Table 2 Population, interventions, comparisons, outcomes, timeframe, study design (PICOTS)

Population

Inclusion

Adults (≥ 18 years old)^a with chronic gastroesophageal reflux disease (GERD)^b with or without other risk factors^c for esophageal adenocarcinoma (EAC).

Adults (≥ 18 years old)^a with chronic GERD with or without other risk factors^c for EAC who have been offered, received, or allocated to receive screening, depending on the design of the study.

Adults (≥ 18 years old)^a with stage 1 EAC, Barrett’s Esophagus (BE) or low- or high-grade dysplasia, with or without chronic GERD as defined in the systematic reviews (SRs)^d

Exclusion

Those diagnosed with other gastro-esophageal conditions (e.g. gastric cancer, esophageal atresia, and other life-threatening esophageal conditions).

Intervention /comparator

Inclusion

KQ1a:

- Screening versus no screening

- One screening modality versus another screening modality

All screening modalities for BE, dysplasia or EAC will be included, such as esophagogastroduodenoscopy (EGD)^e,f EGD^f plus adjunct techniques^g, transnasal endoscopy, cytologic examination

KQ1b:

- One screening modality vs. another screening modality

- One interval of screening vs. another interval of screening

- Timepoint at which to initiate screening vs. another timepoint

- Timepoint at which to cease screening versus. another timepoint

Screening for EAC and other precancerous lesions with any screening modality

Depending on study design, comparators may be:

- No screening^h

- Different screening modality

- Different screening intervals

- Different lengths/duration of screening

- Offered screening but did not receive screening

- No comparison

Management/ treatment for stage 1 EAC, low- or high-grade dysplasia or BE including:

- Pharmacological therapiesⁱ

- Surveillance methods such as: EGD^e,f plus biopsy, EGD^f plus biopsy plus adjunct techniquesj

- Endoscopic or Endoscopic Assisted therapies^k

- Surgery, including fundoplication and esophagectomy

Comparator: No management/treatment compared to another management/treatment regimen, or a combination of management/ treatment strategies.

Exclusion

Outcomes

Inclusion

Critical for decision-making

1. Mortality—all-cause and EAC-related (1, 5 and 10 year or as available)^l,m

2. Survival (1, 5 and 10 year or as available)^l

3. Life threatening, severe, or medically significant consequences (such as requiring hospitalization or prolongation of hospitalization; disabling (limiting self-care or activities of daily living)

Important for decision-making

4. Incidence of EAC (by stage), BE, low- and high-grade dysplasia^m

5. Quality of life (validated scales only; e.g. SF-36, WHOQUAL)

6. Psychological effects (e.g. anxiety and depression)

7. Major or minor medical procedures^m

8. Overdiagnosisⁿ

1. How patients weigh the benefits and harms of screening (e.g. ranking/rating of benefits and harms outcomes)

2. Willingness to be screened

3. Uptake of screening

4. Factors considered in decision to be screened: what components/outcomes of screening do patients place more value on when deciding whether to be screened or not (e.g. potential complications resulting from screening)

5. Intrusiveness of the screening modality

Critical for decision-making

1. Mortality—all-cause and EAC-related (1, 5 and 10 years, or as available)^l

2. Survival (1, 5 and 10 years, or as available)^l

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)

Important for decision-making

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

Post-hoc outcomes:

9. Complete eradication of: intestinal metaplasia/BE, dysplasia, high-grade dysplasia, neoplasia

10. Reduction/regression of BE: in length (cm), in area (%)

11. Treatment Failure (no ablation)

12. EAC recurrence

Timing

No limits

No limits

No limits

Setting

Settings were limited to primary care or settings in which a primary care physician could refer a patient for esophageal screening.

Primary care or other settings generalizable to primary care.

Any setting.

Study designs

Inclusion

Randomized controlled trials (RCTs), including cluster RCTs.

If no or few RCTs (i.e. < 5 trials) are available: Non-RCT, controlled before-after, interrupted times series, cohort studies, case-control studies, limiting to higher levels of evidence depending on the nature and volume of specific study designs.

If no or few RCTs are available for the overdiagnosis outcome, ecological and cohort studies will be considered for all outcomes used for the judgement of overdiagnosis.

Randomized controlled trials

If insufficient data exists:

Controlled clinical trials, controlled before-after, case-controls, cohort, interrupted time series (ITS), and cross-sectional (e.g. surveys)

If insufficient data exists for the above:

Qualitative studies and mixed-methods studies

Systematic reviews of RCTs^o

To be defined as a SR, a review must have met all four of the following criteria: (1) searched at least one database; (2) reported its selection criteria; (3) conducted quality or risk of bias assessment on included studies; and (4) provided a list and synthesis of included studies. SRs that identified observational studies were included if results from RCTs were provided separately.

Exclusion

Cross-sectional studies, case series, case reports, and other publication types (editorials, commentaries, notes, letter, opinions).

Commentaries, opinion, editorials and reviews

SRs that combine results from RCTs with non-RCTs, controlled before-after, interrupted times series, cohort studies, case-control studies, cross-sectional studies, case series, case reports and other publication types (editorials, commentaries, notes, letter, opinions) or SRs that only include non-RCT and observational studies.

Language

Databases

MEDLINE, Embase, Cochrane Library

MEDLINE, Embase, CINAHL, Cochrane Library

MEDLINE, Embase, Cochrane Library (CDSR, DARE, HTA)