Additional Drug Costs Research Articles

Economic burden of short-acting beta-2 agonist (SABA) overuse among asthma patients in Türkiye: a cost analysis with respect to the updated GINA treatment recommendations.

This cost of illness study aimed to determine economic burden of short-acting β2-agonist (SABA) overuse in Türkiye from payer perspective with respect to the updated GINA 2022 treatment recommendations. A total of 3,034,879 asthma patients comprised the study population, via estimations extrapolated from the Türkiye arm of the global SABINA III study. The economic burden (costs related to the drug use and severe exacerbations) was compared in subgroups of overall (≥ 0 canisters/year) vs. GINA-recommended (0-2 canisters/year, hypothetical population) SABA use and in subgroups of appropriate use (0-2 canisters/year, real population) vs. overuse (≥ 3 canisters/year) of SABA with extrapolation of SABINA Türkiye data to the Türkiye asthma population. Recommended SABA use was predicted to prevent 127,505 of 157,512 severe exacerbations per year in mild asthma patients and 2,668,916 of 3,262,800 severe exacerbations per year in moderate-severe asthma patients. Annual cost burden of not applying recommended SABA use (overall [≥ 0 canisters/year] vs. GINA-recommended [0-2 canisters/year] SABA use) in mild asthma and moderate-severe asthma patients was calculated to be €20.43 million and €427.65 million in terms of severe exacerbations, and to be €829,352 and €7.20 million in terms of drug costs, respectively. The total annual economic burden arising from not applying recommended SABA use was estimated to be €456.11 million. Appropriate use (0-2 canisters/year) vs. overuse (≥ 3 canisters/year) of SABA was associated with decreased frequency of severe exacerbations per year in mild asthma (from 129,878 to 27,634) and moderate-severe asthma (from 2,834,611 to 428,189) patients. SABA overuse in mild and moderate-severe asthma patients was estimated to yield an additional annual cost of €16.38 million and €385.59 million, respectively in terms of severe exacerbations, and a total €11.30 million additional drug cost. The overall annual economic burden arising from SABA overuse was estimated to be €413.27 million. The estimated annual total economic burden arising from not applying recommended SABA use (€456.11 million) and SABA overuse (€413.27 million) with respect to the updated GINA 2022 treatment recommendations indicates the substantial cost burden of SABA overuse to the Turkish National Health System, corresponding up to 26% of the total direct cost of asthma reported in our country.

PCN89 Estimating the costs of the management of non-Hodgkin’s lymphoma at a tertiary health institution

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and common type of non-Hodgkin’s lymphoma(NHL). It is of public health importance in Zimbabwe due to the high burden of HIV. The treatment of CD20-positive DLBCL include cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without rituximab (R-CHOP). Adding rituximab results in additional drug and diagnostic costs. Estimating treatment costs is important for budgeting. The aim of this study was to estimate the costs of managing NHL. The medical records of NHL patients at Parirenyatwa Hospital in 2015 were reviewed to determine personnel, drugs, laboratory procedures and other hospital services that were utilized. Micro costing method was used to aggregate the resources, determine unit costs and estimating the total cost of managing NHL. The costing was done from a healthcare provide perspective. The 2015 cost figures were adjusted for inflation to 2019 and reported in United States Dollars. A total of 89 patient records were reviewed with patients having a mean age of 41[4-76] and 64% were male. The majority 87% of the patients treated with CHOP and 17% on R-CHOP. The average cost for managing NHL with CHOP was $1235 per patient per cycle with diagnostic procedures contributing 52% to the figure. R-CHOP costed $2950 per patient per cycle with medications contributing 60%. The management of NHL is associated with substantial healthcare costs. Adding rituximab to CHOP results in significant increase in drug-related costs.

Cost-effectiveness of zanubrutinib versus ibrutinib in adult patients with Waldenström macroglobulinemia in the United States.

e18856 Background: The efficacy of zanubrutinib and ibrutinib was examined in the randomized ASPEN trial (NCT03053440) in adult patients with Waldenström macroglobulinemia (WM). This analysis assessed the cost-effectiveness (CE) of zanubrutinib vs ibrutinib in this population from a US payer perspective. Methods: A 3-state (pre-progression, post-progression, and death) partitioned survival model was used to estimate the life years (LYs), quality-adjusted life years (QALYs), and costs for each treatment over a 30-year lifetime horizon. Overall survival (OS), progression-free survival (PFS), and time-to-discontinuation (TTD) curves were fitted using parametric distributions to extrapolate long-term outcomes. Selection of the parametric models for each outcome and treatment was based on assessments of 1) the proportional hazard assumption, 2) goodness-of-fit, and 3) clinical plausibility of extrapolated mean OS and associated hazard patterns (based on literature and US clinical expert input) and the alignment between PFS and TTD. Background US mortality was accounted for in the model. Utilities were based on the ASPEN EQ-5D data and literature. Costs (2020 US$) included drug (wholesale acquisition cost from RED BOOK) and adverse event management (Healthcare Cost and Utilization Project) for zanubrutinib and ibrutinib, routine care, and terminal care. Sensitivity analyses were conducted to evaluate the impact of parameter uncertainty. All outcomes were discounted at 3% annually. Results: In the base case analyses using the dependent exponential model for all outcomes over a 30-year time horizon, zanubrutinib led to 0.94 LY and 0.84 QALY gained with an additional total drug cost of $11,132. This additional cost was primarily driven by patients staying on zanubrutinib treatment longer as zanubrutinib has longer time to treatment failure. However, this is partially offset by zanubrutinib’s lower monthly drug acquisition, reduced cost of routine care (–$2,935) and terminal care (–$2,964) than ibrutinib. The incremental cost-effectiveness ratio (ICER) of zanubrutinib is $13,205 per QALY gained. The deterministic sensitivity analyses showed that ICER was most sensitive to the monthly costs of routine care. The probabilistic sensitivity analyses showed that the mean probabilistic ICER was $16,804, and that the probability of zanubrutinib being cost-effective was 61% at a willingness-to-pay threshold of $100,000 per QALY gained. Varying the time horizon to 5, 10, or 15 years consistently led to zanubrutinib being dominant (i.e., greater QALYs but lower costs). Conclusions: Zanubrutinib appears to be cost-effective compared with ibrutinib for the treatment of patients with WM in the US.[Table: see text]

Using Real-World Data to Predict Clinical and Economic Benefits of a Future Drug Based on its Target Product Profile.

IntroductionFor a new drug to be developed, the desired properties are described in a target product profile.ObjectiveWe propose a framework for using real-world data to measure the disease-specific costs of the current standard of care and then to project the costs of the proposed new product for early data-driven portfolio decisions to select drug candidates for development.MethodsWe sampled from a cohort of patients representing the current standard of care to generate a hypothetical cohort of patients that fits a given target product profile for a new (hypothetical) treatment. The healthcare costs were determined and compared between standard of care and the new treatment. The approach differed according to the number of outcomes defined in the target product profile, and the cases for one, two, and three outcome variables are described.ResultsBased on assumed hypothetical treatment effect, absolute risk and cost reductions were estimated in a worked example. The median costs per day for one patient were estimated to be $10.37 and $8.39 in the original and hypothetical cohorts, respectively. This means that the assumed target product profile would result in cost savings of $1.98 per day and patient—not accounting for any additional drug costs.ConclusionsWe present a simple approach to assess the potential absolute clinical and economic benefit of a new drug based on real-world data and its target product profile. The approach allows for early data-driven portfolio decisions to select drug candidates based on their expected cost savings.Electronic supplementary materialThe online version of this article (10.1007/s40801-020-00203-w) contains supplementary material, which is available to authorized users.

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy \u2013 the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of ‘personalized’ therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4–5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events.Trial RegistrationClinicalTrials.gov identifier NCT02759120.

Patient Support Program Increased Medication Adherence with Lower Total Health Care Costs Despite Increased Drug Spending.

The U.S. health care system is currently evolving from a volume-based care to a value-based care approach, which is in part supported by the introduction of patient support programs (PSP). For patients treated with adalimumab (ADA), the addition of a dedicated, trained nurse to the PSP (HUMIRA Complete, rolled out nationally in 2015) provides further emphasis on value-based care. To determine the effectiveness of the HUMIRA Complete PSP, including the Nurse Ambassador component, in a real-world setting for patients receiving ADA across a broad range of approved indications (rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, psoriatic arthritis, ankylosing spondylitis, uveitis, and hidradenitis suppurativa). A longitudinal retrospective study was conducted using patient-level data from the HUMIRA Complete PSP data linked to the real-world, patient-level Symphony Health Solutions administrative claims database. Commercially insured patients were included who were aged ≥ 18 years with ≥ 2 diagnoses of an indicated disease who were biologically naive before initiating ADA or who had no claims for synthetic-targeted immune modulator therapy before their earliest ADA claim in the database between January 2015 and February 2017. The first claim had to have occurred in 2015 or later, and continuous medical and drug data coverage were required for ≥ 6 months before and ≥ 12 months after the first ADA claim and index date. PSP patients (with at least an initial and follow-up dedicated nurse call) were matched 1:1 to non-PSP patients based on pharmacy type, indication, and propensity score, estimated with covariates for age, sex, year of first ADA use, and baseline comorbidities. Adherence to ADA was compared using proportion of days covered along with discontinuation of ADA, defined as a gap in treatment greater than the previous days supply with no additional ADA claim, total costs, medical costs, and drug costs (2017 U.S. dollars) over 12 months. Baseline demographic and clinical characteristics were summarized descriptively. Differences between cohorts were assessed using t-tests for adherence and costs and log-rank tests for discontinuation. 2,268 patients (1,134 per group) were included. Baseline characteristics were similar between cohorts after matching. Participation in the PSP was associated with 29.3% higher ADA adherence (64.8% vs. 50.1%; P < 0.0001) and 22.0% lower ADA discontinuation rate (51.4% vs. 65.9%; P < 0.0001). Disease-related medical costs and all-cause medical costs were significantly lower by 35% ($10,162 vs. $15,511; P = 0.005) and 29.2% ($25,074 vs. $35,419; P = 0.0004), respectively, for PSP versus non-PSP patients. Total costs were also lower by 9% ($62,421 vs. $68,706; P = 0.056), and drug costs were 12.2% higher ($37,347 vs. $33,287; P = 0.0016). This retrospective study demonstrates that participation in the PSP augments value-based care by improving outcomes for patients with chronic diseases by helping them not only manage a complex treatment regimen but also lower annual health care costs. Design, study conduct, and financial support for this study were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the manuscript; all authors contributed to the development of the publication and maintained control over the final content. Brixner reports consulting fees from AbbVie, AstraZeneca, Becton Dickinson, Millcreek Outcomes Group, Sanofi, and UCB Pharma. Rubin reports consulting fees from AbbVie, Abgenomics, Allergan, Forward Pharma, Genentech/Roche, Janssen Pharmaceuticals, Merck & Co., Napo Pharmaceuticals, Pfizer, Shire, Takeda, and Target Pharmaceuticals and research support from AbbVie, Genentech/Roche, Janssen Pharmaceuticals, Prometheus Laboratories, Shire, and Takeda. Mease reports grant/research support from AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, SUN Pharma, and UCB; consulting fees from AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, SUN Pharma, and UCB; and served on the speakers bureaus for AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and UCB. Mittal and Ganguli are employees and stockholders of AbbVie. Liu has no financial conflict of interest. Davis is an employee of Medicus Economics, which reports payment from AbbVie to participate in this research. Fendrick reports personal fees from Merck, AstraZeneca, Trizetto, Amgen, Lilly, AbbVie, Johnson & Johnson, and Sanofi; grants from the National Pharmaceutical Council, PhRMA, the Gary and Mary West Health Foundation, the states of New York and Michigan, the Laura and John Arnold Foundation, the Robert Wood Johnson Foundation, and the Agency for Healthcare Research and Quality; and has equity in Zansors, Sempre Health, Wellth, and V-BID Health. Data from this study were presented in part at the Academy of Managed Care & Specialty Pharmacy Annual Meeting; April 25, 2018; Boston, MA.

Impact of plerixafor (mozobil) on hospital efficiency: A single center experience.

Plerixafor (Mozobil) in combination with granulocyte colony-stimulating factor (G-CSF) has shown to increase mobilization of peripheral blood stem cells (PBSC) as compared to G-CSF alone in patients undergoing autologous stem cell transplantation (ASCT). However, up to 25% of patients treated with G-CSF alone still fail mobilization. Adding plerixafor to poor mobilizers allows to rescue these patients from mobilization failure and to reduce the number of apheresis sessions. The goal of this retrospective study was to capture the impact of plerixafor on treatment outcome and on apheresis department efficiency. The latter was measured in terms of time-slots lost, that is, the number of apheresis sessions scheduled but not carried out due to poor mobilization, and the number of elective apheresis sessions performed for patients undergoing extracorporeal photopheresis (ECP). Hospital records of patients treated before and after introduction of plerixafor were collected and analyzed. With plerixafor, the mobilization failure rate dropped from 12% to 4% and the mean number of time-slots lost per patient dropped from 1.39 to 0.89. Additional drug costs due to plerixafor were partially balanced by a reduction in apheresis sessions, resulting in an additional cost of 759€ per ASCT candidate. More importantly, with the use of plerixafor, the availability of time-slots turned from erratic to predictable such that freed capacity could be dedicated to other apheresis procedures. As a result, the number of ECP sessions increased from 0 in 2005 to 685 sessions in 2014.

Cost-Effectiveness Analysis of Regorafenib for Gastrointestinal Stromal Tumour (GIST) in Germany.

No study has compared the cost-effectiveness of active treatment options for unresectable or metastatic gastrointestinal stromal tumours in patients who progressed on or are intolerant to prior treatment with imatinib and sunitinib. The aim of this study was to estimate the cost-effectiveness of regorafenib compared to imatinib rechallenge in this setting in Germany. Hazard ratios for progression-free (PFS) and overall survival (OS) with regorafenib versus imatinib rechallenge were estimated by indirect comparison. A state distribution model was used to simulate progression, mortality and treatment costs over a lifetime horizon. Drug acquisition costs and utilities were derived from clinical trial data and published literature; non-drug costs were not included. The outcomes measured were treatment costs, life-years (LYs) and quality-adjusted life-years (QALYs). The indirect comparison suggested that median PFS and OS were longer with regorafenib compared to imatinib but results were not statistically significant. Regorafenib versus imatinib rechallenge was estimated to have hazard ratios of 0.58 (95% CI 0.31-1.11) for PFS and 0.77 (95% CI 0.34-1.77) for OS, with substantial uncertainty due to the rarity of the disease and small number of patients within the trials. Regorafenib treatment per patient over a lifetime horizon provided an additional 0.61 LYs and 0.42 QALYs over imatinib rechallenge, with additional direct drug costs of €8,773. The incremental cost-effectiveness ratio was €21,127 per QALY gained. At a cost-effectiveness threshold of €50,000 per QALY, regorafenib had a 67% probability of being cost-effective. Based on the currently available clinical data, this analysis suggests that regorafenib is cost-effective compared with imatinib rechallenge in Germany.

DOP030 Anti-TNF re-induction is as effective, simpler and cheaper compared with dose interval shortening following secondary loss of response in Crohn's disease: a dual centre “real world” study

Background: Anti-TNF re-induction (RI) refers to re-dosing infliximab (IFX, 5mg/kg) at weeks 0, 2, 6 or adalimumab (ADA, 160mg, 80mg) at weeks 0, 2, prior to resuming standard IFX (8-weekly) or ADA (2-weekly) dosing. RI presents a simple and cost effective alternative to ongoing dose interval shortening (DIS) to recapture response following secondary loss of response (2°LOR) to maintenance anti-TNF therapy. This study aimed to compare the “real world” cost and efficacy of anti-TNF RI and DIS following 2°LOR in Crohn's Disease (CD) and identify factors associated with durability of response. Methods: CD patients attending two Inflammatory Bowel Disease (IBD) centres in Melbourne, Australia between 1/1/2006–30/8/2016, who developed 2°LOR to maintenance anti-TNF and subsequently underwent RI or DIS, were retrospectively identified from existing IBD databases. DIS was standardised to 6-weekly IFX or weekly ADA. Treatment failure was defined as either CD-related bowel resection, discontinuation of, or switching to another biologic within 12 months of RI or DIS. “Real world” drug costs of RI and DIS were based on Australian Pharmaceutical Benefit Scheme pricing. Non-parametric statistics plus bi- and multivariate linear regression depicting variables associated with time to failure were calculated. Results: Of 423 patients on anti-TNF therapy for CD, 88 (21%) developed 2°LOR to IFX (51, 58%) and ADA (37, 42%) respectively. Median age and disease duration at 2°LOR was 36.6y (17.4–78.0) and 9.4y (0.7–35.2) respectively, with a median duration from anti-TNF initiation to 2°LOR of 2.1y (0.2–8.1). Baseline characteristics were similar between groups, except the RI group had more smokers (48% vs 18%, p<0.01). Subsequent RI or DIS was undertaken in 33 (38%) patients and 55 (62%) patients respectively. Treatment failure rates at 12 months were similar (27% vs 15%, p=0.17). Factors favourably associated with a durable response to either RI or DIS on multivariate linear regression included subtherapeutic serum anti-TNF levels (B 5.37 [4.82, 5.92]), initial RI (B 2.56 [2.24, 2.89]), use of IFX (B 1.52 [1.26, 1.78]), and concurrent, optimised thiopurines (B 0.68 [0.46, 0.91]), p<0.01). RI demonstrated lower median “real world” costs due to fewer anti-TNF doses during the follow-up period (median: AUD $4,839 vs $13,170, doses 2.0 vs 7.4, p<0.01). Figure 1. “Real world” comparison of additional anti-TNF drug costs associated with RI vs DIS. Conclusions: This “real world” study suggests that first-line RI following 2°LOR to anti-TNF therapy in CD was as effective, simpler and cheaper than first-line DIS. Larger prospective evaluation is now planned.

PCV1 - Early HTA in Pharmacogenomics: A Case Example in Cardiovascular Drugs

Objectives: ACE inhibitors (ACEi) are commonly used cardiovascular drugs. These drugs can cause the severe and possibly lethal adverse drug reaction (ADR) angioedema in a very small part (0.2%) of the patients. A pharmacogenomic test could be used to identify patients at risk for this severe ADR and advise them to use another drug. The goal of this study is to assess the test characteristics (cost, sensitivity and specificity) in order for it to be a cost effective test for preventing ACEi-induced angioedema. Furthermore, we assessed the influence of only testing part of the population carrying risk factors for angioedema. Methods: A decision tree was used as angioedema usually occurs within the first year after starting an ACEi and data on long term risk is scarce. Test characteristics were assessed using Monte Carlo simulation. Results: With a willingness-to-pay (WTP) threshold of € 20,000 and € 80,000 per QALY, a 100% sensitive and specific test may have a maximum cost of € 1.29 and € 1.92, respectively. A decrease in specificity has a 10-fold higher impact on the ICER than sensitivity as additional drug costs of false positives rapidly overcome the benefit of preventing angioedema. In order to warrant a € 1.00 test price, specificity needs to be > 95% whilst sensitivity may drop to 70% provided that specificity remains > 98%. African people have a 3.88 times higher risk of developing angioedema than Caucasian people. When only genotyping this population, the maximum test price (100% sensitive and specific) would be € 3.21 and € 5.67 at a WTP threshold of € 20,000 and € 80,000, respectively. Conclusions: A theoretical pharmacogenomic test for ACEi-induced angioedema is only cost-effective at very high specificity, decent sensitivity and a low price. If only used in patients with a high risk on angioedema, the maximum test price could increase to a somewhat more realistic 5 Euro figure.

The additional costs of catheter-related bloodstream infections in intensive care units

The additional costs of health care-associated infections vary depending on the reimbursement systems of different countries. We estimated the additional costs of central venous catheter-related bloodstream infections (CVC-CRBSI) in Japan, which has a universal health insurance system covering all citizens. We conducted a retrospective matched case-control study. Twenty-two patients with CVC-CRBSI were identified among 2,148 patients treated between October 2011 and May 2014 in the intensive care unit of Tokyo Medical University Hospital (1,015 beds). Twenty-two matched controls were selected on the basis of 5 criteria. The drug and medical material costs and technical fees incurred from the date of catheter insertion until hospital discharge were examined using a fee-for-service system. The additional costs of CVC-CRBSI were calculated as the difference between the costs of cases and controls. The contribution of antimicrobial drugs and the causative microorganism to the additional drug costs were also assessed. The additional costs of CVC-CRBSI were estimated at $57,090 per case. Antimicrobial agents comprised only about 10% of the additional drug costs. The additional costs of Candida infection were almost twice those of CVC-CRBSI caused by other microorganisms. The additional costs of CVC-CRBSI in Japan were estimated at $57,090 per case.

Does Good Medication Adherence Really Save Payers Money?

Despite a growing consensus that better adherence with evidence-based medications can save payers money, assertions of cost offsets may be incomplete if they fail to consider additional drug costs and/or are biased by healthy adherer behaviors unobserved in typical medical claims-based analyses. The objective of this study was to determine whether controlling for healthy adherer bias (HAB) materially affected estimated medical cost offsets and additional drug spending associated with higher adherence. A total of 1273 Medicare beneficiaries with diabetes enrolled in Part D plans between 2006 and 2009. Using survey and claims data from the Medicare Current Beneficiary Survey, we measured medical and drug costs associated with good and poor adherence (proportion of days covered ≥ 80% and <80%, respectively) to oral antidiabetic drugs, ACE inhibitors/ARBs, and statins over 2 years. To test for HAB, we estimated pairs of regression models, one set containing variables typically controlled for in conventional claims analysis and a second set with survey-based variables selected to capture HAB effects. We found consistent evidence that controlling for HAB reduces estimated savings in medical costs from better adherence, and likewise, reduces estimates of additional adherence-related drug spending. For ACE inhibitors/ARBs we estimate that controlling for HAB reduced adherence-related medical cost offsets from $6389 to $4920 per person (P<0.05). Estimates of additional adherence-related drug costs were 26% and 14% lower in HAB-controlled models (P < 0.05). These results buttress the economic case for action by health care payers to improve medication adherence among insured persons with chronic disease. However, given the limitations of our research design, further research on larger samples with other disease states is clearly warranted.

Does increased adherence to medications change health care financial burdens for adults with diabetes?

The aim of the present study was to investigate increased out-of-pocket drug costs and financial burdens of achieving adherence to oral antidiabetic medications and medications for prevalent comorbidities. Concurrent adherence to medications, out-of-pocket drug costs, and financial burdens were measured among non-elderly adults with diabetes in the Medical Expenditure Panel Survey. "Financial burden" was defined as spending on health care exceeding 10% of family income. This study simulated the increased out-of-pocket drug costs and financial burdens that would result if non-adherent adults in our sample had obtained sufficient medications to be adherent. For each adult, for all therapeutic classes in which they were non-adherent, we calculated the additional days supplied required to become adherent, as well as out-of-pocket spending on these additional days supplied. Approximately one-quarter adhered to all required medications. Among non-adherent adults with employer-sponsored insurance and public insurance, the mean annual out-of-pocket drug costs of achieving adherence were US$171 and US$68, respectively, which was generally affordable. However, 35.6% of the uninsured lived in families that spent 10% or more of their income on health care. Mean simulated additional out-of-pocket drug costs of achieving adherence were US$310 for the uninsured. These additional drug costs would increase those spending 10% or more of income to 39.6% of the uninsured. Efforts to reduce the costs faced by the uninsured and insured will make adherence more affordable and, therefore, more attainable for some adults with diabetes.

PCN46 - Estimating the Budget Impact of Adding Avastin (Bevacizumab) to Front Line Treatment for Advanced Ovarian Cancer in Brazilian Supplementary Health Care System

Ovarian cancer (OC) is one of the most lethal gynecologic cancers worldwide. According to Brazilian Institute of Cancer (INCA), 6,190 new OC cases were estimated in 2012. During the last 15 years, carboplatin plus paclitaxel (CP) has been established as front-line (FL) standard of care therapy for advanced ovarian cancer, with no significant advances in treatment ever since. Bevacizumab (Bev) in combination with CP was approved in Brazil for FL treatment of advanced epithelial OC on May/2013. Therefore, this study aimed to estimate the economic impact of bevacizumab reimbursement for advanced OC in Brazilian Supplementary Healthcare System. The potential number of eligible patients for CP + Bev in FL therapy for advanced OC was estimated following an epidemiologic approach. It was assumed that Supplementary Healthcare System attendance accounts for 40% of all patients. Additional drug costs and infusion fees were evaluated. The ex-factory price (VAT 18%) and labeled dose were considered. Average therapy duration of CP + bevacizumab was 15 months based on GOG-0218 trial. Costs were reported in Brazilian Reais (BRL1.00≈USD0.44; Jun/2013). A total health assistance budget of BRL 88.1 billion was forecasted for 2013, based on the last updated data from Brazilian National Regulatory Agency for Private Health Insurance and Plans (ANS). A total of 1,287 eligible cases in CP + Bev FL therapy for advanced OC are expected in 2013 in the private setting. Adding bevacizumab to the treatment of all these potential patients would yield an increase of BRL 267 million, corresponding only to an increment around 0.30% on health assistance expenses. Treating all eligible FL advanced OC patients with CP + Bev will potentially result in a low impact in Supplementary Healthcare System budget, associated to unprecedented clinical benefits for this population with a high medical unmet need.

Cost impact of trastuzumab prescribing in the treatment of advanced Her2 positive gastric cancer in Ireland

Gastric and oesophageal combined make up the fifth most common cancer in Ireland after prostate, breast, colorectal and lung cancer. In 2006, there were 820 cases diagnosed accounting for 5% of all invasive cancers (excluding nonmelanoma skin cancer) cases and 8% of cancer deaths in Ireland [1]. The disease has an approximately 20% 5-year survival rate in Ireland, similar to rates in other European countries [2] with one-third of patients presenting with advanced incurable disease at diagnosis. Current treatments include surgery or chemoradiation in the case of early disease, or chemotherapy alone for advanced disease. Many patients will receive a combination of treatment modalities. A study has shown that a proportion of these cancers tests positive for HER2, a receptor tyrosine kinase. Patients treated with trastuzumab (a HER2-targeted therapy) combined with chemotherapy had a better overall survival with a median gain of 2.7 months. A subset analysis based on patients with HER2 3? on immunohistochemistry or HER2 2? with gene amplification, and accounting for 17% of patients tested, had the bulk of the benefit with a 4.2-month improvement in median overall survival [3]. The cost of this treatment is, however, significant. The authors analysed the patients who are potentially eligible for this treatment in a single university hospital in Ireland. In 2006, 166 gastric and oesophageal cancers were diagnosed in our centre, accounting for 20% of the national patient cohort. Thirty-eight percent of the cohort (63 patients) had advanced disease at diagnosis (stage 3 or 4). If 17% of those patients were positive for HER2, as per ToGA post hoc analysis, then 11 patients could be considered for treatment with trastuzumab. The estimated drug cost per year would therefore be €24,000 per patient based on a median eight cycles of treatment, or €264,000 additional drug cost in one institution (Fig. 1 below). In Ireland, 820 patients were diagnosed with gastric or oesophageal cancer in 2006 and this increased by almost 5% in 2007 to 857 patients [4]. If 66% of those were OGJ/gastric tumours and a further 38% of those locally advanced, then 206 patients in Ireland would yield 35 with HER2 positive disease. The Irish national drug cost to treat these patients with targeted therapy would therefore be over €800,000 per year (Fig. 2 below). A QALY (quality adjusted life year) is defined as a year of life, adjusted for its quality or its value. Assuming the quality of life of a patient is the same on chemotherapy or a combination of chemotherapy and trastuzumab [5], and the median survival of 4.2 months or 0.35 years, thus the treatment has a QALY of 0.35. To calculate the cost per QALY, we use the following formula, (c1 c2)/(q1 q2), where c1 is the cost of the new drug, and c2 is the standard drug cost. q1 and q2 are the QALY for the new and old regimens, respectively, and in this case are the same. At a cost of €24,000 per patient for those 0.35 QALYs, this gives an incremental cost effectiveness ratio (ICER) of €68,000 per QALY. In the UK, the current NICE (National Institute for Clinical Excellence) threshold for cost effectiveness is *€60,000, though it may be higher in the palliative setting. I. M. Collins (&) K. O’Byrne Department of Medical Oncology, St James Hospital, Dublin 8, Ireland e-mail: Collins.ian@gmail.com

Pharmacy intervention on antimicrobial management of critically ill patients.

Frequent, suboptimal use of antimicrobial drugs has resulted in the emergence of microbial resistance, compromised clinical outcomes and increased costs, particularly in the intensive care unit (ICU). Mounting on these challenges is the paucity of new antimicrobial agents. The study aims to determine the impact of prospective pharmacy-driven antimicrobial stewardship in the ICU on clinical and potential financial outcomes. The primary objectives were to determine the mean length of stay (LOS) and mortality rate in the ICU resulting from prospective pharmacy interventions on antimicrobial therapy. The secondary objective was to calculate the difference in total drug acquisition costs resulting from pharmacy infectious diseases (ID)-related interventions. In collaboration with an infectious disease physician, the ICU pharmacy team provided prospective audit with feedback to physicians on antimicrobial therapies of 70 patients over a 4-month period in a 31-bed ICU. In comparison with published data, LOS and mortality of pharmacy-monitored ICU patients were recorded. Daily cost savings on antimicrobial drugs and charges for medication therapy management (MTM) services were added to calculate potential total cost savings. Pharmacy interventions focused on streamlining, dose optimization, intravenous-to-oral conversion, antimicrobial discontinuation, new recommendation and drug information consult. Antimicrobial education was featured in oral presentations and electronic newsletters for pharmacists and clinicians. The mean LOS in the ICU was 6 days, which was lower than the published reports of LOS ranging from 11 to 36 days. The morality rate of 14% was comparable to the reported range of 6 to 20% in published literature. The total drug cost difference was a negative financial outcome or loss of USD192 associated with ID-related interventions. In collaboration with the infectious disease physician, prospective pharmacy intervention on antimicrobial therapy in the ICU led to positive clinical outcomes and an additional drug cost expense of USD192.

Explaining Marginal Benefits to Patients, When “Marginal” Means Additional but Not Necessarily Small

Patients and their families want us to be realistic, honest, and caring about their prognosis and their options, even when the news is bad. Most oncologists will tell a patient if he is not curable, but not give specific survival information unless prompted. As an example, chemotherapy for pancreas cancer improves survival and does not worsen quality of life, but the impact on lifespan is small. Patients with advanced pancreas cancer have options that increase their average survival by about 16/100 at 1 year, and by about 9 weeks compared with best supportive care, but almost all patients are dead by 24 months. As an example of "marginal benefit" ("marginal" is defined here as more than that offered by the alternative care, not necessarily small or worthless), erlotinib added to gemcitabine compared with gemcitabine alone improves survival by six additional people at 1 year, and an average of 2 weeks, with no survival tail. In addition, the additional drug cost alone can be more than $12,000 a month. We use this clinical practice as a way to describe marginal benefit to patients. Telling patients that they have incurable disease and that treatment is ineffective is hard. Partly as a result, only about a third of cancer patients are told they are going to die, and those who are not told live no longer but have worse medical outcomes, such as dying on a ventilator and less time with hospice. These difficult conversations can be done if the oncologist has the right medical information, the right script, and some decision aids.

Healthcare Costs and Obesity Prevention

Obesity is a major contributor to the overall burden of disease (also reducing life expectancy) and associated with high medical costs due to obesity-related diseases. However, obesity prevention, while reducing obesity-related morbidity and mortality, may not result in overall healthcare cost savings because of additional costs in life-years gained. Sector-specific financial consequences of preventing obesity are less well documented, for pharmaceutical spending as well as for other healthcare segments. To estimate the effect of obesity prevention on annual and lifetime drug spending as well as other sector-specific expenditures, i.e. the hospital segment, long-term care segment and primary healthcare. The RIVM (Dutch National Institute for Public Health and the Environment) Chronic Disease Model and Dutch cost of illness data were used to simulate, using a Markov-type model approach, the lifetime expenditures in the pharmaceutical segment and three other healthcare segments for a hypothetical cohort of obese (body mass index [BMI] >or=30 kg/m2), non-smoking people with a starting age of 20 years. In order to assess the sector-specific consequences of obesity prevention, these costs were compared with the costs of two other similar cohorts, i.e. a 'healthy-living' cohort (non-smoking and a BMI >or=18.5 and <25 kg/m2) and a smoking cohort. To assert whether preventing obesity results in cost savings in any of the segments, net present values were estimated using different discount rates. Sensitivity analyses were conducted across key input values and using a broader definition of healthcare. Lifetime drug expenditures are higher for obese people than for 'healthy-living' people, despite shorter life expectancy for the obese. Obesity prevention results in savings on drugs for obesity-related diseases until the age of 74 years, which outweigh additional drug costs for diseases unrelated to obesity in life-years gained. Furthermore, obesity prevention will increase long-term care expenditures substantially, while savings in the other healthcare segments are small or non-existent. Discounting costs more heavily or using lower relative mortality risks for obesity would make obesity prevention a relatively more attractive strategy in terms of healthcare costs, especially for the long-term care segment. Application of a broader definition of healthcare costs has the opposite effect. Obesity prevention will likely result in savings in the pharmaceutical segment, but substantial additional costs for long-term care. These are important considerations for policy makers concerned with the future sustainability of the healthcare system.

The Impact of Obesity on Health Service Utilization and Costs in Childhood

Most studies of the economic costs of childhood obesity have focused upon hospitalization for comorbidities of obesity, whereas increased expenditures may also be the result of additional outpatient/emergency room visits or prescription drug expenditures. To quantify the magnitude of increased health-care utilization and expenditures among overweight and obese children, we performed descriptive, bivariate, and multivariable analyses on data from 6- to 19-year olds in the 2002-2005 Medical Expenditure Panel Survey (MEPS), a national probability survey of the noninstitutionalized civilian population in the United States. Compared with normal/underweight children, we found that children who were obese during both years of the MEPS had USD194 higher outpatient visit expenditures, USD114 higher prescription drug expenditures, and USD12 higher emergency room expenditures. Children who were overweight during both years, or overweight in one year and obese in the other had USD79 higher outpatient visit expenditures, USD64 higher prescription drug expenditures, and USD25 higher emergency room expenditures than normal/underweight children. Significantly, increased utilization was noted for outpatient visits, prescription drug use, and emergency room visits. Increased costs and utilization were concentrated among adolescents, though 6-11-year-old children who were obese in both years did have more outpatient visits and expenditures than other children. Extrapolated to the nation, elevated BMI in childhood was associated with USD14.1 billion in additional prescription drug, emergency room, and outpatient visit costs annually. Although further research is needed to identify effective interventions, the immediate economic consequences of childhood obesity are much greater than previously realized, and further reinforce efforts to prevent this major comorbidity are needed.

Trastuzumab: preparation and planning will avoid chaos

AbstractTrastuzumab has been shown to improve disease‐free, and overall, survival in women with early HER2‐positive breast cancer. It is undergoing rapid appraisal by NICE with the aim of providing prompt guidance for use within the NHS. The DOH has pledged to support its use, yet without increasing PCT funding for support services and additional drug costs. The criteria by which PCTs can decide or decline to pay for treatment remain unclear. Copyright © 2006 John Wiley &amp; Sons, Ltd.