Abstract
Objectives In 2012, the National Institute for Health and Care Excellence assessed dasatinib, nilotinib, and standard-dose imatinib as first-line treatment of chronic phase chronic myelogenous leukemia (CML). Licensing of these alternative treatments was based on randomized controlled trials assessing complete cytogenetic response (CCyR) and major molecular response (MMR) at 12 months as primary end points. We use this case study to illustrate the validation of CCyR and MMR as surrogate outcomes for overall survival in CML and how this evidence was used to inform National Institute for Health and Care Excellence's recommendation on the public funding of these first-line treatments for CML. Methods We undertook a systematic review and meta-analysis to quantify the association between CCyR and MMR at 12 months and overall survival in patients with chronic phase CML. We estimated life expectancy by extrapolating long-term survival from the weighted overall survival stratified according to the achievement of CCyR and MMR. Results Five studies provided data on the observational association between CCyR or MMR and overall survival. Based on the pooled association between CCyR and MMR and overall survival, our modeling showed comparable predicted mean duration of survival (21-23 years) following first-line treatment with imatinib, dasatinib, or nilotinib. Conclusions This case study illustrates the consideration of surrogate outcome evidence in health technology assessment. Although it is often recommended that the acceptance of surrogate outcomes be based on randomized controlled trial data demonstrating an association between the treatment effect on both the surrogate outcome and the final outcome, this case study shows that policymakers may be willing to accept a lower level of evidence (i.e., observational association).
| Original language | English |
|---|---|
| Pages (from-to) | 1081-1090 |
| Number of pages | 10 |
| Journal | Value in Health |
| Volume | 16 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Sept 2013 |
Bibliographical note
Funding Information:Source of financial support: Ciani Oriana is currently receiving a Peninsula College of Medicine and Dentistry PhD studentship. This work was supported by the National Institute for Health Research (NIHR) health technology assessment program (project number 08/226/01). The authors thank Rob Anderson and Obioha Ukoumunne for their valuable contribution to the study. R.G. is partially supported by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula and by the European Regional Development Fund and the European Social Fund Convergence Programme for Cornwall and the Isles of Scilly. The views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the NIHR, the Department of Health in England, or the European Union.
Keywords
- chronic myeloid leukemia complete cytogenetic response dasatinib health technology assessment HTA imatinib intermediate outcomes major molecular response nilotinib surrogate end points systematic review technology appraisal
