A Multiple Treatment Comparison of Eleven Disease-Modifying Drugs Used for Multiple Sclerosis.

BACKGROUND: Several disease-modifying drug therapies are available for the treatment of multiple sclerosis (MS). To ensure the most appropriate MS management, we assessed the effectiveness and cost-effectiveness of the disease-modifying medicines used for MS. METHODS: We conducted a systematic review including 11 disease-modifying drugs used for treatment of adult patients diagnosed with relapsing-remitting MS. We performed a network meta-analysis using both direct and indirect evidence. We examined the endpoints, annual relapse, disability progression, mortality, serious adverse events and withdrawal from the study due to adverse events. Cost-effectiveness was assessed by developing a decision model. The model calculated costs and quality-adjusted life years (QALYs) with different treatment strategies. Uncertainties in the parameter values were explored with a probabilistic sensitivity analysis and several scenario analyses. RESULTS: Alemtuzumab 12 mg was the most effective against annual relapse (high quality evidence). For disability progression, dimethyl fumarate 240 mg and fingolimod 0.5 mg and 1.25 mg were more effective treatment alternatives (high quality evidence). For withdrawal due to adverse events, the conclusion is unclear due to the low quality of the available evidence. Peg-interferon beta-1a was associated with more adverse events (than the other treatments). None of the examined treatments had an effect on overall mortality compared to placebo. The economic analysis indicated that alemtuzumab was more effective in terms of QALYs and less costly than the other treatment alternatives. Discarding alemtuzumab, three treatment alternatives (interferon beta-1b (Extavia), peg-interferon beta-1a and natalizumab) could be considered cost-effective depending on the willingness-to-pay (WTP) threshold. Assuming a WTP below EUR 111,690 per QALY, interferon beta-1b (Extavia) was approximately 36% likely to be the most cost-effective treatment, followed by peg-interferon beta-1a (approximately 34% likely). CONCLUSIONS: Our results showed that alemtuzumab can be considered as more effective and less costly than the other treatment alternatives. There is a substantial potential cost saving if more patients start on the more effective and less costly treatment alternatives.

Multiple treatment comparison of seven new drugs for patients with advanced malignant melanoma: a systematic review and health economic decision model in a Norwegian setting.

OBJECTIVE: To assess the relative effectiveness and cost-effectiveness of seven new drugs (cobimetinib, dabrafenib, ipilimumab, nivolumab, pembrolizumab, trametinib and vemurafenib) used for treatment of patients with advanced malignant melanoma in the Norwegian setting. DESIGN: A multiple technology assessment. PATIENTS: Patients with advanced malignant melanoma aged 18 or older. DATA SOURCES: A systematic search for randomised controlled trials in relevant bibliographic databases. METHODS: We performed network meta-analyses using both direct and indirect evidence with dacarbazine as a common comparator. We ranked the different treatments in terms of their likelihood of leading to the best results for each endpoint. The cost-utility analysis was based on a probabilistic discrete-time Markov cohort model. The model calculated the costs and quality-adjusted life years (QALYs) with different treatment strategies from a healthcare perspective. Sensitivity analysis was performed by means of Monte Carlo simulation. RESULTS: Monotherapies with a programmed cell death 1 (PD-1) immune-checkpoint-inhibitor had a higher probability of good performance for overall survival than monotherapies with ipilimumab or BRAF/MEK inhibitors. The combination treatments had all similar levels of effectiveness to the PD-1 immune-checkpoint-inhibitors.PD-1 immune-checkpoint-inhibitors are more effective and more costly compared with ipilimumab in monotherapy. Nivolumab in combination with ipilimumab had higher costs and the same level of effectiveness as the PD-1 immune-checkpoint-inhibitors in monotherapy.BRAF/MEK inhibitor combinations (dabrafenib and trametinib or vemurafenib and cobimetinib) had both similar effectiveness and cost-effectiveness; however, the combination therapies are more likely to give higher quality adjusted life year gains than BRAF or MEK inhibitor monotherapies, but to a higher cost. CONCLUSIONS: None of the drugs investigated can be considered cost-effective at what has normally been considered a reasonable willingness-to-pay (WTP) in Norway. Price reductions (from the official list prices) in the region of 63%-84% would be necessary for these drugs to be cost-effective at a WTP of €55 850 per QALY.

More Use of Peritoneal Dialysis Gives Significant Savings: A Systematic Review and Health Economic Decision Model.

BACKGROUND: Patients with end-stage renal disease (ESRD) are in need of renal replacement therapy as dialysis and/or transplantation. The prevalence of ESRD and, thus, the need for dialysis are constantly growing. The dialysis modalities are either peritoneal performed at home or hemodialysis (HD) performed in-center (hospital or satellite) or home. We examined effectiveness and cost-effectiveness of HD performed at different locations (hospital, satellite, and home) and peritoneal dialysis (PD) at home in the Norwegian setting. METHODS: We conducted a systematic review for patients above 18 years with end-stage renal failure requiring dialysis in several databases and performed several meta-analyses of existing literature. Mortality and major complications that required were our main clinical outcomes. The quality of the evidence for each outcome was evaluated using GRADE. Cost-effectiveness was assessed by developing a probabilistic Markov model. The analysis was carried out from a societal perspective, and effects were expressed in quality-adjusted life-years. Uncertainties in the base-case parameter values were explored with a probabilistic sensitivity analysis. Scenario analyses were conducted by increasing the proportion of patients receiving PD with a corresponding reduction in HD patients in-center both for Norway and Europian Union. We assumed an annual growth rate of 4% in the number of dialysis patients, and a relative distribution between PD and HD in-center of 30% and 70%, respectively. RESULTS: From a societal perspective and over a 5-year time horizon, PD was the most cost-effective dialysis alternative. We found no significant difference in mortality between peritoneal and HD modalities. Our scenario analyses showed that a shift toward more patients on PD (as a first choice) with a corresponding reduction in HD in-center gave a saving over a 5-year period of 32 and 10,623 million EURO, respectively, for Norway and the European Union. CONCLUSIONS: PD was the most cost-effective dialysis alternative and was comparable with HD regarding efficacy outcomes. There are significant saving potentials if more end-stage renal patients are started on PD instead of HD.

Estimating QALY gains in applied studies: a review of cost-utility analyses published in 2010.

Reimbursement agencies in several countries now require health outcomes to be measured in terms of quality-adjusted life-years (QALYs), leading to an immense increase in publications reporting QALY gains. However, there is a growing concern that the various 'multi-attribute utility' (MAU) instruments designed to measure the Q in the QALY yield disparate values, implying that results from different instruments are incommensurable. By reviewing cost-utility analyses published in 2010, we aim to contribute to improved knowledge on how QALYs are currently calculated in applied analyses; how transparently QALY measurement is presented; and how large the expected incremental QALY gains are. We searched Embase, MEDLINE and NHS EED for all cost-utility analyses published in 2010. All analyses that had estimated QALYs gained from health interventions were included. Of the 370 studies included in this review, 48% were pharmacoeconomic evaluations. Active comparators were used in 71% of studies. The median incremental QALY gain was 0.06, which translates to 3 weeks in best imaginable health. The EQ-5D-3L is the dominant instrument used. However, reporting of how QALY gains are estimated is generally inadequate. In 55% of the studies there was no reference to which MAU instrument or direct valuation method QALY data came from. The methods used for estimating expected QALY gains are not transparently reported in published papers. Given the wide variation in utility scores that different methodologies may assign to an identical health state, it is important for journal editors to require a more transparent way of reporting the estimation of incremental QALY gains.

New anticoagulants as thromboprophylaxis after total hip or knee replacement.

OBJECTIVES: Due to a high risk of thromboembolism in patients undergoing major orthopedic surgery, it has become standard practice to give thromboprophylactic treatment. We assessed the relative efficacy and cost-effectiveness of two new oral anticoagulants, rivaroxaban and dabigatran, relative to subcutaneous enoxaparin for the prevention of thromboembolism after total hip replacement (THR) and total knee replacement surgery (TKR). METHODS: We conducted a systematic review of the literature to assess efficacy and safety, and evaluated quality of documentation using GRADE. Cost-effectiveness was assessed by developing a decision model. The model combined two modules; a decision tree for the short-term prophylaxis and a Markov model for the long-term complications and survival gain. RESULTS: For rivaroxaban compared with enoxaparin, we found statistically significant decreases in deep vein thrombosis, but also a trend toward increased risk of major bleeding. For mortality and pulmonary embolism there were no statistically significant differences between the treatments. We did not find statistically significant differences between dabigatran and enoxaparin for our efficacy and safety outcomes. Assuming a willingness to pay of EUR62,500 per QALY, rivaroxaban following THR had a probability of 38 percent, and enoxaparin following TKR had a probability of 34 percent of being cost-effective. Clinical efficacy had the greatest impact on decision uncertainty. CONCLUSIONS: Dabigatran and rivaroxaban are comparable with enoxaparin following THR and TKR regarding the efficacy and safety outcomes. However, there is great uncertainty regarding which strategy is the most cost-effective. More research on clinical efficacy of rivaroxaban and dabigatran is likely to change our results.

Cost effectiveness of open versus laparoscopic living-donor nephrectomy.

BACKGROUND: Kidney transplantation is an essential part of care for patients with end-stage renal disease. The introduction of laparoscopic living-donor nephrectomy (LLDN) has made live donation more advantageous because of less postoperative pain, earlier return to normal activities, and a consequent potential to increase the pool of kidney donors. However, the cost effectiveness of LLDN remains unknown. The aim of this study was to explore the health and cost consequences of replacing open-donor nephrectomy by LLDN. METHODS: Kidney donors were randomized to laparoscopic (n=63) or open surgery (n=59). We obtained data on operating time, personnel costs, length of stay, cost of analgesic, disposable instruments and complications, and indirect costs. Quality of life was captured before the operation and at 1, 6, and 12 months postdonation by means of short form-36. The scores were translated into utilities by means of Brazier's 6D algorithm. RESULTS: The cost per patient was U.S. $55,292 with laparoscopic and U.S. $29,886 with open surgery. The greatest cost difference was in costs attributed to complications (U.S. $33,162 vs. U.S. $4,573). The 1-year quality-adjusted life years (QALYs) were 0.780 and 0.765, respectively for laparoscopic and open surgery. This implies a cost of U.S. $1,693,733 per QALY at 12 months follow-up. Sensitivity analyses indicated that the cost of the major complications in the laparoscopic group and magnitude of QALY gain had the greatest impact on cost effectiveness. CONCLUSIONS: The LLDN is an attractive alternative because it, in general, entails less postoperative pain than open surgery, but it is cost effective only with relatively low rates of complications.