Nonsteroidal Anti-Inflammatory Drugs and Cancer Prevention: Two Studies Examined

The Efficacy of Aspirin in Preventing Colorectal Adenomas

There is a large body of evidence suggesting that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk for colorectal cancer, in both animal and human studies. Various biological mechanisms for how NSAIDs inhibit carcinogenesis have been proposed, including altering metabolism, changes in immune function and modified prostaglandin production by tumors.

Numerous randomized and non-randomized studies have been conducted over the years to examine the association between NSAIDs, such as aspirin and colorectal cancer.

Investigative team #1 conducted a randomized trial in 2003. They believe that non-randomized or observational studies alone are limited in their ability to “establish chemopreventive efficacy.” The objective of their trial was to examine the efficacy of aspirin in preventing recurrent colorectal adenomas in individuals with a recent history of adenomas.

After monitoring participants for 32 months, they provide you with the following table. Assume the outcome status of every study participant could be ascertained by the end of follow up – that is, there was no loss to follow-up.

1. What is the risk of colorectal adenoma in each trial arm? [10 points]

2. Would you conclude that aspirin reduces the risk of recurrent adenomas? If so, why? If not, why not? Base your answers on Q1, not information on statistical significance or biological significance, which is not provided here.  [5 points]

Investigative team #2 conducted a study in 2001 to explore whether use of aspirin has a protective effect on gastric cancer. The “study base consisted of all native Swedes aged 40-79 years, living in 5 Swedish counties […] at any time from February 1989 to January 1995. All gastric adenocarcinoma [cases] in the study base” were included in the study.

There was a very thorough and rigorous process of case ascertainment, with more cases identified via the investigators’ techniques than those captured in the Swedish Cancer Register for those counties. Eligible cases were invited to participate in an interview, 62% agreed. Most of the eligible cases not participating in the study had died, were suffering from terminal illness, or had some other physical or mental illness.

The tumor site and histological type were determined using standard methods. Controls “were randomly selected from a continuously updated population registry covering the entire study base.” Controls were frequency matched to the cases by age and sex. Eligible controls were invited to participate in an interview, and 76% agreed to participate.

Most of the eligible controls who did not participate had refused or had some physical or mental illness. Interviewers were not aware of the study hypothesis. The interviewers could not be blinded to the outcome status of the study participants; however, they were trained to interview all participants in the same manner regardless of outcome status. The participants were asked to report their history of pain reliever use two years prior to the interview – prompted specifically for medication brand names and frequency and dosage of pain relievers per month. The investigators present you with the following table.

1. What type of study design did investigative team #2 conduct? What were the sources of the study participants? Be specific about the sources of the comparison groups.  [10 points]

2. What, if any, concerns regarding threats to the internal validity, specifically selection bias and information bias, might there be in this study, as described? [10 points]

3. Is use of aspirin higher among cases or controls? Given the investigator’s study objective, what do you conclude from these findings? [15 points]