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Picot J, Cooper K, Bryant J, et al. The Clinical Effectiveness and Cost-Effectiveness of Bortezomib and Thalidomide in Combination Regimens with an Alkylating Agent and a Corticosteroid for the First-Line Treatment of Multiple Myeloma: A Systematic Review and Economic Evaluation. Southampton (UK): NIHR Journals Library; 2011 Dec. (Health Technology Assessment, No. 15.41.)
The Clinical Effectiveness and Cost-Effectiveness of Bortezomib and Thalidomide in Combination Regimens with an Alkylating Agent and a Corticosteroid for the First-Line Treatment of Multiple Myeloma: A Systematic Review and Economic Evaluation.
Show detailsThe ranges used for the deterministic analyses and PSAs are reported in this appendix. Where appropriate, parameters were assigned a distribution in the PSA. Distributions were chosen according to the methodology suggested by Briggs and colleagues.103 They suggest that the normal distribution is a ‘candidate distribution for representing the uncertainty in any parameter in the model’. Further, they suggest the beta distribution for binomial outcomes, where parameters can vary between zero and one, for example probabilities, and the gamma distribution for costs where parameters are non-negative.
- Discount rates were varied between 2% and 5% for costs and benefits in the deterministic sensitivity analyses.
- The number of cycles for each of the treatments varied between seven and nine. For each of the interventions, we assumed a range between one fewer than the mean to one more than the mean. The number of cycles was assumed to follow a normal distribution.
- Second-line treatment was varied according to the proportion who had bortezomib and HDD. For MP, MPT and CTDa, the proportion varied between 60% and 80% and for VMP, the proportion varied between 5% and 25%.
- The range for the utility values was assumed to be ± 10% of the mean utility values, based on the uncertainty in the utility values from the MMIX Trial. We analysed the HRQoL data from the MMIX Trial. (AiC and/or CiC information has been removed.) Utility values were sampled from a beta distribution.
- The CR data were obtained from the trials and SEs were derived. Values were sampled from a beta distribution.
- The costs for AEs, bortezomib administration and consultation were assumed to vary within the range ± 30% of the mean and were sampled from a gamma distribution.
- The ranges for the HRs and event rates for the MP survival curves were taken from the trial data. Values were sampled from a log-normal distribution.
- The costs for AEs, bortezomib administration and consultation were varied within ± 30% of the mean for the deterministic sensitivity analysis.
Parameters and distributions for the deterministic and probabilistic sensitivity analyses
| Name | Mean | CI | SE | Distribution | |
|---|---|---|---|---|---|
| Higher | Lower | ||||
| Discount rate | |||||
| Discount rate costs (%) | 3.5 | 5.0 | 2.0 | NA | |
| Discount rate benefits (%) | 3.5 | 5.0 | 2.0 | NA | |
| Cycles of treatment | |||||
| cycle_MP | 8 | 9 | 7 | 0.5102 | Log normal |
| cycle_MPT | 8 | 9 | 7 | 0.5102 | Log normal |
| cycle_VMP | 9 | 10 | 8 | 0.5102 | Log normal |
| cycle_CTDa | 7 | 8 | 6 | 0.5102 | Log normal |
| Subsequent treatment, Bort. | |||||
| Sub_treat_Bort_MP | 70 | 80 | 60 | 5.1020 | Log normal |
| Sub_treat_Bort_MPT | 70 | 80 | 60 | 5.1020 | Log normal |
| Sub_treat_Bort_VMP | 15 | 25 | 5 | 5.1020 | Log normal |
| Sub_treat_Bort_CTDa | 70 | 80 | 60 | 5.1020 | Log normal |
| Utility values | |||||
| u_treatment | 0.58 | 0.639 | 0.522 | 0.030 | Beta |
| u_response | (AiC/CiC information has been removed) | (AiC/CiC information has been removed) | (AiC/CiC information has been removed) | (AiC/CiC information has been removed) | Beta |
| u_progression | 0.68 | 0.748 | 0.612 | 0.035 | Beta |
| CR | |||||
| CR_MP | 0.026 | 0.035 | 0.017 | 0.005 | Beta |
| CR_MPT | 0.142 | 0.307 | 0.066 | 0.084 | Beta |
| CR_VMP | 0.217 | 0.386 | 0.121 | 0.087 | Beta |
| CR_CTDa | (AiC/CiC information has been removed) | (AiC/CiC information has been removed) | (AiC/CiC information has been removed) | (AiC/CiC information has been removed) | Beta |
| AEs (£ per cycle) | |||||
| cAE_MP | 45.63 | 59.32 | 31.94 | 6.98 | Gamma |
| cAE_MPT | 70.40 | 91.52 | 49.28 | 10.78 | Gamma |
| cAE_VMP | 73.16 | 95.11 | 51.21 | 11.20 | Gamma |
| cAE_CTDa | 72.45 | 94.19 | 50.72 | 11.09 | Gamma |
| Other | |||||
| Cost of bortezomib administration (£) | 153.40 | 199.42 | 107.38 | 23.4796 | Gamma |
| Outpatient appointment medical oncology (£) | 121.11 | 157.44 | 84.78 | 18.5372 | Gamma |
| Survival curve parameters | |||||
| Multipliers | |||||
| MP OS baseline curve | 0.028 | 0.039 | 0.020 | 0.0041 | Log normal |
| MP PFS baseline curve | 0.067 | 0.070 | 0.060 | 0.0036 | Log normal |
| HR OS MPT | 0.62 | 0.82 | 0.50 | 0.0714 | Log normal |
| HR OS VMP | 0.62 | 0.83 | 0.51 | 0.0714 | Log normal |
| HR OS CTDa | (AiC/CiC information has been removed) | (AiC/CiC information has been removed) | (AiC/CiC information has been removed) | (AiC/CiC information has been removed) | Log normal |
| HR PFS MPT | 0.58 | 0.77 | 0.49 | 0.0612 | Log normal |
| HR PFS VMP | 0.58 | 0.76 | 0.48 | 0.0612 | Log normal |
| HR PFS CTDa | (AiC/CiC information has been removed) | (AiC/CiC information has been removed) | (AiC/CiC information has been removed) | (AiC/CiC information has been removed) | Log normal |
| Cost of treatments | |||||
| Unit cost bortezomib (£) | 762.38 | 914.86 | 609.90 | 77.7939 | NA |
| Unit cost thalidomide (£) | 298.48 | 358.18 | 238.78 | 30.4571 | NA |
| Dosage thalidomide (mg/day) | 150 | 200 | 100 | 25.5102 | Log normal |
NA, not applicable.
- Parameters included in the sensitivity analyses - The Clinical Effectiveness and...Parameters included in the sensitivity analyses - The Clinical Effectiveness and Cost-Effectiveness of Bortezomib and Thalidomide in Combination Regimens with an Alkylating Agent and a Corticosteroid for the First-Line Treatment of Multiple Myeloma: A Systematic Review and Economic Evaluation
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