example from medical to surgery) Patient outcomes Impact of treatment on symptoms Activity of disease Development of complications Crohn’s disease progression Treatment morbidity Quality of life Patients with suspected or established fistulising perianal Crohn’s disease Clinical examination involving patient history, assessment of symptoms, blood tests. MRI pelvis Endoanal ultrasound Surgical examination CT = computer tomography, MRI = magnetic resonance imaging, SBFT = small bowel follow through, TP = true positives, FP = false positives. Review of literature Literature sources and search strategies The medical literature was searched to identify relevant studies and reviews for the period up to November 2013. Searches were conducted via MEDLINE, The Cochrane Library (including Cochrane Reviews, NHS-EED, DARE and HTA), clinical registers and HTA sites (Table 6). Reference lists of the selected studies were manually searched. Table 6: Electronic databases searched Database Period covered MEDLINE via OVID MEDLINE Up to 11 November 2013 The Cochrane Library NHS-EED Cochrane Reviews DARE HTA Up to 15 November 2013 Clinical Registers Current Controlled Trials ControlledTrials.gov Australian New Zealand Clinical Trials Registry WHO International Clinical Trials Registry Platform HTA websites International Network of Agencies for Health Technology Assessment (INAHTA) NHS Centre for Reviews and Dissemination databases The search terms used included ‘Crohn’ ‘Crohn’s’ ‘enteritis’‘enterocolitis’ ‘small bowel’ ‘pelvic sepsis’ ‘fistula’‘magnetic resonance’ ‘MRI’ ‘MRE’ ‘fistulising’ and ‘perianal’. Search terms were confined to the title, abstract or keywords fields. Full details of the search strategies are provided in Appendix B. Title and abstracts were screened by two evaluators for potential relevance and omitted where appropriate. Of those remaining, full text articles were retrieved and examined in more depth. Table 7 provides full details of the a priori inclusion and exclusion criteria used for the studies included for this assessment.
Appendix D Studies included in the review Study profiles of included systematic reviews Author/Year Objective of report Number and publication dates Population considered in included studies, Test comparison Conclusions/recommendation Quality assessment Wu et al (2013) To evaluate the overall diagnostic accuracy of MRI is assessing the activity of CD in the small bowel. 17 studies (n=725 patients) Search methods: Publications from Jan 2001 to Sept 2011 were selected from MEDLINE, EMBASE and other electronic databases. Studies were included if MRI was used to assess active CD in the small bowel, 9/14 QUADAS criteria were fulfilled for methodological quality, sufficient raw data were reported, studies applied histopathologic and ileocolonoscopy assessment as referent standard, >10 patients. Mean age 8 to 77 years Patients in MR can be used to evaluate active CD. Test: MR Comparator: None Referent: Ileocolonoscopy and histopathologic assessment. MRI has high sensitivity and specificity for diagnosis of active CD in the small bowel and is a suitable modality for imaging and surveillance of active CD. HIGH QUALITY Was the research question specified? Yes Was the search strategy explicit and comprehensive? Yes Were the eligibility criteria explicit and appropriate? Yes Was a quality assessment of included studies undertaken? Yes Were the methods of the appraisal reproducible? Yes Were sources of heterogeneity explored? Yes Was a summary of the main results clear and appropriate? Yes Meta-analysis pooled results: Sensitivity 0.87 (95%CI: 0.77, 0.93) I2 = 0.98 (strong evidence of significant heterogeneity) Specificity 0.91 (95%CI: 0.81, 0.96) Overall AUC(ROC) 0.95 (95%CI: 0.93, 0.97) Authors conclusions: Results showed MRI had good diagnostic accuracy and good clinical utility Using meta-regression analyses, magnet strength and experience of the radiologist were the most important variables influencing sensitivity. Common weaknesses in the included studies were whether interpretation of pathology was blinded from MRI. Funnel plot asymmetry tests showed no major publication bias.
Cheriyan et al (2012) Ireland, single centre N=57 Objective: To determine whether MR enterography influenced the medical an surgical management of patients with small bowel CD design: Retrospective, consecutive Timing: 01/2007-12/2010 Index test: MR enterography Comparator test: n/a Timing interval: n/a Reference test: n/a Test interpretation: MR enterography evaluated by one radiologist with expertise in gastrointestinal imaging. Inclusion/exclusion criteria Inclusion: histologically confirmed CD, underwent MR enterography for symptom and disease assessment Exclusion: Management options not clearly stated after MR enterography, or occurred after 1 month of MR enterography Patient characteristics: Age/Gender: 47% male, median age 36 years (range 16-68), prior surgery 39 (68%) Length of time with disease: 9.5 years (range 1 – 35) Prior tests: Not stated Clinical characteristics: Symptoms not stated 68% had previous surgery Change in management 7 patients had normal MR enterography 50 patients had abnormal MR enterography (5 stricturing, 17 active, 14 both active and structuring) 6/7 patients with normal MR enterography had no change in management 42 patients had a change in management, 22 (53%) had medical intervention and 20 (47%) underwent surgery. Conclusion: High clinical impact on patient management. Patients with abnormal imaging had significantly more changes in management both surgical and medical. level of evidence: IV Quality: Q3 POOR Comparison: C1: other comparison (no comparison) Applicability: P2 limited (unclear) QUADAS Prospective: no Consecutive: unclear/yes Explicit selection criteria: yes Reference standard: n/a Test interval in days/weeks: n/a and ref std well described/reproducible: yes Tests assessed and independent of ref std: n/a Ref std assessed and blinded to other tests: n/a Routine clinical data available: yes Uninterpretable/intermed results reported: no withdrawals explained: n/a Sufficient data for 2x2 table: n/a Relevant population: yes Applicable comparator: n/a Applicable intervention: yes
Sanka et al (2012) England, single centre N=34 Objective: To report on the outcomes of performing magnetic resonance enteroclysis in the diagnosis and management of children with inflammatory bowel disease. Study design: Retrospective Timing: 09/2008-11/2010 Index test: MR enteroclysis. Previous afternoon upper endoscopy to place naso-jejunal tube. Comparator test: n/a Timing interval: n/a Reference test: n/a Test interpretation: MR enteroclysis evaluated by one radiologist with expertise in gastrointestinal imaging. Inclusion/exclusion criteria Inclusion: confirmed or suspected CD or ulcerative colitis Exclusion: not stated Patient characteristics: Age/Gender: 45% male, mean age 15.3 years, CD confirmed in 19 patients Length of time with disease: not stated Prior tests: Not stated Clinical characteristics: Symptoms not stated Confirming a diagnosis 8 normal MRE – patients discharged 1 normal MRE – no changes Changes in management 2 patients commenced azathioprine 7 patients commenced infliximab, 4 had ileo-caecal resection, adalimumab in 3 patients, 1 patient referred to psychological support, 6 patients for complx, 5 normal and continued current management, 1 significant complx, Other – one underwent surgery, one patient commenced methotrexate Limitations in use of MR enterocylsis 2 patients did not complete MR enterogclysis (1 extreme discomfort from stricture, 1 claustrophobia) NHMRC level of evidence: IV Quality: Q3 POOR Comparison: C1: other comparison (no comparison) Applicability: P2 limited (unclear) QUADAS Prospective: no Consecutive: unclear/yes Explicit selection criteria: yes Reference standard: n/a Test interval in days/weeks: n/a Tests and ref std well described/reproducible: yes Tests assessed and independent of ref std: n/a Ref std assessed and blinded to other tests: n/a Routine clinical data available: yes Uninterpretable/intermed results reported: no withdrawals explained: yes Sufficient data for 2x2 table: n/a Relevant population: yes Applicable comparator: n/a Applicable intervention: yes
Schmidt et al (2010) Switzerland, single centre N=57 Objective: To assess the agreement between MR enterography and CT enterography in assessing extent of small bowel CD in patients design: Prospective Timing: Not stated Index test: MR enterography Comparator test: CT enterography Timing interval: < 24 hours Reference test: Composite of surgery, endoscopy and follow-up Test interpretation: 3 radiologists, independent and blind assessments Inclusion/exclusion criteria Inclusion: histologically proven CD, emergency presentation for acute exacerbation Exclusion: contraindications for MRI acute or chronic renal failure, lack of proof of CD Patient characteristics: Age/Gender: 69% male, CD confirmed, mean age 33.5 range (17-69 years) Length of time with disease: Median 10 years tests: Not stated. Clinical characteristics: Not stated Test Accuracy Bowel wall thickening MR enterography Sensitivity: 84% Specificity: 91% CT enterography Sensitivity: 93% Specificity: 67% Fistula MR enterography Sensitivity: 86% Specificity: 93% CT enterography Sensitivity: 89% Specificity: 98% Abscess MR enterography Sensitivity: 79% Specificity: 99% CT enterography Sensitivity: 83% Specificity: 97% NHMRC level of evidence: IV Quality: Q2 MEDIUM Comparison: CX: comparison Applicability: P1 applicable QUADAS Prospective: yes Consecutive: yes Explicit selection criteria: yes Reference standard: composite Valid: yes Applied to all patients: yes Test interval in days/weeks: Comparator: same day Ref std: not stated Tests and ref std well described/reproducible: yes Tests assessed and independent of ref std: no Ref std assessed and blinded to other tests: no Routine clinical data available: yes Uninterpretable/intermed results reported: no Study withdrawals explained: none Sufficient data for 2x2 yes Relevant population: yes Applicable comparator: yes Applicable intervention: yes