Jennifer G. Gaultney

Real‐world health care costs of relapsed/refractory multiple myeloma during the era of novel cancer agents

What is known and objective:  High costs of novel agents increasingly put pressure on limited healthcare budgets. Demonstration of their real‐world costs and cost‐effectiveness is often required for reimbursement. However, few published economic evaluations of novel agents for multiple myeloma exist. Moreover, existing cost analyses were heavily based on conventionally treated patients. We investigated real‐world health care costs of relapsed/refractory multiple myeloma in Dutch daily practice.

Application of cost–effectiveness analysis to demonstrate the potential value of companion diagnostics in chronic myeloid leukemia

AIM A cost-effectiveness analysis was performed to assess the potential value of companion diagnostics in supporting treatment decisions for dasatinib and nilotinib in chronic myeloid leukemia. MATERIALS & METHODS A decision model was developed, and model inputs were taken from the literature and publicly available sources. The perspective of the healthcare sector in the Netherlands was used. Sensitivity and scenario analyses were performed to assess uncertainty in the results. RESULTS Companion diagnostics could improve health and reduce costs, despite the estimates being uncertain owing to limited evidence for comparative effectiveness between dasatinib and nilotinib. The results were sensitive to the cost of treatment, utility of progression and progression-free survival. CONCLUSION This case demonstrates the use of cost-effectiveness analysis at an early stage of health technology assessment to generate economic evidence for the use of companion diagnostics in treatment decisions and to support decision-making for their development.

Critical review of economic evaluations in multiple myeloma: An overview of the economic evidence and quality of the methodology

Continued expansion in the availability of costly alternative therapies in multiple myeloma will enhance the role of economic evaluations in reimbursement decisions and amendments to the treatment guidelines. The quality of economic evaluations should be taken into account by clinicians involved in decision-making. A systematic review and critique of the methodology was performed to assess the trends and quality in economic evaluations in multiple myeloma to date. A literature search was conducted to identify full economic evaluations in multiple myeloma as of December 2009. Details of the economic evaluation methods applied were extracted. Each study underwent a quality assessment based on the Drummond checklist for appraisal of high-quality economic evaluations in health care. Eighteen published economic evaluations were identified. Stem cell transplantation in combination with intensive chemotherapy has been demonstrated to be cost-effective, while interferon alpha is generally ineffective at additional costs. Evaluations have become less frequent in the last decade, especially for newer therapies despite their important contribution to improvements in outcomes. The quality of the methodology applied and its documentation can be improved in many aspects. As users of the results of economic evaluations, clinicians involved in guiding decision-making should be critical of the quality of economic evaluations in multiple myeloma. To ensure access to and identification of high-quality studies, researchers conducting economic evaluations of future advances should strive towards evaluations that fulfil the Drummond criteria and are properly documented.

Practical feasibility of outcomes research in oncology: lessons learned in assessing drug use and cost-effectiveness in The Netherlands.

OBJECTIVE To investigate the practical feasibility to develop evidence on drug use and cost-effectiveness in oncology practice. PATIENTS AND METHODS Feasibility was examined using three Dutch case studies. Each case study investigated the degree of appropriate drug use and its incremental cost-effectiveness. Detailed data were retrospectively collected from hospital records. In total, 391, 316 and 139 patients with stage III colon cancer, metastatic colorectal cancer and multiple myeloma were included in 19, 29 and 42 hospitals, respectively. RESULTS The methods used in the case studies were feasible to develop evidence on some aspects of drug use including types of treatments used, dosages, dose modifications and healthcare costs. Aspects such as baseline patient characteristics, reasons to start or stop a treatment and treatment effects were less feasible because of missing values. Despite difficulties to correct for confounding by indication, it was possible to estimate incremental cost-effectiveness by synthesising evidence in two of the three case studies. CONCLUSION It is possible to generate evidence about drug use and cost-effectiveness in oncology practice to facilitate informed decision-making by both payers and physicians. This can improve quality of care and enhance the efficient allocation of resources. However, the optimal approach differs between drugs and their indications. Generating high-quality evidence requires active interdisciplinary collaboration. Patient registries can facilitate data collection but cannot resolve all issues. In most circumstances it is inevitable to use data-synthesis to obtain valid incremental cost-effectiveness estimates, but for some indications it will not be feasible to derive a valid and precise estimate.

Novel anticancer agents for multiple myeloma: a review of the evidence for their therapeutic and economic value

Recent advances in oncology treatment have improved patient outcomes at the expense of increasing healthcare costs. The indication multiple myeloma is especially characterized by a recent and continuing flood of expensive novel agents. A review encompassing all elements necessary to perform an economic evaluation of novel agents for multiple myeloma was conducted for thalidomide, bortezomib and lenalidomide. Improvements in efficacy have led to a switch from conventional therapy to novel agents as standard therapy. Incremental cost–effectiveness ratios for novel agents alone or in combination with conventional agents were generally regarded to be within acceptable ranges. Conflicting results were reported for the incremental cost–effectiveness of bortezomib versus lenalidomide, as unresolved questions remain regarding their comparative effectiveness. Future economic evaluations will require an assessment of the cost–effectiveness of these agents in terms of sequence within the treatment paradigm and in combination with one another.

Efficient Allocation of Novel Agents in Multiple Myeloma: A Work in Progress

This commentary examines key questions regarding the use of novel agents in multiple myeloma, addressed by two articles in this months issue.

Policymaker, Please Consider Your Needs Carefully: Does Outcomes Research in Relapsed or Refractory Multiple Myeloma Reduce Policymaker Uncertainty Regarding Value for Money of Bortezomib?

INTRODUCTION Dutch policy regulations require outcomes research for the assessment of appropriate drug use and cost-effectiveness after 4 years of temporary reimbursement. We investigated whether outcomes research reduced policymaker uncertainty regarding the question whether the costs are worth public funding. METHODS Our cohort study included 139 patients with relapsed/refractory multiple myeloma who were treated outside of a clinical study; 72 received bortezomib and 67 did not receive bortezomib. Detailed data were retrospectively collected from medical records in 38% of Dutch hospitals. RESULTS All patients received second-line treatment; 65%, 40%, and 14%, received three, four, or five or more lines of therapy. Neither a specific treatment sequence nor an appropriate comparator could be identified because of large variation in regimes. Kaplan-Meier curves showed an increased overall survival (mean [median] 29.5 [33.2] vs. 28.0 [21.6] months) for patients treated with bortezomib (Wilcoxon P = 0.01). Total mean costs were €81,626 (range €17,793-€229,783) and €52,760 (range €748-€179,571) for patients receiving bortezomib and patients not receiving bortezomib, respectively. Patients treated with bortezomib, however, were not comparable to other patients despite attempts to correct for confounding. Therefore, it was impossible to develop a feasible model to obtain a valid incremental cost-effectiveness estimate. CONCLUSIONS It was possible to develop evidence on bortezomibs use, effects, and costs in everyday practice. Much uncertainty, however, remained regarding its cost-effectiveness. Policymakers should carefully consider whether outcomes research sufficiently decreases uncertainty or whether other options (e.g., finance- and/or outcomes-based risk-sharing arrangements) are more appropriate to ensure sufficient value for money of expensive drugs.

Experience with outcomes research into the real-world effectiveness of novel therapies in Dutch daily practice from the context of conditional reimbursement

Policymakers more often request outcomes research for expensive therapies to help resolve uncertainty of their health benefits and budget impact at reimbursement. Given the limitations of observational data, we assessed its usefulness in evaluating clinical outcomes for bortezomib in advanced multiple myeloma patients. Data were retrospectively collected from patients included in the pivotal Assessment of Proteasome Inhibition for Extending Remissions trial (APEX; n=333) and two groups of daily practice patients treated with bortezomib following progression from upfront therapy (n=201): real-world patients treated as of May 2009 (RW-1; n=72) and June 2012 (RW-2; n=129). Prognosis, treatment, and effectiveness were compared. Outcomes research was useful for policymakers for addressing to whom and how bortezomib was administered in daily practice. It was limited however in generating robust evidence on real-world safety and effectiveness. The quality of real-world evidence on effectiveness was low due to missing data in patient charts, existing treatment variation and the dynamics in care during the novel drugs initial market uptake period. Policymakers requesting real-world evidence on clinical outcomes for reimbursement decisions should be aware of these limitations and advised to carefully consider beforehand the type of evidence that best addresses their needs for the re-assessment phase.

CN7 TREATMENT VARIATION COMPLICATES REAL-WORLD PHARMACOECONOMICS: DAILY CLINICAL PRACTICE OF BORTEZOMIB IN RELAPSED OR REFRACTORY MULTIPLE MYELOMA

patients. A typical PCU admits patients in the final phase of life. A high quality of care by a multi disciplinary team (including nurses, physicians, psychologists, music therapy, physiotherapy and others) results in substantial costs (recent survey in German PCUs: on average ~a400/day). The average length of stay is in the range of 11–15 days, the proportion of discharged patients varies between 40–70%, for the remaining patients the admission ends not unexpectedly with the death of the patients. The gain in utility close to death is difficult to estimate, but even high assumptions (e.g. 0,5) result in costs for QALYs, which are unexpectedly high. Scenario 1: 14, 0.5, 30, 0.5, 400, 192455 a; scenario 2: 14, 0.7,30, 0.5, 400, 172545 a; scenario 3: 14, 0.5, 30, 0.3, 400, 320758 a; scenario 4: 10, 0.5, 30, 0.5, 400, 182500 a for length of stay (d), proportion surviving, survival after discharge (d), gain in utility, cost/day, resulting cost / QALY. People experiencing the sheer necessity of palliative care for a death with dignity may use these data as an argument against the QALY concept. Only by including longterm changes e.g. in the utility gain experienced by relatives (small gains over a long period in several persons, e.g. by avoiding pathological grief) the model results in costs/QALY which seem acceptable.

Potential therapeutic and economic value of risk-stratified treatment as initial treatment of multiple myeloma in Europe

Biomarkers associated with prognosis in multiple myeloma (MM) can be used to stratify patients into risk categories. An attractive alternative to uniform treatment (UT), risk-stratified treatment (RST) is proposed where high-risk patients receive bortezomib-based regimens while standard-risk patients receive alternative less costly regimens. An early Markov-type decision analytic model evaluated the potential therapeutic and economic value of different RST strategies compared with UT in MM patients in key European countries. Results suggest RST strategies were both cheaper and more effective than UT across all countries, with the molecular marker-only strategy RST-SKY92 producing maximum health gains (0.031-0.039 QALYs). The conclusions remained consistent in the univariate sensitivity analyses. These findings should encourage stakeholders to support the adoption of RST approaches in MM.