[Federal Register Volume 84, Number 226 (Friday, November 22, 2019)]
[Notices]
[Pages 64523-64527]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-25414]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality


Supplemental Evidence and Data Request on Management of Primary 
Headache During Pregnancy

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 Management of 
Primary Headache during Pregnancy, 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published and unpublished pertinent scientific information will improve 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 30 days after date of 
publication.

ADDRESSES: 
    Email submissions: [email protected].
    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: [email protected].

SUPPLEMENTARY INFORMATION: The Agency for Healthcare Research and 
Quality has commissioned the Evidence-based Practice Centers (EPC) 
Program to complete a review of the evidence Management of Primary 
Headache during Pregnancy. AHRQ is conducting this systematic review 
pursuant to Section 902(a) of the Public Health Service Act, 42 U.S.C. 
299a(a).
    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

[[Page 64524]]

conducted). We are looking for studies that report on Management of 
Primary Headache during Pregnancy, including those that describe 
adverse events. The entire research protocol is available online at: 
https://effectivehealthcare.ahrq.gov/products/headaches-pregnancy/protocol.
    This is to notify the public that the EPC Program would find the 
following information on Management of Primary Headache during 
Pregnancy 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.
    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)

    KQ 1: What are the (comparative) benefits and harms of 
interventions to prevent attacks of primary headache in women who are 
pregnant (or attempting to become pregnant), postpartum, or 
breastfeeding?
    KQ 1a. Do the (comparative) benefits and harms vary by phase (i.e., 
preconception, first trimester of pregnancy, second trimester of 
pregnancy, third trimester of pregnancy, postpartum, breastfeeding)?
    KQ 1b. Do the (comparative) benefits and harms vary by type of 
primary headache (i.e., migraine, tension headache, cluster headache, 
and other trigeminal autonomic cephalgias)?
    KQ 2: What are the (comparative) benefits and harms of 
interventions to treat acute attacks of primary headache in women who 
are pregnant (or attempting to become pregnant), postpartum, or 
breastfeeding?
    KQ 2a. Do the (comparative) benefits and harms vary by phase (i.e., 
preconception, first trimester of pregnancy, second trimester of 
pregnancy, third trimester of pregnancy, postpartum, breastfeeding)?
    KQ 2b. Do the (comparative) benefits and harms vary by type of 
primary headache (i.e., migraine, tension headache, cluster headache, 
and other trigeminal autonomic cephalgias)?

Contextual Question

    What is the available evidence concerning levels in maternal serum/
blood, fetal/infant serum/blood, breast milk, amniotic fluid, meconium, 
cord blood, or child urine of drugs used to prevent or treat attacks of 
primary headache in women who are pregnant (or attempting to become 
pregnant), postpartum, or breastfeeding?

Study Eligibility Criteria

    We had discussions with a Technical Expert Panel (TEP) during which 
we reviewed the specific eligibility criteria. As part of the 
discussions, we asked the TEP to provide guidance on prioritizing 
outcomes and selecting among harms/adverse events of interest.

KQ 1 (Prevention of Primary Headache)

    Population(s):

 Women who are pregnant (or attempting to become pregnant/in 
the preconception phase), postpartum (defined as up to 12 months post-
delivery), or breastfeeding (for any length of time) with history of 
primary headache
    [cir] Migraine, tension headache, cluster headache or other 
trigeminal autonomic cephalgia (TACs)
    [cir] Women attempting to become pregnant include those actively 
planning pregnancy, by any method, who may wish to use only treatments 
found to be safe and effective during pregnancy.

 Exclude: Women with history of secondary headache of any 
origin
    Interventions:

 Pharmacologic interventions
    [cir] Tricyclic antidepressants (e.g., amitriptyline, 
nortriptyline, imipramine)
    [cir] Beta blockers (e.g., metoprolol, propranolol, nadolol, 
atenolol, timolol, nebivolol)
    [cir] Calcium channel blockers (e.g., verapamil, nimodipine, 
nifedipine, nicardipine)
    [cir] Other antihypertensive medications (e.g., lisinopril, 
candesartan, clonidine)
    [cir] Antiepileptic drugs (e.g., divalproex sodium, sodium 
valproate, valproic acid, topiramate, gabapentin, carbamazepine, 
lamotrigine)
    [cir] Serotonin and norepinephrine reuptake inhibitors (SSNRIs) 
(e.g., venlafaxine, duloxetine)
    [cir] Benzodiazepines (e.g., clonazepam)
    [cir] N-methyl-D-aspartate (NMDA) receptor antagonists (e.g., 
memantine)
    [cir] Calcitonin gene-related peptide (CGRP) inhibitors (e.g., 
erenumab, fremanezumab, galcanezumab)
    [cir] Antihistamines (e.g., cyproheptadine)
    [cir] Antimanic agents (e.g., lithium)
    [cir] Tetracyclic antidepressants (e.g., mirtazapine)
    [cir] Corticosteroids (e.g., methylprednisolone, triamcinolone 
acetonide, combinations of local anesthetics and corticosteroids)
    [cir] Other pharmacologic interventions used to prevent primary 
headache (whether or not available or approved in the United States)
 Non-pharmacologic interventions
    [cir] Supplements (e.g., riboflavin, magnesium, coenzyme Q10, 
melatonin, feverfew, butterbur, frankincense)
    [cir] Nerve blocks (e.g., occipital nerve blocks, sphenopalantine 
ganglion blocks, trigger point injections)
    [cir] Chemodenervation (e.g., onabotulinum toxin A, abobotulinum 
toxin A)
    [cir] Physical therapy
    [cir] Hydration
    [cir] Noninvasive neuromodulation devices (e.g., transcutaneous

[[Page 64525]]

electrical nerve stimulation, transcranial magnetic stimulation, 
transcutaneous vagal stimulation, remote electrical neurostimulation)
    [cir] Behavioral therapy (e.g., cognitive behavioral therapy, diet 
therapy, sleep therapy, exercise therapy, support group therapy)
    [cir] Complementary therapies (e.g., biofeedback, acupuncture, 
mindfulness-based stress reduction)
    [cir] Other non-pharmacologic interventions used to prevent primary 
headache

    Comparators:

 Pharmacologic interventions
    [cir] Other class
    [cir] Other drug within class
    [cir] Same drug(s), different route, treatment duration, initiation 
time, or other aspect
    [cir] As comparator to nonpharmacologic intervention
 Nonpharmacologic interventions
    [cir] Other nonpharmacologic intervention class
    [cir] Other nonpharmacologic intervention, within class
    [cir] As comparator to pharmacologic intervention
 No pharmacologic or nonpharmacologic interventions
    [cir] Placebo
    [cir] No intervention

    Outcomes: (* denotes important outcomes that will be used when 
developing Strength of Evidence tables)

 Acute headache attacks*
    [cir] Occurrence of acute headache attacks
    [cir] Frequency of acute headache attacks
    [cir] Severity of acute headache attacks
    [cir] Duration of acute headache attacks
 Headache-related symptoms (e.g., nausea/vomiting, 
photosensitivity, dizziness)*
    [cir] Occurrence of headache-related symptoms
    [cir] Frequency of headache-related symptoms
    [cir] Severity of headache-related symptoms
    [cir] Duration of headache-related symptoms
    [cir] Most bothersome symptom
 Emergency department visits, clinic visits, or 
hospitalizations*
 Quality of life*
 Functional outcomes
    [cir] Impact on family life
    [cir] Employment/school attendance
    [cir] Time spent managing disease
 Resource use
 Acceptability of intervention by patients
 Patient satisfaction with intervention
 Number of prescribed medications
 Number of days with acute medication use
 Adverse events
    [cir] Maternal
    [ssquf] Serious maternal adverse events*
     ``Serious'' adverse events (including those that are 
composite outcomes), as defined by study authors
     Cardiovascular outcomes, such as stroke, myocardial 
infarction
    [ssquf] Non-serious maternal adverse events
     Nonobstetrical (e.g., maternal weight gain, tachycardia, 
hypertension, gastrointestinal)
     Preterm labor, cesarean section
     Reduced breast milk production
     Symptoms related to withdrawal of medication
    [ssquf] Discontinuation of intervention (or of study participation) 
due to maternal adverse events*
    [cir] Fetal/infant
    [ssquf] Serious fetal/infant adverse events*
     ``Serious'' adverse events (including those that are 
composite outcomes), as defined by study authors
     Death--spontaneous abortion, stillbirth, infant death
     Preterm birth
     Low birth weight for gestational age
     Congenital anomalies or other newborn abnormalities
     Perinatal complications, e.g., low APGAR score, 
respiratory distress, neonatal intensive care unit time
     Neurodevelopmental--social, emotional, or cognitive delay 
or disability
    [ssquf] Non-serious fetal/infant adverse events
     Breastfeeding--delayed initiation, cessation, reduced 
frequency, reduced volume of breast milk
     Poor infant attachment/bonding
     Symptoms related to withdrawal of medication
    [ssquf] Discontinuation of intervention (or of study participation) 
due to fetal/infant adverse events*

    Potential Modifiers:

 Phase
    [cir] Preconception
    [cir] First trimester
    [cir] Second trimester
    [cir] Third trimester
    [cir] Postpartum
    [cir] Breastfeeding
 Type of primary headache
    [cir] Migraine
    [cir] Tension headache
    [cir] Cluster headache
    [cir] Other TACs

    Timing:

 Any

    Setting:

 Any

    Design:

 Randomized controlled trials
 Nonrandomized comparative studies, including pre-post studies
 Single group studies
 N-of-1 studies
 Case-control studies
 Case reports or series of case reports
 Cross-sectional studies/surveys
    [cir] Prospective or retrospective (all applicable study types)
 For harms, we will start by searching for existing systematic 
reviews of interventions used during pregnancy, postpartum, or 
breastfeeding, regardless of their indication (i.e., for any disease/
condition, not only primary headaches). We will not enforce a date 
restriction when screening for eligible systematic reviews, but when 
multiple eligible systematic reviews exist for a certain drug/class of 
drugs, we will use the most recent or most complete one.
    [cir] We will subsequently search for, and include, large primary 
studies of interventions not adequately covered by the existing 
systematic reviews of harms. The specific eligibility criteria 
(particularly pertaining to study design, minimum sample size, and 
publication date) will be determined based on available EPC resources, 
the number of interventions without adequate existing systematic 
reviews, and the volume of potentially eligible studies.
    [cir] For harms, we will also search the U.S. Food and Drug 
Administration, other international equivalent agencies, and 
pharmacopoeia.

KQ 2 (Treatment of Primary Headache)

    Population(s):

 Women who are pregnant (or attempting to become pregnant/in 
the preconception phase), postpartum (defined as up to 12 months post-
delivery), or breastfeeding (for any length of time) with acute attacks 
of primary headache
    [cir] Migraine, tension headache, cluster headache, or other 
trigeminal autonomic cephalgia (TACs)
    [cir] Women attempting to become pregnant include those actively 
planning pregnancy, by any method, who may wish to use only treatments 
found to be safe and effective during pregnancy.
 Exclude: Women with attacks of secondary headache of any 
origin

    Interventions:

 Pharmacologic interventions
    [cir] Analgesics/antipyretics (e.g., acetaminophen)

[[Page 64526]]

    [cir] Nonsteroidal antiinflammatory drugs (NSAIDs) (e.g., 
ibuprofen, naproxen, aspirin, celecoxib, ketorolac, indomethacin, 
ketoprofen, diclofenac, mefenamic acid)
    [cir] Other over-the-counter analgesics (e.g., combination aspirin, 
acetaminophen, and caffeine; combination acetaminophen, isometheptene, 
and dichloralphenazone)
    [cir] Antiemetics: dopamine receptor antagonists (e.g., 
metoclopramide, promethazine, prochlorperazine, droperidol, 
chlorpromazine)
    [cir] Antiemetics: 5HT3 antagonists (e.g., ondansetron)
    [cir] Antihistamines (e.g., meclizine, diphenhydramine, 
dimenhydrinate, promethazine)
    [cir] Central nervous system stimulants (e.g., caffeine)
    [cir] Muscle relaxants (e.g., baclofen, tizanidine, metaxalone, 
carisoprodol)
    [cir] Corticosteroids (e.g., prednisolone, prednisolone, 
methylprednisolone, dexamethasone, betamethasone)
    [cir] Triptans/Serotonin receptor agonists (e.g., sumatriptan, 
frovatriptan, naratriptan, rizatriptan, almotriptan, eletriptan, 
zolmitriptan, combination sumatriptan and naproxen)
    [cir] Opioid containing analgesics (e.g., codeine, hydrocodone, 
oxycodone, morphine, meperidine, tramadol, butorphanol, nalbuphine)
    [cir] Butalbital-containing analgesics (e.g., butalbital; 
combination butalbital and acetaminophen; combination butalbital, 
aspirin, and caffeine)
    [cir] Ergot products (e.g., dihydroergotamine, ergotamine, 
combination ergotamine and caffeine)
    [cir] Sympathomimetic amines (e.g., isometheptene)
    [cir] Topical anesthetics (e.g., lidocaine)
    [cir] Antipsychotics (e.g., chlorpromazine, olanzapine)
    [cir] Somatostatin analogs (e.g., octreotide)
    [cir] Intravenous magnesium
    [cir] Other pharmacologic interventions used to treat acute attacks 
of primary headache (whether or not available or approved in the United 
States)
 Non-pharmacologic interventions
    [cir] Hydration
    [cir] Physical therapy
    [cir] Procedures (e.g., occipital nerve blocks, sphenopalantine 
ganglion blocks, trigger point injections)
    [cir] Noninvasive neuromodulation devices (e.g., transcutaneous 
electrical nerve stimulation, transcranial magnetic stimulation, 
transcutaneous vagal stimulation, remote electrical neurostimulation)
    [cir] Behavioral therapy (e.g., cognitive behavioral therapy, diet 
therapy, sleep therapy, exercise therapy, support group therapy)
    [cir] Supplements (e.g., magnesium, cannabidiol)
    [cir] Complementary therapies (e.g., biofeedback, acupuncture, 
mindfulness-based stress reduction)
    [cir] Other non-pharmacologic interventions used to treat acute 
attacks of primary headache

    Comparators:

 Pharmacologic interventions
    [cir] Other class
    [cir] Other drug within class
    [cir] Same drug(s), different route, treatment duration, initiation 
time, or other aspect
    [cir] As comparator to nonpharmacologic intervention
 Nonpharmacologic interventions
    [cir] Other nonpharmacologic intervention class
    [cir] Other nonpharmacologic intervention, within class
    [cir] As comparator to pharmacologic intervention
 No pharmacologic or nonpharmacologic interventions
    [cir] Placebo
    [cir] No intervention
    Outcomes (* denotes important outcomes that will be used when 
developing Strength of Evidence tables):

 Acute headache attack*
    [cir] Severity of acute headache attack
    [cir] Resolution of acute headache attack
    [cir] Duration of acute headache attack
 Headache-related symptoms (e.g., nausea/vomiting, 
photosensitivity)*
    [cir] Severity of headache-related symptoms
    [cir] Resolution of headache-related symptoms
    [cir] Duration of headache-related symptoms
    [cir] Most bothersome symptom
 Emergency department visits, clinic visits, or 
hospitalizations*
 Quality of life*
 Functional outcomes
    [cir] Impact on family life
    [cir] Employment/school attendance
    [cir] Time spent managing disease
 Resource use
 Acceptability of intervention by patients
 Patient satisfaction with intervention
 Number of prescribed medications
 Adverse events
    [cir] Maternal
    [ssquf] Serious maternal adverse events*
     ``Serious'' adverse events (including those that are 
composite outcomes), as defined by study authors
     Cardiovascular outcomes, such as stroke, myocardial 
infarction
    [ssquf] Non-serious maternal adverse events
     Nonobstetrical (e.g., maternal weight gain, tachycardia, 
hypertension, gastrointestinal)
     Preterm labor, cesarean section
     Reduced breast milk production
     Symptoms related to withdrawal of medication
    [ssquf] Discontinuation of intervention (or of study participation) 
due to maternal adverse events*
    [cir] Fetal/infant
    [ssquf] Serious fetal/infant adverse events*
     ``Serious'' adverse events (including those that are 
composite outcomes), as defined by study authors
     Death--spontaneous abortion, stillbirth, infant death
     Preterm birth
     Low birth weight for gestational age
     Congenital anomalies or other newborn abnormalities
     Perinatal complications, e.g., low APGAR score, 
respiratory distress, neonatal intensive care unit time
     Neurodevelopmental--social, emotional, or cognitive delay 
or disability
[ssquf] Non-serious fetal/infant adverse events
     Breastfeeding--delayed initiation, cessation, reduced 
frequency, reduced volume of breast milk
     Poor infant attachment/bonding
     Symptoms related to withdrawal of medication
[ssquf] Discontinuation of intervention (or of study participation) due 
to fetal/infant adverse events *

    Potential Modifiers:

 Phase
    [cir] Preconception
    [cir] First trimester
    [cir] Second trimester
    [cir] Third trimester
    [cir] Postpartum
    [cir] Breastfeeding
 Type of primary headache
    [cir] Migraine
    [cir] Tension headache
    [cir] Cluster headache
    [cir] Other TACs

    Timing:

 Any

    Setting:

 Any

    Design:

 Randomized controlled trials
 Nonrandomized comparative studies, including pre-post studies
 Single group studies
 N-of-1 studies
 Case-control studies

[[Page 64527]]

 Case reports or series of case reports
 Cross-sectional studies/surveys
    [cir] Prospective or retrospective (all applicable study types)
 For harms, we will start by searching for existing systematic 
reviews of interventions used during pregnancy, postpartum, or 
breastfeeding, regardless of their indication (i.e., for any disease/
condition, not only primary headaches). We will not enforce a date 
restriction when screening for eligible systematic reviews, but when 
multiple eligible systematic reviews exist for a certain drug/class of 
drugs, we will use the most recent or most complete one.
    [cir] We will subsequently search for, and include, large primary 
studies of interventions not adequately covered by the existing 
systematic reviews of harms. The specific eligibility criteria 
(particularly pertaining to study design, minimum sample size, and 
publication date) will be determined based on available EPC resources, 
the number of interventions without adequate existing systematic 
reviews, and the volume of potentially eligible studies.
    [cir] For harms, we will also search the U.S. Food and Drug 
Administration, other international equivalent agencies, and 
pharmacopoeia.

    Dated: November 19, 2019.
Virginia Mackay-Smith,
Associate Director.
[FR Doc. 2019-25414 Filed 11-21-19; 8:45 am]
BILLING CODE 4160-90-P