The rising cost of commonly used emergency department medications (2006-15).

OBJECTIVE: We determine how aggregate costs have changed for commonly used emergency department (ED) medications, and assess drivers of cost increases. METHODS: Using the National Hospital Ambulatory Medical Care Survey (NHAMCS), we identified the top 150 ED medications administered and prescribed at discharge in 2015. We used average wholesale prices (AWP) for each year from 2006 to 15 from the Red Book (Truven Health Analytics Inc.). Average wholesale price per patient (AWPP) was calculated by dividing AWP by drug uses. This was then multiplied by the total drug administrations or prescriptions to estimate the total cost in a given the year. All prices were converted to 2015 dollars. RESULTS: Aggregate costs of drugs administered in the ED increased from $688.7 million in 2006 to $882.4 million in 2015. For discharge prescriptions, aggregate costs increased from $2.031 billion in 2006 to $4.572 billion in 2015. AWPP for drugs administered in the ED in 2015 was 14.5% higher than in 2006 and 24.3% higher at discharge. The largest absolute increase in AWPP for drugs administered was for glucagon, which increased from $111 in 2006 to $235 in 2015. The largest AWPP increase at discharge was for epinephrine auto-injector, which increased from $124 in 2006 and to $481 in 2015. CONCLUSION: Over the course of the study period, the aggregate costs of the most common medications administered in the ED increased by 28% while the costs of medications prescribed at discharge increased 125%.

Biologic Agents for the Treatment of Anaphylaxis.

Several biologic therapies and new devices are emerging as potential preventive treatment of anaphylaxis. However, adrenaline (epinephrine) is still the first-line treatment of any type of anaphylaxis. Biologic drugs, such as omalizumab, although not US Food and Drug Administration approved for anaphylaxis, have been used as therapeutic adjuvants in the preventive treatment of anaphylaxis, but cost-effectiveness should be considered individually.

Cost-effectiveness of adrenaline for out-of-hospital cardiac arrest.

BACKGROUND: The 'Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration In Cardiac Arrest' (PARAMEDIC2) trial showed that adrenaline improves overall survival, but not neurological outcomes. We sought to determine the within-trial and lifetime health and social care costs and benefits associated with adrenaline, including secondary benefits from organ donation. METHODS: We estimated the costs, benefits (quality-adjusted life years (QALYs)) and incremental cost-effectiveness ratios (ICERs) associated with adrenaline during the 6-month trial follow-up. Model-based analyses explored how results altered when the time horizon was extended beyond 6 months and the scope extended to include recipients of donated organs. RESULTS: The within-trial (6 months) and lifetime horizon economic evaluations focussed on the trial population produced ICERs of £1,693,003 (€1,946,953) and £81,070 (€93,231) per QALY gained in 2017 prices, respectively, reflecting significantly higher mean costs and only marginally higher mean QALYs in the adrenaline group. The probability that adrenaline is cost-effective was less than 1% across a range of cost-effectiveness thresholds. Combined direct economic effects over the lifetimes of survivors and indirect economic effects in organ recipients produced an ICER of £16,086 (€18,499) per QALY gained for adrenaline with the probability that adrenaline is cost-effective increasing to 90% at a £30,000 (€34,500) per QALY cost-effectiveness threshold. CONCLUSIONS: Adrenaline was not cost-effective when only directly related costs and consequences are considered. However, incorporating the indirect economic effects associated with transplanted organs substantially alters cost-effectiveness, suggesting decision-makers should consider the complexity of direct and indirect economic impacts of adrenaline. TRIAL REGISTRATION: ISRCTN73485024 . Registered on 13 March 2014.

The cost-effectiveness of requiring universal vs contextual self-injectable epinephrine autoinjector for allergen immunotherapy.

BACKGROUND: Aeroallergen immunotherapy (AIT) is a safe and effective disease-modifying treatment associated with rare therapy-associated fatality. Significant practice variation surrounds universal or contextual prescription of self-injectable epinephrine (SIE) for patients receiving AIT. OBJECTIVE: To characterize the cost-effectiveness of a universal vs contextual SIE requirement for patients receiving AIT. METHODS: An economic evaluation using cohort and microsimulation was performed from both the societal and health care sector perspectives for patients undergoing AIT, assessing a universal requirement to fill SIE prescriptions at the outset of therapy compared with requiring this only after a systemic reaction to immunotherapy (SRIT). RESULTS: A universal SIE requirement for AIT is not cost-effective, with the incremental cost-effectiveness ratio for this strategy estimated at $669,327,730 per quality-adjusted life-year (QALY). In the microsimulation (n = 10,000), the mean (SD) costs of a universal approach exceeded that of a more context-specific strategy where SIE was only prescribed for patients after an initial SRIT ($19,653.36 [$4296.66] vs $16,232.14 [$5204.32]), and given the effects on rates of AIT discontinuation, the universal approach was less effective (mean [SD], 25.555 [2.285] QALYs) compared with a contextualized approach (mean [SD], 25.579 [2.345] QALYs). Universal SIE prescription could be cost-effective if it provided a 1000 times protection against AIT fatality at a value-based cost of $24, and the annual AIT fatality rates unrealistically exceed 2.6 per 10,000 patients. CONCLUSION: In a simulation of potential SIE-prescribing strategies for patients receiving AIT, a universal approach to an epinephrine autoinjector requirement was not cost-effective when compared with an approach in which an SIE is prescribed only to patients with prior SRIT.

Evaluation of the healthcare resource use and the related financial costs of managing peanut allergy in the United Kingdom.

Aims: We aimed to estimate the resource use and associated costs for patients with peanut allergy (PA) compared to matched controls. Methods: This was a retrospective cohort study using data from the UK Clinical Practice Research Datalink and Hospital Episode Statistics. PA patients were matched to two control cohorts: the first (simple-matched) were matched 1:1 on year of birth, general practice, gender and registration year. The second (atopy-matched) were matched on the same characteristics plus presence/absence of an atopic condition. Prescriptions and primary and secondary care contacts were compared between cases and controls. Results: 15,483 peanut-allergic patients were identified: 13,609 (87.9%) were simple-matched and 9,320 (60.2%) atopy-matched. The total per person annual incremental health-care costs associated with PA were £253 (atopy-matched) and £333 (simple-matched). For those with PA and a prior anaphylaxis incremental costs were £662, for those prescribed an epinephrine autoinjector incremental costs were £392. Extrapolated to the U.K. population, total excess costs of PA were between £33 and 44 million in 2015. Conclusions: Patients with PA had increased health-care contacts and consequently increased associated costs compared to controls. Observation bias should be considered in interpretation, but this study suggests that PA presents significant burden to health-care systems.

Cost-Effectiveness of Stock Epinephrine Autoinjectors on Commercial Aircraft.

BACKGROUND: In-flight food-allergic reactions are rare events, but given increasing reports, grass-root advocates have lobbied to replace aircraft emergency kit epinephrine ampules with autoinjectors. OBJECTIVE: To evaluate the cost-effectiveness of stock epinephrine on commercial aircraft. METHODS: We conducted a Markov model with microsimulation of food-allergic individuals over an 80-year time horizon to evaluate the cost-effectiveness of supplementing airline medical kits with epinephrine autoinjectors (eg, providing autoinjector twin-packs in addition to the epinephrine ampule in the medical kit), versus not doing so, using a per-plane annual value-based cost ceiling of $338 (the value-based ceiling for school stock epinephrine). We assumed that autoinjector availability reduced fatality risk by 10%. RESULTS: Equipping all commercial aircraft with autoinjectors cost $2,470,422/year ($0.08/passenger-at-risk), from a societal perspective and when distributed over all at-risk travelers. Over the model horizon, the supplemental autoinjector strategy cost $32,329.29 (standard deviation [SD], $4024.32) versus $32,326.70 (SD $4024.29), produced 26.8917 quality-adjusted life-years (QALYs) (SD, 2.9720) versus 26.8915 (SD, 2.9725), with a lower fatality rate (0.00012; SD, 0.01095 vs 0.00015; SD, 0.1225) versus the ampule-only strategy. The incremental cost-effectiveness ratio of supplemental airline epinephrine autoinjectors was $10,766/QALY in the base-case analysis. The supplemental model remained cost-effective at a willingness to pay threshold of $100,000/QALY if it produced a minimum 1.4% annual food allergy fatality risk reduction, and dominated if it lowered diversion risk or event-related medical care costs-per-event by 10%, respectively. CONCLUSIONS: Under base-case scenarios, an airline supplemental stock epinephrine model is cost-effective, with a high value-based cost-ceiling and low annual cost per passenger-at-risk of $0.08.

Analysis of Value-Based Costs of Undesignated School Stock Epinephrine Policies for Peanut Anaphylaxis.

Importance: Children experiencing anaphylaxis at school may lack access to a personal epinephrine device, prompting recent legislation permitting undesignated (eg, non-student specific) stock epinephrine autoinjector units at school. However, epinephrine device costs vary, and the cost-effectiveness of undesignated school stock epinephrine is uncharacterized to date. Objective: To define value-based strategies for undesignated school stock epinephrine programs. Design, Setting, and Participants: Markov simulations of the Chicago Public Schools system were used over extended time horizons to model 2 school stock epinephrine autoinjector policies to provide access for at-risk students. The dates of the data used in the analysis were September 2017 to June 2018 (the 2017-2018 school year). Main Outcomes and Measures: This study compared the following 3 strategies: no school undesignated epinephrine supply, school undesignated supplemental epinephrine supply (supplemental model), and school undesignated universal epinephrine supply (universal model). The base-case model assumed a 10-fold reduced fatality risk with having undesignated stock epinephrine units available vs not having undesignated stock epinephrine units available. Costs of school stock epinephrine units available for acquisition by schools were evaluated from a societal perspective. Quality-adjusted life-years (QALYs) and total epinephrine acquisition expenses were calculated. Results: Based on Markov simulations of the Chicago Public Schools system (371 382 students), the cost was $107 816 (95% CI, $107 382-$108 250) for no school undesignated epinephrine supply compared with $108 160 (95% CI, $107 725-$108 595) for the supplemental model and $100 397 (95% CI, $99 979-$100 815) for the universal model. Undesignated stock epinephrine improved outcomes, with 26.869 (95% CI, 26.841-26.897) QALYs accrued as the model concluded compared with 26.867 (95% CI, 26.839-26.896) QALYs for the strategy without undesignated stock epinephrine. When comparing supplemental model stock epinephrine to the strategy without undesignated devices, the incremental cost-effectiveness ratio was high at $268 811 per QALY in the base-case simulation. However, the cost of the supplemental model fell below $100 000 per QALY when the annual undesignated epinephrine acquisition costs did not exceed $338 per school (compared with stock epinephrine unavailability). The universal model dominated all others and was associated with significant cost savings ($7419 per student at risk who would otherwise be prescribed an individual school epinephrine supply). Conclusions and Relevance: Undesignated school stock epinephrine is cost-effective at device acquisition costs not exceeding $338 per school per year, although a universal model vs a supplemental model is associated with superior health and economic outcomes.

Allergy and Asthma: Anaphylaxis.

Anaphylaxis is an allergic reaction that occurs rapidly after exposure and is life-threatening. After symptoms of anaphylaxis occur, there is no way to reliably predict whether the patient's condition could progress quickly and become life-threatening. Immediate injection of intramuscular epinephrine is the first-line emergency treatment for anaphylaxis. Other drugs such as corticosteroids or antihistamines are secondary options and should not delay epinephrine administration. The most commonly prescribed form of epinephrine is the costly brand name autoinjector, but less expensive alternatives exist, including generic autoinjectors and prefilled epinephrine syringes. Epinephrine prescriptions should be combined with action plans that guide parents and caregivers on appropriate use. Access to epinephrine at schools, even for students who do not have a prescription, is an important component of preparedness for anaphylaxis.

Hyperinflation of Vasopressors (Vasopressin, Norepinephrine, Ephedrine, etc).

PURPOSE: Hyperinflation refers to the increasing cost of drugs which occurs due to continued drug shortages and rebranding. Hyperinflation has significant implications in increasing overall healthcare costs with reduced reimbursement, increased patient acuity, and an aging population, but published strategies to reduce costs and minimize waste are limited. OBJECTIVE: To describe the hyperinflation and cost mitigation strategies of three vasopressor medications, vasopressin, epinephrine, and ephedrine. CONCLUSION: The steep increase in medications is expected to continue, and mitigation strategies to reduce waste and select the most cost effective therapy to offset the price increase is crucial for healthcare systems.

Association of Fatality Risk With Value-Based Drug Pricing of Epinephrine Autoinjectors for Children With Peanut Allergy: A Cost-effectiveness Analysis.

Importance: The high cost of self-injectable epinephrine autoinjectors may represent a barrier to community anaphylaxis management. Value-based pricing can provide a benchmark for rational epinephrine autoinjector costs. Objective: To define value-based pricing of community epinephrine autoinjectors. Design, Setting, and Participants: In an economic evaluation study using a cost-effectiveness birth cohort model over an extended 80-year time horizon, Markov simulations of children with peanut allergy evaluated cost ceilings for value-based epinephrine prices in peanut allergy. Simulation inputs included all-cause age-adjusted mortality (2013 US life tables), 2013 published food allergy fatality rates, 2017 rates of autoinjector device carriage, and 2016 published market costs of self-injectable epinephrine. All costs were expressed in 2018 US dollars and discounted at 3% per annum. Exposures: Cohorts of children with peanut allergy prescribed epinephrine autoinjectors were compared with those not receiving personal epinephrine prescriptions. Children without epinephrine autoinjectors assumed 10-fold to 100-fold fatality risk increases. Costs were evaluated from a societal perspective. Main Outcomes and Measures: Fatality risk, quality-adjusted life-years, and incremental cost-effectiveness ratio. Results: A total of 100 000 simulated infants with peanut allergy entered each strategy, with two-thirds of the group receiving annual personal epinephrine prescriptions and using those devices appropriately when indicated. Over the time horizon, the cost of anaphylaxis preparedness and treatment in those with personal epinephrine devices was $25 478 (95% CI, $25 399-$25 557) compared with $654 (95% CI, $645-$663) for those without personal epinephrine, resulting in an average food allergy fatality of 0.00056 (95% CI, 0.000414-0.000706) per patient prescribed self-injectable epinephrine and 0.00148 (95% CI, 0.001242-0.001718) in those not prescribed self-injectable epinephrine. The value-based price (incremental cost-effectiveness ratio, $100 000 per quality-adjusted life-year) for personal epinephrine based on 10-fold fatality risk difference was $24. At a market cost of $715 per twin pack, the autoinjector incremental cost-effectiveness ratio was $2 742 697 per quality-adjusted life-year. If a hypothetical fatality risk protection from personal epinephrine was modeled at 100-fold, the value-based price ceiling for a personal autoinjector was $264. Conclusions and Relevance: In a simulation of children with peanut allergy, a value-based epinephrine cost has a ceiling of $24 for a personal autoinjector, even at an exaggerated fatality risk.

Economic evaluation of epinephrine auto-injectors for peanut allergy.

BACKGROUND: Three commercial epinephrine auto-injectors were available in the United States in the summer of 2016: EpiPen, Adrenaclick, and epinephrine injection, USP auto-injector. OBJECTIVE: To describe the variation in pharmacy costs among epinephrine auto-injector devices in New England and evaluate the additional expense associated with incremental auto-injector costs. METHODS: Decision analysis software was used to evaluate costs of the most and least expensive epinephrine auto-injector devices for children with peanut allergy. To evaluate regional variation in epinephrine auto-injector costs, a random sample of New England national and corporate pharmacies was compared with a convenience sample of pharmacies from 10 Canadian provinces. RESULTS: Assuming prescriptions written for 2 double epinephrine packs each year (home and school), the mean costs of food allergy over the 20-year model horizon totaled $58,667 (95% confidence interval [CI] $57,745-$59,588) when EpiPen was prescribed and $45,588 (95% CI $44,873-$46,304) when epinephrine injection, USP auto-injector was prescribed. No effectiveness differences were evident between groups, with 17.19 (95% CI 17.11-17.27) quality-adjusted life years accruing for each subject. The incremental cost per episode of anaphylaxis treated with epinephrine over the model horizon was $12,576 for EpiPen vs epinephrine injection, USP auto-injector. EpiPen costs were lowest at Canadian pharmacies ($96, 95% CI $85-$107). There was price consistency between corporate and independent pharmacies throughout New England by device brand, with the epinephrine injection, USP auto-injector being the most affordable device. CONCLUSION: Cost differences among epinephrine auto-injectors were significant. More expensive auto-injector brands did not appear to provide incremental benefit.