Cost-Effectiveness of Surgery for Spinal Metastasis: A Systematic Review.

BackgroundTo insert a drug into the Hospital Pharmaceutical Formulary (HPF) it is necessary to carry out a drug-economic analysis. The health economics study offers analysis tools such as Net Monetary...

66 Background: This systematic review and meta-analysis compared incremental cost-effectiveness ratios (ICERs) of cancer drugs and their relationship with society’s willingness to pay (WTP) across different countries, scenarios and indications. Methods: We sought for cost-effectiveness studies in PubMed, Embase, Cochrane and LILACS published from December 2012 to December 2017. CAR-T cell therapies were excluded given short follow-up. We converted ICERs value and respective annualized 1time the Gross Domestic Product per capita (GDP) - used as a proxy for WTP threshold - into purchase-parity-power dollars (PPP) for better economic reality comparisons. Economics data came from the International Monetary Fund website. Characteristics studied in the distribution of ICERs values were compared using the Mann-Whitney or Kruskal-Wallis U-test with multiple comparison correction and simple linear regression. The chance of ICER being below the 1x GDP threshold was expressed as odds ratio and 95% confidence interval, calculated by logistic regression. Results: We retrieved 354 drug-versus-drug different assessments. PPPconversion increased median ICER of middle-income countries ($32k to $68k;P < 0.001). Median ICER was highest in USA ($154k), followed by other high-income countries ($76k; P < 0.001). In multiple regression, anti-VEGF (P < 0.001) and US-led (P = 0.03) studies had highest ICERs, while curative therapies (p = 0.02) had the lowest ones. 22% of studies were below the WTP bar, none of anti-VEGF, sipuleucel, anti-CD-30, castration-resistant, hepatocarcinoma, and renal cell ones. Immune checkpoint inhibition (OR 8.70; P = 0.045) and middle-income (OR 7.40; P < 0.001) studies were more likely above WTP, whereas curative therapies were more likely below WTP. Conclusions: Cancer therapies’ cost exceeding the WTPs is a worldwide pattern, with some factors related to ICER variation. These findings may foster better understanding and aid stakeholders deal with the global issue of high oncology care costs.

Cost Effectiveness of Achieving Targets of Low-Density Lipoprotein Particle Number Versus Low-Density Lipoprotein Cholesterol Level

PCN159 - The Cost–Effectiveness Of Regorafenib In The Treatment Of Patients With Metastatic Colorectal Cancer (Mcrc) Who Have Progressed After Standard Therapies In Turkey

Pioglitazone has been approved in Europe for oral combination therapy for type 2 diabetes mellitus. Along with other agents of the thiazolidinedione class, it has a novel intracellular mechanism of action. Clinical trials with pioglitazone have confirmed a strong product profile in terms of control of blood glucose and lipids. However, the drug acquisition cost for pioglitazone is greater than standard medications for type 2 diabetes. Long-term data regarding the cost effectiveness of pioglitazone-based combination therapy are not available. To evaluate, using a decision analysis model, the cost effectiveness of pioglitazone-based combination therapy compared with relevant alternative medications for the treatment of type 2 diabetes in Germany. This study compared the clinical effects and costs of pioglitazone 30 mg added to metformin in patients who failed metformin monotherapy and pioglitazone added to a sulphonylurea in patients who failed sulphonylurea monotherapy, with the most relevant treatment alternatives. A published and validated Markov model was adapted to reflect the management of type 2 diabetes. This simulated the number of severe complications occurring and the mean life expectancy of a diabetic cohort, which was based on the overweight group of the UK Prospective Diabetes Study at year 6 of follow-up. Drug treatment costs, other costs for general management of type 2 diabetes and the costs of complications were combined to compute overall lifetime treatment costs from the perspective of the German statutory healthcare system in 2002. Combination therapy with pioglitazone/metformin was associated with a higher life expectancy (15.2 years) relative to sulphonylurea/metformin (14.9 years) or acarbose/metformin (14.7 years). Likewise, pioglitazone/sulphonylurea (15.5 years) was superior to metformin/sulphonylurea (14.9 years) and acarbose/sulphonylurea (14.8 years). Undiscounted incremental cost-effectiveness ratios in comparison to the next best strategy were euro20,002 per life-year gained (LYG) for pioglitazone/metformin versus sulphonylurea/metformin, and euro8707 per LYG for pioglitazone/sulphonylurea versus metformin/sulphonylurea. After discounting costs and life expectancy at 5% per year, the incremental cost-effectiveness ratio was euro47 636 per LYG for pioglitazone/metformin versus sulphonylurea/metformin, and euro19 745 per LYG for pioglitazone/sulphonylurea versus metformin/sulphonylurea. In this model, with its underlying assumptions and data, combination therapy with pioglitazone increased life expectancy in overweight type 2 diabetes patients at acceptable cost compared with other well established medications in Germany. These findings should be re-evaluated as soon as additional evidence becomes available from the currently ongoing long-term clinical and economic studies.

To evaluate the cost-effectiveness of sotorasib versus docetaxel in non-small cell lung cancer (NSCLC) patients with KRASG12C mutation from the China and United States'social perspective. A Markov model that included three states (progression-free survival, post-progression survival, and death) was developed. Incremental cost-effectiveness ratio (ICER), quality-adjusted life-year (QALY), and incremental QALY were calculated for the two treatment strategies. One-way sensitivity analysis was used to investigate the factors that had a greater impact on the model results, and tornado diagrams were used to present the results. Probabilistic sensitivity analysis was performed with 1,000 Monte Carlo simulations. Assume distributions based on parameter types and randomly sample all parameter distributions each time., The results were presented as cost-effectiveness acceptable curves. This economic evaluation of data from the CodeBreak 200 randomized clinical trial. In China, sotorasib generated 0.44 QAYL with a total cost of $84372.59. Compared with docetaxel, the ICER value of sotorasib was $102701.84/QALY, which was higher than willingness to pay (WTP), so sotorasib had no economic advantage. In the US, sotorasib obtained 0.35 QALY more than docetaxel, ICER was $15,976.50/QALY, which was more than 1 WTP but less than 3 WTP, indicating that the increased cost of sotorasib was acceptable. One-way sensitivity analysis showed that the probability of sotorasib having economic benefits gradually increased when the cost of follow-up examination was reduced in China. And there was no influence on the conclusions within the range of changes in China. When the willingness to pay (WTP) exceeds $102,500, the probability of sotorasib having cost effect increases from 0% to 49%. Sotorasib had a cost effect from the perspective in the United States. However, sotorasib had no cost effect from the perspective in China, and only when the WTP exceeds $102,500, the probability of sotorasib having cost effect increases from 0% to 49%.

The competitive worldwide economic environment and ever-increasing costs of health care have created a setting in which understanding costs and making sure that we achieve good value in health care are paramount. One approach to seeking value is through the use of cost-effectiveness analysis. Although this science is now several decades old, it has been refined over the last several years, with increasingly sophisticated statistical and standardized methods.1,2 Is cost-effectiveness analysis useful? Does it help in medical decision making and in allocation of scarce resources? In the accompanying article, “Cost, Effectiveness, and Cost-Effectiveness” Diamond and Kaul3 argue that cost-effectiveness analysis is not a useful approach. Although we agree with many of the points that Diamond and Kaul raise, we do not agree with their conclusion. Cost-effectiveness analysis involves an assessment of both cost and effectiveness. The distribution of each needs to be understood. A cost-effectiveness analysis is only as valid as its underlying measures of effectiveness and cost, a discussion that is beyond the scope of this article. However, the methods to make these assessments vary considerably. There are standards for cost-effectiveness, but at times, perfectly adhering to these standards is not realistic, and compromises are often made that may be entirely scientifically legitimate.4 Cost-effectiveness is, by nature, incremental. Thus, it is necessary to look at the added costs compared with a control group. Selection of the appropriate control group is a challenge itself. At times, the appropriate control is placebo, and at other times, it is active therapy; the appropriate control is dependent on the clinical question being asked. However, when cost-effectiveness analysis is conducted using data from a clinical trial, the selection of the control group will not be a decision that the analyst can affect (at least after the trial has been completed). When …

The phase III NOTABLE trial has revealed that nimotuzumab plus gemcitabine achieves greater clinical benefit in the first-line treating K-Ras wild type locally advanced (LA) or metastatic pancreatic cancer (mPC), compared to gemcitabine. Hence, herein, we examined the cost-efficiency of introducing nimotuzumab to gemcitabine, relative to gemcitabinealone, in first-line K-Ras wild type LA or mPC therapy from a Chinese payer perspective. We generated an exhaustive decision-analytical Markov model using three exclusive health states to incorporate both clinical and economic consequences of nimotuzumab plus gemcitabine versus gemcitabine alone as first-line therapy patients with K-Ras wild type LA or mPC. Using a 10-year lifetime horizon, we assessed the total medical expenditure, quality-adjusted life years (QALYs), and incremental cost‒effectiveness ratio (ICER) as the primary surrogate outcomes of our model. Sensitivity analyses were conducted via alteration of internally tweakable parameters, and further subgroup analyses were conducted as needed. The overall health surrogate outcomes were 2.94 QALYs ($215,799) among patients with nimotuzumab plus gemcitabine and 1.83 QALYs ($86,039) among patients with gemcitabine alone (ICER value, $117,263/QALY; Incremental net health benefit [INHB] value, − 2.46/QALY). Based on our sensitivity analysis, among all parameters, progression-free survival (PFS) utility was of utmost importance, and it exerted a considerable impact on our model. The ICER consistently well exceeded the willingness-to-pay (WTP) threshold and negative INHBs were observed across all patient subcategories with zero alteration recorded as cost-effective in the subgroup analyses. Nimotuzumab plus gemcitabine, relative to gemcitabine alone, is not a cost-effective first-line treatment among patients with K-Ras wild type LA or mPC at the current prices offered in China.

Objective: To estimate the incremental cost-effectiveness ratio of different diagnostic schemes in newborns of mothers with a clinical history of infection with Toxoplasma gondii during the pregnancy, in order to increase the detected cases of congenital toxoplasmosis.Methods: We built a decision tree in TreeAge®, with identified infection cases as an outcome, in which three diagnostic strategies were considered: i) IgG, IgM and IgA together, in the face of negative results in IgA and IgM, Western Blot confirmation, and in the face of negative results in the all three tests but IgG positive, monthly monitoring of the newborn for six months and then every three months until the first year with with IgG; ii) IgM and IgA together, with Western -Blot confirmation for negatives; and iii) Western Blot. The costs were included from the perspective of the Colombian health system, expressed in Colombian pesos of 2010. The information of medicines costs was obtained from 2008 SISMED, and the value of the procedures was calculated by adjusting the values of the Manual of Rates ISS 2001 30% (1), these values were compared with information of the costs supplied by three EPS. The discount rate was 0%. Sensitivity analyzes were performed univariate and probabilistic cost-effectiveness. Univariate and probabilistic sensitivity analyzes were performed for costs and effectiveness.Results: The most effective and expensive strategy is i) (based on IgG, IgM and IgA), followed by ii) (based on IgM and IgA and iii) (Western Blot). The incremental cost effectiveness ratio (ICER) of strategy ii) against iii) is $ 6,189,871. This ICER is sensitive to the cost and the sensitivity of Western Blot, and the prevalence of congenital toxoplasmosis. The ICER of strategy i) against ii) is $ 65,529,979, a result that is sensitive to the prevalence of congenital toxoplasmosis, the sensitivity of the joint test of IgM and IgA and the sensitivity of Western Blot. The probabilistic sensitivity analysis shows that, for a willingness to pay (WTP) per correctly identified case below $6,5 million pesos, the strategy with higher probability of being cost effective is iii); between $6,5 million and $74 million pesos, is strategy ii); for a WTP above $74 million pesos, is strategy i).Conclusions: The cost-effective alternative for Colombia depends on the WTP for additional case of congenital toxoplasmosis detected. Below $6,5 million pesos, strategy iii) is more likely to be cost effective; between $6,5 million and $74 million pesos, strategy ii); and above $74 million pesos, strategy i). The WTP should take into account the cost for the society of neurological lesions and blindness caused by the infection. As the results are sensitive to the prevalence of the infection, it is important to advance in the knowledge of this value for different regions in the country.

Introduction: Strictures in Crohn's disease (CD) increase the likelihood of requiring surgery, which is costly and invasive. In the last two decades, endoscopic therapies including endoscopic balloon dilation (EBD) and endoscopic stricturotomy (ESt) have emerged as effective and less invasive therapies for CD strictures.1 ESt in particular is advantageous for longer, fibrotic strictures, or strictures adjacent to anatomic structures requiring precision, and has shown a high rate of surgery-free survival.2-4 We therefore assessed the cost-effectiveness of ESt as compared to surgical resection for CD strictures. Methods: A microsimulation state-transition model compared ESt to surgical resection for patients with primary or anastomotic CD strictures. Our primary outcome was quality-adjusted life years (QALYs) over ten years, and strategies were compared at a willingness to pay (WTP) of $100,000/QALY from a societal perspective. Costs (2022 $US) and ICERs were calculated. Deterministic 1-way and probabilistic analyses assessed model uncertainty. Results: The surgery strategy cost more than 2.5 times the endoscopic stricturotomy strategy, but resulted in nine higher QALYs per 100 persons (Table). Overall, surgery had an ICER of $308,787/QALY, making ESt more cost-effective. The median number of endoscopic stricturotomies was 4 in the ESt strategy and 0 in the surgery strategy; the median number of surgeries was 0 and 2 respectively. One-way sensitivity analyses showed that quality of life after ESt as compared to that after surgery, probabilities of requiring repeated interventions, and surgical mortality and cost were the most influential parameters in our model (Figure). Probabilistic sensitivity analyses favored ESt in 65.5% of iterations. Conclusion: Endoscopic stricturotomy is cost-effective for managing primary or anastomotic Crohn's disease strictures. Post-intervention quality of life and probabilities of requiring repeated interventions exert most influence on cost-effectiveness; the decision between ESt and surgery should be made considering patients' risk and quality of life preferences. 1. Lee KE et al. Dig Dis Sci. 2022 Mar 15.2. Lan N et al. Gastrointest Endosc. 2019 Aug;90:259-268.3. Zhang LJ et al. Gastroenterol Rep (Oxf). 2019 Oct;8:143-150. 4. Lan N et al. Inflamm Bowel Dis. 2018 Mar;24:897-907.Figure 1.: Tornado diagram showing main drivers (variables and sensitivity ranges) of the incremental cost-effectiveness ratio (ICER). †Multiplicative factor by which probability Tables are multiplied. Abbreviations: CD (Crohn's disease), ESt (Endoscopic stricturotomy), ICER (Incremental cost-effectiveness ratio), Max (Maximum), WTP (Willingness to pay) Table 1. - Base Case Cost-Effectiveness Analysis Results Cost ($) Incremental Cost ($) Effectiveness (QALY) Incremental Effectiveness (QALY) ICER ($/QALY) Endoscopic Stricturotomy 16,748 6.28 Resection Surgery 45,135 28,388 6.37 9 QALYs per 100 persons 308,787 Abbreviations: QALY (Quality-adjusted life year), ICER (Incremental cost-effectiveness ratio).

e20567 Background: Sotorasib was used for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer with KRASG12Cmutation who had received at least one systematic therapy, showing good antitumor activity and safety. However, it was unclear whether the high-cost sotorasib was cost-effective. Methods: A Markov model was developed to compare the lifetime cost and efficacy of sotorasib to treat non-small cell lung cancer with KRASG12C mutation from the CodeBreak 200 randomized placebo-controlled trial, which included 345 patients with previously treated non-small cell lung cancer with KRASG12C mutation. Incremental cost-effectiveness ratio(ICER), quality-adjusted life-year (QALY), incremental QALY were calculated for the 2 treatment strategies. One-way sensitivity analysis was used to investigate the factors that had a greater impact on the model results, and tornado diagram was used to verify the model stability, probabilistic sensitivity analysis was performed by Monte Carlo simulation, random factors were introduced into the model to simulate a certain number of large samples, and the results were presented as cost-effectiveness acceptable curves. Results: This economic evaluation of data from the CodeBreak 200 randomized trial. In China, sotorasib generated 0.44 QAYL with a total cost of $84372.59. Compwered with docetaxel, the ICER value of sotorasib was $102701.84/QALY, which was higher than WTP, so sotorasib had no economic advantage. In the US, sotorasib obtained 0.35 QALY more than docetaxel, ICER was $15,976.50 /QALY, which was low than WTP, indicating that the increased cost of sotorasib was acceptable. Conclusions: Sotorasib had cost effect from the perspective of the US. Howere, sotorasib had no cost effect from the perspective of China, and only when the willingness to pay(WTP) exceeds $102,500, the probability of sotorasib having cost effect increases from 0 to 49%.

Background: Trastuzumab has achieved widespread approval and funding across much of the developed world for metastatic and, later, adjuvant HER2/neu positive breast cancer. This success may be attributed to a favorable therapeutic index and incremental cost-effectiveness ratio (ICER). Has the success of trastuzumab been replicated by newer therapeutics? Methods: The societal marginal benefit gained from a new drug can be estimated by calculating the difference between the incremental quality-adjusted life-years gained (QALY) and the maximum willingness-to-pay (WTP) for the increase in health by society. A systematic review was employed to amass all English-language cost-effectiveness analyses (CEA) on small-molecule inhibitors and monoclonal antibodies approved for the treatment of solid malignancies. Searches of PubMed and EMBASE provided citations published between 1995 and February 5, 2012. Two reviewers each independently assessed the eligibility of all abstracts and subsequently abstracted data from published abstracts and manuscripts. CEAs comparing two experimental treatments to each other were excluded. Incremental costs and ICERs were converted from their native currency to U.S. dollars according to their average exchange-rates since publication. Results: Of the 1,576 citations identified, 60 were included in the final analysis. Tumor-types studied included breast, colorectal, gastric, gastrointestinal stromal, head and neck, non-small cell lung, ovarian, hepatocellular, and renal cancers, and pancreatic neuro-endocrine tumor. Studies originated from USA (14%), continental Europe (37%), England (12%), Canada (12%), Asia (11%), and Latin America (12%). Median WTP was $65,000 (range $30,000-$297,000). 92% of all CEAs included considered to be cost-effective by the CEA's authors. Trastuzumab was studied for breast cancer treatment by 13 CEAs in the adjuvant setting and by 3 CEAs in the metastatic setting. Trastuzumab is significantly more cost-effective than other targeted treatments (mean ICER $32,000 vs. $108,000, p = 0.001). 84% of trastuzumab studies found its ICER<$40,000, but only 32% of other CEAs met this threshold. Trastuzumab may be more cost-effective if employed in the adjuvant setting compared to the metastatic setting (mean ICER $18,000 vs. $29,000, p = 0.12). After trastuzumab, the most favorable treatments by ICER were imatinib for GIST, cetuximab with radiation for head and neck cancer, and sorafenib for hepatocellular carcinoma. There was no apparent relationship between the country of origin in which the CEA was conducted and the ICER estimate. Conclusion: Trastuzumab represents a significant achievement in clinical medicine and also provides greater value than newer targeted chemotherapy, in general. Newer therapeutics are being priced close to the maximum WTP of society. Adjuvant therapy may prove more cost-effective than therapy in the metastatic setting. Unless better pricing arrangements can be made or future therapies produce greater incremental clinical benefits for the same cost, it seems unlikely that the societal success of trastuzumab will be replicated. However, this analysis assumes that maximizing societal health, not profit, is of primary concern. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-15-02.

PHP150 Searching for a Threshold in Hungary

The ARROW study demonstrated favorable clinical efficacy and safety of pralsetinib (PRL) in treating rearranged during transfection (RET) fusion positive non-small cell lung cancer (NSCLC) in clinical trials. However, due to the high cost of PRL, evaluating its cost-effective characteristics is crucial. Currently, there has been no cost-effectiveness analysis specifically for PRL. Therefore, the aim of this study was to assess the cost-effectiveness characteristics of using PRL as a first-line therapy versus reserving it until the second-line versus solely relying on chemotherapy from the perspective of payers in the United States. A Markov model was developed to evaluate the 3 above mentioned PRL-based treatment strategies. Clinical data from the ARROW trial were incorporated into the model, and costs and utilities values were obtained through previously published literature and public databases, with both being discounted at 3% per year. To ensure the robustness of the model, both probabilistic and univariate sensitivity analyses were performed. The primary endpoints included quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Compared to chemotherapy, the use of PRL in the first-line therapy resulted in an additional 0.07 QALYs at a cost of $133,561, with an ICER of $1,353,849.65 per QALY. Similarly, when used in the second-line setting, PRL led to an additional 0.09 QALYs at a cost of $92,797, with an ICER of $559,232.70 per QALY. The ICER value in the first-line or in the second-line therapy strategy was higher than the US willingness-to-pay (WTP) threshold of $150,000 per QALY. Univariable sensitivity analyses revealed that the cost of PRL and the utility of progressed disease had the most significant impact on the ICER. To be considered cost-effective at a WTP threshold of $150,000 per QALY, the cost of PRL would need to be reduced by 71.34% in first-line treatment or 84.49% in second-line treatment. Based on current pricing, neither PRL as first-line nor second-line therapy was found to be cost-effective for patients with RET fusion-positive advanced NSCLC compared to chemotherapy. Reserving PRL until second-line therapy may be a compromise approach to maintaining control over healthcare expenses yet still achieving favorable clinical outcomes.

Cost effectiveness of immune checkpoint inhibitors for treatment of Hepatocellular Carcinoma: A systematic review and Meta-analysis