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Taylor SA, Mallett S, Bhatnagar G, et al. Magnetic resonance enterography compared with ultrasonography in newly diagnosed and relapsing Crohn’s disease patients: the METRIC diagnostic accuracy study. Southampton (UK): NIHR Journals Library; 2019 Aug. (Health Technology Assessment, No. 23.42.)
This chapter contains material that is reproduced from Taylor et al.40 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/. The text below includes minor additions and formatting changes to the original text.
Recruitment began in December 2013 and was completed in September 2016. Overall, 518 participants were assessed for eligibility, of whom 183 were excluded, predominantly because they did not meet the inclusion criteria or declined participation (Table 2).
Reasons for exclusion of screened patients
Of the 335 participants who entered the trial, 51 were subsequently excluded (Table 3). The most frequent reason was an ultimate diagnosis other than CD (31 participants).
Reasons for participant withdrawal
The final cohort was 284 participants (133 and 151 in new diagnosis and suspected relapse cohorts, respectively) (Figure 2). Appendix 5, Table 44, shows the recruitment and withdrawal numbers for each of the eight recruitment sites. Figure 2 is the patient flow diagram.
The demographic data of the final study cohort are shown in Table 4. There were marginally more men in the new diagnosis cohort and more women in the suspected relapse cohort. Overall, 154 (54%) participants were female. In the suspected relapse cohort, 101 (67%) participants had had CD for ≥ 6 years and 53 (35%) and 14 (9%) had a stricturing or penetrating disease phenotype, respectively.
Demographics of final study cohort
Participants had a range of presenting symptoms, notably abdominal pain and diarrhoea (see Appendix 6, Table 45). In general, symptoms were similar between the two cohorts, although the proportion of participants reporting bloody diarrhoea was higher in those participants newly diagnosed, and a greater proportion of those participants with relapse reported obstructive symptoms. There were no reported major adverse events following MRE or US.
The available small bowel imaging tests (including third tests generated by a discrepancy for SBCD presence or location between MRE and US), CRP and FC levels, HBI and surgical resection specimens available to the consensus panels are shown in Table 5. A total of 10 (8%) new diagnosis participants did not undergo full colonoscopy despite this being planned at recruitment. Of these, five underwent flexible sigmoidoscopy instead, and the remaining either declined or had a change in their clinical investigational plan. Colonoscopy data were available for 66 (44%) of the suspected relapse cohort participants. There was a range of small bowel imaging tests available over and above MRE and US, including CapE, BaFT and CTE.
Range of investigations available to the consensus reference panel
Based on the consensus reference standard, 233 (82%) participants had SBCD (meeting the requirements of the sample size calculation), which was active in 209 (89%) (Table 6). A total of 129 (45%) participants had colonic CD, which was active in 126 (98%). Participants often fulfilled more than one criterion for active disease (raised CRP/FC levels, ulceration at endoscopy, histopathological evidence of inflammation) (see Table 6). The prevalence of SBCD was similar between the new diagnosis and suspected relapse cohorts, although colonic CD tended to be more prevalent in the former. The prevalence of activity was high when disease was present and was also similar between the two cohorts.
Per-participant disease presence and activity according to the consensus reference standard
The presence and activity of SBCD and colonic CD according to individual bowel segments is shown in Appendix 7, Table 46. The prevalence of individual small bowel segmental disease was similar between the new diagnosis and suspected relapse cohorts, although segmental colonic CD was more prevalent in the former.
A total of 21 participants had enteric fistulae and seven participants had an intra-abdominal abscess. Specifically, three (2%) and four (3%) participants had an abscess in the new diagnosis cohort and in the suspected relapse cohort, respectively. A total of 10 (8%) and 11 (7%) participants had a fistula in the new diagnosis cohort and in the suspected relapse cohort, respectively.
There were 61 bowel segments considered to have a stenosis causing obstruction: 18 in the new diagnosis cohort and 43 in the suspected relapse cohort.
The practitioners’ opinion on the quality of segmental visualisation for both MRE and US according to the participant cohort is shown in Appendix 8, Tables 47 and 48. In general, visualisation of ileal and terminal ileal segments was rated as at least moderate in > 90% of participants on both MRE and US, with no major difference between cohorts. Visualisation of the duodenum was rated as poor in 15 out of 133 (11%) new diagnosis participants and 18 out 151 (12%) suspected relapse participants on MRE, and in 23 out of 133 (17%) new diagnosis participants and 27 out of 151 (18%) suspected relapse participants for US. Jejunal visualisation tended to be better on US, for example rated as poor in 23 out of 151 (15%) suspected relapse participants on MRE compared with 8 out of 151 (5%) on US. Colonic visualisation was inferior to that of the small bowel on both MRE and US but better on US than MRE for five out of six segments. For example, visualisation of the descending colon was rated as good in 58 out of 133 (44%) new diagnosis participants using MRE compared with 92 out of 133 (69%) new diagnosis participants on US. The only exception was the rectum, where visualisation was rated as poor in 74 out of 133 (56%) new diagnosis participants on US compared with 40 out of 133 (30%) new diagnosis participants on MRE.
In total, 53 participants (24 new diagnosis and 29 suspected relapse participants) were discrepant for SBCD presence or location between MRE and US, of whom 48 had an additional small bowel imaging test available to the consensus panel. Of these, 17 (71%) new diagnosis participants and 17 (59%) suspected relapse participants were discrepant for the presence of terminal ileal disease. The full range of imaging and endoscopic data available to the consensus panels for these participants is shown in Appendix 9, Table 49.
Appendix 10, Table 50, provides the raw data for the primary outcome and main secondary outcome.
For SBCD extent, MRE sensitivity (i.e. presence and correct segmental location) was 80% (95% CI 72% to 86%), compared with 70% (95% CI 62% to 78%) for US, a difference of 10% (95% CI 1% to 18%), which was statistically significant (p = 0.027) (Table 7 and Figure 3).
Per-participant sensitivity and specificity for disease presence and extent against the consensus reference standard (both cohorts combined)
Magnetic resonance enterography specificity for SBCD extent was also significantly greater than that of US [95% (95% CI 85% to 98%) vs. 81% (95% CI 64% to 91%), respectively, a difference of 14% (95% CI 1% to 27%)].
The potential impact of staging SBCD extent with either MRE or US in a theoretical 1000-participant cohort is shown in Figure 4.
Regardless of location, sensitivity of MRE for SBCD presence was 97% (95% CI 91% to 99%), significantly greater than that of US [92% (95% CI 84% to 96%)] [a difference of 5% (95% CI 1% to 9%)]. MRE and US specificity for SBCD presence was 96% (95% CI 86% to 99%) and 84% (95% CI 65% to 94%), respectively: a difference of 12% (95% CI 0% to 25%). The potential impact of staging SBCD presence with either MRE or US in a theoretical 1000-participant cohort is shown in Appendix 11, Figure 11.
There were no significant differences in sensitivity or specificity between MRE and US for colonic CD extent or presence (see Table 7), although for both tests sensitivities were considerably less than for SBCD. MRE was 64% (95% CI 50% to 75%) sensitive for colonic CD presence but just 22% (14% to 32%) sensitive for extent (which required correct identification of involved colonic segments); the corresponding figures for US were 73% (59% to 83%) and 17% (10% to 27%).
The sensitivity and specificity for individual small bowel and colonic segments is given in Table 8. Although the study was not powered to detect differences on a segmental level, MRE was significantly more sensitive than US for ileal disease [84% (95% CI 67% to 93%) vs. 56% (95% CI 38 to 73), respectively]. Sensitivity for the eight diseased duodenal segments was low, at 25% (95% CI 7% to 59%), for both MRE and US. Sensitivity for jejunal disease was 71% (95% CI 38% to 91%) for MRE and 63% (95% CI 32% to 86%) for US. For five out of six colonic segments, sensitivity was ≈40–50% for both tests. However, sensitivity for rectal disease was significantly lower for US [22% (95% CI 13% to 35%)] than for MRE [44% (95% CI 32% to 58%)], with a difference of 22% (95% CI 9% to 35%).
Per-segment sensitivity and specificity for disease presence against the consensus reference standard (both cohorts combined)
The sensitivity and specificity of MRE and US for SBCD and colonic CD presence and extent according to the participant cohort is shown in Table 9. Sensitivities of both tests for SBCD presence and extent in the new diagnosis and suspected relapse participant cohorts were very similar to those sensitivities estimated across all participants (see Table 7), although differences were not statistically significant (the study was not powered to detect differences in the cohorts).
Sensitivity and specificity for disease presence and extent against the consensus reference standard according to participant cohort
However, US had significantly greater sensitivity for colonic CD presence than MRE in the new diagnosis cohort [67% (95% CI 49% to 81%) vs. 47% (95% CI 31% to 64%), respectively: a difference 20% (95% CI 1% to 39%)]. For both MRE and US, sensitivity for colonic CD presence was higher in the suspected relapse participant cohort, although the estimated sensitivity for colonic CD extent was poor for both: MRE had 17% (95% CI 9% to 30%) sensitivity for colonic CD extent in the new diagnosis cohort and 31% (95% CI 17% to 48%) sensitivity in the suspected relapse cohort. The corresponding figures for US were 9% (95% CI 4% to 19%) and 33% (95% CI 19% to 51%), respectively.
The sensitivity and specificity for individual small bowel and colonic segments according to participant cohort is given in Appendix 12, Table 51. In general, sensitivities of both tests for small bowel segmental disease presence in the new diagnosis and suspected relapse cohorts were very similar to those sensitivities estimated across all participants, although we note that the study was not powered to detect differences in the cohorts (see Table 8). MRE had 100% (95% CI 61% to 100%) sensitivity for jejunal disease in the suspected relapse cohort, compared with 43% (95% CI 16% to 75%) in the new diagnosis cohort, although there were only six and seven positive segments in each cohort, respectively. Sensitivity for colonic segmental disease was higher in the suspected relapse cohort than in the new diagnosis cohort for both MRE and US, consistent with the findings across all participants (see Tables 7 and 8).
Colonoscopy data were available for 186 participants (123 in the new diagnosis cohort and 63 in the suspected relapse cohort). The sensitivity and specificity of MRE and US for terminal ileal and colonic segmental disease against an ileocolonoscopic standard of reference is shown in Table 10.40 MRE had a sensitivity of 97% (95% CI 91% to 99%) for terminal ileal disease presence, compared with a sensitivity of 91% (95% CI 79% to 97%) for US: a difference of 6% (95% CI –1% to 12%), which is similar to the 5% sensitivity difference between the tests for the presence of SBCD against the consensus reference standard (see Table 7). However, specificity was low, at 41% (95% CI 21% to 64%) for MRE and 33% (95% CI 15% to 57%) for US. Sensitivity for colonic CD presence was modest for both MRE and US [41% (95% CI 26% to 58%) and 49% (95% CI 33% to 65%)] and somewhat lower than the consensus reference standard, which included the 98 participants without ileocolonoscopy. The differences between MRE and US were not statistically significant (the study was not powered to detect differences based on a colonoscopic standard of reference alone).
Sensitivity and specificity for terminal ileal and colonic CD presence against an ileocolonoscopic reference (both cohorts combined)
The sensitivity and specificity of MRE and US for terminal ileal and colonic segmental disease against an ileocolonoscopic standard of reference according to the participant cohort is show in Appendix 13, Table 52.
Magnetic resonance enterography detected five out of seven (71%) abscesses and 18 out of 21 (86%) participants with enteric fistulae, compared with three out of seven (43%) and 11 out of 21 (52%) for US, respectively. Of the 61 participants with a stenosis considered to be causing obstruction by the consensus reference standard, MRE detected 33 (54%) and US detected 20 (33%) of these. There were 52 false-positive segments for stenosis on MRE and 45 for US.
Magnetic resonance enterography per-participant sensitivity for active SBCD was 96% (95% CI 92% to 99%), compared with 90% (95% CI 82% to 95%) for US: a difference of 6% (95% CI 2% to 11%), which was statistically significant (Table 11). Specificity for active SBCD and accuracy for active colonic CD were not significantly different between the two tests (see Table 11).
Per-participant sensitivity and specificity for the presence of active disease against the consensus reference standard (both cohorts combined)
The sensitivity and specificity of MRE and US for detecting active SBCD and colonic CD according to the participant cohort is shown in Appendix 14, Table 53. Sensitivity and specificity for active SBCD according to the participant cohort were very similar to those estimated across all participants, although sensitivity for active colonic CD was generally higher in the suspected relapse cohort than in the new diagnosis cohort.
The sensitivity and specificity of MRE and US for active terminal ileal and colonic CD across all participants (n = 186) against an ileocolonoscopic standard of reference is show in Table 12 and, according to participant cohort, in Appendix 15, Table 54. Overall, MRE had significantly greater sensitivity for endoscopically diagnosed active terminal ileal disease than US [97% (95% CI 91% to 99%) vs. 86% (95% CI 70% to 95%), respectively]. There were no differences in sensitivity for active colonic CD. Sensitivity and specificity for active disease according to the participant cohort were very similar to those estimated across all participants.
Sensitivity and specificity for presence of active terminal ileal and colonic CD vs. ileocolonoscopy reference (both cohorts combined)
The numbers of MRE and US equivocal observations (i.e. marked with a confidence score of 3 or 4 by the practitioner) for disease presence are shown in Table 13. Overall, there were relatively few instances of equivocal scores for either SBCD presence [3% (9/284) for MRE; 6% (17/284) for US] or for colonic CD presence [4% (12/284) for MRE; 6% (18/284) for US]. Of the nine equivocal MRE scores for SBCD presence, eight were disease positive by the consensus reference standard and one was disease negative. Conversely, of the 12 equivocal MRE scores for colon disease presence, five were disease positive by the consensus reference standard and seven were disease negative.
Number of equivocal MRE and US findings for per-participant disease presence (both cohorts combined)
Of the 17 equivocal US scores for SBCD presence, 12 were disease positive by the consensus reference standard and five were disease negative. Of the 18 equivocal US scores for colon disease presence, 13 were disease positive by the consensus reference standard and five were disease negative.
Overall, of the 21 MRE scores for small bowel or colonic CD presence, 12 were in the new diagnosis cohort and nine were in the suspected relapse cohort. Of the 35 equivocal US scores, 20 were in the new diagnosis cohort and 15 were in the suspected relapse cohort.
The number of equivocal scores for disease activity (Table 14) was higher than for disease presence. Specifically, for small bowel activity, 7% (19/284) of scores were equivocal for MRE and 11% (31/284) of scores were equivocal for US; for colonic CD activity, 6% (17/284) of scores were equivocal for MRE and 7% (19/284) of scores were equivocal for US.
Number of equivocal MRE and US findings for per-participant disease activity (both cohorts combined)
When equivocal scores were treated as disease negative, MRE sensitivity for SBCD extent (i.e. presence and correct segmental location) was 75% (95% CI 67% to 82%), compared with 60% (95% CI 51% to 68%) for US: a difference of 15% (95% CI 6% to 25%), which was statistically significant (Table 15). However, specificity was not significantly different, increasing to 90% (95% CI 77% to 96%) for US compared with 96% (95% CI 86% to 99%) for MRE.
Per-participant sensitivity and specificity for SBCD extent against the consensus reference standard (both cohorts combined). Equivocal MRE and US results considered disease negative
The number of perceptual errors for MRE and US based on retrospective consensus panel review is shown in Appendix 16, Table 55. Detecting perceptual errors is intended to improve understanding of the maximum theoretical accuracy of the technology after correcting for any reader errors.
Overall, the rates of perceptual error were relatively low, and similar between MRE and US. Specifically, across the 284-participant cohort, 22 (8%) participants had perceptual errors on MRE, compared with 33 (12%) on US. Similarly, in the colon, 25 (9%) participants had perceptual errors on MRE, compared with 23 (8%) on US. For both modalities, all perceptual errors were false negative, with no false-positive errors.
The sensitivity and specificity for SBCD extent according to the recruitment site is shown in Table 16. Data are combined for the lower-recruiting sites.
Per-participant sensitivity and specificity for SBCD extent against the consensus reference standard according to recruitment site (both cohorts combined)
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