PROSPERO

International prospective register of systematic reviews

Benefits and harms of treatment options for esophageal adenocarcinoma and

precancerous conditions: a protocol for an overview of systematic reviews
Candyce Hamel, Stéphane Groulx, Marion Doull, Andrew Beck, Adrienne Stevens, Becky Skidmore, Avijit
Chatterjee, Lorenzo Ferri, Donna Maziak, Scott Klarenbach, Harminder Singh, Brett Thombs, Brenda Wilson,
Nadera Ahmadzai, Brian Hutton, Beverley Shea, Paul James Belletrutti, Laura Targownik, Heather Limburg,
Rachel Rodin, Julian Little (senior author)., David Moher (senior author).

Citation
Candyce Hamel, Stéphane Groulx, Marion Doull, Andrew Beck, Adrienne Stevens, Becky
Skidmore, Avijit Chatterjee, Lorenzo Ferri, Donna Maziak, Scott Klarenbach, Harminder Singh,
Brett Thombs, Brenda Wilson, Nadera Ahmadzai, Brian Hutton, Beverley Shea, Paul James
Belletrutti, Laura Targownik, Heather Limburg, Rachel Rodin, Julian Little (senior author)., David
Moher (senior author).. Benefits and harms of treatment options for esophageal adenocarcinoma
and precancerous conditions: a protocol for an overview of systematic reviews. PROSPERO 2018
CRD42018084825 Available from:
http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018084825

Review question
What is the effectiveness of treatment for stage 1 esophageal adenocarcinoma (EAC) and precancerous
conditions (Barrett's Esophagus, low- and high-grade dysplasia) in adults?

Searches
Development of the search strategy was tested through an iterative process by an experienced medical
information specialist in consultation with the review team. Using the OVID platform, we will search Ovid
MEDLINE®, Ovid MEDLINE® Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Embase
Classic + Embase.

Another expert librarian will peer review the strategy using the PRESS 2015 guideline. Relevant grey
literature will be searched, using the CADTH Grey Matters checklist. Totality of grey literature searches will
be limited to 40 hours of work by one team member.
Searches for primary studies published since the date of last search of the systematic reviews included in the
overview will not be undertaken.

Types of study to be included

Systematic reviews of randomized controlled trials (RCTs). Systematic reviews that include observational
studies may be included if results from RCTs are provided separately from observational studies.

Condition or domain being studied

Stage 1 esophageal adenocarcinoma and precancerous condition of BE, low- and high-grade dysplasia.

Participants/population
Adults aged 18 years and older

Intervention(s), exposure(s)
Management and treatment strategies for stage 1 EAC or precancerous conditions (BE, low- or high- grade
dysplasia), including:
1) Pharmacological therapies, such as proton pump inhibitors and H2 receptor antagonists;
2) Surveillance methods (primarily diagnostic procedures to enhance early detection);
3) Endoscopic or endoscopic assisted therapies, such as ablative techniques (eliminate all dysplastic

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mucosa) and mechanical methods (remove targeted superficial tissue of the GI tract); and
4) Surgery, including laparoscopic anti-reflux surgery (i.e., fundoplication) and esophagectomy.
Additional relevant treatment approaches not listed will be considered for inclusion.

Comparator(s)/control
Comparators could include the following:
- No management/treatment
- Any other management/treatment strategies
- A combination of management/treatment strategies

Primary outcome(s)
1. Mortality - all-cause and EAC-related (1, 5 and 10 year, or as available)*
2. Survival (1, 5 and 10 year, or as available)*
3. Progression from non-dysplastic BE to BE with dysplasia, progression from low-grade to high-grade
dysplasia, progression to EAC
4. Life threatening, severe, or medically significant consequences (such as requiring hospitalization or
prolongation of hospitalization; disabling (limiting self-care or activities of daily living)
5. Quality of life (validated scales only; e.g. SF-36, WHOQUAL)
6. Major or minor medical procedures
7. Psychological effects (e.g., anxiety, stress)
8. Overtreatment
*from the time of allocation to screening or control arm

Timing and effect measures

Secondary outcome(s)
Not applicable.

Timing and effect measures

Data extraction (selection and coding)

One reviewer will extract data by using a data extraction form developed a priori. Data will be verified by a
second reviewer and discrepancies will be resolved through discussion if needed, with a third reviewer. If
unclear whether a review meets the eligibility, the review will be excluded. We will extract data on the
characteristics of the SR (PICO), the included studies with specifics related to the study design, population
(e.g., sex, age), outcomes (including definitions and timing of assessment), quality/risk of bias (by
domain/construct if available), the methods of analysis, results including subgroup analysis and GRADE or
other quality assessments if performed across studies, and any limitations noted by the systematic review
authors or by the overview research team. We will extract data at face value for how it was synthesized
and/or reported in the included reviews. No additional information from primary studies will be extracted or
assessed, such as outcome data or performing risk of bias assessments, nor will we conduct any quality
control to verify the accuracy of the reviews’ data extractions or risk of bias assessments for their included
studies. If the review information does not allow for clean data extraction we will extract the relevant items
and provide a commentary of the review.

Risk of bias (quality) assessment

The methodological quality of included reviews will be assessed by one reviewer using the AMSTAR tool. A
second reviewer will perform verification on all studies and any discrepancies will be resolved through
discussion or if needed, with a third reviewer.

Strategy for data synthesis

GRADE methodology will be done according to intervention/comparisons of each review and will not be done
across reviews. Which may mean that if one review assesses a broader grouping of an intervention, it would
overlap with a GRADE table from another review that addresses a subset. These results will not be

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integrated but will be commented on in the text. If available, we will report results for GRADE using the
summary of findings tables provided in the review and reasons for downgrading for each outcome. If GRADE
methodology was not used, we will attempt to conduct GRADE assessments using the available information
in the reviews. We will provide our best interpretation based on the available information and note limitations
or concerns. If it is not possible to perform GRADE, we will report this. If GRADE is not provided in an
included review, primary studies will not be sought to extract and evaluate information to develop GRADE
tables. We will not conduct any quality control checks to verify the accuracy of the selected reviews’ quality
of evidence assessments.
Presentation of results will be organized according to the scope of disease being treated and by intervention.
A narrative summary of each included review will be provided including: Characteristics of the included
reviews; AMSTAR quality assessments; Summary of the quality of evidence within each review and by
outcome using GRADE, if available; Review findings, summarized in narrative and/or tabular form.
Characteristics of each review will be examined (e.g., participants, interventions) in order to group similar
reviews for comparison and summary of results; such comparisons would assess only the extent of
concordance or discordance of the reviews’ results and not combine reviews together per se. Where
discordance occurs, we will explore reasons for discordance using the Jadad (1997) framework as a guide,
in addition to any other considerations that may be apparent. Synthesis of the evidence will be presented in
such a way to avoid inappropriate indirect comparisons of the evidence, which can only be done properly
with network meta-analyses, and in light of content overlap (where applicable), limitations, and other
considerations (e.g., reporting issues) of the included reviews.

Analysis of subgroups or subsets

None planned.

Contact details for further information

Candyce Hamel
cahamel@ohri.ca

Organisational affiliation of the review

Ottawa Hospital Research Institute
http://www.ohri.ca/

Review team members and their organisational affiliations

Ms Candyce Hamel. Knowledge Synthesis Group, Ottawa Hospital Research Institute, The Ottawa Hospital,
Ottawa, Ontario, Canada
Dr Stéphane Groulx. Department of Community Health Sciences, University of Sherbrooke, Sherbrooke,
Quebec, Canada
Dr Marion Doull. Global Health and Guidelines Division, Public Health Agency of Canada, Ottawa, Ontario,
Canada
Mr Andrew Beck. Knowledge Synthesis Group, Ottawa Hospital Research Institute, The Ottawa Hospital,
Ottawa, Ontario, Canada
Ms Adrienne Stevens. Knowledge Synthesis Group, Ottawa Hospital Research Institute, The Ottawa
Hospital, Ottawa, Ontario, Canada
Ms Becky Skidmore. Knowledge Synthesis Group, Ottawa Hospital Research Institute, The Ottawa Hospital,
Ottawa, Ontario, Canada
Dr Avijit Chatterjee. Division of Gastroenterology, The Ottawa Hospital, Ottawa, Ontario, Canada
Dr Lorenzo Ferri. Division of Thoracic and Upper Gastrointestinal Surgery, McGill University Health Centre,
Montreal, Quebec, Canada
Dr Donna Maziak. Division of Thoracic Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada
Dr Scott Klarenbach. Department of Medicine, University of Alberta, Calgary, Alberta, Canada
Dr Harminder Singh. Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
Dr Brett Thombs. Faculty of Medicine, McGill University; Lady Davis Institute for Medical Research, Jewish
General Hospital, Montreal, Quebec, Canada
Dr Brenda Wilson. Department of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario,

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International prospective register of systematic reviews

Canada
Ms Nadera Ahmadzai. Knowledge Synthesis Group, Ottawa Hospital Research Institute, The Ottawa
Hospital, Ottawa, Ontario, Canada
Dr Brian Hutton. Knowledge Synthesis Group, Ottawa Hospital Research Institute, The Ottawa Hospital;
Department of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario,
Canada
Dr Beverley Shea. Ottawa Methods Centre, Ottawa Hospital Research Institute, The Ottawa Hospital;
Department of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario,
Canada
Dr Paul James Belletrutti. Division of Gastroenterology and Hepatology, University of Calgary, Calgary,
Alberta, Canada
Dr Laura Targownik. Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
Ms Heather Limburg. Global Health and Guidelines Division, Public Health Agency of Canada, Ottawa,
Ontario, Canada
Dr Rachel Rodin. Global Health and Guidelines Division, Public Health Agency of Canada, Ottawa, Ontario,
Canada
Dr Julian Little (senior author).. Department of Epidemiology and Public Health, Faculty of Medicine,
University of Ottawa; Clinical Epidemiology Program, Ottawa Hospital Research Institute, The Ottawa
Hospital, Ottawa, Ontario, Canada
Dr David Moher (senior author).. Knowledge Synthesis Group, Ottawa Hospital Research Institute, The
Ottawa Hospital; Department of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa,
Ottawa, Ontario, Canada

Collaborators
Mr Raymond Daniel. Knowledge Synthesis Group, Ottawa Hospital Research Institute, The Ottawa Hospital,
Ottawa, Ontario, Canada

Anticipated or actual start date

15 January 2018

Anticipated completion date

31 August 2018

Funding sources/sponsors
Public Health Agency of Canada with funds distributed by the Nova Scotia Health Research Foundation

Conflicts of interest
Language
English

Country
Canada

Stage of review
Review_Ongoing

Subject index terms status

Subject indexing assigned by CRD

Subject index terms

Adenocarcinoma; Adenocarcinoma Of Esophagus; Esophageal Neoplasms; Humans; Precancerous
Conditions

Date of registration in PROSPERO

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International prospective register of systematic reviews

16 February 2018

Date of publication of this version

16 February 2018

Details of any existing review of the same topic by the same authors
Stage of review at time of this submission

Stage Started Completed

Preliminary searches Yes Yes
Piloting of the study selection process Yes Yes

Formal screening of search results against eligibility criteria Yes No

Data extraction No No
Risk of bias (quality) assessment No No

Data analysis No No

Versions
16 February 2018

PROSPERO
This information has been provided by the named contact for this review. CRD has accepted this information in good
faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration
record, any associated files or external websites.

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