Step

(1)

Appendices

Appendix A. Search strategy

PubMed (Date Run: 17/03/18)

Step Search strategy Found Time

#1 Search ("adenoma"[MeSH Terms] OR "adenoma"[All Fields])

AND English[lang] Filters: English Language 88873 13:18:35

#2

Search ("random allocation"[MeSH Terms] OR ("random"[All Fields] AND "allocation"[All Fields]) OR "random allocation"[All

Fields] OR "randomized"[All Fields]) AND English[lang] Filters:

English Language

745200 13:18:42

#3 Search (miss rate[All Fields] OR miss rates[All Fields]) AND English[lang] Filters: English Language

397 13:18:50

#4 #1 AND #2 AND #3 66 13:18:58

Cochrane Central Register of Clinical Trials database search strategy (Date Run: 17/03/18)

ID Search strategy Found

#1 MeSH descriptor: [Adenoma] explode all trees 1102

#2 Miss rate (Word variations have been searched) 626

#3 #1 and #2 and #3 35

32 Trials and 3 Reviews

(2)

Appendix B. PRISMA 2009 Checklist

Section/topic # Checklist item Reported

on page # TITLE

Title 1 Identify the report as a systematic review, meta-analysis, or both. 1

ABSTRACT

Structured summary 2 Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and

implications of key findings; systematic review registration number.

2

INTRODUCTION

Rationale 3 Describe the rationale for the review in the context of what is already known. 4

Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons,

outcomes, and study design (PICOS). 4

METHODS

Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide

registration information including registration number. 5

Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered,

language, publication status) used as criteria for eligibility, giving rationale. 5

Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify

additional studies) in the search and date last searched. 5

Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be

repeated. 5,6

Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable,

included in the meta-analysis). 6

Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes

for obtaining and confirming data from investigators. 6

Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and

simplifications made. 7

Risk of bias in individual

studies 12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was

done at the study or outcome level), and how this information is to be used in any data synthesis. 7

Summary measures 13 State the principal summary measures (e.g., risk ratio, difference in means). 7,8

Synthesis of results 14 Describe the methods of handling data and combining results of studies, if done, including measures of consistency

(e.g., I²⁾for each meta-analysis. 8

(3)

Risk of bias across studies 15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective

reporting within studies). 8

Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating

which were pre-specified. 8

RESULTS

Study selection 17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at

each stage, ideally with a flow diagram. 10

Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and

provide the citations. 10

Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12). 12

Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each

intervention group (b) effect estimates and confidence intervals, ideally with a forest plot. 12-16

Synthesis of results 21 Present results of each meta-analysis done, including confidence intervals and measures of consistency. 12-16

Risk of bias across studies 22 Present results of any assessment of risk of bias across studies (see Item 15). 12-16

Additional analysis 23 Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]). 12-16 DISCUSSION

Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to

key groups (e.g., healthcare providers, users, and policy makers). 17-21

Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of

identified research, reporting bias). 17-21

Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research. 17-21 FUNDING

Funding 27 Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the

systematic review. NA

(4)

Appendix C – Risk of bias assessment per included study – Authors’ judgement per domain – Support for judgement Hewett et al. 2010

Bias Authors'

judgement Support for judgement

Random sequence generation (selection bias) Low risk

“Patients were randomly assigned by a research assistant, by using a computer- generated randomization sequence (blinded block sizes of 10), to undergo either initial CFC or regular colonoscopy.”

Allocation concealment (selection bias) Low risk

“Randomization used concealed allocation with a sealed, opaque envelope with content that designated CFC or regular colonoscopy.”

Blinding of participants and personnel

(performance bias) High risk

Unable to blind personnel and participants due to different technologies used.

Outcome is likely to be influenced by lack of personnel blinding.

Blinding of outcome assessment (detection

bias) High risk

Due to trial design, Endoscopist performing the second procedure was aware of the results of index procedure. Outcome assessment is likely to be influenced by lack of blinding.

Incomplete outcome data (attrition bias) Low risk

No missing outcome data.

Selective reporting (reporting bias) Low risk

The study protocol is available and all of the study’s pre-specified outcomes that are of interest in the review have been reported in the pre-specified way

(5)

Appendix C – Risk of bias assessment per included study – Authors’ judgement per domain – Support for judgement Hewett et al. 2010

“Patients were randomly assigned by a research assistant, by using a computer- generated randomization sequence (blinded block sizes of 10), to undergo either initial CFC or regular colonoscopy.”

“Randomization used concealed allocation with a sealed, opaque envelope with content that designated CFC or regular colonoscopy.”

bias) High risk

No missing outcome data.

(6)

Leufkens et al. 2011

“Subjects were randomized by using a Web-based randomization module stratified by center and individual endoscopist”

Allocation concealment (selection bias) Unclear risk

Authors do not report the exact method of allocation concealment Blinding of participants and personnel

bias) High risk

Per protocol analysis performed after exclusion of balanced proportion of patients with similar reasons between the two allocation groups.

The study protocol is available and all of the study’s pre-specified outcomes that are of interest in the review have been reported in the pre-specified way.

(7)

Halpern et al. 2014

“Patients were randomized to “Group A” or “Group B,” with 1:1 allocation and stratified by center (with a block size of 6), via a computer-generated randomization scheme created by SAS version 9.3 statistical software (SAS Institute, Cary, North Carolina, USA)”

“Patients were enrolled by the study investigators and allocated to one of the study groups by opening one of the sequentially numbered, sealed envelopes. The colonoscopist was blinded to the allocation group until the patient entered the procedure room.”

bias) High risk

The study protocol is available and the main of the study’s pre-specified outcomes that are of interest in the review have been reported in the pre-specified way.

(8)

Granlek et al. 2014

Random sequence generation (selection bias) Low risk “Patients were randomly assigned (1:1), by computer-generated randomisation with block design (20 patients per block), to receive same-day, back-to-back tandem colonoscopy with either full-spectrum colonoscopy or standard forward- viewing colonoscopy, followed immediately by the other procedure”

“Immediately before start of the colonoscopy examinations, the site study coordinator opened the concealed allocation card to reveal group allocation. Until that moment, the endoscopist was masked to group assignment; patients were not masked.”

bias) High risk

(9)

Dik et al. 2015

“Randomization was performed using computer-generated randomization blocks (1 : 1) with eight patients per block.”

“The study site coordinator did not reveal the randomly assigned allocation until the start of the colonoscopy. Until that moment, patients and endoscopists were blinded to the allocation.”

bias) High risk

(10)

Papanikolaou et al. 2017

“Randomization was performed by one of the coordinators who did not actively participate in endoscopies. Patients were randomly assigned (1:1), by computer- generated randomization with block design (10 patients per block) to undergo sameday, back-to-back tandem colonoscopy with either FSC or CC/ R first, followed immediately by the other procedure, by the same endoscopist.”

“The endoscopist was unaware of group allocation until the site study coordinator opened the concealed allocation card to reveal group allocation immediately before starting the colonoscopy.”

bias) High risk

Authors reported a protocol violation issue since 26 patients did not undergo right-colon examination with conventional scope retroflexion without proper explanation; these patients were excluded from analysis and they were substituted by 26 new patients, using the same randomization allocation.

Therefore, per protocol analysis was performed after exclusion of balanced proportion of patients with similar reasons between the two allocation groups.

(11)

De Palma et al. 2017

“A computer-generated sequence randomly allocated blocks of eight patients to receive, with a 1:1 ratio, either standard colonoscopy (SC) or EndoCuff assisted colonoscopy (EAC), immediately followed by the other procedure.”

“Doctors screening and informing patients for trial participation were blinded to the block size. After receiving appropriate consent from the patient, a trained doctor opened the envelope containing the allocation card.”

Neither participants nor personnel were blinded to allocation group. Outcome is likely to be influenced by lack of blinding.

bias) High risk

Endoscopist performing the second procedure was aware of the results of index procedure. Outcome assessment is likely to be influenced by lack of blinding..

(12)

Triantafyllou et al. 2017

“We randomly assigned participants (1 : 1), by computer-generated randomization with a block design (10 patients per block), to undergo same-day back-to-back tandem colonoscopy with either Endocuff-assisted colonoscopy or conventional colonoscopy being performed first, followed immediately by the other procedure, performed by the same endoscopist.”

“Just before starting the examinations, the site study coordinator opened the concealed envelope to reveal group allocation to the endoscopist.”

bias) High risk

No incomplete outcome data.

(13)

Rey et al. 2017

Random sequence generation (selection bias) High risk

"Authors enrolled patients on a 1:1 basis into 1 of the 2 study arms (initial withdrawal of the G-EYE-assisted HD+ endoscope or initial withdrawal of the HD+

standard colonoscope) on the day of the investigation”. No exact method of random sequence generation is provided.

Allocation concealment (selection bias) Unclear risk

Authors do not report the exact method of allocation concealment.

bias) Unclear risk

No incomplete outcome data.

Selective reporting (reporting bias) Unclear risk

Protocol available but the published paper does not report on serrated lesions detection rate that consisted one of the predetermined primary outcome (serrated lesions detection rate)