Online Content Table: Summary of Characteristics of Economic Evaluations(Publication Date

Online Content Table: Summary of characteristics of economic evaluations(publication date order)

Study, country / Objective and target population (perspective) / Design, method and time horizon / Outcomes / Costs / Data sources / Author's conclusion / Manufacturer support?
O’Day et al., 2011 [1] USA / CEA ofnatalizumabvsfingolimodin RRMS (TPP) / A mathematical model which extrapolated RCT data over 2 years / Relapse rates / Direct medical costs / Effectiveness/clinical data from two RCTs [2, 3]
Cost data were based on product labelling, drug acquisition costs and assumptions and a US study of costs of relapses [4]. / Natalizumab dominated fingolimod being less costly and more effective in avoiding relapses / Biogen
Rajagopalan et al., 2011[5]USA / Costs and outcomes of IM interferon beta-1a, SC interferon beta-1a, interferon beta-1b and glatiramer in MS (TPP) / A retrospective pre-post study of costs and outcomes based on 12 months of medical insurance claims / Sick leave and short term disability absences / Direct medical costs
Indirect costs / Cost data and workplace absence data taken from a US commercial medical insurance claim database / IM INFβ-1a significantly reduced sick leave absences and costs. INFβ-1b significantly reduced sick leave costs. / Biogen
Noyes et al., 2011 [6] USA / CUA of IM interferon beta-1a, SC interferon-1b, IV interferon beta-1b, glatiramervs basic supportive care in RRMS and SPMS (Societal) / A mathematical model simulated EDSS progression over 10 years (annual cycles) based on patient-level data from a US cohort / QALYs; relapse free years / Direct medical and non medical costs;
Indirect costs / Clinical data were based on the Sonya Slifka cohort study [7] and RCTs [2, 8-11].
Cost and utility data were based on the Sonya Slifka cohort study [7]. / All disease modifying drugs produced modest health gains at very high cost. / None stated
Becker & Dembeck, 2011 [12] USA / CEA of IM interferon beta-1a, SC interferon-1a, SC interferon beta-1b, glatiramervs no active treatment in RRMS (TPP) / A spreadsheet model simulated EDSS progression over two years. / EDSS progression steps; relapses avoided / Direct medical costs
/ Effectiveness/clinical data from four RCTs [8-10, 13]
Cost data were obtained from a previously published model (Goldberg et al., 2009) [14]. / All disease modifying drugswere assessed as cost-effective compared to no treatment. / Biogen
Curkendall et al., 2011 [15] USA / Costs and outcomes of early versus delayed disease modifying drugs CIS (TPP) / A retrospective study of costs and outcomes based on 12 months of medical insurance claims / Hospitalisations / Direct medical costs / Cost data and hospitalisation data taken from US commercial and Medicare medical insurance claim databases. / Early treatment with disease modifying drugs was associated with fewer hospitalisations. The higher costs of treatment were offset by reduced direct medical costs / Bayer
Tappenden et al., 2010[16] UK / CUA of stem cell transplantation vsmitoxantrone in SPMS (TPP) / Markov model with health states defined by EDSS stages simulated lifetime disease progression using annual transition probabilities derived from two patient registries / QALYs
/ Direct medical costs / Clinical data were sourced from on unpublished a European and a French patient registry.
Cost data were from UK industry HTA submissions, and official UK tariff lists. Utility values were based on a UK patient survey [17] / Stem cell implantation was potentially cost effective depending on duration of treatment effectiveness. / None stated
Nuijten et al., 2010 [18]Germany / CEA of SC interferon beta-1a, IM interferon beta-1a, interferon beta 1b, glatiramervs no active treatment in RRMS (Societal, TPP in sensitivity analysis) / Markov model with health states defined by EDSS stages and relapses simulated relapse and disease progression over 4 years using annual probabilities / Relapses avoided / Direct medical and non medical costs;
Productivity losses
Informal care
/ Clinical data were based on RCTs [9, 13, 19-21], a Canadian natural history study [22] and a US cost of relapse study [4].
Cost data were sourced from a German cost study [23], and pharmaceutical industry data. / SC INFβ-1a was the most cost-effective disease modifying drugwhen compared to no active treatment / Merck
Bakhshai et al., 2010 [24]USA / CEA of natalizumabvsglatiramer, IM interferon beta-1a, IM interferon beta-1b, SC interferon beta-1a in RRMS (TPP) / Retrospective budget impact analysis model over two years / Relapses avoided / Direct medical costs / Clinical data were based on pooled data from five RCTs [9, 13, 20, 25, 26].
Cost data consisted of assumptions based on product labelling, insurance claims data and a US study of the costs of relapse [4]. / Natalizumab was assessed as cost-effective compared to other disease modifying drugs. / Unclear
Tan et al., 2010 [27] USA / Costs and outcomes of a specialty care management plan versus standard care (TPP) / A retrospective study of costs and outcomes based on 12 months of medical insurance claims / Hospitalisations / Direct medical costs / Cost data and hospitalisation data taken from a US commercial medical insurance claim database / Outcomes improved, however, reduced medical costs did not offset increased drug costs / None stated
Earnshaw et al., 2009 [28]USA / CEA/CUA of Glatiramer and Natalizumabvs symptom management in RRMS (TPP;
Societal) / Markov model with health states defined by EDSS stages simulated lifetime disease progression with monthly probabilities of disability progression and relapse rates / QALYs; life years; relapse free years; years spent in EDSS 0-5.5; proportion of patients progressing to EDSS≥6.0 / Direct medical and non medical costs;
Productivity costs;
Informal care costs / Clinical data were derived from two RCTs [2, 13], two follow up studies [11, 29], the London, Ontario cohort [30], a Swedish cohort [31] and a US relapse study [32].
Cost data were based on an earlier model [33], commercial data, and assumptions based on product labelling. Utility values were sourced from a US patient survey [34] and a previously published model [35]. / Both glatiramer and natalizumab were associated with QALY gains but at high cost. Both were cost saving from a societal perspective due to lost worker productivity. / Teva Neuroscience
Tappenden et al., 2009 [36]USA / CUA of interferon beta-1a (6 MIU, 22 µg, 44 µg), interferon beta-1b (8 MIU),glatiramervs best supportive care in RRMS and SPMS (TPP) / Markov model with health states defined by EDSS stages simulated disease progression over 50 years based on annual transit probabilities / QALYs
/ Direct medical costs / Clinical data were based on seven RCTs identified through a systematic review [8, 9, 11, 13, 20, 21, 26, 37-40]; and the London, Ontario cohort [30].
Cost data were based on the Sonya Slifka cohort [7] and a US study of relapse costs [4]. Utility data were based on 784 patients in a Canadian patient registry. / Further research was needed into long term clinical effectiveness and cost-effectiveness / None stated
Goldberg et al., 2009 [14]USA / CEA of IM interferon beta-1a, SC interferon-1a, SC interferon beta-1b, glatiramervs no active treatment in RRMS (TPP) / Spreadsheet model simulated relapse and progression rates over two years. / EDSS progression steps;
Relapse rates / Direct medical costs
/ Clinical data were based on four RCTs [8-10, 13]
Cost data were based on product labelling, expert opinion, a US study of relapse costs [4] and a US survey of costs of MS [34]. / Interferon beta-1a SC, Interferon beta-1b SC and GA were the most cost effective interventions compared to no treatment. / EMD Serono
Chiao et al., 2009[41] USA / CEA of natalizumabvsglatiramer, IM interferon beta-1a, SC interferon beta-1a, SC interferon beta-1b in RRMS and SPMS (TPP) / Retrospective budget impact analysis model over two years / Relapses avoided / Direct medical costs / Clinical data were based on pooled data from five RCTs [2, 9, 13, 20, 26]
Cost data were based on product labelling, drug acquisition costs and assumptions and a US study of costs of relapses [4]. / Natalizumabwas assessed as the most cost-effective in terms of the total cost per relapse avoided. / Biogen
Kobelt et al., 2009 [42]France / CUA of a hypothetical disease modifying treatment vs no treatment in MS (TPP;
Societal) / Markov model with health states defined by EDSS stages simulating disease progression over 20 years / QALYs
/ Direct medical and non medical costs;
Informal care;
Indirect costs / Clinical data were based on Swedish patient registry and a French epidemiological cohort [43].
Costs and utilities data were based on a survey of 1355 French patient association members conducted by the authors. / Disease modifying drugs added QALYs with moderately increased costs over a 20-year time horizon. / None stated
Higginson et al., 2009 [44] UK / CEA of palliative care teams vs best usual care in severe MS (Societal) / Economic evaluation conducted alongside a 24 week RCT / PROMS,
Caregiver burden / Direct medical and non medical costs; Informal care / Cost and outcome data were collected as part of the RCT. / Palliative care teams achieved comparable clinical outcomes to usual care with lower costs. / None stated
Castelli-Haleyet al., 2008 [45]USA / CEA of glatiramervs interferon beta-1a in MS (TPP) / A mathematical model used regression analyses to predict costs and outcomes based on two years of medical insurance claims / Probability of relapse
/ Direct medical costs / Cost data and medical data taken from a US commercial medical insurance claim database / Glatiramer was associated with lower probability of relapse and lower costs. / Teva Neuroscience
Lazzaro et al., 2009 [46]Italy / CUA of interferon beta-1b treatment commenced at CIS diagnosis vs MS diagnosis (TPP;
Societal) / An epidemiological model simulated the annual incidence of CIS and annual conversion rate to a confirmed MS diagnosis over 25 years. / QALYs
/ TPP version: direct medical costs;
Societal version: Direct medical costs, Indirect costs, Informal care / Clinical data were based data based on an RCT [47] and assumptions.
Cost data were based on an Italian cost of illness study [48] and official Italian tariffs. Utility values were derived from a European study of MS health state values [49]. / Early treatment with interferon beta-1b was cost-effective from the TPP and cost saving from a societal perspective. / Bayer
Guo et al., 2009 [50]USA / CEA of SC vs IM interferon-1a in RRMS (TPP) / Discrete event simulation based on patient-level data from an RCT simulated clinical progression over 4 years / Relapses avoided;
Relapse-free days per patient / Direct medical costs / Clinical inputs obtained from an RCT [10, 26, 40], and a Swedish natural history study [31].
Cost data were based on three US/Canadian cost studies [4, 34, 51] / SC interferon beta-1a achieved better relapse outcomes at a cost the authors judged to be 'reasonable trade-off' between costs and outcomes. / Merck Serono
Gani et al., 2008 [52]UK / CUA of natalizumabvs interferon beta-1b, glatiramer or best supportive care in highly active RRMS (Societal) / Markov model with health states defined by EDSS stages simulating clinical progression over 30 years using annual probabilities derived from an RCT and other sources / QALYs
/ Direct medical and non medical costs;
Indirect costs / Clinical data were based on an RCT [2], and a UK MS patient survey [17].
Cost data were sourced from a UK cost study [53]and official sources. Utility data were derived from a UK patient survey [17] and other sources. / Natalizumab increased QALYs compared to other options at a cost likely to be judged as cost-effective from both a UK TPP and societal perspective. / Biogen
Kobelt et al., 2008[54] Sweden / CUA of natalizumabvs current disease modifying drugs in RRMS (TPP;
Societal) / Markov model with health states defined by EDSS stages, relapses and treatment status simulating
clinical progression over 20 years in 3 month cycles / QALYs
/ Direct medical and non medical costs;
Indirect costs; informal care / Clinical data were based on an RCT [2]; matched data from a Swedish MS patient registry; and the London, Ontario natural history study [30].
Cost and utility data were based on a cross-sectional study of 1339 Swedish patients [55]. / Natalizumab was more effective than current disease modifying drugs at a similar cost. / Biogen
Bell et al., 2007 [33]USA / CUA and CEA of SC glatiramer, IM interferon beta-1a, SC interferon beta-1a, SC interferon beta-1bvs symptom management in RRMS (Societal) / Markov model with health states defined by EDSS stages and relapse simulating lifetime disease progression with monthly transit and relapse probabilities derived from RCTs and natural history studies / QALYs; relapse free years; years spent in EDSS 0.0-5.5;
life-years / Direct medical and non medical,
productivity losses, informal care / Clinical data were based on RCTs, prospective RCT extensions and long term follow up studies [8-11, 13, 20, 26, 29, 56-58] and two natural history studies [30, 31].
Cost data based on a web-based survey of US RRMS patients [59], three studies of worker productivity in MS [60-62] and other official sources.
Utility data were based on studies of US patients [34, 63] / All strategies improved QALYs at high cost. Glatiramer was considered the best strategy. / Teva Neuroscience
Iskedjian et al., 2005[64] Canada / CUA and CEA of interferon beta-1avs IV methylprednisolone in single demyelinating events (TPP;
Societal) / Markov model with health states defined by EDSS stage and symptoms simulated progression over a 12 to 15 year period from a single demyelinating event to clinically definite MS / Monosymptomatic life years (MLY) in pre-confirmed MS state; Quality adjusted MLY / TPP version: direct medical costs;
Societal version: direct medical costs plus lost productivity and leisure time,
Informal care / Clinical data were based on a three-year RCT [65] and the London, Ontario cohort study [30].
Cost data were based on a Canadian cost of illness study[51]. Utility data were based on Canadian [51] and Swedish [66] studies. / IFN b-1a IM was considered cost-effective compared to methylprednisolone. Early treatment also improved cost-effectiveness compared to other studies in confirmed MS. / Biogen
Prosser et al., [63]2004 USA / CUA of interferon beta-1a, interferon beta-1b, glatiramervs no treatment in RRMS, SPMS and PRMS (Societal) / Markov model with health states defined by EDSS stages and relapses simulated natural history , treatment effects and costs over 10 years in monthly cycles / QALYs / Direct healthcare costs;
Informal care
/ Clinical data were based on five RCTs [8, 9, 13, 20, 67] and two natural history studies [30, 31]. Monthly relapse rates were based on 3 natural history studies [32, 68, 69] and expert opinion.
MS-related costs were based on two US cross-sectional surveys [70, 71]. Other sources included drug wholesale prices, official government tariffs and assumptions. Relapse costs were based on hospital data and assumptions.
Utility values were based on a US community and MS patient survey [72]. / Cost-effectiveness results for all treatments were unfavourable with modest benefits outweighed by side effects and high costs. / None stated
Kobelt et al., 2003 [73]Sweden / CUA of interferon beta 1-bvs no drug in highly active RRMS and SPMS (Societal;
TPP in sensitivity analysis) / Markov model with health states defined by EDSS stages simulating progression over 10 years (3 monthly cycles). / QALYs / Direct medical and non medical costs;
Informal care;
Productivity losses / Clinical data were based on two five-year RCTs [20, 37]; the London, Ontario natural history study [30] and Swedish cost and utility data from a population-based observational study [66]. / Interferon beta-1b was cost-effective for patients with more active MS over 20 yr time horizon / Schering
Lepen et al., 2003 [74]UK; France / CEA of Interferon beta-1avs placebo in RRMS (perspective not stated) / A time series regression model projected outcomes from an RCT and costs over 10 years. / EDSS-months of disability / Cost components were not specified / Clinical data were based on the active and placebo arms of an RCT [10, 26] and a survey of costs for French RRMS patients [75]. / SC interferon beta-1a was cost-effective in reducing MS related-disability. / Serono
Chilcott et al., 2003[35] UK / CUA of interferon beta-1a (6 MIU, 22 µg, 44 µg), interferon beta-1b (8 MIU), glatiramervs conventional treatment in RRMS and SPMS (TPP) / Markov model with health states defined by EDSS stages simulating disease progression over 20 years with the annual transit probabilities / QALYs
/ Cost components were not specified / Data were based on five published RCTs [8, 9, 13, 26, 37]; commercial-in-confidence sources for clinical effectiveness and utility data; the London, Ontario natural history study [30]; annual relapse rates from a cohort study [76]; and a British cost study [77]. / Further research was needed to reduce uncertainty around CEA inputs / None stated
Touchette et al., 2003 [78]USA / CUA of mitoxantrone/SC interferon beta-1bvs best supportive care in SPMS or PRMS (TPP;
Societal) / Markov model with health states defined by EDSS stage and relapse simulated clinical progression over 10 years with annual transition rates / QALYs
/ Direct medical and non medical costs; Indirect costs;
Informal care / Clinical data were derived from two RCTs [37, 79]; US cost studies [80]; a Canadian [51] cost study; assumptions based on product labeling; and utility values from a UK HTA report [81]. / Mitoxantrone was likely to be cost-effective adding costs and QALYs from the TPP and cost saving from a societal perspective. Interferon beta-1badd more QALYs but at much higher cost and was not likely to be cost-effective in this group / Immunex
Bose et al., 2002 [82]UK / CUA and CEA of glatiramervs best supportive care in RRMS (perspective stated as TPP) / Up to 8 years of patient level RCT data were combined with cost and natural history data / QALYs; disability units (EDSS stages) avoided;
relapses avoided / Direct medical and non medical costs,
Caregiver costs
/ Clinical data were based on a pivotal RCT [11]; the London Ontario natural history cohort [83]; cost and utility data came from two UK studies [75, 81]. / Glatiramer achieved better outcomes at higher costs which were considered cost-effective from a UK TPP. / Aventis
Kobelt et al., 2002 [84]Sweden / CUA of interferon beta-1bvs no treatment in SPMS (Societal) / Markov model with health states defined by EDSS stage simulating clinical progression over 10 years (3 month cycles) / QALYs
/ Direct medical and nonmedical costs;
Informal care;
Indirect costs / Clinical data were based on a three-year RCT [37] and the London, Ontario cohort [30].
Cost and utility data were derived from a cross-sectional postal survey of Swedish patients [66] / Interferon beta-1b was cost-effective compared to no treatment in SPMS from a Swedish societal perspective. / None stated
Nuijten et al., 2002 [85] UK / CUA of interferon beta-1bvs no preventative treatment in RRMS and SPMS (TPP) / Markov model with health states defined by EDSS stage, relapse and treatment compliance simulating lifetime clinical progression in three year cycles / QALYs
/ Direct medical and non medical costs;
Indirect costs;
Informal care / Clinical progression data were derived from RCTs [20, 26, 37, 86] and the London, Ontario natural history study [68]. Cost and utility data came from two UK studies [75, 81]. / Interferon beta-1b increased QALYs but was not cost-effective from the UK TPP. / None stated
Pozzilli et al., 2002 [87] / CEA of home based management vs hospital based supportive care in SP, PP and RRMS (TPP) / Economic evaluation conducted alongside a 12 month RCT / Functioning,
SF-36 / Direct medical and non medical care costs / Cost and outcome data were collected as part of the RCT. / Home care reduced direct health care costs with comparable outcomes and was potentially cost-effective / None stated
Phillips et al., 2001 [88]UK / CUA of interferon beta-1b vs standard care in RRMS (Societal) / Markov model with health states defined by EDSS stages simulated clinical progression over 20 years / QALYs
/ Direct medical and non medical;
Indirect costs;
Informal care / Clinical progression data were based on an RCT and follow up data [8, 20] and unpublished drug company data. Cost and utility data were based on a UK study [77]. / Interferon beta-1b increased QALYs and costs and was cost-effective from the UK societal perspective. / Schering
Brown et al., 2000 [89]Canada / CEA of interferon beta-1bvs conventional care in RRMS (TPP) / Epidemiological model simulated clinical progression over 40 years in cohorts of 1,000 females and 1,000 males. / Disability years avoided; relapses avoided / Direct medical costs / Clinical data were based on one extended RCT [8, 20] and a 25-year Swedish natural history cohort [31]. Cost data were based on a Canadian HTA [90]. / Cost per disability year avoided was quite high. Further research was recommended. / None stated
Kendrick et al., 2000 [91]UK / CUA of interferon beta-1bvs standard care in RRMS (TPP;
Societal) / Mathematical model which extrapolated RCT data to simulate clinical progression in EDSS defined disability and relapses over 20 years in annual cycles / QALYs / Direct medical and nonmedical costs;
Indirect costs;Informal care / Clinical data were based on an RCT [9].
Cost and utility data came from two UK studies [75, 81]. / The additional QALYs associated with interferon beta-1b were cost-effective from the UK TPP and cost saving from the societal perspective. / None stated
Kobelt et al., 2000 [92]Sweden / CUA of interferon beta-1bvs placebo in SPMS (Societal) / Markov model with health states defined by EDSS stage simulating clinical progression over 10 years (3 month cycles) / QALYs
/ Direct medical and nonmedical costs;
Informal care;
Indirect costs / Clinical data were based on active and placebo arms of a three year RCT [37].
Cost and utility data were derived from a cross-sectional postal survey of Swedish patients [66]. / Interferon beta-1b was cost-effective compared to no treatment in SPMS from a Swedish societal perspective. / Schering
Forbes et al., 1999 [93]UK / CUA of interferon beta-1b vs best practice in SPMS (TPP;
Societal in sensitivity analysis) / Decision analytic model simulated progression over 30 months in MS disability and relapse / QALYs; relapses avoided; Proportion of patients wheelchair dependent / Direct medical costs / Clinical data were based on an RCT[37] and hospital case records.
Cost data were based on a UK patient association survey [94] and local hospital reference costs for relapses.
Utilities were based on a patient survey (n=84) conducted by authors. / Interferon beta-1b achieved modest QALY gains at high cost and was not cost-effective from a UK TPP. / None stated
Parkin et al 2000[95]UK / CUA and CEA of interferon beta-1b vs standard management in RRMS (TPP) / Markov model with health states defined by EDSS stages simulated clinical progression over 5 years / QALYs; relapses avoided / Direct medical and social care costs / Clinical data were based on an RCT [8, 20] and the London Ontario cohort study [30, 68]. Cost and utility data were based on a patient survey and medical record checks conducted by the authors. / Interferon beta-1b achieved small but important QALY gains but at very high cost.
Improved outcome measurement needed. / None stated

References