John Hornberger

Impact of a 21-gene RT-PCR assay on treatment decisions in early-stage breast cancer: an economic analysis based on prognostic and predictive validation studies.

The prognostic accuracy for distant recurrence‐free survival using a 21‐gene reverse‐transcriptase polymerase chain reaction (RT‐PCR) assay underwent validation in 668 lymph node‐negative, estrogen receptor‐positive women with early‐stage breast cancer receiving tamoxifen on National Surgical Adjuvant Breast Program (NSABP) B‐14. The predictive accuracy for treatment efficacy also underwent validation in 651 patients randomized on NSABP B‐20 and 645 patients on NSABP B‐14.

Cost-Effectiveness of a Vaccine To Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults

Context A recent large trial proved that a live attenuated varicella-zoster virus vaccine reduced the incidence and severity of herpes zoster in older adults. Contribution This decision model suggests that vaccination could improve quality-adjusted survival by small amounts. Vaccination is, however, unlikely to cost less than

A cost-effectiveness analysis of prescribing strategies in the management of gastroesophageal reflux disease.

100000 per quality-adjusted life year gained unless the vaccination cost is less than

Challenges in the Development and Reimbursement of Personalized Medicine—Payer and Manufacturer Perspectives and Implications for Health Economics and Outcomes Research: A Report of the ISPOR Personalized Medicine Special Interest Group

200 and duration of vaccine efficacy exceeds 20 years. Targeting adults 60 to 69 years of age rather than those older than 80 years of age would be most cost-effective. Cautions We do not yet know how long the vaccine remains effective. The Editors Herpes zoster results from reactivation of latent varicella-zoster virus (VZV) infection residing in sensory ganglia. The disease presents as a clinical syndrome characterized by a painful vesicular eruption (1). In the United States, herpes zoster affects about 300000 to 600000 persons annually (2). Sequelae occur in about 12% of cases and include postherpetic neuralgia (PHN) (7.9%), bacterial skin infections (2.3%), ocular complications (such as uveitis and keratitis) (1.6%), motor neuropathy (0.9%), meningitis (0.5%), and herpes simplex virus oticus (0.2%) (3). Herpes zoster incidence is approximately 2.2 cases per 1000 person-years and peaks at 14.2 cases per 1000 person-years for individuals older than age 75 years (4, 5). The Shingles Prevention Study examined whether vaccination with a live attenuated VZV vaccine would decrease the incidence and severity of herpes zoster and PHN in adults 60 years of age or older (6). Vaccination statistically significantly reduced the incidence of zoster from 11.12 to 5.42 cases per 1000 person-years. Median follow-up was 3.1 years, and relative risk reduction was 51.3% (95% CI, 44.2% to 57.6%). The incidence of PHN at 90 days was reduced from 1.38 cases to 0.46 case per 1000 person-years, and relative risk reduction was 66.5% (CI, 47.5% to 79.2%). The published price for the pediatric VZV vaccine (Varivax, Merck & Co., Whitehouse Station, New Jersey) is

Effects of a Self-Administered Previsit Questionnaire to Enhance Awareness of Patients' Concerns in Primary Care

56.90 for the Centers for Disease Control and Prevention (CDC) and

Clinical Validity/Utility, Change in Practice Patterns, and Economic Implications of Risk Stratifiers to Predict Outcomes for Early-Stage Breast Cancer: A Systematic Review

66.81 for the private sector (7). In an editorial accompanying the Shingles Prevention Study report, Gilden (8) suggested that a price of

Prostate-specific antigen is not excretedby human kidney or eliminated by routine hemodialysis

500 for the adult vaccine would probably be cost-effective and would perhaps even be cost-saving. Even at a cost of

Clinical validity of cytochrome P450 metabolism and serotonin gene variants in psychiatric pharmacotherapy

56.90 for the vaccine, the estimated U.S. expenditures for the vaccine could exceed

Risks and costs of end-stage renal disease after heart transplantation

2.8 billion if routine vaccination were recommended for all adults 60 years of age or older (more than 49 million people in 2005). Policy decisions about such a large public expenditure should be based on further assessment of the programs clinical and economic implications. We performed an analysis of the cost-effectiveness of VZV vaccination in immunocompetent older adults. Methods We constructed a decision theoretical model with Microsoft Office Excel 2003 and Microsoft Visual Basic 6.3 software (Microsoft Corp., Redmond, Washington) to compare the clinical and economic effects of VZV vaccination with those of no vaccination in older adults (Figure 1). At a given time, a patient may be in one of a finite number of health states. Events are modeled as transitions from one state to another. For each state, a utility is assigned as an adjustment factor for quality of life. Utility weights typically range from 0 to 1, in which 0 represents a state as bad as death, 1 represents perfect health, and values between 0 and 1 represent states between these extremes. The contribution to total utility, commonly called quality-adjusted life-years (QALYs), of a particular state consists of the length of time spent in a state multiplied by the utility of that state. Figure 1. Markov state transition model. A patient occupies a tunnel state (white boxes) for 1 cycle only. Curved arrows denote death. The effect of herpes zoster on burden of illness in the model reflects the findings of the Shingles Prevention Study (6). PHN = postherpetic neuralgia. The target population is immunocompetent persons 60 years of age or older (median age, 69 years) with a history of VZV infection (6). The representative person starts without herpes zoster but may later experience clinical herpes zoster (6). Six months after onset of acute zosterthe duration of follow-up of a zoster episode in the Shingles Prevention Studythe patient may experience persistent PHN (9) or have no zoster-related sequelae. Risk for a subsequent case of herpes zoster is equal to that of the first event (4, 1014). Data Sources We conducted searches of English-language literature published from 1966 to March 2006 by using PubMed. We specifically looked for original-data studies that provided descriptive statistics pertinent to the following questions: What is the duration of PHN? What is the duration of vaccine efficacy? What is the lost work productivity due to an episode of acute zoster? What are the costs of an acute zoster episode and PHN? The Appendix provides details of these searches. Data and Assumptions The model captures 3 effects of vaccination: 1) incidence of herpes zoster, 2) zoster-specific burden of illness, and 3) incidence and duration of PHN among patients with herpes zoster (Table 1). Table 1. Model Assumptions* The Shingles Prevention Study (6) provided data on the age-related incidence of herpes zoster. The number of persons needed to vaccinate to prevent 1 herpes zoster episode over the 3.1 years of the Shingles Prevention Study varied from 46 persons 65 to 69 years of age to 152 persons 85 to 89 years of age. Investigators of the Shingles Prevention Study selected the participants burden of illness as the protocol-specified primary end point. They obtained burden-of-illness scores from patient responses to the worst pain question of the Zoster Brief Pain Inventory (9). Responses could range from no pain (score of 0) to pain as bad as you can imagine (score of 10). Analysts computed the burden-of-illness score as the area under the curve of pain scores reported over the 182 days of follow-up from onset of herpes zoster (score range, 0 to 1813). They assigned a score of 0 to participants who never experienced herpes zoster and defined PHN as a burden-of-illness score of 3 or higher occurring after 90 days from the onset of a zoster rash. The mean burden-of-illness score for participants who had herpes zoster was 147.1 for vaccinated patients and 177.7 for unvaccinated patients (15). Among the 315 vaccinated persons who developed acute zoster, 27 (8.6%) cases of PHN occurred, and 9 (2.9%) of these cases lasted longer than 6 months. Among the 642 unvaccinated persons who developed acute zoster, 80 (12.5%) cases of PHN occurred, and 33 (5.1%) of these cases lasted longer than 6 months. The daily resolution rate varied between 0.63% and 1.48%, with no reported difference between study groups. We assumed an average daily rate of resolution for both groups of 1.1%. At this rate, more than half of patients would resolve PHN by 8 months after the onset of acute zoster (range, 6 to 18 months). The probability of death in the Shingles Prevention Study was 0.013% and did not differ between the vaccinated and unvaccinated study groups (6). We assumed that the risk for zoster-related death increased with age, as reported elsewhere (16). We also considered the age- and sex-specific risk for death from other conditions in the model. Vaccine-related injection site reactions occurred in 31.7% of patients (range, 28.3% to 32.6%), consisting of erythema (28.8%), pain or tenderness (26%), swelling (21.7%), pruritus (6.1%), warmth (1.4%), hematoma (0.2%), or rash (0.2%) (6). We assumed that the average duration of symptoms was 2 days (range, 0 to 5 days). The duration of vaccine efficacy beyond the median 3.1-year duration of follow-up in the Shingles Prevention Study is unknown. On the basis of Japanese and U.S. studies, the CDC reports that protection for children lasts for at least 15 to 25 years with the childhood VZV vaccine (28). However, the CDC cautions that protection is never known when a vaccine is first introduced, and surveillance studies of the childhood vaccine that assess the durability of efficacy are ongoing. Given this uncertainty, we estimated the cost-effectiveness of adult VZV vaccination for durations of efficacy ranging from 3 to 30 years. Utilities We assigned utilities to the health states in the model: no zoster, acute zoster, and PHN. A paper by the investigators of the Shingles Prevention Study estimated utilities by using the EuroQoL visual analogue scale (VAS) scores (9). At baseline in the Shingles Prevention Study, the utility for no herpes zoster was 0.860. Among participants with PHN, the mean utility was 0.594. We applied a range of utilities in sensitivity analyses. We computed QALYs as the sum of mean discounted durations of health states weighted by the utility for each health state. We calculated incremental cost-effectiveness ratios as the difference in discounted costs between vaccination and no vaccination (incremental costs per herpes zoster case avoided) divided by the difference in benefits (QALYs gained). Costs We collected costs from various published sources. Smith and Roberts (26) provided a detailed synthesis of 5 studies on the costs (in 1995 U.S. dollars) of managing herpes zoster in immunocompetent persons. We replicated their study method by using the same cost categories, but we updated inputs by using contemporary data sources. We included costs of 2 physician office visits for an established patient (Current Procedural Terminology [CPT] 99213) (17). Antivirals for herpes zoster include acyclovir, 800 mg, taken orally 5 times daily for 7 days; famciclovir, 750 mg, taken orally once daily for 7 days; and valacyclovir, 1000 mg, taken orally 3 times daily for 7 days. We used average wholesale prices published in Mosbys Drug Consult 2006 (1820) and retail prices from

DECIDING ELIGIBILITY FOR TRANSPLANTATION WHEN A DONOR KIDNEY BECOMES AVAILABLE

OBJECTIVE:Patients who have uncomplicated gastroesophageal-reflux disease (GERD) typically present with heartburn and acid regurgitation. We sought to determine the cost-effectiveness of H2-receptor antagonists (H2RAs) and proton-pump inhibitors (PPIs) as first-line empiric therapy for patients with typical symptoms of GERD.METHODS:Decision analysis comparing costs and benefits of empirical treatment with H2RAs and PPIs for patients presenting with typical GERD was employed. The six treatment arms in the model were: 1) Lifestyle therapy, including antacids; 2) H2RA therapy, with endoscopy performed if no response to H2RAs; 3) Step up (H2RA-PPI) Arm: H2RA followed by PPI therapy in the case of symptomatic failure; 4) Step down arm: PPI therapy followed by H2RA if symptomatic response to PPI, and antacid therapy if response to H2RA therapy; 5) PPI-on-demand therapy: 8 wk of treatment for symptomatic recurrence, with no more than three courses per year; and 6) PPI-continuous therapy. Measurements were lifetime costs, quality-adjusted life years (QALYs) gained, and incremental cost effectiveness.RESULTS:Initial therapy with PPIs followed by on-demand therapy was the most cost-effective approach, with a cost-effectiveness ratio of