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Final Research Plan

Vitamin D Deficiency: Screening

March 24, 2014

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

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The final Research Plan is used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Report forms the basis of the USPSTF Recommendation Statement on this topic.

The draft Research Plan was available for comment from February 26 until March 25, 2013 at 5:00 p.m., ET.

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Select Text Description below for details.

Text Description

The figure is an analytic framework that depicts the pathway that asymptomatic adults may experience during screening for vitamin D deficiency. The figure shows that adults who undergo screening for vitamin D deficiency may be identified as being vitamin D deficient or experience adverse effects related to screening. The figure shows the next steps in the pathway for those who are vitamin D deficient is receiving treatment for vitamin D deficiency and adverse effects related to treatment. The pathway shows outcomes of interest after screening and treatment to be decreased morbidity from selected conditions, reduced disability, improved psychosocial functioning, and reduced mortality.

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  1. Is there direct evidence that screening for vitamin D deficiency results in improved health outcomes?
    1. Are there differences in efficacy between patient subgroups (as defined by risk factors for vitamin D deficiency, such as age 65 years and older, sex, race/ethnicity, body mass index, ultraviolet [UV] exposure, and institutionalization)?
  2. What are the harms of screening (e.g., risk of procedure, false-positive or false-negative results)?
  3. Does treatment of vitamin D deficiency with vitamin D supplementation (with or without calcium) lead to improved health outcomes?
    1. Are there differences in efficacy between patient subgroups (as defined by risk factors for vitamin D deficiency, such as age 65 years and older, sex, race/ethnicity, body mass index, UV exposure, and institutionalization)?
  4. What are the adverse effects of treatment of vitamin D deficiency with vitamin D supplementation?
    1. Are there differences in adverse effects between patient subgroups (as defined by risk factors for vitamin D deficiency, such as age 65 years and older, sex, race/ethnicity, body mass index, UV exposure, and institutionalization)?
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Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. What are the risk factors for vitamin D deficiency?
  2. What is the association between serum 25-hydroxyvitamin D levels and health outcomes?
  3. What is the effect of vitamin D (with or without calcium) on intermediate outcomes (e.g., blood pressure, bone mineral density, glucose tolerance, and lipid levels)?
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The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions (KQs).

  Include Exclude
Population KQs 1, 2: Adults age ≥18 years who are generally healthy

KQs 3, 4: Adults age ≥18 years who are generally healthy with vitamin D deficiency

KQs 1–4: Study participants are either:

  • Unselected or low-risk
  • Selected for increased risk of vitamin D deficiency based on certain characteristics, including older age, darker skin pigmentation (black or Hispanic), obesity, or institutionalization
 Selected populations with conditions including the following:
  • Clinical signs of vitamin D deficiency
  • Osteoporosis
  • Malabsorption
  • Granuloma forming disorders
  • Chronic kidney disease
  • Hepatic failure
  • Cancer
  • Coronary heart disease
  • Diabetes/glucose intolerance
  • Immune disorders
  • High risk of falls
Interventions
  • Vitamin D2 or vitamin D3 (with or without calcium)
  • Food-based interventions, if dose of vitamin D is quantified and doses differ between comparison groups
  • Nonoral routes of vitamin D delivery
  • Dietary intake (unless a food-based intervention, as described under inclusion criteria)
  • UV light exposure
  • Multivitamins
Comparisons KQs 1, 2: Screening

KQs 3, 4: Placebo, no treatment, usual care

 KQs 1, 2: No screening

KQs 3, 4: Different doses of vitamin D
Outcomes KQs 1, 3: Health outcomes include:
  • Decreased morbidity from osteoporosis/fractures, falls, diabetes mellitus, cardiovascular disease, cancer, immune diseases
  • Improved depression; improved psychosocial functioning as measured by quality of life instruments
  • Physical fitness capacity or performance; physical functioning as measured by physical subscales of quality of life measures
  • Disability (global measures only, such as activities of daily living)
  • Mortality
  • Outcomes reported at ≥8 weeks after start of intervention or baseline assessment (if the intervention start cannot be determined) (required)

KQs 2, 4: Health outcomes include:

  • Mortality
  • Renal outcomes (e.g., stones)
  • Soft tissue calcification
  • Adverse events (e.g., gastrointestinal issues)
 KQs 1, 3:
  • Improved functioning (except as enumerated under health outcomes)
  • Intermediate physiological outcomes (examined as contextual question)
  • Behavioral changes (e.g., physical activity, diet)
  • Outcomes reported <8 weeks after start of intervention or baseline assessment (if time from intervention start cannot be determined)
Settings
  • Studies conducted in primary care, feasible for conducting in primary care, or feasible for referral from primary care, including institutionalized settings
  • In order for an intervention to be feasible for primary care referral, it must be conducted as part of a health care setting or be widely available in the community at a national level
  • United States, Canada, United Kingdom, and other geographic settings generalizable to the United States
  • Studies performed in countries with populations not similar to the United States
  • Studies conducted in schools or work sites, unless primary care feasible
Timing KQs 1, 3: At least 8 weeks

KQs 2, 4: Any duration

 KQs 1, 3: Less than 8 weeks

KQs 2, 4: None
Study Designs KQs 1, 3: Systematic reviews or meta-analyses of randomized or controlled clinical trials, primary reports of randomized or controlled clinical trials

KQs 2, 4: Above, plus large cohort studies or case-control studies; studies must have an appropriate comparison group

 KQs 1, 3: Nonsystematic reviews, letters to the editor, cohort or case-control studies, noncomparative studies, and comparative efficacy trials

KQs 2, 4: Nonsystematic reviews, letters to the editor, noncomparative studies, and comparative efficacy trials
Search Criteria OVID MEDLINE® (1946 to January 2013), Cochrane Central Register of Controlled Trials (through January 2013), Cochrane Database of Systematic Reviews (through January 2013), and Cochrane Methodology Register (1st Quarter 2013) will be searched for relevant English-language studies, systematic reviews, and meta-analyses  
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The draft Research Plan was posted for public comment on the U.S. Preventive Services Task Force (USPSTF) Web site from February 26 to March 25, 2013. The USPSTF received several comments requesting it consider including children and adolescents in the review. The USPSTF decided not to broaden the scope of the review to include persons younger than age 18 years because of the significantly different approaches needed for studying vitamin D deficiency in children and adolescents. Several comments asked for clarification of how this review fits into the USPSTF's recommendation on vitamin D and calcium supplementation to prevent fractures. The populations studied in this review are likely to be different from those studied in the other vitamin D recommendation. This review focuses on vitamin D supplementation in persons who are vitamin D deficient, whereas the other recommendation included persons with and without vitamin D deficiency.

Several comments asked how the USPSTF will determine vitamin D deficiency when currently there is no consensus on the definition of a normal vitamin D level and there are challenges with the laboratory tests used to assess those levels. It is not the USPSTF's intent to define vitamin D deficiency or determine the reliability and validity of vitamin D assays. The review will address these issues by carefully tracking study-level data on definitions of deficiency/insufficiency, baseline vitamin D levels, type of assay used, and other characteristics and will assess these definitions as sources of heterogeneity. Finally, several comments asked the USPSTF to consider other data sources in addition to randomized, controlled trials. The USPSTF will use data from observational studies when appropriate to address contextual questions and identify potential harms.

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