An Expert Consensus to Standardise Definitions, Diagnosis and Treatment Targets for Anti–fibrotic Stricture Therapies in Crohn's Disease

F. Rieder; D. Bettenworth; C. Ma; C. E. Parker; L. A. Williamson; S. A. Nelson; G. van Assche; A. Di Sabatino; Y. Bouhnik; R. W. Stidham; A. Dignass; G. Rogler; S. A. Taylor; J. Stoker; J. Rimola; M. E. Baker; J. G. Fletcher; J. Panes; W. J. Sandborn; B. G. Feagan; V. Jairath

Disclosures

Aliment Pharmacol Ther. 2018;48(3):347-357. 

In This Article

Materials and Methods

Systematic Review of Literature

The systematic review and consensus process focused solely on small bowel strictures, since these are most common.[7] Furthermore, colonic strictures harbour the risk for malignancy[15] and accordingly, may not be a primary initial target for anti–fibrotic therapies. PubMed, EMBASE and the Cochrane Library (CENTRAL) were searched from inception to July 31, 2017 to identify definitions, instruments and trial design features used for assessment of CD–associated strictures. Keywords included ('Crohn's disease' OR 'small bowel') AND ('stricture' OR 'fibrosis' OR 'stenosis' OR 'dilation'). A recursive search of bibliographies of relevant articles was also performed. Eligible studies enrolled adult patients (>18 years) and provided information on how stricture was defined, the modality of diagnosis and treatment target(s). Controlled trials, cohort studies, case–control studies and cross–sectional studies were included. Non–English language publications, case series and case reports were excluded.

Four reviewers (FR, DB, CM and CP) independently screened citations and abstracts. The full–text publications of potentially eligible studies were reviewed in duplicate by 2 pairs of researchers (FR and DB, CM and CP). Variables pertaining to clinical, endoscopic and radiologic definitions of strictures, diagnostic modality and clinical trial design were extracted independently and in duplicate by the same 2 pairs. Disagreements regarding inclusion or extraction were resolved through discussion, or arbitration was performed by VJ.

Expert Consensus Process

Recruitment of experts. Ten experienced gastroenterologists and 5 experienced radiologists from the United States, Canada, the Netherlands, Belgium, Spain, Italy, France, Switzerland, UK and Germany were chosen to participate. Panelists were selected based on publication record, international reputation in stricturing CD, and experience in trial design, drug development and clinical epidemiology; these criteria took precedence over global representation. After reviewing a list of experts in the above areas, the final selection of participants was performed by FR, BF and VJ. Given that this project had the purpose of providing a framework for the development of medical therapy for CD–associated strictures, surgeons and pathologists were not included.

Modified RAND/UCLA appropriateness methodology was used to assess the face validity (the extent to which an item appears to address the concept it purports to measure) and feasibility of items identified in the systematic review. Additional items were included based upon the opinion of the panelists after distribution of the initial item list. RAND/UCLA appropriateness methodology employs a modified Delphi panel approach to combine the best available evidence with the clinical experience of relevant experts.[16] This process is widely accepted, iterative and evidence–based.

First panel meeting and initial survey. Items identified by systematic review and an introductory panel meeting were circulated via an online survey. Panelists anonymously rated the appropriateness of each item on a scale from 1 to 9 (1 = inappropriate, 9 = highly appropriate).

Second and third panel meeting and final survey. Results of the initial survey were distributed to panelists and discussed in a moderated teleconference. Areas of disagreement regarding item appropriateness were identified and panelists were asked to explain the rationale behind their responses. In accordance with RAND/UCLA appropriateness methodology, no attempt was made to force the panel to consensus. The survey was revised based on the second panel meeting to improve clarity and a second survey was circulated. One key item (#30) was chosen by the panel for re–discussion based on an unexpected disagreement in survey round two. The item was discussed via e–mail, and a third survey consisting only of this item was circulated.

Analysis of Panel Results

Each survey item was classified as inappropriate, uncertain or appropriate based on the median panel rating and degree of panel disagreement (median 1–3 without disagreement = inappropriate; median 4–6 or any median with disagreement = uncertain; median 7–9 without disagreement = appropriate).[14] Disagreement was considered present when 2 or more panelists rated appropriateness in each extreme 3–point region (1–3 and 7–9).

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