↓ Skip to main content

Bounding the per-protocol effect in randomized trials: an application to colorectal cancer screening

Overview of attention for article published in Trials, November 2015
Altmetric Badge

Mentioned by

12 X users


21 Dimensions

Readers on

65 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Bounding the per-protocol effect in randomized trials: an application to colorectal cancer screening
Published in
Trials, November 2015
DOI 10.1186/s13063-015-1056-8
Pubmed ID

Sonja A. Swanson, Øyvind Holme, Magnus Løberg, Mette Kalager, Michael Bretthauer, Geir Hoff, Eline Aas, Miguel A. Hernán


The per-protocol effect is the effect that would have been observed in a randomized trial had everybody followed the protocol. Though obtaining a valid point estimate for the per-protocol effect requires assumptions that are unverifiable and often implausible, lower and upper bounds for the per-protocol effect may be estimated under more plausible assumptions. Strategies for obtaining bounds, known as "partial identification" methods, are especially promising in randomized trials. We estimated bounds for the per-protocol effect of colorectal cancer screening in the Norwegian Colorectal Cancer Prevention trial, a randomized trial of one-time sigmoidoscopy screening in 98,792 men and women aged 50-64 years. The screening was not available to the control arm, while approximately two thirds of individuals in the treatment arm attended the screening. Study outcomes included colorectal cancer incidence and mortality over 10 years of follow-up. Without any assumptions, the data alone provide little information about the size of the effect. Under the assumption that randomization had no effect on the outcome except through screening, a point estimate for the risk under no screening and bounds for the risk under screening are achievable. Thus, the 10-year risk difference for colorectal cancer was estimated to be at least -0.6 % but less than 37.0 %. Bounds for the risk difference for colorectal cancer mortality (-0.2 to 37.4 %) and all-cause mortality (-5.1 to 32.6 %) had similar widths. These bounds appear helpful in quantifying the maximum possible effectiveness, but cannot rule out harm. By making further assumptions about the effect in the subpopulation who would not attend screening regardless of their randomization arm, narrower bounds can be achieved. Bounding the per-protocol effect under several sets of assumptions illuminates our reliance on unverifiable assumptions, highlights the range of effect sizes we are most confident in, and can sometimes demonstrate whether to expect certain subpopulations to receive more benefit or harm than others. Clinicaltrials.gov identifier NCT00119912 (registered 6 July 2005).

X Demographics

X Demographics

The data shown below were collected from the profiles of 12 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 65 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 65 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 10 15%
Student > Ph. D. Student 8 12%
Student > Master 8 12%
Student > Bachelor 4 6%
Professor 4 6%
Other 11 17%
Unknown 20 31%
Readers by discipline Count As %
Medicine and Dentistry 24 37%
Social Sciences 4 6%
Nursing and Health Professions 3 5%
Computer Science 3 5%
Environmental Science 2 3%
Other 6 9%
Unknown 23 35%