Draft Research Plan

Screening for Colorectal Cancer

Note: This is a draft Research Plan. This draft is distributed solely for the purpose of receiving public input. It has not been disseminated otherwise by the USPSTF.

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

This draft Research Plan is available for comment from January 9 until February 5, 2014 at 5:00 p.m., ET. You may wish to read the entire Research Plan before you comment.

I. Proposed Analytic Framework

Select Text Description below for details.

Abbreviations: CT = computed tomography; FIT = fecal immunochemical test; Flex Sig = flexible sigmoidoscopy; gFOBT = Guaiac fecal occult blood test; mSEPT9 = circulating methylated septin 9 DNA.

[D] Select for Text Description.

II. Proposed Key Questions to Be Systematically Reviewed

What is the effectiveness (or comparative effectiveness) of screening programs based on any of the following screening tests (alone or in combination) in reducing a) incidence of and b) mortality from colorectal cancer?
- Colonoscopy
- Flexible sigmoidoscopy
- Computed tomography (CT) colonography
- Fecal screening tests:
  - (Any) Guaiac fecal occult blood test (gFOBT)
  - Fecal immunochemical test (FIT)
  - Fecal DNA test
- Blood screening test:
  - Circulating methylated septin 9 DNA (mSEPT9)
What are the test performance characteristics (e.g., sensitivity and specificity) of the following screening tests (alone or in combination) for detecting a) colorectal cancer, b) advanced adenomas, and c) adenomatous polyps based on size?
- Colonoscopy
- Flexible sigmoidoscopy
- CT colonography
- Fecal screening tests:
  - High-sensitivity gFOBT
  - FIT
  - Fecal DNA test
- Blood screening test:
  - mSEPT9
a) What are the adverse effects (i.e., serious harms) of the different screening tests (either as a single application or in a screening program)? b) Do adverse effects vary by important subpopulations (e.g., by age)?

III. Proposed Contextual Questions

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

What are the current rates of overall screening for colorectal cancer and screening with specific tests in the United States?
What is the adherence to testing for each of the currently available screening tests? What is the adherence to followup diagnostic colonoscopy for abnormal screening test results (i.e., fecal testing, flexible sigmoidoscopy, CT colonography)?
Do rates of screening or adherence to screening tests vary by important subpopulations (i.e., by age, sex, race/ethnicity)?
What is the likelihood of progression or regression of small adenomas (i.e., 6 to 9 mm) to colorectal cancer?
What is the distribution of colorectal lesions (colorectal cancer, advanced adenomas, small adenomatous polyps) by location in the colon (e.g., proximal versus distal colon)?
Does the distribution of lesions in the colon vary by important subpopulations (i.e., by age, sex, race/ethnicity)?

IV. Proposed Research Approach

The Proposed 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 Report. Criteria are overarching as well as specific to each of the key questions (KQs).

	Include	Exclude
Populations	Age ≥40 years, average-risk or unselected populations; screening populations (i.e., asymptomatic)	Populations selected for personal or family history of colorectal cancer, known genetic susceptibility syndromes (e.g., Lynch syndrome, familial adenomatous polyposis), or personal history of inflammatory bowel disease; nonscreening populations (e.g., persons who are symptomatic, screen positive, have iron deficiency anemia, or are under surveillance for a previous colorectal lesion)
Settings	Settings representative of community practice for flexible sigmoidoscopy and colonoscopy studies; developed countries (i.e., rated “very high” on the Human Development Index)	Primarily research-based settings (or select academic settings that would not be applicable to most practice settings) for endoscopy studies (e.g., small studies aimed at evaluating new endoscopy technologies, studies with operator or resource characteristics not applicable to community practice); developing countries
Screening tests	KQ 1: Any program of colorectal screening, including endoscopy, imaging, and fecal or blood testing KQs 2, 3: Colonoscopy; flexible sigmoidoscopy; CT colonography; fecal screening tests, such as gFOBT (e.g., Hemoccult SENSA®), FIT (quantitative and qualitative testing), and fecal DNA test; blood screening tests (i.e., mSEPT9)	KQs 2, 3: Hemoccult II (review of test performance and harms limited to high-sensitivity gFOBT); stool testing using in-office digital rectal examination; double contrast barium enema; capsule endoscopy (e.g., PillCam®); magnetic resonance colonography
Comparisons	KQ 1: No screening or alternate screening strategy KQ 2: Diagnostic accuracy studies that use colonoscopy as a reference standard KQ 3: No comparator necessary
Outcomes	KQ 1: Colorectal cancer incidence (by stage), interval colorectal cancer; colorectal cancer– specific or all-cause mortality KQ 2: Test performance, including sensitivity and specificity (per person); positive and negative predictive value (per person); yield and miss rates (per lesion) for structural examinations (i.e., colonoscopy, flexible sigmoidoscopy, CT colonography) For detection of colorectal cancer, advanced adenoma (high-grade dysplasia, villous histology, and/or ≥10 mm), and/or adenomatous polyps by size (i.e., ≤5 mm, 6–9 mm, ≥10 mm) By location in colon (e.g., proximal versus distal) KQ 3: Serious adverse events requiring unexpected or unwanted medical attention and/or resulting in death (e.g., requiring hospitalization), including but not limited to perforation, major bleeding, severe abdominal symptoms, and cardiovascular events; extra-colonic findings and subsequent diagnostic workup and adverse events from diagnostic testing for incidental findings on CT colonography; radiation exposure per CT colonography examination	KQ 1: Incidence of adenomas or advanced neoplasia (composite outcome of advanced adenomas and colorectal cancer) KQ 3: Minor adverse events defined as those not necessarily needing or resulting in medical attention (e.g., patient dissatisfaction, anxiety/worry, minor gastrointestinal complaints)
Study Design	KQs 1–3: Fair- to good-quality studies; studies published between January 1, 2008 and May 31, 2014 (bridge searches will be conducted as required to keep review current at time of publication) KQ 1: Systematic reviews (of included study designs); randomized, controlled trials; selected well-designed controlled clinical trials; cohort studies; or case-control studies KQ 2: Systematic reviews (of included study designs), trials, cohort or well-conducted nested case-control diagnostic accuracy studies, screening registry studies KQ 3: Systematic reviews (of included study designs); randomized, controlled trials; controlled clinical trials; large screening registry or database observational studies; cohort studies; systematically selected case series	KQs 1–3: Poor-quality studies with a fatal flaw; studies with a publication date outside of review window KQ 1: Decision analyses KQ 2: Diagnostic accuracy studies without colonoscopy as a reference standard, diagnostic accuracy studies without representation of a full spectrum of disease (e.g., case-control studies, excluded indeterminate results)

AHRQ Publication No. 14-05203-EF-5
Current as of January 2014

Internet Citation:

U.S. Preventive Services Task Force. Screening for Colorectal Cancer: Draft Research Plan. AHRQ Publication No. 14-05203-EF-5. http://www.uspreventiveservicestaskforce.org/draftresplan.htm