`[Federal Register Volume 89, Number 229 (Wednesday, November 27, 2024)]
[Notices]
[Pages 93603-93606]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-27798]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality


Supplemental Evidence and Data Request on Dietary Intake of 
Polyunsaturated Fatty Acids and Plasma Lipid and Cardiovascular Events

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

ACTION: Request for supplemental evidence and data submission.

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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 Dietary Intake 
of Polyunsaturated Fatty Acids and Plasma Lipid and Cardiovascular 
Events, 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 Access to published and unpublished 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 December 27, 2024.

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: Kelly Carper, Telephone: 301-427-1656 
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 for Dietary Intake of 
Polyunsaturated Fatty Acids and Plasma Lipid and Cardiovascular Events. 
AHRQ is conducting this review pursuant to section 902 of the Public 
Health Service Act, 42 U.S.C. 299a.
    The EPC Program is dedicated to identifying as many studies as 
possible that are relevant to the questions for each of its reviews. In 
order to do so, we are supplementing the usual manual and electronic 
database searches of the literature by requesting information from the 
public (e.g., details of studies conducted). We are looking for studies 
that report on Dietary Intake of Polyunsaturated Fatty Acids and Plasma 
Lipid and Cardiovascular Events. The entire research protocol is 
available online at: https://effectivehealthcare.ahrq.gov/products/polyunsaturated-fatty/protocol.
    This is to notify the public that the EPC Program would find the 
following information on Dietary Intake of Polyunsaturated Fatty Acids 
and Plasma Lipid and Cardiovascular Events helpful:
    [ssquf] A list of completed studies that your organization has 
sponsored for this topic. 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, if 
relevant: 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 topic. In the list, please provide the 
ClinicalTrials.gov trial number or, if the trial is not registered, the 
protocol for the study including, if relevant, 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 topic 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 topics 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://effectivehealthcare.ahrq.gov/email-updates.
    The 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 effects of different dietary polyunsaturated 
fatty acid intake on plasma lipid concentrations in the general 
population?
    KQ 2: What are the effects of different dietary polyunsaturated 
fatty acid intake on cardiovascular events in the general population?

                 PICOTS (Populations, Interventions, Comparators, Outcomes, Timing, and Setting)
 [Study eligibility criteria based on Population, Intervention, Comparator, Outcome (PICO), and other elements]
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               Element                             Inclusion criteria                    Exclusion criteria
----------------------------------------------------------------------------------------------------------------
Population...........................  Both Key Questions:                         Both Key Questions:

[[Page 93604]]

 
                                       General population, without CVD, with or     Participants with a
                                        without modifiable CV risk factors,         health-related condition or
                                        including                                   taking medications that
                                       [cir] Dyslipidemia (including if taking      impact fat absorption, fat
                                        lipid-lowering medications)                 metabolism.
                                       [cir] Overweight/obese                       Participants taking
                                       [cir] Hyperglycemia and related              weight loss medications,
                                        conditions, including type 2 diabetes       including glucagon-like
                                       [cir] Hypertension/high blood pressure       peptide-1 agonists.
                                       Key Question 1:                              Undernourished,
                                       Children and adults                          underweight, stunted, or
                                       Key Question 2:                              wasted participants.
                                       Adults (>=18 years old)                      Participants who are
                                                                                    pre- or post-bariatric
                                                                                    surgery.
                                                                                    Participants with
                                                                                    other chronic diseases
                                                                                    (e.g., cancer,
                                                                                    gastrointestinal disease,
                                                                                    rheumatic disease, chronic
                                                                                    kidney disease, neurologic
                                                                                    diseases), including type 1
                                                                                    diabetes.
                                                                                    Participants with
                                                                                    clinical CVD (e.g., history
                                                                                    of myocardial infarction,
                                                                                    angina, stroke, arrhythmia),
                                                                                    including congenital heart
                                                                                    diseases, or familial
                                                                                    hypercholesterolemia.
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Interventions........................  Both Key Questions:                         Both Key Questions:
                                       Dietary intake of                            Studies that do not
                                       Total n-3 or total n-6 PUFA                  quantify PUFA intake as
                                       Individual PUFA (e.g., linoleic, ALA, EPA,   either g/day or % of total
                                        DHA)                                        energy intake from PUFA.
                                       Combination of long-chain PUFA (e.g.,        Analyses with PUFA
                                        EPA+DHA+DPA; DHA+ALA)                       intake as a continuous
                                       PUFA intake must be defined or described     variable.
                                        prospectively                               Fatty acid intake
                                       Studies must specify daily quantity of       via infusion (not orally).
                                        PUFA intake                                 Food products or
                                       Key Question 1:                              dietary supplements not
                                       For studies in children,                     widely available to U.S.
                                       [cir] Include multicomponent interventions   consumers.
                                        (e.g., diet + exercise vs. exercise)        Multi-component
                                       [cir] Infant formula                         interventions (e.g.,
                                                                                    exercise + diet vs. exercise
                                                                                    or plant sterols + diet vs.
                                                                                    plant sterols) that do not
                                                                                    isolate the effect or
                                                                                    association of PUFA.
                                                                                    Multi-component
                                                                                    interventions of statins +
                                                                                    diet where statins are being
                                                                                    initiated. Dietary
                                                                                    interventions among existing
                                                                                    statin users will be
                                                                                    included.
                                                                                    Interventions
                                                                                    designed to induce weight
                                                                                    loss or treat overweight and
                                                                                    obesity through energy
                                                                                    restriction or hypocaloric
                                                                                    diets.
                                                                                    Interventions
                                                                                    designed for the purposes of
                                                                                    treating medical conditions
                                                                                    other than modifiable CV
                                                                                    risk factors.
                                                                                    DHA and/or EPA n-3
                                                                                    FA dose >4 g/d.
                                                                                    Enteral feeding.
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Comparators..........................  Both Key Questions:                         Both Key Questions:
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                                       Dietary intake of a different level of      Diets with a caloric intake
                                        fatty acids relevant to the exposure        that are significantly
                                       No added/supplement PUFA                     higher or lower than the
                                       Placebo supplements                          intervention/exposure diet.
                                                                                   Diets or interventions that
                                                                                    vary substantially in intake
                                                                                    of macronutrients (or other
                                                                                    factors) other than the
                                                                                    intervention and comparator
                                                                                    of interest.
                                                                                   Different PUFA dietary
                                                                                    exposure (e.g., comparison
                                                                                    of undefined quantiles).
Outcomes.............................  Key Question 1:                             Key Question 1:
                                        Plasma lipoprotein concentrations   Total cholesterol
                                       [cir] LDL cholesterol (LDL-c)                (TC).
                                       [cir] HDL cholesterol (HDL-c)                TC:HDL ratio.
                                       [cir] Non-HDL-cholesterol                    LDL:HDL ratio.
                                       [cir] Triglycerides (triacylglycerol) (Tg)   Chylomicrons.
                                       [cir] Lipoprotein(a)                         VLDL-c.
                                       [cir] Apolipoprotein B (ApoB)                IDL-c.
                                                                                    Other
                                                                                    apolipoproteins.
                                                                                    Lipoprotein
                                                                                    profiles.
                                                                                    Evaluations of fatty
                                                                                    acid biomarker levels.

[[Page 93605]]

 
                                       Key Question 2:                             Key Question 2:
                                        Cardiovascular events               Other cardiac or
                                       [cir] Atherosclerotic cardiovascular         vascular related outcomes.
                                        disease (total)                             Participant reported
                                       [cir] Major adverse cardiac (or cerebral)    events.
                                        events (MAC[C]E)
                                       [cir] Specific cardiovascular events
                                       [ssquf] Myocardial infarction
                                       [ssquf] Coronary heart/artery disease
                                       [ssquf] Peripheral vascular/artery disease
                                       [cir] Revascularization (for studies
                                        published after 1995)
                                       [cir] Cardiovascular disease-related
                                        mortality
                                       [cir] Stroke
                                       [cir] Incident atrial fibrillation
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Subgroups/effect modifiers of          Both Key Questions:                         None.
 interest.
                                        Specific life stages
                                       [cir] Infants (for Key Question 1 only)
                                       [cir] Children and adolescents (for Key
                                        Question 1 only)
                                       [cir] Adults (19-64)
                                       [cir] Older adults (>=65)
                                       [cir] Pregnant or postpartum
                                       [cir] Menopausal status
                                        Other characteristics
                                       [cir] Sex (male, female)
                                       [cir] Socioeconomic status
                                       [cir] Social determinants of health
                                       [cir] Race/ethnicity
                                       [cir] Physical activity level
                                       [cir] Anthropometry
                                       [cir] Health status, including type 2
                                        diabetes
                                       [cir] Percent of total energy intake
                                        replaced
                                       [cir] Dietary trans fatty acid intake
                                       [cir] Baseline lipid concentrations
                                       [cir] Dietary cholesterol intake
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Design...............................  Key Question 1:                             Both Key Questions:
                                        Studies of adults                   Observational
                                       [cir] Parallel or cross-over randomized      studies that do not account
                                        controlled trials (RCTs)                    for confounders.
                                       [ssquf] n >=25/group *                       Analyses of dietary
                                        Studies of children                 fat as a continuous variable
                                       [cir] Parallel or cross-over RCTs            (e.g., RR per g/day intake)
                                       [ssquf] n >=25/group *                       without an analysis at a
                                       [cir] Nonrandomized comparative studies      threshold (e.g., RR for > vs
                                       [ssquf] Must account for potential           < threshold).
                                        confounders                                 All other study
                                       [ssquf] n >=50/group *                       designs.
                                       Key Question 2:
                                        Studies of adults
                                       [cir] Parallel or cross-over RCTs
                                       [ssquf] n >=25/group *
                                       [cir] Nonrandomized comparative studies
                                       [ssquf] Must account for potential
                                        confounders
                                       [ssquf] Dietary intake must be defined or
                                        described prospectively
                                       [ssquf] We will aim for a minimum of about
                                        10 observational studies for each
                                        specific PUFA--CV event pair (e.g., EPA
                                        and stroke). We will thus select the
                                        largest observational studies within each
                                        category.[dagger]
                                       [ssquf] n >=100/group
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Timing...............................  Key Question 1:                             None.
                                        Minimum intervention length: 4
                                        weeks
                                        In cross-over studies, any change
                                        in outcome measure must exclude data from
                                        the first week after end of any prior
                                        treatments

[[Page 93606]]

 
                                       Key Question 2:
                                        Minimum follow-up
                                       [cir] If population has no CV risk factors
                                        (or unselected general population): 10
                                        years
                                       [cir] If population has one or more CV
                                        risk factors: 5 years
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Setting..............................   General community settings,         Hospital or other
                                        including nursing homes, assisted living    acute care settings.
                                        facilities, etc.                            Institutionalized,
                                                                                    confined settings (e.g.,
                                                                                    prisons).
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Publication..........................   English language
                                        Published in peer-reviewed
                                        journals
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* Minimum sample size may be altered depending on the number of eligible studies found.
[dagger] Applying this approach for the 2016 AHRQ report n-3 fatty acids and cardiovascular disease (https://doi.org/10.23970/AHRQEPCERTA223), we included: for cardiac event outcomes, observational studies with at least
  10,000 participants; for stroke outcomes, at least 3000 participants; for arrhythmia outcomes, at least 2000
  participants; congestive heart failure outcomes, at least 700 participants; and for peripheral vascular
  disease events and MACE outcomes, at least 500 participants. In all instances, if a study meets eligibility
  criteria for any outcome, we will extract all outcomes of interest from that study; therefore, there will be
  multiple instances of studies being included for an outcome even though the study might not have met study
  size criteria for that specific outcome.
CV = cardiovascular; CVD = cardiovascular disease; PUFA = polyunsaturated fatty acids; ALA = alpha-linolenic
  acid; EPA = eicosapentaenoic aci; DHA= docosahexaenoic acid; DPA = docosapentaenoic acid; n-3 = Omega 3; n-6 =
  Omega 6; FA = fatty acid; c = cholesterol; LDL = low-density lipoprotein; IDL = intermediate-density
  lipoprotein; HDL high-density lipoprotein; TC--total cholesterol; Tg = Triglycerides/Triacylglycerols; apoA =
  apolipoprotein; MAC[C]E = Major adverse cardiac (or cerebro) events; BMI = body mass index; KQ = key question;
  N = number of participants.


    Dated: November 21, 2024.
Marquita Cullom,
Associate Director.
[FR Doc. 2024-27798 Filed 11-26-24; 8:45 am]
BILLING CODE 4160-90-P`