Cost-effectiveness analysis comparing single-pill combination of perindopril/amlodipine/indapamide to the free equivalent combination in patients with hypertension from an Italian national health system perspective.

OBJECTIVE: To evaluate the cost-effectiveness of a single-pill combination (SPC) of perindopril/amlodipine/indapamide versus its free equivalent combination (FEC) in adults with hypertension in Italy. METHODS: A Markov model was developed to perform a cost-utility analysis with a lifetime horizon and an Italian healthcare payer's perspective. In the model, the additional effect of the SPC on blood pressure level compared with the FEC was translated into a decreased risk of cardiovascular events and CKD, which was modeled via Framingham risk algorithms. Difference in persistence rates of SPC and FEC were modeled via discontinuation rates. RESULTS: A perindopril/amlodipine/indapamide SPC is associated with lower cost and better health outcomes compared to its FEC. Over a lifetime horizon, it is associated with a 0.050 QALY gain and cost savings of €376, resulting from lower cardiovascular event rates. In the alternative scenario, where different approach for modeling impact of adherence was considered, incremental gain of 0.069 QALY and savings of €1,004 were observed. Results were robust to sensitivity and scenario analyses, indicating that use of this SPC is a cost-effective strategy. CONCLUSIONS: The findings indicate that a perindopril/amlodipine/indapamide SPC is a cost-saving treatment option for hypertension in Italy, compared to its FEC.

The impact of non-pharmacological interventions on adherence to medication and persistence in dyslipidaemia and hypertension: a systematic review.

INTRODUCTION: Suboptimal medication adherence is common among patients with cardiovascular diseases. We sought evidence on non-pharmacological interventions used to support adherence for patients with hypertension and/or dyslipidemia. METHODS: We searched MEDLINE, EMBASE, MEDLINE In-Process, ClinicalTrials.gov, EUCTR, and conference proceedings from July 2011 to July 2021 to identify trials evaluating effects of health education, phone reminders, or digital interventions on medication adherence or persistence of adult patients with hypertension and/or dyslipidemia. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool v2. RESULTS: Of 64 studies, 62 used health education approaches (e.g. educational interviews, motivational meetings, advice from physicians, and mobile health content), 16 phone reminders (e.g. text reminders, electronic pill-box linked reminders, bi-directional text messaging), and 10 digital applications as interventions (e.g., various self-management applications). All studies assessed medication adherence; only two persistence. Overall, 30 studies (83%) assessing health education approaches alone and 25 (78%) combined with other strategies, 12 (75%) phone reminders and eight studies (80%) digital applications combined with other strategies reported improved medication adherence. Two studies assessing health education approaches reported improved persistence. CONCLUSIONS: Our findings indicate non-pharmacological interventions may positively impact adherence. Therefore, 'beyond the pill' approaches could play a role in preventing cardiovascular diseases.

Impact of poor medication adherence on clinical outcomes and health resource utilization in patients with hypertension and/or dyslipidemia: systematic review.

INTRODUCTION: We aimed to summarize evidence on the effect of poor medication adherence on clinical outcomes and health resource utilization (HRU) among patients with hypertension and/or dyslipidemia. AREAS COVERED: A systematic review of studies reporting clinical outcomes and HRU for patients by status of adherence to antihypertensives and/or lipid-lowering medications was searched using Embase, MEDLINE, and MEDLINE In-Process and supplemented by manual searches of conference abstracts. In total, 45 studies were included, with most being retrospective observational studies (n = 36). Patients with poor adherence to antihypertensives and lipid-lowering medications compared with those with good adherence showed less reduction of blood pressure (BP) and low-density lipoprotein cholesterol (LDL-c) after 6-12 months follow-up (∆ systolic BP: 1.2 vs. -4.5 mmHg; ∆LDL-c: -14.0 to -18.9 vs. -34.1 to -42.0 mg/dL). Poor adherence was also significantly associated with a higher risk of cardiovascular events (HR: 1.1-1.9) and mortality (HR: 1.4-1.8) in patients with hypertension and dyslipidemia and increased HRU (i.e. outpatient visits, risk of cardiovascular-related and all-cause hospitalization, annual inpatient days, total health-care costs). EXPERT OPINION: Poor adherence is associated with poor clinical outcomes and increased HRU, highlighting the need to enhance medication adherence in patients with hypertension and/or dyslipidemia.

High blood pressure is a leading cause of death and disease burden followed by high lipid levels in blood. Due to the silent nature of the diseases, patients can fall short of optimal medicinal treatment adherence and persistence, leading to poor outcomes and disease complications. The effectiveness of medicinal interventions depends on the appropriate medication-taking behavior of patients as lower adherence can lead to poor treatment benefits. Research was conducted to look for published studies that assessed the effect of lower medication adherence on clinical outcomes and health resource use among patients with high blood pressure, high lipid levels in blood, or both. Researchers were able to find 45 already published studies, from which 32 evaluated the use of blood pressure lowering medications and 7 evaluated the use of lipid-lowering medications, while 6 included patients treated with both types of medications. Refill of pharmacy prescription records was the most common method of assessing treatment adherence. Researchers found that patients with lower adherence to these medications compared with those with good adherence showed less decrease in blood pressure levels and less improvement in blood lipid levels after 6­12 months of follow-up. Patients who had lower adherence also had higher rates of cardiovascular events and deaths and increased usage of health services including visits to outpatient clinics, getting admitted to hospitals, and a longer stay of hospitalizations, leading to a higher overall healthcare cost. These findings suggest lower adherence is associated with poor clinical outcomes and increased health-care resource usage, highlighting the need to improve medication adherence in patients with high blood pressure and high lipid levels in blood.

Impact of single-pill combinations versus free-equivalent combinations on adherence and persistence in patients with hypertension and dyslipidemia: a systematic literature review and meta-analysis.

OBJECTIVES: Hypertension is a leading cause of death and disease burden followed by dyslipidemia. Their asymptomatic nature leads to low adherence and persistence to treatments. A systematic literature review (SLR) investigated the impact of single-pill-combinations (SPC) compared to free-equivalent combination (FEC) on adherence, persistence, clinical outcomes, healthcare resource utilization (HCRU), and patient-reported outcomes, in patients with hypertension, dyslipidemia, or both. METHODS: MEDLINE, MEDLINE-IN-PROCESS, Embase, and Cochrane were searched from inception until 11 May 2021, for studies comparing SPC against FEC in patients with hypertension and/or dyslipidemia. Patient characteristics, study design, therapies, measures of adherence or persistence, clinical outcomes, and follow-up were extracted. RESULTS: Among 52 studies identified in the SLR, 27 (n = 346,030 patients) were included in the meta-analysis. SPCs were associated with significantly improved adherence compared with FEC, as assessed through medication-possession-ratio ≥80% (odds ratio (OR) 0.42, p < 0.01) and proportion of days covered ≥80% (OR 0.45, p < 0.01). SPC also improved persistence (OR 0.44, p < 0.01) and systolic blood pressure (SBP) reduction (mean difference -1.50, p < 0.01) compared with the FEC. CONCLUSIONS: SPC use resulted in significantly improved adherence, persistence, and SBP levels compared with FEC in patients with hypertension. The findings support SPC use in reducing the burden of hypertension and dyslipidemia.

High blood pressure is a leading cause of death and disease burden followed by high lipid levels in the blood. Due to the silent nature of the diseases, patients can fall short of optimal medical treatment adherence and persistence, leading to poor outcomes and disease complications. Simplification of the treatment regimen can be achieved using SPC therapies. The study was conducted to look for published studies that compared the use of SPC with FEC in patients with high blood pressure, high lipid levels in the blood, or both. The researchers were able to find 52 already published studies, of which, 27 studies reported adherence, persistence, and SBP reduction which were included in the data analysis. Researchers found SPCs to be associated with much greater improved adherence and persistence and a higher reduction in SBP when compared with FEC in high blood pressure patients. These findings support SPC use in reducing the burden of high blood pressure and high lipid levels in the blood.

Ivabradine in patients with heart failure: a systematic literature review.

Background: Heart failure is a chronic disease linked with significant morbidity and mortality, and uncontrolled resting heart rate is a risk factor for adverse outcomes. This systematic literature review aimed to assess the efficacy, safety, and patient-reported outcomes (PROs) of ivabradine in patients with heart failure (HF) with reduced ejection fraction (HFrEF) in randomized controlled trials (RCTs) and observational studies. Methods: We searched electronic databases from their inception to July 2021 to include studies that reported on efficacy, safety, or PROs of ivabradine in patients with HFrEF. Results: Of 1947 records screened, 51 RCTs and 6 observational studies were identified. Ivabradine on top of background therapy demonstrated a significant reduction in composite outcomes including hospitalization for HF or cardiovascular death. In addition, observational studies suggested that ivabradine was associated with a significant reduction in mortality. Across all studies, ivabradine use on top of background therapy was associated with greater reductions in heart rate, improved EF, and improved health-related quality of life (QoL) and comparable risk of total adverse events compared to those treated with background therapy alone. Conclusions: Ivabradine on top of background therapy is beneficial for heart rate, hospitalization risk for HF, mortality, EF, and patients' QoL. Moreover, these benefits were achieved with no significant increase in the overall risk of total adverse events.

Framework and case study for establishing impactful global health programs through academia - biopharmaceutical industry partnerships.

BACKGROUND: The field of global health has grown with multiple different public and private stakeholders engaging in the effort to improve health outcomes for underserved populations around the world. There is, however, only limited published guidance on how to promote successful partnerships between academia and the biopharmaceutical industry. OBJECTIVE: This analysis will provide a framework for developing successful partnerships around five central principles. This framework will then be applied to two representative pharmacy collaboration case studies focused on training and donations. FRAMEWORK DESCRIPTION AND CASE STUDY FINDINGS: Within the Academic Model Providing Access to Healthcare (AMPATH), successful collaborations between the biopharmaceutical industry philanthropic entities and academic partners have consistently prioritized 1) contextualization, 2) collaboration, 3) local priorities, 4) institutional commitment, and 5) integration. In the first case study, the application of this framework to clinical pharmacy training activities sponsored by Celgene and implemented by the Purdue Kenya Partnership has helped the program transition from an entirely donor dependent training program to a revenue generating, locally administered program which is now recognized and accredited by the Kenyan government. In the second case study, medication donations from Eli Lilly and Company have been converted from a traditional donation program in one Kenyan health facility to a replicable and sustainable supply chain model which has been expanded to more than 70 public sector facilities across western Kenya. CONCLUSION: Adherence to the five core principles of the proposed framework can help guide partnerships between academic institutions and the biopharmaceutical industry to advance healthcare services for underserved populations around the world. As large-scale government-based development agencies continue to primarily focus on specific disease states, biopharmaceutical industry-based collaborations can help initiate activities in underfunded therapeutic areas such as non-communicable diseases.

Identifying Psoriasis and Psoriatic Arthritis Patients in Retrospective Databases When Diagnosis Codes Are Not Available: A Validation Study Comparing Medication/Prescriber Visit-Based Algorithms with Diagnosis Codes.

BACKGROUND: Using diagnosis code-based algorithms is the primary method of identifying patient cohorts for retrospective studies; nevertheless, many databases lack reliable diagnosis code information. OBJECTIVES: To develop precise algorithms based on medication claims/prescriber visits (MCs/PVs) to identify psoriasis (PsO) patients and psoriatic patients with arthritic conditions (PsO-AC), a proxy for psoriatic arthritis, in Canadian databases lacking diagnosis codes. METHODS: Algorithms were developed using medications with narrow indication profiles in combination with prescriber specialty to define PsO and PsO-AC. For a 3-year study period from July 1, 2009, algorithms were validated using the PharMetrics Plus database, which contains both adjudicated medication claims and diagnosis codes. Positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of the developed algorithms were assessed using diagnosis code as the reference standard. Chosen algorithms were then applied to Canadian drug databases to profile the algorithm-identified PsO and PsO-AC cohorts. RESULTS: In the selected database, 183,328 patients were identified for validation. The highest PPVs for PsO (85%) and PsO-AC (65%) occurred when a predictive algorithm of two or more MCs/PVs was compared with the reference standard of one or more diagnosis codes. NPV and specificity were high (99%-100%), whereas sensitivity was low (≤30%). Reducing the number of MCs/PVs or increasing diagnosis claims decreased the algorithms' PPVs. CONCLUSIONS: We have developed an MC/PV-based algorithm to identify PsO patients with a high degree of accuracy, but accuracy for PsO-AC requires further investigation. Such methods allow researchers to conduct retrospective studies in databases in which diagnosis codes are absent.

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.

Rare Disease Terminology and Definitions-A Systematic Global Review: Report of the ISPOR Rare Disease Special Interest Group.

BACKGROUND: At present, there is no universal definition of rare disease. OBJECTIVE: To provide an overview of rare disease definitions currently used globally. METHODS: We systematically searched for definitions related to rare disease from organizations in 32 international jurisdictions. Descriptive statistics of definitions were generated and prevalence thresholds were calculated. RESULTS: We identified 296 definitions from 1109 organizations. The terms "rare disease(s)" and "orphan drug(s)" were used most frequently (38% and 27% of the definitions, respectively). Qualitative descriptors such as "life-threatening" were used infrequently. A prevalence threshold was specified in at least one definition in 88% of the jurisdictions. The average prevalence threshold across organizations within individual jurisdictions ranged from 5 to 76 cases/100,000 people. Most jurisdictions (66%) had an average prevalence threshold between 40 and 50 cases/100,000 people, with a global average of 40 cases/100,000 people. Prevalence thresholds used by different organizations within individual jurisdictions varied substantially. Across jurisdictions, umbrella patient organizations had the highest (most liberal) average prevalence threshold (47 cases/100,000 people), whereas private payers had the lowest threshold (18 cases/100,000 people). CONCLUSIONS: Despite variation in the terminology and prevalence thresholds used to define rare diseases among different jurisdictions and organizations, the terms "rare disease" and "orphan drug" are used most widely and the average prevalence threshold is between 40 and 50 cases/100,000 people. These findings highlight the existing diversity among definitions of rare diseases, but suggest that any attempts to harmonize rare disease definitions should focus on standardizing objective criteria such as prevalence thresholds and avoid qualitative descriptors.

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.

Impact of patient programs on adherence and persistence in inflammatory and immunologic diseases: a meta-analysis.

OBJECTIVES: Patient adherence and persistence is important to improve outcomes in chronic conditions, including inflammatory and immunologic (I&I) diseases. Patient programs that aim at improving medication adherence or persistence play an essential role in optimizing care. This meta-analysis assessed the effectiveness of patient programs in the therapeutic area of I&I diseases. METHODS: A global systematic literature review was conducted with inclusion criteria of: patient programs in I&I diseases; published in English language between January 2008 and September 2013; and reporting measures of adherence or persistence, including medication possession ratio >80% and persistence rate. A meta-analysis was performed using a random effects model. Subgroup analyses based on the type of program was performed whenever feasible. RESULTS: Of 67 studies reviewed for eligibility, a total of 17 studies qualified for inclusion in the meta-analysis. Overall, patient programs increased adherence (odds ratio [OR]=2.48, 95% confidence interval [CI]=1.68-3.64, P<0.00001) as compared with standard of care. Combination patient programs that used both informational and behavioral strategies were superior in improving adherence (OR=3.68, 95% CI=2.20-6.16, P<0.00001) compared with programs that used only informational (OR=2.16, 95% CI=1.36-3.44, P=0.001) or only behavioral approaches (OR=1.85, 95% CI=1.00-3.45, P=0.05). Additionally, patients were more likely to be persistent (OR=2.26, 95% CI=1.16-4.39, P=0.02) in the intervention group as compared with the control group. Persistence (in days) was significantly (P=0.007) longer, by 42 additional days, in the intervention group than in the control group. CONCLUSIONS: Patient programs can significantly improve adherence as well as persistence in the therapeutic area of I&I diseases. Programs employing a multimodal approach are more effective in improving adherence than programs with informational or behavioral strategies alone. This in turn may improve patient outcomes.

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.

Melding regulatory, pharmaceutical industry, and U.S. payer perspectives on improving approaches to heterogeneity of treatment effect in research and practice.

Effective pursuit of the science and management of heterogeneity of treatment effect (HTE) relies on the mutual understanding of the perspectives of, and collaboration among, the various stakeholders in health care. In this article, we compare, contrast, and endeavor to find areas of alignment across the perspectives of three such stakeholders -regulators, the biopharmaceutical and device industry, and U.S. payers. First, we discuss how evidence of HTE is generated and could be improved upon. For pharmaceuticals, much of the initial research is conducted by the pharmaceutical industry, guided by basic science but also delimited by potential markets, regulatory approval requirements, trial size considerations, and payer expectations for evidence of value. Once a drug is marketed, further evidence can be generated via combining trial data, conducting meta-analysis, and analyzing real-world results through observational research designs; we explore how these efforts can benefit from cooperation across these stakeholders. Second, we discuss the equally important utilization of HTE evidence so that physicians and patients have access to and can benefit from the learnings from this research. Research findings must be translated into actionable information and guidelines that can be incorporated into everyday practice. Doing so requires interaction and collaboration among all involved, based on facilitated communication as well as further evaluation research. We provide examples of several cross-sectorial initiatives that are under way in this area. Finally, we explore some economic aspects of HTE research as part of the drug development, marketing, and treatment process. Understanding the economic incentives present is fundamental to aligning those incentives to improve the availability and utilization of HTE evidence. Clear understandings among regulators, pharma, and payers about high-value targets, methods to efficiently generate and communicate information, and value propositions can lead to "win-win" scenarios for patients, individual payers, the health care system overall, and the future of drug development in producing new medicines.

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.