Supplementary Table 1 Risk of bias of each study in detail Random Sequence Generation (selection bias) Allocation Concealment (Selection Bias) Blinding of Participants and Personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias) Selective reporting (reporting bias) Other bias Cole et al. (2007)17 in blocks of 6. Treatment assignments were concealed from participants and study staff except for the pharmacists. Placebo tablets were identical in appearance to folic acid tablets. See above. Placebo tablets were identical in appearance to folic acid tablets. Treatment study staff except for the pharmacists. No information on how this was done. Drop outs reported: Phase 1: died (n=34), lost to follow up (n=9). Phase 2: died (n=16), lost to follow up (n=31). After randomization, there was limited separate reporting on the outcome of the six sub-groups. The reasons for these omissions are thought to be that the author was focusing on the placebo or folic acid group (with our without the two different doses of aspirin) as a whole. Power calculations were performed and sufficient sample numbers acquired. Jaszewski et al. (2008)19 Randomization was performed using a "stratified randomization block". No other information was provided. Selected assignment was made in advance and recorded in sealed envelopes, numbered consecutively. Unspecified. Unspecified. No consort flow diagram. 139 eligible subjects randomized. 94 completed the 3 year 43 dropped out - unrelated deaths (n=28), relocation (n=15). Very high level of deaths despite excluding for co-morbidities. Analysis on 49 (intervention) and 45 (control). In drop-out subjects, there was no statistically significant difference in key demographics. Not clear how many were in each group at baseline as numbers in chart incorrect. Recurrent adenomas reported as mean number rather than relative risk. Data from paper cannot therefore be used in Inconsistencies in baseline data provided. No calculations were performed.
figures. Baseline characteristics of participants included in the final analysis were similar to all randomly assigned participants. In the 194 participants who did not receive an endoscopy, characteristics such as age or severity of adenoma at baseline, that may have affected the likelihood of a follow up, did not differ significantly at baseline. Bonelli et al. (2012)21 No further information provided than randomization lists stratified by centre were provided by the pharmaceutical company. Each centre received a random list where the assigned treatment was indicated by the label numbers of the bottles containing the pills with no reference to their contents. The active compound and the placebo had an identical appearance and that the bottles and pills contained no reference to their contents. Double blinded but no further information States that the trial was double blinded but no further information about blinding of personnel was provided. All drop outs reported: intervention (n=36): refused follow up colonoscopy (n=29), died (n=6), cancer (n=1); control (n=45): refused follow up colonoscopy (n=35), died (n=9), cancer (n=1). Apparently free of selective outcome reporting - all stated outcomes reported. Power calculations provided but required sample size not met. No collection of information on confounding factors at baseline. Limburg et al. (2011)23 "Dynamic allocation procedure". No information provided. Some interventions were delivered as tablets and some as powder. Also different dosages used. No information provided. Low drop-out rate and drop out reasons provided: lost to follow up (n=3), withdrew consent (n=2), medical contraindications (n=1), other (n=2). Apparently free of selective outcome reporting - all stated outcomes reported. Power calculations provided but required sample size not met.
Principi et al. (2013)24 Computer generated. Unspecified. States that the patients and investigators were blinded to assignment without providing any further information. States that both LI and intensity staining were calculated by two independent observers in a blinded fashion without providing any further information. Much higher percentage withdrawal in intervention than control group. 7 out of 30 patients withdrew from the intervention group (4 withdrew consent before T60 colonoscopy and 3 were lost to T60 colonoscopy). 3 out of 30 patients withdrew from the control group (3 withdrew consent before T60 colonoscopy). Apparently free of selective outcome reporting - all stated outcomes reported. calculations provided but required sample size not met. Shimizu et al. (2008)22 Not described. Unspecified. No blinding of participants because the control group received no placebo supplement. States that endoscopists were blinded to the study group but no further information provided. 8 patients were lost to follow up in intervention arm only as they could not be reached from the day after the initiation of the trial. No intention to treat analysis included. Author refers to it in the discussion and states that the results were insignificant. Apparently free of selective outcome reporting - all stated outcomes reported. calculations not provided.