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Biomedical subjects

S G Pauker

Publications and source records attributed to S G Pauker.

At least 19 recordsLinked to original sources
PubMed2001

Using observational data to estimate prognosis: an example using a coronary artery disease registry.

With the proliferation of clinical data registries and the rising expense of clinical trials, observational data sources are increasingly providing evidence for clinical decision making. These data are viewed as complementary to randomized clinical trials (RCT). While not as rigorous a methodological design, observational studies yield important information about effectiveness of treatment, as compared with the efficacy results of RCTs. In addition, these studies often have the advantage of providing longer-term follow-up, beyond that of clinical trials. Hence, they are useful for assessing and comparing patients' long-term prognosis under different treatment strategies. For patients with coronary artery disease, many observational comparisons have focused on medical therapy versus interventional procedures. In addition to the well-studied problem of treatment selection bias (which is not the focus of the present study), three significant methodological problems must be addressed in the analysis of these data: (i) designation of the therapeutic arms in the presence of early deaths, withdrawals, and treatment cross-overs; (ii) identification of an equitable starting point for attributing survival time; (iii) site to site variability in short-term mortality. This paper discusses these issues and suggests strategies to deal with them. A proposed methodology is developed, applied and evaluated on a large observational database that has long-term follow-up on nearly 10 000 patients.

Analysis of Variance↗
PubMed2001

When should an effective treatment be used? Derivation of the threshold number needed to treat and the minimum event rate for treatment.

Clinicians and patients must decide when treatment effects are large enough to more than offset the adverse effects and costs of therapy. Calculation of the number of patients one needs to treat (NNT) in order to prevent one patient from having the target event is one tool to help with this decision. Clinicians should treat patients when the NNT is lower than a threshold NNT at which point the therapeutic risk equals the therapeutic benefit. We aimed: (1) to identify the determinants of the threshold NNT, and (2) to derive equations for the explicit estimation of the threshold NNT and of the minimum expected rate of target event, without treatment, above which treatment is justified. We conceived the threshold number needed to treat to prevent one target event as the point at which the benefits of treating that number of patients equal the negative consequences of treating that same number of patients. After identifying the various elements comprising the treatment impact, we equated the benefits and negative consequences and solved the equation for threshold NNT. We then derived the minimum expected rate of target event which would justify treatment. We derived an equation that relates the threshold NNT to the treatment-attributable adverse event rates (AER) and the relative values (RV) of the adverse events compared to that of the target event prevented. Specifically, the threshold NNT, denoted NNT(T) is given by NNT(T) = 1/(AER(1).RV(1) +...+ AER(n).RV(n)). We also derived a more complex equation which addresses the costs incurred by treatment and costs avoided by preventing target events. Solving the equation that includes costs requires specifying both the value of preventing a target event and the values of adverse treatment effects in economic units. The threshold NNT and the relative risk reduction (RRR) for the target event determine the minimum target event rate above which treatment is justified. This minimum event rate for treatment is 1/(NNT(T).RRR). The values that clinicians and patients use determine the threshold NNT and therefore also the minimum target event rate, without treatment, above which treatment is justified. Quantification of the determinants of the threshold NNT and of the minimum event rate to justify treatment can assist clinicians and patients in the explicit use of underlying values when making treatment decisions.

Cost-Benefit Analysis↗
PubMed2000

Cost effectiveness of ribavirin/interferon alfa-2b after interferon relapse in chronic hepatitis C.

PURPOSE: Many patients with chronic hepatitis C who are treated with interferon suffer a relapse after an initial response. About half of these patients have a sustained virological response to retreatment with the combination of ribavirin and interferon alfa-2b. The aim of this study was to estimate the cost effectiveness of retreatment with combination therapy versus interferon alone for patients who have previously relapsed after interferon. SUBJECTS AND METHODS: Data from a randomized trial among 345 relapsed patients that compared combination therapy with interferon alone were used to project lifelong clinical and economic outcomes. Natural history and economic estimates (discounted at 3% per year) were based upon published literature, expert panel estimates, and cost and reimbursement data. RESULTS: Compared with retreatment with interferon alone, combination therapy should prolong life expectancy by about 2 discounted quality-adjusted life years (3 life years, undiscounted) while increasing costs modestly. The results were robust, maintaining an advantage to combination therapy in sensitivity analysis for all subgroups and with reasonable variations in all model parameters. CONCLUSION: For patients with chronic hepatitis C who relapse after an initial response to interferon alone, retreatment with the combination of ribavirin and interferon alfa-2b should prolong life and be cost effective.

Adult↗
PubMed2000

Cytomegalovirus immune globulin after liver transplantation: a cost-effectiveness analysis.

OBJECTIVE: Cytomegalovirus (CMV) immune globulin (CMVIG) has been shown to significantly reduce severe CMV-associated disease complicating orthotopic liver transplant (OLT). We evaluated the economic impact of severe CMV-associated disease and calculated the marginal cost-effectiveness (C/E) of routine prophylaxis with CMVIG after OLT. DESIGN: C/E analysis. SETTING: Four teaching hospitals in Boston. PATIENTS: Patients who underwent OLT from January 1988 through June 1990. MEASUREMENTS: We gathered actual cost data of hospital care for patients enrolled in a clinical trial of CMVIG prophylaxis in OLT. We calculated average outpatient expenses from a separate group of patients undergoing OLT and developed a regression model to estimate costs during the first year post-transplant (R2 = 0.77). Based on this model, we calculated variable costs (in 1999 US dollars) for all patients in the randomized trial. From the published literature we obtained the probability of CMV outcomes and of long-term survival after OLT. We then developed a decision analytical model to determine an incremental C/E ratio, using a Markov simulation to estimate long-term survival and long-term costs. We discounted costs and life-years at 3% and 5% per yr. RESULTS: Based on the efficacy rate of 54% in the controlled trial, we estimate that CMVIG will increase life expectancy by 0.65 discounted years at an additional cost of $11,600, providing a marginal C/E ratio of $17,900/yr life saved. Examining the confidence limits of efficacy, we estimate that CMVIG will have a marginal C/E ratio of $66,200 gained/yr at an efficacy of 11% and $14,000 gained/yr at an efficacy of 83%. CONCLUSION: After OLT, prophylactic CMVIG has an incremental C/E ratio comparable to that of other well-accepted medical therapies and should be used routinely in these patients.

Cost-Benefit Analysis↗
PubMed2000

Cost-effectiveness of 24 or 48 weeks of interferon alpha-2b alone or with ribavirin as initial treatment of chronic hepatitis C. International Hepatitis Interventional Therapy Group.

OBJECTIVE: Initial therapy with ribavirin and interferon alpha-2b results in a higher sustained virological response than interferon alone, but this regimen is expensive. We aimed to examine the cost-effectiveness of 24- or 48-wk initial treatment with combination therapy versus interferon alone for patients who have chronic hepatitis C. METHODS: Data from recent randomized clinical trials comparing combination therapy to interferon alone were applied to a previously published computer cohort simulation to project lifelong clinical and economic outcomes. Natural history and economic estimates were based on published literature, expert panel estimates, and actual variable cost and reimbursement data. RESULTS: Using treatment stopping rules, sustained viral negative response rates would be 33.1% and 39.8% for patients receiving 24 versus 48 wk of ribavirin/interferon, compared with 14.3% for 48 wk of interferon alone. Compared to the interferon alone strategy, 24 or 48 wk of combination therapy should prolong life expectancy by 1.4 to 2.0 yr at marginal cost-effectiveness ratios of $4,400 to $5,400 per discounted quality-adjusted life-year (DQALY) gained. Compared to 24 wk of combination therapy, 48 wk of combination therapy should prolong life expectancy by 0.6 yr at a marginal cost-effectiveness ratio of $7,700 per DQALY gained. The results were robust, with 24 or 48 wk of combination therapy remaining preferred and cost-effective in sensitivity analysis compared with interferon alone. CONCLUSION: For patients with chronic hepatitis C, 24 or 48 wk of ribavirin and interferon should prolong life and be cost-effective when compared with 48 wk, of interferon alone.

Adult↗
PubMed1999

Individualizing therapy to prevent long-term consequences of estrogen deficiency in postmenopausal women.

BACKGROUND: Alendronate sodium and raloxifene hydrochloride were recently approved for the prevention of postmenopausal osteoporosis, but data on their clinical efficacy are limited. We compared these drugs with hormone replacement therapy (HRT) to help women and physicians guide postmenopausal treatment decisions. OBJECTIVE: To help physicians understand how they can best help women choose the most beneficial therapy after menopause based on their individual risk profile. METHODS: We developed a decision analytic Markov model to compare the effects of alendronate therapy, raloxifene therapy, and HRT on risks of hip fracture, coronary heart disease (CHD), breast cancer, and life expectancy. Regression models linked individual risk factors to future disease risks and were modified by drug effects on bone density, lipid levels, and associated breast cancer effects. RESULTS: Hormone replacement therapy, alendronate therapy, and raloxifene therapy have similar predicted efficacies in preventing hip fractures (estimated relative risk, 0.57, 0.54, and 0.58, respectively). Hormone replacement therapy should be more than 10 times more effective than raloxifene therapy in preventing CHD, but raloxifene therapy may not induce breast cancer. Women at low risk for hip fracture, CHD, and breast cancer do not benefit significantly from any treatment. Among women at average risk, HRT was preferred unless raloxifene therapy could reduce the risk of breast cancer by at least 66%, compared with a 47% increase for HRT. Women at high risk for CHD benefit most from HRT; women at high risk for breast cancer but low risk for CHD benefit most from raloxifene therapy, but only if it lowers the risk of breast cancer. CONCLUSION: Because of significant differences in the impact of these drugs, treatment choice depends on an individual woman's risk for hip fracture, CHD, and breast cancer.

Alendronate↗
PubMed1997

Estimates of the cost-effectiveness of a single course of interferon-alpha 2b in patients with histologically mild chronic hepatitis C.

BACKGROUND: Chronic hepatitis C is a major cause of illness and death in the United States. Interferon-alpha 2b can induce clinical, biochemical, and virologic remission in some patients with chronic hepatitis C, but the long-term cost-effectiveness of this treatment, particularly in patients with histologically mild disease, is unknown. OBJECTIVE: To estimate the cost-effectiveness of interferon-alpha 2b in mild chronic hepatitis C. DESIGN: Meta-analysis of five prospective trials and cost-effectiveness analysis. Projection of the clinical and economic outcomes expected from loss of hepatitis C virus was done by using a Markov simulation. The potential effect of uncertainty in the model assumptions was tested by using sensitivity analyses. DATA SOURCES: Search of the MEDLINE database, opinions of expert panels, hospital cost data, and adjusted physician charges. PATIENTS: Hypothetical cohorts with histologically mild chronic hepatitis C. INTERVENTION: The model assumed a single 6-month course of recombinant interferon-alpha 2b. MEASUREMENTS: Life expectancy, quality-adjusted life expectancy, costs, and marginal cost-effectiveness ratios from a managed care perspective. RESULTS: In 27% of patients with mild chronic hepatitis C treated with interferon-alpha 2b for 6 months, serum alanine aminotransferase levels permanently returned to normal and viral status remained negative. The model estimated that interferon-alpha 2b treatment in this population should increase life expectancy by 3.1 years if given at 20 years of age, by 1.5 years at 35 years of age, and by 22 days at 70 years of age; discounted marginal cost-effectiveness ratios are $500, $1900, and $62,000 per year of life gained, respectively. Varying the long-term response rates and progression rates for mild and moderate chronic hepatitis to near zero in sensitivity analyses substantially affected the results: Ratios ranged from $31,000 for a 20-year-old patient to $640,000 for a 70-year-old patient. CONCLUSIONS: On the basis of estimations in this mathematical model of the natural history of chronic hepatitis C, treating mild chronic hepatitis with interferon-alpha 2b should prolong life expectancy at a reasonable marginal cost per year of life gained, particularly in younger patients.

Alanine Transaminase↗