[Federal Register Volume 78, Number 128 (Wednesday, July 3, 2013)]
[Notices]
[Pages 40147-40149]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-15730]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality


Scientific Information Request on Vitamin D and Calcium

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

ACTION: Request for Scientific Information Submissions.

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SUMMARY: The Agency for Healthcare Research and Quality (AHRQ) is 
seeking scientific information submissions from the public on Vitamin D 
and Calcium. Scientific information is being solicited to inform the 
Vitamin D and Calcium: A Systematic Review of Health Outcomes project, 
which is currently being conducted by the Evidence-based Practice 
Centers for the AHRQ Effective Health Care Program. Access to published 
and unpublished pertinent scientific information on vitamin D and 
calcium will improve the quality of this systematic review. AHRQ is 
conducting this systematic review pursuant to Section 1013 of the 
Medicare Prescription Drug, Improvement, and Modernization Act of 2003, 
Public Law 108-173, and Section 902(a) of the Public Health Service 
Act, 42 U.S.C. 299a(a).

DATES: Submission Deadline on or before August 2, 2013.

ADDRESSES: 
    Online submissions: http://effectivehealthcare.AHRO.gov/index.cfm/submitscientific-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, PO 
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: Robin Paynter, Research Librarian, 
Telephone: 503-220-8262 ext. 58652 or Email: src.org">SIPS@epc-src.org.

SUPPLEMENTARY INFORMATION: The Agency for Healthcare Research and 
Quality has commissioned the Effective Health Care (EHC) Program 
Evidence-based Practice Centers to complete a review of the evidence 
for Vitamin D and Calcium: A Systematic Review of Health Outcomes.
    The EHC 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 vitamin D and calcium, including those that describe 
adverse events, as specified in the key questions detailed below. The 
entire research protocol, including the key questions, is also 
available online at: http://effectivehealthcare.AHRQ.gov/search-forquides-reviews-and-reports/?pageaction=displayproduct&productID=1529
    This notice is to notify the public that the EHC program would find 
the following information on Vitamin D and Calcium helpful:
     A list of completed studies your company has sponsored for 
this indication. In the list, indicate whether results are available on 
ClinicalTrials.gov along with the ClinicalTrials.gov trial number.
     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.
     A list of ongoing studies your company 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.
     A description of whether the above studies constitute ALL 
Phase II and above clinical trials sponsored by your company for this 
indication and an index outlining the relevant information in each 
submitted file.
    Your contribution is very beneficial to the 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; 
pharmacoeconomic,

[[Page 40148]]

pharmacokinetic or pharmacodynamic studies; study types not included in 
the review; or information on indications not included in the review 
cannot be used by the Effective Health Care 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 EHC 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/.

Key Question 1

    What is the effect of vitamin D intake or combined vitamin D plus 
calcium intake (but not calcium intake alone) on clinical outcomes, 
including cardiovascular diseases, cancer, immune function, pregnancy 
or birth outcomes, mortality, fracture, renal outcomes, and soft tissue 
calcification (the current report excludes two outcomes included in the 
original 2009 report: growth and weight management).

Population(s)

     The primary population of interest is generally healthy 
people with no known disorders, with the following exceptions. Studies 
that include broad populations might include some individuals with 
diseases or who are at risk for diseases.
     Studies of individuals with previous cancer, previous 
fractures, or precancerous conditions will be included.
     With the exception of studies of older adults, studies in 
which more than 20 percent of the participants have been diagnosed with 
a disease will be excluded.
     For clinical outcomes of cardiovascular disease (CVD), 
only studies of adults will be included (>=18 years of age).

Interventions

     For observational studies (exposures):

 Serum concentration of 25-hydroxyvitamin D [25(OH)D] or 1,25- 
dihydroxyvitamin D [1,25(0i1)2D] and method used
     Dietary intake of calcium from food and supplements
     Calcium balance
     For interventional studies:
     Vitamin D supplements with known doses
     Calcium supplements if co-administered with vitamin D
     Food-based interventions in which the doses of vitamin D 
and calcium were quantified and in which the doses differ between 
comparison groups

Comparators

 For observational studies:
     Lower serum concentrations of vitamin D
 For interventional studies:
     Placebo, non-fortified/supplemented food

Outcomes

 CVD clinical outcomes
 Cardiac events or symptoms
 Cerebrovascular events
 Peripheral vascular events or symptoms
 Cardiovascular death
 Study-specific combinations of cardiovascular events
 Total cancer
 Prostate cancer
 Colorectal cancer
 Breast cancer
 Pancreatic cancer
 Cancer-specific mortality
 Immune function clinical outcomes
 Infectious disease
 Autoimmune diseases
 Infectious disease-specific mortality
 Pregnancy-related outcomes
 Preterm birth or low birth weight
 Infant mortality
 Mortality, all cause
 Bone health, clinical outcomes
 Rickets
 Fracture
 Falls or muscle strength
 Adverse effects of intervention(s)
 All-cause mortality
 Cancer incidence and cancer-specific mortality
 Renal outcomes
 Soft tissue calcification
 (Other) adverse events from vitamin D or vitamin D plus 
calcium supplements

Timing

     Timing of interventions or exposures will not be pre-
specified, with the exception that cross-sectional and retrospective 
case-control studies will not be included (nested case controls within 
prospective cohort studies will be included).
     For studies with multiple follow-up periods, the longest 
follow-up times will be preferentially considered.

Settings

     Settings will not be pre-specified.

Key Question 2

    What is the effect of vitamin D or combined vitamin D and calcium 
intake on-surrogate or intermediate outcomes such as hypertension, 
blood pressure, and bone mineral density?

Populations

     As described for KQ 1, with the exception that for blood 
pressure and other CVD intermediate outcomes, only studies of adults 18 
years of age or older will be included.

Interventions

     As described for KQ 1, with the following exceptions:

     For CVD outcomes, only randomized controlled trials (RCTs) 
will be included
     For bone health outcomes, only RCTs of greater than 1 year 
in duration will be included

Comparators

     As described for KQ 1.

Outcomes

     As specified in the original 2009 report, unless otherwise 
noted:

     CVD intermediate outcomes
     Cancer intermediate outcomes (colorectal adenoma, aberrant 
crypt cells, and mammographic breast density)
     Bone health intermediate outcomes (only bone mineral 
density/content)
     Pregnancy-related intermediate outcomes
     Pre-eclampsia
     High blood pressure with or without proteinuria

Timing

     As described for KQ 1, except for intermediate bone health 
for which studies of less than 1 year in duration will be excluded.

Settings

     As described for KQ 1.

Key Question 3

    What is the association between serum 25(OH)D concentrations and 
clinical outcomes?*

Populations

     As described for KQ 1.

Interventions

     Serum concentration of 25(OH)D or 1,25 (OH)2D and the 
method used.

Comparators

     The serum concentration of 25(OH)D or 1,25 (OH)2D and the 
method used for the placebo or other comparison group.

Outcomes

     As described for KQ 1.

Timing

     As described for KQ 1.

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Settings

     As described for KQ 1.

Key Question 4

    What is the effect of vitamin D or combined vitamin D and calcium 
intake on serum 25(OH)D concentrations?

Populations

     As described for KQ 1.

Interventions

     Randomized controlled trials (RCTs) identified to answer 
all other KQs.

Comparators

     Placebo or lower dose supplement.

Outcomes

     Dose-response relationship between intake levels and 
indices of exposure.

Timing

     As described for KQs 1 and 2.

Settings

     As described for KQs 1 and 2.

Key Question 5

    What is the association between serum 25(OH)D concentration and 
surrogate or intermediate outcomes?

Populations

     As described for KQ 2.

Interventions

     As described for KQ 2.

Comparators

     As described for KQ 2.

Outcomes

     As described for KQ 2.

Timing

     As described for KQ 2.

Settings

     As described for KQ 2.

    Dated: June 21, 2013.
Carolyn M. Clancy,
 Director, AHRQ.

[FR Doc. 2013-15730 Filed 7-2-13; 8:45 am]
BILLING CODE 4160-90-M