Risk of Developing Comorbidities Among Women with Endometriosis: A Retrospective Matched Cohort Study.

BACKGROUND: Endometriosis has been associated with higher rates of various chronic conditions, but its epidemiological data are fragmented and dated. We sought to compare the incidence of developing commonly occurring comorbidities among patients with and without endometriosis in a large, contemporary patient cohort that reflects real-world clinical practice. MATERIALS AND METHODS: A cohort of women aged 18-49 with incident endometriosis was extracted from the 2006-2015 de-identified Clinformatics® DataMart commercial insurance claims database (OptumInsight, Eden Prairie, MN). Endometriosis was identified by International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 617.x on ≥1 inpatient or emergency department claim or ≥2 outpatient claims. Nonendometriosis control patients were exactly matched 4:1 to cases based on state, insurance plan type, and age (±1 year). Based on a literature review and expert consultation, 22 comorbidities were identified for analysis. The risk of developing a comorbidity post-index date was analyzed with stratified Cox proportional hazards models. RESULTS: There were 26,961 cases and 107,844 controls. Mean age was 36 years. The adjusted risk of developing a comorbid condition among endometriosis cases was statistically significantly higher than the matched controls for all 22 comorbidities (p ≤ 0.001) and was at least twice as large for nine comorbidities (infertility/subfertility, ovarian cyst, uterine fibroids, pelvic inflammatory disorder, interstitial cystitis, irritable bowel syndrome, constipation/dyschezia, ovarian cancer, and endometrial cancer). CONCLUSION: The incidence of developing many comorbidities was significantly higher among endometriosis patients compared with matched women without endometriosis. Additional research is needed to establish the implications for healthcare resource use.

Reintervention Rates After Myomectomy, Endometrial Ablation, and Uterine Artery Embolization for Patients with Uterine Fibroids.

BACKGROUND: Women with uterine fibroids (UF) may undergo less invasive procedures than hysterectomy, including myomectomy, endometrial ablation (EA), and uterine artery embolization (UAE); however, long-term need for reintervention is not well characterized. We estimated reintervention rates for 5 years and identified predictors of reintervention. MATERIALS AND METHODS: A longitudinal retrospective cohort study was conducted in women in MarketScan® Commercial Claims and Encounters (Truven Health Analytics) aged 18-49 years with UF diagnosis before myomectomy, EA, or UAE from 2008 to 2014. Patients were categorized by initial procedure (index date) and required to have ≥12 months of continuous coverage before and after. Kaplan-Meier analyses and Cox proportional hazard models were used to estimate survival without reintervention and hazard of reintervention for 5 years. RESULTS: The study included 35,631 women with myomectomy (n = 13,804: 8,018 abdominal, 941 hysteroscopic, and 4,845 laparoscopic), EA (n = 17,198), and UAE (n = 4,629). Myomectomy had the lowest 12-month reintervention rate (4.2%), followed by UAE (7.0%), then EA (12.4%; both p < 0.001 relative of myomectomy). Estimates of 5-year reintervention rates were 19% for myomectomy (17%, 28%, and 20% for abdominal, hysteroscopic, and laparoscopic, respectively), 33% for EA, and 24% for UAE. EA and UAE had adjusted hazard ratios of 2.63 (95% confidence interval [CI], 2.44-2.83) and 1.56 (95% CI, 1.42-1.72). Prior anemia, bleeding, pelvic inflammatory disease, and abdominal and pelvic pain increased the hazard of reintervention. CONCLUSION: Reintervention rate estimates ranged from 17% to 33% for 5 years after myomectomy, EA, and UAE for patients with UF. Risk of requiring reintervention should be considered during treatment selection.

Real-World Evaluation of Direct and Indirect Economic Burden Among Endometriosis Patients in the United States.

INTRODUCTION: The prevalence of endometriosis and the need for treatment in the USA has led to the need to explore the contemporary cost burden associated with the disease. This retrospective cohort study compared direct and indirect healthcare costs in patients with endometriosis to a control group without endometriosis. METHODS: Women aged 18-49 years with endometriosis (date of initial diagnosis = index date) were identified in the Truven Health MarketScan® Commercial database between 2010 and 2014 and female control patients without endometriosis were matched by age and index year. The following outcomes were compared: healthcare resource utilization (HRU) during the 12-month pre- and post-index periods (including inpatient admissions, pharmacy claims, emergency room visits, physician office visits, and obstetrics/gynecology visits), annual direct (medical and pharmacy) and indirect (absenteeism, short-term disability, and long-term disability) healthcare costs during the 12-month post-index period (in 2014 US$). Multivariate analyses were conducted to estimate annual total direct and indirect costs, controlling for demographics, pre-index clinical characteristics, and pre-index healthcare costs. RESULTS: Overall, 113,506 endometriosis patients and 927,599 controls were included. Endometriosis patients had significantly higher HRU during both the pre- and post-index periods compared to controls (p < 0.0001, all categories of HRU). Approximately two-thirds of endometriosis patients underwent an endometriosis-related surgical procedure (including laparotomy, laparoscopy, hysterectomy, oophorectomy, and other excision/ablation procedures) in the first 12 months post-index. Mean annual total adjusted direct costs per endometriosis patient during the 12-month post-index period was over three times higher than that for a non-endometriosis control [$16,573 (standard deviation (SD) = $21,336) vs. $4733 (SD = $14,833); p < 0.005]. On average, incremental direct and indirect 12-month costs per endometriosis patient were $10,002 and $2132 compared to their matched controls (p < 0.005). CONCLUSIONS: Endometriosis patients incurred significantly higher direct and indirect healthcare costs than non-endometriosis patients. FUNDING: AbbVie Inc.

The economic impact of switching from Synthroid for the treatment of hypothyroidism.

AIMS: To compare hypothyroidism-related costs for patients who continuously used Synthroid and patients who switched from Synthroid to alternative therapies. MATERIALS AND METHODS: Truven's Health Analytics MarketScan Commercial Claims and Encounters database from January 1, 2007 to June 30, 2014 was queried for US adults diagnosed with hypothyroidism who initiated Synthroid and adhered to such therapy for at least 6 months. Propensity score matching matched continuous users of Synthroid to patients who switched from Synthroid to alternative levothyroxine agents. Kruskal-Wallis tests assessed differences between the matched cohorts in several categories of costs, including disease-related drug costs, non-drug medical costs, and total direct medical costs. RESULTS: There were 10,159 individuals included in the study, with 7,991 continuous users of Synthroid and 2,168 switchers. After matching (n = 2,052 for each cohort), continuous use of Synthroid was associated with significantly lower hypothyroidism-related non-drug medical costs ($595 vs $1,023; p = .003) and reduced hypothyroidism-related total medical costs ($757 vs $1,132; p = .010), despite being associated with significantly higher drug costs ($161 vs $109; p < .001). Hypothyroidism-related total medical costs rose as the number of switches of hypothyroidism treatment increased, with continuous users having significantly lower hypothyroidism-related total medical costs ($757) compared with patients who switched twice ($1,179; p = .001) or three or more times ($1,268; p = .004). LIMITATIONS: The analyses focused on continuously insured patients who were adherent to Synthroid for at least 6 months and results may not be generalizable. The reliance on claims data does not allow for clinical examination of hypothyroidism or inclusion of some factors that may be associated with outcomes. The analyses assume that all prescriptions filled are taken as prescribed. CONCLUSIONS: Results indicate that there are significant direct economic healthcare costs associated with switching from Synthroid to alternative levothyroxine therapies, and that these costs increase as patients switch therapies more frequently.

Impact of uterine fibroid symptoms on health-related quality of life of US women: evidence from a cross-sectional survey.

BACKGROUND: Uterine fibroids (UF) are associated with significant health-related quality of life (HRQL) impact. This study examined the impact of UF symptoms on HRQL. METHODS: An online cross-sectional survey of 18 to 49 year old US women was conducted and collected demographics, UF prevalence, symptoms, and HRQL using the UFS-QOL. Descriptive statistics were used to examine the impact of symptom presence, severity, bothersomeness, and number of UF symptoms on HRQL. Analyses were weighted to match the US female population distribution. Multivariate regressions were performed with each subscale as a dependent variable to examine the impact of individual UF symptoms on HRQL. RESULTS: A total of 59,411 (15.5%) panel members completed the prevalence screener; 4848 met inclusion criteria; 955 had UF and no hysterectomy. Mean age was 40.3; 58% were white; 63% were married/civil union. Common UF symptoms were: lower back pain (65%), fatigue/weariness (63%), bloating (61%), pelvic pain/cramping during menses (63%), and heavy bleeding during menses (54%). Mean UFS-QoL subscale scores were significantly (p < .05) worse among women with a UF symptom versus women without the symptom. Women who rated their UF symptoms as severe had significantly (p < .001) worse UFS-QoL scores than women with mild or moderate symptoms. UFS-QoL subscale scores worsened as the number of symptoms increased. In the regressions, the presence of bleeding and non-bleeding symptoms were related to worse UFS-QoL subscale scores. CONCLUSION: HRQL among women with UF was significantly impacted by UF-related symptoms. Greater impact was observed as the number and severity of symptoms increased.

Examining the Relationship Between Symptomatic Burden and Self-reported Productivity Losses Among Patients With Uterine Fibroids in the United States.

OBJECTIVE: To evaluate the impact of uterine fibroid symptoms on employment and household productivity. METHODS: An online survey of US women between 18 and 54 was conducted. Productivity was assessed using the health related productivity questionnaire (HRPQ). Descriptive statistics and logistic multivariable regressions examined the relationship between uterine fibroids (UF) symptom experience and employment and household productivity. RESULTS: Of 1365 eligible women, 873 (64.0%) were employed. Women lost an average of 0.8 hours to employment-related absenteeism and 4.4 hours due to employment-related presenteeism for 5.1 hours of employment productivity lost/week. Women lost an average of 1.4 hours due to household-related absenteeism and 1.6 hours due to household-related presenteeism for a total of 3.0 hours of household lost productivity. Productivity losses increased with increases in symptom burden. CONCLUSION: UF has a substantial impact on employment-related and household-related productivity.

The Effect of Endometriosis Symptoms on Absenteeism and Presenteeism in the Workplace and at Home.

BACKGROUND: Characterized by pain symptoms, endometriosis affects women's productivity in their prime working years. OBJECTIVE: To evaluate the effect of individual endometriosis symptoms on household chore and employment productivity as measured by presenteeism and absenteeism in a population survey of women with endometriosis. METHODS: An online survey of U.S. women was conducted to evaluate the prevalence of endometriosis, as well as symptoms, demographics, and clinical characteristics of the respondents. Women aged 18-49 years (inclusive) with endometriosis completed the Health-related Productivity Questionnaire to assess presenteeism and absenteeism for employed and household work. Descriptive statistics were used to describe the sample, survey responses, and the effect of endometriosis symptom severity on household chore and employment productivity. Regression analyses were performed to examine the effect of individual endometriosis symptoms on employment and household productivity lost because of presenteeism and absenteeism. RESULTS: Of 59,411 women who completed the prevalence screener, 5,879 women (9.9%) met the inclusion criteria for completing the survey; 1,318 women (2.2%) reported endometriosis and at least 1 hour of scheduled household chores in the past 7 days. Of these, 810 women had least 1 hour of scheduled employment in the past 7 days. Mean age was 34.6 years (standard error [SE] ± 0.32); 77.2% of the women were white; 59.3% were married or in a civil union; and 59.1% were employed full or part time. Women with endometriosis had a weekly loss of an average of 5.3 hours (SE ± 0.4) because of employment presenteeism, 1.1 hours (SE ± 0.2) of employment absenteeism, 2.3 (SE ± 0.2) hours of household presenteeism, and 2.5 (SE ± 0.2) hours of household absenteeism. Hourly losses in employment and household chore productivity were significantly greater with increasing symptom severity (mild vs. severe: 1.9 vs. 15.8 total employment hours lost and 2.5 vs. 10.1 total household hours lost; P < 0.0001). Women who experienced 3 endometriosis symptoms concurrently lost a significantly greater number of employment hours because of absenteeism and presenteeism compared with those experiencing 1 or 2 symptoms (P < 0.001). Regression analyses showed that a range of endometriosis symptoms predicted employment and household losses because of presenteeism and absenteeism. CONCLUSIONS: There was a significant relationship between the number and patient-reported severity of endometriosis symptoms experienced and hours of employment and household productivity lost because of presenteeism and absenteeism. Study findings indicate a need for guidance strategies to help women and employers manage endometriosis so as to reduce productivity loss. DISCLOSURES: The design and financial support for this study was provided by AbbVie. AbbVie participated in data analysis, interpretation of data, review, and approval of the manuscript. Coyne and Gries are employees of Evidera- Evidence, Value & Access by PPD and were paid scientific consultants for AbbVie in connection with this study. Soliman, Castelli-Hayley, and Snabes are AbbVie employees and may own AbbVie stock or stock options. Surrey is affiliated with Colorado Center for Reproductive Medicine and was paid by AbbVie as a consultant for this project. Surrey serves as a consultant for AbbVie outside of this project. All authors participated in data analysis and interpretation, and contributed to the development of the manuscript. The authors maintained control over the final contents of the manuscript and the decision to publish. Study concept and design were contributed by Soliman, Coyne, Gries, and Castelli-Haley. Soliman, Castelli-Haley, Coyne, and Gries collected the data, and data interpretation was performed by Snabes, Surrey, Soliman, Coyne, and Gries. The manuscript was written and revised by Soliman, Coyne, and Gries, along with the other authors.

The burden of endometriosis symptoms on health-related quality of life in women in the United States: a cross-sectional study.

INTRODUCTION: To examine the symptomatic burden of endometriosis on health-related quality of life (HRQL) in women in the United States (US). METHODS: A cross sectional web-based survey study was conducted among women using survey panels. The survey included study-specific questions and standardized HRQL questionnaires. Participants reviewed a list of endometriosis symptoms and selected all symptoms they had ever or were currently experiencing. For current symptoms, participants rated the severity and bothersomeness of each symptom. Participants completed the endometriosis health profile (EHP-30) core questionnaire. Descriptive analyzes were performed and multivariate regressions were run with each EHP subscale as a dependent variable to examine the impact of symptoms while controlling for age and comorbid conditions. RESULTS: Mean age of the 1269 women was 34.3 ± 0.3; 78% were white. At least 75% reported having ever experienced: pelvic pain/cramping during their menstrual period, anxiety/stress, lower back pain or fatigue/weariness/anemia. EHP-30 scores ranged from 33.6 (95% CI: 31.4, 35.8) (social support) to 37.8 (95% CI: 35.5, 40.1) (control and powerlessness), indicating moderate HRQL impact. For all but one domain and one symptom, EHP-30 scores were significantly higher (worse) for women who had individual endometriosis-related symptoms than for those who did not. EHP-30 scores consistently deteriorated with each increase in the number of symptoms experienced and by increasing perceived disease severity. Pelvic pain/cramping during menstrual period, irregular periods and general abdominal pain were significantly associated with the EHP-30 domain scores in the regression models. CONCLUSION: Experiencing endometriosis symptoms is associated with lower HRQL. Importantly, as symptom severity and number of symptoms increase, HRQL further deteriorates.

Incremental direct and indirect cost burden attributed to endometriosis surgeries in the United States.

OBJECTIVE: To compare direct and indirect costs between endometriosis patients who underwent endometriosis-related surgery (surgery cohort) and those who have not received surgery (no-surgery cohort). DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): Endometriosis patients (aged 18-49 years) with (n = 124,530) or without (n = 37,106) a claim for endometriosis-related surgery were identified from the Truven Health MarketScan Commercial and Health and Productivity Management databases for 2006-2014. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Primary outcomes were healthcare utilization during 12-month pre- and post-index periods, annual direct (healthcare) and indirect (absenteeism and short- and long-term disability) costs during the 12-month post-index period (in 2014 US dollars). Indirect costs were assessed for patients with available productivity data. RESULT(S): Patients in the surgery cohort had significantly higher healthcare resource utilization during the post-index period and had mean annual total adjusted post-index direct costs approximately three times the costs among patients in the no-surgery cohort ($19,203 [SD $7,133] vs. $6,365 [SD $2,364]; average incremental annual direct cost = $12,838). The mean cost of surgery ($7,268 [SD $7,975]) was the single largest contributor to incremental annual direct cost. Mean estimated annual total indirect costs were $8,843 (surgery cohort) vs. $5,603 (no-surgery cohort); average incremental annual indirect cost = $3,240. CONCLUSION(S): Endometriosis patients who underwent surgery, compared with endometriosis patients who did not, incurred significantly higher direct costs due to healthcare utilization and indirect costs due to absenteeism or short-term disability. Regardless of the surgery type, the cost of index surgery contributed substantially to the total healthcare expenditure.

Analysis of Adherence, Persistence, and Surgery Among Endometriosis Patients Treated with Leuprolide Acetate Plus Norethindrone Acetate Add-Back Therapy.

BACKGROUND: Endometriosis affects over 10 million women in the United States. Depot leuprolide acetate (LA), a gonadotropin-releasing hormone agonist, has been used extensively for the treatment of women with endometriosis but is associated with hypoestrogenic symptoms and bone mineral density loss. The concomitant use of add-back therapies, specifically norethindrone acetate (NETA), can alleviate these adverse effects. OBJECTIVE: To compare adherence to and persistence with LA treatment and time to endometriosis-related surgery among women treated with NETA and women treated with LA plus other add-back therapies or LA only. METHODS: This retrospective analysis was conducted using Truven Health MarketScan Commercial Claims and Encounters Database. Women with a diagnosis of endometriosis (ICD-9-CM code 617.xx) who initiated LA (index date) in 2005-2011 were selected for inclusion. Additional requirements were 12 months of continuous enrollment pre- and post-index and no evidence of endometriosis-related surgeries pre-index or up to 30 days post-index; no pre-index use of estrogen or noncontraceptive hormones; and no diagnoses of uterine fibroids, malignant neoplasms, infertility, or pregnancy. Patients were characterized as using NETA; other add-back therapies (estrogens, progestins, or estrogen-progestin combinations); or no add-back therapy. Adherence to and persistence with LA were measured over the 6 months following the index date using outpatient medical and pharmacy claims. Patients were considered adherent if their proportion of days covered was greater than or equal to 0.80. Persistence was operationalized as time to discontinuation, defined as a continuous gap of > 60 days without LA on hand. Time to endometriosis-related surgery (laparotomy, laparoscopy, excision/ablation/fulguration, oophorectomy, and hysterectomy) was measured over the 12 months following the index date. Surgeries were identified from inpatient and outpatient medical claims using procedure codes. Outcomes were compared among cohorts using multivariable logistic and Cox proportional hazards regression models controlling for demographics and baseline clinical characteristics. RESULTS: The final sample included 3,114 women, with a mean age of 36.9 years. The majority of women used LA only with no add-back therapy (n = 1,963, 63.0%), while 15.1% (n = 470) used NETA, and 21.9% (N = 681) used other add-back therapies. During the 6-month follow-up, more patients in the LA plus NETA cohort were adherent to LA therapy compared with LA only (47.2% vs. 31.5%, P < 0.001), and fewer patients discontinued (37.9% vs. 59.6%, P < 0.001). Additionally, fewer patients underwent endometriosis-related surgery in the 12 months after LA initiation in the LA plus NETA cohort (12.6% vs. 16.9%, P = 0.021). In multivariable models, women who initiated LA plus NETA or LA plus other add-back therapies had a higher likelihood of being adherent to LA than LA only patients (OR = 1.91, 95% CI = 1.55-2.36 and OR = 1.95, 95% CI = 1.63-2.34) and lower likelihood of LA discontinuation (HR = 0.54, 95% CI = 0.46-0.63 and HR = 0.59, 95% CI = 0.52-0.68). NETA patients had a lower surgery rate in the 12-month post-index period compared with other add-back patients (HR = 0.68, 95% CI = 0.50-0.93) or LA only patients (HR = 0.69, 95% CI = 0.52-0.92). CONCLUSIONS: For women with endometriosis, treatment with LA and concomitant add-back therapies was associated with better adherence to and persistence with LA over the 6 months following initiation, compared with treatment with LA only. The increased adherence and persistence to LA may translate into decreased need for surgical intervention, although fewer endometriosis-related surgeries were only observed in the 12 months following LA initiation for patients using concomitant NETA add-back therapy. These results support an increased and earlier use of NETA add-back therapy among women who initiate LA. DISCLOSURES: This study was funded by AbbVie, which also markets the endometriosis drugs Lupron and Lupaneta Pack. AbbVie participated in the study design, research, data collection, analysis and interpretation, writing, review, and approval of this publication. Soliman and Castelli-Haley are employees of AbbVie and may own AbbVie stock or stock options. Bonafede and Farr are employees of Truven Health Analytics, which received a research contract to conduct this study with and on behalf of AbbVie. Winkel is a clinical professor in the Department of Obstetrics and Gynecology at Georgetown University in Washington, DC, and has served in a consulting role on research to AbbVie for this project. An earlier version of the current research was presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 20th Annual International Meeting; Philadelphia, PA; May 2015. All authors participated in data analysis and interpretation and contributed to the development of the manuscript.

Analysis of subsequent surgery rates among endometriosis patients who underwent surgery with and without concomitant leuprolide acetate therapy.

Objective To compare subsequent endometriosis-related surgery following initial laparoscopy among women treated with leuprolide acetate (LA) or other endometriosis therapies versus women who received no pharmacotherapy. Research design and methods This retrospective cohort analysis utilized MarketScan Commercial claims data. Women with endometriosis aged 18-49 who underwent laparoscopy between 1 January 2005 and 31 December 2011 were identified using diagnosis and procedures codes and were categorized into four cohorts based on claims within 90 days of laparoscopy: surgery plus adherent LA, surgery plus non-adherent LA, surgery plus other therapy, and surgery alone. Patients with proportion of days covered ≥0.80 in the 6 months after laparoscopy were considered adherent to LA. Main outcome measures Subsequent endometriosis-related surgery (laparoscopy, laparotomy or other excision/ablation/fulguration of endometriosis lesions, oophorectomy, or hysterectomy) was measured in the 6 and 12 months following initial laparoscopy. Risk of subsequent surgery was compared using multivariable Cox proportional hazards modeling. Results Most women were treated with surgery only (n = 9865); fewer were treated with LA (adherent: n = 202; non-adherent: n = 490) or other therapies (n = 230). The proportion of patients with subsequent surgery ranged from 2.0% to 10.0% during the 6 month follow-up (12 month: 9.7% to 13.5%). Adherent LA use was associated with significantly lower risk of surgery compared to surgery alone (hazard ratio [HR] = 0.31, p = 0.020) while use of other therapies was associated with significantly higher risk (HR = 1.51, p = 0.045) over the 6 month follow-up. There was no significant difference between the surgery plus non-adherent LA and surgery only cohort over 6 months (p = 0.247). The association between adherent LA and subsequent surgery was not significant over the 12 month follow-up. Conclusion Therapy with LA after laparoscopy for endometriosis was associated with lower risk of subsequent surgery at 6 months among women who were adherent to LA. Key limitations include lack of ability to capture disease severity which may have resulted in uncontrolled confounding.

Costs of Parkinson's disease in a privately insured population.

BACKGROUND: This is the first analysis to estimate the costs of commercially insured patients with Parkinson's disease (PD) in the USA. Prior analyses of PD have not examined costs in patients aged under 65 years, a majority of whom are in the workforce. OBJECTIVE: Our objective was to estimate direct and indirect costs associated with PD in patients under the age of 65 years who are newly diagnosed or have evidence of advanced PD. METHODS: PD patients were selected from a commercially insured claims database (N > 12,000,000; 1999-2009); workloss data were available for a sub-sample of enrollees. Newly diagnosed patients with evidence of similar disorders were excluded. Patients with evidence of advanced PD disease, including ambulatory assistance device users (PDAAD) and institutionalized (PDINST) patients, as well as newly diagnosed PD patients, were analyzed. Each PD cohort was age-, gender- and region-matched to controls without PD. Direct (i.e. insurer payments to providers) and indirect (i.e. workloss) costs were reported in $US, year 2010 values, and were descriptively compared using Wilcoxon rank sum tests. RESULTS: Patients had excess mean direct PD-related costs of $US4,072 (p < 0.001; N = 781) in the year after diagnosis. The PDAAD cohort (N = 214) had excess direct PD-related costs of $US26,467 (p < 0.001) and the PDINST cohort (N = 156) had excess direct PD-related costs of $US37,410 (p < 0.001) in the year after entering these states. Outpatient care was the most expensive cost source for newly diagnosed patients, while inpatient care was the most expensive for PDAAD and PDINST patients. Excess indirect costs were $US3,311 (p < 0.05; N = 173) in the year after initial diagnosis. CONCLUSIONS: Direct costs for newly diagnosed PD patients exceeded costs for controls without PD, and increased with PD progression. Direct costs were approximately 6-7 times higher in patients with advanced PD than in matched controls. Indirect costs represented 45 % of total excess costs for newly diagnosed PD patients.

Burden of a multiple sclerosis relapse: the patient's perspective.

BACKGROUND: Relapses are a common feature of relapsing-remitting multiple sclerosis (RRMS) and increasing severity has been shown to be associated with higher healthcare costs, and to result in transient increases in disability. Increasing disability likely impacts work and leisure productivity, and lowers quality of life. OBJECTIVE: The objective of this study was to characterize from the patient's perspective the impact of a multiple sclerosis (MS) relapse in terms of the economic cost, work and leisure productivity, functional ability, and health-related quality of life (HR-QOL), for a sample of patients with RRMS in the US treated with immunomodulatory agents. METHODS: A cross-sectional, web-based, self-report survey was conducted among members of MSWatch.com, a patient support website now known as Copaxone.com. Qualified respondents in the US had been diagnosed with RRMS and were using an immunomodulatory agent. The survey captured costs of RRMS with questions about healthcare resource utilization, use of community services, and purchased alterations and assistive items related to MS. The Work and Leisure Impairment instrument and the EQ-5D were used to measure productivity losses and HR-QOL (health utility), respectively. The Goodin MS neurological impairment questionnaire was used to measure functional disability; questions were added about relapses in the past year. RESULTS: Of 711 qualified respondents, 67% reported having at least one relapse during the last year, with a mean of 2.2 ± 2.3 relapses/year. Respondents who experienced at least one relapse had significantly higher mean annual direct and indirect costs compared with those who did not experience a relapse ($US38 458 vs $US28 669; p = 0.0004) [year 2009 values]. Direct health-related costs accounted for the majority of the increased cost ($US5201; 53%) and were mainly due to increases in hospitalizations, medications, and ambulatory care. Indirect costs, including informal care and productivity loss, accounted for the additional 47% of increased cost ($US4588). Accounting for the mean number of relapses associated with these increased costs, the total economic cost of one relapse episode could be estimated at about $US4449, exclusive of intangible costs. The mean self-reported Expanded Disability Status Scale (EDSS) score, derived from the Goodin MS questionnaire, was significantly higher with relapse than with a clinically stable state (EDSS 4.3 vs 3.7; p < 0.0001), while the mean health utility score was significantly lower with relapse compared with a clinically stable state (0.66 vs 0.75; p = 0.0001). The value of these intangible costs of relapse can be estimated at $US5400. The overall burden (direct, indirect, and intangible costs) of one relapse in patients treated with immunomodulatory agents is therefore estimated conservatively at $US9849. CONCLUSIONS: This study shows that from a patient's perspective an MS relapse is associated with a significant increase in the economic costs as well as a decline in HR-QOL and functional ability.

Psychometric validation of the revised SCOPA-Diary Card: expanding the measurement of non-motor symptoms in Parkinson's disease.

BACKGROUND: To identify key non-motor symptoms of Parkinson's disease (PD) to include in a daily diary assessment for off-time, revise the Scales for Outcomes of Parkinson's disease Diary Card (SCOPA-DC) to include these non-motor symptoms, and investigate the validity, reliability and predictive utility of the Revised SCOPA-DC in a U.S. population. METHODS: A convenience sample was used to recruit four focus groups of PD patients. Based on findings from focus groups, the SCOPA-DC was revised and administered to a sample of 101 PD patients. Confirmatory factor analysis was conducted to test the domain structure of the Revised SCOPA-DC. The reliability, convergent and discriminant validity, and ability to predict off-time of the Revised SCOPA-DC were then assessed. RESULTS: Based on input from PD patients, the Revised SCOPA-DC included several format changes and the addition of non-motor symptoms. The Revised SCOPA-DC was best represented by a three-factor structure: Mobility, Physical Functioning and Psychological Functioning. Correlations between the Revised SCOPA-DC and other Health-Related Quality of Life scores were supportive of convergent validity. Known-groups validity analyses indicated that scores on the Revised SCOPA-DC were lower among patients who reported experiencing off-time when compared to those without off-time. The three subscales had satisfactory predictive utility, correctly predicting off-time slightly over two-thirds of the time. CONCLUSIONS: These findings provide evidence of content validity of the Revised SCOPA-DC and suggest that a three-factor structure is an appropriate model that provides reliable and valid scores to assess symptom severity among PD patients with symptom fluctuations in the U.S.

Examination of the UPDRS bradykinesia subscale: equivalence, reliability and validity.

Administering items or subscales separately from the measure for which they were designed to be a part may have unintended consequences for research and practice in Parkinson's disease (PD). The current study tested the equivalence of the bradykinesia subscale when administered alone versus as a component of the full 14-item Unified Parkinson's Disease Rating Scale (UPDRS) motor examination, as well as examined the reliability and validity of the bradykinesia subscale. The study sample consisted of 112 patients with PD. Patients were randomly assigned to either the bradykinesia subscale alone group (n = 56), who were administered the bradykinesia subscale separately from the rest of the UPDRS motor examination, or the full scale group (n = 56), who were administered the UPDRS motor examination in its standard format. The two one-sided t-test (TOST) procedure was used to test for mean equivalency between the two administration groups. Additionally, reliability and validity analyses were performed. The bradykinesia subscale mean scores from the full scale group and the subscale alone group were not statistically equivalent. However, in both groups, the bradykinesia subscale had exceptional reliability and was strongly and similarly related to age, activities of daily living, disability, and other assessments of motor symptom severity. The bradykinesia subscale is a valid and reliable assessment when administered separately from the rest of the UPDRS motor examination; however, caution should be taken when comparing mean scores across studies or occasions when different administrations are used.

Drug therapies for Parkinson's disease: A database analysis of patient compliance and persistence.

BACKGROUND: Evaluating medication adherence in Parkinson's disease (PD) is important to avoid erroneously attributing suboptimal patient outcomes from poor compliance to disease progression or adverse responses to medications. OBJECTIVE: This study of patients with PD who were new to PD drug therapy examined patient compliance and persistence, by drug, to provide a comprehensive investigation of medication-taking behavior in PD. METHODS: A retrospective analysis of patients receiving a new PD drug between March 1 and May 31, 2007, was conducted, using the IMS Health longitudinal prescription database, which contains ∼50% of all retail prescriptions and <150 million patients in the United States. Patients were considered to have received a new PD drug if they initiated PD therapy for the first time, added adjunctive PD therapy, or switched one PD drug for another. Patients were categorized as naive to PD therapy (NT) or having prior PD therapy (PT), which included adjunctive use and switches. The PD medications evaluated were rasagiline, levodopa/carbidopa, levodopa/carbidopa/entacapone, the catechol-O-methyltransferase (COMT) inhibitors (entacapone and tolcapone), pramipexole, ropinirole, and selegiline. The study consisted of a 12-month look-back period (during which patients were required to be active in the database), a 3-month selection period (during which patients received their first prescription), and a 12-month observation period. Compliance was measured using the medication possession ratio (MPR; defined as the number of days' supply of medication divided by the number of available days of therapy, from first dispense date in the selection period to last dispense date in the observation period); noncompliance was defined as an MPR ≤80%. Persistence was measured as the duration (days) of uninterrupted therapy. RESULTS: A total of 29,682 patients with PD (19,673 NT, 10,009 PT) received a new PD drug and were analyzed. Of the 19,510 patients included in the compliance analysis, 10,438 (53.5%) had compliance rates >80% and 9072 (46.5%) were noncompliant. For all patients (NT and PT), compliance rates were significantly higher for patients taking rasagiline than for those taking other PD medications (all P < 0.001). For all patients, the highest mean number of persistent days of treatment (147.5) was reported for rasagiline, followed by levodopa/carbidopa/ entacapone (146.9); persistence for both of these drugs was significantly higher than that for the comparator medications (rasagiline vs levodopa/carbidopa, P = 0.002; rasagiline vs pramipexole, P = 0.003; rasagiline vs COMT inhibitors, ropinirole, and selegiline, all P < 0.001; levodopa/carbidopa/entacapone vs levodopa/carbidopa, P = 0.005; levodopa/carbidopa/entacapone vs pramipexole, P = 0.006; levodopa/carbidopa/entacapone vs COMT inhibitors, ropinirole, and selegiline, all P < 0.001). Almost half of the patients (13,103; 44.1%) remained on their PD medication ≥90 days. CONCLUSIONS: This study found a differential compliance and persistence across PD drug therapies. The compliance rate for rasagiline was significantly higher than that for all of the other PD medications. In addition, rasagiline and levodopa/carbidopa/entacapone were associated with significantly higher persistence rates than were the other PD medications.

Glatiramer acetate and interferon beta-1a for intramuscular administration: a study of outcomes among multiple sclerosis intent-to-treat and persistent-use cohorts.

OBJECTIVE: To study outcomes of multiple sclerosis (MS) patients treated with either glatiramer acetate (Copaxone) or interferon beta-1a for once-weekly, intramuscular administration (Avonex). METHODS: An 'intent-to-treat' (ITT) cohort (n=1282) was established, consisting of patients diagnosed with MS who began therapy on either glatiramer acetate (GA) or intramuscular interferon beta-1a (IFN beta-1a-IM) and had continuous insurance coverage from 6 months before to 24 months after the date when they began taking the medication. A 'persistent use' (PU) cohort (n=639) was also constructed, consisting of individuals who, in addition to the criteria listed above, had a claim for GA or IFN beta-1a-IM within 28 days of the end of the 2-year post-period. Data were obtained from the i3 InVision Data Mart Database from July 2001 to June 2006. Multivariate regressions were used to examine both the 2-year total direct medical costs and the likelihood of relapse associated with the use of each of these alternative MS medications. A relapse was defined as either being hospitalized with a principal diagnosis of MS or having an outpatient visit with a MS diagnosis followed within 7 days by a claim for a corticosteroid. All regressions controlled a wide range of factors that may potentially affect outcomes. RESULTS: In the ITT cohort, patients who started therapy on GA had a significantly lower 2-year risk of relapse (10.01 vs. 5.18%; p=0.0034) as well as significantly lower 2-year total medical costs ($44,201 vs. $41,121; p=0.0294). In the PU cohort, patients who used GA also had a significantly lower 2-year risk of relapse (7.25 vs. 2.16%; p=0.0048) as well as significantly lower total medical costs ($67,744 vs. 63,714; p=0.0445). LIMITATIONS: The analyses relies on an administrative claims database of an insured population and hence, may not be generalizeable to other populations. In addition, such a database precludes measurement of lost work time, unemployment, caregiver burden or other costs associated with MS. CONCLUSIONS: Results from this study indicate that the use of GA is associated with significantly lower probability of relapse as well as significantly lower 2-year total direct medical costs than IFN beta-1a-IM.

Cost sharing, benefit design, and adherence: the case of multiple sclerosis.

PURPOSE: The authors focus on understanding the relationship between costs and cost sharing on medication adherence for individuals who initiated a disease-modifying therapy (DMT) for the treatment of multiple sclerosis (MS). DMTs reduce the risk of relapse and are an essential component of MS treatment. Furthermore, the authors compare monthly payment levels for copayments versus coinsurance and estimate the effects on adherence. METHODS: Using the MarketScan Commercial Claims and Encounters database evidence from July 1 2005 to March 31 2008, the authors employ a multivariate two-stage least-squares model (2SLS) to examine the impact of copayments or coinsurance on the medication possession ratio (MPR). FINDINGS: Descriptive results show that the mean out-of-pocket (OOP) costs of DMT per month were higher for patients with coinsurance than for patients with copayments. For the cohort of patients with copayment there was little difference in monthly copayments across adherence thresholds. Regression analysis shows that an increase in cost sharing reduces adherence overall, but this effect was small and insignificant in the copayment cohort. In contrast, in the coinsurance cohort increased cost sharing was significantly associated with decreased adherence to DMT medication; with a 10% increase in cost sharing leading to an 8.6% decline in adherence. IMPLICATIONS: Employers increasingly rely on coinsurance, despite evidence that reliance on coinsurance results in lower adherence. Our research findings suggest that coinsurance appears to be a greater obstacle to compliance, confirming predictions found in the theoretical literature. ORIGINALITY: This research converted counts of injectable treatments into a continuous adherence measure. Previous literature on cost sharing did not examine MS.

Cost effectiveness of glatiramer acetate and natalizumab in relapsing-remitting multiple sclerosis.

BACKGROUND: Disease-modifying drugs are a significant expenditure for treating multiple sclerosis. Natalizumab (NZ) has been shown to be effective in reducing relapses and disease progression. However, assessment of the cost effectiveness of NZ compared with other disease-modifying drugs in the presence of long-term data has been limited. OBJECTIVE: To assess the lifetime cost effectiveness from the US healthcare and societal perspectives of glatiramer acetate (GA) and NZ (both given with symptom management) relative to symptom management alone in patients with relapsing-remitting multiple sclerosis (RRMS) using evidence from long-term published studies. METHODS: A Markov model was developed with patients transitioning through health states based on Kurtzke's expanded disability status scale (EDSS). Patients were >/=18 years of age with RRMS, EDSS <6.0 and receiving treatment. Treatment effects were obtained from clinical trials for years 1 and 2 of therapy and long-term clinical assessments thereafter. Transitions were adjusted for discontinuation and persistent NZ antibodies. Patients incurred drug, other medical and lost worker productivity costs. Patient quality of life was considered in the form of utilities, which were taken from assessments of patients with MS. Costs were valued in 2007 $US, and costs and outcomes were discounted at 3% per annum. Various parameters and assumptions were tested in one-way sensitivity analyses, and scenario-based analyses were also performed. RESULTS: Remaining lifetime, direct medical costs for patients receiving GA or NZ versus symptom management were $US408 000, $US422 208 and $US341 436, respectively. Patients receiving GA or NZ benefited from increased years in EDSS 0.0-5.5 (1.18 and 1.09, respectively), years relapse-free (1.30 and 1.18) and QALYs (0.1341 and 0.1332). The incremental cost per QALY for GA or NZ compared with symptom management was $US496 222 and $US606 228, respectively, excluding lost worker productivity costs. GA was associated with a cost saving compared with NZ. The incremental cost per QALY results were sensitive to changes in time horizon, disease progression and drug costs. Improved QALYs for NZ were sensitive to changes in the clinical effect of NZ on disease progression and discontinuation over time. CONCLUSIONS: GA or NZ in RRMS patients is associated with increased benefits compared with symptom management, albeit at higher costs. Although year 1 and 2 disease progression and relapse rates were better for NZ than GA, long-term evidence may show GA to have similar, if not improved, clinical benefit.

Glatiramer acetate and interferon beta-1b: a study of outcomes among patients with multiple sclerosis.

INTRODUCTION: To study the medical cost and probability of relapse in patients with multiple sclerosis (MS) treated with either glatiramer acetate (GA) or interferon beta-1b (IFN beta.1b). METHODS: Data were obtained from the i3 InVision Data Mart Database from July 2001 to June 2006. We established an "intent-totreat" (ITT) cohort (n=842) of patients diagnosed with MS who began treatment with either GA or IFN beta-1b and had continuous insurance coverage from 6 months before to 2 years after the date when they began taking the medication. We also created a "continuous use" (CU) cohort (n=418) of individuals who, in addition to the criteria listed above, used either GA or IFN beta-1b within 28 days of the end of the 2-year postperiod. Using multivariate regressions, we examined both the 2-year total average direct medical costs and the likelihood of relapse within this period associated with the use of each of these MS medications. We defined relapse as being either hospitalization with a principal diagnosis of MS or having an outpatient visit with a diagnosis of MS and then prescribed steroids within a 7-day period. All regression analyses controlled for a wide range of factors that may potentially affect outcomes. RESULTS: In the ITT cohort, patients who started treatment with GA had a significantly lower 2-year estimated risk of relapse (13.54% vs. 5.31%; P=0.0006). In the CU cohort, patients who used GA also had a significantly lower 2-year estimated risk of relapse (10.91% vs. 2.09%; P=0.0018), as well as significantly lower average total medical costs ($53,157 vs. $48,130; P=0.0345). CONCLUSIONS: Results from this study indicate that users of GA have a significantly lower probability of 2-year relapse than users of IFN beta-1b. In addition, among continuous users, the 2-year total average direct medical costs are significantly lower for users of GA than for users of IFN beta-1b.