Final Research Plan: Aspirin to Prevent Cancer
Final Research Plan for Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: Preventive Medication
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 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.
The figure is an analytic framework that depicts the seven Key Questions that will be addressed in the systematic review. The figure illustrates how aspirin chemoprevention may influence mortality outcomes (KQ 1) in adults age 40 years and older who are taking (or are eligible for taking) aspirin for the primary prevention of cancer. The figure also depicts how this intervention may affect intermediate outcomes, including cancer incidence (KQ 2), colorectal cancer mortality (KQ 3), colorectal cancer incidence (KQ 4), and adenoma incidence (KQ 5). In addition, the figure depicts whether aspirin use for chemoprevention has any potential harms (KQs 6 and 7).
Key Questions to Be Systematically Reviewed
- 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?
- 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?
- Does regular aspirin use reduce colorectal cancer mortality in adults without a history of colorectal cancer, familial adenomatous polyposis (FAP), or Lynch syndrome?
- Does regular aspirin use reduce the incidence of colorectal cancer in adults without a history of colorectal cancer, FAP, or Lynch syndrome?
- Does regular aspirin use reduce the incidence of colorectal adenoma in adults without a history of colorectal cancer, FAP, or Lynch syndrome?
- 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?
- 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?
* 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.
- What are the relative and absolute contraindications for regular aspirin use?
- 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?
- 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).
|Aim/Condition||Any indication; cancer incidence and deaths reported as an outcome:
||Secondary or tertiary prevention of cancer; treatment of cancer; cancer remission; cancer recurrence; cancer metastases|
|Populations||Adults age 40 years and older||
Both intervention and control groups may be taking other medications or supplements
|Outcomes||KQs 1, 2 (health and cancer outcomes):
KQs 3–5 (colorectal cancer outcomes):
KQs 6, 7 (harms):
KQs 6, 7 (harms):
|Study Design||KQs 1–5:
KQs 6, 7:
KQs 6, 7:
|Timing of outcome assessment||12 months or longer||Less than 12 months|
|Country||Any country with a 2013 Human Development Index of “Very High”||Any country with less than a Human Development Index of “Very High”|
|Language||English||Languages other than English|
|Study Quality||Good and fair quality, according to USPSTF criteria||Poor quality, as defined by design-specific USPSTF criteria|
Response to Public Comment
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.
Internet Citation: Final Research Plan: Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: Preventive Medication. U.S. Preventive Services Task Force. October 2013.