Estimating outcomes and cost effectiveness using a single-arm clinical trial: ofatumumab for double-refractory chronic lymphocytic leukemia
Tóm tắt
Ofatumumab (Arzerra®, Novartis) is a treatment for chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab [double refractory (DR-CLL)]. Ofatumumab was licensed on the basis of an uncontrolled Phase II study, Hx-CD20-406, in which patients receiving ofatumumab survived for a median of 13.9 months. However, the lack of an internal control arm presents an obstacle for the estimation of comparative effectiveness. The objective of the study was to present a method to estimate the cost effectiveness of ofatumumab in the treatment of DR-CLL. As no suitable historical control was available for modelling, the outcomes from non-responders to ofatumumab were used to model the effect of best supportive care (BSC). This was done via a Cox regression to control for differences in baseline characteristics between groups. This analysis was included in a partitioned survival model built in Microsoft® Excel with utilities and costs taken from published sources, with costs and quality-adjusted life years (QALYs) were discounted at a rate of 3.5% per annum. Using the outcomes seen in non-responders, ofatumumab is expected to add approximately 0.62 life years (1.50 vs. 0.88). Using published utility values this translates to an additional 0.30 QALYs (0.77 vs. 0.47). At the list price, ofatumumab had a cost per QALY of £130,563, and a cost per life year of £63,542. The model was sensitive to changes in assumptions regarding overall survival estimates and utility values. This study demonstrates the potential of using data for non-responders to model outcomes for BSC in cost-effectiveness evaluations based on single-arm trials. Further research is needed on the estimation of comparative effectiveness using uncontrolled clinical studies.
Tài liệu tham khảo
Coiffier B, Lepretre S, Pedersen LM, Gadeberg O, Fredriksen H, van Oers MH, et al. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1–2 study. Blood. 2008;111(3):1094–100.
Freedman B. Equipoise and the ethics of clinical research. N Engl J Med. 1987;317(3):141–5.
Center for drug evaluation and research. ofatumumab: clinical review and evaluation. 2009. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/125326s000_MedR.pdf. Accessed 12 Jan 2016.
US. Food and Drug Administration (FDA). Ofatumumab. 2009. http://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm188221.htm. Accessed 29 Apr 2014.
European Medicines Agency (EMA). Public summary of opinion on orphan designation ofatumumab for the treatment of chronic lymphocytic leukemia. 2010. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2009/11/human_orphan_000468.jsp&mid=WC0b01ac058001d12b. Accessed 29 Apr 2014.
ClinicalTrials.gov. Ofatumumab + chlorambucil vs chlorambucil monotherapy in previously untreated patients with chronic lymphocytic leukemia (complement 1) [NCT00748189]. 2008. http://clinicaltrials.gov/ct2/show/NCT00748189?term=ofatumumab+chronic+lymphocytic&rank=14. Accessed 29 Apr 2014.
Sutton A, Ades AE, Cooper N, Abrams K. Use of indirect and mixed treatment comparisons for technology assessment. Pharmacoeconomics. 2008;26(9):753–67.
National Institute for Health and Clinical Excellence (NICE). Final appraisal determination: imatinib for chronic myeloid leukemia. 2003. https://www.nice.org.uk/guidance/ta70/documents/final-appraisal-determination-imatinib-for-chronic-myeloid-leukemia2. Accessed 29 Apr 2014.
National Institute for Health and Care Excellence (NICE). NICE DSU technical support document 17: the use of observational data to inform estimates of treatment effectiveness in technology appraisal: methods for comparative individual patient data. 2015. http://www.nicedsu.org.uk/TSD17%20-%20DSU%20Observational%20data%20FINAL.pdf. Accessed 12 Jan 2017.
National Institute for Health and Care Excellence (NICE). NICE DSU technical support document 18: methods for population-adjusted indirect comparisons in submissions to NICE. 2016. http://www.nicedsu.org.uk/TSD18%20Population%20adjustment%20TSD%20-%20FINAL.pdf. Accessed 12 Jan 2017.
Tam CS, O’Brien S, Lerner S, Khouri I, Ferrajoli A, Faderl S, et al. The natural history of fludarabine-refractory chronic lymphocytic leukemia patients who fail alemtuzumab or have bulky lymphadenopathy. Leuk Lymphoma. 2007;48(10):1931–9.
Fraser G, Smith CA, Imrie K, Meyer R, Hematology Disease Site Groupof Cancer Care Ontario’s Program in Evidence-Based C. Alemtuzumab in chronic lymphocytic leukemia. Curr Oncol. 2007;14(3):96–109.
Lemery SJ, Zhang J, Rothmann MD, Yang J, Earp J, Zhao H, et al. US Food and Drug Administration approval: ofatumumab for the treatment of patients with chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab. Clin Cancer Res. 2010;16(17):4331–8.
Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O’Brien S, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996;87(12):4990–7.
Wierda WG, Kipps TJ, Mayer J, Stilgenbauer S, Williams CD, Hellmann A, et al. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2010;28(10):1749–55.
Curtis L. Unit costs of health and social care 2009. 2009. http://www.pssru.ac.uk. Accessed 29 Apr 2014.
National Health Service (NHS). Reference costs 2008–2009. 2010. http://webarchive.nationalarchives.gov.uk/+/www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_111591. Accessed 29 Apr 2014.
Ferguson J, Tolley K, Gilmour L, Priaulx J. Health state preference study mapping the change over the course of the disease process in chronic lymphocytic leukemia (CLL) ISPOR 11th Annual European Congress. Athens. 8–11 November 2008. Poster PCN79.
National Institute for Health and Clinical Excellence (NICE). Guide to the methods of technology appraisal. 2008. http://www.nice.org.uk/media/B52/A7/TAMethodsGuideUpdatedJune2008.pdf. Accessed 29 Apr 2014.
HM Treasury. The green book: appraisal and evaluation in central government. 2009. https://www.gov.uk/government/publications/the-green-book-appraisal-and-evaluation-in-central-governent. Accessed 29 Apr 2014.
National Institute for Health and Clinical Excellence (NICE). TA202: ofatumumab for the treatment of chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab. 2010. http://www.nice.org.uk/nicemedia/live/13240/51314/51314.pdf. Accessed 29 Apr 2014.
Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, et al. Consolidated health economic evaluation reporting standards (CHEERS)—explanation and elaboration: a report of the ISPOR health economic evaluation publication guidelines good reporting practices task force. Value Health. 2013;16(2):231–50.
F. Hoffmann-La Roche Ltd. Roche Statement: another milestone in clinical data sharing: new system for requesting analyzable patient-level data begins on 1 January 2014. 2014. http://www.roche.com/media/med-stat-2014-01-02.htm. Accessed 29 Apr 2014.