A systematic review identified randomised controlled trials (RCTs) assessing
drug and nutritional agents for the prevention of CRC or
adenomatous polyps. A separate search identified qualitative studies relating to individuals' views, attitudes and beliefs about
chemoprevention. MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, CINAHL, the Cochrane Database of Systematic Reviews, Cochrane CENTRAL Register of Controlled Trials, DARE, NHS-EED (NHS Economic Evaluation Database), HTA database, Science Citation Index, BIOSIS previews and the Current Controlled Trials research register were searched in June 2008. Data were extracted by one reviewer and checked by a second.
REVIEW METHODS: The search identified 44 relevant RCTs and six ongoing studies. A small study of
aspirin in FAP patients produced no statistically significant reduction in
polyp number but a possible reduction in
polyp size. There was a statistically significant 21% reduction in risk of
adenoma recurrence [relative risk (RR) 0.79, 95% confidence interval (CI) 0.68 to 0.92] in an analysis of
aspirin versus
no aspirin in individuals with a history of
adenomas or CRC. In the general population, a significant 26% reduction in CRC incidence was demonstrated in studies with a 23-year follow-up (RR 0.74, 95% CI 0.57 to 0.97). Non-
aspirin NSAID use in FAP individuals produced a non-statistically significant reduction in
adenoma incidence after 4 years of treatment and follow-up and reductions in
polyp number and size. In individuals with a history of
adenomas there was a statistically significant 34% reduction in
adenoma recurrence risk (RR 0.66, 95% CI 0.60 to 0.72) and a statistically significant 55% reduction in advanced
adenoma incidence (RR 0.45, 95% CI 0.35 to 0.58). No studies assessed the effect of non-
aspirin NSAIDs in the general population. There were no studies of
folic acid in individuals with FAP or HNPCC. There was no significant effect of
folic acid versus placebo on
adenoma recurrence (RR 1.16, 95% CI 0.97 to 1.39) or advanced
adenoma incidence in individuals with a history of
adenomas. In the general population there was no significant effect of
folic acid on risk of CRC (RR 1.13, 95% CI 0.77 to 1.64), although studies were of relatively short duration.
Calcium use by FAP patients produced no significant reduction in
polyp number or
disease progression. In individuals with a history of
adenomas there was a statistically significant 18% reduction in risk of
adenoma recurrence (RR 0.82, 95% CI 0.69 to 0.98) and a non-significant reduction in risk of advanced
adenomas (RR 0.77, 95% CI 0.50 to 1.17). In the general population there was no significant effect of
calcium on risk of CRC (RR 1.08, 95% CI 0.87 to 1.34), although studies were of relatively short duration. There were no studies of
antioxidant use in individuals with FAP or HNPCC, and in individuals with a history of
adenomas no statistically significant differences in relative risk of
adenoma recurrence were found. In the general population there was no difference in incidence of CRC (RR 1.00, 95% CI 0.88 to 1.13) with
antioxidant use compared with no
antioxidant use. Twenty studies reported qualitative findings concerning
chemoprevention. People are more likely to use
NSAIDs if there is a strong perceived need. Perceptions of risk and benefit also influence decision-making and use. People have fewer concerns about using
antioxidants or other supplements, but their perception of the benefits of these agents is less well-defined. The model analysis suggested that the most cost-effective age-range policy in the general population would be to provide
chemoprevention to all individuals within the general population from age 50 to 60 years. The use of
aspirin in addition to screening within the general population is likely to result in a discounted cost per life-year gained of around 10,000 pounds and a discounted cost per quality-adjusted life-year (QALY) gained of around 23,000 pounds compared with screening alone. In the intermediate-risk group the most economically viable age-range policy would be to provide
chemoprevention to individuals following polypectomy aged 61 to 70 years.
Calcium is likely to have a discounted cost per QALY gained of around 8000 pounds compared with screening alone. Although
aspirin in addition to screening should be more effective and less costly than screening alone, under the current assumptions of benefits to harms of
aspirin and
calcium,
aspirin is expected to be extendedly dominated by
calcium.
LIMITATIONS: