{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T19:02:59Z","timestamp":1784660579273,"version":"3.55.0"},"reference-count":34,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"unspecified","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment Programme","doi-asserted-by":"publisher","award":["NIHR 176061"],"award-info":[{"award-number":["NIHR 176061"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,7,1]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To review how statistically non-significant indirect treatment comparison (ITC) results are interpreted within National Institute for Health and Care Excellence (NICE) cost-comparison evaluations (CCEs) and develop a framework to support interpretations of these results from Bayesian network meta-analyses (NMAs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A systematic review of CCEs between 2017 (first introduced) and April 2025. A framework (point-and-density plots) was developed to better interpret statistically non-significant NMA results for CCEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data sources<\/jats:title>\n                    <jats:p>CCEs were identified through NICE website searches, references of similar reviews and communications with NICE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Eligibility criteria<\/jats:title>\n                    <jats:p>NICE technology appraisals (from 2017) that followed a CCE approach ab initio, had final guidance available and used non-statistically significant ITC results were included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data extraction and synthesis<\/jats:title>\n                    <jats:p>A single reviewer performed screening and data extraction with validation by a second reviewer. Narrative syntheses were performed separately for company, External Assessment Group (EAG) and committee perspectives. Point-and-density plots combine elements of forest plots and density plots alongside reporting the probability that a treatment is non-inferior relative to a comparator. These were applied to a recent CCE (TA1019) for crovalimab for patients with paroxysmal nocturnal haemoglobinuria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 41 CCEs, EAGs raised concerns about statistically non-significant ITC results while companies relied heavily on them. Only \u223c32% of CCEs applied formal methods to explore ITC result uncertainty.<\/jats:p>\n                    <jats:p>For the example framework analysis, comparisons of crovalimab to eculizumab (mean difference (MD): 0.018; 95% CIs \u22120.22 to 0.25) and ravulizumab (MD: 0.079; 95% CIs \u22120.25 to 0.41) were statistically non-significant, with non-inferiority not demonstrated. However, point-and-density plots indicated a 95.9% and 86.3%\u2009probability of non-inferiority of crovalimab versus eculizumab and ravulizumab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Interpretations of statistically non-significant ITC results are inconsistent within individual CCEs and across appraisals. Implementation of the presented recommendations and framework would improve the consistency and robustness of CCEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD420251034143.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-112164","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T18:58:09Z","timestamp":1784660289000},"page":"e112164","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical similarity in cost-comparison evaluations: a systematic review of current methods in NICE appraisals and the development of a framework for the formal assessment of clinical similarity"],"prefix":"10.1136","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9049-3421","authenticated-orcid":false,"given":"Steven J","family":"Edwards","sequence":"first","affiliation":[{"name":"BMJ Technology Assessment Group (BMJ-TAG), BMJ Group, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J","family":"Burgess","sequence":"additional","affiliation":[{"name":"BMJ Technology Assessment Group (BMJ-TAG), BMJ Group, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0496-9671","authenticated-orcid":false,"given":"Nicole","family":"Downes","sequence":"additional","affiliation":[{"name":"BMJ Technology Assessment Group (BMJ-TAG), BMJ Group, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Ip","sequence":"additional","affiliation":[{"name":"BMJ Technology Assessment Group (BMJ-TAG), BMJ Group, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archie","family":"Walters","sequence":"additional","affiliation":[{"name":"BMJ Technology Assessment Group (BMJ-TAG), BMJ Group, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Dadswell","sequence":"additional","affiliation":[{"name":"BMJ Technology Assessment Group (BMJ-TAG), BMJ Group, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"2026072106401871000_16.7.e112164.1","unstructured":"National Institute for Health and Care Excellence (NICE) . 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