Critical appraisal:Veenhof AA, Sietses C, von Blomberg BM, van Hoogstraten IM, vd Pas MH, Meijerink WJ, et al 2011 2

Risk of bias assessment: Randomised Controlled Trial (Cochrane risk of bias tool)

Random sequence generation

Describe the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups.

In June 2006, the VU University Medical Center (VUmc) initiated participation in the COLOR II trial; a randomized study comparing laparoscopic to open TME in patients with non-metastasized rectal cancer. All patients who were randomized until December 2008 for the COLOR II trial at the VUmc were included into this sub-study.

The online protocol document details the following "Randomization for all centers will be done through the internet:"
Randomization is stratified for each participating center, planned procedure, radiotherapy and sex.

What was the risk of bias from the random sequence generation?

Low

Allocation concealment

Describe the method used to conceal the allocation sequence in sufficient detail to determine whether intervention allocations could have been foreseen in advance of or during, enrolment.

Not described

What was the risk of bias from the allocation concealment?

Unclear

Blinding

Describe all measures used, if any, to blind outcome assessors from knowledge of which intervention a participant received. Provide any information relating to whether the intended blinding was effective.

Not described.

What was the risk of bias from the blinding of participants and personnel and outcome assessors?

Unclear

Incomplete outcome data

Describe the completeness of outcome data for each main outcome, including attrition and exlusions from the analysis. State whether attrition and exclusions were reported, the numbers in each intervention group (compared with total randomized participants), reasons for attrition/exclusions where reported, and any re-inclusions in analyses performed by the review authors.

Only a small subset of 40 patients from the whole trial.

What was the risk of bias from incomplete outcome data?

Low

Selective outcome reporting

State how the possibility of selective outcome reporting was examined by the review authors and what was found.

The primary endpoints of the study were to demonstrate differences in inflammatory response by evaluating proinflammatory

cytokines (interleukin-6 and interleukin-8) and C-reactive protein (CRP); immune status by evaluating white blood cells and HLA-DR expression on monocytes; and stress response by evaluating cortisol, prolactin, and growth hormone in both groups of patients.

Complications and morbidity defined in the study protocol.

What was the risk of bias from selective outcome reporting? Assessments should be made for each main outcome (or class of outcomes).

Low