80 FR 48107 - Agency for Healthcare Research and Quality

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Federal Register Volume 80, Issue 154 (August 11, 2015)

Page Range		48107-48110
FR Document		2015-19658
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 Omega 3 Fatty Acids and Maternal and Child Health, which is currently being conducted by the AHRQ's Evidence-based Practice Centers (EPC) Programs. Access to published and unpublished pertinent scientific information will improve the quality of this review.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).
Federal Register, Volume 80 Issue 154 (Tuesday, August 11, 2015)
[Federal Register Volume 80, Number 154 (Tuesday, August 11, 2015)]
[Notices]
[Pages 48107-48110]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2015-19658]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


Agency for Healthcare Research and Quality

Scientific Information Request on Omega 3 Fatty Acids and 
Maternal and Child Health

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 Omega 3 Fatty 
Acids and Maternal and Child Health, which is currently being conducted 
by the AHRQ's Evidence-based Practice Centers (EPC) Programs. 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published and unpublished pertinent scientific information will improve 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 September 10, 2015.

ADDRESSES: Online submissions: http://effectivehealthcare.AHRQ.gov/index.cfm/submit-scientific-information-packets/. Please select the 
study for which you are submitting information from the list to upload 
your documents.
    Email submissions: src.org">SIPS@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. 58653 or Email: src.org">SIPS@epc-src.org.

SUPPLEMENTARY INFORMATION: 
    The Agency for Healthcare Research and Quality has commissioned the 
Evidence-based Practice Centers (EPC) Programs to complete a review of 
the evidence for Omega 3 Fatty Acids and Maternal and Child Health.
    The EPC Program is dedicated to identifying as many studies as 
possible that are relevant to the questions for

[[Page 48108]]

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 Omega 3 Fatty Acids and Maternal 
and Child Health, including those that describe adverse events.
    The entire research protocol, including the key questions, is also 
available online at: http://effectivehealthcare.AHRQ.gov/search-for-guides-reviews-and-reports/?pageaction=displayProduct&productID=2083.
    This notice is to notify the public that the EPC Program would find 
the following information on Omega 3 Fatty Acids and Maternal and Child 
Health 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 will be 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: http://effectivehealthcare.AHRQ.gov/index.cfm/join-the-email-list1/.
    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: http://effectivehealthcare.AHRQ.gov/search-for-guides-reviews-and-reports/?pageaction=displayProduct&productID=2083.

The Key Questions

KQ 1. Maternal Exposure

    [cir] What is the efficacy of maternal interventions involving--or 
association of maternal exposures to--n-3 Fatty Acids (FA) 
(eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], EPA+DHA 
[long-chain n-3 FA], docosapentaenoic acid [DPA], alpha-linolenic acid 
[ALA], stearidonic acid [SDA] or total n-3 FA) on the following:
    [ssquf] Duration of gestation in women with or without a history of 
preterm birth (less than 37 weeks gestation)
    [ssquf] Incidence of preeclampsia/eclampsia/gestational 
hypertension in women with or without a history of preeclampsia/
eclampsia/gestational hypertension
    [ssquf] Incidence of birth of small-for-gestational age human 
infants
    [ssquf] Incidence of ante- and/or postnatal depression in women 
with or without a history of major depression or postpartum depression
    [cir] What are the associations of maternal biomarkers of n-3 
intake during pregnancy and the outcomes identified above?
    [cir] What are the effects of potential confounders or interacting 
factors (such as other nutrients or use of other supplements, or 
smoking status)?
    [cir] How is the efficacy or association of n-3 FA on the outcomes 
of interest affected by the ratio of different n-3 FAs, as components 
of dietary supplements or biomarkers?
    [cir] How does the ratio of n-6 FA to n-3 FA intakes or biomarker 
concentrations affect the efficacy or association of n-3 FA on the 
outcomes of interest?
    [cir] Is there a threshold or dose-response relationship between n-
3 FA exposures and the outcomes of interest or adverse events?
    [cir] How does the duration of the intervention or exposure 
influence the effect of n-3 FA on the outcomes of interest?

KQ 2. Fetal/childhood exposures

    [cir] What is the influence of maternal intakes of n-3 fatty acids 
or the n-3 fatty acid content of maternal breast milk (with or without 
knowledge of maternal intake of n-3 FA) or n-3 FA-supplemented infant 
formula or intakes of n-3 FA from sources other than maternal breast 
milk or supplemented infant formula on the following outcomes in term 
or preterm human infants?
    [ssquf] Growth patterns
    [ssquf] Neurological development
    [ssquf] Visual function
    [ssquf] Cognitive development
    [ssquf] Autism
    [ssquf] Learning disorders
    [ssquf] Attention Deficit Hyperactivity Disorder (ADHD)
    [ssquf] Atopic dermatitis
    [ssquf] Allergies
    [ssquf] Respiratory illness
    [cir] What are the associations of the n-3 FA content or the n-6/n-
3 FA ratio of maternal or fetal or child biomarkers with each of the 
outcomes identified above?

KQ 3. Maternal or childhood adverse events:

    [cir] What are the short and long term risks related to maternal 
intake of n-3 FA during pregnancy or breastfeeding on:
    [ssquf] Pregnant women
    [ssquf] Breastfeeding women
    [ssquf] Term or preterm human infants at or after birth
    [cir] What are the short and long term risks associated with 
intakes of n-3 FA by human infants (as maternal breast milk or infant 
formula supplemented with n-3 FA)?
    [cir] Are adverse events associated with specific sources or doses?

PICOTS (Population, Intervention, Comparator, Outcome, Timing, Setting)

Population(s)

 KQ 1 (Maternal Exposures and Outcomes)

    [cir] Healthy pregnant women (for outcomes of birth weight, 
intrauterine growth restriction/small for gestational age, duration of 
gestation, risk of pre-eclampsia, eclampsia, or pregnancy hypertension)
    [cir] Pregnant women with a history of pre-eclampsia, eclampsia, or 
pregnancy hypertension (only for outcome of risk of pre-eclampsia, 
eclampsia, or pregnancy hypertension)
    [cir] Pregnant women with a history of major depressive disorder or 
postpartum depression (only for the outcome of risk for peripartum 
depression)

[[Page 48109]]

 KQ 2 (In Utero and Postnatal (Through the First Year of Life) 
Exposures and Outcomes)

    [cir] Healthy preterm or full term infants of healthy women/mothers 
whose n-3 fatty acid exposures were monitored during pregnancy
    [cir] Breastfed infants of healthy mothers whose n-3 fatty acid 
exposure was monitored and/or who participated in an n-3 fatty acid 
intervention during breastfeeding beginning at birth
    [cir] Healthy preterm or full term infants with and without family 
history of respiratory conditions (for outcomes related to atopic 
dermatitis, allergy, respiratory conditions) of mothers whose n-3 
exposures were monitored during pregnancy and/or breastfeeding
    [cir] Healthy children or children with a family history of a 
respiratory disorder, a cognitive or visual development disorder, 
autism spectrum disorder, ADHD, or learning disabilities, age 0 to 18 
years who participated in an n-3 fatty acid-supplemented infant formula 
intervention or an n-3 supplementation trial during infancy

 KQ 3 (Adverse Events Associated With n-3 Interventions)

    [cir] Healthy pregnant women or pregnant women in the other 
categories described above
    [cir] Offspring of women enrolled in an n-3 fatty acid intervention 
during pregnancy
    [cir] Offspring of women whose exposure to n-3 fatty acids was 
assessed during pregnancy
    [cir] Children whose exposure to n-3 fatty acids (through breast 
milk, infant formula, or supplementation) was monitored during the 
first year of life

Interventions/Exposures

     Interventions (KQ1, 2, 3 unless specified):
    [cir] N-3 fatty acid supplements (e.g., EPA, DHA, ALA, singly or in 
combination
    [cir] N-3 fatty acid supplemented foods (e.g., eggs) with 
quantified n-3 content
    [cir] High-dose pharmaceutical grade n-3 fatty acids, e.g., 
Omacor[supreg], Ropufa[supreg], MaxEPA[supreg], Efamed, Res-Q[supreg], 
Epagis, Almarin, Coromega, Lovaza[supreg], Vascepa[supreg] (icosapent 
ethyl)
    [ssquf] Exclude doses of more than 6g/d, except for trials that 
report adverse events
    [cir] N-3 fatty acid enriched infant formulae (KQ2,3)
    [ssquf] E.g., Enfamil[supreg] Lipil[supreg]; Gerber[supreg] Good 
Start DHA & ARA[supreg]; Similac[supreg] Advance[supreg]
    [ssquf] N-3 enriched follow-up formulae
    [ssquf] Exclude parenterally administered sources
    [cir] Marine oils, including fish oil, cod liver oil, and menhaden 
oil with quantified n-3 content
    [cir] Algal or other marine sources of omega-3 fatty acids with 
quantified n-3 content
     Exposures (KQ1,2)
    [cir] Dietary n-3 fatty acids from foods if concentrations are 
quantified in food frequency questionnaires
    [cir] Breast milk n-3 fatty acids (KQ2)
    [cir] Biomarkers (EPA, DHA, ALA, DPA, SDA), including but not 
limited to the following:
    [ssquf] Plasma fatty acids
    [ssquf] Erythrocyte fatty acids
    [ssquf] Adipocyte fatty acids

Comparators

     Inactive comparators:
    [cir] Placebo (KQ1, 2, 3)
    [cir] Non-fortified infant formula (KQ2)
     Active comparators
    [cir] Different n-3 sources
    [cir] Different n-3 concentrations (KQ1, 2, 3)
    [cir] Alternative n-3 enriched infant formulae (KQ2)
    [cir] Soy-based infant formula (KQ2)
    [cir] Diet with different level of Vitamin E exposure

Outcomes

     Maternal outcomes (KQ1)
    [cir] Blood pressure control
    [ssquf] Incidence of gestational hypertension
    [ssquf] Maternal blood pressure
    [ssquf] Incidence of pre-eclampsia, eclampsia
    [cir] Peripartum depression
    [ssquf] Incidence of antepartum depression \10\
    [ssquf] Incidence of postpartum depression, e.g.
    [ssquf] Edinburgh Postnatal Depression scale
    [ssquf] Structured Clinical Interview (SCI)
    [cir] Gestational length
    [ssquf] Duration of gestation
    [ssquf] Incidence of preterm birth
    [cir] Birth weight
    [ssquf] Mean birth weight
    [ssquf] Incidence of low birth weight/small for gestational age
     Pediatric Outcomes (KQ2)
    [cir] Neurological/visual/cognitive development
    [ssquf] Visual development, e.g.
    [ssquf] Visual evoked potential acuity
    [ssquf] Visual acuity testing
    [ssquf] Teller's Acuity Card test
    [ssquf] Electroretinography
    [ssquf] Cognitive/neurological development, e.g.
    [ssquf] EEGs as measure of maturity
    [ssquf] Psychomotor developmental index from Bayley's scales
    [ssquf] Bayley's mental development index
    [ssquf] Knobloch, Passamanick, and Sherrard's developmental 
Screening Inventory scores
    [ssquf] Neurological impairment assessment
    [ssquf] Active sleep, quiet sleep, sleep-wake transition, 
wakefulness
    [ssquf] Fagan Test of Infant Intelligence
    [ssquf] Stanford-Binet IQ
    [ssquf] Receptive Vocabulary
    [ssquf] Peabody Picture Vocabulary Test-Revised
    [ssquf] Auditory development
    [ssquf] Nerve conduction test
    [ssquf] Latency Auditory evoked potential
    [cir] Risk for ADHD
    [ssquf] Studies will be included only if they employ a validated 
evaluation procedure
    [ssquf] E.g., Wechsler Intelligence Scale for Children
    [ssquf] Behavioral rating scales, e.g., Connors, Vanderbilt, and 
Barkley scales
    [cir] Risk for Autism spectrum disorders
    [ssquf] Studies will be included only if they employ a validated 
evaluation procedure
    [ssquf] E.g., Modified Checklist of Autism in Toddlers
    [cir] Risk for learning disabilities
    [ssquf] Studies will be included only if they employ a validated 
evaluation procedure
    [cir] Risk for atopic dermatitis
    [cir] Risk for allergies
    [ssquf] Studies will be included only if they employ a validated 
allergy assessment procedure, preferably challenge
    [cir] Incidence of respiratory disorders
    [ssquf] Spirometry in children 5 and over (peak expiratory flow 
rate [PEFR] and forced expiratory volume in 1 second [FEV1])
     KQ 3: Adverse effects of intervention(s)
    [cir] Incidence of specific adverse events reported in trials by 
study arm

Timing

     Duration of intervention or follow-up
    [cir] Key Question 1,3 (maternal interventions/exposures):
    [ssquf] Interventions implemented anytime during pregnancy but 
preferably during the first or second trimester
    [ssquf] Followup duration is anytime during pregnancy (for maternal 
outcomes of pre/eclampsia or maternal hypertension); term (for outcomes 
related to birth weight, duration of pregnancy); or within the first 6 
months postpartum (for the outcome of postpartum depression)
    [cir] Key Question 2, 3 (infant exposures):
    [ssquf] Interventions implemented within one month of birth or 
exposures measured within 1 month of birth

[[Page 48110]]

    [ssquf] Followup duration is 0 to 18 years

Settings

     Community-dwelling individuals seen by primary care 
physicians or obstetricians in private or academic medical practices 
(KQ1, 3)
     Community dwelling children seen in outpatient health care 
or educational settings (KQ2, 3)
    Study designs will be limited to Randomized Controlled Trials, 
prospective cohort studies, and nested case control studies (cross-
sectional, retrospective cohort, and case study designs will be 
excluded; studies must have measure of intake/exposure prior to 
outcome). Language will be restricted to English. Only peer-reviewed 
studies will be included; unpublished studies will not be included.

Sharon B. Arnold,
Deputy Director.
[FR Doc. 2015-19658 Filed 8-10-15; 8:45 am]
 BILLING CODE 4160-90-P
Federal Register / Vol. 80, No. 154 / Tuesday, August 11, 2015 / Notices 48107

diabetes (in studies of CVD outcomes Æ Supraventricular arrhythmia, new DEPARTMENT OF HEALTH AND
and risk factors)? diagnosis HUMAN SERVICES
PICOTS (Population, Intervention, Æ Major vascular interventions/
Agency for Healthcare Research and
Comparator, Outcome, Timing, Setting) procedures (e.g, revascularization,
Quality
thrombolysis, lower extremity
Populations amputation, defibrillator placement)
• Healthy adults (≥18 yr) without CVD Scientific Information Request on
• Major CVD risk factors (intermediate Omega 3 Fatty Acids and Maternal and
or with low to intermediate risk for
outcomes): Child Health
CVD
• Adults at high risk for CVD (e.g., with Æ Blood pressure (new-onset AGENCY: Agency for Healthcare Research
diabetes, cardiometabolic syndrome, hypertension, systolic, diastolic, and and Quality (AHRQ), HHS.
hypertension, dyslipidemia, non- mean arterial pressure)
ACTION: Request for Scientific
dialysis chronic kidney disease) Æ Key plasma lipids (i.e., high density Information Submissions.
• Adults with clinical CVD (e.g., history lipoprotein cholesterol [HDL-c], low
of myocardial infarction, angina, density lipoprotein cholesterol [LDL- SUMMARY: The Agency for Healthcare
transient ischemic attacks) c], total/HDL-c ratio, LDL-c/HDL-c Research and Quality (AHRQ) is seeking
• Exclude populations chosen for scientific information submissions from
ratio, triglycerides)
having a non-CVD or non-diabetes- the public. Scientific information is
related disease (e.g., cancer, • Adverse events (e.g., bleeding, major being solicited to inform our review of
gastrointestinal disease, rheumatic gastrointestinal disturbance), only Omega 3 Fatty Acids and Maternal and
disease, dialysis) from intervention studies of Child Health, which is currently being
supplements conducted by the AHRQ’s Evidence-
Interventions/Exposures
Timing based Practice Centers (EPC) Programs.
• n-3 FA supplements Access to published and unpublished
• n-3 FA supplemented foods (e.g.,
• Clinical outcomes, including new- pertinent scientific information will
eggs)
• n-3 FA content in diet (e.g., from food onset hypertension (all study improve the quality of this review.
frequency questionnaires) designs): ≥1 year followup (and AHRQ is conducting this systematic
• Biomarkers of n-3 FA intake intervention duration, as applicable) review pursuant to Section 902(a) of the
• n-3 content of food or supplements • Intermediate outcomes (blood Public Health Service Act, 42 U.S.C.
must be quantified (e.g., exclude fish pressure and plasma lipids) (all study 299a(a).
diet studies where only servings/week designs): ≥1 month followup DATES: Submission Deadline on or
defined, Mediterranean diet studies • Adverse events (all study designs): No before September 10, 2015.
without n-3 quantified). n-3 ADDRESSES: Online submissions: http://
minimum followup
quantification can be of total n-3 FA, effectivehealthcare.AHRQ.gov/
of a specific n-3 FA (e.g., ALA) or of Setting index.cfm/submit-scientific-information
combined EPA+DHA (‘‘marine oil’’). -packets/. Please select the study for
• Exclude n-3 FA dose ≥6 g/day (except Community-Dwelling (Non-
Institutionalized) Individuals Study which you are submitting information
for adverse events) from the list to upload your documents.
• Exclude weight loss interventions Design
Email submissions: SIPS@epc-src.org.
Comparators • Randomized Controlled Trials (RCTs) Print submissions:
(all outcomes) Mailing Address:
• Placebo or no n-3 FA intervention
• Different n-3 FA source intervention Portland VA Research Foundation,
• Randomized cross-over studies (blood
• Different n-3 FA concentration Scientific Resource Center, ATTN:
pressure and plasma lipids, adverse Scientific Information Packet
intervention events), minimum washout period to
• Different n-3 FA dietary exposure Coordinator, P.O. Box 69539, Portland,
be determined OR 97239.
(e.g., comparison of quantiles)
• Different n-3 FA biomarker levels • Prospective nonrandomized Shipping Address (FedEx, UPS, etc.):
(e.g., comparison of quantiles) comparative studies (clinical Portland VA Research Foundation,
outcomes, adverse events) Scientific Resource Center, ATTN:
Outcomes Scientific Information Packet
• Prospective cohort (single group)
• All-cause mortality studies, where groups are compared Coordinator, 3710 SW U.S. Veterans
• Cardiovascular, cerebrovascular, and based on n-3 FA intake or intake Hospital Road, Mail Code: R&D 71,
peripheral vascular events: biomarker values (clinical outcomes) Portland, OR 97239.
Æ Fatal vascular events (e.g., due to FOR FURTHER INFORMATION CONTACT:
myocardial infarction, stroke) • Exclude: Retrospective or case control
Ryan McKenna, Telephone: 503–220–
Æ Non-fatal vascular events (e.g., studies or cross-sectional studies (but
8262 ext. 58653 or Email: SIPS@epc-
myocardial infarction, stroke/ include prospective nested case src.org.
cardiovascular accident, transient control studies). Studies must have
ischemic attack, unstable angina) measure of intake prior to outcome. SUPPLEMENTARY INFORMATION:
The Agency for Healthcare Research
asabaliauskas on DSK5VPTVN1PROD with NOTICES

Æ Coronary heart disease, new diagnosis • Minimum sample sizes (All outcomes:
Æ Congestive heart failure, new and Quality has commissioned the
To be determined) Evidence-based Practice Centers (EPC)
diagnosis
Æ Cerebrovascular disease, new • English language publications Programs to complete a review of the
diagnosis evidence for Omega 3 Fatty Acids and
Sharon B. Arnold,
Æ Peripheral vascular disease, new Maternal and Child Health.
diagnosis Deputy Director. The EPC Program is dedicated to
Æ Ventricular arrhythmia, new [FR Doc. 2015–19659 Filed 8–10–15; 8:45 am] identifying as many studies as possible
diagnosis BILLING CODE 4160–90–P that are relevant to the questions for

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Document Modified: 2016-09-27 22:25:31
Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Request for Scientific Information Submissions.
Dates		Submission Deadline on or before September 10, 2015.
Contact		Ryan McKenna, Telephone: 503-220-8262 ext. 58653 or Email: [email protected]
FR Citation		80 FR 48107