The value of survival gains in myelodysplastic syndromes.

OBJECTIVES: To measure the value of survival gains attributable to the introduction of 3 novel therapies for myelodysplastic syndromes (MDS). STUDY DESIGN: Retrospective study of patients diagnosed with MDS in the Surveillance, Epidemiology and End Results Program (SEER) registry, clinical trial evidence for MDS therapies, and claims data. METHODS: We used multivariate Cox proportional hazards models to estimate the increase in survival associated with the introduction of the 3 new therapies for patients diagnosed with MDS from 2001 to 2011 in the SEER cancer registry. Increases in survival associated with the 3 novel therapies were estimated using retrospective survival analyses and published clinical trial evidence. MDS treatment costs were estimated using Ingenix claims data and used to calculate the share of the value of survival gains retained by patients. RESULTS: We estimated that the introduction of these 3 therapies is associated with a hazard ratio of 0.901 (P <.10), and a 73% increase in median survival from 33 to 57 months. We estimated that for current and future MDS patients, these 3 therapies will generate over $193 billion in cumulative value through extensions in patient survival. CONCLUSIONS: This study demonstrates that the value of recently approved innovative therapies in MDS is large and that the value of survival gains in MDS far outweighs their costs.

The Value of Survival Gains in Pancreatic Cancer from Novel Treatment Regimens.

BACKGROUND: Metastatic pancreatic cancer (mPC) is associated with low survival, with less than 10% of patients surviving 5 years. Recent therapies improve survival outcomes where few alternative therapies exist, but few economic analyses measure the value of survival gains attributable to new therapies. OBJECTIVE: To estimate the value of survival gains in advanced or mPC attributable to the introduction of novel treatment regimens. METHODS: Multivariate Cox proportional hazards models were used to estimate real-world survival gains associated with the introduction of gemcitabine (GEM) for patients diagnosed with stage IV or unstaged mPC in the Surveillance, Epidemiology, and End Results Program cancer registries. Then, evidence from clinical trials was used to evaluate the survival gains associated with nab-paclitaxel + gemcitabine (nP +GEM) and FOLFIRINOX (FFX) relative to GEM. The survival estimates and clinical trial evidence were used to calibrate an economic model and assess the cumulative value of survival gains in mPC to patients. Costs of treatment were calculated based on published cost-effectiveness studies. RESULTS: We estimated that the introduction of GEM in 1996 was associated with a hazard ratio of 0.920 (P < 0.05) and an increase in median survival from 3.1 to 4.5 months. Results suggested that the value of survival gains attributable to GEM equaled about $71,000 per patient, while the value attributable to nP + GEM was an additional $56,700. Estimates for the value of survival gains per patient, net of total incremental lifetime treatment costs (drugs, adverse events, and other costs), were $50,294 for GEM and an additional $31,900 for nP + GEM. Clinical trials and cost-effectiveness studies reported an overall survival gain from FFX that was larger than, but statistically similar to, nP + GEM and had greater risk of adverse events and total incremental costs. We estimated that the total value of survival gains to mPC patients, net of total costs, associated with GEM was up to $47.6 billion, and the additional values attributable to nP+GEM and FFX were up to $39.0 billion and $26.3 billion, respectively. CONCLUSIONS: Historically, mPC patients have faced high disease burden and had few treatment options. Treatments introduced since 1996 have led to improved survival, with varying costs associated with treatment and adverse events. Accounting for total incremental costs, the majority of the value of survival gains from GEM and nP+GEM was retained by mPC patients, highlighting the value of innovation in settings where survival is low and few alternative therapies exist. DISCLOSURES: Support for this research was provided by Celgene. Precision Health Economics was compensated by Celgene for work on this study. MacEwan is an employee of, and Yin is a consultant to, Precision Health Economics. Kaura and Khan are employees of Celgene. Study concept and design were contributed primarily by Yin and MacEwan, along with Kaura and Khan. MacEwan collected the data, and data interpretation was performed primarily by MacEwan and Yin, along with Kaura and Khan. The manuscript was written and revised by MacEwan, Yin, Kaura, and Khan.

Returns to Society from Investment in Cancer Research and Development.

BACKGROUND: Since the start of the War on Cancer there have been enormous investments in improving oncology treatment. The return to society generated by this investment is unknown. We estimate the returns generated over the previous four decades and extrapolate future returns from current investment in cancer R&D. METHODS: Using data on cancer incidence, mortality, and treatment-specific R&D expenditures from 1973 to 2010, we used regression models and two-sided significance tests to relate investment in cancer treatment R&D to cancer mortality, by tumor type. For investment, we used a measure of the knowledge stock generated by cancer treatment R&D expenditures over the previous 25 years to capture the cumulative benefits of past innovations and advances in treatment. RESULTS: Investment of an additional $1 million in cervical, breast, colorectal, and prostate cancer between 1973 and 1990 was associated with a cumulative return of more than $5 million from cancer R&D by 2010. Through 2010, investment in cancer R&D was associated with average benefits in excess of costs in all but two cancers, ovarian and pancreatic. Regarding future returns, we estimated that each additional $1 million invested in cancer treatment research and development in 2010 will produce over $28 million in value over the following 50 years. CONCLUSIONS: The return to society from spending on cancer treatment R&D is large, but varies across tumor types.

Quantifying Gains in the War on Cancer Due to Improved Treatment and Earlier Detection.

INTRODUCTION: There have been significant improvements in both treatment and screening efforts for many types of cancer over the past decade. However, the effect of these advancements on the survival of cancer patients is unknown, and many question the value of both new treatments and screening efforts. METHODS: This study uses a retrospective analysis of SEER Registry data to quantify reductions in mortality rates for cancer patients diagnosed between 1997 and 2007. Using variation in trends in mortality rates by stage of diagnosis across cancer types, we use logistic regression to decompose separate survival gains into those attributable to advances in treatment versus advances in detection. We estimate the gains in survival due to gains in both treatment and detection overall and separately for 15 of the most common cancer types. RESULTS: We estimate that 3-year cancer-related mortality of cancer patients fell 16.7% from 1997 to 2007. Overall, advances in treatment reduced mortality rates by approximately 12.2% while advances in early detection reduced mortality rates by 4.5%. The relative importance of treatment and detection varied across cancer types. Improvements in detection were most important for thyroid, prostate and kidney cancer. Improvements in treatment were most important for non-Hodgkins lymphoma, lung cancer and myeloma. CONCLUSION: Both improved treatment options and better early detection have led to significant survival gains for cancer patients diagnosed from 1997 to 2007, generating considerable social value over this time period.

Quality-adjusted cost of care: a meaningful way to measure growth in innovation cost versus the value of health gains.

Technology drives both health care spending and health improvement. Yet policy makers rarely see measures of cost growth that account for both effects. To fill this gap, we present the quality-adjusted cost of care, which illustrates cost growth net of growth in the value of health improvements, measured as survival gains multiplied by the value of survival. We applied the quality-adjusted cost of care to two cases. For colorectal cancer, drug cost per patient increased by $34,493 between 1998 and 2005 as a result of new drug launches, but value from offsetting health improvements netted a modest $1,377 increase in quality-adjusted cost of care. For multiple myeloma, new therapies increased treatment cost by $72,937 between 2004 and 2009, but offsetting health benefits lowered overall quality-adjusted cost of care by $67,863. However, patients with multiple myeloma on established first-line therapies saw costs rise without corresponding benefits. All three examples document rapid cost growth, but they provide starkly different answers to the question of whether society got what it paid for.

Cancer mortality reductions were greatest among countries where cancer care spending rose the most, 1995-2007.

Health care spending and health outcomes vary markedly across countries, but the association between spending and outcomes remains unclear. This inevitably raises questions as to whether continuing growth in spending is justified, especially relative to the rising cost of cancer care. We compared cancer care across sixteen countries over time, examining changes in cancer spending and two measures of cancer mortality (amenable and excess mortality). We found that compared to low-spending health systems, high-spending systems had consistently lower cancer mortality in the period 1995-2007. Similarly, we found that the countries that increased spending the most had a 17 percent decrease in amenable mortality, compared to 8 percent in the countries with the lowest growth in cancer spending. For excess mortality, the corresponding decreases were 13 percent and 9 percent. Additionally, the rate of decrease for the countries with the highest spending growth was faster than the all-country trend. These findings are consistent with the existence of a link between higher cancer spending and lower cancer mortality. However, further work is needed to investigate the mechanisms that underlie this correlation.

Effectiveness of a Patient Support Program in Supporting Access to Therapy for Solid Tumor Malignancies.

Background: Certain governmental agencies, patient advocacy organizations, and pharmaceutical manufacturers have implemented programs to assist patients in overcoming barriers to accessing healthcare. Recently, such programs have expanded their services, helping both uninsured and insured patients to navigate the complex healthcare system, and assisting with increasing out-of pocket costs and copays for the drugs. Objective: To better understand the effect of patient support programs on access to therapy for solid tumor malignancies, this study evaluated service use, case outcomes, and patient characteristics from a manufacturer-sponsored program in the United States. Methods: Sociodemographic characteristics, services use rates, and outcomes by case and insurance type were evaluated at the patient- and case-level in a random sample of patients prescribed nab-paclitaxel for solid tumor malignancies who enrolled in the Celgene Patient Support (CPS) program (April 2011-November 2013). Results: This analysis included 4566 patients (8134 cases); most patients were female (64.7%), aged <65 years (59.2%), in the South (53.9%), and treated in community settings (87.9%). Patients were primarily insured by Medicare (38.5%) or commercial plans (37.3%), or were uninsured (16.6%). Following benefits investigations for new patients entering the program (98.5%), CPS provided support to obtain free medicine (29.4%), appeal denial of coverage (15.0%), receive commercial co-payment assistance (8.1%), or obtain prior payer authorization (1.3%). Nab-paclitaxel was provided at no cost in 89.4% of cases where patients sought financial support; payer reimbursement was obtained in 63.2% of reimbursement appeals. Of commercially-insured patients who required assistance with co-payments and met financial criteria, 93.3% received a mean of $597 in co-payment support. Conclusion: The CPS program was successful in gaining access to therapy. Healthcare providers and both insured or uninsured patients accessed CPS for prior authorization/precertification, appeals support, and financial support through the Free Medication Program and the Commercial Co-Pay program.

Use of the Functional Assessment of Cancer Therapy--anemia in persons with myeloproliferative neoplasm-associated myelofibrosis and anemia.

BACKGROUND: Anemia is common in myeloproliferative neoplasm (MPN)-associated myelofibrosis. The Functional Assessment of Cancer Therapy (FACT) measurement system is a patient-reported outcomes instrument that documents symptoms of the diverse aspects of cancer treatment. One FACT version, FACT-Anemia (FACT-An), documents symptoms of anemia related to cancer. The FACT-An has been validated in diverse cancer populations, but not in MPN-associated myelofibrosis. OBJECTIVE: Our aim was to evaluate the relationship between anemia response to therapy with pomalidomide with or without corticosteroids and patient-reported outcomes using the FACT-An instrument. METHODS: Data were obtained from a Phase II, randomized, double-blind Bayesian pick-the-winner trial of prednisone and pomalidomide in patients with MPN-associated myelofibrosis and anemia (red blood cell-transfusion dependence). Details of the study, including definitions of anemia, anemia response, red blood cell-transfusion, red blood cell-transfusion dependence, and red blood cell-transfusion independence, are reported. Change in quality of life from randomization to the last cycle of therapy was evaluated using the FACT-An Physical Well Being, Functional Well Being, Trial Outcome Index, and Anemia domains. Clinically important differences were used to determine the smallest difference in scores that patients perceived as beneficial in the FACT-An domains of interest. Patients were classified as meeting clinically important differences for responsiveness if their change score from baseline was >1 SEM, indicating improvement. RESULTS: Eighty-five patients were studied. Thirty-one patients (37%) were classified as anemia responders by prospectively defined criteria. Across all FACT-An domains, anemia responders showed greater improvement in Physical Well Being, Functional Well Being, and Trial Outcome Index scores than did nonresponders. This improvement began at the second 28-day cycle of therapy and was sustained. CONCLUSIONS: We show a correlation between anemia response and improved quality of life measured by the FACT-An instrument in patients with MPN-associated myelofibrosis and anemia.

Association of health-related quality of life with gender in patients with B-cell chronic lymphocytic leukemia.

PURPOSE: This analysis examined associations between gender and health-related quality of life (HRQOL) in patients with B-cell chronic lymphocytic leukemia (CLL) as they initiate therapy for CLL outside the clinical trial setting. METHODS: Baseline data were collected as part of Connect® CLL Registry, a prospective observational study initiated in community, academic, and government centers. Patient demographics and clinical characteristics were provided by clinicians. Patients reported HRQOL using the Brief Fatigue Inventory (BFI), EQ-5D, and Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu). Mean scores were analyzed, with statistical significance of differences determined by ANOVA. Multivariate analysis also considered age and line of therapy. RESULTS: Baseline HRQOL data were available for 1,140 patients: 710 (62 %) men and 430 (38 %) women from 161 centers. Patients were predominantly white (89 %) with mean age 69 ± 11 years. Women reported significantly worse global fatigue (P <0.0001), fatigue severity (P <0.0001), and fatigue-related interference (P = 0.0005) versus men (BFI). Pain/discomfort (P = 0.0077), usual activities (P = 0.0015), and anxiety/depression (P = 0.0117) were significantly worse in women than in men (EQ-5D). With women reporting a better social/family score (P = 0.0238) and men reporting a better physical score (P = 0.0002), the mean FACT-G total score did not differ by gender. However, the mean FACT-Leu total score was better among men versus women (P = 0.0223), primarily because the mean leukemia subscale score was significantly better among men (P <0.0001). Multivariate analysis qualitatively confirmed these findings. CONCLUSIONS: Connect® CLL Registry results indicate that significant differences exist in certain HRQOL domains, as women reported greater levels of fatigue and worse functioning in physical domains.

Effect of a patient support program on access to oral therapy for hematologic malignancies.

PURPOSE: The results of a study assessing the effectiveness of a manufacturer-sponsored assistance program for patients prescribed oral cancer therapies are presented. METHODS: Rates of dispensing success were evaluated in a random sample of patients (n = 1000) who enrolled in the Celgene Patient Support (CPS) program for assistance obtaining lenalidomide or thalidomide over a two-year period and a control group of patients (n = 1000) who registered to receive the drugs under restricted-distribution protocols but did not receive CPS assistance. The main study outcomes were (1) the proportion of patients who actually received medication and (2) the time from prescription approval to the initial dispensing of medication. RESULTS: Despite the complex access issues faced by program enrollees, the proportion of CPS participants who received medication (89%) was comparable to the proportion of patients who received medication in the control cohort (91%). The median time from the approval of prescriptions to the initial dispensing of medication was also comparable in the CPS and control groups (eight days versus five days). The study also evaluated the reasons why medication was not dispensed to CPS enrollees in some cases. CONCLUSION: The percentage of patients who were dispensed prescriptions for lenalidomide or thalidomide did not differ significantly between those who were enrolled in a patient assistance program and those who were not. The median time between prescription authorization and first dispensing was comparable among program and nonprogram patients.

A cost-effectiveness analysis of using azacitidine vs. decitabine in treating patients with myelodysplastic syndromes.

OBJECTIVE: Azacitidine and decitabine are used to treat patients with myelodysplastic syndromes (MDS) in the United States (US). This study sought to assess their relative cost-effectiveness. DESIGN AND METHODS: The authors developed a cost-effectiveness Markov model (1-month cycles) tracking hypothetical cohorts of MDS patients treated with azacitidine or decitabine over 2 years. The model used a US payer perspective and 2009 costs. Health states modeled included MDS with Transfusion Dependence, MDS with Transfusion Independence, Progression to Acute Myelogenous Leukemia (AML), and Death. Incremental cost-effectiveness outcomes included cost per quality-adjusted life year (QALY), cost per life year (LY), cost per patient-month of transfusion independence, and cost per case of AML progression avoided. One-way sensitivity analyses were performed on key model parameters. RESULTS: Compared to decitabine, azacitidine was associated with better survival (1.512 LYs vs 1.292), more QALYs gained (1.041 vs 0.870), more patient-months with transfusion independence (8.328 vs 6.224), and a greater proportion of patients avoiding progression to AML (50.9% vs 28.5%). Total per-patient costs over 2 years for azacitidine were lower than for decitabine ($150,322 vs $166, 212). LIMITATIONS: To inform and update the model over time, it will be important that randomized or observational clinical studies be conducted to directly compare azacitidine and decitabine, provide new information on how these medicines are used, and on their relative clinical effectiveness. CONCLUSION: Results demonstrate that azacitidine provides greater clinical benefit and costs less than decitabine across all key outcomes. These results accentuate the positive role of azacitidine in providing cost-effective care for MDS.

Risk-factor clustering and cardiovascular disease risk in hypertensive patients.

BACKGROUND: Patients with hypertension often have other major risk factors for cardiovascular disease (CVD). Little is known, however, about the extent of risk-factor clustering in these patients and its importance in CVD risk and medical-care costs. METHODS: Study subjects were selected from the electronic medical records system of Kaiser Permanente Northwest, a large health maintenance organization, and included all patients aged > or =35 years with hypertension who were free of CVD in 1998. Subjects were stratified into eight risk-factor clusters based on whether or not they also had diabetes, hyperlipidemia, or a high body mass index (BMI). The risk of cardiovascular events was examined in each cluster over 6 years beginning January 1, 1999, using Kaplan-Meier methods and Cox proportional hazards models. Cumulative total medical-care costs (per patient) over 6 years also were examined. RESULTS: A total of 57,573 patients with hypertension who were free of CVD in 1998 were identified; 56% of subjects also had diabetes, hyperlipidemia, or high BMI. In analyses controlling for age, sex, and smoking status, the relative risk of cardiovascular events over 6 years was highest for patients with comorbid diabetes, ranging from 2.07 (95% confidence interval, 1.86-2.30) for those with diabetes only to 2.80 (95% confidence interval, 2.48-3.17) for those with diabetes, hyperlipidemia, and high BMI. Cumulative medical-care costs generally increased with additional risk factors. Comorbid diabetes had the greatest impact on costs over 6 years. CONCLUSIONS: More than 50% of patients with hypertension also had diabetes, hyperlipidemia, or high BMI. Patients with these additional risk factors (especially diabetes) had a substantially higher CVD risk and medical-care costs.

Development of the Health and Work Questionnaire (HWQ): an instrument for assessing workplace productivity in relation to worker health.

BACKGROUND: Workplace productivity evaluations often involve subjective assessments. This study was performed to develop and validate a new multidimensional instrument, the Health and Work Questionnaire (HWQ), for measuring workplace productivity and worker heath. METHODS: In a prospective, non-randomized study, objective and subjective workplace productivity (measured with the HWQ) was assessed among 96 current, 94 former, and 104 non-smoking volunteer reservation agents at a US-based international airline. RESULTS: Six HWQ sub-scales were identified from factor analyses: productivity, concentration/focus, supervisor relations, impatience/irritability, work satisfaction, and non-work satisfaction. Non-smokers (individuals who had never smoked) had higher scores on all scales. The HWQ scale scores all correlated significantly with the objective measure "Time Lost"; two of the scales correlated significantly with the summary objective performance measure. Magnitudes of the significant correlations were modest (0.12 to 0.22). CONCLUSIONS: The HWQ may be useful for evaluating the impact of interventions on workplace productivity. Additional validation research on the HWQ is recommended before use as a primary measure in studies of worker productivity.

Health care costs among smokers, former smokers, and never smokers in an HMO.

OBJECTIVE: We estimate long-term health care costs of former smokers compared with continuing and never smokers using a retrospective cohort study of HMO enrollees. Previous research on health care costs associated with former smokers has suggested that quitters may incur greater health care costs than continuing smokers, therefore, getting people to quit creates more expensive health care consumers. We studied the trend in cost for former smokers over seven years after they quit to assess how the cessation experience impacts total health care cost. DATA SOURCES/STUDY SETTING: Group Health Cooperative (GHC), a nonprofit mixed model health maintenance organization in western Washington state. STUDY DESIGN: Retrospective cohort study using automated and primary data collected through telephone interviews. PRINCIPAL FINDINGS: We find that former smokers' costs are significantly greater (p<.05) in the year immediately following cessation relative to continuing smokers, but former smokers' costs fall in year two. This decrease maintains throughout the six-year follow-up period. Although former smokers cost more than continuing smokers in the year after cessation, this increase appears to be transient. Long-term costs for former smokers are not statistically different from those of continuing smokers and cumulative health care expenses are lower by the seventh year postquit. Our evidence suggests that smoking cessation does not increase long-term heath care costs. CONCLUSIONS: Health care costs among former smokers increase relative to continuing smokers in the year after cessation but fall to a level that is statistically indistinguishable in the second year postquit. Any net increase in costs among former smokers relative to continuing smokers appears compensated for within two years post-quit and is maintained for at least six years after cessation.