{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T02:29:36Z","timestamp":1785205776994,"version":"3.55.0"},"reference-count":7,"publisher":"National Institute for Health and Care Research","issue":"Suppl 1","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["09\/96-01"],"award-info":[{"award-number":["09\/96-01"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:p>This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of ofatumumab for the treatment of refractory chronic lymphocytic leukaemia (CLL), based upon the manufacturer\u2019s submission (MS) to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The submitted clinical evidence included one study: a non-randomised, single-arm study. Two other studies were identified but both were non-comparative and provided evidence for therapies other than ofatumumab. For this reason these studies were not discussed in full in the main body of the submission. In the Hx-CD20-406 study, the overall response rate was 58% (99% confidence interval 40% to 74%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Complete resolution of constitutional symptoms and improved performance status occurred in 57% of patients. Median progression-free survival (PFS) and overall survival (OS) times were 5.7 and 13.7 months, respectively. The most common adverse events during treatment were infusion reactions and infections, which were primarily grade 1 or 2 events. The MS concluded that ofatumumab provides a new, effective and well-tolerated therapy for patients with CLL who are refractory to both fludarabine and alemtuzumab [double refractory (DR)]. The ERG undertook a critical appraisal of the submission. The ERG had a number of concerns regarding the manufacturer\u2019s estimates of effectiveness based on evidence from a single-arm, non-randomised study. An \u2018area-under-the-curve\u2019 or \u2018partitioned-survival\u2019 model was used to project expected clinical and economic outcomes for patients with DR CLL who were assumed to receive ofatumumab or best supportive care (BSC). The model had a three-state structure: \u2018alive pre-progression\u2019, \u2018alive post progression\u2019 and \u2018dead\u2019. Overall, the modelling approach is reasonable given the limited evidence available for the drug in the patient population under review. However, a number of uncertainties were identified in the economic evaluation; for example, the BSC arm used data from patients in the Hx-CD20-406 study who did not respond to ofatumumab treatment \u2013 \u2018non-responders\u2019 \u2013 and the ofatumumab arm used data from all of those treated in the Hx-CD20-406 study. Further uncertainty arose regarding the choice of utilities, the omission of 17p and 11q chromosomal deletions as factors in the Cox proportional hazards models for PFS and OS, and the omission of the costs of drugs in progressive disease. It was felt that these factors biased cost-effectiveness in favour of ofatumumab. When revisions were made to the assumptions in the model based on the ERG\u2019s review of the published and submitted evidence, the revised base-case incremental cost-effectiveness ratio for ofatumumab increased to \u00a381,500 per quality-adjusted life-year. The final appraisal determination was issued by NICE in September 2010 (<jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.nice.org.uk\/nicemedia\/live\/12264\/50758\/50758.pdf\" xlink:role=\"web\">www.nice.org.uk\/nicemedia\/live\/12264\/50758\/50758.pdf<\/jats:uri>).<\/jats:p>","DOI":"10.3310\/hta15suppl1-07","type":"journal-article","created":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T18:12:28Z","timestamp":1613067148000},"page":"61-67","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Ofatumumab for the treatment of chronic lymphocytic leukaemia in patients who are refractory to fludarabine and alemtuzumab: a critique of the submission from GSK"],"prefix":"10.3310","volume":"15","author":[{"given":"M","family":"Hoyle","sequence":"first","affiliation":[{"name":"PenTAG, Peninsula College of Medicine and Dentistry, Universities of Exeter and Plymouth, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Crathorne","sequence":"additional","affiliation":[{"name":"PenTAG, Peninsula College of Medicine and Dentistry, Universities of Exeter and Plymouth, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Garside","sequence":"additional","affiliation":[{"name":"PenTAG, Peninsula College of Medicine and Dentistry, Universities of Exeter and Plymouth, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Hyde","sequence":"additional","affiliation":[{"name":"PenTAG, Peninsula College of Medicine and Dentistry, Universities of Exeter and Plymouth, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6221","published-online":{"date-parts":[[2011,5]]},"reference":[{"key":"key20210211165110006_ref1-bib1","unstructured":"National Institute for Health and Clinical Excellence (NICE). Guide to the methods of technology appraisal. London: NICE; 2008."},{"key":"key20210211165110006_ref1-bib2","unstructured":"National Institute for Health and Clinical Excellence (NICE). Single technology appraisal: ofatumumab for the treatment of refractory chronic lymphocytic leukaemia \u2013 final scope. London: NICE; 2009."},{"key":"key20210211165110006_ref1-bib3","unstructured":"Centre for Reviews and Dissemination (CRD). Systematic reviews: CRD\u2019s guidance for undertaking reviews in healthcare. York: CRD, University of York; 2009."},{"key":"key20210211165110006_ref1-bib4","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1080\/10428190701573257","article-title":"The natural history of fludarabine-refractory chronic lymphocytic leukaemia patients who fail alemtuzumab or have bulky lymphadenopathy","volume":"48","author":"Tam","year":"2007","journal-title":"Leuk Lymphoma"},{"key":"key20210211165110006_ref1-bib5","doi-asserted-by":"crossref","first-page":"475","DOI":"10.3324\/haematol.11903","article-title":"High dose methylprednisolone and rituximab is an effective therapy in advanced refractory chronic lymphocytic leukaemia resistant to fludarabine therapy","volume":"93","author":"Dungarwalla","year":"2008","journal-title":"Haematologica"},{"key":"key20210211165110006_ref1-bib6","volume-title":"Health state preference study mapping the changes over the course of the disease process in chronic lymphocytic leukemia (Poster no PCN79)","author":"Ferguson"},{"key":"key20210211165110006_ref1-bib7","volume-title":"Briefing paper for methods review workshop on key issues in utility measurement","author":"National Institute for Health and Clinical Excellence","year":"2007"}],"container-title":["Health Technology Assessment"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/njl-admin.nihr.ac.uk\/document\/download\/2035706","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/publications\/hta15suppl1-07\/hta15suppl1-07.xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/njl-admin.nihr.ac.uk\/document\/download\/2035706","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T15:37:40Z","timestamp":1692113860000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/hta\/hta15suppl1-07"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5]]},"references-count":7,"aliases":["10.3310\/hta15suppl1\/07"],"journal-issue":{"issue":"Suppl 1","published-online":{"date-parts":[[2011,5]]}},"alternative-id":["10.3310\/hta15suppl1-07"],"URL":"https:\/\/doi.org\/10.3310\/hta15suppl1-07","relation":{},"ISSN":["1366-5278","2046-4924"],"issn-type":[{"value":"1366-5278","type":"print"},{"value":"2046-4924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,5]]},"assertion":[{"value":"This content has been made freely available to all.","name":"free","label":"Free to read"},{"value":"4-2010","name":"date_of_ERG_submission","label":"Date of ERG submission","group":{"name":"article_history","label":"Article History"}},{"value":"6-2010","name":"editorial_review_begun","label":"Editorial review begun","group":{"name":"article_history","label":"Article History"}},{"value":"9-2010","name":"accepted_for_publication","label":"Accepted for publication","group":{"name":"article_history","label":"Article History"}}]}}