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To appraise the economics of a recurrence score (RS), based on an assay that predicts distant recurrence-free survival in lymph-node-negative (LN-), estrogen-receptor-positive (ER+) patients with early-stage breast cancer receiving tamoxifen.Cost-utility analyses using a decision analytic model.Using a Markov model, we forecast overall survival, costs, and cost effectiveness of using the RS in patients classified as having low or high risk of distant recurrence based on National Comprehensive Cancer Network (NCCN) clinical guidelines. Data from a large multicenter clinical trial (NSABP B-14) were analyzed to derive risk classification based on guideline criteria and RS assignments. Efficacy of adjuvant chemotherapy (CT) on distant recurrence-free survival (DRFS) was based on published meta-analyses of CT trials. The analysis took a societal perspective, considering survival, quality of life, and relevant costs.Fifty-three patients (8%) were classified as having low risk of distant recurrence by NCCN guidelines and the RS reclassified 15 of these patients (28%) to an intermediate/high-risk group. The remaining 615 patients (92%) were classified at high risk of distant recurrence by NCCN guidelines and the RS reclassified 300 of these patients (49%) to a low-risk group. Among a hypothetical cohort of 100 patients, RS is predicted on average to increase quality-adjusted survival by 8.6 years and reduce overall costs by $202 828. RS was cost saving in more than two-thirds of probabilistic simulations, with cost effectiveness most influenced by the propensity to administer CT based on RS results, and by the proportion of patients at low risk as defined by NCCN guidelines.The RS predicts more accurately than current guidelines recurrence risk in LN-, ER+ patients with early-stage breast cancer. If applied appropriately, the assay is predicted to increase quality-adjusted survival and save costs.

For patients with anthracycline-pretreated metastatic breast carcinoma, capecitabine plus docetaxel significantly increased overall survival compared with docetaxel alone. The current study evaluated the cost-effectiveness of the capecitabine/docetaxel combination versus docetaxel monotherapy, comparing the gain in quality-adjusted survival with associated health care costs.Patients were randomized to receive 21-day cycles of oral capecitabine 1250 mg/m2 twice daily, on Days 1-14, plus docetaxel 75 mg/m2 Day 1 (n = 255), or docetaxel 100 mg/m2 on Day 1 (n = 256). Health and cost outcomes in the two arms were compared, and cost-effectiveness was estimated. Data on survival time and medical care resource use were prospectively collected in the trial. Costs associated with medical care resource use and quality-of-life adjustments were obtained from the published literature. The incremental cost-effectiveness ratio was calculated as the cost per quality-adjusted life year (QALY) gained.Capecitabine/docetaxel increased the median overall survival by 3 months compared with docetaxel alone (14.5 vs. 11.5 months). The mean quality-adjusted survival was increased by 1.8 months in the capecitabine/docetaxel group. The total medical-resource utilization cost per patient was 8.9% higher with the combination: 24,475 dollars for combination therapy versus 22,477 dollars for single-agent docetaxel. The mean cost per QALY gained with combination therapy was 13,558 dollars (standard deviation, 6742 dollars). Cost savings due to reduced docetaxel dose and hospital use were the major cost offsets with the combination. Sensitivity analyses showed that varying the mean hospital cost per day from the 5th to the 95th percentile resulted in cost-utility ratios ranging from 20,326 dollars to as low as 6360 dollars.Capecitabine/docetaxel was a cost-effective treatment in patients with anthracycline-pretreated advanced breast carcinoma, and had an incremental cost-effectiveness ratio that compares very favorably with that of many other oncology therapies.

BACKGROUND Findings from the Groupe d'Etude des Lymphomes Adultes LNH 98-5 study showed that rituximab added to combined cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) prolonged progression-free survival and overall survival in adults age ≥ 60 years with diffuse large B-cell non-Hodgkin lymphoma (DLBCL). The current study was conducted to investigate the incremental cost utility of the addition of rituximab to CHOP (R-CHOP) compared with CHOP alone. METHODS Clinical prognosis of the time to disease progression and death was estimated using published evidence from the LNH 98-5 study (n = 399 patients) that was linked mathematically to published long-term outcome data on patients with DLBCL. Drug-acquisition costs were based on published data from formulary pricing sources, and the costs of cancer surveillance and end-of-life care were based on published literature sources. The authors assessed cost utility as the difference in costs between R-CHOP and CHOP divided by the increase in expected overall survival adjusted for quality of life. RESULTS Over 5 years, it was projected that R-CHOP would prolong overall survival by 1.04 years. The mean cumulative cost of CHOP was $3358, and the mean cost of R-CHOP was $17,225, resulting in a cumulative net increase of $13,867. The posttreatment cancer surveillance cost for CHOP was $3950, compared with $5202 for R-CHOP. It was estimated that R-CHOP would have a cost-utility ratio of $19,297 per year of life gained compared with CHOP when adjusted for quality of life. R-CHOP remained cost effective over wide ranges of variables in sensitivity analyses. CONCLUSIONS Compared with CHOP alone, it was predicted that R-CHOP would be cost effective in elderly patients with DLBCL. Cancer 2005. © 2005 American Cancer Society.

Objectives: Mathematical modeling is used widely in economic evaluations of pharmaceuticals and other healthcare technologies. Users of models in government and the private sector need to be able to evaluate the quality of models according to scientific criteria of good practice. This report describes the consensus of a task force convened to provide modelers with guidelines for conducting and reporting modeling studies. Methods: The task force was appointed with the advice and consent of the Board of Directors of ISPOR. Members were experienced developers or users of models, worked in academia and industry, and came from several countries in North America and Europe. The task force met on three occasions, conducted frequent correspondence and exchanges of drafts by electronic mail, and solicited comments on three drafts from a core group of external reviewers and more broadly from the membership of ISPOR. Results: Criteria for assessing the quality of models fell into three areas: model structure, data used as inputs to models, and model validation. Several major themes cut across these areas. Models and their results should be represented as aids to decision making, not as statements of scientific fact; therefore, it is inappropriate to demand that models be validated prospectively before use. However, model assumptions regarding causal structure and parameter estimates should be continually assessed against data, and models should be revised accordingly. Structural assumptions and parameter estimates should be reported clearly and explicitly, and opportunities for users to appreciate the conditional relationship between inputs and outputs should be provided through sensitivity analyses. Conclusions: Model-based evaluations are a valuable resource for health-care decision makers. It is the responsibility of model developers to conduct modeling studies according to the best practicable standards of quality and to communicate results with adequate disclosure of assumptions and with the caveat that conclusions are conditional upon the assumptions and data on which the model is built.

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.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.Initial therapy with PPIs followed by on-demand therapy was the most cost-effective approach, with a cost-effectiveness ratio of $20,934 per QALY gained for patients with moderate to severe GERD symptoms, and $37,923 for patients with mild GERD symptoms. This therapy was also associated with the greatest gain in discounted QALYs. The PPI-on-demand strategy was more effective and less costly than the H2RA followed by PPI strategy or the other treatment arms. The results were not highly sensitive to cost of therapy, QALY adjustment from GERD symptoms, or the success rate of the lifestyle arm. However, when the success rate of the PPI-on-demand arm wasor =59%, the H2RA-PPI arm was the preferred strategy.For patients with moderate to severe symptoms of GERD, initial treatment with PPIs followed by on-demand therapy is a cost-effective approach.

Serum levels of prostate-specific antigen have assumed a prominent clinical role in the management of prostate cancer. Little is known about the production of prostate-specific antigen, its mechanism of entry into the serum in normal and pathologic states, and mechanism(s) of removal from the serum. This study examined nephrostomy urine specimens, finding no significant excretion of prostate-specific antigen into the renal pelvic urine. Similarly, no significant lowering of serum prostate-specific antigen levels occurred during routine hemodialysis in men with chronic renal failure, nor were ambulatory, pre-dialysis serum prostate-specific antigen levels in these same men with chronic renal failure elevated. It appears unlikely that the kidney plays a significant role in the clearance of prostate-specific antigen from human serum.

Corticosteroids are an essential component of most immunosuppressive regimens currently used in renal transplantation because of their efficacy in reducing acute rejection and improving graft survival. Steroids, however, are associated with numerous side effects that lead to increased patient morbidity and mortality. The incidence and economic cost of steroid-related side effects have not been quantitatively assessed. Thus, based on a systematic review of the published literature, we estimated the incidence of steroid-related hypertension (15%), posttransplantation diabetes mellitus (10%), peripheral fractures (2% per year), avascular necrosis of the hip (8%), and cataracts (22%). In addition, we estimated that approximately 5% of patients who have cataracts or avascular necrosis of the hip require surgery. We used these literature-based estimates in a model to project the costs of treating side effects over a 10-year posttransplantation time frame for a 50-patient cohort that represented an average-sized renal transplant center. Steroid-induced hypertension and its complications were the most expensive side effect ($93,900), followed closely by posttransplantation diabetes ($89,700) and avascular necrosis of the hip ($61,700). Cataracts and peripheral bone fractures were less costly ($16,300 and $4,300, respectively). The cumulative projected 10-year cost of all side effects for the 50-patient cohort was $265, 900, or $5,300 per transplant patient. Steroid-related side effects add to the long-term cost of medical care of renal transplant recipients. These costs provide a rationale for further investigation of steroid-sparing immunosuppression protocols.

Clinicians and patients make many decisions in situations where optimal treatment is uncertain. Despite well-published advantages of clinical trials for reducing such uncertainties, a trial may not be conducted because the sample size indicated by classical, hypothesis-testing methods is so large that no one institution could afford to sponsor the trial. By explicitly taking into consideration the costs and benefits of a trial, Bayesian statistical methods permit estimation of the value to a health care organization conducting a randomized trial instead of continuing to treat patients in the absence of more information. This paper describes a method for calculating the cost-benefit to a health care organization conducting a clinical trial, and the expected sample size to adequately resolve the uncertainties about which treatment is better. The method is illustrated in the case of a proposed clinical trial of a drug to prevent multiorgan system failure and death in patients admitted to the Stanford University surgical intensive care unit. This method should permit health care organizations to evaluate a proposed trial's expected cost-benefit and the expected sample size that will resolve the question of interest, and thereby assist in the process of deciding whether to conduct the trial.

To determine if a self-administered previsit questionnaire designed to increase awareness of patients’ concerns alters the visit duration, content of the discussion, and patient and physician satisfaction. A balanced, two-arm trial in which physicians were randomized. Two primary-care clinics affiliated, with a university hospital. Ten physicians and 201 continuitycare patients. In intervention visits, patients completed a previsit questionnaire asking about the desire for medical information, psychosocial assistance, therapeutic listening, general health advice, and biomedical treatment. Physicians reviewed questionnaires with patients during the visit. We used audiotapes of encounters to quantify the duration of the encounter and measured the number and type of diagnoses discussed in the visit, and patient and physician satisfaction with the encounter. Intervention visits were 34% longer (increase of 6.8 minutes; 95% confidence interval, [CI] 0.4, 13.2) than control visits with most of the additional time spent in discussion of biomedical diagnoses (3.35 minutes; 95% CI 0.00, 6.72) and in the performance of the physical examination (2.7 minutes; 95% CI 0.5 4.9). The number of diagnoses discussed per visit was 30% higher in intervention visits (increase of 1.7 diagnoses per visit; 95% CI 0.3, 3.2), but patients’ satisfaction with these visits tended to be lower. Using a previsit questionnaire to increase awareness of the patients’ concerns may entail a trade-off between conflicting goals: trying to respond to patient concerns while not significantly increasing the cost per visit. A future challenge is to develop and refine techniques with sufficient efficacy to justify the expense of implementing the intervention and the longer visit needed to respond adequately to patients’ concerns.

The constraints on medical-care resources can give rise to the question of the cost- effectiveness of permitting repeat medical procedures when some patients may die without undergoing even a first procedure. Using kidney transplantation as an example, this study estimates the cost-effectiveness of patients' having available the option of a repeat medical procedure in the event the first procedure fails. Specifically, the anal ysis examines the effect on transplant candidates of having the option of kidney re transplantation, if and when retransplantation might be needed. Data sources include the U.S. Renal Data System (USRDS) Case-Mix Severity Study, Health Care Financ ing Administration (HCFA) data, and a MEDLINE search. Outcome measures include life expectancy, quality-adjusted life expectancy, lifetime costs of medical care, and mar ginal cost-effectiveness from a societal perspective. By avoiding lifelong dialysis after graft failure, first-transplant candidates gain an average of 47 quality-adjusted days with a retransplantation policy, despite the prolongation of time to first transplant by an average of 30 quality-adjusted days. The lifetime cost of medical care per first- transplant candidate is $1,210 higher with a retransplantation policy compared with the no-retransplantation policy; its societal cost-effectiveness is estimated to be $9,656 per quality-adjusted life-year saved. The retransplantation policy provides the greatest improvement in quality-adjusted life expectancy for younger candidates. In the case of kidney transplantation, the cost-effectiveness of a repeat transplant, on average, com pares favorably with those of other medical strategies in common practice. As re sources become increasingly constrained, this study demonstrates a framework for considering the cost-effectiveness of repeat medical procedures. Key words: kidney transplantation; decision analysis; cost-effectiveness analysis; ethics; rationing. (Med Decis Making 1997;17:363-372))

Study objectives To assess the health and cost effects of a patient's risk-taking attitudes about diagnostic tests. Design Cost-effectiveness analysis. Setting Diagnostic testing strategies used in the evaluation of a patient with a radiographically detected lung lesion were evaluated. Strategies included combinations of sputum, fine-needle aspiration, bronchoscopy, thoracoscopy, and expectant management. Patients Patient data were obtained from the Survival Epidemiology and End Results Program, MEDLINE search, National Center for Health Statistics, and the Universities of Iowa and Stanford, and Kaiser Permanente Hospital. Interventions Different patient risk-taking attitudes were simulated using decision analysis. Measurements: Lifetime cost of medical care, life expectancy, and cost effectiveness. Results The cost effectiveness of competing strategies depended on patient attitudes about taking risks. For a patient averse to expectantly waiting without definitive knowledge of whether cancer was or was not present, testing strategies using invasive procedures, such as thoracoscopy, were more cost effective. In contrast, for a patient who was identical except that he or she was averse to tests with higher morbidity and mortality, strategies that involved expectantly waiting, instead of more invasive tests, were more cost effective. Small changes in some risk-taking attitudes resulted in large changes in cost effectiveness. Conclusions Risk-taking attitudes influenced the cost effectiveness of testing strategies. Consideration of patient risk-taking attitudes in diagnostic testing appears warranted in setting clinical policies and making individual decisions.

Objective: The authors reviewed data involving the impact of providing psychotherapy for psychiatric disorders on costs of care. Method: In a search of the MEDLINE database limited to peer-reviewed papers published from 1984 through 1994, 686 articles were identified. Forty-one articles, covering 35 studies, were found in which the intervention tested was psychotherapeutic and the study included measures of outcome that had some implications for cost. The exclusion criteria for reviewing these studies included absence of a comparison group, a focus on medical disorders instead of psychiatric illnesses, and outcomes that did not include cost data or measures from which costs could be inferred. On this basis, 18 of the 35 studies were selected for analysis. The studies were categorized according to whether or not subjects were randomly assigned to study groups. Two reviewers independently read each study to identify the following characteristics: inclusion criteria, exclusion criteria, types of interventions, main outcome variables, sample size, and statistical tests for significant differences between treatments. Outcomes had to include actual cost accounting or data on medical care utilization or work functioning. Results: The findings of eight (80%) of the 10 clinical trials with random assignment and all eight (100%) of the studies without random assignment suggested that psychotherapy reduces total costs. Conclusions: Psychotherapy appears to have a beneficial impact on a variety of costs when used in the treatment of the most severe psychiatric disorders, including schizophrenia, bipolar affective disorder, and borderline personality disorder. Much of that impact accrues from reductions in inpatient treatment and decreases in work impairment. (Am J Psychiatry 1997; 154:147‐155)

e16044 Background: Only a minority of prostate cancer patients with adverse pathology and biochemical recurrence (BCR) post radical prostatectomy (RP) experience metastasis and die from prostate cancer. Improved risk prediction models using genomic information may enable clinicians to better weigh the risk of metastasis and the morbidity and costs of treatment in a clinically heterogeneous population. We present a clinical utility study that evaluates the influence on urologist treatment recommendations for patients at risk of metastasis using a genomic-based prediction model (Decipher). Methods: A prospective, pre-post design was used to assess urologist treatment recommendations following RP in both the adjuvant (without any evidence of PSA rise) and salvage (BCR) settings. Urologists were presented de-identified pathology reports and genomic classifier (GC) test results for 24 patients from a previously conducted GC validation study in high-risk post RP men. Participants were fellowship trained, high-volume urologic oncologists (n=21) from 18 US institutions. Treatment recommendations for secondary therapy were made based solely on clinical information (pre-GC) and then with genomic biomarker information (post-GC). This study was approved by an independent IRB. Results: Treatment recommendations changed from pre-GC to post- GC in 43% of adjuvant, and in 53% of salvage setting case evaluations. In the adjuvant setting, urologists changed their treatment recommendations from treatment (i.e. radiation and/or hormones) to close observation post-GC in 27% of cases. However, for cases with low GC risk (

e22172 Background: A retrospective registry study has shown that gene-expression profiling (GEP) of the tissue of origin (Pathwork Tissue of Origin Test) of metastatic or poorly differentiated cancer changes the working diagnosis and management for the majority of patients. The FDA-cleared GEP test determines similarity of tumors of uncertain origin to gene expression patterns representing 60 morphologies in 15 cancer types. Inability to identify cancer primary sites presents challenges for patient treatment, outcomes, and prognosis. This study aims to prospectively assess impact of GEP on physician decisions and patient outcomes. Methods: A prospective, observational study is examining GEP’s impact on treatment changes and outcomes in adult patients with difficult-to-diagnose cancers. The study is assessing changes in diagnosis, management, oncologist confidence and perception of the test’s clinical utility, survival, therapy response, and other outcomes over 2 years of follow-up. Results before and after GEP are presented here for 18 patients. The study is designed to enroll 300 patients overall. Results: The primary working diagnosis changed for 37% of patients: 4 whose physicians obtained a working diagnosis while previously not having a tissue-specific diagnosis, and 3 for whom the primary diagnosis changed. After GEP, all patients had a working diagnosis. At least one aspect of management plans changed for 65% patients after GEP. Chemotherapy was ordered for 2 more patients and the regimen changed for 3 others; surgery was performed for 4 fewer, radiation for 1 fewer, and hospice for 2 more patients. After obtaining results from GEP, 58% of the treating oncologists “agreed” or “strongly agreed” that they were confident in both their diagnosis and treatment. Seventy-two percent believed that their changes in management would lead to improvement in at least one outcome (survival, response rate, time to relapse, quality of life, or patient anxiety). Conclusions: Current results of this prospective study are consistent with results of the prior retrospective study: GEP significantly changed and improved physician confidence in their diagnosis and treatment. Clinical trial information: NCT01649453.

3640 Background: Prior economic analysis of a 12-gene assay (Oncotype DX), compared with patterns of care reported in the NCCN database of patients with stage II, T3, DNA mismatch repair proficient (MMR-P) colon cancer, predicted that the assay would save medical costs and improve patient well-being (Hornberger et al. Value Health 2012). This study assessed the validity of those findings with actual adjuvant chemotherapy (aCT) recommendations. Methods: Outcomes and costs were estimated for patients with stage II, T3, MMR-P colon cancer using a Markov model. A study of 141 patients from 17 sites in the Mayo Clinic Cancer Research Consortium collected data on aCT recommended before and after knowledge of the 12-gene assay results (Srivastava et al. abstract). Quality-adjusted life years (QALY) and medical resource use after recurrence were computed using guideline-validated state-transition probability estimation methods. Risk of progression and incidence of adverse events with different aCT regimens were based on published literature. Drug and administration costs for aCT were obtained from 2012 Medicare fee schedules. One-way sensitivity analyses were conducted to evaluate parameter influence on economic impact. Results: After receiving the 12-gene assay results, physician recommendations in favor of aCT decreased 22% (95% CI 11%-32%; McNemar test p75% due to generic substitution. Conclusions: The 12-gene assayhas been shown to alter aCT recommendations for patients with stage II, T3, MMR-P colon cancer. This study provides real-world confirmation that these aCT changes reduce direct medical costs and improve patient well-being.

Abstract 2063 Introduction Rituximab in combination with chemotherapy is a recommended regimen for non-Hodgkin's lymphoma (NHL), which has been shown in randomized trials and real-world studies to provide a survival benefit compared with chemotherapy alone. Per the US Prescribing Information (USPI), rituximab is typically administered over 4–6 hours for the first infusion and 3–4 hours for subsequent infusions. A 90-minute infusion schedule for rituximab has been found to be safe and feasible in NHL patients who tolerate their first infusion administered at the standard rate and who do not have significant cardiovascular disease or high circulating lymphocytes. This study's primary objective was to assess the cost from a US societal perspective of faster 90-minute rituximab infusion vs the conventional 4–6 hour rituximab infusion. Methods Analyses were performed in accordance with best research guidelines of the International Society of Pharmacoeconomic Outcomes and Research. The target population was patients with previously untreated diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) who were scheduled to receive rituximab 375 mg/m2plus CHOP or CVP chemotherapy. Medical resources assessed were: chemotherapy administration, chemotherapy and pre-treatment drugs, and Grade 3/4 adverse events. Indirect costs include societal resources such as income foregone by patients and informal caregivers/spouses as a result of visit duration for infusion. Trial data were used to extract event rates of adverse events and duration of infusions, and patient drop-out rate by cycle. Prices for medical resources were obtained from publicly available Medicare Fee Schedules. Per capita hourly wage rates were extracted from statistics of the US Labor Department. Outcomes were costs per year for patients treated in the US and cost per infusion and per course of therapy in 2012 US dollars. Results A projected 23,519 newly diagnosed DLBCL and FL patients comprise the target population. Estimated total direct medical cost for conventional infusion is $925,318,162 and $9,855,416 in foregone income for patients and caregivers. The 90-minute infusion reduced direct medical costs by $22,362,397 (2%) and foregone income for patients and caregivers by $5,115,629 (52%). The average cost savings were $359 per infusion and $2,119 per course. The most influential parameters were administration cost and patient foregone income due to time for infusions. The savings per course may be greater if infusion centers are able to spread fixed costs, e.g., overhead, among a greater number of patients resulting from increased capacity to schedule more patients. Conclusion The 90-minute rituximab infusion has been found to be a safe and feasible alternative to conventional rituximab infusion for patients with untreated DBLCL or FL. In an era of landmark legislation (The Patient Protection and Affordable Care Act of 2010) designed to address concerns about rising costs of healthcare and place more emphasis on patient-centered research, the faster rituximab infusion regimen offers direct medical savings and reduces foregone income to patients and caregivers. Disclosures: Hornberger: Cedar Associates LLC: Employment; Genentech, A Member of the Roche Group: Research Funding. Off Label Use: Rituxan (Rituximab) - faster infusion is off-label. Dai:Cedar Associates: Employment; Genentech, Inc, A Member of the Roche Group: Research Funding. Goertz:Genentech, Inc, A Member of the Roche Group: Employment, Equity Ownership. Dawson:Genentech, A Member of the Roche Group: Employment, Equity Ownership. Reyes:Genentech, Inc, A Member of the Roche Group: Employment, Equity Ownership.

10584 Background: Expected survival is an important factor in treatment selection and patient decision making. Gene expression profiling for tissue of origin (GEP TOO) can be used to classify metastatic and poorly-differentiated tumors according to the most likely primary site for difficult-to-diagnose tumors. The Pathwork Tissue of Origin Test, (Redwood City, CA) generates Similarity Scores (SS), one for each of the 15 tissues on the Tissue of Origin Test Panel and sum to 100. The highest SS has been validated as the most likely tissue of origin in a large validation study (Pillai et al. 2010). This abstract reports the relationship between the highest SS for a sample and patient survival. Methods: Two cohorts were analyzed in IRB-approved studies. Cohort 1 consisted of 45 patients with carcinoma of unknown primary treated empirically with therapy for carcinoma of unknown primary with known outcome data including survival. Cohort 2 consisted of 107 patients receiving the TOO test in routine clinical practice and included in a decision impact registry study. The relationship between the highest SS generated by the TOO test was examined using parametric (Gamma) and non-parametric (Cox Proportional Hazards) regression models with covariates of age, gender and median survival of the cancer type indicated. Logrank tests were performed to compare survival in patients with SS above or below 50 in each cohort. Results: The highest SS generated by the TOO Test was strongly and positively correlated with patient survival in both Cohort 1 (p = 0.0093, Cox PH) and in Cohort 2 (p=0.0045, Gamma). In Cohort 1, survival for patients with a SS < 50 was 5.9 mos and for patients with a SS ≥ 50 was 9.7 mos (p=0.03, logrank). In Cohort 2, survival for patients with a SS < 50 was 10.6 mos and 22.6 mos for patients with a SS ≥ 50 (p=0.0073, logrank). Conclusions: The Similarity Scores generated by GEP TOO Test have been validated as an aid to diagnosis for difficult-to-diagnose malignancies. Two independent studies of this GEP TOO Test demonstrated a strong positive relationship between the highest SS and survival. This has the potential to expand the clinical utility of this test beyond diagnosis to include prognosis. Further studies to examine this question are underway.

Background: Gene expression profiling (GEP) reliably supplements traditional clinicopathological information on the tissue of origin (TOO) in metastatic or poorly differentiated cancer. A cost-effectiveness analysis of GEP TOO testing versus usual care was conducted from a third-party payer perspective in the United States. Methods: A retrospective, observational study examined treatment changes in patients whose physicians had received the GEP TOO test results to help diagnose the tissue-site of their patient's malignancy and to guide appropriate therapy. Changes in planned chemotherapy, surgery, radiation therapy, added blood tests, imaging investigations, and referral to hospice care before and after the GEP TOO test results were recorded. The effect of changes in chemotherapy on survival were based on randomized controlled trials informing appropriate use of chemotherapy cited in National Comprehensive Cancer Network (NCCN) and Up-to-Date guidelines. Drug and administration costs were based on average doses reported in NCCN guidelines. Centers for Medicare and Medicaid Services (CMS) fee schedules were used to obtain other unit costs. Quality-of-life weights were obtained from literature sources. Changes in overall survival, costs, and cost per quality-adjusted life year (QALY) gained were estimated using bootstrap methods. Results: Use of chemotherapy regimens consistent with guidelines for the final tumor-site diagnosis increased significantly from 42% to 65% (net difference 23%; p< 0.001). Overall survival was projected to increase from 15.9 months to 19.5 months (mean difference 3.6 months, 95%CI [2.0, 5.1]). The average increase in survival adjusted for quality of life was 2.7 months (95%CI [1.4, 3.9]), and average third-party payer costs per patient increased by $10,360 (95% CI [$5,668, $15,053]). The cost per QALY gained was $46,858 (95% CI [$17,995, $75,718]). Conclusions: GEP TOO testing significantly altered clinical practice patterns for treating metastatic cancer of uncertain primary. It is projected to increase overall survival, QALYs, and costs, resulting in an expected cost per QALY of less than $50,000.

397 Background: An important step for a novel test is assessing its clinical utility and real-world effect on diagnosis and patient management. This report describes completed results of a cohort of physicians who have ordered a gene expression profile assay for identification of tumor tissue of origin (Pathwork Tissue of Origin Test) for patients with difficult-to-diagnose primary cancers and their subsequent treatment and survival. Methods: The IRB-approved registry collected data from participating physicians who have ordered the Tissue of Origin test. A detailed interview was conducted using both a web-based questionnaire and a confirmatory telephone interview with the physicians. Chart survey included collection of data on patient demographics, diagnostic procedures including imaging and immunohistochemistry as well as therapy. The physicians were queried regarding their working diagnoses and treatment recommendations prior to and after Tissue of Origin Test result availability. Date of death was also obtained with a minimum of one year follow-up from date of biopsy. Results: One hundred seven patients (61 women) have been studied and 65 participating physicians have completed the interview. Results indicate that most patients underwent extensive evaluation (≥ 10 IHC) prior to gene expression analysis. After receiving test results, physicians changed the primary site diagnosis for 53 patients (50%, CI [43,58%]; p Conclusions: This registry study confirms that in patients with difficult-to-diagnose primary cancers, extensive baseline diagnostics are common and less than half of the patients have an established working diagnosis. Results indicate that the Tissue of Origin Test led to a change in working diagnosis and changed treatment recommendations in over half the patients. Survival outcomes compare favorably to historical controls in treatment trials where median survival is generally less than one year.

e18544 Background: Maintenance rituximab (R) therapy every two months for 2 years after chemoimmunotherapy (R-Chemo) has demonstrated improved progression-free survival (PFS) in previously untreate...

e21093 Background: An important step for validating a novel diagnostic is the assessment of its real-world clinical utility. Gene expression profiling (Pathwork Tissue of Origin Test) is recently a...

459 Background: An important step for a novel test is assessing its clinical utility and real-world effect on diagnosis and patient management. This report describes the results of a survey of physicians who have ordered a gene expression profile assay for identification of tumor tissue of origin (Pathwork Tissue of Origin Test) for patients with difficult-to-diagnose primary cancers. Methods: The IRB-approved registry collects data from participating physicians who have ordered the Tissue of Origin test for their patients. To minimize recall bias, a detailed interview is conducted using both a web-based questionnaire and a confirmatory telephone interview with the physicians. Chart survey includes collection of data on patient demographics, diagnostic procedures including imaging and pathology including immunohistochemistry as well as therapy. The physicians are queried regarding their working diagnoses and treatment recommendations prior to and after Tissue of Origin Test result availability. Results: Enrollment in the registry is ongoing. Fifty-nine patients (34 women) have been studied and 48 participating physicians have completed the interview. Survey results suggest that most patients have undergone extensive evaluation including multiple imaging tests (median, 6) and exhaustive immunohistochemistry (median, 10) prior to gene expression analysis. For these 59 pts, based on clinicopathologic evaluation, physicians reported working diagnoses for 46% of patients prior to test results and 83% after test results. Treatment recommendations were changed for 53% of patients. The majority (70%) of treatment changes were for chemotherapy. Physicians (n=26) reported that the Tissue of Origin test decreased the diagnosis associated anxiety in 62% of patients. Conclusions: This ongoing registry study confirms that in patients with difficult-to-diagnose primary cancers, extensive baseline diagnostics is not uncommon and less than half of the patients have an established working diagnosis. Survey results suggest that the Tissue of Origin Test led to a change in working diagnosis and changed treatment recommendations in over half the patients. [Table: see text]

491 Background: Uncertainty exists regarding the use of adjuvant therapy in patients with stage II colon cancer. To assist decision making, we compared quality-adjusted life expectancy and costs associated with using a multigene recurrence score (RS) assay with the use of clinicopathological factors currently recommended in clinical guidelines. Methods: A state-transition (Markov) model was developed to assess outcomes associated with the use of the RS (Oncotype Dx gene expression assay) in adjuvant therapy decisions in stage II colon cancer (excluding T4 tumors and those with deficient DNA mismatch repair). RS test characteristics were based on results reported from a randomized controlled trial (QUASAR, Kerr et al. ASCO, 2009). Current rates of administering adjuvant chemotherapy (aCTX) as a function of age, lymphatic invasion, tumor stage, and number of lymph nodes examined was derived from the NCCN Colon/Rectum Cancer Outcomes study (Earle et al, J Surg Oncol, 2009). Effects of aCTX on recurrence risk were based on published data. Medicare fee schedules were used to estimate cost; toxicities, recurrence, and quality-of-life adjustments were obtained from published studies. Results: Treatment decisions based on RS and a patient's years of life remaining without cancer recurrence would reduce aCTX use by 17% compared with current treatment patterns, and increase quality-adjusted life expectancy by an average of 0.035 years. With lower use of aCTX, direct medical costs are expected to decrease by an average of $2,971 per patient. One-way sensitivity analysis predicts overall QALY improvement with the RS through a range of variables, with the results most sensitive to the disutility associated with aCTX use. Sensitivity analyses also show the assay to be cost-saving under a variety of conditions. Conclusions: Clinical use of a multigene RS to assess risk of recurrence in T3 stage II colon cancers with intact mismatch repair is likely to improve quality-adjusted life expectancy and be cost-saving from a societal perspective. Patient age and disutility associated with chemotherapy are important considerations in adjuvant treatment decisions. [Table: see text]

Case-mix adjusted mortality rates for patients undergoing hemodialysis for ESRD increased during the 1980s, despite the introduction of advanced dialysis technologies. Variations in dialysis practices suggest that excess mortality may be caused by inadequate uremic-toxin clearances. Cost-effectiveness analysis was used to assess whether attempts to improve uremic-toxin clearance are cost effective, assuming that these therapies are clinically effective. The medical literature was surveyed by the use of MEDLINE to assess the likelihood of clinical outcomes on the basis of the type of treatment given to the patient. Options considered in the model were delivered fractional urea clearance (Kt/V), dialysis-treatment duration, type of dialyzer membrane, dialysate, and ultrafiltration. Clinical outcomes included in the model were survival, severity of uremic symptoms, hospital days per year, and intradialytic hypotension and symptoms. Lifetime costs were calculated from data collected from a northern California dialysis center and abstracted from the literature. In the base-case scenario, it was assumed that increasing Kt/V to levels greater than 1 was effective in reducing morbidity and mortality. Under these assumptions, outpatient cost increased significantly, but the cost effectiveness of Kt/V equal to 1.5 was less than $50,000 per quality-adjusted life-year saved. These calculations indicate that, if higher levels of Kt/V prove clinically effective, they are also cost effective.

High-flux dialysis is a new method for providing routine-maintenance hemodialysis to patients with endstage renal disease. It promises to shorten the duration of the dialysis session, but poses potential clinical risks to patients and financial risks to dialysis centers because of the high unit cost of purchasing new dialysis equipment. We retrospectively evaluated the cost-effectiveness of high-flux dialysis compared to conventional dialysis in a hospital-based center. The center provided only conventional dialysis until March 1989, when it initiated high-flux dialysis. The estimated annual costs of treatment were US $31,249 (high-flux) and $32,562 (conventional). The rate of hospital admissions was almost identical in both groups (conventional, 1.29 admissions per year; high-flux, 1.24 admissions per year; p = 0.23). Predicted prolongation of life expectancy with high-flux dialysis was significantly higher after statistical adjustment for observable patient characteristics (1.8 to 4.5 years; p

TO THE EDITOR: Lo et al reported the first prospective treatment impact study of the 21-gene recurrence score (RS) assay (Oncotype DX, Genomic Health, Redwood City, CA) in the United States, administered to 89 women. They cited our economic analyses of the RS, where we found that the RS should be associated with similar efficacy and lower costs. As these estimates were based on projected treatment changes reported during early adoption of the RS, Lo et al suggested that “it would be interesting to recalculate cost-effectiveness based on a 20% to 30% treatment change resulting from the use of the RS assay, with most resulting in less chemotherapy use.” Wehaveperformedtheeconomicanalyses suggested,applyingtheir estimates, and also estimating effectiveness as quality-adjusted years of life gained (QALYs) associated with lower rate of chemotherapyrelated adverse events and reduced 10-year distant recurrence rate. The average QALY gained exceeded 0.2 years, and was associated with a direct medical savings of $2,099 for chemotherapy drugs, $902 for supportive care, $1,049 for management of adverse events, and $230 resulting from fewer recurrences. Including the cost of the RS, the average total direct medical savings exceeded $300 dollars per patient tested. As reported in the original economic analyses, results may vary for other centers based on their unit costs, use of medical resources (eg, type of chemotherapy used and level of supportive care), selection of patients to be tested, and how physicians and patient elect to interpret the test results. The estimates herein are likely to be conservative from a societal perspective as they exclude indirect costs associated with work productivity and the rare but meaningful consequences of chemotherapy on fertility and risk of secondary chemotherapy–related cancers. Our economic models also have been applied to the largest managed care organization in Israel. The managed care organization found the RS resulted in a 16% treatment change, associated with an average 0.17-year gain in QALYs. Unit costs are lower for cancer management in Israel, such that RS resulted in higher average cost per patient tested. The cost per QALY gained was $10,770, which was well within acceptable economic boundaries for adopting technologies in Israel. Altogether, these studies demonstrate that our early projections of the economic impact of the RS were credible.

e16500 Background: R-FC significantly increases progression-free survival (PFS) compared to FC in previously untreated CLL (phase III trial ML 17102-CLL-8). A cost-effectiveness analysis was conduc...

e16529 Background: Both NCCN and ASCO guidelines recommend a 21-gene RT-PCR assay to help determine the recurrence risk and adjuvant chemotherapy responsiveness of estrogen-receptor-positive, node-...

Cost-effectiveness analysis is emerging as an approach for determining the relative value of health care programs, technologic innovations, and clinical decisions. Increasingly, patients' stated values for quality of life are applied as adjustment in these analyses; the results may vary depending on how individuals assess their well-being. We interviewed 58 patients with chronic renal failure to determine the level of agreement among six methods for assessing well-being, and to determine the effects of variation in assessed well-being on the results of a cost-effectiveness analysis of in-center hemodialysis. Patients reported well-being using the Sickness Impact Profile, Campbell Index of Well-being, Kaplan-Bush Index of Well-being, categorical scaling, standard gamble, and time trade-off. We found that patient well-being was substantially higher as evaluated by the Sickness Impact Profile compared to the other five methods. The Sickness Impact Profile and the Kaplan-Bush Index of Well-being provided much narrower distributions of assessed values relative to other measures. Correlations among assessment methods were poor (Spearman rank-correlation coefficients range: 0.094-0.519). Discrepancies among indices were particularly vivid when we evaluated data at the individual level; many patients reported a high level of well-being according to one index and a low level of well-being according to a different index. The cost effectiveness of in-center hemodialysis varied from $34,893 to $45,254 per quality-adjusted life-year saved according to the Sickness Impact Profile and standard-gamble technique respectively. The substantial variability in patients' stated quality of life may preclude the use of a single method to analyze the cost effectiveness of a health program.

Background: Extended Rituximab (R) therapy after CVP (cyclophosphamide, vincristine, prednisone) induction in the first-line treatment of low-grade, CD20-positive, B-cell NHL significantly prolongs progression-free survival (PFS). A societal cost-effectiveness analysis is performed to estimate projected lifetime clinical and economic implications of this treatment. Methods: A Markov model with 3 health states (progression-free, post-progression, and death) was developed to estimate the direct medical costs and quality-adjusted life-years (QALYs) for a representative patient cohort with low-grade, CD20-positive, B-cell NHL. Kaplan-Meier estimates of PFS and overall survival (OS) up to 4 years are obtained from the ECOG/CALGB intergroup E1496 trial. After 4 years, transition rates are assumed to be the same in both arms. Costs include drug and administration costs, adverse events, treatment of relapses, and end-of-life costs. Incremental costs associated with R are based on Medicare reimbursement rates and published drug prices. Utilities are derived from the literature and a 3% discount rate is employed. Results: Projected mean OS is 1.2-yrs longer for patients assigned to extended R therapy versus observation alone (15.2 v 14.0 yrs). Extended R therapy is estimated to cost $42,822 on average, with an expected gain of 0.85 years of quality-adjusted survival. Over a lifetime, the cost per QALY gained is $57,515. Sensitivity analyses performed on all variables contributing to the model results showed that utility for follicular NHL patients (range: 0.68–1) and number of R infusions (range: 8–17) most influence the incremental cost-effectiveness ratio (ICER). Conclusion: The ICER of extended R dosing following CVP induction remains well below the threshold considered acceptable for oncology in the United States. Additional analysis of long term follow-up data will be useful for further evaluation of clinical and economic implications of this treatment for low-grade, CD20-positive, B-cell NHL patients.

6024 Background: The prognostic accuracy of a 21-gene RT-PCR assay has undergone validation in 668 evaluable LN-, ER+ early stage breast cancer patients receiving tamoxifen on NSABP B-14 (Paik, NEJM 2004) and its economic evaluation (Hornberger, Am J Man Care 2005). Assay predictive accuracy for response to chemotherapy or tamoxifen has also undergone recent validation in 651 patients on NSABP B-20 and 645 patients on NSABP B-14 (Paik, SABCS 2004). Methods: Based on the model recurrence score (RS), women with LN−, ER+ breast cancer with and without adjuvant chemotherapy (C) or tamoxifen (T) were classified as high (RS ≥31), intermediate (RS 18–30) or low (RS [Table: see text] [Table: see text]

6036 Background: Guidelines for LN-, ER+ adjuvant therapy stratify women into risk categories to optimize decisions concerning adjuvant CT use. A 21 gene RT-PCR assay, Oncotype DX™ Recurrence Score...