Budget impact analysis of the novel PD-1 inhibitor toripalimab versus pembrolizumab in recurrent or metastatic nasopharyngeal carcinoma.

AIM: To estimate the budget impact of adding a toripalimab regimen as a treatment option to the existing pembrolizumab regimen, both including gemcitabine and cisplatin, in untreated recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) using the published wholesale acquisition cost (WAC) and average sales price (ASP). METHODS: Budget impact analysis comparing a treatment mix "without" versus "with" the toripalimab regimen in the US eligible annual incident R/M NPC population, a 3-year time horizon, toripalimab/pembrolizumab market splits of 60/40 (Y1) and 80/20 (Y2/3), and medication adjustments for discontinuation or progression. Cost inputs included drugs, administration, and adverse event (AE) management. The models were replicated for a hypothetical 1-million-member health plan in which costs per-member-per-month (PMPM) and per-member-per-year (PMPY) were estimated. One-way (OWSA) and probabilistic sensitivity analyses (PSA) as well as scenario analyses were performed. RESULTS: In the "without" scenario, the 3-year WAC-based costs for the pembrolizumab regimen total $1,449,695,333 ($1,305,632,448 for treatment and $144,062,885 for managing AEs). In the "with" scenario, total 3-year costs for pembrolizumab decline to $380,012,135 with toripalimab adding $885,505,900 ($779,206,567 for treatment and $106,299,333 for AE management). Annual net savings range from $46,526,152 in 2024 to $71,194,214 in 2026, for 3-year savings of $184,177,298. Associated net savings in a 1-million-member health plan are $543,068 over 3 years with savings of $0.045 PMPM and $0.543 PMPY. The ASP-based model shows similar patterns with 3-year net savings of $174,235,983 in the US incident population and savings of $0.043 PMPM and $0.514 PMPY in a 1-million-member health plan. The PSA support base case findings; OWSA and scenario analyses reveal how parameter variability impacts results. CONCLUSION: Savings between $174 million and $184 million can be achieved from treating 60% of R/M NPC patients in year 1 and 80% in years 2 and 3 with the toripalimab regimen over a similar pembrolizumab regimen.

Toripalimab, a human monoclonal anti-body that targets PD-1, was recently approved by the US Food and Drug Administration (FDA) for the first-line treatment of adults with metastatic or recurrent, locally advanced nasopharyngeal carcinoma (NPC), in combination with gemcitabine and cisplatin. We evaluated how much it would cost a payor to cover the FDA-approved toripalimab plus gemcitabine and cisplatin regimen (the toripalimab regimen) to a non-FDA-approved pembrolizumab plus gemcitabine and cisplatin regimen (the pembrolizumab regimen). With no trial data available for such pembrolizumab regimen, we assumed that it would be comparable to the toripalimab regimen in efficacy and safety. Our model adopted a 3-year time horizon and assumed a 60/40 market share split in year 1 and an 80/20 market split in years 2 and 3. It included two US cost inputs: the wholesale acquisition cost (WAC) or "list price" at market entry and, as no average sales price (ASP) will be available for toripalimab for several quarters, a toripalimab price point of 80% of the pembrolizumab ASP. We adjusted for patients whose cancer progressed or who discontinued treatment to determine the number of fully-treated-patient-equivalents. We found that treating 60% of NPC patients in year 1 and 80% in years 2 and 3 with the toripalimab regimen instead of the pembrolizumab regimen generates, for the entire adjusted patient population, savings ranging from $174 million when using ASP to $184 million when using WAC.

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 15­69 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.

Cost-effectiveness of Favipiravir in moderately to severely ill COVID-19 patients in the real-world setting of Saudi arabian pandemic referral hospitals.

Purpose: We aimed to evaluate the cost effectiveness of Favipiravir treatment versus standard of care (SC) in moderately to severely ill COVID-19 patients from the Saudi healthcare payer perspective. Methods: We used the patient-level simulation method to simulate a cohort of 415 patients with moderate to severe COVID-19 disease who were admitted to two Saudi COVID-19 referral hospitals: 220 patients on Favipiravir and 195 patients on SC. We estimated the incremental cost-effectiveness ratio (ICER) of Favipiravir versus SC in terms of the probability to be discharged alive from hospital and the mean time in days to discharge one patient alive. The model was performed twice: first, using unweighted, and second, using weighted clinical and economic data. Weighting using the inverse weight probability method was performed to achieve balance in baseline characteristics. Results: In the unweighted model, base case (probabilistic) ICER estimates favored Favipiravir at savings of Saudi Riyal (SAR)1,611,511 (SAR1,998,948) per 1% increase in the probability of being discharged alive. As to mean time to discharging one patient alive, ICERs favored Favipiravir at savings of SAR11,498 (SAR11,125). Similar results were observed in the weighted model with savings using Favipiravir of SAR1,514,893 (SAR2,453,551) per 1% increase in the probability of being discharged alive, and savings of SAR11,989 (SAR11,277) for each day a patient is discharged alive. Conclusion: From the payer perspective, the addition of Favipiravir in moderately to severely ill COVID-19 patients was cost-savings over SC. Favipiravir was associated with a higher probability of discharging patients alive and lower daily spending on hospitalization than SC.

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.

Validation of the Arabic version of medication adherence report scale questionnaire and beliefs about medication -specific questionnaire: A factor analysis study.

Medication Adherence Report Scale questionnaire (MARS-5) and the Beliefs about Medication Questionnaire-specific (BMQ-specific) are well known tools to assess adherence to medication and beliefs of chronic patients. However, validated Arabic versions of such questionnaires are lacking. We aim to validate the Arabic versions of BMQ-specific and MARS-5. In this study, a cross-sectional study was performed between November 2019 and March 2020. Participants were reached from secondary and tertiary care clinics in Jordan. Exploratory factor analysis (EFA) and Confirmatory Factor analysis (CFA) were conducted to validate the employed questionnaires on the tested sample. The internal consistency of the questionnaires was assessed by calculating Cronbach's alpha, and Cronbach's alpha if item is deleted. A total of 485 patients who met the inclusion criteria were recruited. The mean age of the participants was 57.14 years (22-82 years); and 39% of the participants were older than 65 years. The most common chronic diseases reported by participants were hypertension and diabetes mellitus, 35.7 and 32.2% respectively. EFA suggested two-factor model for BMQ-specific and one-factor model for MARS-5 which was confirmed by CFA analyses. The resulted Cronbach's alphas of the questionnaires ranged from 0.89-0.93. Both analyses showed that the Arabic versions of both MARS-5 and BMQ-specific are valid and can be used for the suggested study population. Further validation-based research may enhance the transcultural adaptation of such questionnaires.

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.

Meta-Analysis of Same-Day Pegfilgrastim Administration Stratified by Myelotoxic Febrile Neutropenia Risk and Tumor Type.

Background: Pegfilgrastim is recommended to be administered at least 24 hours following the completion of chemotherapy, yet some clinicians use a same-day administration protocol. In this meta-analysis, we compared the incidence of chemotherapy-induced (febrile) neutropenia (CIN/FN) as well as CIN/FN-related chemotherapy disruptions in cancer patients provided with pegfilgrastim same-day vs. next-day. Methods: Six databases were searched for comparative studies of same-day vs. next-day pegfilgrastim administration. Fixed or random-effects meta-analyses were conducted to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Results: Thirteen studies were included in this meta-analysis. The FN OR for same-day vs. next-day administration was 1.48 (95% CI = 1.06-2.08) across all cycles, attributable mainly to studies of high FN risk (OR = 2.46, 95% CI = 1.04-5.83) vs. intermediate FN risk regimens (OR = 1.41, 95% CI = 0.95-2.10), and breast cancer (OR = 3.15, 95% CI = 1.24-8.01) vs. non-Hodgkin lymphoma (NHL; OR = 1.48, 95% CI = 0.98-2.23) and gynecologic cancers (OR = 0.64, 95% CI = 0.11-3.85). Where available, ORs for first cycle of chemotherapy, grades 3 and/or 4 CIN, and chemotherapy dose delays or reductions were in line with these findings. Conclusion: In this independent study, same-day pegfilgrastim administration may or may not increase the likelihood of FN, grades 3 and/or 4 CIN, and chemotherapy dose reductions or delays; and this may be a function of the myelotoxicity of the regimens (elevated in high-risk but not intermediate-risk regimens) and tumor type (elevated in breast but not in NHL or gynecologic cancers). With due caution, same-day pegfilgrastim administration may be safe and beneficial in intermediate-risk regimens and selected tumor types.

What Are the Factors Associated with Nonadherence to Medications in Patients with Chronic Diseases?

Introduction: Adherence to medications is very crucial for an optimized clinical outcome in the management of chronic diseases. Beliefs about medications and other factors can significantly affect adherence to chronic medications. The objective of the present research was to identify the associated factors of adherence to medication in Jordanian patients with chronic diseases utilizing a stepwise binary logistical regression model. Methods: A cross-sectional study was carried out between November 2018 and March 2020. The participants were reached from secondary and tertiary care setting clinics in Jordan. The recruited patients were asked to report their attitudes of adherence to medications and beliefs about medications via filling out the MARS-5 and BMQ-specific tools. Sociodemographic data were also collected from the recruited patients and included in the regression model. A stepwise binary logistical regression model was applied to identify the associated factors of adherence to chronic medications in the tested sample. Results: A total of 485 patients who met the inclusion criteria were recruited. The mean age of the participants was 57.14 (age ranged from 22 to 82 years). Around 39% of the participants were older than 65 years. Most of the patients were either hypertensive or diabetic (35.7% and 32.2%, respectively). The logistic regression model indicated that necessity beliefs are strongly associated with adherence (OR 4.22), while concerns beliefs, dosage frequency and having medical insurance were negatively associated with adherence (OR 0.73, 0.74 and 0.26, respectively), with a p-value ≤ 0.05. Conclusions: Both the MARS-5 and BMQ-specific questionnaires were applied successfully on the tested sample. Better attention should be paid to the logistic regression model variables that were associated with adherence in order to guarantee optimal treatment outcomes in the treatment of chronic diseases.

Gender-stratified hierarchical modeling of patient and physician determinants of antihypertensive treatment outcomes: pooled analysis of seven prospective real-world studies with 17,044 patients.

OBJECTIVE: Seven prospective real-world studies conducted in general practices in Belgium of antihypertensive treatment with valsartan-centric regimens were pooled to examine similarities and differences in determinants of blood pressure (BP) values (mmHg) and BP control rates between female and male patients. METHODS: Pooled analysis of a total evaluable sample of 17,044 patients, including 8273 (48.5%) women and 8771 men (51.5%) treated over approximately 90 days with valsartan-centric regimens in second or later line. Hierarchical linear and logistic regressions were applied to identify patient- and physician-related determinants of BP outcomes and a potential physician class effect. RESULTS: Reductions in BP (mmHg) over 90 days were similar for women and men, and so were changes in BP control rates. Approximately a quarter of the variance in 90 day BP values was attributable to a physician class effect. Both gender groups shared some patient- and physician-related determinants of BP outcomes, though often varying in degree of influence. Analyses also revealed gender-specific determinants. Among others, modifiable/manageable patient-related determinants included BP at hypertension diagnosis (proxy for time of diagnosis), risk factors, antihypertensive treatment and adherence; while among the physician-related determinants clinical experience in hypertension treatment was modifiable/manageable. CONCLUSION: Valsartan-centric treatment regimens are associated with significant reductions in BP level and improvement in BP control in both women and men. The determinants revealed in modeling provide guidance to clinicians in the common and differential management of hypertension in female and male patients.

Hierarchical modeling of blood pressure determinants and outcomes following valsartan treatment in hypertensive patients with known comorbidities: pooled analysis of six prospective real-world studies including 11,999 patients.

AIMS: Six prospective real-world studies of antihypertensive treatment with valsartan-centric regimens were pooled to: (1) examine the effectiveness of ∼90 days of second- or later-line valsartan treatment in hypertensive patients with known comorbidities; and (2) identify physician- and patient-related determinants associated with systolic (SBP) and diastolic blood pressure (DBP) outcomes in these patients. METHODS AND MATERIALS: A pooled analysis was performed of an evaluable sample of 11,999 hypertensive patients with known comorbidities treated ∼90 days with valsartan-centric regimens. We applied hierarchical linear and logistic regression models to identify determinants of blood pressure (BP) outcomes and a potential physician class effect. RESULTS: Valsartan regimens resulted in mean (SD) SBP and DBP reductions of 18.0 (15.8) mmHg and 9.5 (10.1) mmHg, respectively, at ∼90 days, yielding SBP, DBP and combined SBP/DBP control rates of 44.0%, 67.2% and 39.3%, respectively. About a quarter of the variance in 90 day BP values was attributable to a physician class effect. BP outcomes declined with physicians' increasing years in practice and being male. At the patient level, BP outcomes declined with SBP and DBP at diagnosis; diabetes; higher cholesterol and BMI; lower valsartan and hydrochlorothiazide (HCTZ) doses; and concomitant anti-hypertensives. Older age was associated with improved DBP. A proxy of physician vigilance, cardiovascular disease history, was associated with improved BP outcomes, as were patient adherence and higher doses of valsartan in combination with HCTZ. CONCLUSIONS: Valsartan-centric regimens have significant BP lowering benefits in this pooled sample of patients with known comorbidities. Many observed determinants of BP outcomes are modifiable or manageable.

Ex Ante Economic Evaluation of Arg389 Genetically Targeted Treatment with Bucindolol versus Empirical Treatment with Carvedilol in NYHA III/IV Heart Failure.

OBJECTIVE: The Beta-Blocker Evaluation Survival Trial showed no survival benefit for bucindolol in New York Heart Association (NYHA) class III/IV heart failure (HF) with reduced ejection fraction, but subanalyses suggested survival benefits for non-Black subjects and Arg389 homozygotes. We conducted an ex ante economic evaluation of Arg389 targeted treatment with bucindolol versus carvidolol, complementing a previous ex ante economic evaluation of bucindolol preceded by genetic testing for the Arg389 polymorphism, in which genetic testing prevailed economically over no testing. METHODS: A decision tree analysis with an 18-month time horizon was performed to estimate the cost effectiveness/cost utility of trajectories of 100%, 50%, and 0% of patients genetically tested for Arg389 and comparing bucindolol with empirical carvedilol treatment as per prior BEST subanalyses. Incremental cost-effectiveness/cost-utility ratios (ICERs/ICURs) were estimated. RESULTS: Race-based analyses for non-White subjects at 100% testing showed a loss of (0.04) life-years and (0.03) quality-adjusted life-years (QALYs) at an incremental cost of $2185, yielding a negative ICER of ($54,625)/life-year and ICUR of ($72,833)/QALY lost; at 50%, the analyses showed a loss of (0.27) life-years and (0.16) QALYs at an incremental cost of $1843, yielding a negative ICER of ($6826)/life-year and ICUR of ($11,519)/QALY lost; at 0%, the analyses showed a loss of (0.33) life-years and (0.30) QALYs at an incremental cost of $1459, yielding a negative ICER of ($4421)/life-year and ICUR of ($4863)/QALY lost. Arg389 homozygote analyses at 100% testing showed incremental gains of 0.02 life-years and 0.02 QALYs at an incremental cost of $378, yielding an ICER of 18,900/life-year and ICUR of $18,900/QALY gained; at 50%, the analyses showed a loss of (0.24) life-years and (0.09) QALYs at an incremental cost of $1039, yielding a negative ICER of ($4329)/life-year and ICUR of ($9336)/QALY lost; at 0%, the analyses showed a loss of (0.33) life-years and (0.30) QALYs at an incremental cost of $1459, yielding a negative ICER of ($4421)/life-year and ICUR of ($4863)/QALY lost. CONCLUSION: This independent ex ante economic evaluation suggests that genetically targeted treatment with bucindolol is unlikely to yield clinicoeconomic benefits over empirical treatment with carvedilol in NYHA III/IV HF.

Insulin injection technique in the western region of Algeria, Tlemcen.

INTRODUCTION: Algeria has more than 1.7 million diabetic patients on to whom a descriptive assessment particularly on the insulin usage behaviors has not yet been initiated, although is needed. This study aims to provide a descriptive analysis of how Algerian diabetic patients perceive and apply insulin injection techniques. METHODS: using the "patient" questionnaire within the Injection Technique Questionnaire (ITQ) 2016 survey, this study assessed the insulin injection practices of 100 patients recruited over a seven-month period in western Algeria at the Tlemcen University Hospital Center. The results of this study are compared to those of the ITQ 2016 survey. RESULTS: pens are the instruments of injection for 98% of Algerians who continue to use mostly long needles of 6- and 8-mm, although 4mm needles are the recommended safer option. Insulin analogues (fast and basal) are plebiscite. Arms and thighs are the preferred injection sites; the abdomen (the preferred site elsewhere) is neglected for reasons to be investigated. The correct re-suspension technique for cloudy insulin is unknown. Extensive pen needle re-use (10+ times) for over half of the patients exposes them to both higher intramuscular (IM) injection risk and lipohypertrophy (LH). Injection training is performed in Algeria by the diabetologist. CONCLUSION: this study describes for the first time Algerian patients´ insulin injection technique. It highlights their skills and identifies many deficiencies which patients and professionals must correct given the issues in this area.

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.