Cost-utility and expected value of perfect information related to trabectedin in the treatment of metastatic soft-tissue sarcoma: the publicly funded comments explored
Authors: E.J. Soini
Journal: Annals of Oncology (2011)

I read with interest the comments by Blomqvist, Johansson and Tarkkanen [1.Blomqvist C. Johansson R. Tarkkanen M. Trabectedin in the treatment of metastatic soft-tissue sarcoma: cost-effectiveness and cost-utility are yet to be proved.Ann Oncol. 2011; 22: 988Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] (later, the commentators). Three key issues had been misunderstood concerning the article [2.Soini E.J. García San Andrés B. Joensuu T. Trabectedin in the treatment of metastatic soft tissue sarcoma: cost-effectiveness, cost-utility and value of information.Ann Oncol. 2011; 22: 215-223Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar], which reported the cost-effectiveness analysis (CEA) of trabectedin in the treatment of metastatic soft-tissue sarcoma (mSTS) after anthracycline/ifosfamide: means were mixed with medians [1.Blomqvist C. Johansson R. Tarkkanen M. Trabectedin in the treatment of metastatic soft-tissue sarcoma: cost-effectiveness and cost-utility are yet to be proved.Ann Oncol. 2011; 22: 988Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar], the CEA [2.Soini E.J. García San Andrés B. Joensuu T. Trabectedin in the treatment of metastatic soft tissue sarcoma: cost-effectiveness, cost-utility and value of information.Ann Oncol. 2011; 22: 215-223Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar] followed the official Finnish setting and guidance for health economic evaluations [3.Oikeusministeriön Julkaisuja no 201 Ohje Terveystaloudellisen Selvityksen Laatimiseksi. Edita, Helsinki, Finland2009Google Scholar] and the data presented [1.Blomqvist C. Johansson R. Tarkkanen M. Trabectedin in the treatment of metastatic soft-tissue sarcoma: cost-effectiveness and cost-utility are yet to be proved.Ann Oncol. 2011; 22: 988Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] was not comparable/related to the CEA [2.Soini E.J. García San Andrés B. Joensuu T. Trabectedin in the treatment of metastatic soft tissue sarcoma: cost-effectiveness, cost-utility and value of information.Ann Oncol. 2011; 22: 215-223Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar]. Ideally, survival times should be reported as exhaustive means together with Kaplan–Meier curves based on a large-enough randomized clinical trial, as this would enable an unbiased analysis of hazard ratios—the time-to-event summary statistic of choice [4.Liberati A. Altman D.G. Tetzlaff J. et al.The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.Ann Intern Med. 2009; 151: W65-W94Crossref PubMed Scopus (3900) Google Scholar]. However, most trials provide median survivals when all patients have not met the end points and the valid estimation of means based on the censored data could result in statistical modelling/estimation. While it is possible to carry out CEAs and indirect comparisons (ICs), including meta-analyses based on mean time-to-event data [5.Tierney J.F. Stewart L.A. Ghersi D. et al.Practical methods for incorporating summary time-to-event data into meta-analysis.Trials. 2007; 8: 16Crossref PubMed Scopus (3996) Google Scholar], medians are not a suitable basis for IC [4.Liberati A. Altman D.G. Tetzlaff J. et al.The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.Ann Intern Med. 2009; 151: W65-W94Crossref PubMed Scopus (3900) Google Scholar] or CEA. Firstly, the commentators [1.Blomqvist C. Johansson R. Tarkkanen M. Trabectedin in the treatment of metastatic soft-tissue sarcoma: cost-effectiveness and cost-utility are yet to be proved.Ann Oncol. 2011; 22: 988Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] mixed estimated means and censored medians, and Soini et al. [2.Soini E.J. García San Andrés B. Joensuu T. Trabectedin in the treatment of metastatic soft tissue sarcoma: cost-effectiveness, cost-utility and value of information.Ann Oncol. 2011; 22: 215-223Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar] do not mention median anywhere. The claim ‘ . . . the median survival benefit . . . ’ [1.Blomqvist C. Johansson R. Tarkkanen M. Trabectedin in the treatment of metastatic soft-tissue sarcoma: cost-effectiveness and cost-utility are yet to be proved.Ann Oncol. 2011; 22: 988Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] is not from the CEA (for example [2.Soini E.J. García San Andrés B. Joensuu T. Trabectedin in the treatment of metastatic soft tissue sarcoma: cost-effectiveness, cost-utility and value of information.Ann Oncol. 2011; 22: 215-223Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar] page 218 ‘ . . . mean overall survival . . . ’). The expected value of continuous distribution is mean. The setting [3.Oikeusministeriön Julkaisuja no 201 Ohje Terveystaloudellisen Selvityksen Laatimiseksi. Edita, Helsinki, Finland2009Google Scholar] appraises the use of expected values, and the costs and effectiveness should be reported in equivalent statistics. Thus, the mean survivals and mean costs were reported [2.Soini E.J. García San Andrés B. Joensuu T. Trabectedin in the treatment of metastatic soft tissue sarcoma: cost-effectiveness, cost-utility and value of information.Ann Oncol. 2011; 22: 215-223Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar]. Sometimes, parametric survival models can be used to estimate the mean survivals [6.Soini E.J. Martikainen J.A. Nousiainen T. Treatment of follicular non-Hodgkin’s lymphoma with or without rituximab: cost-effectiveness and value of information based on a 5-year follow-up.Ann Oncol. 2011; 22: 1189-1197Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar]. Medians are problematic if a relatively large number of patients have not met the end points of interest or, especially, if the survival distribution related to different treatments is skewed in a different magnitude. Thus, and due to the uncertainty of IC, linear interpolation with 20% cut-off was used to estimate the mean survivals (compare Appendix 1 in [2.Soini E.J. García San Andrés B. Joensuu T. Trabectedin in the treatment of metastatic soft tissue sarcoma: cost-effectiveness, cost-utility and value of information.Ann Oncol. 2011; 22: 215-223Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar]). Secondly, the CEA [2.Soini E.J. García San Andrés B. Joensuu T. Trabectedin in the treatment of metastatic soft tissue sarcoma: cost-effectiveness, cost-utility and value of information.Ann Oncol. 2011; 22: 215-223Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar] was carried out during the latter part of 2008 and followed the official setting [3.Oikeusministeriön Julkaisuja no 201 Ohje Terveystaloudellisen Selvityksen Laatimiseksi. Edita, Helsinki, Finland2009Google Scholar], which appraises comparison against the labelled/evident treatments. The postulated comparison against gemcitabine + docetaxel [1.Blomqvist C. Johansson R. Tarkkanen M. Trabectedin in the treatment of metastatic soft-tissue sarcoma: cost-effectiveness and cost-utility are yet to be proved.Ann Oncol. 2011; 22: 988Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] seems implausible based on the studies found in the PubMed in 2008 and March 2011. In 2008, the scientific evidence/labelling/authorization of gemcitabine + docetaxel in mSTS was not established. Still the efficacy evidence of gemcitabine + docetaxel is controversial [7.Patrikidou A. Domont J. Cioffi A. Le Cesne A. Treating soft tissue sarcomas with adjuvant chemotherapy.Curr Treat Options Oncol. 2011; 12: 21-31Crossref PubMed Scopus (46) Google Scholar], there can be number of safety issues, the reported trials are small/narrow/heterogeneous/enriched/multiple-line studies, and the patient populations [7.Patrikidou A. Domont J. Cioffi A. Le Cesne A. Treating soft tissue sarcomas with adjuvant chemotherapy.Curr Treat Options Oncol. 2011; 12: 21-31Crossref PubMed Scopus (46) Google Scholar, 8.Le Cesne A. Domont J. Gioffi A. et al.Mapping the literature: role of trabectedin as a new chemotherapy option in advanced pretreated soft tissue sarcoma.Drugs Today. 2009; 45: 403-421Crossref PubMed Scopus (15) Google Scholar, 9.Casali P.G. Blay J.Y. ESMO/CONTICANET/EUROBONET Consensus Panel of experts Soft tissue sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2010; 21: v198-v203Abstract Full Text Full Text PDF PubMed Scopus (224) Google Scholar, 10.Hensley M.L. Update on gemcitabine and docetaxel combination therapy for primary and metastatic sarcomas.Curr Opin Oncol. 2010; 22: 356-361Crossref PubMed Scopus (26) Google Scholar] are far from comparable to the patients in the CEA [2.Soini E.J. García San Andrés B. Joensuu T. Trabectedin in the treatment of metastatic soft tissue sarcoma: cost-effectiveness, cost-utility and value of information.Ann Oncol. 2011; 22: 215-223Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar]. Research will show how the treatments perform [11.Grimer R. Judson I. Peake D. Seddon B. Guidelines for the management of soft tissue sarcomas.Sarcoma. 2010; (506182)Google Scholar]. Finally, the commentators state that the data [1.Blomqvist C. Johansson R. Tarkkanen M. Trabectedin in the treatment of metastatic soft-tissue sarcoma: cost-effectiveness and cost-utility are yet to be proved.Ann Oncol. 2011; 22: 988Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] given in the background of the article [2.Soini E.J. García San Andrés B. Joensuu T. Trabectedin in the treatment of metastatic soft tissue sarcoma: cost-effectiveness, cost-utility and value of information.Ann Oncol. 2011; 22: 215-223Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar] raise issues. However, none of the points they [1.Blomqvist C. Johansson R. Tarkkanen M. Trabectedin in the treatment of metastatic soft-tissue sarcoma: cost-effectiveness and cost-utility are yet to be proved.Ann Oncol. 2011; 22: 988Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] make have any impact on the CEA results [2.Soini E.J. García San Andrés B. Joensuu T. Trabectedin in the treatment of metastatic soft tissue sarcoma: cost-effectiveness, cost-utility and value of information.Ann Oncol. 2011; 22: 215-223Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar]. If anything, their mixing references [1.Blomqvist C. Johansson R. Tarkkanen M. Trabectedin in the treatment of metastatic soft-tissue sarcoma: cost-effectiveness and cost-utility are yet to be proved.Ann Oncol. 2011; 22: 988Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] with different base populations raise issues. For example, the results [12.Fiore M. Casali P. Miceli R. et al.Prognostic effect of re-excision in adult soft tissue sarcoma of the extremity.Ann Surg Oncol. 2006; 13: 110-117Crossref PubMed Scopus (117) Google Scholar] referred to [1.Blomqvist C. Johansson R. Tarkkanen M. Trabectedin in the treatment of metastatic soft-tissue sarcoma: cost-effectiveness and cost-utility are yet to be proved.Ann Oncol. 2011; 22: 988Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] only apply for resectable/local extremity-STS and not to the base population of our CEA [2.Soini E.J. García San Andrés B. Joensuu T. Trabectedin in the treatment of metastatic soft tissue sarcoma: cost-effectiveness, cost-utility and value of information.Ann Oncol. 2011; 22: 215-223Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar]: the commentators [1.Blomqvist C. Johansson R. Tarkkanen M. Trabectedin in the treatment of metastatic soft-tissue sarcoma: cost-effectiveness and cost-utility are yet to be proved.Ann Oncol. 2011; 22: 988Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] exclude some 41% (597 versus 1013 [12.Fiore M. Casali P. Miceli R. et al.Prognostic effect of re-excision in adult soft tissue sarcoma of the extremity.Ann Surg Oncol. 2006; 13: 110-117Crossref PubMed Scopus (117) Google Scholar]) of the extremity-STS patients (with the highest risk for metastasis). Furthermore, the growth rates [1.Blomqvist C. Johansson R. Tarkkanen M. Trabectedin in the treatment of metastatic soft-tissue sarcoma: cost-effectiveness and cost-utility are yet to be proved.Ann Oncol. 2011; 22: 988Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] apply to pulmonary/lung metastases and are mainly from the 1980s. I agree that stable disease (SD) may be hard to capture. However, SD and progression states had an equivalent quality of life (EuroQoL 5D, 15D, Short Form 6D) value and the equivalent monthly costs after the comparator drugs had been administered [2.Soini E.J. García San Andrés B. Joensuu T. Trabectedin in the treatment of metastatic soft tissue sarcoma: cost-effectiveness, cost-utility and value of information.Ann Oncol. 2011; 22: 215-223Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar]: the exclusion of SD would not change the primary results. To sum up, the publicly funded comments ([1.Blomqvist C. Johansson R. Tarkkanen M. Trabectedin in the treatment of metastatic soft-tissue sarcoma: cost-effectiveness and cost-utility are yet to be proved.Ann Oncol. 2011; 22: 988Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] compare [13.Konsernihallinto Kilpailutetun Erityisvaltionosuusmäärärahan (EVO) Käytön Ohjeistus. Helsingin ja Uudenmaan Sairaanhoitopiiri, Helsinki, Finland2009Google Scholar] page 2) raised some of the common issues [6.Soini E.J. Martikainen J.A. Nousiainen T. Treatment of follicular non-Hodgkin’s lymphoma with or without rituximab: cost-effectiveness and value of information based on a 5-year follow-up.Ann Oncol. 2011; 22: 1189-1197Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 14.Soini E. Incremental or average cost-utility of routine cataract surgery?.Health Qual Life Outcomes. 2006; 4 ([comment]): 74Crossref PubMed Scopus (43) Google Scholar, 15.Laine J. Soini E. Martikainen J. Taloudellisen arvioinnin asema terveydenhuollon menetelmien käyttöönotossa. Esimerkkinä kansallinen rokotusohjelma.Fin Med J. 2010; 65: 1019-1024Google Scholar, 16.Soini E. Harvinaissairauksien taloudellinen arviointi: mitä päätöksien tueksi tulisi tuottaa?.Harvinaiset Sairaudet -lehti. 2011; 1: 26-31Google Scholar, 17.Laine J. Soini E. Martikainen J. Toiveena taloudellisen arvioinnin lisääntyvä hyödyntäminen.Fin Med J. 2010; 65: 1025-1026Google Scholar]. None.