Colon cancer screenings more effective than previously thought: study

Colon cancer screening reduces cancer rates much more than previous analyzes of randomized trials suggest, according to a study co-authored by an MIT economist that takes a new look at data from five trials.

About 1% of participants in a given trial develop colon cancer in the decade following the trial. The new results, based on data from trials in half a dozen countries, show that screening reduces this rate by about 0.5%. This is double the impact previously estimated; previous studies placed the screening effect at around a quarter of a percentage point.

“The effect of being screened is about half a percentage point, or double the previously published results that focused on the effect of being invited to a screening,” says MIT econometrician Josh Angrist. The large magnitude of this effect relative to baseline strengthens the case for colorectal screening (CRC), he adds.

The results are important, Angrist says, because many trial subjects who had the option of being screened by colonoscopy or sigmoidoscopy decide to skip it. Previous studies fail to adequately explain such “non-compliance” with planned treatment.

“Nonadherence is prevalent in randomized clinical trials, especially those offering relatively unpleasant interventions like CRC screening,” Angrist says. “Offers of free colonoscopy are not always met with enthusiasm.”

This poses a problem for trial analysis because, even if screening offers are randomly assigned in randomized screening trials, the decision to screen may be far from random.

The article titled “Instrumental variable methods reconcile the effects of screening intention in pragmatic cancer screening trials” was published Friday in Proceedings of the National Academy of Sciences. The authors are Angrist, Ford Professor of Economics at MIT, and Peter Hull Ph.D. ’17, professor of economics at Brown University.

Get tested, not just be asked to do it

The effectiveness of cancer screening is the subject of an active research literature. It may seem like it’s always important to get screened for cancer, but many complicating factors, including the risk of false positives and resulting overtreatment, motivate research into the benefits and costs of such procedures.

The Angrist and Hull study examines data from five major randomized clinical trials of colorectal cancer screening. Four of the screenings used sigmoidoscopies (partial colonoscopies), while one offered full colonoscopies. All trials were randomized, with a treatment group randomly selected and a control group that remained mostly screened.

However, in each trial, the number of participants in the treatment group who were actually screened varied widely, from 42% to 87%, well below the number offered the opportunity to be screened.

“In many clinical trials, many people may not be treated as planned,” Angrist says. “Cancer screening trials are a context where this is particularly problematic.”

Previous studies focused on comparisons based on randomly assigned screening offers, without appropriate adjustment for the number of people actually screened. The core of the new analysis adjusts for the effects of screening intention to produce valid measures of the effect on people who were actually screened.

The adjustment uses an econometric method called “instrumental variables” – “IV” to economists – which, in this case, captures the effect of screening on those who were selected.

“Cancer screening trials, with their substantial non-compliance with treatment protocol, are actually an ideal scenario for IV,” says Angrist.

The new analysis also resolves a key conundrum of previous studies: the variability of results from trial to trial. Angrist and Hull found that the IV estimates from the five trials lined up remarkably well, showing a fairly consistent 0.5 percentage point decrease in cancer incidence among those screened.

“Across five different trials and a set of subgroups, the results are consistent, even though the effects of ITS were quite different across trials,” says Angrist, referring to the effect-driven estimates screening offers. “Once you make the compliance adjustment, they cluster around half a percent.”

Use the toolkit

Angrist is a longtime econometrician who has worked to improve the tools social scientists use to estimate causal effects in a wide variety of areas, including education, labor economics, health care, etc. His methods have also been adopted by some biostatisticians.

“But not enough,” Angrist said. “Peter Hull and I decided to show the power of IV to generate new discoveries in this important area.”

Angrist shared the 2021 Nobel Prize in Economics with David Card of the University of California, Berkeley and Guido Imbens of Stanford University for their work on econometric tools. Angrist’s Nobel citation describes his theoretical work with Imbens on IV, which first showed that IV methods capture what are called “local average treatment effects.” In the context of CRC screening trials, this is simply the average effect of screening on those screened.

Angrist and Hull conclude their article by calling for IV analysis to be made a routine part of clinical research.

“If you want to encourage a reluctant patient to have a colonoscopy, you shouldn’t explain to them the effect of being invited for screening, you should explain to them the effect of actually being screened,” says Angrist. “And that’s a much bigger number.”

This story is republished courtesy of MIT News (web.mit.edu/newsoffice/), a popular site that covers news about MIT research, innovation and education.