The economic impact of tobacco smoking and secondhand smoke exposure in Jordan: estimating the direct and indirect costs.

Aim: To quantify the economic burden associated with tobacco smoking among smokers aged 30-69 years, and second-hand smokers (SHS) aged 15-69 years in Jordan.Materials and Methods: A prevalence-based analysis was conducted in alignment with the Economics of Tobacco Toolkit developed by the WHO. The time-horizon of the analysis was one year (2019). Direct and indirect costs were estimated using data from the 2019 Global Burden of Diseases study. The analysis targeted the Jordanian population of smokers aged 30-69 years, and SHS aged 15-69 years. Adjustments were applied for age, gender, and smoking-related diseases. Direct costs were estimated using the smoking-attributable fraction (SAF) and national health expenditures. Indirect costs were divided into morbidity and mortality components. A discount rate of 3.0% and an annual productivity growth rate of 1.0% were assumed in modelling future economic losses. A sensitivity analysis was conducted on the lower and upper estimates of data used in this study.Results: The cost of tobacco smoking and SHS exposure was estimated at US$2,108 million (95% confidence interval [CI]=US$2,003 million-US$2,245 million). This represents 4.7% (95%CI = 4.5%-5.0%) of national gross domestic product (GDP). Direct costs accounted for 3.1% of national GDP. Tobacco smoking accounted for 85.0% of total cost and SHS exposure accounted for 15.0% of total cost. Direct costs accounted for 67.0% of total cost, while indirect morbidity and mortality costs accounted for 9.0% and 24.0% of total cost, respectively. Non-communicable diseases accounted for 96.0% of total direct costs compared to communicable diseases (4.0% of total direct costs).Conclusions: Smoking cessation interventions such as raising taxes on cigarettes, protecting people from tobacco smoke, warning labels, plain packaging, and bans on advertising, are crucial for controlling national expenditures for treating smoking-related diseases and for averting future economic losses.

In this work, we aimed to calculate the annual economic impact of tobacco smoking in Jordan in 2019. We used the World Health Organization toolkit methodology to estimate both the direct and indirect costs associated with smoking nationally. Our focus was on Jordanian smokers aged 30-69 years and people exposed to second-hand smoke aged 15-69 years.Direct costs were calculated using epidemiological data on the proportion of health expenditures attributable to smoking and the national health expenditures. Indirect costs were divided into two components: morbidity and mortality. We also projected future economic losses, assuming a 3.0% discount rate and a 1.0% annual growth rate of productivity.Our study estimated that the cost of smoking and exposure to second-hand smoke was US$2,108 million (US$2,003 million-US$2,245 million), which accounted for 4.7% (4.5%-5.0) of Jordan's gross domestic product. The majority of the cost (85.0%) was due to direct smoking, while 15.0% was due to exposure to second-hand smoke. Direct costs made up 67.0% of the total cost, while the costs related to morbidity and mortality accounted for 9.0% and 24.0% of the total cost, respectively.In conclusion, our study emphasized that tobacco smoking has a significant economic impact on Jordan. Therefore, it is crucial to implement effective smoking cessation programs, such as enforcing existing anti-tobacco policies and raising taxes. These measures can help control national expenditures for treating smoking-related diseases and prevent future economic losses.

The status and preparation for the next decade of biosimilars in the Middle Eastern and North African region.

INTRODUCTION: Little is known about the status and the future potential of biosimilars in the Middle East and North Africa (MENA) region. AREAS COVERED: This perspective provides insights into the current regulatory landscape of some MENA countries, currently available biosimilars, the potential of biosimilars in the next decade, and challenges to overcome. EXPERT OPINION: Given the economic and demographic heterogeneity across the MENA countries, biosimilars could reduce significant economic unmet needs in these countries. In the next decade, biosimilars may witness higher approval rates and market share over their originators in the MENA countries. We argue that the regulatory bodies in the MENA countries should adopt the new policies of the FDA, the EMA, and the WHO, that aim to ease the biosimilar approval process. These policies are to adopt technology in the process of approval; engage health technology assessment bodies in price assessment; provide educational materials to increase awareness among providers, patients, and payers. Further, MENA countries should upgrade the external-reference pricing systems to more sophisticated ones that consider the heterogeneity in economics and needs.

Cost-efficiency analysis and expanded treatment access modeling of conversion to rituximab biosimilars from reference rituximab in Jordan.

AIM: To assess the cost-efficiency and expanded access of three rituximab biosimilars versus the reference rituximab from the perspective of the Jordanian national health payer. METHODS: A 1-year cost-efficiency and expanded access model of conversion from reference rituximab (Mabthera) to the approved biosimilars (Truxima, Rixathon, and Tromax) to assess five metrics: total annual cost to treat a hypothetical patient; head-to-head cost comparison; changes in patients' access to rituximab; number-needed-to-convert (NNC) to provide an additional 10 patients access to a rituximab treatment; and relative amount of Jordanian Dinar (JOD) spent on rituximab options. The model included rituximab doses at 100 mg/10 ml and 500 mg/50 ml and considered both cost-saving and cost-wastage scenarios. Costs of treatments were based on the fiscal year 2022 tender prices received by the Joint Procurement Department (JPD). RESULTS: Rixathon was associated with the lowest average annual cost per patient (JOD2,860) across all six indications among all rituximab comparators, followed by Truxima (JOD4,240), Tromax (JOD4,365) and reference Mabthera (JOD11,431). The highest percentage of patient access to rituximab treatment (321%) was achieved when switching patients from Mabthera to Rixathon in the RA and PV indications. At four patients, Rixathon was associated with the lowest NNC to provide an additional 10 patients access to rituximab treatment. For each JOD1 spent on Rixathon, an additional JOD3.21 must be spent on Mabthera, an additional JOD0.55 on Tromax, and an additional JOD0.53 on Truxima. CONCLUSION: Rituximab biosimilars were associated with cost savings in all approved indications in Jordan compared to reference rituximab. Rixathon was associated with the lowest annual cost, the highest percentage of expanded patient access for all six indications, and the lowest NNC providing 10 additional patients with access.

Economic Evaluation of Three BRAF + MEK Inhibitors for the Treatment of Advanced Unresectable Melanoma With BRAF Mutation From a US Payer Perspective.

BACKGROUND: The combinations of BRAF + MEK inhibitors-encorafenib (ENC) + binimetinib (BIN), cobimetinib (COB) + vemurafenib (VEM), and dabrafenib (DAB) + trametinib (TRA)-are recommended for the treatment of BRAF-mutated advanced melanoma. OBJECTIVE: To assess the cost-effectiveness and cost-utility of ENC + BIN versus COB + VEM versus DAB + TRA from a US payer perspective. METHODS: A Markov model was constructed to simulate a hypothetical cohort over a time horizon of 10 years. The overall survival (OS) and progression-free survival (PFS) curves were independently digitized from a randomized controlled trial for ENC + BIN and fitted using R software. Published and indirectly estimated hazard ratios were used to fit OS and PFS curves for COB + VEM and DAB + TRA. Costs, life-year gains, and quality-adjusted life years (QALYs) associated with the 3 treatment combinations were estimated. A base case analysis and probabilistic sensitivity analysis (PSA) were conducted to estimate the incremental cost-utility ratio (ICUR). A discount rate of 3.5% was applied on cost and outcomes. RESULTS: The ENC + BIN versus COB + VEM comparison was associated with an ICUR of $656 233 per QALY gained. The ENC + BIN versus DAB + TRA comparison was associated with an ICUR of $3 135 269 per QALY gained. The DAB + TRA combination dominated COB + VEM. The base case analysis estimates were confirmed by the PSA estimates. ENC + BIN was the most cost-effective combination at a high willingness-to-pay (WTP) threshold of $573 000 per QALY and $1.5 million/QALY when compared to COB + VEM and DAB + TRA, respectively. CONCLUSION AND RELEVANCE: Given current prices and acceptable WTP thresholds, our study suggests that DAB + TRA is the optimum treatment. In this study, ENC + BIN was cost-effective only at a very high WTP per QALY threshold.

Economic analysis of glucagon like peptide-1 receptor agonists from the Saudi Arabia payer perspective.

Objectives: To perform a cost of control analysis of glucagon like peptide-1 receptor agonists (GLP1RA) in Saudi Arabia (SA) and determine the economic impact of adopting GLP1RAs. Methods: A budget impact model that captures the cost of control model was constructed to simulate hypothetical patient on six treatment options: a current mix of 60% liraglutide and 40% dulaglutide, semaglutide, liraglutide, dulaglutide, exenatide, and lixisenatide. We estimated the relative amounts of SAR spend to achieve HbA1c targets (≤6.5% or < 7.0%). For each treatment option, annual treatment cost, proportion of patients achieving HbA1c targets, and cost to treat major adverse cardiovascular events (MACE) were aggregated to estimate the cost of control per patient per year (CCPPPY) over 5-year horizon (2021-2025). Probabilistic sensitivity analysis (PSA) was performed as a confirmatory analysis. Results: The CCPPPY to achieve HbA1c ≤ 6.5%/<7.0% using current mix, semaglutide, liraglutide, dulaglutide, exenatide, and lixisenatide were SAR 17,097/SAR 14,113, SAR 12,889/SAR 11,123, SAR 15,594/SAR 12,892, SAR 19,184/SAR 15,940, SAR 580,211/SAR 380,936, and SAR 246,570/SAR 143,759, respectively. The relative amounts of SAR spend to achieve HbA1c ≤ 6.5%/<7.0% relative to 1 SAR on semaglutide in case of adopting current mix, liraglutide, dulaglutide, exenatide, and lixisenatide were SAR 1.42/SAR 1.18, SAR 1.30/SAR 1.07, SAR 1.60/SAR 1.33, SAR 48.33/SAR 31.73, and SAR 20.54/SAR 11.97, respectively. These results were confirmed in the PSA. Conclusions: Semaglutide 1 mg once weekly was the most economically favorable GLP1RA; associated with the least CCPPPY, and amount of SAR spent to achieve HbA1c of ≤6.50%/<7.00% versus all other GLP1RAs.

Cost-effectiveness of palonosetron and dexamethasone-based triple and quadruple regimens in preventing highly emetogenic chemotherapy-induced nausea and vomiting.

OBJECTIVE: Cost-effectiveness analyses that consider all currently used antiemetics in the case of emetogenic chemotherapy-induced nausea and vomiting (CINV) have not been performed yet. We aim to compare the cost-effectiveness of olanzapine (OLA), or/and neurokinin-1 receptor antagonists (NK-1-RAs), in combination with palonosetron (PAL) and dexamethasone (DEX) in preventing highly emetogenic CINV. METHODS: Two decision analytic models were constructed. The first model was based on overall complete response (CR); the second model was based on rate of absence of nausea. Four antiemetic regimens PAL + DEX, NK-1-RAs + PAL + DEX, OLA + PAL + DEX, and PAL + NK-1-RA + DEX + OLA were compared in terms of cost, overall CR and rate of absence of nausea. Base case incremental cost-effectiveness ratio (ICER) estimates were calculated. The study was from the US payer perspective. RESULTS: In terms of CR, the PAL + NK-1-RA + DEX + OLA was associated with the highest gains in the percentage of CR among all treatment regimens at base case ICERs of $4220 versus PAL + DEX, $4656 versus NK-1-RA + PAL + DEX, $16,471 versus OLA + PAL + DEX. In term of rate of absence of nausea, the PAL + NK-1-RA + DEX + OLA was associated with the highest rate of absence of nausea among all the treatment regimens at base case ICERs of $2291 versus PAL + DEX, $1304 versus NK-1-RA + PAL + DEX, $2657 versus OLA + PAL + DEX. CONCLUSION: from an economic perspective, our study revealed that whether to use overall CR or/and rate of absence of nausea as determinants in the antiemetic decision for the CINV patients, the CR-based-, and rate of absence of nausea-based cost-effectiveness analyses, showed negotiable ICER estimates for the treatment PAL + NK-1-RA + DEX + OLA over the combinations PAL + DEX, NK-1-RA + PAL + DEX, and OLA + PAL + DEX regimens.

Pricing methods in outcome-based contracting: δ3: reference-based pricing.

AIMS: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The third dimension (δ3) estimates prices on the basis of international drug price referencing methods. We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib. MATERIALS AND METHODS: The reference-based pricing dimension utilizes a six-step method: (1) selecting foreign countries based on a set of four criteria (drug is available in the foreign country, price information is available in the foreign country, foreign countries are members within the organization for Economic Co-operation and Development, pricing methods in the foreign countries involve value assessment); (2) adjusting for exchange rates; (3) generating reference price (RP) scenarios; (4) adjusting with the medical inflation rate; (5) pooling all generated RP scenarios and calculating average and standard deviation (SD); (6) and Monte Carlo Simulation (MCS) to estimate the dimension-specific DSPReference. A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-year (2019-2021). RESULTS: The United Kingdom and Canada met the four criteria. For the osimertinib 1-year contract price, the average of eight RP scenarios, adjusted for inflation by 0.44%, was $8,892 (SD = $2,606) for a 30-day prescription. MCS yielded a DSPReference estimate of $9,395 or -35.72% of the wholesale acquisition cost (WAC) of $14,616. For the 2-year contract, the average, adjusted for inflation by 0.72%, was $8,928 (SD = $2,610). MCS yielded a DSPReference estimate of $9,442 or -35.40% of the WAC of $14,616. CONCLUSIONS: We demonstrated that international price referencing methods can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

Pricing methods in outcome-based contracting: δ2: willingness-to-pay-based pricing.

AIMS: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The second dimension (δ2) estimates prices on the basis of four willingness-to-pay (WTP) thresholds. We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib. MATERIALS AND METHODS: Eight WTP scenarios based on four levels of real gross domestic product per capita (<1GDP/capita, 1 × GDP/capita, 3 × GDP/capita, and >3 × GDP/capita) and two market conditions (monopolistic versus competitive) were assumed. The incremental cost-utility ratio (ICUR) was applied to differently to both markets. In the monopolistic market, assuming no competitors, the cost/QALY ratio for a drug was used; whereas in the competitive market, assuming competitors, the incremental cost-utility ratio (ICUR) was applied. One-way sensitivity analyses were performed and predictive equations were specified to estimate the prices of treatment for the resulting eight WTP scenarios; for which subsequently the average and standard deviation were calculated. A gamma distribution was specified and Monte Carlo Simulation (MCS) was applied to estimate the dimension-specific price based on WTP (DSPWTP). A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-year (2019-2021). The 2018 wholesale acquisition cost (WAC) of $14,616 (30-day prescription) was used to estimate the DSPWTP for each contract. RESULTS: The 1-year estimates averaged $4,654 (SD=$6,462) and the MCS yielded a DSPWTP of $4,547 or -68.89% of the 2018 WAC for a 30-day prescription. The 2-year estimates averaged $4,7667 (SD=$6,480) with the MCS generating a DSPWTP of $4,704 or -67.82% of the WAC. CONCLUSIONS: We demonstrated that WTP-based methods that include various WTP thresholds and market conditions generate price estimates across these thresholds and market conditions that can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

Pricing methods in outcome-based contracting: δ4: safety-based pricing.

AIMS: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The fourth dimension (δ4) estimates prices on the basis of assessments of the safety of the drug using an ex ante analysis based on clinical trial data. We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib. MATERIALS AND METHODS: The safety-based pricing dimension utilizes a four-step method: 1) pooling adverse events (AE), standardizing, estimating 95%Cis, and adjusting for time; 2) estimating correction factors and corrected probabilities of AEs; 3) estimating the probability of at least one adverse event (AE) occurring and leading to treatment discontinuation; and 4) estimating ranges for payback percentages and performing Monte Carlo Simulation to estimate a DSPSafety. A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-year (2019-2021). We estimated the DSPSafety based on the grade 3/4 AEs observed for osimertinib and standard of care. The 2018 wholesale acquisition cost (WAC) of osimertinib at $14,616 for a 30-day prescription was used. RESULTS: AEs3/4 were retrieved from the FLAURA trial. In the 1-year contract, the DSPSafety of osimertinib was estimated at $14,627 (or +0.08% the 2018 WAC) for a 30-day prescription. In the 2-year contract, the DSPSafety of osimertinib was estimated at $14,516 (or -0.68% the 2018 WAC) for a 30-day prescription. CONCLUSIONS: We demonstrated that ex ante pricing methods-based paybacks for safety issues leading to treatment discontinuation can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

Pricing methods in outcome-based contracting: δ5: risk of efficacy failure-based pricing.

AIMS: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The fifth dimension (δ5) estimates prices on the basis of the risk of efficacy failure of a drug. We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib. MATERIALS AND METHODS: The risk of efficacy failure pricing dimension utilizes a seven-step method: (1) defining risk; (2) extracting data; (3) predicting models; (4) performing Monte Carlo Simulation (MCS) to estimate risk of efficacy failure; 5) estimating ranges for a payback; (6) adjusting for medical inflation; and (7) performing Monte Carlo Simulation (MCS) to estimate the DSPRisk of efficacy failure. A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-year (2019-2021). We estimated the risk of efficacy failure for osimertinib in terms of overall and progression-free survival versus standard of care. We used the estimated risk to estimate the price reduction on the wholesale acquisition cost (WAC) for the two hypothetical contracts: a 1-year (2019-2020) and 2-year contract (2019-2021). From this we estimated the DSPRisk of efficacy failure. RESULTS: Based on the risk of OS and PFS efficacy failure for osimertinib in OS and PFS, in the 1-year contract, the DSPRisk of efficacy failure was estimated at $12,652 (or -13.44% the 2018 WAC) for a 30-day prescription. For the 2-year contract (2019-2021), the DSPRisk of efficacy failure was estimated at $13,019 (or -10.93% the 2018 WAC). CONCLUSIONS: We demonstrated that pricing methods based on risk of efficacy failure methods can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

Pricing methods in outcome-based contracting: δ6: adherence-based pricing.

AIMS: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The sixth dimension (δ6) estimates prices on the basis of adherence to the prescribed regimen, whereby manufacturers provide payers with adherence-enhancing programs and whereby payers implement these programs and provide adherence data to the manufacturer. We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib. MATERIALS AND METHODS: We propose two paybacks based on adherence: in-advance (based on clinical trial data) and in-arrear (based on real-world data). The risk of efficacy failure pricing dimension utilizes a 7-step method: 1) defining efficacy endpoints; 2) extracting data; 3) predicting models; 4) estimating in-advance and in-arrear paybacks; 5) suggesting ranges for in-advance and in-arrear paybacks; 6) adjusting for medical inflation; and 7) performing Monte Carlo Simulation (MCS) to estimate the DSPAdherence. A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-year (2019-2021). The 2018 wholesale acquisition cost (WAC) for a 30-day prescription was used and inflated as needed. Herein, the DSPAdherence is estimated exclusively in terms of in-advance payback because real-world data about osimertinib are not yet available and thus the in-arrear payback cannot yet be estimated. RESULTS: For the 1-year contract, the average price for osimertinib was $13,798 (SD=$1,265) and the DSPAdherence was $13,785 (or -5.69% of the 2018 WAC) for a 30-day prescription. For the 2-year contract, the average price was $12,555 (SD=$2,847) and the DSPAdherence was $12,582 (or -13.92% of the 2018 WAC). CONCLUSIONS: We demonstrated that adherence-based pricing methods can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting. The proof-of-concept exercise needs to be expanded with the in-arrear pricing method based on real world data to be secured.

Pricing methods in outcome-based contracting: δ1: cost effectiveness analysis and cost-utility analysis-based pricing.

AIMS: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The first dimension (δ1) estimates prices on the basis of cost-effectiveness (CEA) and cost-utility analysis (CUA). We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib. MATERIALS AND METHODS: CEA and CUA were performed using established methods. Probabilistic sensitivity analyses (PSA) were performed to generate cost-effectiveness acceptability curves (CEAC), specifically the PSA incremental cost-effectiveness (PSA ICER) and incremental cost-utility ratio generated CEACs (PSA ICUR). Price of treatment was estimated at three certainty levels (0%, turning point%, 100%). The marketed drug price at turning point was used to estimate prices at 0% and 100% certainty levels, as per PSA ICER and PSA ICUR-generated CEACs. The resulting prices were pooled, inflated, and simulated by Monte Carlo Simulation (MCS) methods to estimate the dimension-specific price based on CEA and CUA (DSPCEA/CUA). A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-years (2019-2021). RESULTS: Turning points were estimated at the 50% certainty level in both PSA ICER and ICUR-generated CEACS. At these points, the wholesale acquisition cost for osimertinib was $14,616 (30-day prescription); inflated by 0.44% for 1-year and by 0.72% for 2-year contracts. Additional prices at 0% and 100% certainty levels were quantified based on the PSA ICER and ICUR-generated CEACs. The MCS yielded a DSPCEA/CUA of $16,391 for the 1-year contract and a DSPCEA/CUA at $16,677 for the 2-year contract for a 30-day prescription. CONCLUSIONS: We demonstrated that conventional CEA and CUA methods generate price estimates at varying levels of certainty that can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

Pricing methods in outcome-based contracting: integration analysis of the six dimensions (6 δs).

AIMS: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The six dimensions have been described separately: (δ1) cost-effectiveness analysis and cost-utility analysis-based pricing; (δ2) willingness-to-pay-based pricing; (δ3) reference-based pricing; (δ4) safety-based pricing; (δ5) risk of efficacy failure-based pricing; and (δ6) adherence-based pricing. The final step is to integrate the various dimension-specific pricing estimates into a composite estimate termed the All-Dimensional Price (ADP). We describe the methodology for this integration and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib. MATERIALS AND METHODS: For better accuracy in estimating the ADP, we used the prices generated from the six dimensions at scenario levels, not at the dimension-specific price (DSP) level. We pooled the price estimates and performed Monte Carlo Simulations (MCS) for the price scenarios generated by the six dimensions. We used the results of the proof-of-concept exercise involving osimertinib in NSCLC with EGFR mutation to estimate the ADP in two hypothetical contracts: 1-year (2019-2020) and 2-year contract (2019-2021). RESULTS: The average of the 30-day prescription estimates from the six dimensions averaged $10,819 (SD=$8,486) for the 1-year contract and $10,730 (SD=$8,500) for the 2-year contract. MCS yielded for the 1-year contract an ADP of $10,959 (or -25.02% the 2018 WAC price) and an ADP for the 2-year contract was $10,788 (or -26.19% the 2018 WAC price). CONCLUSIONS: We demonstrated that the integration of the prices from the six dimensions of the Six Delta platform and market conditions is feasible and yields multidimensional prices estimates to support outcome-based pricing/contracting.

Economic Evaluation of Talimogene Laherparepvec Plus Ipilimumab Combination Therapy vs Ipilimumab Monotherapy in Patients With Advanced Unresectable Melanoma.

Importance: A phase 2 trial comparing talimogene laherparepvec plus ipilimumab vs ipilimumab monotherapy in patients with advanced unresectable melanoma found no differential benefit in progression-free survival (PFS) but noted objective response rates (ORRs) of 38.8% (38 of 98 patients) vs 18.0% (18 of 100 patients), respectively. Objective: To perform an economic evaluation of talimogene laherparepvec plus ipilimumab combination therapy vs ipilimumab monotherapy. Design, Setting, and Participants: For PFS, cost-effectiveness and cost-utility analyses using a 2-state Markov model (PFS vs progression or death) was performed. For ORRs, cost-effectiveness analysis of the incremental cost of 1 additional patient achieving objective response was performed. In this setting based on a US payer perspective (2017 US dollars), participants were patients with advanced unresectable melanoma. Main Outcomes and Measures: The PFS life-years and PFS quality-adjusted life-years were determined, and the associated incremental cost-effectiveness ratios (ICERs) and incremental cost-utility ratios (ICURs) were estimated. Also estimated was the ICER per 1 additional patient (out of 100 treated patients) achieving objective response. Base-case analyses were validated by sensitivity analyses. Results: In PFS analyses, the cost of talimogene laherparepvec plus ipilimumab ($494 983) exceeded the cost of ipilimumab monotherapy ($132 950) by $362 033. The ICER was $2 129 606 per PFS life-years, and the ICUR was $2 262 706 per PFS quality-adjusted life-year gained. Probabilistic sensitivity analyses yielded an ICER of $1 481 208 per PFS life-year gained and an ICUR of $1 683 191 per PFS quality-adjusted life-year gained. In 1-way sensitivity analyses, the PFS hazard ratio and the utility of response were the most influential parameters. Talimogene laherparepvec plus ipilimumab has a 50% likelihood of being cost-effective at a willingness-to-pay threshold of $1 683 191 per PFS quality-adjusted life-year gained. In ORR analyses, talimogene laherparepvec plus ipilimumab ($474 904) vs ipilimumab alone ($132 810), a $342 094 difference, yielded an ICER of $1 629 019 per additional patient achieving objective response. In subgroup analyses by disease stage and BRAFV600E mutation status, ICERs ranged from $1 069 044 to $17 104 700 per 1 additional patient achieving objective response. Conclusions and Relevance: The cost to gain 1 additional progression-free quality-adjusted life-year, 1 additional progression-free life-year, or to have 1 additional patient attain objective response is about $1.6 million. This amount may be beyond what payers typically are willing to pay. Combination therapy of talimogene laherparepvec plus ipilimumab does not offer an economically beneficial treatment option relative to ipilimumab monotherapy at the population level. This should not preclude treatment for individual patients for whom this regimen may be indicated.

Economic evaluation of a pharmacogenomic multi-gene panel test to optimize anti-hypertension therapy: simulation study.

AIMS: Hypertension is the strongest modifiable risk factor for cardiovascular disease, affecting 80 million individuals in the US and responsible for ∼360,000 deaths, at total annual costs of $93.5 billion. Antihypertension therapies guided by single genotypes are clinically more effective and may avert more adverse events than the standard of care of layering anti-hypertensive drug therapies, thus potentially decreasing costs. This study aimed to determine the economic benefits of the implementation of multi-gene panel guided therapies for hypertension from the payer perspective within a 3-year time horizon. MATERIALS AND METHODS: A simulation analysis was conducted for a panel of 10 million insured patients categorized clinically as untreated, treated but uncontrolled, and treated and controlled over a 3-year treatment period. Inputs included research data; empirical data from a 11-gene panel with known functional, heart, blood vessel, and kidney genotypes; and therapy efficacy and safety estimates from literature. Cost estimates were categorized as related to genetic testing, evaluation and management, medication, or adverse events. RESULTS: Multi-gene panel guided therapy yielding savings of $6,256,607,500 for evaluation and management, $908,160,000 for medications, and $37,467,508,716 for adverse events, after accounting for incremental genetic testing costs of $2,355,540,000. This represents total 3-year savings of $42,276,736,216, or a 47% reduction, and 3-year savings of $4,228 and annual savings of $1,409 per covered patient. CONCLUSIONS: A precision medicine approach to genetically guided therapy for hypertension patients using a multi-gene panel reduced total 3-year costs by 47%, yielding savings exceeding $42.3 billion in an insured panel of 10 million patients. Importantly, 89% of these savings are generated by averting specific adverse events and, thus, optimizing choice of therapy in function of both safety and efficacy.