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For reference, Novantrone costs about $3,000 a year plus infusion expenses and can only be done a limited number of times for safety reasons and has some potential serious side effects. Tysabri runs as much as $70,000 a year. The below study found that the estimated cost of HSCT was less than £3000 (or $4700) per quality-adjusted life year. For comparison, "current MS drug therapy cost effectiveness has been estimated to be between $80,000 to 168,000 per avoided relapse or upwards of $73,000 per incremental quality-adjusted life year." Wow. - Dave
Autologous haematopoietic stem cell transplantation for secondary progressive multiple sclerosis: an exploratory cost-effectiveness analysis
Tappenden P, Saccardi R, Confavreux C, Sharrack B, Muraro PA, Mancardi GL, Kozak T, Farge-Bancel D, Madan J, Rafia R, Akehurst R, Snowden J
CRD summary
This study examined the cost-effectiveness of autologous haematopoietic stem cell transplantation (HSCT), compared with mitoxantrone, for patients with secondary progressive multiple sclerosis. The authors concluded that autologous HSCT could be cost-effective, but high-quality trials were required to verify their findings. The methods were satisfactory and the details of the derivation of the effectiveness and cost data were reported. The results were given in full and the conclusions appear to be appropriate.
Type of economic evaluation
Cost-utility analysis
Study objective
The objective was to examine the cost-effectiveness of autologous haematopoietic stem cell transplantation (HSCT), compared with mitoxantrone, in the treatment of patients with secondary progressive multiple sclerosis (SPMS).
Interventions
Mitoxantrone was a common treatment for SPMS. Described as a type II topoisomerase inhibitor with antineoplastic and immuno-suppressive effects, it had a maximum cumulative lifetime dose of 120mg and was usually administered in monthly 20mg doses for six months. This was compared with autologous HSCT, which gave intensive immune suppression to patients with severe autoimmune and inflammatory diseases.
Location/setting
UK/in-patient secondary care.
Methods
Analytical approach:
A decision-analytic Markov model was used to evaluate the incremental cost-effectiveness of autologous HSCT versus mitoxantrone, based on an indirect comparison between two registry datasets. The time horizon was the lifetime of the patient. The authors reported that the perspective was that of the UK NHS and Personal Social Services.
Effectiveness data:
The effectiveness data were mainly from two multiple sclerosis registries; the European Group for Blood and Marrow Transplantation (EBMT) database, and the Clinique de Neurologie, Lyon, registry. Transplant-related mortality for autologous HSCT was from published studies. The data from these two registries produced the main measures, which were the relative effectiveness of autologous HSCT versus mitoxantrone and the incidence of multiple sclerosis (MS) relapse.
Monetary benefit and utility valuations:
The utility data were from a published study, which derived them from a total of 2,048 patients (Orme, et al. 2007, see 'Other Publications of Related Interest' below for bibliographic details).
Measure of benefit:
Quality-adjusted life-years (QALYs) gained were the benefit measure and future benefits were discounted at an annual rate of 3.5%.
Cost data:
The direct costs were those of: mitoxantrone; treatment of drug-related adverse events; diagnostic tests; non-study medications; autologous HSCT; and MS disease management. The resource use was from a variety of sources. The probability of adverse events was from a large randomised controlled trial of mitoxantrone in MS. The hospital costs were from NHS Reference Costs and drug costs were from the British National Formulary. Autologous HSCT costs were from tariffs used in the Sheffield Teaching Hospitals NHS Foundation Trust. The disease management costs were from a submission to the National Institute for Health and Clinical Excellence (NICE) on the management of rapidly evolving MS. All costs were reported in UK pounds sterling (£) and discounted at an annual rate of 3.5%.
Analysis of uncertainty:
Three scenarios were analysed with different progression rules. Scenario one was pessimistic (for HSCT), using six-month sustained progression from baseline Expanded Disability Status Scale (EDSS) score. Scenario two was a middle scenario, using sustained progression confirmed at the next clinic, which could be earlier than six months. Scenario three was optimistic, using any sustained increase in EDSS irrespective of baseline score. One-way sensitivity analyses were performed by varying the autologous HSCT transplant-related mortality, the disease management costs, the costs of autologous HSCT, the discount rate, and other parameters.
Results
Autologous HSCT was cost-effective compared with mitoxantrone, at the accepted UK cost per QALY threshold, but the results varied substantially in the scenario analyses.
In scenario one (pessimistic), HSCT generated additional costs of £24,540, over mitoxantrone, and 1.02 fewer QALYs. HSCT was dominated by mitoxantrone as it was more costly and less effective. In scenario two (middle ground), HSCT generated additional costs of £17,136, over mitoxantrone, and additional QALYs of 0.23. Compared with mitoxantrone, the incremental cost-utility ratio for HSCT was £74,210 per QALY. In scenario three (optimistic), HSCT generated additional costs of £3,883, over mitoxantrone, and additional QALYs of 1.40. Compared with mitoxantrone, the incremental cost-utility ratio was £2,783 per QALY.
The sensitivity analysis showed that these results were sensitive to varying the HSCT procedural costs and the HSCT-related mortality.
Authors' conclusions
The authors concluded that HSCT could be cost-effective, but large high-quality trials were required to verify their findings.
CRD commentary
Interventions:
The interventions were reported clearly and in detail and they appear to have been appropriate comparators. The usual care was included.
Effectiveness/benefits:
The effectiveness data were mainly from two registries of MS patients, which could have biases, such as inclusion bias, prevalent in non-randomised studies. The authors reported this limitation to their study and stated that there were no published randomised controlled trial data available. The measure of benefit appears to have been appropriate as does the evidence used to derive the QALYs, but the original article should be consulted to fully assess the data quality.
Costs:
The perspective was explicitly reported and it seems that no major relevant costs were omitted for this health and social care perspective. The sources for the unit costs and resource data were reported, but the price year was not and this will hamper any future inflationary exercises. The time horizon and discount rate were reported.
Analysis and results:
The available information was appropriately synthesised, using a decision-analytic Markov model. Details of the model were reported, including a diagram. The impact of uncertainty was tested in three scenario analyses, as well as multiple one-way sensitivity analyses. A probabilistic sensitivity analysis was not undertaken, due to the absence of trial information. The authors stated that the substantial gaps in the evidence meant that their results should be treated with caution.
Concluding remarks:
The methods were satisfactory and the details on the derivation of the effectiveness and cost data were reported. The results were given in full and the conclusions appear to be appropriate.
Funding
No funding received.
Bibliographic details
Tappenden P, Saccardi R, Confavreux C, Sharrack B, Muraro PA, Mancardi GL, Kozak T, Farge-Bancel D, Madan J, Rafia R, Akehurst R, Snowden J. Autologous haematopoietic stem cell transplantation for secondary progressive multiple sclerosis: an exploratory cost-effectiveness analysis. Bone Marrow Transplantation 2010; 45(6): 1014-1021
PubMedID
19855441
Tappenden P, Saccardi R, Confavreux C, Sharrack B, Muraro PA, Mancardi GL, Kozak T, Farge-Bancel D, Madan J, Rafia R, Akehurst R, Snowden J
CRD summary
This study examined the cost-effectiveness of autologous haematopoietic stem cell transplantation (HSCT), compared with mitoxantrone, for patients with secondary progressive multiple sclerosis. The authors concluded that autologous HSCT could be cost-effective, but high-quality trials were required to verify their findings. The methods were satisfactory and the details of the derivation of the effectiveness and cost data were reported. The results were given in full and the conclusions appear to be appropriate.
Type of economic evaluation
Cost-utility analysis
Study objective
The objective was to examine the cost-effectiveness of autologous haematopoietic stem cell transplantation (HSCT), compared with mitoxantrone, in the treatment of patients with secondary progressive multiple sclerosis (SPMS).
Interventions
Mitoxantrone was a common treatment for SPMS. Described as a type II topoisomerase inhibitor with antineoplastic and immuno-suppressive effects, it had a maximum cumulative lifetime dose of 120mg and was usually administered in monthly 20mg doses for six months. This was compared with autologous HSCT, which gave intensive immune suppression to patients with severe autoimmune and inflammatory diseases.
Location/setting
UK/in-patient secondary care.
Methods
Analytical approach:
A decision-analytic Markov model was used to evaluate the incremental cost-effectiveness of autologous HSCT versus mitoxantrone, based on an indirect comparison between two registry datasets. The time horizon was the lifetime of the patient. The authors reported that the perspective was that of the UK NHS and Personal Social Services.
Effectiveness data:
The effectiveness data were mainly from two multiple sclerosis registries; the European Group for Blood and Marrow Transplantation (EBMT) database, and the Clinique de Neurologie, Lyon, registry. Transplant-related mortality for autologous HSCT was from published studies. The data from these two registries produced the main measures, which were the relative effectiveness of autologous HSCT versus mitoxantrone and the incidence of multiple sclerosis (MS) relapse.
Monetary benefit and utility valuations:
The utility data were from a published study, which derived them from a total of 2,048 patients (Orme, et al. 2007, see 'Other Publications of Related Interest' below for bibliographic details).
Measure of benefit:
Quality-adjusted life-years (QALYs) gained were the benefit measure and future benefits were discounted at an annual rate of 3.5%.
Cost data:
The direct costs were those of: mitoxantrone; treatment of drug-related adverse events; diagnostic tests; non-study medications; autologous HSCT; and MS disease management. The resource use was from a variety of sources. The probability of adverse events was from a large randomised controlled trial of mitoxantrone in MS. The hospital costs were from NHS Reference Costs and drug costs were from the British National Formulary. Autologous HSCT costs were from tariffs used in the Sheffield Teaching Hospitals NHS Foundation Trust. The disease management costs were from a submission to the National Institute for Health and Clinical Excellence (NICE) on the management of rapidly evolving MS. All costs were reported in UK pounds sterling (£) and discounted at an annual rate of 3.5%.
Analysis of uncertainty:
Three scenarios were analysed with different progression rules. Scenario one was pessimistic (for HSCT), using six-month sustained progression from baseline Expanded Disability Status Scale (EDSS) score. Scenario two was a middle scenario, using sustained progression confirmed at the next clinic, which could be earlier than six months. Scenario three was optimistic, using any sustained increase in EDSS irrespective of baseline score. One-way sensitivity analyses were performed by varying the autologous HSCT transplant-related mortality, the disease management costs, the costs of autologous HSCT, the discount rate, and other parameters.
Results
Autologous HSCT was cost-effective compared with mitoxantrone, at the accepted UK cost per QALY threshold, but the results varied substantially in the scenario analyses.
In scenario one (pessimistic), HSCT generated additional costs of £24,540, over mitoxantrone, and 1.02 fewer QALYs. HSCT was dominated by mitoxantrone as it was more costly and less effective. In scenario two (middle ground), HSCT generated additional costs of £17,136, over mitoxantrone, and additional QALYs of 0.23. Compared with mitoxantrone, the incremental cost-utility ratio for HSCT was £74,210 per QALY. In scenario three (optimistic), HSCT generated additional costs of £3,883, over mitoxantrone, and additional QALYs of 1.40. Compared with mitoxantrone, the incremental cost-utility ratio was £2,783 per QALY.
The sensitivity analysis showed that these results were sensitive to varying the HSCT procedural costs and the HSCT-related mortality.
Authors' conclusions
The authors concluded that HSCT could be cost-effective, but large high-quality trials were required to verify their findings.
CRD commentary
Interventions:
The interventions were reported clearly and in detail and they appear to have been appropriate comparators. The usual care was included.
Effectiveness/benefits:
The effectiveness data were mainly from two registries of MS patients, which could have biases, such as inclusion bias, prevalent in non-randomised studies. The authors reported this limitation to their study and stated that there were no published randomised controlled trial data available. The measure of benefit appears to have been appropriate as does the evidence used to derive the QALYs, but the original article should be consulted to fully assess the data quality.
Costs:
The perspective was explicitly reported and it seems that no major relevant costs were omitted for this health and social care perspective. The sources for the unit costs and resource data were reported, but the price year was not and this will hamper any future inflationary exercises. The time horizon and discount rate were reported.
Analysis and results:
The available information was appropriately synthesised, using a decision-analytic Markov model. Details of the model were reported, including a diagram. The impact of uncertainty was tested in three scenario analyses, as well as multiple one-way sensitivity analyses. A probabilistic sensitivity analysis was not undertaken, due to the absence of trial information. The authors stated that the substantial gaps in the evidence meant that their results should be treated with caution.
Concluding remarks:
The methods were satisfactory and the details on the derivation of the effectiveness and cost data were reported. The results were given in full and the conclusions appear to be appropriate.
Funding
No funding received.
Bibliographic details
Tappenden P, Saccardi R, Confavreux C, Sharrack B, Muraro PA, Mancardi GL, Kozak T, Farge-Bancel D, Madan J, Rafia R, Akehurst R, Snowden J. Autologous haematopoietic stem cell transplantation for secondary progressive multiple sclerosis: an exploratory cost-effectiveness analysis. Bone Marrow Transplantation 2010; 45(6): 1014-1021
PubMedID
19855441