Validation of modeled pharmacoeconomic claims in formulary submissions

Abstract

Modeled or simulated claims for costs and outcomes are a key element in formulary submissions and comparative assessments of drug products and devices; however, all too often these claims are presented in a form that is either unverifiable or potentially verifiable but in a time frame that is of no practical use to formulary committees and others who may be committed to ongoing disease-area and therapeutic-class reviews. On the assumption that formulary committees are interested in testable predictions for product performance in target populations and ongoing disease area and therapeutic reviews, the methodological standards that should be applied are those that are accepted in the natural sciences. Claims should be presented in a form that is amenable to falsification. If not, they have no scientific standing. Certainly one can follow ISPOR-SMDM standards for validating the assumptions underpinning a model or simulation. There is clearly an important role for simulations as an input to policy initiatives and developing claims for healthcare interventions and testable hypotheses; however, one would not evaluate such claims on the realism or otherwise of the model. The only standard is one of the model’s ability to predict outcomes successfully in a time frame that is practical and useful. No other standard is acceptable. This sets the stage for an active research agenda.     

Predictive validation of modeled health technology assessment claims: lessons from NICE

Abstract

The use of cost-effectiveness modeling to prioritize healthcare spending has become a key foundation of UK government policy. Although the preferred method of evaluation—cost-utility analysis—is not without its critics, it represents a standard approach that can arguably be used to assess relative value for money across a range of disease types and interventions. A key limitation of economic modeling, however, is that its conclusions hinge on the input assumptions, many of which are derived from randomized controlled trials or meta-analyses that cannot be reliably linked to real-world performance of treatments in a broader clinical context. This means that spending decisions are frequently based on artificial constructs that may project costs and benefits that are significantly at odds with those that are achievable in reality. There is a clear agenda to carry out some form of predictive validation for the model claims, in order to assess not only whether the spending decisions made can be justified post hoc, but also to ensure that budgetary expenditure continues to be allocated in the most rational way. To date, however, no timely, effective system to carry out this testing has been implemented, with the consequence that there is little objective evidence as to whether the prioritization decisions made are actually living up to expectations. This article reviews two unfulfilled initiatives that have been carried out in the UK over the past 20 years, each of which had the potential to address this objective, and considers why they failed to deliver the expected outcomes.     

Embracing invention similarity for the measurement of vertically overlapping claims

ABSTRACT

Clear and well-defined patent rights can incentivize innovation by granting monopoly rights to the inventor for a limited period of time in exchange for public disclosure of the invention. However, with cumulative innovation, when a product draws from intellectual property held across multiple firms (including fragmented intellectual property or patent thickets), contracting failures may lead to suboptimal economic outcomes. However, an alternative theory, developed by a variety of scholars, contends that patent thickets have a more ambiguous effect. Researchers have developed several measures to gauge the extent and impact of cumulative innovation and the various channels of patent thickets. This paper contends that mis-measurement may contribute to the incoherence and overall lack of consensus within the patent thickets literature. Specifically, the literature is missing a precise measure of vertically overlapping claims. We propose a new measure of vertically overlapping claims that incorporates invention similarity to more precisely identify inventive overlap. The measure defined in this paper will enable more accurate measurement, and allow for novel economic research on cumulative innovation, fragmentation in intellectual property, and patent thickets within and across all patent jurisdictions.     

Medical chart validation of an algorithm for identifying multiple sclerosis relapse in healthcare claims

Abstract

Objective:

Relapse is a common measure of disease activity in relapsing-remitting multiple sclerosis (MS). The objective of this study was to test the content validity of an operational algorithm for detecting relapse in claims data.

Methods:

A claims-based relapse detection algorithm was tested by comparing its detection rate over a 1-year period with relapses identified based on medical chart review. According to the algorithm, MS patients in a US healthcare claims database who had either (1) a primary claim for MS during hospitalization or (2) a corticosteroid claim following a MS-related outpatient visit were designated as having a relapse. Patient charts were examined for explicit indication of relapse or care suggestive of relapse. Positive and negative predictive values were calculated.

Results:

Medical charts were reviewed for 300 MS patients, half of whom had a relapse according to the algorithm. The claims-based criteria correctly classified 67.3% of patients with relapses (positive predictive value) and 70.0% of patients without relapses (negative predictive value; kappa 0.373: p?<?0.001). Alternative algorithms did not improve on the predictive value of the operational algorithm. Limitations of the algorithm include lack of differentiation between relapsing-remitting MS and other types, and that it does not incorporate measures of function and disability.

Conclusions:

The claims-based algorithm appeared to successfully detect moderate-to-severe MS relapse. This validated definition can be applied to future claims-based MS studies.     

Migraine burden and costs in France: a nationwide claims database analysis of triptan users

Objectives: To estimate the burden of migraine in the population of French patients identified as specific migraine acute treatment users compared to a control group.

Methods: A cross-sectional retrospective analysis was performed on the Echantillon Généraliste des Bénéficiaires claims database, a 1/97 random sample of the French public insurance database. A representative sample of all adults with at least one delivery of triptans, ergot derivatives or acetylsalicylic acid/metoclopramide (all drugs with a specific label in migraine acute treatment – SMAT) in 2014 was selected with a control group matched on age, gender and geographic region. Among triptan users, a sub-group of over-users was defined according to their level of triptan uptake expressed in defined daily doses (DDD – a standard daily dose of treatment of acute migraine) per month over 3?months and more, was also compared with controls. The cost analysis was performed in a societal perspective for direct costs. Sick leave indirect costs were estimated using the human capital approach.

Results: In total 8639 SMAT users (mean age: 44.6?years; 78.7% women) were selected representing a crude prevalence rate of 1.7%. The annual per capita total healthcare expenditures were higher by €280 in this group compared to controls (€2463 vs. €2183). Triptans contributed 47.8% to this extra cost. They used significantly (p?Conclusions: Due to its high prevalence, migraine costs generate a significant societal burden. The group of over-users concentrates high per capita direct and indirect costs.     

False claims in politics: Evidence from the US

In this paper, we use data on 2459 public claims made by 444 politicians from the leading US fact-checking site (PolitiFact) to provide an empirical analysis of false claims in politics, shedding light on their characteristics within an advanced democracy. The frequency of falsehoods differs according to party affiliation and topic, with false claims more likely on such topics as elections, health, labor, taxes and values. For Republican politicians, falsehood pays off in the short run, as it is associated with greater political support.     

我国慈善事业透明化设计原则与路径选择

2011年被称为我国慈善透明问责年,如何让我国慈善事业健康发展、少走弯路,关键问题是透明度建设。因此,我国慈善事业透明化的设计原则应为改进原则、平等自愿原则、科学自由原则,路径选择为官方慈善组织转型和民间慈善组织借鉴路径。     

Economic outcomes of exenatide vs liraglutide in type 2 diabetes patients in the United States: results from a retrospective claims database analysis

Abstract

Objective:

The safety and efficacy of the GLP-1 receptor agonists exenatide BID (exenatide) and liraglutide for treating type 2 diabetes mellitus (T2DM) have been established in clinical trials. Effective treatments may lower overall treatment costs. This study examined cost offsets and medication adherence for exenatide vs liraglutide in a large, managed care population in the US.

Methods:

This was a retrospective cohort analysis comprising adult patients with T2DM who initiated exenatide or liraglutide between 1/1/2010 and 6/30/2010 and had 6 months pre-index and post-index continuous eligibility. Patients were propensity score-matched to controls for baseline differences. Medication adherence was measured by proportion of days covered (PDC). Paired t-test and McNemar’s test were used to compare outcomes.

Results:

Matched exenatide and liraglutide cohorts (n?=?1347 pairs) had similar average total 6-month follow-up costs ($6688 vs $7346). However, exenatide patients had significantly lower mean pharmacy costs ($2925 vs $3272, p?<?0.001). Among liraglutide patients, patients receiving the 1.8?mg dose had significantly higher average total costs compared to those receiving the 1.2?mg dose ($8031 vs $6536, p?=?0.026), with higher mean pharmacy costs in the 1.8?mg cohort ($3935 vs $3146, p?<?0.001). There were no significant differences in inpatient or outpatient costs or medication adherence between groups (mean PDC: exenatide 56% vs liraglutide 57%, p?=?0.088).

Limitations:

The study assumed that all information needed for case classification and matching of cohorts was present and not differential across cohorts. The study did not control for covariates that were unavailable, such as HbA1c and duration of diabetes.

Conclusions:

Patients initiating exenatide vs liraglutide for T2DM had similar medication adherence and total healthcare costs; however, exenatide patients had significantly lower total pharmacy costs. Patients prescribed 1.8?mg liraglutide had significantly higher costs compared to those on 1.2?mg.     

诚信的经济学分析

本文以信息经济、交易费用、产权和博弈论为依据分析诚信和诚信缺失问题,探讨诚信与市场经济运行的内在关系.用社会生产方式对立统一运动的辩证观点,阐述诚信是经济范畴又不是经济范畴;从社会物质文明和精神文明协调发展的角度,说明构建与市场经济相适应的社会诚信体系的重要现实意义和历史意义.     

Treatment patterns and healthcare resource utilization and costs in heavy menstrual bleeding: a Japanese claims database analysis

Aims: Heavy menstrual bleeding (HMB) is a highly prevalent condition, characterized by excessive menstrual blood loss and cramping, that interferes with activities of daily life. The aim of this study was to investigate treatment patterns in HMB in Japan, and to assess healthcare resource utilization and costs among women newly-diagnosed with the condition.

Materials and methods: This study retrospectively analyzed health insurance data available in the Japan Medical Data Center (JMDC) database on women aged 18–49 years who were newly-diagnosed with primary or secondary HMB. Treatment patterns were analyzed, and healthcare utilization and costs were evaluated and compared to matched controls.

Results: The study included a total of 635 patients, 210 with primary HMB and 425 with secondary HMB. In the primary HMB cohort, 60.0% of patients received one or more pharmacological or surgical treatments, compared with 76.2% in the secondary HMB cohort. The most commonly prescribed medications in all patients were hemostatic agents (28.7%), traditional Chinese medicine (TCM) (12.1%), and low-dose estrogen progestins (LEPs) (10.1%). After adjustment for patient baseline characteristics, healthcare costs were 1.93-times higher in primary HMB cases (p?<?.0001) and 4.44-times higher in secondary HMB cases (p?<?.0001) vs healthy controls. Outpatient care was the main cost driver.

Limitations: The main limitations of this study are related to its retrospective nature, and the fact that only reimbursed medications were captured in the source database.

Conclusions: A substantial proportion of HMB patients did not receive the recommended treatments. Healthcare costs were considerably increased in the presence of an HMB diagnosis.     

The market value of preventive activities: A contingent-claims approach

We use a contingent-claims approach to determine the market value of preventive investments. We show that the lower the initial probability of accident, the greater is the market value of a reduction in this probability. Besides, at initially low probabilities, ceteris paribus, the market gives a higher value to a reduction in accident probability when aggregate (correlated) catastrophic risks rather than independent ones are involved. The reverse occurs at initially high probabilities.     

Inflation targeting credibility and reputation: The consequences for the interest rate

The measurement of credibility and reputation is fundamental for the analysis of countries which adopted inflation targeting. Under this perspective, the objective of this article is to illustrate which measures of credibility and reputation are most useful in predicting variations of interest rates. Given a specific inflation target, this relationship is valuable for central bankers as well as for private agents trying to predict the central bank's policies. Due to the fact that Brazil represents a potential laboratory experiment in which the effects of an adoption of inflation targeting after more than a half decade can be observed, an analysis through several indices and its relation with the basic interest rate is made. The findings denote that the credibility indices based on reputation represent an alternative in the cases where the series of inflation expectation are not available. Furthermore, the empirical evidence confirms the hypothesis that higher credibility implies lower variations in the interest rate for controlling inflation.     

Raising an inflation target: The Japanese experience with Abenomics

This paper draws from Japan׳s recent monetary experiment to examine the effects of an increase in the inflation target during a liquidity trap. We review Japanese data and examine through a VAR model how macroeconomic variables respond to an identified inflation target shock. We apply these findings to calibrate the effect of a shock to the inflation target in a new-Keynesian DSGE model of the Japanese economy. We argue that imperfect observability of the inflation target and a separate exchange rate shock are needed to successfully account for the behavior of nominal and real variables in Japan since late 2012. Our analysis indicates that Japan has made some progress towards overcoming deflation, but further measures are needed to raise inflation to 2 percent in a stable manner.     

政府公信力与区域经济增长——基于新经济地理学的空间经济分析

政府公信力反映了公众对政府行为的满意程度,对区域经济发展具有重要的影响作用。政府公信力具有明显的空间差异性,是区域经济发展的重要空间向度。基于新经济地理学的空间经济建模技术,显著具有空间差异性的政府公信力完全可以纳入到空间经济增长理论模型当中,这不仅可以深入探究政府公信力在区域经济增长中的作用机制,而且通过理论分析和模型推演还可以进一步揭示出,政府公信力在区域经济增长的路径选择上具有重要的作用,是区域经济差异化的重要推进力量。     

所有者和经营者的风险偏好与最佳报酬安排

从委托代理矛盾入手，对所有者与经营者的行为进行分析，按照效用最大化原则建立了委托代理矛盾的数学模型，并对模型求解，得出风险偏好与报酬安排的最佳关系。所有者与经营者的关系是委托代理关系，风险偏好是契约安排的最重要的一个参数；只要所有者与经营者的剩余索取权之比等于他们各自的风险偏好之比，就可以得到最佳的激励报酬安排。     

计量经济学应用研究的可信性革命

可信性是计量经济学应用研究的重要问题,其核心在于实现经济理论、统计学、数学在实证研究中的科学结合。本文基于国际计量经济学界对可信性问题的三次大讨论取得的重要进展,厘清了计量经济学探索客观经济世界过程的本质特征;进而针对应用研究中存在的滥用和错用现象,从计量经济模型的随机性设定、经济变量之间的因果关系识别以及模型的统计适切性评价等三个方面阐述计量经济学应用研究的可靠性来源。我国计量经济学的应用研究面临进一步提高可信性的重要问题,需要全面吸收和借鉴国际计量经济学界对于可信性问题的成果,改变研究模式和教学模式。     

A note on the welfare consequences of wage indexing in a stochastic economy

This note surveys the welfare and real consequences of wage indexing in a stochastic economy whose monetary authority lacks credibility. It shows in a unified framework that those consequences might differ markedly depending on the nature and timing of the dominant disturbance in that economy. It finally provides a closed-form expression of the optimal level of wage indexing when all the shocks are taken into account.Received: July 2002, Accepted: February 2004, JEL Classification: E61Pierre-Guillaume Méon: I thank Giuseppe Diana and an anonymous referee for helpful comments and suggestions. The remaining errors are definitely mine.     

Medical cost,incidence rate,and treatment status of gastroesophageal reflux disease in Japan: analysis of claims data

Objectives: Published reports have shown the prevalence and incidence of gastroesophageal reflux disease (GERD) is increasing in Japan. The objective of this study is to examine change in GERD incidence, and to understand current patient demographics, medical costs, treatment status, and the suitability of current treatment based on analysis of an insurance claims database.

Methods: An insurance claims database with data on ～1.9 million company employees from January 2005 to May 2015 was used. Prevalence, demographics, and medical costs were analyzed by cross-sectional analysis, and incidence and treatment status were analyzed by longitudinal analysis among newly-diagnosed GERD patients.

Results: GERD prevalence in 2014 was 3.3% among 20–59 year-olds, accounting for 40,134 people in the database, and GERD incidence increased from 0.63% in 2009 to 0.98% in 2014. In 2014, mean medical cost per patient per month for GERD patients aged 20–59 was JPY 31,900 (USD 266 as of January 2016), which was ～2.4-times the mean national healthcare cost. The most frequently prescribed drugs for newly-diagnosed GERD patients were proton pump inhibitors (PPIs). Although PPIs were prescribed more often in patients with more doctor visit months, over 20% of patients that made frequent doctor visits (19 or more visits during a 24 calendar months period) were prescribed PPIs during only 1 calendar month or not at all.

Limitations: The database included only reimbursable claims data and, therefore, did not cover over-the-counter drugs. The database also consisted of employee-based claims data, so included little data on people aged 60 years and older.

Conclusions: Given the increasing incidence of GERD in Japan there is a need for up-to-date information on GERD incidence. This study suggests that some GERD patients may not be receiving appropriate treatment according to Japanese guidelines, which is needed to improve symptom control.     

The economics of upper gastrointestinal bleeding in a US managed-care setting: a retrospective,claims-based analysis

Abstract

Objective: To assess 12-month healthcare resource utilization and costs associated with upper gastrointestinal (UGI) bleeding events.

Methods: Patients hospitalized with a UGI bleeding event were identified in US national health-plan claims data (1999–2003) and propensity matched to control patients without UGI bleeding in the same health plan. Matching criteria included age, gender, index date, Charlson Comorbidity Index score, geographic region, and prior medical utilization.

Results: A total of 9,033 UGI-bleed patients and 579,018 control patients met the inclusion criteria, yielding 4,651 matched pairs. After matching, differences between the UGI bleed and general population cohorts remained for office visits, ER visits, and ER costs during the 6-month baseline period prior to the index date. During the 12 months following the index date, both UGI-related healthcare utilization and total healthcare, medical, and pharmacy costs incurred by the UGI-bleed cohort were significantly greater (p<?0.0001) than those incurred by the general population cohort (mean of $20,405 vs. 3,652), even after excluding the initial hospitalization costs (mean of $11,228 vs. 3,652). Costs were primarily due to inpatient hospitalizations (mean of $13,059 for the UGI-bleed cohort vs. $729 for the general population cohort) and ambulatory services (mean of $4,037 for the UGI-bleed cohort vs. $1,537 for the general population cohort). Sixteen percent of the UGI-bleed cohort had a GI-related hospitalization, and about 40% of total costs occurred after the initial hospitalization.

Conclusions: Patients with UGI bleeds experienced significantly higher (p<?0.0001) 12-month health-resource utilization and costs than patients without UGI bleeds. This study provides empirical evidence of the long-term economic burden associated with UGI bleeding. Interpretation of the results should take into account the lack of available information in claims data that could have an effect on study outcomes, such as particular clinical and disease-specific parameters that are not mitigated by propensity score and comorbidity index matching. In addition, this study is limited by the intensive demographic matching that was done between the two cohorts, which may have eliminated the sickest UGI patients and the healthiest general health-plan population patients.