Real-world palbociclib dosing patterns and implications for drug costs in the treatment of HR+/HER2- metastatic breast cancer.

BACKGROUND: This study described real-world palbociclib dosing patterns and associated impacts on treatment costs for HR+/HER2- metastatic breast cancer (mBC) in the US. METHODS: Postmenopausal women with HR+/HER2- mBC who initiated palbociclib-based therapy (initiation date = index date) between 02/03/2015 (palbociclib approval) and 02/29/2016, and continuous quarterly activity 1 year before and 6 months after the index date, were identified in the Symphony Health Solutions database. Rates of 1) dose reduction (≥25 mg dose decrease/daily), and 2) reduction or interruption (>60 day gap in continuous drug supply) were assessed using Kaplan-Meier analyses. Drug wastage cost was estimated based on overlapping days between two prescription fills: the last original dose fill and the first reduced dose fill. RESULTS: 1,242 patients initiated palbociclib-based therapy (mean age = 62.7 years, median follow-up = 8.7 months). During the 12-month post-index period, across the first four lines, dose reduction rates were 31.9-33.7% and dose reduction/interruption rates were 63.5-80.9%. A total of 411 (33.1%) patients changed dose, among whom 128 (31.1%) experienced prescription fill overlap (average = 11.1 days). Mean potential drug wastage cost among patients with fill overlap was $5,471. CONCLUSIONS: Most patients receiving palbociclib experienced dose reduction or interruption early in treatment; the associated drug wastage may lead to considerable costs.

Burden of illness and healthcare resource use in United States patients with sporadic inclusion body myositis.

INTRODUCTION: We analyzed the burden of illness of sporadic inclusion body myositis (sIBM) patients and the costs to the healthcare system. METHODS: A retrospective cohort analysis of 333 sIBM patients aged ≥ 50 years was performed using United States (U.S.) claims data. sIBM patients were matched in a 1:5 ratio to randomly selected individuals with ≥1 healthcare encounter within the year of index date. RESULTS: sIBM patients presented with higher rates of disease- and muscle-related conditions, such as myalgia, myositis, muscle weakness, dysphagia, pneumonia, and falls. Use of healthcare resources, including physical therapy, office visits, emergency room (ER) visits, and hospitalizations, was greater in sIBM patients. This was also reflected in significantly higher overall healthcare costs in the sIBM population driven mainly by more all-cause office visits, all-cause ER visits and hospitalizations. CONCLUSIONS: sIBM imposes a substantial burden on U.S. patients in terms of additional healthcare usage and associated costs. Muscle Nerve 56: 861-867, 2017.

Budget impact of perampanel as adjunctive treatment of uncontrolled partial-onset and primary generalized tonic-clonic seizures in the United States.

PURPOSE: To evaluate the budget impact (BI) of adopting perampanel for adjunctive treatment of partial-onset seizures (POS), with or without secondarily generalized seizures, and the adjunctive treatment of primary generalized tonic-clonic seizures (PGTCS) in patients 12years or older in the United States. METHODS: A BI model was developed to estimate the potential BI of adopting adjunctive perampanel from a US payer (direct costs only) and societal (direct and indirect costs) perspective over a 5-year period. Efficacy data for perampanel and antiepileptic drug (AED) maintenance therapy were obtained from perampanel phase III clinical trials. Drug, direct medical (healthcare provider, emergency room, and hospitalizations), and indirect (productivity loss) costs were obtained from appropriate sources (e.g., AnalySource® Online [wholesale acquisition costs], 2013 Optum Insight Clinformatics Database [market share percentages, direct medical costs per unit], and 2011-2013 National Health and Wellness Survey [NHWS; healthcare resource utilization, overall work impairment, and baseline distribution of patients across the 4 health states]). Mapping of seizure frequency to medical resource utilization and work impairment was obtained from Kantar Health's NHWS. RESULTS: In a hypothetical health plan of 1 million members, 660 (0.066%) members ≥12years old had uncontrolled POS (395 [59.8%]) or PGTCS (265 [40.2%]). During the first 5years of adoption of perampanel, absolute BI (including drug, direct medical, and indirect costs) was $852, $2124, $3855, $5318, and $6397, respectively, for a cumulative absolute BI of $18,545. Drug cost was estimated to increase by $13,888, $34,646, $62,863, $86,728, and $104,326, respectively; however, this cost would be mostly offset by decreases in direct medical ($5041, $12,576, $22,818, $31,481, and $37,869, respectively) and indirect ($7995, $19,946, $36,190, $49,929, and $60,060, respectively) costs. Total per-member-per-month cost (drug and direct medical costs) was estimated to increase by $0.0007, $0.0018, $0.0033, $0.0046, and $0.0055 from years 1 to 5. CONCLUSIONS: Based on results of this BI model, increased cost of adopting perampanel in a health plan of 1 million members would be minimal for payers, and societal costs would be close to neutral.

Comparison of hospitalization risk and associated costs among patients receiving sargramostim, filgrastim, and pegfilgrastim for chemotherapy-induced neutropenia.

BACKGROUND: Sargramostim is a granulocyte-macrophage-colony-stimulating factor (GM-CSF). Unlike filgrastim and pegfilgrastim, which are granulocyte-colony-stimulating factors (G-CSFs), sargramostim activates a broader range of myeloid lineage-derived cells. Therefore, GM-CSF might reduce infection risk more than the G-CSFs. This study compared real-world infection-related hospitalization rates and costs in patients using G/GM-CSF for chemotherapy-induced neutropenia. METHODS: This retrospective matched-cohort study analyzed nationally representative health insurance claims in the United States from 2000 through 2007. The sample population included patients who received chemotherapy and G/GM-CSF. G/GM-CSF treatment episodes began with the first administration of G/GM-CSF and ended when a subsequent administration was >28 days after a prior administration. Sargramostim patients were matched 1:1 with filgrastim and pegfilgrastim patients based on gender and birth year. Outcomes included infection-related hospitalization rates and the associated costs. Hospitalization rates were analyzed using univariate and multivariate Poisson methods; covariates included myelosuppressive agents received, tumor type, anemia, and comorbidities. RESULTS: A total of 990 sargramostim-filgrastim and 982 sargramostim-pegfilgrastim matched pairs were analyzed. Cohorts were similar with regard to age, gender, and comorbid conditions. Several differences were observed with regard to tumor type, anemia, and chemotherapy, but no systematic trends were apparent. Sargramostim patients experienced a 56% lower risk of infection-related hospitalizations compared with filgrastim and pegfilgrastim patients. Infection-related hospitalization costs were 84% and 62% lower for sargramostim patients compared with patients treated with filgrastim and pegfilgrastim, respectively. CONCLUSIONS: Among patients with or at risk for chemotherapy-induced neutropenia, these data indicated that use of sargramostim was associated with a reduced risk of infection-related hospitalization and lower associated costs compared with filgrastim or pegfilgrastim.

Zoledronic acid and skeletal complications in patients with solid tumors and bone metastases: analysis of a national medical claims database.

BACKGROUND: Bone is among the most common sites of metastasis in patients with advanced cancer, and the development of bone metastases places patients at increased risk for skeletal complications. METHODS: This retrospective claims analysis included only patients with a diagnosis of bone metastasis who had a single type of solid tumor of the breast (women), prostate, or lung and experienced >or=1 skeletal complication between January 2002 and October 2005. RESULTS: The mean follow-up (+/-standard deviation) for zoledronic acid (ZA)-treated patients versus untreated patients was 12.2 +/- 9.05 months versus 8.7 +/- 9.28 months, respectively (P < .001). The monthly rate of skeletal complications in ZA-treated patients versus untreated patients was 0.29 +/- 0.3 per month versus 0.43 +/- 0.4 per month, respectively (P < .001). Persistent ZA use was associated with longer follow-up duration (P < .05) and a greater probability of continuing follow-up. Greater persistency was associated with lower monthly rates of skeletal complications (P < .05). The length of follow-up for ZA use according to the recommended dosing schedule was 17.11 months compared with 9.93 months for nonrecommended schedules and 8.68 months for no treatment (analysis of variance; P < .001). The rate of skeletal complications with ZA use on the recommended schedule was 0.16 events per month versus 0.31 events per month for nonrecommended schedules and 0.43 events per month for no treatment. In the subgroup analysis, the mean time to first complication was 185 +/- 210 days in the ZA-treated group versus 98 +/- 161 days in the untreated group (P < .0001). The mean time from the first complication to the second complication was 111 +/- 124 days in the ZA-treated group versus 86 +/- 114 days in the untreated group (P < .05). CONCLUSIONS: Real-world evidence indicated that ZA reduced the skeletal morbidity rate and delayed the time to skeletal complications.

Cost-effectiveness of letrozole versus tamoxifen as initial adjuvant therapy in hormone receptor-positive postmenopausal women with early-stage breast cancer.

BACKGROUND: In Breast International Group (BIG) 1-98, a randomized, double-blind trial comparing 5 years of initial adjuvant therapy with letrozole versus tamoxifen in postmenopausal women with hormone receptor-positive early breast cancer, letrozole significantly improved disease-free survival by 19% and reduced risk of breast cancer recurrence by 28% and distant recurrence by 27%. PATIENTS AND METHODS: A Markov model was used to estimate the incremental cost per quality-adjusted life year (QALY) gained with 5 years of initial adjuvant therapy with letrozole versus tamoxifen from a US health care system perspective. Probabilities and costs of breast cancer recurrence and treatment-related adverse events and health-state utilities were based on published results of BIG 1-98 and other published studies. Costs and QALYs were estimated over the lifetime of a cohort of postmenopausal women with hormone receptor-positive early breast cancer, aged 60 years at initiation of therapy. In our base case, we assumed that benefits of letrozole on risk of breast cancer recurrence are maintained for 5 years after therapy discontinuation ("carry-over effect") and examined the effects of this assumption on results in sensitivity analyses. RESULTS: Under base-case assumptions, letrozole yields an additional 0.409 QALYs versus tamoxifen at an additional cost of $9705, yielding a cost per QALY gained for letrozole versus tamoxifen of $23,743 (95% confidence interval, $14,087-$51,129). Assuming no carry-over effects, letrozole yields 0.264 QALYs at a cost of $10,341, for a cost per QALY gained of $39,098 (95% confidence interval, $23,968- $83,501). CONCLUSION: In postmenopausal women with hormone receptor-positive early breast cancer, initial adjuvant treatment with letrozole is cost-effective from the US health care system perspective.

Direct medical costs of constipation in the United States.

This study estimated the total medical cost of care and described characteristics of patients with constipation in the United States. The 2001 National Ambulatory Medical Care Survey, National Hospital Ambulatory Medical Care Survey, and National Hospital Discharge Survey were used to provide national estimates. Patients diagnosed with constipation, or whose constipation was a reason for the visit, were identified. Medicare reimbursement rates based on recognized diagnostic and procedural codes were used to value each visit related to constipation. Constipation was a diagnosis or reason for seeking care in an estimated 5.7 million ambulatory visits and was the primary diagnosis or reason for 2.7 million of those visits. Of these visits, 1,838,493 were outpatient physician, 297,927 were outpatient hospital, and 555,432 were emergency department. Constipation was the primary diagnosis in 38,361 additional inpatient visits. Total cost was dollar 235 million per year, with 55% incurred from inpatient care and 23%, 16%, and 6% from ED, outpatient physician, and outpatient hospital settings, respectively. Constipation is treated primarily in ambulatory settings, but the costs of inpatient care exceed those of ambulatory care.

Total costs of IBS: employer and managed care perspective.

Irritable bowel syndrome (IBS) is a common gastrointestinal motility disorder that typically affects persons of working age and is costly to employers. The financial burden attributable to the direct (use of healthcare resources) and indirect (missed days from work [absenteeism] and loss of productivity while at work [presenteeism]) costs of IBS is similar to that of other common long-term medical disorders, such as asthma, migraine, hypertension, and congestive heart failure. The symptoms of IBS are significantly bothersome and place a substantial burden on the personal and working lives of patients. As with other long-term medical conditions that have a significant impact on productivity, directed efforts by employers can address IBS in the workplace and thereby potentially decrease its impact. In this article, the symptoms of IBS and its impact on patients and on society as a whole are discussed; options are outlined by which employers can help reduce the total costs of IBS, including lost productivity (both absenteeism and presenteeism), in the workplace.

Impairment in work productivity and health-related quality of life in patients with IBS.

Irritable bowel syndrome (IBS) is a long-term and episodic medical disorder shown to have an impact on work productivity and health-related quality of life (QOL). The objective of this study was to assess the impact of IBS on work productivity and on health-related QOL in an employed population in the United States and to quantify the cost of these factors to the employer. A 2-phase survey was sent to the workforce of a large US bank to assess the presence of IBS among employees and to measure their work productivity (absenteeism [time lost from work] and presenteeism [reduced productivity at work]) and health-related QOL. Forty-one percent of the 1776 employees responding to both phases of the survey met the Rome II criteria for IBS. Employees with IBS reported a 15% greater loss in work productivity because of gastrointestinal symptoms than employees without IBS and had significantly lower Medical Outcomes Study Short Form 36 (SF-36) scores than those without IBS. IBS was associated with a 21% reduction in work productivity, equivalent to working less than 4 days in a 5-day workweek. Employees with IBS also had significantly lower scores on all domains of the SF-36, indicating poorer functional outcomes. Reduced work productivity and diminished QOL of these magnitudes may have substantial financial impact on employers.

Budget impact of tegaserod on a managed care organization formulary.

We sought to develop a budget impact model that assesses the economic effect of adding tegaserod for the management of irritable bowel syndrome (IBS) with constipation to the formulary of a managed care organization (MCO). The model estimates the per patient economic impact and the per member, per month (PMPM) economic impact of patients 6 months before and 6 months after the initiation of tegaserod. Resource utilization data, taken from medical and pharmacy administrative claims data, were based on a retrospective, longitudinal study of 3365 patients administered tegaserod through a large, geographically diverse MCO. Costs were estimated for 2 patient subgroups, women with IBS and other gastrointestinal (GI) diagnoses. Sensitivity analyses were performed by varying several model input parameters. The base-case model resulted in an incremental PMPM budget impact associated with the use of tegaserod of 0.01 dollars. Total per patient budget impact (for all resources, including tegaserod) for a 6-month period was 274.34 dollars for women with IBS and 301.84 dollars for women with other GI diagnoses. Overall, 25.9% (29.0% for women with IBS group and 21.9% for women with other GI diagnoses group) of the cost of tegaserod was offset by decreases in resource utilization. Key drivers of post-tegaserod reductions in resource costs were hospital stays, outpatient office visits, emergency department visits, endoscopic procedures, and nonendoscopic procedures. Tegaserod therapy can decrease GI-related resource utilization, resulting in a significant cost-offset percentage. When the associated budget impact of adding tegaserod to its formulary is absorbed across an entire MCO population, the PMPM impact of tegaserod is small.

Effectiveness of tegaserod therapy on GI-related resource utilization in a managed care population.

This study sought to determine the real-world effectiveness of tegaserod therapy on gastrointestinal (GI)-related resource utilization in a managed care population with a retrospective, longitudinal pre-/post-parallel cohort study of tegaserod users and a matched reference cohort of tegaserod nonusers through medical and pharmacy claims data from a large, geographically diverse, managed care organization. Continuously enrolled benefit-eligible patients newly initiated on tegaserod therapy (index prescription) were identified between August 1, 2002, and June 30, 2003, and were categorized (using International Statistical Classification of Diseases, 9th Revision, Clinical Modification codes) as having irritable bowel syndrome (IBS) or another GI-related disorder (e.g., gastroesophageal reflux disease). GI-related resource utilization (office visits, hospitalizations, emergency department visits, endoscopic and nonendoscopic procedures, and GI drug prescriptions) was determined for the 6-month period before and after the index prescription date for tegaserod users and nonusers. The study population consisted of 3365 tegaserod users and 3364 matched nonusers. Within-cohort differences before and after therapy were tested using the Wilcoxon signed rank test. The mean age of 3365 tegaserod users and 3364 matched nonusers was 47 years (+/-15 years); 92% were women, 47% had an index diagnosis of IBS, and 53% had an index diagnosis of another GI-related disorder. Within-cohort GI resource utilization comparisons before and after therapy initiation showed significant decreases (P < .01) in all utilization categories, except GI drug prescriptions, for tegaserod users; these decreases were not consistently observed for matched nonusers. Tegaserod use appeared to be associated with consistent decreases in GI-related resource utilization after 6 months of therapy; similarly consistent reductions were not observed in tegaserod nonusers. These early findings suggest that tegaserod may provide important clinical and economic benefits.

Tegaserod treatment for IBS: a model of indirect costs.

Irritable bowel syndrome (IBS) has been associated with substantial time lost from work (absenteeism) and reduced productivity at work (presenteeism), which are the indirect costs of illness. This article presents a productivity model demonstrating the indirect costs associated with IBS and the reduction in those costs for a cohort of female employees hypothetically treated with tegaserod, a new selective serotonin (5-hydroxytryptamine [5-HT]) type 4 (5-HT4) receptor agonist, which is approved by the US Food and Drug Administration for treating women with IBS-C. The model is based on economic and epidemiologic published literature and clinical trial results. In this model, tegaserod treatment resulted in 1882 dollars in avoided lost productivity per treated female employee. Considering only the benefits of decreased work loss and the costs of medical therapy, the model predicts a benefit/cost ratio of 3.75 in the base case. From an employer's perspective, medical therapy for IBS with tegaserod is cost-effective under a series of assumptions for the treatment of women with IBS with constipation.

Quality of life in managed care patients with irritable bowel syndrome.

The relationship between the severity of abdominal discomfort/pain and generic and disease-specific quality of life (QoL) was explored in patients with irritable bowel syndrome in an MCO. Subjects were stratified into four symptom-severity groups. Descriptive and multivariate analyses were used to examine the relationship of QoL to severity of abdominal discomfort/pain. Generic and disease-specific QoL scores declined as severity of abdominal discomfort/pain increased. The lowest 36-Item Short-Form Health Survey scores for respondents with the most severe abdominal discomfort/pain were for role physical (24.2 +/- 35.4) and vitality (33.7 +/- 19.2). In multivariate regression models controlling for age, sex, work status and education, severity of abdominal discomfort/pain was a significant independent predictor of QoL.

Utilization patterns and net direct medical cost to Medicaid of irritable bowel syndrome.

BACKGROUND: Patients with irritable bowel syndrome are frequent users of the health care system. DESIGN AND METHODS: This retrospective matched case-control study assessed the economic impact of irritable bowel syndrome on the Medicaid program by comparing the health care utilization and expenditures of Medicaid patients with irritable bowel syndrome in California and North Carolina with age-, sex-, and race-matched control groups without the syndrome. RESULTS: Average annual Medicaid expenditures per case of diagnosed irritable bowel syndrome were 2952 dollars and 5908 dollars in California and North Carolina, respectively; corresponding unadjusted net incremental expenditures were 962 dollars and 2191 dollars, respectively. In both states, patients with irritable bowel syndrome incurred greater costs than controls for physician visits, outpatient visits, and prescription drugs. CONCLUSIONS: Irritable bowel syndrome was shown to impose an economic burden on the Medicaid program. The cost of treating patients with irritable bowel syndrome is higher than the cost of treating matched ambulatory Medicaid recipients without the condition.

The economic consequences of irritable bowel syndrome: a US employer perspective.

BACKGROUND: The objective of this study was to measure the direct costs of treating irritable bowel syndrome (IBS) and the indirect costs in the workplace. This was accomplished through retrospective analysis of administrative claims data from a national Fortune 100 manufacturer, which includes all medical, pharmaceutical, and disability claims for the company's employees, spouses/dependents, and retirees. METHODS: Patients with IBS were identified as individuals, aged 18 to 64 years, who received a primary code for IBS or a secondary code for IBS and a primary code for constipation or abdominal pain between January 1, 1996, and December 31, 1998. Of these patients with IBS, 93.7% were matched based on age, sex, employment status, and ZIP code to a control population of beneficiaries. Direct and indirect costs for patients with IBS were compared with those of matched controls. RESULTS: The average total cost (direct plus indirect) per patient with IBS was 4527 dollars in 1998 compared with 3276 dollars for a control beneficiary (P<.001). The average physician visit costs were 524 dollars and 345 dollars for patients with IBS and controls, respectively (P<.001). The average outpatient care costs to the employer were 1258 dollars and 742 dollars for patients with IBS and controls, respectively (P<.001). Medically related work absenteeism cost the employer 901 dollars on average per employee treated for IBS compared with 528 dollars on average per employee without IBS (P<.001). CONCLUSION: Irritable bowel syndrome is a significant financial burden on the employer that arises from an increase in direct and indirect costs compared with the control group.

Irritable bowel syndrome, health care use, and costs: a U.S. managed care perspective.

OBJECTIVE: We performed an evaluation of patient symptoms, health care use, and costs to define the burden of illness of irritable bowel syndrome (IBS) and the relation to the severity of abdominal pain/discomfort in a large health maintenance organization. METHODS: All 6500 adult health maintenance organization members who had undergone flexible sigmoidoscopy in the year 2000 were mailed a questionnaire that elicited Rome I symptom criteria and severity ratings for abdominal pain/discomfort. Multiple health care use measures were obtained from various administrative databases. IBS patients were compared with a control group of non-IBS subjects, and analyses were adjusted for age and sex. RESULTS: We received 2613 (40.2%) responses. Compared with non-IBS subjects over 2 yr, IBS patients had more outpatient visits (medical, surgery, and emergency, p < 0.05), were hospitalized more often (p < 0.05), and had more total outpatient prescriptions (p < 0.05) and IBS-related prescriptions (p < 0.05). Over 1 yr, total costs were 51% higher in IBS patients, who also had higher costs for outpatient visits, drugs, and radiology and laboratory tests (p < 0.05). Total costs were increased by 35%, 52%, and 59% in IBS patients with mild, moderate, and severe symptoms of abdominal pain/discomfort compared with non-IBS subjects (p < 0.05). CONCLUSIONS: Using Rome I symptom criteria, we found that IBS is associated with a broad pattern of increased health care use and costs. The severity of abdominal pain/discomfort is a significant predictor of health care use and costs for patients with IBS compared with non-IBS subjects.

Resource utilization associated with irritable bowel syndrome in the United States 1987-1997.

This study uses national databases to examine the impact of irritable bowel syndrome (IBS) on resource utilization in the United States. Approximately 1.5-2.7 million physician visits (599-1,043 per 100,000) yearly were related to IBS, with 45.3% seen by gastroenterologists, and 89% prescribed medications. Rates of physician visits by women were approximately 2.4-3.3 times higher than that for men. The average number of medication prescribed per visit was 1.83. Approximately 89% of the visits were prescribed with medications. The rate of hospitalization (5.1 per 100,000 in 1997) decreased by 60% and length of stay decreased from 5.5 to 3.1 days in the past decade. The average charges of IBS-related hospitalization were US$7,882. Our study found an apparent decreasing trend of IBS-related hospitalizations and no marked increase in office consultations in the past decade. However, a better case identification criterion is necessary to estimate the true disease burden.