Empirical estimation of life expectancy from large clinical trials: use of left-truncated, right-censored survival analysis methodology.

In the current era of ever-increasing health care costs, economic analyses are an essential component in the comprehensive evaluation of new medical interventions. Cost-effectiveness analysis (CEA)--the most common form of economic analysis used in medicine--aids policy-makers in determining how to allocate finite health care dollars among possible alternative therapies. CEA relates the incremental benefits of a new technology to its incremental costs in a cost-effectiveness (CE) ratio. Although the generally agreed-upon standard of presentation for the CE ratio is the lifetime perspective (incremental lifetime cost to add one life year), this perspective presents an obvious challenge to the statistical analyst. Most large clinical trials collect limited follow-up data, and yet their findings form the basis of therapeutic recommendations that often extend far beyond the limits of the empirical data. Although clinical practice guidelines do not yet require explicit modeling to examine the long-term implications of their recommendations, health policy analyses routinely rely upon such extrapolations. This paper describes methods for using empirical patient-level data to extrapolate survival in large clinical trials and cohorts beyond a limited follow-up period in which most patients remain alive in order to estimate the entire survival distribution for a cohort of patients. We accomplish this task through a novel combination of models that estimate the hazard rate not only as a function of time but also as a function of patient age. Extrapolation of survival beyond a limited time frame is made possible by capitalizing on the extensive latitude of survival information available across the range of ages represented in the data. Variations in approach are presented, and issues arising in these analyses are discussed. The proposed methodology is developed, applied, and evaluated in both a large clinical trial cohort with 5-year follow-up on over 23,000 patients and a large observational database with long-term follow-up on over 4000 patients.

Cost-effectiveness of defibrillator therapy or amiodarone in chronic stable heart failure: results from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT).

BACKGROUND: In the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), implantable cardioverter-defibrillator (ICD) therapy significantly reduced all-cause mortality rates compared with medical therapy alone in patients with stable, moderately symptomatic heart failure, whereas amiodarone had no benefit on mortality rates. We examined long-term economic implications of these results. METHODS AND RESULTS: Medical costs were estimated by using hospital billing data and the Medicare Fee Schedule. Our base case cost-effectiveness analysis used empirical clinical and cost data to estimate the lifetime incremental cost of saving an extra life-year with ICD therapy relative to medical therapy alone. At 5 years, the amiodarone arm had a survival rate equivalent to that of the placebo arm and higher costs than the placebo arm. For ICD relative to medical therapy alone, the base case lifetime cost-effectiveness and cost-utility ratios (discounted at 3%) were dollar 38,389 per life-year saved (LYS) and dollar 41,530 per quality-adjusted LYS, respectively. A cost-effectiveness ratio < dollar 100,000 was obtained in 99% of 1000 bootstrap repetitions. The cost-effectiveness ratio was sensitive to the amount of extrapolation beyond the empirical 5-year trial data: dollar 127,503 per LYS at 5 years, dollar 88,657 per LYS at 8 years, and dollar 58,510 per LYS at 12 years. Because of a significant interaction between ICD treatment and New York Heart Association class, the cost-effectiveness ratio was dollar 29,872 per LYS for class II, whereas there was incremental cost but no incremental benefit in class III. CONCLUSIONS: Prophylactic use of single-lead, shock-only ICD therapy is economically attractive in patients with stable, moderately symptomatic heart failure with an ejection fraction < or = 35%, particularly those in NYHA class II, as long as the benefits of ICD therapy observed in the SCD-HeFT persist for at least 8 years.

Vasopeptidase inhibitor reduces inhospital costs for patients with congestive heart failure: results from the IMPRESS trial. Inhibition of Metallo Protease by BMS-186716 in a Randomized Exercise and Symptoms Study in Subjects With Heart Failure.

BACKGROUND: The Inhibition of Metallo Protease by BMS-186716 in a Randomized Exercise and Symptoms Study in Subjects With Heart Failure (IMPRESS) clinical trial randomized patients with congestive heart failure to a daily regimen of either omapatrilat or lisinopril. At 24 weeks, patients randomized to omapatrilat had a significant reduction in the combined end point of death, hospitalization, or discontinuation of study drug for worsening heart failure when compared with patients randomized to lisinopril. They also had significantly fewer serious cardiac adverse events. OBJECTIVE: This study sought to determine the economic consequences of the lower event rates of patients who were given omapatrilat. METHODS: Economic outcomes (major hospitalizations and their associated medical costs) were compared between treatment groups and assessed by use of the societal perspective. Hospitalization information was obtained from the IMPRESS trial's standardized case report and serious adverse event forms. Hospital costs were evaluated by means of assigning each hospital admission a diagnosis-related group and an average cost for physician and hospital services. Emergency department visits were included only when they were made for worsening heart failure and were assigned costs equivalent to the average hospital and physician Medicare reimbursement for these visits in Duke University Medical Center's heart failure program. Drug costs were not assessed. RESULTS: Although the typical patient in both treatment groups was event-free, there was a trend toward a greater number of hospitalizations in the patients given lisinopril than in the patients given omapatrilat (P =.07). Differences in the distribution of cardiac hospitalizations between patients given lisinopril and patients given omapatrilat were significant (P =.03). There was a trend toward lower medical costs at 24 weeks in patients given omapatrilat versus patients given lisinopril ($1930 vs $2002, P =.09). Considering only cardiac medical costs, this trend toward reduced medical costs was significant ($1240 vs $1442, P =.03). CONCLUSIONS: At 24 weeks, patients with heart failure treated with omapatrilat had fewer hospitalizations and lower medical costs than patients treated with lisinopril. However, drug treatment costs were not available for this analysis.

Obesity and long-term clinical and economic outcomes in coronary artery disease patients.

OBJECTIVE: Obesity is an important risk factor for coronary artery disease (CAD); however, its effect on acute coronary syndrome (ACS) patients' long-term clinical and economic outcomes has not been quantified. We assessed the impact of increasing body mass index (BMI) on 10-year outcomes for ACS patients. RESEARCH METHODS AND PROCEDURES: ACS patients with significant CAD receiving an initial cardiac catheterization at Duke University Medical Center between 1986 and 1997 were included. Patients with a BMI < 18.5 kg/m(2) were excluded; the remaining patients were classified by BMI as normal, overweight, obese, or very obese. Medical costs were estimated from a prior ACS clinical trial with costs adjusted to 1997 dollars and discounted at 3% per annum. RESULTS: There were 9405 patients with data available for analysis. Follow-up was complete on >95% of patients. Patients who were obese at baseline increased from 20% to 33% between 1986 and 1997. Increased BMI was associated with younger age, multi-morbidity, and less severe CAD at baseline. It was also associated with more clinical events, higher cumulative inpatient medical costs, and significant differences in unadjusted survival at 10 years. However, it was not associated with differences in 10-year survival after adjusting for baseline characteristic differences. DISCUSSION: Obese ACS patients are younger and are hospitalized more frequently during the first 10 years of their illness than are non-obese patients. They also incur higher cumulative inpatient medical costs, especially the very obese. These findings highlight the opportunities for therapeutic benefit that aggressive weight management and secondary prevention may provide this population.