Person:

Bretthauer, Michael

Background: 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. Results: 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. Conclusions: 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. Trial registration Clinicaltrials.gov identifier NCT00119912 (registered 6 July 2005) Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-1056-8) contains supplementary material, which is available to authorized users.

Background and study aims Some guidelines recommend a minimum standard of 90 % cecal intubation rate (CIR) in routine clinics and 95 % in screening colonoscopy, while others have not made this distinction – both with limited evidence to support either view. This study questions the rationale for making such differentiation. Patients and methods We assessed cecum intubation rates amongst colonoscopies recorded in the Norwegian national quality register Gastronet by 35 endoscopists performing both clinical and screening colonoscopies. Colonoscopies were categorized into primary screening colonoscopy, work-up colonoscopy of screen-positives and clinical colonoscopy or surveillance. Cases with insufficient bowel preparation or mechanical obstruction were excluded. Endoscopists were categorized into “junior” and “senior” endoscopists depending on training and experience. Univariable and multivariable logistic regression analyses were applied. Results During a 2-year period, 10,267 colonoscopies were included (primary screening colonoscopy: 746; work-up colonoscopy of screen-positives: 2,604; clinical colonoscopy or surveillance: 6917). The crude CIR in clinical routine colonoscopy, primary screening colonoscopy and work-up colonoscopy was 97.1 %, 97.1 % and 98.6 %, respectively. In a multiple logistic regression analysis, there were no differences in CIR between the 3 groups. Poor bowel cleansing and female sex were independent predictors for intubation failure. Conclusion Cecal intubation rate in clinical colonoscopies and colonoscopy screening are similar. There is no reason to differentiate between screening and clinical colonoscopy with regard to CIR.