Health Care Cost Reductions with Machine Learning-Directed Evaluations during Radiation Therapy - An Economic Analysis of a Randomized Controlled Study.

BACKGROUND: Machine learning (ML) may cost-effectively direct health care by identifying patients most likely to benefit from preventative interventions to avoid negative and expensive outcomes. System for High-Intensity Evaluation During Radiation Therapy (SHIELD-RT; NCT04277650) was a single-institution, randomized controlled study in which electronic health record-based ML accurately identified patients at high risk for acute care (emergency visit or hospitalization) during radiotherapy (RT) and targeted them for supplemental clinical evaluations. This ML-directed intervention resulted in decreased acute care utilization. Given the limited prospective data showing the ability of ML to direct interventions cost-efficiently, an economic analysis was performed. METHODS: A post hoc economic analysis was conducted of SHIELD-RT that included RT courses from January 7, 2019, to June 30, 2019. ML-identified high-risk courses (≥10% risk of acute care during RT) were randomized to receive standard of care weekly clinical evaluations with ad hoc supplemental evaluations per clinician discretion versus mandatory twice-weekly evaluations. The primary outcome was difference in mean total medical costs during and 15 days after RT. Acute care costs were obtained via institutional cost accounting. Physician and intervention costs were estimated via Medicare and Medicaid data. Negative binomial regression was used to estimate cost outcomes after adjustment for patient and disease factors. RESULTS: A total of 311 high-risk RT courses among 305 patients were randomized to the standard (n=157) or the intervention (n=154) group. Unadjusted mean intervention group supplemental visit costs were $155 per course (95% confidence interval, $142 to $168). The intervention group had fewer acute care visits per course (standard, 0.47; intervention, 0.31; P=0.04). Total mean adjusted costs were $3110 per course for the standard group and $1494 for the intervention group (difference in means, $1616 [95% confidence interval, $1450 to $1783]; P=0.03). CONCLUSIONS: In this economic analysis of a randomized controlled, health care ML study, mandatory supplemental evaluations for ML-identified high-risk patients were associated with both reduced total medical costs and improved clinical outcomes. Further study is needed to determine whether economic results are generalizable. (Funded in part by The Duke Endowment, The Conquer Cancer Foundation, the Duke Department of Radiation Oncology, and the National Cancer Institute of the National Institutes of Health [R01CA277782]; ClinicalTrials.gov number, NCT04277650.).

Evaluating registry-based trial economics: Results from the STRESS clinical trial.

Background: Registry-based trials have the potential to reduce randomized clinical trial (RCT) costs. However, observed cost differences also may be achieved through pragmatic trial designs. A systematic comparison of trial costs across different designs has not been previously performed. Methods: We conducted a study to compare the current Steroids to Reduce Systemic inflammation after infant heart surgery (STRESS) registry-based RCT vs. two established designs: pragmatic RCT and explanatory RCT. The primary outcome was total RCT design costs. Secondary outcomes included: RCT duration and personnel hours. Costs were estimated using the Duke Clinical Research Institute's pricing model. Results: The Registry-Based RCT estimated duration was 31.9 weeks greater than the other designs (259.5 vs. 227.6 weeks). This delay was caused by the Registry-Based design's periodic data harvesting that delayed site closing and statistical reporting. Total personnel hours were greatest for the Explanatory design followed by the Pragmatic design and the Registry-Based design (52,488 vs 29,763 vs. 24,480 h, respectively). Total costs were greatest for the Explanatory design followed by the Pragmatic design and the Registry-Based design ($10,140,263 vs. $4,164,863 vs. $3,268,504, respectively). Thus, Registry-Based total costs were 32 % of the Explanatory and 78 % of the Pragmatic design. Conclusion: Total costs for the STRESS RCT with a registry-based design were less than those for a pragmatic design and much less than an explanatory design. Cost savings reflect design elements and leveraging of registry resources to improve cost efficiency, but delays to trial completion should be considered.

Index and follow-up costs of endovascular abdominal aortic aneurysm repair from the Endurant Stent Graft System Post Approval Study (ENGAGE PAS).

OBJECTIVE: Trials for endovascular aneurysm repair (EVAR) report lower perioperative mortality and morbidity, but also higher costs compared with open repair. However, few studies have examined the subsequent cost of follow-up evaluations and interventions. Therefore, we present the index and 5-year follow-up costs of EVAR from the Endurant Stent Graft System Post Approval Study. METHODS: From August 2011 to June 2012, 178 patients were enrolled in the Endurant Stent Graft System Post Approval Study de novo cohort and treated with the Medtronic Endurant stent graft system (Medtronic Vascular, Santa Rosa, Calif), of whom 171 (96%) consented for inclusion in the economic analysis and 177 participated in the quality-of-life (QOL) assessment over a 5-year follow-up period. Cost data for the index and follow-up hospitalizations were tabulated directly from hospital bills and categorized by Uniform Billing codes. Surgeon costs were calculated by Current Procedural Terminology codes for each intervention. Current Procedural Terminology codes were also used to calculate imaging and clinic follow-up reimbursement as surrogate to cost based on year-specific Medicare payment rates. Additionally, we compared aneurysm-related versus nonaneurysm-related subsequent hospitalization costs and report EuroQol 5D QOL dimensions. RESULTS: The mean hospital cost per person for the index EVAR was $45,304 (interquartile range [IQR], $25,932-$44,784). The largest contributor to the overall cost was operating room supplies, which accounted for 50% of the total cost at a mean of $22,849 per person. One hundred patients had 233 additional post index admission inpatient admissions; however, only 32 readmissions (14%) were aneurysm related, with a median cost of $13,119 (IQR, $4570-$24,153) compared with a nonaneurysm-related median cost of $6609 (IQR, $1244-$26,466). Additionally, 32 patients were admitted a total of 37 times for additional procedures after index admission, of which 14 (38%) were aneurysm-related. The median cost of hospitalization for aneurysm-related subsequent intervention was $22,023 (IQR, $13,177-$47,752), compared with a median nonaneurysm-related subsequent intervention cost of $19,007 (IQR, $8708-$33,301). After the initial 30-day visit, outpatient follow-up imaging reimbursement averaged $550 per person per year ($475 for computed tomography scans, $75 for the abdomen), whereas annual office visits averaged $107 per person per year, for a total follow-up reimbursement of $657 per person per year. There were no significant differences in the five EuroQol 5D QOL dimensions at each follow-up compared with baseline. CONCLUSIONS: Costs associated with index EVAR are driven primarily by cost of operating room supplies, including graft components. Subsequent admissions are largely not aneurysm related; however, cost of aneurysm-related hospitalizations is higher than for nonaneurysm admissions. These data will serve as a baseline for comparison with open repair and other devices.

Assessing the Financial Value of Patient Engagement: A Quantitative Approach from CTTI's Patient Groups and Clinical Trials Project.

BACKGROUND: While patient groups, regulators, and sponsors are increasingly considering engaging with patients in the design and conduct of clinical development programs, sponsors are often reluctant to go beyond pilot programs because of uncertainty in the return on investment. We developed an approach to estimate the financial value of patient engagement. METHODS: Expected net present value (ENPV) is a common technique that integrates the key business drivers of cost, time, revenue, and risk into a summary metric for project strategy and portfolio decisions. We assessed the impact of patient engagement on ENPV for a typical oncology development program entering phase 2 or phase 3. RESULTS: For a pre-phase 2 project, the cumulative impact of a patient engagement activity that avoids one protocol amendment and improves enrollment, adherence, and retention is an increase in net present value (NPV) of $62MM ($65MM for pre-phase 3) and an increase in ENPV of $35MM ($75MM for pre-phase 3). Compared with an investment of $100,000 in patient engagement, the NPV and ENPV increases can exceed 500-fold the investment. This ENPV increase is the equivalent of accelerating a pre-phase 2 product launch by 2½ years (1½ years for pre-phase 3). CONCLUSIONS: Risk-adjusted financial models can assess the impact of patient engagement. A combination of empirical data and subjective parameter estimates shows that engagement activities with the potential to avoid protocol amendments and/or improve enrollment, adherence, and retention may add considerable financial value. This approach can help sponsors assess patient engagement investment decisions.

Predictors of long-term clinical endpoints in patients with refractory angina.

BACKGROUND: Clinical outcomes in patients with refractory angina (RA) are poorly characterized and variably described. Using the Duke Database for Cardiovascular Disease (DDCD), we explored characteristics that drive clinical endpoints in patients with class II to IV angina stabilized on medical therapy. METHODS AND RESULTS: We explored clinical endpoints and associated costs of patients who underwent catheterization at Duke University Medical Center from 1997 to 2010 for evaluation of coronary artery disease (CAD) and were found to have advanced CAD ineligible for additional revascularization, and were clinically stable for a minimum of 60 days. Of 77 257 cardiac catheterizations performed, 1908 patients met entry criteria. The 3-year incidence of death; cardiac rehospitalization; and a composite of death, myocardial infarction, stroke, cardiac rehospitalization, and revascularization were 13.0%, 43.5%, and 52.2%, respectively. Predictors of mortality included age, ejection fraction (EF), low body mass index, multivessel CAD, low heart rate, diabetes, diastolic blood pressure, history of coronary artery bypass graft surgery, cigarette smoking, history of congestive heart failure (CHF), and race. Multivessel CAD, EF<45%, and history of CHF increased risk of mortality; angina class and prior revascularization did not. Total rehospitalization costs over a 3-year period per patient were $10 185 (95% CI 8458, 11912) in 2012 US dollars. CONCLUSIONS: Clinically stable patients with RA who are medically managed have a modest mortality, but a high incidence of hospitalization and resource use over 3 years. These findings point to the need for novel therapies aimed at symptom mitigation in this population and their potential impact on health care utilization and costs.

Impact of pediatric exclusivity on drug labeling and demonstrations of efficacy.

BACKGROUND: Besides vaccines and otitis media medicines, most products prescribed for children have not been studied in the pediatric population. To remedy this, Congress enacted legislation in 1997, known as pediatric exclusivity (PE), which provides 6 months of additional market protection to drug sponsors in exchange for studying their products in children. METHODS: We reviewed requests for pediatric studies and subsequent labeling for drugs granted PE from 1998 through 2012. Regression analysis estimates the probability of demonstrating efficacy in PE trials. Variables include therapeutic group, year of exclusivity, product sales, initiation process, and small disease population. RESULTS: From 1998 through 2012, the US Food and Drug Administration issued 401 pediatric study requests. For 189 drugs, studies were completed and granted exclusivity. A total of 173 drugs (92%) received new pediatric labeling, with 108 (57%) receiving a new or expanded pediatric indication. Three drugs had non-efficacy trials. Efficacy was not established for 78 drugs. Oncology, cardiovascular, and endocrine drugs were less likely to demonstrate efficacy (P < .01) compared with gastrointestinal and pain/anesthesia drugs. Drugs studied later in the program were less likely to demonstrate efficacy (P < .05). Sales, initiation process, and small disease population were not significant predictors. CONCLUSIONS: Most drugs (173; 92%) granted exclusivity added pediatric information to their labeling as a result of PE, with 108 (57%) receiving a new or expanded pediatric indication. Therapeutic area and year of exclusivity influenced the likelihood of obtaining a pediatric indication. Positive and negative outcomes continue to inform the construct of future pediatric trials.

Reduced length of hospital stay in colorectal surgery after implementation of an enhanced recovery protocol.

BACKGROUND: Enhanced recovery after surgery (ERAS) is a multimodal approach to perioperative care that combines a range of interventions to enable early mobilization and feeding after surgery. We investigated the feasibility, clinical effectiveness, and cost savings of an ERAS program at a major U. S. teaching hospital. METHODS: Data were collected from consecutive patients undergoing open or laparoscopic colorectal surgery during 2 time periods, before and after implementation of an ERAS protocol. Data collected included patient demographics, operative, and perioperative surgical and anesthesia data, need for analgesics, complications, inpatient medical costs, and 30-day readmission rates. RESULTS: There were 99 patients in the traditional care group, and 142 in the ERAS group. The median length of stay (LOS) was 5 days in the ERAS group compared with 7 days in the traditional group (P < 0.001). The reduction in LOS was significant for both open procedures (median 6 vs 7 days, P = 0.01), and laparoscopic procedures (4 vs 6 days, P < 0.0001). ERAS patients had fewer urinary tract infections (13% vs 24%, P = 0.03). Readmission rates were lower in ERAS patients (9.8% vs 20.2%, P = 0.02). DISCUSSION: Implementation of an enhanced recovery protocol for colorectal surgery at a tertiary medical center was associated with a significantly reduced LOS and incidence of urinary tract infection. This is consistent with that of other studies in the literature and suggests that enhanced recovery programs could be implemented successfully and should be considered in U.S. hospitals.

Economic analysis of endovascular repair versus surveillance for patients with small abdominal aortic aneurysms.

BACKGROUND: The Positive Impact of EndoVascular Options for Treating Aneurysms Early (PIVOTAL) trial enrolled individuals with small (4.0- to 5.0-cm diameter) abdominal aortic aneurysms (AAA) and reported no difference in rupture or aneurysm-related death for patients who received early endovascular repair (EVAR) vs surveillance with serial imaging studies. We evaluated resource use, medical cost, and quality of life outcomes associated with the PIVOTAL treatment strategies. METHODS: This prospective economic and quality of life study was conducted within a randomized trial, with PIVOTAL sites participating in the quality of life (n = 67) and economic (n = 63) studies. The PIVOTAL trial randomized 728 patients (366 early EVAR and 362 surveillance). We used information from 701 quality of life (351 early EVAR and 350 surveillance) and 614 economic (314 early EVAR and 300 surveillance) study participants enrolled in the PIVOTAL trial. The main outcome measures were total medical costs and the aneurysm repair rate at 48 months. RESULTS: After 6 months, the rate of aneurysm repair was 96 vs 10 per 100 patients in the early EVAR and surveillance groups, respectively (difference, 86; 95% confidence interval [CI], 82-90; P < .0001), and total medical costs were greater in the early EVAR group ($33,471 vs $5520; difference, $27,951; 95% CI, $25,156-$30,746; P < .0001). In months 7 through 48, however, the rate of aneurysm repair was 54 per 100 patients in the surveillance group, and total medical costs were higher for patients in the surveillance vs the early EVAR group ($40,592 vs $15,197; difference, $25,394; 95% CI, $15,184-$35,605; P < .0001). At 48 months' follow-up, early EVAR patients had greater cumulative use of AAA repair (97 vs 64 per 100 patients; difference, 34; 95% CI, 21-46; P < .0001), but there was no difference in total medical costs ($48,669 vs $46,112; difference, $2557; 95% CI, -$8043 to $13,156; P = .64). After discounting at 3% per annum, total medical costs for early EVAR and surveillance patients remained similar ($47,765 vs $43,532; difference, 4232; 95% CI, -$5561 to $14,025; P = .40). There were no treatment-related differences in quality of life at 24 months. CONCLUSIONS: A treatment strategy involving early repair of smaller AAA with EVAR is associated with no difference in total medical costs at 48 months vs surveillance with serial imaging studies. Longer follow-up is required to determine whether the late medical cost increases observed for surveillance will persist beyond 48 months.

The UCSD shortness of breath questionnaire has longitudinal construct validity in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease that often causes disabling dyspnea. In IPF and other lung diseases, patient-reported outcomes (PROs)-questionnaires designed to gather information from the patient's perspective-can determine whether therapies affect dyspnea or other outcomes meaningful to patients. Before a PRO can be used confidently as an outcome measure in a longitudinal trial, studies must demonstrate the PRO's ability to capture change over time in the target population. Our goal in this study was to examine whether the UCSD Shortness of Breath Questionnaire does so in patients with IPF. METHODS: We used data from the Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis (STEP-IPF) to perform analyses that examined associations between UCSD scores and five external measures (anchors) at baseline and over time. Anchors included the Activity domain from St. George's Respiratory Questionnaire (SGRQ-A), the Physical Functioning domain from the SF-36 (SF36-PF), forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and distance walked during a timed walk test (6MWD). Linear regression models were used to examine relationships between UCSD scores and anchors over time. RESULTS: At baseline, UCSD scores were weakly correlated with percent predicted FVC (-0.21, p = 0.005) and percent predicted DLCO (-0.20, p = 0.008), moderately correlated with 6MWD (-0.39, p < 0.0001) and strongly correlated with SGRQ-A (0.79, p < 0.0001) and SF36-PF (-0.72, p < 0.0001). Change over time in UCSD scores was associated with change in FVC (estimate = 2.54, standard error [SE] = 1.23, p = 0.04), SGRQ-A (estimate = 7.94, SE = 1.11, p < 0.0001), SF36-PF (estimate = 6.00, SE = 1.13, p < 0.0001), and 6MWD (estimate = 4.23, SE = 1.18, p = 0.0004) but not DLCO (estimate = 0.33, SE = 1.33, p = 0.80). CONCLUSIONS: These results support the validity of the UCSD to assess change in dyspnea over time in patients with IPF.

Assessing the economic attractiveness of coronary artery revascularization in chronic kidney disease patients.

Chronic kidney disease (CKD) is associated with increased morbidity and mortality in coronary artery disease (CAD) patients. We compared the economic attractiveness of CAD revascularization procedures in patients with and without CKD. Our population included 6218 patients with significant CAD undergoing cardiac catheterization at Duke University between 1996 and 2001, with follow-up through 2002. We investigated the influence of CKD (creatinine clearance < 60 mL/min) upon 3-year survival and medical costs in our CAD population. Coronary artery bypass graft (CABG) surgery was an economically attractive alternative vs. percutaneous coronary intervention (PCI) or medical therapy for all patients with left main disease, three-vessel CAD patients without CKD, and two-vessel CAD patients with CKD. Medical therapy was an economically attractive strategy vs. CABG surgery or PCI for three-vessel CAD patients with CKD, two-vessel CAD patients without CKD, and all single-vessel CAD patients.

Long-term clinical and economic analysis of the Endeavor zotarolimus-eluting stent versus the cypher sirolimus-eluting stent: 3-year results from the ENDEAVOR III trial (Randomized Controlled Trial of the Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System Versus the Cypher Sirolimus-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions).

OBJECTIVES: The aim of this study was to evaluate clinical and economic outcomes for subjects receiving zotarolimus-eluting (ZES) (n = 323) versus sirolimus-eluting stents (SES) (n = 113) in the ENDEAVOR III (Randomized Controlled Trial of the Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System Versus the Cypher Sirolimus-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions) clinical trial. BACKGROUND: Although previous clinical trials have evaluated long-term clinical outcome for drug-eluting stents, none considered their economic implications. METHODS: We analyzed case report form information with quality-of-life adjustment and Medicare cost weights applied from secondary sources; compared differences in clinical outcomes, quality-adjusted survival, medical resource use, and medical costs; and evaluated cost-effectiveness through 3-year follow-up. RESULTS: The use of ZES versus SES reduced the 3-year rates/100 subjects of death or myocardial infarction (3.9 vs. 10.8; difference, -6.9; 95% confidence interval [CI]: -13.0 to 0.8; p = 0.028), with no difference in target vessel revascularization rates (17.9 vs. 12.2; difference, 5.7; 95% CI: -3.7 to 15.1; p = 0.23) but greater use of coronary artery bypass graft (CABG) surgery (3.5 vs. 0.0; difference 3.5; 95% CI: 1.3 to 5.7; p = 0.002). After discounting at 3% per annum, total medical costs for ZES versus SES were similar ($23,353 vs. $21,657; difference, $1,696; 95% CI: -$1,089 to $4,482, p = 0.23), and the 3-year cost-effectiveness ratio was $57,002/quality-adjusted life year. CONCLUSIONS: Despite a reduction in death or myocardial infarction and no difference in total revascularizations, medical costs were not decreased due to increased CABG repeat revascularization procedures for subjects receiving ZES versus SES. If future trials observe similar differences, improved safety with no difference in medical costs, the use of ZES versus SES will be a clinically and economically attractive treatment strategy. (The Medtronic Endeavor III Drug Eluting Coronary Stent System Clinical Trial [ENDEAVOR III]; NCT00217256).

Outcomes of second revascularization procedures after stent implantation.

Drug-eluting stents (DES) reduce subsequent revascularization procedures. Although randomized trials have compared DES to brachytherapy and balloon angioplasty (PTCA) for in-stent restenosis, few long-term comparisons have been made to bare metal stents (BMS) or bypass surgery (CABG), particularly following second procedures. We sought to assess the association between revascularization modality and long-term clinical outcomes of patients receiving a second procedure for coronary artery disease. Between January 2000 and July 2005, 4,666 consecutive patients underwent initial coronary stent implantation (DES or BMS). From this population we identified 569 patients undergoing a second target vessel revascularization (DES, BMS, PTCA or CABG). Outcomes were assessed at 6, 12, and 24 months after the second procedure, with follow-up through September 2006. Adjusted cumulative incidence rates were calculated using inverse probability weighted estimators. We found that at 24 months, there were no significant differences in death or myocardial infarction for PTCA, BMS, DES, and CABG (17.7%, 14.9%, 7.5%, and 10.2%, p = 0.26[3dfl]). DES patients had lower rates of death or myocardial infarction or third target vessel procedures than patients receiving PTCA (14.6% vs. 30.0%, p = 0.01) and BMS (14.6% vs. 42.2%, p < 0.01), but rates similar to CABG patients (14.6% vs. 14.6%, p = 0.99). For patients undergoing a second revascularization procedure, PTCA, BMS, DES, and CABG are associated with a similar risk of death or nonfatal myocardial infarction. DES and CABG are associated with lower rates of third revascularization procedures compared to PTCA and BMS. Further studies are needed to determine the optimum application for CABG vs. DES as a second or third revascularization procedure.

Effect of medical management on recurrent stone formation following percutaneous nephrolithotomy.

PURPOSE: Percutaneous nephrolithotomy is a commonly used procedure for treatment of large or complex renal calculi. In some instances postoperative residual stone fragments are an unavoidable result. Yet to our knowledge no study has examined the impact of medical management on stone formation in patients with or without residual fragments following percutaneous nephrolithotomy. Thus, we have conducted the first investigation of aggressive medical management following percutaneous nephrolithotomy and its impact on stone formation rates in patients with and without residual fragments. MATERIALS AND METHODS: A total of 70 patients who underwent percutaneous nephrolithotomy and received counseling regarding selective medical management following a comprehensive metabolic evaluation, were identified. Patients were placed into 4 groups following percutaneous nephrolithotomy, that is stone-free or residual fragments, who underwent or did not undergo medical therapy. New stone formation was assessed by spontaneous stone passage in the absence of residual stone fragments, stone passage without change in the number of residual fragments, surgical removal of newly formed stones, or appearance of new stones or increase in size of stone or fragments on abdominal radiographs. Stone remission rates were also calculated. RESULTS: Selective medical therapy significantly decreased stone formation rates in the stone-free (0.67 stones per patient per year vs 0.02) and residual fragment groups (0.67 stones per patient per year vs 0.02) as determined by the Wilcoxon signed rank test (p<0.0001). Moreover, remission was observed in a higher proportion of patients in the medically treated stone-free and residual fragment groups (87% and 77%) when compared to the same groups without medical therapy (29% and 21%, chi-square test p<0.0001). CONCLUSIONS: Our findings suggest that comprehensive metabolic evaluation and aggressive medical management can control active stone formation and growth in patients with or without residual stone fragments after percutaneous nephrolithotomy. Given the inherent morbidity and increased costs attendant with repeat procedures, medical management should be instituted in patients following percutaneous nephrolithotomy without regard to stone-free status.

Economic return of clinical trials performed under the pediatric exclusivity program.

CONTEXT: In 1997, Congress authorized the US Food and Drug Administration (FDA) to grant 6-month extensions of marketing rights through the Pediatric Exclusivity Program if industry sponsors complete FDA-requested pediatric trials. The program has been praised for creating incentives for studies in children and has been criticized as a "windfall" to the innovator drug industry. This critique has been a substantial part of congressional debate on the program, which is due to expire in 2007. OBJECTIVE: To quantify the economic return to industry for completing pediatric exclusivity trials. DESIGN AND SETTING: A cohort study of programs conducted for pediatric exclusivity. Nine drugs that were granted pediatric exclusivity were selected. From the final study reports submitted to the FDA (2002-2004), key elements of the clinical trial design and study operations were obtained, and the cost of performing each study was estimated and converted into estimates of after-tax cash outflows. Three-year market sales were obtained and converted into estimates of after-tax cash inflows based on 6 months of additional market protection. Net economic return (cash inflows minus outflows) and net return-to-costs ratio (net economic return divided by cash outflows) for each product were then calculated. MAIN OUTCOME MEASURES: Net economic return and net return-to-cost ratio. RESULTS: The indications studied reflect a broad representation of the program: asthma, tumors, attention-deficit/hyperactivity disorder, hypertension, depression/generalized anxiety disorder, diabetes mellitus, gastroesophageal reflux, bacterial infection, and bone mineralization. The distribution of net economic return for 6 months of exclusivity varied substantially among products (net economic return ranged from -$8.9 million to $507.9 million and net return-to-cost ratio ranged from -0.68 to 73.63). CONCLUSIONS: The economic return for pediatric exclusivity is variable. As an incentive to complete much-needed clinical trials in children, pediatric exclusivity can generate lucrative returns or produce more modest returns on investment.

Local cost structures and the economics of robot assisted radical prostatectomy.

PURPOSE: Robot assisted prostatectomy (RAP) is more costly than traditional radical retropubic prostatectomy (RRP) under the cost structures at certain hospitals. However, this finding may not be the case in all care settings. We investigated the sensitivity of RAP and RRP inpatient costs to variations in length of stay (LOS), local hospitalization costs and robotic case volume in the specialist and generalist settings. MATERIALS AND METHODS: We developed a model of RAP vs RRP costs in the specialist and generalist settings using published data on operative time and LOS, and cost data from our academic medical center. All inpatient cost centers were included, namely surgery costs, professional fees, postoperative care, robotic equipment and service. Extensive 1 and 2-way sensitivity analyses were performed. RESULTS: Our base case model demonstrated a cost premium for RAP vs RRP of USD $783 and $195 in the specialist and generalist settings, respectively. Sensitivity analysis of our model assumptions demonstrated that RAP could achieve cost equivalence with RRP at a surgical volume of 10 cases weekly. If case volume increased to 14 cases weekly, RAP would be less expensive than RRP in some practice settings in which RAP LOS was less than 1.5 days. CONCLUSIONS: The inpatient costs of robotic assisted prostatectomy are volume dependent and cost equivalence with generalist radical retropubic prostatectomy is possible at higher volume RAP specialty centers. While RAP may be cost competitive with RRP at high cost hospitals or high volume RAP specialist centers, this procedure would exist at a cost premium to RRP in other practice settings.

Economic analysis of the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT-3) study: costs of reperfusion strategies in acute myocardial infarction.

BACKGROUND: The ASSENT-3 study examined the safety and efficacy of 3 alternative regimens for ST-elevation acute myocardial infarction: full-dose tenecteplase (TNK-tPA) plus enoxaparin; half-dose TNK-tPA plus unfractionated heparin plus abciximab; and full-dose TNK-tPA plus unfractionated heparin. OBJECTIVE: The aim of the study was to examine the resource and economic effects of the 3 regimens in ASSENT-3 using empirically collected data from the trial. METHODS: Cost estimates for each resource use component collected in ASSENT-3 were derived from Medicare reimbursement rates and from detailed billing data collected as part of a previous study. Costs of study drugs were estimated using average wholesale prices. All analyses were by intention to treat. Resource use and medical costs were examined first in the United States alone, and then in the entire cohort. RESULTS: Differences in costs across treatment arms were primarily due to differences in cost of study medication. Irrespective of source of cost weights, the least expensive alternative among the 3 treatment regimens was TNK-tPA and enoxaparin. Although not statistically significant, in 80% of 1000 bootstrap replications, the TNK-tPA enoxaparin arm was associated with 30-day cost savings relative to the unfractionated heparin arm. CONCLUSION: The favorable clinical outcomes demonstrated for enoxaparin arm relative to the unfractionated heparin arm in ASSENT-3 were accompanied by a favorable distribution of costs and support the designation of this regimen as economically attractive by conventional benchmarks.

Surgeons' economic profiles: can we get the "right" answers?

Hospitals and payers use economic profiling to evaluate physician and surgeon performance. However, there is significant variation in the data sources and analytic methods that are used. We used information from a hospital's cardiac surgery and cost accounting information systems to create surgeon economic profiles. Three scenarios were examined: (1) surgeon modeled as fixed effect with no patient-mix adjustment; (2) surgeon modeled as fixed effect with patient-mix adjustment; (3) and surgeon modeled as random effect with patient-mix adjustment. We included 574 patients undergoing coronary artery bypass surgery at Baptist Medical Center, Oklahoma City, OK between July 1, 1995 and April 30, 1996. We found that profiles reporting unadjusted average surgeon costs may incorrectly identify high- and low-cost outliers. Adjusting for patient-mix differences and treating surgeons as random effects was the preferred approach. These results demonstrate the need for hospitals to reexamine their economic profiling methods.

Economic impact of drug-eluting stents on hospital systems: a disease-state model.

BACKGROUND: Drug-eluting intracoronary stents decrease restenosis and later revascularization. The US Department of Health and Human Services (HHS), recognizing the financial and clinical impact of this technology, recently proposed accelerated reimbursement to hospitals. METHODS AND RESULTS: A disease state-transition computer model simulated the clinical and economic consequences to hospitals of drug-eluting stents over 5 years. Model parameters combined information from a longitudinal clinical database, a hospital cost-accounting system, and a survey instrument. Simulations were repeated 1000 times for each set of parameters. With 85% of stent procedures shifted to drug-eluting stents in the first year of availability, the mean number of repeat revascularizations dropped by 60.4% at year 5. With no changes in reimbursement policy, a hospital with a catheterization laboratory volume of 3112 patients yearly converted from a 2.01 million dollars (M) annual profit to an 8.10 M dollars loss in the first year (95% CI 8.09 M dollars to 8.12 M dollars) and 8.7 M dollars annual losses in later years. This represented an overall change in cash flow of 55.71 M dollars (95% CI 55.66 M dollars to 55.76 M dollars) away from the hospital over 5 years. The incremental reimbursement proposed by HHS reduced this loss to 4.75 M dollars in the first year and to 5.6 M dollars annually thereafter. In sensitivity analyses, the conversion of patients from bypass surgery to drug-eluting stents was the largest driver of overall cash flow shifts. CONCLUSIONS: Although Medicare has proposed to increase reimbursement to ease the impact of drug-eluting stents on hospitals, this increase will not totally offset the costs.