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Biomedical subjects

Alan M Garber

Publications and source records attributed to Alan M Garber.

At least 19 recordsLinked to original sources

Systematic review: the safety and efficacy of growth hormone in the healthy elderly.

BACKGROUND: Human growth hormone (GH) is widely used as an antiaging therapy, although its use for this purpose has not been approved by the U.S. Food and Drug Administration and its distribution as an antiaging agent is illegal in the United States. PURPOSE: To evaluate the safety and efficacy of GH therapy in the healthy elderly. DATA SOURCES: The authors searched MEDLINE and EMBASE databases for English-language studies published through 21 November 2005 by using such terms as growth hormone and aging. STUDY SELECTION: The authors included randomized, controlled trials that compared GH therapy with no GH therapy or GH and lifestyle interventions (exercise with or without diet) with lifestyle interventions alone. Included trials provided GH for 2 weeks or more to community-dwelling participants with a mean age of 50 years or more and a body mass index of 35 kg/m2 or less. The authors excluded studies that evaluated GH as treatment for a specific illness. DATA EXTRACTION: Two authors independently reviewed articles and abstracted data. DATA SYNTHESIS: 31 articles describing 18 unique study populations met the inclusion criteria. A total of 220 participants who received GH (107 person-years) completed their respective studies. Study participants were elderly (mean age, 69 years [SD, 6]) and overweight (mean body mass index, 28 kg/m2 [SD, 2]). Initial daily GH dose (mean, 14 microg per kg of body weight [SD, 7]) and treatment duration (mean, 27 weeks [SD, 16]) varied. In participants treated with GH compared with those not treated with GH, overall fat mass decreased (change in fat mass, -2.1 kg [95% CI, -2.8 to -1.35] and overall lean body mass increased (change in lean body mass, 2.1 kg [CI, 1.3 to 2.9]) (P < 0.001), and their weight did not change significantly (change in weight, 0.1 kg [CI, -0.7 to 0.8]; P = 0.87). Total cholesterol levels decreased (change in cholesterol, -0.29 mmol/L [-11.21 mg/dL]; P = 0.006), although not significantly after adjustment for body composition changes. Other outcomes, including bone density and other serum lipid levels, did not change. Persons treated with GH were significantly more likely to experience soft tissue edema, arthralgias, carpal tunnel syndrome, and gynecomastia and were somewhat more likely to experience the onset of diabetes mellitus and impaired fasting glucose. LIMITATIONS: Some important outcomes were infrequently or heterogeneously measured and could not be synthesized. Most included studies had small sample sizes. CONCLUSIONS: The literature published on randomized, controlled trials evaluating GH therapy in the healthy elderly is limited but suggests that it is associated with small changes in body composition and increased rates of adverse events. On the basis of this evidence, GH cannot be recommended as an antiaging therapy.

Aged↗

The cost-effectiveness of therapy with teriparatide and alendronate in women with severe osteoporosis.

BACKGROUND: Teriparatide is a promising new agent for the treatment of osteoporosis. METHODS: The objective of this study was to evaluate the cost-effectiveness of teriparatide-based strategies compared with alendronate sodium for the first-line treatment of high-risk osteoporotic women. We developed a microsimulation with a societal perspective. Key data sources include the Study of Osteoporotic Fractures, the Fracture Intervention Trial, and the Fracture Prevention Trial. We evaluated postmenopausal white women with low bone density and prevalent vertebral fracture. The interventions were usual care (UC) (calcium or vitamin D supplementation) compared with 3 strategies: 5 years of alendronate therapy, 2 years of teriparatide therapy, and 2 years of teriparatide therapy followed by 5 years of alendronate therapy (sequential teriparatide/alendronate). The main outcome measure was cost per quality-adjusted life-year (QALY). RESULTS: For the base-case analysis, the cost of alendronate treatment was 11,600 dollars per QALY compared with UC. The cost of sequential teriparatide/alendronate therapy was 156,500 dollars per QALY compared with alendronate. Teriparatide treatment alone was more expensive and produced a smaller increase in QALYs than alendronate. For sensitivity analysis, teriparatide alone was less cost-effective than alendronate even if its efficacy lasted 15 years after treatment cessation. Sequential teriparatide/alendronate therapy was less cost-effective than alendronate even if fractures were eliminated during the alendronate phase, although its cost-effectiveness was less than 50,000 dollars per QALY if the price of teriparatide decreased 60%, if used in elderly women with T scores of -4.0 or less, or if 6 months of teriparatide therapy had comparable efficacy to 2 years of treatment. CONCLUSIONS: Alendronate compares favorably to interventions accepted as cost-effective. Therapy with teriparatide alone is more expensive and produces a smaller increase in QALYs than therapy with alendronate. Sequential teriparatide/alendronate therapy appear expensive but could become more cost-effective with reductions in teriparatide price, with restriction to use in exceptionally high-risk women, or if short courses of treatment have comparable efficacy to that observed in clinical trials.

Aged↗

Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging.

CONTEXT: Women with inherited BRCA1/2 mutations are at high risk for breast cancer, which mammography often misses. Screening with contrast-enhanced breast magnetic resonance imaging (MRI) detects cancer earlier but increases costs and results in more false-positive scans. OBJECTIVE: To evaluate the cost-effectiveness of screening BRCA1/2 mutation carriers with mammography plus breast MRI compared with mammography alone. DESIGN, SETTING, AND PATIENTS: A computer model that simulates the life histories of individual BRCA1/2 mutation carriers, incorporating the effects of mammographic and MRI screening was used. The accuracy of mammography and breast MRI was estimated from published data in high-risk women. Breast cancer survival in the absence of screening was based on the Surveillance, Epidemiology and End Results database of breast cancer patients diagnosed in the prescreening period (1975-1981), adjusted for the current use of adjuvant therapy. Utilization rates and costs of diagnostic and treatment interventions were based on a combination of published literature and Medicare payments for 2005. MAIN OUTCOME MEASURES: The survival benefit, incremental costs, and cost-effectiveness of MRI screening strategies, which varied by ages of starting and stopping MRI screening, were computed separately for BRCA1 and BRCA2 mutation carriers. RESULTS: Screening strategies that incorporate annual MRI as well as annual mammography have a cost per quality-adjusted life-year (QALY) gained ranging from less than 45,000 dollars to more than 700,000 dollars, depending on the ages selected for MRI screening and the specific BRCA mutation. Relative to screening with mammography alone, the cost per QALY gained by adding MRI from ages 35 to 54 years is 55,420 dollars for BRCA1 mutation carriers, 130,695 dollars for BRCA2 mutation carriers, and 98,454 dollars for BRCA2 mutation carriers who have mammographically dense breasts. CONCLUSIONS: Breast MRI screening is more cost-effective for BRCA1 than BRCA2 mutation carriers. The cost-effectiveness of adding MRI to mammography varies greatly by age.

Adult↗

To use technology better.

Although technological innovation can improve health outcomes, the precise magnitude of the contribution and its value are not easily measured. The findings reported by Jonathan Skinner and colleagues temper the favorable conclusions reached by observing correlations between improvement in heart attack outcomes over time with spending on medical products and services. Improvements in health care depend not only on producing better technologies, but also on using technology better.

Acute Disease↗

The effect of geriatrics evaluation and management on nursing home use and health care costs: results from a randomized trial.

BACKGROUND: The Geriatric Evaluation and Management study was developed to assess the impact of a comprehensive geriatric assessment service on the care of the elderly. OBJECTIVES: We sought to evaluate the cost and clinical impact of inpatient units and outpatient clinics for geriatric evaluation and management. RESEARCH DESIGN: We undertook a prospective, randomized, controlled trial using a 2x2 factorial design, with 1-year follow-up. SUBJECTS: A total of 1388 participants hospitalized on either a medical or surgical ward at 11 participating Veterans Affairs medical centers were randomized to receive either inpatient geriatric unit (GEMU) or usual inpatient care (UCIP), followed by either outpatient care from a geriatric clinic (GEMC) versus usual outpatient care (UCOP). MEASURES: We measured health care utilization and costs. RESULTS: Patients assigned to the GEMU had a significantly decreased rate of nursing home placement (odds ratio=0.65; P=0.001). Neither the GEMU nor GEMC had any statistically significant improvement effects on survival and only modest effects on health status. There were statistically insignificant mean cost savings of $1027 (P=0.29) per patient for the GEMU and $1665 (P=0.69) per patient for the GEMC. CONCLUSIONS: Inpatient or outpatient geriatric evaluation and management units didn't increase the costs of care. Although there was no effect on survival and only modest effects on SF-36 scores at 1-year follow-up, there was a statistically significant reduction in nursing home admissions for patients treated in the GEMU.

Aged↗

Cost-effectiveness of defending against bioterrorism: a comparison of vaccination and antibiotic prophylaxis against anthrax.

BACKGROUND: Weaponized Bacillus anthracis is one of the few biological agents that can cause death and disease in sufficient numbers to devastate an urban setting. OBJECTIVE: To evaluate the cost-effectiveness of strategies for prophylaxis and treatment of an aerosolized B. anthracis bioterror attack. DESIGN: Decision analytic model. DATA SOURCES: We derived probabilities of anthrax exposure, vaccine and treatment characteristics, and their costs and associated clinical outcomes from the medical literature and bioterrorism-preparedness experts. TARGET POPULATION: Persons living and working in a large metropolitan U.S. city. TIME HORIZON: Patient lifetime. PERSPECTIVE: Societal. INTERVENTION: We evaluated 4 postattack strategies: no prophylaxis, vaccination alone, antibiotic prophylaxis alone, or vaccination and antibiotic prophylaxis, as well as preattack vaccination versus no vaccination. OUTCOME MEASURES: Costs, quality-adjusted life-years, life-years, and incremental cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: If an aerosolized B. anthracis bioweapon attack occurs, postexposure prophylactic vaccination and antibiotic therapy for those potentially exposed is the most effective (0.33 life-year gained per person) and least costly (355 dollars saved per person) strategy, as compared with vaccination alone. At low baseline probabilities of attack and exposure, mass previous vaccination of a metropolitan population is more costly (815 million dollars for a city of 5 million people) and not more effective than no vaccination. RESULTS OF SENSITIVITY ANALYSIS: If prophylactic antibiotics cannot be promptly distributed after exposure, previous vaccination may become cost-effective. LIMITATIONS: The probability of exposure and disease critically depends on the probability and mechanism of bioweapon release. CONCLUSIONS: In the event of an aerosolized B. anthracis bioweapon attack over an unvaccinated metropolitan U.S. population, postattack prophylactic vaccination and antibiotic therapy is the most effective and least expensive strategy.

Anthrax↗

Trends in implantable cardioverter-defibrillator racial disparity: the importance of geography.

OBJECTIVES: The study was designed to determine whether racial disparity in utilization of the implantable cardioverter-defibrillator (ICD) has improved over time, and whether small-area geographic variation in ICD utilization contributed to national levels of racial disparity. BACKGROUND: Although racial disparities in cardiac procedures have been well-documented, it is unknown whether there has been improvement over time. Low ICD utilization rates in predominantly black geographic areas may have exacerbated national levels of disparity. METHODS: Discharge abstracts from elderly black and white Medicare beneficiaries hospitalized with ventricular arrhythmias from 1990 to 2000 were analyzed to determine if ICD implantation occurred within 90 days of initial hospitalization. Multivariate logistic regression models were constructed to assess the relationship between ICD implantation, year of admission, and the percentage of black inhabitants in each patient's county of hospitalization while controlling for clinical, hospital, and demographic characteristics. RESULTS: There was improvement in ICD implantation racial disparity: In the period 1990 to 1992, black patients had an odds ratio of 0.52 (95% confidence interval [CI] 0.42 to 0.64) for receiving an ICD compared with whites. However, by 1999 to 2000, the odds ratio for blacks had risen to 0.69 (95% CI 0.61 to 0.78) (test-for-trend p=0.01). Approximately 20% of this trend could be explained by reduction in geographic variation in ICD use between areas with larger black and predominantly white populations. CONCLUSIONS: Rates of ICD implants became more equal among whites and blacks during the 1990s, although persistent disparity remained at the decade's end. Geographic equalization in cardiovascular procedure rates may be an essential mechanism in rectifying disparities in health care.

Black or African American↗

Technology diffusion, hospital variation, and racial disparities among elderly Medicare beneficiaries: 1989-2000.

BACKGROUND: Low rates of technology utilization in hospitals with high proportions of black inpatients may be a remediable cause of healthcare disparities. OBJECTIVES: Our objective was to determine how differences in technology utilization among hospitals contributed to racial disparity and if temporal reduction in hospital procedure rate variation resulted in decreased racial disparity for these technologies. METHODS: We identified 2,348,952 elderly Medicare beneficiaries potentially eligible for 1 of 5 emerging medical technologies from 1989-2000 and determined if these patients had received the indicated procedure within 90 days of their qualifying hospital admission. Initial multivariate regression models adjusted for age, race, sex, admission year, clinical comorbidity, community levels of education and income, and academic/urban hospital admission. The inpatient racial composition of each patient's admitting hospital and time-race interactions were added as covariates to subsequent models. RESULTS: Blacks had significantly lower adjusted rates (P < 0.001) compared with whites for tissue replacement of the aortic valve, internal mammary artery coronary bypass grafting, dual-chambered pacemaker implantation, and lumbar spinal fusion. Hospitals with > 20% black inpatients were less likely to perform these procedures on both white and black patients than hospitals with < 9% black inpatients, and racial disparity was greater in hospitals with larger black populations. There were no temporal reductions in racial disparities. CONCLUSIONS: Blacks may be disadvantaged in access to new procedures by receiving care at hospitals that have both lower procedure rates and greater racial disparity. Policies designed to ameliorate racial disparities in health care must address hospital variation in the provision of care.

Aged↗

Consequences of health trends and medical innovation for the future elderly.

Recent innovations in biomedicine seem poised to revolutionize medical practice. At the same time, disease and disability are increasing among younger populations. This paper considers how these confluent trends will affect the elderly's health status and health care spending over the next thirty years. Because healthier people live longer, cumulative Medicare spending varies little with a beneficiary's disease and disability status upon entering Medicare. On the other hand, ten of the most promising medical technologies are forecast to increase spending greatly. It is unlikely that a "silver bullet" will emerge to both improve health and dramatically reduce medical spending.

Aged↗

The costs of decedents in the Medicare program: implications for payments to Medicare + Choice plans.

OBJECTIVE: To discuss and quantify the incentives that Medicare managed care plans have to avoid (through selective enrollment or disenrollment) people who are at risk for very high costs, focusing on Medicare beneficiaries in the last year of life-a group that accounts for more than one-quarter of Medicare's annual expenditures. DATA SOURCE: Medicare administrative claims for 1994 and 1995. STUDY DESIGN: We calculated the payment a plan would have received under three risk-adjustment systems for each beneficiary in our 1995 sample based on his or her age, gender, county of residence, original reason for Medicare entitlement, and principal inpatient diagnoses received during any hospital stays in 1994. We compared these amounts to the actual costs incurred by those beneficiaries. We then looked for clinical categories that were predictive of costs, including costs in a beneficiary's last year of life, not accounted for by the risk adjusters. DATA EXTRACTION METHODS: The analyses were conducted using claims for a 5 percent random sample of Medicare beneficiaries who died in 1995 and a matched group of survivors. PRINCIPAL FINDINGS: Medicare is currently implementing the Principal Inpatient Diagnostic Cost Groups (PIP-DCG) risk adjustment payment system to address the problem of risk selection in the Medicare+Choice program. We quantify the strong financial disincentives to enroll terminally ill beneficiaries that plans still have under this risk adjustment system. We also show that up to one-third of the selection observed between Medicare HMOs and the traditional fee-for-service system could be due to differential enrollment of decedents. A risk adjustment system that incorporated more of the available diagnostic information would attenuate this disincentive; however, plans could still use clinical information (not included in the risk adjustment scheme) to identify beneficiaries whose expected costs exceed expected payments. CONCLUSIONS: More disaggregated prospective risk adjustment methods and alternative payment systems that compensate plans for delivering care to certain classes of patients should be considered to ensure access to high-quality managed care for all beneficiaries.

Actuarial Analysis↗

Trends in inpatient treatment intensity among Medicare beneficiaries at the end of life.

OBJECTIVE: Although an increasing fraction of Medicare beneficiaries die outside the hospital, the proportion of total Medicare expenditures attributable to care in the last year of life has not dropped. We sought to determine whether disproportionate increases in hospital treatment intensity over time among decedents are responsible for the persistent growth in end-of-life expenditures. DATA SOURCE: The 1985-1999 Medicare Medical Provider Analysis and Review (MedPAR) and Denominator files. STUDY DESIGN: We sampled inpatient claims for 20 percent of all elderly fee-for-service Medicare decedents and 5 percent of all survivors between 1985 and 1999 and calculated age-, race-, and gender-adjusted per-capita inpatient expenditures and rates of intensive care unit (ICU) and intensive procedure use. We used the decedent-to-survivor expenditure ratio to determine whether growth rates among decedents outpaced growth relative to survivors, using the growth rate among survivors to control for secular trends in treatment intensity. Data Collection. The data were collected by the Centers for Medicare and Medicaid Services. PRINCIPAL FINDINGS: Real inpatient expenditures for the Medicare fee-for-service population increased by 60 percent, from $58 billion in 1985 to $90 billion in 1999, one-quarter of which were accrued by decedents. Between 1985 and 1999 the proportion of beneficiaries with one or more intensive care unit (ICU) admission increased from 30.5 percent to 35.0 percent among decedents and from 5.0 percent to 7.1 percent among survivors; those undergoing one or more intensive procedure increased from 20.9 percent to 31.0 percent among decedents and from 5.8 percent to 8.5 percent among survivors. The majority of intensive procedures in the United States were performed in the more numerous survivors, although in 1999 50 percent of feeding tube placements, 60 percent of intubations/tracheostomies, and 75 percent of cardiopulmonary resuscitations were in decedents. The proportion of beneficiaries dying in a hospital decreased from 44.4 percent to 39.3 percent, but the likelihood of being admitted to an ICU or undergoing an intensive procedure during the terminal hospitalization increased from 38.0 percent to 39.8 percent and from 17.8 percent to 30.3 percent, respectively. One in five Medicare beneficiaries who died in the hospital in 1999 received mechanical ventilation during their terminal admission. CONCLUSIONS: Inpatient treatment intensity for all fee-for-service beneficiaries increased between 1985 and 1999 regardless of survivorship status. Absolute changes in per-capita hospital expenditures, ICU admissions, and intensive inpatient procedure use were much higher among decedents. Relative changes were similar except for ICU admissions, which grew faster among survivors. The secular decline in in-hospital deaths has not resulted in decreased per capita utilization of expensive inpatient services in the last year of life. This could imply that net hospital expenditures for the dying might have been even higher over this time period if the shift toward hospice had not occurred.

Aged↗

Impacts of informal caregiver availability on long-term care expenditures in OECD countries.

OBJECTIVE: To quantify the effects of informal caregiver availability and public funding on formal long-term care (LTC) expenditures in developed countries. DATA SOURCE/STUDY SETTING: Secondary data were acquired for 15 Organization for Economic Cooperation and Development (OECD) countries from 1970 to 2000. STUDY DESIGN: Secondary data analysis, applying fixed- and random-effects models to time-series cross-sectional data. Outcome variables are inpatient or home heath LTC expenditures. Key explanatory variables are measures of the availability of informal caregivers, generosity in public funding for formal LTC, and the proportion of the elderly population in the total population. DATA COLLECTION/EXTRACTION METHOD: Aggregated macro data were obtained from OECD Health Data, United Nations Demographic Yearbooks, and U.S. Census Bureau International Data Base. PRINCIPAL FINDINGS: Most of the 15 OECD countries experienced growth in LTC expenditures over the study period. The availability of a spouse caregiver, measured by male-to-female ratio among the elderly, is associated with a $28,840 (1995 U.S. dollars) annual reduction in formal LTC expenditure per additional elderly male. Availability of an adult child caregiver, measured by female labor force participation and full-time/part-time status shift, is associated with a reduction of $310 to $3,830 in LTC expenditures. These impacts on LTC expenditure vary across countries and across time within a country. CONCLUSIONS: The availability of an informal caregiver, particularly a spouse caregiver, is among the most important factors explaining variation in LTC expenditure growth. Long-term care policies should take into account behavioral responses: decreased public funding in LTC may lead working women to leave the labor force to provide more informal care.

Adult↗

Cost-effectiveness of bypass surgery versus stenting in patients with multivessel coronary artery disease.

PURPOSE: To compare the cost-effectiveness of surgical and angioplasty-based coronary artery revascularization techniques, in particular, angioplasty with primary stenting. METHODS: We used data from the Study of Economics and Quality of Life, a substudy of the Bypass Angioplasty Revascularization Investigation (BARI), to measure the outcomes and costs of angioplasty and bypass surgery in patients with multivessel coronary artery disease who had not undergone prior coronary artery revascularization. Using a Markov decision model, we updated the outcomes and costs to reflect technology changes since the time of enrollment in BARI, and projected the lifetime costs and quality-adjusted life-years (QALYs) for the two procedures from the time of initial treatment through death. We accounted for the effects of improved procedural safety and efficiency, and prolonged therapeutic effects of both surgery and stenting. This study was conducted from a societal perspective. RESULTS: Surgical revascularization was less costly and resulted in better outcomes than catheter-based intervention including stenting. It remained the preferred strategy after adjusting the stent outcomes to eliminate the costs and events associated with target lesion restenosis. Among angioplasty-based strategies, primary stent use cost an additional 189,000 US dollars per QALY gained compared with a strategy that reserved stent use for treatment of suboptimal balloon angioplasty results. CONCLUSION: Bypass surgery results in better outcomes than angioplasty in patients with multivessel disease, and at a lower cost.

Angioplasty, Balloon, Coronary↗

Racial disparity in cardiac procedures and mortality among long-term survivors of cardiac arrest.

BACKGROUND: It is unknown whether white and black Medicare beneficiaries have different rates of cardiac procedure utilization or long-term survival after cardiac arrest. METHODS AND RESULTS: A total of 5948 elderly Medicare beneficiaries (5429 white and 519 black) were identified who survived to hospital discharge between 1990 and 1999 after admission for cardiac arrest. Demographic, socioeconomic, and clinical information about these patients was obtained from Medicare administrative files, the US census, and the American Hospital Association's annual institutional survey. A Cox proportional hazard model that included demographic and clinical predictors indicated a hazard ratio for mortality of 1.30 (95% CI 1.09 to 1.55) for blacks aged 66 to 74 years compared with whites of the same age. The addition of cardiac procedures to this model lowered the hazard ratio for blacks to 1.23 (95% CI 1.03 to 1.46). In analyses stratified by race, implantable cardioverter-defibrillators (ICDs) had a mortality hazard ratio of 0.53 (95% CI 0.45 to 0.62) for white patients and 0.50 (95% CI 0.27 to 0.91) for black patients. Logistic regression models that compared procedure rates between races indicated odds ratios for blacks aged 66 to 74 years of 0.58 (95% CI 0.36 to 0.94) to receive an ICD and 0.50 (95% CI 0.34 to 0.75) to receive either revascularization or an ICD. CONCLUSIONS: There is racial disparity in long-term mortality among elderly cardiac arrest survivors. Both black and white patients benefited from ICD implantation, but blacks were less likely to undergo this potentially life-saving procedure. Lower rates of cardiac procedures may explain in part the lower survival rates among black patients.

Aged↗

Cost-effectiveness of recombinant human activated protein C and the influence of severity of illness in the treatment of patients with severe sepsis.

PURPOSE: To evaluate the cost-effectiveness of recombinant human activated protein C (rhAPC) compared with usual therapy for patients with severe sepsis, and also to determine the influence that severity of illness exerts on cost-effectiveness. MATERIALS AND METHODS: We use a Markov model-based cost-effectiveness analysis of treatment strategies for patients with severe sepsis. Therapy includes treatment with either rhAPC and usual therapy, or usual therapy alone. Probabilities for clinical outcomes were obtained from a large randomized clinical trial comparing the use of rhAPC with placebo (PROWESS study) and from outcomes literature for patients with severe sepsis and its complications. Cost estimates were based on Medicare reimbursement rates, Health Care Financing Administration information and the literature. Outcome measures include life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness. RESULTS: Compared with usual therapy alone, rhAPC treatment for patients with very severe sepsis (APACHE II score > or = 25) was associated with an incremental cost-effectiveness ratio of $13 493/QALY. Treatment of patients with less severe sepsis with rhAPC (APACHE II score < 25) had an incremental cost-effectiveness ratio of $403,000/QALY. For patients with very severe sepsis the incremental cost-effectiveness ratio for treatment with rhAPC remained under $30,000/QALY, over a broad range of variables, including costs of rhAPC, costs of acute care and costs and probabilities of complications of treatment. For patients with less severe sepsis, drug costs would need to fall well below current market price before achieving cost-effectiveness. A probabilistic sensitivity analysis comparing rhAPC treatment with usual therapy for patients with very severe sepsis showed that < 1% of Monte Carlo simulations had incremental cost-effectiveness ratios > $50,000/QALY. CONCLUSIONS: The use of rhAPC for the treatment of patients with very severe sepsis, as determined by APACHE II score > or = 25, appears cost-effective, while treatment of patients with APACHE II score < 25 is not cost-effective.

APACHE↗