TABLE 114Manufacturer submission for dasatinib (CP): critical appraisal checklist

Dimension of qualityCriteria met?Comments
S1Statement of decision problem/objectiveYesCost-effectiveness modelling of treatment with dasatinib vs treatment with HDI or nilotinib in adults with CML-CP resistant or intolerant to previous therapy including imatinib. NICE is the primary decision-maker
S2Statement of scope/perspectiveYesNHS perspective. Model inputs are consistent with the perspective. Scope of the model stated and justification given. Outcomes consistent with perspective and scope of the model
S3Rationale for structureYesModel structure has been described and is largely consistent with the progression of CML. The model uses the relationship between response to treatment and long-term survival to estimate long-term benefits. Sources of data used to develop the model structure are specified. Other model structures were considered
S4Structural assumptionsYesModel assumptions were stated and justified
S5Strategies/comparatorsYesA clear definition of the comparators is provided and justified. Not all the comparators identified in the scope are evaluated – the analysis is limited to those believed to be most relevant

Differences in the baseline characteristics of individuals in the single-arm studies of dasatinib, nilotinib and HDI may render comparison invalid; these differences are not explored
S6Model typeYesThe model type is appropriate for this type of decision problem
S7Time horizonYesThe time horizon is lifetime (100 years), which is appropriate to capture differences between treatment options. Treatment is continued until disease progression or until no longer tolerated. Owing to the extensive data extrapolation needed to model a 100-year time horizon and a sensitivity analysis with a 5-year time horizon is also included
S8Disease states/pathwaysYesThe disease states reflect the biological pathway of the disease (CP, AP, BC and death) and the level of response on initiating treatment (initial best response and no initial response). Progression within CP prior to progressing to AP does not appear to be captured in the model
S9Cycle lengthYesThe cycle length is defined (monthly) and is justified in terms of the natural history of the disease and the frequency of follow-up of CML patients
D1Data identificationYesData identification methods are described. The data for the main clinical parameters have been taken from single-arm clinical studies. Data choices have been justified. The quality of the data has not been assessed. The use of health-care resources in the treatment of CML and the management of serious AEs was estimated by UK clinical experts; the methods of data collection are described. Health-state utilities were elicited in a cross-sectional study; the methods are described
D2Pre-model data analysisYesCosts of health-care resource use. Utility values for serious AEs
D2aBaseline dataPartialAll data are derived from single-arm studies. Data for dasatinib are sourced from data on file; data for HDI and nilotinib are sourced from the systematic literature review

The model does not use a baseline risk of disease progression or baseline treatment strategy directly. Levels of response to treatment are considered comparable to baseline risk as they determine the probability of disease progression for the rest of the analysis

Monthly rates of progression were calculated from the dasatinib clinical studies and applied in the model regardless of treatment

A half-cycle correction was used in the model; it is not clear whether or not this was applied to both costs and outcomes
D2bTreatment effectsPartialAll data are derived from single-arm studies

ImR and ImI populations were not considered separately

The model uses the relationship between attainment of a MCyR and OS seen with imatinib and assumes that the relationship will also be true for dasatinib and nilotinib

Survival at 24 months is used for dasatinib and nilotinib and survival at 3 months for HDI. Methods of data extrapolation are not described, but disease progression is assumed to occur at a constant monthly rate

The model assumes that individuals move directly from CP to AP, which may not be an accurate reflection of clinical reality. The literature suggests that individuals may progress within CP without meeting the criteria for AP. This is not captured in the model

Progression rates based on molecular response are assumed to be the same as CCyR owing to the lack of available data

Data used to derive treatment effects are likely to be subject to a large amount of uncertainty due to the range of sources from which they have been elicited and the length of extrapolation necessary to inform a 100-year model
D2cQoL weights (utilities)YesThe methods of utility derivation are described. Utilities were commissioned in a cross-sectional study of 100 representative unaffected individuals in the UK using the time trade-off method and the EQ-5D instrument. The impacts of serious AEs on health utility were taken from non-CML literature. The values used for CP/response are similar to those collected in the IRIS study of imatinib
D3Data incorporationYesData incorporated into the model are referenced and generally well described. For the probabilistic sensitivity analysis, the input parameters and choice of distribution are described

All effectiveness data used in the model are derived from single-arm studies; although this is described, the impact of the uncertainty associated with these methods is not explored
D4Assessment of uncertaintyPartialAll types of uncertainty have been discussed, although only parameter uncertainty is explored to any extensive degree (through probabilistic sensitivity analysis)
D4aMethodologicalNoOther modelling methods were considered possible; however, a Markov model was considered to be the most appropriate and alternative modelling approaches were not developed
D4bStructuralPartialThis model is subject to a large amount of structural uncertainty that has not been discussed. Only the effect of differing time horizons was explored; the model has been run with two time horizons, 100 years (lifetime) and 5 years
D4cHeterogeneityYesNo subgroup analyses were conducted; given the data available this is reasonable
D4dParameterYesOne-way and probabilistic sensitivity analyses have been performed
C1Internal consistencyYesThe report states that the internal validity of the model was tested by using extreme values in the input parameters
C2External consistencyPartialThe report states that results of the model have been compared with those of other published economic analyses and against study data. However, it is also agreed that given the limited details available for previously published studies meaningful comparisons are difficult to perform. Few details of validation against study data are provided

From: Appendix 4, Appraisal of economic evaluations in industry submissions: checklists

Cover of Dasatinib and Nilotinib for Imatinib-Resistant or -Intolerant Chronic Myeloid Leukaemia: A Systematic Review and Economic Evaluation
Dasatinib and Nilotinib for Imatinib-Resistant or -Intolerant Chronic Myeloid Leukaemia: A Systematic Review and Economic Evaluation.
Health Technology Assessment, No. 16.22.
Rogers G, Hoyle M, Thompson Coon J, et al.
Southampton (UK): NIHR Journals Library; 2012 Apr.
© 2012, Crown Copyright.

Included under terms of UK Non-commercial Government License.

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