Early analysis shows that endoscopic flexor hallucis longus transfer has a promising cost-effectiveness profile in the treatment of acute Achilles tendon ruptures.

PURPOSE: Current options for treating an Achilles tendon rupture (ATR) include conservative and surgical approaches. Endoscopic flexor hallucis longus (FHL) transfer has been recently proposed to treat acute ruptures, but its cost-effectiveness potential remains to be evaluated. Therefore, the objective of this study was to perform an early cost-effectiveness analysis of endoscopic FHL transfer for acute ATRs, comparing the costs and benefits of current treatments from a societal perspective. METHODS: A conceptual model was created, with a decision tree, to outline the main health events during the treatment of an acute ATR. The model was parameterized using secondary data. A systematic review of the literature was conducted to gather information on the outcomes of current treatments. Data related to outcomes of endoscopic FHL transfers in acute Achilles ruptures was obtained from a single prospective study. Analysis was limited to the two first years. The incremental cost-effectiveness ratio was the main outcome used to determine the preferred strategy. A willingness-to-pay threshold of $100,000 per quality-adjusted life-year was used. Sensitivity analyses were performed to determine whether changes in input parameters would cause significant deviation from the reference case results. Specifically, a probability sensitivity analysis was conducted using Monte Carlo simulations, and a one-way sensitivity analysis was conducted by sequentially varying each model parameter within a given range. RESULTS: For the reference case, incremental cost-effectiveness ratios exceeded the willingness-to-pay threshold for all the surgical approaches. Overall, primary treatment was the main cost driver. Conservative treatment showed the highest direct costs related to the treatment of complications. In the probabilistic sensitivity analysis, at a willingness-to-pay threshold of $100,000, open surgery was cost-effective in 50.9%, minimally invasive surgery in 55.8%, and endoscopic FHL transfer in 72% of the iterations. The model was most sensitive to parameters related to treatment utilities, followed by the costs of primary treatments. CONCLUSION: Surgical treatments have a moderate likelihood of being cost-effective at a willingness-to-pay threshold of $100,000, with endoscopic FHL transfer showing the highest likelihood. Following injury, interventions to improve health-related quality of life may be better suited for improved cost-effectiveness. LEVEL OF EVIDENCE: Level III.

Economics of Beta-Cell Replacement Therapy.

PURPOSE OF REVIEW: Type 1 diabetes impacts 1.3 million people in the USA with a total direct lifetime medical cost of $133.7 billion. Management requires a mix of daily exogenous insulin administration and frequent glucose monitoring. Decision-making by the individual can be burdensome. RECENT FINDINGS: Beta-cell replacement, which involves devices protecting cells from autoimmunity and allo-rejection, aims at restoring physiological glucose regulation and improving clinical outcomes in patients. Given the significant burden of T1D in the healthcare systems, cost-effectiveness analyses can drive innovation and policymaking in the area. This review presents the health economics analyses performed for donor-derived islet transplantation and the possible outcomes of stem cell-derived beta cells. Long-term cost-effectiveness of islet transplantation depends on the engraftment of these transplants, and the expenses and thresholds assumed by healthcare systems in different countries. Early health technology assessment analyses for stem cell-derived beta-cell replacement suggest manufacturing optimization is necessary to reduce upfront costs.

Bringing Stem Cell-Based Therapies for Type 1 Diabetes to the Clinic: Early Insights from Bioprocess Economics and Cost-Effectiveness Analysis.

Differentiation of pluripotent stem cells (PSCs) into ß cells could provide insulin independence for type 1 diabetes (T1D) patients. This approach would reduce the clinical complications that most patients managed on intensive insulin therapy (IIT) face. However, bottlenecks of PSC manufacturing and limited engraftment of encapsulated cells hinder the long-term effectiveness of these therapies. A bioprocess decision-support tool is combined with a disease state-transition model to evaluate the cost-effectiveness of the stem cell-based therapy against IIT. Clinical effectiveness is assessed in quality-adjusted life years (QALYs). Manufacturing costs per patient reduce from $430 000 to $160 000 with optimization of batch size and annual demand. For 96% of the patients, cell therapy improves the quality of life compared to IIT. Cost savings are achieved for 2% of the population through prevention of renal disease. The therapy is cost-effective for 3.4% of patients when a willingness to pay (WTP) of up to $150 000 per QALY is considered. A 75% cost reduction in the cell therapy price increases cost-effectiveness likelihood to 51% at $100 000 per QALY. This study highlights the need for scalable manufacturing platforms for stem cell therapies, as well as to prioritizing access to the therapy to patients with an increased likelihood of costly complications.

Modeling biological and economic uncertainty on cell therapy manufacturing: the choice of culture media supplementation.

AIM: To evaluate the cost-effectiveness of autologous cell therapy manufacturing in xeno-free conditions. MATERIALS & METHODS: Published data on the isolation and expansion of mesenchymal stem/stromal cells introduced donor, multipassage and culture media variability on cell yields and process times on adherent culture flasks to drive cost simulation of a scale-out campaign of 1000 doses of 75 million cells each in a 400 square meter Good Manufacturing Practices facility. RESULTS & CONCLUSION: Passage numbers in the expansion step are strongly associated with isolation cell yield and drive cost increases per donor of $1970 and 2802 for fetal bovine serum and human platelet lysate. Human platelet lysate decreases passage numbers and process costs in 94.5 and 97% of donors through lower facility and labor costs. Cost savings are maintained with full equipment depreciation and higher numbers of cells per dose, highlighting the number of cells per passage step as the key cost driver.

Medical Students Who Pursue a Joint MD/MBA Degree: Who Are They and Where Are They Heading?

Increasingly, health care is being delivered in large, complex organizations, and physicians must learn to function effectively in them. As a result, several medical and business schools have developed joint programs to train physician leaders who receive both medical degree (MD) and master of business administration (MBA) degrees. We examined several themes in relation to these programs, revolving around concerns about who is attracted to them and whether exposure to the differing cultures of medicine and business have an impact on the professional identities of their graduates as manifested in their motivations, aspirations, and careers. We addressed these issues by studying students in the joint MD/MBA program at Harvard Medical School (HMS) and Harvard Business School (HBS). Our data came from several internal sources and a survey of all students enrolled in the joint program in spring 2013. We found relatively few differences between joint program students and equivalent cohorts of HMS students in terms of personal characteristics, preadmission performance, and performance at HMS and HBS. Contrary to the concerns that such programs may draw students away from medicine, the vast majority embraced careers involving extensive postgraduate medical training, with long-term plans that leveraged their new perspectives and skills to improve health care delivery.

Vaccine availability in the United States during the 2009 H1N1 outbreak.

OBJECTIVE: After initial flu cases are reported, months elapse before vaccine becomes available. The authors report the experience of US states during the fall of 2009 on H1N1 vaccine availability in relation to the occurrence of disease. DESIGN: The authors used data from the Centers for Disease Control and prevention and state health departments to approximate second wave H1N1 epidemic curves. The authors compared these curves to two sources of vaccine distribution data-shipment and administration. RESULTS: Ten states received their first shipments of vaccine after the epidemic peaked, four states during the week of the peak, and 10 states only 1 week prior to the peak. In nearly half of all states, the epidemic had already begun to decline before any individuals could have been protected. CONCLUSIONS: A sensible approach would be to highlight the importance of diligent hygienic behavior and to reduce the rate of human-to-human contacts before vaccine is available.

A framework to evaluate the economic impact of pharmacogenomics.

INTRODUCTION: Pharmacogenomics and personalized medicine promise to improve healthcare by increasing drug efficacy and minimizing side effects. There may also be substantial savings realized by eliminating costs associated with failed treatment. This paper describes a framework using health claims data for analyzing the potential value of pharmacogenomic testing in clinical practice. METHODS: We evaluated a model of alternate clinical strategies using asthma patients' data from a retrospective health claims database to determine a potential cost offset. We estimated the likely cost impact of using a hypothetical pharmacogenomic test to determine a preferred initial therapy. We compared the annualized per patient costs distributions under two clinical strategies: testing all patients for a nonresponse genotype prior to treating and testing none. RESULTS: In the Test All strategy, more patients fall into lower cost ranges of the distribution. In our base case (15% phenotype prevalence, 200 US dollars test, 74% overall first-line treatment efficacy and 60% second-line therapy efficacy) the cost savings per patient for a typical run of the testing strategy simulation ranged from 200 US dollars to 767 US dollars (5th and 95th percentile). Genetic variant prevalence, test cost and the cost of choosing the wrong treatment are key parameters in the economic viability of pharmacogenomics in clinical practice. CONCLUSIONS: A general tool for predicting the impact of pharmacogenomic-based diagnostic tests on healthcare costs in asthma patients suggests that upfront testing costs are likely offset by avoided nonresponse costs. We suggest that similar analyses for decision making could be undertaken using claims data in which a population can be stratified by response to a drug.

The economic burden of anemia in cancer patients receiving chemotherapy.

BACKGROUND: Anemia is one of the most common hematologic complications of cancer and cytotoxic treatment. The economic burden associated with anemia in patients with malignancy has not yet been extensively studied. METHODS: Patients receiving chemotherapy within 6 months of initial cancer diagnosis were identified in a database of commercial health-care service claims and encounters. Patients with anemia were identified through a coded diagnosis of anemia, transfusion, or erythropoietin treatment. Exponential conditional mean models and a decomposition analysis were used to analyze mean 6-month health-care expenditures. RESULTS: Twenty-six percent (26%) of 2760 cancer patients with recently diagnosed invasive cancer treated with chemotherapy had anemia. Mean (SD) 6-month unadjusted total expenditures were 62,499 dollars (78,016 dollars) for anemic patients and 36,871 dollars (52,308 dollars) for nonanemic patients (P < 0.0001), with inpatient services representing the largest cost differential between the groups. The adjusted mean 6-month expenditure for the average anemic patient receiving chemotherapy was 57,209 dollars. If anemic patients had the same average health status as nonanemic patients, their predicted 6-month expenditures would have been 19% lower (46,237 dollars). Alternatively, if anemic patients had the same expenditure structure or parameter estimates as nonanemic patients, their predicted expenditures would have been 51% lower (27,847 dollars). Thus, for any given health status, treating a patient who is anemic is associated with considerably higher expenditures. CONCLUSIONS: Anemia among cancer patients receiving chemotherapy is associated with a substantial burden in terms of direct medical costs. Implications for the treatment of anemia are suggested by this research and should be confirmed in prospective studies.

Benefit plan design and prescription drug utilization among asthmatics: do patient copayments matter?

The ratio of controller-to-reliever medication use has been proposed as a measure of treatment quality for asthma patients. In this study we examine the effects of plan-level mean out-of-pocket asthma medication patient copayments and other features of benefit plan design on the use of controller medications alone, controller and reliever medications (combination therapy), and reliever medications alone. The 1995--2000 MarketScan claims data were used to construct plan-level out-of-pocket copayment and physician/practice prescriber preference variables for asthma medications. Separate multinomial logit models were estimated for patients in fee-for-service (FFS) and non-FFS plans relating benefit plan design features, physician/practice prescribing preferences, patient demographics, patient comorbidities, and county-level income variables to patient-level asthma treatment patterns. We find that the controller-to-reliever ratio rose steadily over 1995--2000, along with out-of-pocket payments for asthma medications, which rose more for controllers than for relievers. After controlling for other variables, however, plan-level mean out-of-pocket copayments were not found to have a statistically significant influence on patient-level asthma treatment patterns. On the other hand, physician/practice prescribing patterns strongly influenced patient-level treatment patterns. There is no strong statistical evidence that higher levels of out-of-pocket copayments for prescription drugs influence asthma treatment patterns. However, physician/practice prescribing preferences influence patient treatment.

The use of disease-modifying new drugs for multiple sclerosis treatment in private-sector health plans.

OBJECTIVES: The aims of this study were to estimate the effects of demographics, location, severity of multiple sclerosis (MS), comorbidities, plan type, coinsurance levels, and time of entry into the sample on the use of disease-modifying agents. METHODS: A retrospective analysis of medical claims data from 1996 through 2000 was conducted with a sample of MS patients covered by self-insured, employer-sponsored health plans. Proportional hazard analysis with the SAS procedure for proportional hazards regression was used to estimate the impact of the factors of interest on the use of disease-modifying agents. A simulation was conducted to assess the impact of changing drug copayments on the use of disease-modifying agents for MS. RESULTS: The sample included 1807 patients. Patients were followed for as long as possible, but most were observed for <3 years; the mean (SD) follow-up time was 972.88 (440.59) days. Most factors associated with the use of disease-modifying agents were immutable. They included the following: high severity of illness (only marginally related; P = NS); history of seizures (P = 0.03), depression (P < 0.01), or heart disease (P = 0.01); census region of location (P < 0.01); union membership or association with a union member (P < 0.01); drug copayment requirements (P < 0.05); and year of entry into the sample (P < 0.01). In the simulation, a 50% reduction in drug copayments was associated with an increase of the proportion of patients treated with disease-modifying drugs from 41.2% to 54.7%. Patients' and physicians' preferences for treatment could not be measured directly. The true onset of MS may be unknown for many patients, but this would be the case even if medical records or other data were used for this study. CONCLUSIONS: Our analyses showed an association between copayments and the use of disease-modifying drugs for MS. Insurance policies can be tailored to influence the use of disease-modifying drugs, enhancing the quality of care for MS patients and reducing price-related barriers to beneficial treatment. Future research should test whether reducing copayments for MS treatment would reduce the use of other health care services (via better MS treatment that modifies the course of illness), or whether the use of disease-modifying drugs would increase total costs to the plan, resulting in slightly higher premiums.

Costs of antidepressant medications associated with inadequate treatment.

OBJECTIVE: To determine the costs of antidepressant medications used during inadequate treatment. STUDY DESIGN: Retrospective database analysis of pharmacy claims made by patients who were treated under routine clinical conditions from July 1, 1999, through September 30, 2002. PATIENTS AND METHODS: Our participants included 21,632 patients enrolled in a commercial HMO who had a primary care physician associated with our healthcare system. Patients never receiving at least a minimum likely effective antidepressant dose for at least 90 days were defined as having inadequate treatment. This study calculated the costs of antidepressants involved with inadequate treatment at the level of the patient and the medication trial. RESULTS: A majority of patients (51%) received inadequate treatment. Of overall antidepressant costs, 16% were incurred during trials for patients never adequately treated. The majority of inadequate trials were short and unlikely to have been effective. Most patients (64%) had only a single trial of antidepressants. Venlafaxine, fluoxetine, and sertraline had significantly lower first-trial inadequacy rates compared with the most commonly prescribed agent, citalopram. CONCLUSIONS: Improved patient care quality and lower antidepressant costs could result if clinicians and healthcare systems focus on reducing short trial rates. Initiating treatment with agents least likely to be discontinued prematurely may be helpful.

Prescriber intent, off-label usage, and early discontinuation of antidepressants: a retrospective physician survey and data analysis.

BACKGROUND: Many patients discontinue antidepressant therapy long before the 6-month minimum duration recommended for the treatment of major depression and many other diagnoses. We explore various possibilities, including prescriber intent and patient diagnosis, to explain some of this early discontinuation. METHOD: Patients from a single health maintenance organization who filled at least 1 prescription for an antidepressant during the first 4 months of 2001 and who did not fill an antidepressant prescription in the 6 months prior were identified retrospectively. Prescribers of those patients' antidepressants were surveyed for patient diagnosis and length of intended treatment with antidepressant medication. Actual length of treatment was then obtained from pharmacy data and correlated with survey data and other variables. RESULTS: Prescriber surveys were returned for 51% (485/951) of the patients identified. Surveys indicated that for 34% of initial antidepressant prescriptions, < 6 months of treatment was intended. Important determinants of the length of antidepressant therapy included prescriber specialty area, number of prescribers, prescriber intent, diagnosis, specific antidepressant used, and concomitant benzodiazepine use. CONCLUSIONS: Prescriber intention to treat many patients with short courses of antidepressants, often for off-label, non-mental health indications, was correlated with early discontinuation and needs further study of both its rationale and efficacy. Although less prevalent, short-term treatment of mental health disorders, including depression, was also intended by psychiatrists and other prescribers. The widespread practice of intended short-term treatment with antidepressants needs to be understood better, since it results in guideline-incompatible, early antidepressant discontinuation.

Impact of clinical trial results on national trends in alpha-blocker prescribing, 1996-2002.

CONTEXT: Research on factors that influence prescribing patterns and the extent of change produced by clinical trial findings is limited. OBJECTIVE: To examine the changes in prescribing of alpha-blockers for hypertension treatment before and after the April 2000 publication of the unfavorable Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) early termination involving the study's doxazosin mesylate arm. Changes in prescribing were considered in the context of other potential concurrent influences on medication use between 1996 and 2002, including changes in alpha-blocker drug prices, generic conversion, drug promotion, and competition. DESIGN, SETTING, AND PATIENTS: Using 2 national pharmaceutical market research reports published by IMS HEALTH, alpha-blocker prescription orders reported in the National Prescription Audit-a random computerized sample of about 20 000 of 29 000 retail, independent, and mail order pharmacies and mass merchandise and discount houses--and office-based physician alpha-blocker prescribing patterns reported in the National Disease and Therapeutic Index--a random stratified sample of about 3500 physician offices--were tracked. OUTCOME MEASURES: Trends in physician-reported use of alpha-blockers and alpha-blocker prescribing and dispensing by US pharmacies. RESULTS: There were steady increases in alpha-blocker new prescriptions, dispensed prescriptions, and physician drug use from 1996 through 1999. There was a moderate reversal in these trends following ALLHAT early termination and subsequent publications in early 2000. Between 1999 and 2002, new annual alpha-blocker prescription orders declined by 26% (from 5.15 million to 3.79 million), dispensed prescriptions by 22% (from 17.2 million to 13.4 million), and physician-reported drug use by 54% (from 2.26 million to 1.03 million). Other potential influences did not appear to have contributed significantly to this decline although cessation of alpha-blocker marketing may have hastened the decline. CONCLUSIONS: Modest yet statistically significant declines in the use of doxazosin and other alpha-blockers coincided with the early termination of the ALLHAT doxazosin arm. Although physicians responded to this new evidence, strategies to augment the impact of clinical trials on clinical practice are warranted.

A statistical analysis of the magnitude and composition of drug promotion in the United States in 1998.

BACKGROUND: Although pharmaceutical industry marketing and other factors may influence physician decisions regarding medication prescribing in the United States, little information is available about the composition of promotional efforts by promotional mode and medication class. OBJECTIVES: The aims of this study were to determine the magnitude of expenditures for common modes of promotion and to delineate patterns of promotional strategies for particular classes of medications. METHODS: Nationally representative data on expenditures (in US $) for the 250 most promoted medications in the United States in 1998 were available from an independent pharmaceutical market research company for the 5 most commonly used modes of promotion. Key patterns of drug promotion were identified by descriptive statistics, a cluster analysis of expenditures by class, and an analysis of expenditure concentration. RESULTS: In 1998, the pharmaceutical industry spent $12,724 million promoting its products in the United States, of which 85.9% was accounted for by the top 250 drugs and 51.6% by the top 50 drugs. Direct-to-consumer (DTC) advertising was more concentrated on a small subset of medications than was promotion to professionals. Overall, 1998 expenditures were dominated by free drug samples provided to physicians (equivalent retail cost of $6602 million) and office promotion ($3537 million), followed by DTC advertising ($1337 million), hospital promotion ($705 million), and advertising in medical journals ($540 million). Four distinct patterns of expenditures were observed: promotion to office physicians with little consumer promotion (14 drug classes); dual focus on office physicians and consumer advertising (4 drug classes); predominant DTC advertising (1 class: smoking-cessation products); and promotion to office- and hospital-based professionals without consumer advertising (1 class: narcotic analgesics). CONCLUSIONS: The present findings reinforce the perception that the pharmaceutical industry invests heavily in promoting its products and demonstrates that promotional expenditures are concentrated on a small number of medications. Although promotion to professionals remains dominant, DTC advertising has become key for a subset of common medications

Treatment costs of venlafaxine and selective serotonin-reuptake inhibitors for depression and anxiety.

In this article, health care expenditures are assessed for patients diagnosed with depression who are being treated with either venlafaxine (immediate or extended release) or a selective serotonin-reuptake inhibitor (SSRI). Patients beginning treatment for a new depressive episode were identified retrospectively from 1994 to 1998. Before beginning therapy, patients prescribed venlafaxine (N = 353) had more nonmental illnesses (0.84 vs. 0.75 clinical events/patient, respectively; P < .01) and hospitalizations for mental illness (0.56 vs. 0.30 hospitalizations/patient; P = .06) than patients prescribed SSRIs (N = 7,330). In the six months after initiating treatment, venlafaxine was associated with lower hospitalization expenditures for nonmental illness than were SSRIs ($206 vs. $472, respectively; P = .02), but total health care expenditures were not significantly different.