U.S. Preventive Services Task Force banner
U.S. Preventive Services Task Force

You Are Here: U.S. Preventive Services Task Force > Topic Index > Aspirin Use for the Primary Prevention of Cancer > Final Research Plan


Final Research Plan

Aspirin Use for the Primary Prevention of Cancer


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. To view the draft Research Plan, click here.

A related final Research Plan on aspirin use for the primary prevention of cardiovascular events is available here.


I. Analytic Framework

Select Text Description below for details.

Abbreviations: ASA = aspirin; CRC=colorectal cancer.

[D] Select for Text Description.

II. Key Questions to Be Systematically Reviewed

  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.

III. Contextual Questions

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?

IV. Research Approach

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).

Category Included Excluded
Aim/Condition Any indication; cancer incidence and deaths reported as an outcome:
  • Primary prevention of cancer
  • Primary prevention of cardiovascular disease (secondary prevention of cardiovascular disease for sensitivity analyses)
Secondary or tertiary prevention of cancer; treatment of cancer; cancer remission; cancer recurrence; cancer metastases
Populations Adults age 40 years and older
  • Nonhuman populations
  • Children and adolescents (age <18 years)
  • Studies in which the majority of participants are age <40 years
  • Pregnant women
  • Institutionalized persons (psychiatric inpatients)
  • Persons in long-term care
  • Postsurgical patients
  • Persons who are contraindicated or not eligible for aspirin chemoprevention
  • Symptomatic patients (e.g., those undergoing a diagnostic colonoscopy)
Intervention Aspirin:
  • Oral
  • Minimum of 75 mg every day or every other day
  • No maximum limit
  • Exposure of at least 12 months
  • Formulations include tablet, enteric coated tablets, chewable tablets, and effervescent tablets

Both intervention and control groups may be taking other medications or supplements

  • Irregular or occasional aspirin use
  • Other nonaspirin, nonsteroidal anti-inflammatory drugs
  • Delivered via nonoral routes
  • Dosage information not reported
  • Nontablet oral formulations (e.g., gum)
  • Co-administration with other chemopreventive (e.g., tamoxifen) or potentially chemopreventive agents (e.g., vitamin E) or lifestyle interventions (e.g., diet, exercise)
  • Co-administration with other nonaspirin antithrombotic medications (e.g., warfarin, other antiplatelet agents)
Comparator
  • Placebo
  • No intervention
  • Comparative effectiveness (any active agent or intervention, such as pharmacological or lifestyle intervention)
Outcomes KQs 1, 2 (health and cancer outcomes):
  • Incidence of cancer
  • Cancer-related mortality
  • All-cause mortality

KQs 3–5 (colorectal cancer outcomes):

  • Colorectal cancer incidence
  • Colorectal cancer mortality
  • Colorectal adenoma incidence
  • Advanced adenoma incidence
  • Advanced neoplasia

KQs 6, 7 (harms):

  • Gastrointestinal bleeding
  • Hemorrhagic stroke
  • Other serious harms (e.g., age-related macular degeneration)
Cancer specific:
  • Biomarkers
  • Biologic or physiologic markers of cancer (e.g., serum prostate-specific antigen, breast density)
  • Precancerous markers
  • Progression or metastasis
  • Recurrence

KQs 6, 7 (harms):

  • Postoperative or minor bleeding
Study Design KQs 1–5:
  • Randomized, controlled trials
  • Controlled clinical trials
  • Systematic reviews and meta-analyses of randomized, controlled trials for evidence on benefits

KQs 6, 7:

  • Randomized, controlled trials
  • Controlled clinical trials
  • Systematic reviews and meta-analyses for evidence of harms
  • Large prospective cohort studies
  • Patient registries
KQs 1–5:
  • Factorial designed studies in which the aspirin versus placebo group is not reported separately
  • Observational studies
  • Commentaries
  • Editorials
  • Narrative reviews

KQs 6, 7:

  • Case reports
  • Case-control studies
  • Small or retrospective cohort studies
  • Case series
  • Commentaries
  • Editorials
  • Narrative reviews
Setting Outpatient Exclusively inpatient
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

V. 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.

AHRQ Publication No. 13-05193-EF-5
Current as of October 2013


Internet Citation:

U.S. Preventive Services Task Force. Aspirin Use for the Primary Prevention of Cancer: Final Research Plan. AHRQ Publication No. 13-05193-EF-5. http://www.uspreventiveservicestaskforce.org/uspstf13/asprcolo/asprcanfinalresplan.htm



USPSTF Program Office   540 Gaither Road, Rockville, MD 20850