Final Research Plan
Celiac Disease: Screening
November 03, 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.
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 Review will form the basis of the USPSTF Recommendation Statement on this topic.
This draft Research Plan was available for comment from July 31 until August 27, 2014 at 5:00 p.m., ET.
Abbreviation: KQ=key question.
This figure depicts the analytic framework that outlines the evidence areas covered in the research plan, including populations, screening, treatment, and outcomes. The populations include adults, adolescents, and children who are asymptomatic for celiac disease. “Asymptomatic” persons are defined as those without known celiac disease and who have not sought evaluation for potential celiac disease; some asymptomatic persons may have mild, nonspecific symptoms. After screening, an overarching arrow leads to clinical health outcomes to represent the effect of screening on clinical health outcomes. An initial branch in the framework splits patients into those with normal versus abnormal test results after screening, and assesses the harms of screening. A subsequent branch from persons with abnormal test results leads to treatment, and an arrow from treatment assesses resulting harms. Clinical health outcomes include mortality and morbidity, such as cancer incidence, gastrointestinal outcomes, mood and anxiety disorders, child growth outcomes, health outcomes resulting from nutritional deficiencies (such as symptomatic or severe anemia) and quality of life.
- What is the effectiveness of screening versus not screening for celiac disease in asymptomatic adults, adolescents, or children on morbidity, mortality, or quality of life?
- What is the effectiveness of targeted* versus universal screening for celiac disease in asymptomatic adults, adolescents, or children on morbidity, mortality, or quality of life?
- What are the harms of screening for celiac disease?
- What is the accuracy of screening tests for celiac disease?
- Does treatment of screen-detected celiac disease lead to improved morbidity, mortality, or quality of life compared with no treatment?
- Does treatment of screen-detected celiac disease lead to improved morbidity, mortality, or quality of life compared with treatment initiated after clinical diagnosis?
- What are the harms associated with treatment of celiac disease?
*Targeted screening refers to testing in patients with a family history or other risk factors for celiac disease.
Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.
- Among patients without overt symptoms, what is the prevalence of celiac disease in children, adolescents, and adults in the United States?
- What is the natural history of subclinical or silent celiac disease?
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 | |
|---|---|---|
| Populations |
KQs 1–3: Asymptomatic adults, adolescents, or children age ≥3 years without known celiac disease who have not sought evaluation for potential celiac disease; some “asymptomatic” individuals may have mild, nonspecific symptoms. Studies of asymptomatic patients at higher risk (including patients with type 1 diabetes) will be included
KQ 4: Asymptomatic adults, adolescents, or children age ≥3 years without known celiac disease. Studies of asymptomatic patients at higher risk (including patients with type 1 diabetes) will be included KQs 5–7: Patients with screen-detected celiac disease; if evidence in such patients is unavailable or very limited, patients with mild celiac disease will be included. Studies of asymptomatic patients at higher risk (including patients with type 1 diabetes) will be included |
KQs 1–3: Symptomatic persons seeking evaluation for potential celiac disease |
| Interventions |
KQs 1, 2: Serologic screening (immunoglobulin A [IgA] anti-tissue transglutaminase [TTG] antibody or other commonly used tests)
KQ 3: Serologic screening (IgA TTG antibody or other commonly used tests); diagnostic testing, with or without biopsy KQ 4: Serologic screening (IgA TTG antibody or other commonly used tests); questionnaires KQs 5–7: Gluten-free diet |
|
| Comparators |
KQ 1: Screening vs. no screening
KQ 2: Targeted vs. universal screening KQ 4: Endoscopy with biopsy KQ 5: Screen-detected treatment vs. no treatment KQ 6: Screen-detected celiac disease vs. disease detected after clinical diagnosis |
|
| Outcomes |
KQs 1, 2, 5, 6: Morbidity (including outcomes related to nutritional deficiencies, such as symptomatic or severe anemia [i.e., requiring treatment]), gastrointestinal outcomes (e.g., diarrhea, cramping, bloating), cancer incidence, mood and anxiety disorders, child growth outcomes, infection rates, and quality of life; mortality
KQ 3: Labeling, complications/harms from workup/biopsy, and overdiagnosis KQ 4: Sensitivity, specificity, positive and negative predictive values, area under the receiver operating curve, and other measures of diagnostic test accuracy KQ 7: Any harms of treatment |
KQs 1, 2, 5, 6: Laboratory values for nutritional or other deficiencies |
| Settings | KQs 1–3: Primary care | KQs 1–3: Specialty clinics |
| Study designs |
KQs 1–3, 7: Randomized, controlled trials; controlled observational studies; systematic reviews
KQ 4: Studies evaluating diagnostic accuracy of serologic screening or questionnaires compared with intestinal biopsy; systematic reviews KQs 5, 6: Randomized, controlled trials; systematic reviews |
KQ 4: Case-control studies |
The draft Research Plan was posted for public comment on the U.S. Preventive Services Task Force (USPSTF) Web site from July 31 to August 27, 2014. In response to public comments, the USPSTF added mood and anxiety disorders and symptomatic or severe (i.e., requiring treatment) anemia as potential health outcomes, and clarified that targeted screening refers to testing patients with a family history or other risk factors for celiac disease. In addition, the USPSTF revised the Analytic Framework to show that the target population is asymptomatic persons. It also revised the inclusion and exclusion criteria to clarify that some studies for key questions related to screening may include “asymptomatic” patients with mild, nonspecific symptoms; studies of patients with mild celiac disease will be included for key questions related to treatment if evidence on patients with screen-detected celiac disease is unavailable or very limited.