Simulation of Health and Economic Benefits of Extended Observation of Resolved Anaphylaxis

Abstract

Importance: Biphasic anaphylaxis may occur in up to 20% of patients with anaphylaxis; however, the optimal observation time of patients with resolved anaphylaxis is unknown.

Objective: To characterize the cost-effectiveness of short vs prolonged medical observation times after resolved anaphylaxis.

Design, setting, and participants: An economic evaluation was performed of computer-simulated adult patients observed in outpatient allergy clinics and emergency departments, with rates of biphasic anaphylaxis derived from a 2019 meta-analysis.

Exposures: Computer-simulated patients (10 000 per strategy) were randomized to undergo 1 hour of medical observation (associated with 95% negative predictive value of biphasic anaphylaxis) or 6 or more hours of observation (associated with a 97.3% negative predictive value of biphasic anaphylaxis).

Main outcomes and measures: Cost-effectiveness of 6- to 24-hour medical observation of resolved anaphylaxis evaluated at willingness-to-pay thresholds of $10 000 per case of biphasic anaphylaxis observed and $10 million per death prevented, assuming that observation is associated with a 10- to 1000-fold reduction in the risk of death due to biphasic anaphylaxis.

Results: Biphasic anaphylaxis occurred after hospital discharge in 365 patients observed for 1 hour and in 213 patients undergoing prolonged observation. From a health care sector perspective, with medical observation costs of $286.92 per hour, the incremental cost of extended medical observation of resolved anaphylaxis (1 hour vs 6 hours) was $62 374 per case of biphasic anaphylaxis identified ($68 411 from the societal perspective). In Monte Carlo simulations, with hourly costs ranging from $100 to $500 and extended observation ranging from 6 to 24 hours (health care sector perspective), the mean (SD) costs were $295.36 ($81.22) for 1 hour of observation vs $3540.42 ($1626.67) for extended observation. The incremental cost-effectiveness ratio was $213 439 per biphasic anaphylaxis observed ($230 202 from the societal perspective). A 6-hour observation could be cost-effective if the risk of biphasic anaphylaxis after 1-hour observation of resolved anaphylaxis was 17% or if hourly observation costs were less than $46 in the base case. Cost-effectiveness could also be achieved (willingness-to-pay of $10 million per death prevented, health care sector perspective) when a baseline fatality rate of 0.33% per biphasic anaphylactic event was assumed, with a no greater than 24% relative risk of fatality associated with 6-hour observation.

Conclusions and relevance: This study indicates that prolonged medical observation (6-24 hours) for resolved anaphylaxis may not be cost-effective for patients at low risk for biphasic anaphylaxis; however, in particular clinical circumstances of low observation costs, high postdischarge risk of biphasic anaphylaxis, or large incremental fatality risk reduction associated with extended observation, longer medical observation can be justified.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Shaker reported that he is a member of the Joint Taskforce on Allergy Practice Parameters and that his brother is CEO of Altrix Medical. Dr Wallace reported serving on the advisory boards and/or speaker bureaus for Sanofi, Kaleo, OptiNose, and ALK; serving as a consultant for Mylan; and serving as co-chair of the Joint Taskforce on Allergy Practice Parameters. Dr Golden reported receiving grants and personal fees from Genentech, grants from Stallergenes/Greer, personal fees from Sandoz and Aquestive, and personal fees and royalties from UpToDate outside the submitted work, and serving as a consultant for ALK and as co-chair of the Joint Task Force on Allergy Practice Parameters. Dr Oppenheimer reported receiving personal fees from GlaxoSmithKline, AstraZeneca, Novartis, and Sanofi and royalties from Up-To-Date; serving as an editor for Annals of Allergy Asthma Immunology, AllergyWatch, and Current Opinion of Allergy; and serving as a board liaison for the American Board of Internal Medicine and the American Board of Allergy and Immunology, and as a member of the Joint Taskforce on Allergy Practice Parameters. Dr Greenhawt reported being an expert panel and coordinating committee member of the National Institute of Allergy and Infectious Diseases–sponsored Guidelines for Peanut Allergy Prevention; having served as a consultant for the Canadian Transportation Agency, Thermo Fisher, Intrommune, and Aimmune Therapeutics; being a member of physician and/or medical advisory boards for Aimmune Therapeutics, DBV Technologies, Sanofi/Genzyme, Genentech, Nutricia, Kaleo Pharmaceutical, Nestle, Aquestive, Allergy Therapeutics, Allergenis, Aravax, Prota, International Food Protein Induced Enterocolitis Syndrome Association, and Monsanto; being a member of the scientific advisory council for the National Peanut Board; receiving honoraria for lectures from Thermo Fisher, Aimmune, DBV, Before Brands, multiple state allergy societies, the American College of Allergy Asthma and Immunology, and the European Academy of Allergy and Clinical Immunology; receiving personal fees from Aquestive; being an associate editor for the Annals of Allergy, Asthma, and Immunology; and being a member of the Joint Taskforce on Allergy Practice Parameters.

Figures

Figure 1.. Sensitivity Analysis (Cost per Biphasic Anaphylaxis Episode Observed)

A, Deterministic sensitivity analysis of risk for biphasic anaphylaxis (after complete resolution) is shown. If the risk for biphasic anaphylaxis exceeds 17% (dotted vertical line), then extended observation for 6 hours would cost less than $10 000 per case of biphasic anaphylaxis identified. B, Sensitivity analysis of direct hourly costs is shown. If the direct hourly cost of observation is less than $46 (dotted vertical line), 6-hour observation could be cost-effective (willingness-to-pay = $10 000 per observed biphasic anaphylaxis episode).

Figure 2.. Tornado Diagram of Deterministic Sensitivity Analyses

Incremental cost-effectiveness ratio (ICER) is shown in 2019 US dollars (cost per biphasic anaphylaxis episode observed). Tornado diagram shows deterministic sensitivity analyses, with light blue bars representing assumptions above and dark blue bars representing assumptions below the base case analysis.

Figure 3.. Cost-effectiveness Acceptability Curve (Cost per Biphasic Anaphylaxis Episode Observed)

Probabilistic sensitivity analysis (1000 simulations) is shown. Across modal distributions, extended observation (≥6 hours) is not cost-effective compared with 1-hour observation after anaphylaxis resolution at a willingness-to-pay of $10 000 per biphasic anaphylaxis episode observed.