Value-Based Pricing for Emerging Gene Therapies: The Economic Case for a Higher Cost-Effectiveness Threshold.

While one-time gene replacement therapies may offer transformative innovation for the management of ultrarare, health-catastrophic diseases, they also pose challenges to the current U.S. health care system. Historically, the United States and other countries have demonstrated a willingness to support higher prices for health gains in rare diseases. However, payers may be ill-prepared to address reimbursement based on single administrations associated with gene therapies. As yet, there is no consensus on how to appropriately reward gene therapy innovation. The purpose of this article is to characterize challenges for traditional approaches to assessing the value of one-time gene replacement therapies and to provide a health economic rationale for a higher value-based cost-effectiveness threshold (CET). There is a general recognition that ultrarare, health-catastrophic conditions should be judged against a higher CET. The Institute for Clinical and Economic Review in the United States has discussed a range of up to $500K per quality-adjusted life-year (QALY) gained for ultrarare diseases, and the National Institute for Health and Care Excellence in the United Kingdom has described a variable threshold up to £300,000 per QALY depending on the magnitude of the health gains. In practice, health technology assessment decision makers often make comparisons to "benchmarks" to justify both standard and extraordinary CETs. We briefly review and present a list of relevant benchmarks. We also sketch out how a broader concept of value could provide the basis for higher CETs for some ultrarare diseases. This approach is outlined by the recent International Society for Pharmacoeconomics and Outcomes Research Special Task Force on Value Assessment Frameworks. In addition to the QALY gains, other elements of value related to uncertainty may also be important. They include insurance value, severity of disease, real option value, value of hope, and equity. A gene therapy currently in development for the treatment of spinal muscular atrophy (SMA) provides an exemplar for discussing the issues that accompany one-time gene replacement therapies. It is imperative that we find a consensus on how to appropriately reward value created by these gene therapies to incentivize appropriate risk taking and investments by their developers-a higher CET would, by economic logic, support a higher value-based price. If consensus on appropriate rewards cannot be found for safe and effective gene therapies for diseases such as SMA with clear criticality and unmet need, it will be even more difficult to do so for diseases where the value provided is less apparent. DISCLOSURES: Funding for the writing of this article was provided by AveXis Pharmaceuticals, which reviewed the manuscript and contributed feedback during manuscript development. The authors had final editorial control. Jackson and Paul are employees of MME, a biopharmaceutical consulting firm that received funding from AveXis for work on this project. Jackson and Paul also report consulting fees from numerous other biopharmaceutical companies outside of this project. Garrison reports consulting fees from AveXis for work on this project and advisory/consultancy fees from BioMarin, Roche, Novartis, and Pfizer unrelated to this project. Kenston is a former employee of AveXis and reports consulting fees from AveXis for this project and for other projects outside of this work.

Store and prescription characteristics associated with primary medication nonadherence.

BACKGROUND: Primary medication nonadherence (PMN) is any instance whereby patients fail to initiate a pharmacotherapy regimen after receiving a prescription for new therapy. The Pharmacy Quality Alliance (PQA) has proposed a standardized definition for PMN and a quality measure to assess the rates of PMN in community pharmacies. OBJECTIVES: To (a) measure PMN using the proposed PQA measure with data available from a pharmacy dispensing system and (b) identify the prescription-level (patient, prescriber, and medication) and store-level (store and neighborhood) characteristics associated with PMN. METHODS: This study was approved by a southern university institutional review board, and a data use agreement was in place. A large national pharmacy grocery chain provided de-identified, transactional data for 2010 through January 2012, for 100 pharmacies (de-identified unique patient and store codes were available). The proposed PQA-PMN measure was used, and PMN rates were calculated. Investigators examined adult individuals with a new electronic prescription for any of the included medications during the measurement period and determined whether the medication or an appropriate alternative was claimed within 30 days. Multilevel logistic regression with a random intercept was used to evaluate prescription-level and store-level predictors of PMN. Prescription-level variables included prescriber type, PQA-defined drug class, patient gender and age, whether the prescription was accompanied by another prescription on the same day, payment source, and out-of-pocket costs. A daily average prescription volume variable was calculated for each pharmacy as a store-level variable. Additional store-level variables were derived from the 2007-2011 American Community Survey, available from the U.S. Census Bureau (median household income, educational level, percentage of minorities, and percentage aged 65 years and over in the census tracts where the pharmacies are located).  RESULTS: Of the e-prescriptions during the 1-year measurement period, 29,238 were for new therapies as defined by the PMN measure, and 3,570 (12.2%) of those new prescriptions were not claimed within a 30-day period. There was significant variability among the pharmacies (intraclass correlation coefficient=0.140). In the adjusted multilevel model, the estimated odds of an unclaimed prescription were significantly different among drug classes comprising the PQA-PMN measure and were higher as out-of-pocket costs increased, when the prescription was accompanied by another prescription on the same day, and for primary care physicians relative to physician assistants and advanced practice nurses. The estimated odds were slightly higher for younger individuals, when originating at stores with lower prescription volumes and when originating at stores located in neighborhoods with higher household incomes. Although neither the gender of the patient nor the payment source were related to whether the prescription went unclaimed in the multivariable model, these variables, along with out-of-pocket costs and the accompaniment of the prescription with another prescription on the same day, were involved in cross-level interactions with household income and educational level.  CONCLUSIONS: This study is one of the first to use pharmacy prescription data to calculate PMN using the PQA standardized measure and to identify prescription-level and store-level factors associated with PMN. PMN remains a significant challenge in this setting, and there is significant variation in the outcome among pharmacies in the same chain, even after accounting for several potential store-level predictors. There is considerable opportunity for quality improvement to reduce the number of unclaimed prescriptions. Efforts directed at further understanding this behavior and how to design tailored interventions to reduce its occurrence are warranted.