-src.org.
Print submissions:
Mailing Address: Portland VA Research Foundation, Scientific
Resource Center, ATTN: Scientific Information Packet Coordinator, P.O.
Box 69539, Portland, OR 97239.
Shipping Address (FedEx, UPS, etc.): Portland VA Research
Foundation, Scientific Resource Center, ATTN: Scientific Information
Packet Coordinator, 3710 SW U.S. Veterans Hospital Road, Mail Code: R&D
71, Portland, OR 97239.
FOR FURTHER INFORMATION CONTACT: Ryan McKenna, Telephone: 503-220-8262
ext. 51723 or Email: src.org">SIPS@epc-src.org.
SUPPLEMENTARY INFORMATION: The Agency for Healthcare Research and
Quality has commissioned the
[[Page 10016]]
Evidence-based Practice Centers (EPC) Program to complete a review of
the evidence for Treatment-Resistant Depression: A Narrative and
Systematic Review of Definitions and Methods in Clinical Research
Studies.
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 Treatment-Resistant Depression: A Narrative and
Systematic Review of Definitions and Methods in Clinical Research
Studies, including those that describe adverse events. The entire
research protocol, including the key questions, is also available
online at: https://www.ahrq.gov/sites/default/files/wysiwyg/research/findings/ta/topicrefinement/trdepression-protocol.pdf
This is to notify the public that the EPC Program would find the
following information on Treatment-Resistant Depression (TRD): A
Narrative and Systematic Review of Definitions and Methods in Clinical
Research Studies 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, please provide 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 EPC Program. The
contents of all submissions will be made available to the public upon
request. Materials submitted must be publicly available or can 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.
The draft of this review will be posted on AHRQ's EPC Program Web
site 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://subscriptions.ahrq.gov/accounts/USAHRQ/subscriber/new?topic_id=USAHRQ_18.
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. The entire research
protocol, is available online at: https://www.ahrq.gov/sites/default/files/wysiwyg/research/findings/ta/topicrefinement/trdepression-protocol.pdf
The Key Questions
Narrative Review Questions: Based on a literature search for
consensus statements, guidelines, materials from the U.S. Food and Drug
Administration (FDA), the U.S. National Institutes of Health (NIH), and
the U.S. Substance Abuse and Mental Health Services Administration
(SAMHSA); systematic reviews; and on a review of UpToDate, an evidence-
based, peer reviewed clinical information source, we will address the
key questions (Key Questions [KQs] 1 through 5, with their
subquestions) listed below. In addition, we will use information from
the Medicare Evidence Development and Coverage Advisory Committee
(MEDCAC) panel meeting on April 27, 2016, to augment our reporting on
TRD definitions, study design issues, and the related topics. The
specific issues are:
KQ 1. What definitions of TRD are found in this literature? What
consensus, if any, exists about the best definition(s) for this
condition?
KQ 2. What methods do investigators use to diagnose this condition
in clinical research? What consensus, if any, exists about the best
measure(s) to use? Does the setting of the medical visit influence the
choices that investigators make about the diagnostic tool they use?
KQ 3. What measures have been developed to determine the success
and failure of treatment in clinical research studies of TRD?
I. What consensus, if any, exists about the best measure(s) to
investigate treatments for TRD? What are the main points of agreement
about such measures?
II. Are these measures physician-reported or patient-reported?
III. What are the psychometric properties of these measures? Is the
minimum significant clinical difference defined for these measures?
IV. Compare and contrast these measures in how they describe:
A. Change in depression scores as measured by depression scales
B. Change in depressive symptomatology (e.g., sleep disorders,
fatigue, weight change, cognition)
C. Change in measures of anhedonia
D. Change in measures of functional capacity (e.g., physical
functioning, ability to care for self)
E. Change in measures of quality of life
F. Change in measures of suicide ideation
G. Change in suicide attempts
H. Other
KQ 4. What types of research designs are used to study TRD?
I. What consensus, if any, exists about the type of study design that
best minimizes bias and the placebo effect in this field?
II. If no consensus exists about study designs to accomplish these
goals, what are the trends in study designs for assessing interventions
for TRD? Do these trends reflect long-lasting (e.g., traditional)
designs or short-lived, evolving, or newly emerging designs?
III. What consensus, if any, exists about the appropriate length of a
trial?
KQ 5. What are the risk factors for TRD?
Systematic Review Questions: From a systematic literature search
for individual studies on TRD. We will address the KQs 6 through 11
with their subquestions as listed below.
KQ 6. What variables were considered for TRD patients in these
studies? Specify at least the factors listed below.
I. Patient Characteristics:
A. Age
B. Type of depressive episode (unipolar, bipolar, psychotic,
atypical, other)
C. Number of depression relapses and time to relapse
D. Psychiatric comorbidities
[[Page 10017]]
E. Medical comorbidities (e.g., diabetes, cardiac disease, renal
disease, dementia and other cognitive abnormalities)
F. Suicidal ideation
G. Suicide attempts
H. Duration of symptoms
I. Screening tools used to make the diagnosis
J. Diagnostic tools to confirm the diagnosis
II. Prior Treatments:
A. The number, duration, dosage, or classes of antidepressants
attempted for each trial of therapy
B. The number of failed trials of adequate therapy
C. The number of prior treatment trials that patients did not
tolerate
D. The use of augmentation and combination pharmacological
therapies for each attempted treatment trial
E. The use of electroconvulsive therapy
F. The use of psychotherapy
III. Diagnostic characteristics
A. The use of structured versus unstructured diagnostic assessments
B. Scores on standardized and validated depression rating
instruments
C. Setting in which the diagnosis was made (i.e., primary care,
generalized psychiatric setting, specialty psychiatric setting, other)
KQ 7. How do these inclusion criteria compare or contrast with the
definition(s) of TRD noted in the Narrative Questions?
KQ 8. What were primary characteristics of included studies?
I. What was the main design of each included study (e.g., randomized
controlled trial with blinding; interrupted time series; use of
placebo, wait-list, or sham procedure)?
II. Were run-in or wash-out periods (or both) used in included studies?
If so, how long were they?
III. How long was each included study?
KQ 9. How were included studies designed to account for the risk
factors for TRD (see Narrative Question #5)? If the following
characteristics are not noted above as risk factors, how did included
studies account for at least the following: Age, sex, race,
socioeconomic status, duration of symptoms, disease severity, co-
existing medical and psychiatric conditions, and placebo effect?
KQ 10. What are relationships between risk factors and various
results of included studies?
I. Using regression analysis or other statistical techniques, determine
whether the risk factors for Narrative Review Question #5 and
Systematic Review Question # 9 can be correlated with study results
(i.e., the magnitude of treatment effects)?
II. What is the influence of placebo response on the magnitude of
treatment effects for different types of interventions?
III. Does study duration moderate the influence of placebo response?
KQ 11. What variables or information did included studies report?
Specifically:
I. What measures are used to define end points in these TRD trials?
II. In addition to the measures noted for Narrative Review Question #3,
did these studies record:
A. Adherence to treatment
B. Attrition from care
C. Changes in patient-selected factors of importance (i.e., outcome
measures identified by patient as important)
D. Changes in employment or disability status
E. Changes in use of medical resources (e.g., hospitalizations,
emergency room or physician visits)
F. Time to relapse
PICOTS (Populations, Interventions, Comparators, Outcomes, Time Frames,
Settings)
Population(s)
All adults (>18 years old) identified as having a depressive
episode (including major depressive disorder [MDD] and bipolar
disorder) who have not responded to treatment(s). The depressive
episode must be part of a major depressive disorder or a bipolar
disorder. Studies of people without a primary diagnosis of major
depressive disorder or bipolar disorder, or without evidence of
treatment nonresponse, will be excluded.
Interventions
Any pharmacologic intervention tested as a treatment for TRD as a
primary therapy or as an augmentation agent to an existing primary
therapy.
I. Antidepressants (e.g., selective serotonin reuptake inhibitors,
serotonin-norepinephrine reuptake inhibitors, tricyclic
antidepressants, monoamine oxidase inhibitors atypical agents)
II. Atypical antipsychotics
III. Anticonvulsants
IV. Mood stabilizers
V. Psychostimulants
VI. Agents approved by the FDA for other indications but tested in TRD
populations (e.g., ketamine, levothyroxine [T3], clonidine)
Any nonpharmacologic device or procedure tested as a treatment for
TRD as a primary therapy or as augmentation to an existing primary
therapy and identified as a TRD option by a consensus statement,
guideline, the MEDCAC panel, or systematic review (e.g., ECT,
repetitive transcranial magnetic stimulation, vagus nerve stimulation,
deep brain stimulation, cranial electrotherapy stimulation).
Any nonpharmacologic intervention tested as a treatment for TRD as
a primary therapy or as augmentation to an existing primary therapy and
identified as a TRD option by a consensus statement, guideline, the
MEDCAC panel, or systematic review.
I. Complementary and alternative medication therapies
II. Psychotherapy
III. Exercise
Comparators
All comparative studies with a concurrent control group or a
control group from an interrupted time-series study. These designs
exclude pre/post studies that did not conduct interrupted time-series
analyses.
Outcomes
Mental health outcomes identified in previous depression
comparative effectiveness review work as either critical or important
for decision making:
I. Benefits that are reported as primary endpoints (or outcomes) for a
trial. Such outcomes could include: Reduction in suicidal ideation or
suicide attempts
A. Quality of life
B. Response to treatment
C. Remission
D. Change in depressive severity
E. Functional capacity (physical and cognitive functioning measured
by validated scales)
F. Speed of remission
G. Speed of response
H. Intervention durability (rates or counts of recurrence of a
depressive episode for those who have remitted)
II. Adverse events from the intervention identified as either critical
or important for decision making. Serious adverse events per FDA
definition (rates or counts)
A. Overall adverse events (rates or counts)
B. Treatment discontinuations attributed to adverse events (rates
or counts)
Time Frames
I. Any study duration.
[[Page 10018]]
Settings
I. All settings.
Our population of interest is adults 18 years of age or older with
depression who have not responded to treatment(s). The depressive
illness can be part of either major depressive disorder or a bipolar
disorder, but one of these diagnoses must be a primary diagnosis. For
example, schizophrenia with a secondary diagnosis of MDD, or dysthymia,
would not be eligible for this report. If a study involves both
eligible and ineligible patients and does not report data separately,
that whole study will be excluded. Populations with no evidence of
treatment nonresponse (e.g., a study in which the absence of treatment
response is not part of the selection criteria) will not be eligible.
Eligible interventions include those that have both been tested as
a treatment targeting TRD in adults and been identified by guidelines,
consensus statements, the MEDCAC panel, or systematic reviews as
alternatives for TRD treatment. These criteria ensure consideration of
interventions with a minimum threshold amount of data addressing its
effectiveness in TRD populations. Comparison groups include concurrent
control groups (e.g., active, sham, or placebo) and a control group
from an interrupted time series.
We will require outcomes to have been identified previously as the
most meaningful to depression management decision making. In our
earlier comparative effectiveness work on depression, we asked our
Technical Expert Panel and Key Informants to rank the relative
importance of these outcomes following a process proposed by the GRADE
Working Group.30 We used SurveyMonkey(copyright) for an anonymous
ranking of the relative importance of outcomes. Participants used a 9-
point Likert scale to rank outcomes into three categories: (1) Critical
for decision making, (2) important but not critical for decision
making, and (3) of low importance for decision making. They identified
six outcomes as critical and five as important, and they supported the
inclusion of an additional depressive outcome (change in depressive
severity). For one of the adverse events outcomes, serious adverse
events, we will use the FDA definition and will consider physical,
psychological, and cognitive events. We will require relevant studies
for the current project to report on at least 1 of these 12 outcomes.
All study durations and all settings are eligible. Pre/post studies
that do not use interrupted time series analyses will be excluded,
because potential confounding from multiple sources renders
questionable the ability of these study designs to support causal
inferences. We will include English-language articles and exclude
studies that are not published fully in English.
Sharon B. Arnold,
Acting Director.
[FR Doc. 2017-02622 Filed 2-8-17; 8:45 am]
BILLING CODE 4160-90-P
