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 will form the basis of the USPSTF Recommendation Statement on this topic.

The draft Research Plan was available for comment from June 13 until July 10, 2013 at 5:00 p.m., ET.

Abbreviations: ASA = aspirin; CRC=colorectal cancer.

1. Does regular aspirin use reduce total cancer mortality or all-cause mortality in adults who take (or are eligible for taking) aspirin for the primary prevention of cancer?
   1. Does the effect of aspirin vary by a priori subgroups, such as age, sex, race/ethnicity, baseline cancer risk†, or comorbid conditions*?
   2. Does the effect of aspirin vary by delivery of intervention (e.g., dose, frequency, duration, formulation, recency of use)?
2. Does regular aspirin use reduce the incidence of cancer in adults who take (or are eligible for taking) aspirin for the primary prevention of cancer?
   1. Does the effect of aspirin vary by a priori subgroups, such as age, sex, race/ethnicity, baseline cancer risk†, or comorbid conditions*?
   2. Does the effect of aspirin vary by delivery of intervention (e.g., dose, frequency, duration, formulation, recency of use)?
3. Does regular aspirin use reduce colorectal cancer mortality in adults without a history of colorectal cancer, familial adenomatous polyposis (FAP), or Lynch syndrome?
   1. Does the effect of aspirin vary by a priori subgroups, such as age, sex, race/ethnicity, baseline cancer risk†, or comorbid conditions*?
   2. Does the effect of aspirin vary by delivery of intervention (e.g., dose, frequency, duration, formulation, recency of use)?
4. Does regular aspirin use reduce the incidence of colorectal cancer in adults without a history of colorectal cancer, FAP, or Lynch syndrome?
   1. Does the effect of aspirin vary by a priori subgroups, such as age, sex, race/ethnicity, baseline cancer risk†, or comorbid conditions*?
   2. Does the effect of aspirin vary by delivery of intervention (e.g., dose, frequency, duration, formulation, recency of use)?
5. Does regular aspirin use reduce the incidence of colorectal adenoma in adults without a history of colorectal cancer, FAP, or Lynch syndrome?
   1. Does the effect of aspirin vary by a priori subgroups, such as age, sex, race/ethnicity, baseline cancer risk†, or comorbid conditions*?
   2. Does the effect of aspirin vary by delivery of intervention (e.g., dose, frequency, duration, formulation, recency of use)?
6. What are the serious harms of regular aspirin use for the primary prevention of cancer (at the dosage and duration required to achieve a preventive health effect) in adults who are appropriate for aspirin chemoprevention?
   1. Does the effect of aspirin vary by a priori subgroups, such as age, sex, race/ethnicity, baseline cancer risk†, comorbid conditions*, or concomitant medication use‡?
   2. Does the effect of aspirin vary by delivery of intervention (e.g., dose, frequency, duration, formulation, recency of use)?
7. What are the serious harms of regular aspirin use for the prevention of colorectal cancer (at the dosage and duration required to achieve a preventive health effect) in adults without a history of colorectal cancer, FAP, or Lynch syndrome?
   1. Does the effect of aspirin vary by a priori subgroups, such as age, sex, race/ethnicity, baseline cancer risk†, comorbid conditions*, or concomitant medication use‡?
   2. Does the effect of aspirin vary by delivery of intervention (e.g., dose, frequency, duration, formulation, recency of use)?

* The following prevalent comorbid conditions that may be affected by aspirin use in terms of benefits or harms are proposed: diabetes, liver disease, ulcer disease, and previous gastrointestinal bleeding.
† Baseline cancer risk includes family history and other potential risk factors, if specified in the literature.
‡ Medications include nonaspirin, nonsteroidal anti-inflammatory drugs and selective serotonin reuptake inhibitors.

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

1. What are the relative and absolute contraindications for regular aspirin use?
2. What valid risk prediction tools to determine bleeding risk (e.g., gastrointestinal bleeding, hemorrhagic stroke, other major bleeding) are available for persons who are not contraindicated for regular aspirin use for the primary prevention of colorectal cancer, cardiovascular disease, or cancer in general?
3. What is the persistence of continued regular use in persons who initiate aspirin use for the prevention of colorectal cancer, cardiovascular disease, or cancer in general?

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

The draft Research Plan, entitled “Aspirin Use for the Prevention of Colorectal Cancer,” was posted for public comment on the U.S. Preventive Services Task Force (USPSTF) Web site from June 13 to July 10, 2013. The USPSTF reviewed and considered all comments received and made changes to the Research Plan in response. The most significant change is expansion of the scope of outcomes evaluated from colorectal cancer to all types of cancer. As part of the increased scope, three Key Questions (KQs 1, 2, and 6) and two Contextual Questions (1 and 2) were added to the Research Plan. A proposed Contextual Question on harms of concomitant medication use was integrated into the appropriate Key Questions.

Other changes included modifying the age range for the population of interest from age 18 years and older to age 40 years and older. This better reflects the potential target population for the intervention and aligns this Research Plan with the companion Research Plan on aspirin use for the prevention of cardiovascular events. In addition, the term “regular” aspirin use was substituted for “low dose” aspirin use to avoid confusion. The variety of dosages used in the trials will be characterized in the evidence report.