PND32 Potential Humanistic Benefits of Pegylation in the Treatment of Multiple Sclerosis: A Systematic Review of the Literature

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VALUE IN HEALTH 15 (2012) A1–A256

PND27 MODEL OF RASAGILINE VERSUS STANDARD OF CARE FOR PARKINSON’S DISEASE: COMPARISON OF PROGRESSION EFFECTS Johnson S1, Wang ST1, Birnbaum H1, Grubb E2 1 Analysis Group, Inc., Boston, MA, USA, 2Teva Pharmaceuticals, Kansas City, MO, USA

OBJECTIVES: To incorporate the rasagiline effects observed in the ADAGIO trial into a 25-year Parkinson’s Disease (PD) progression model. A model evaluating economic gains from slowing progression was previously developed but progression reduction effects had been hypothetical; including rasagiline effects would be informative. METHODS: A disease progression model based on 10 cohort studies containing 3318 patients was used to assess the expected time to progression through Hoehn and Yahr (H&Y) stages one to 5 for those untreated with rasagiline. ADAGIO’s relative difference in the Activities of Daily Living-Unified Parkinson’s Disease Rating Scale (ADL-UPDRS) from week 0 to 36 for placebo vs. rasagiline (1 mg/day) were used to parameterize the reduction in progression rate for rasagiline. Relative differences in total UPDRS change were also evaluated. Effects observed in the clinical trials were assumed to persist over the course of the model. Medicare claims data for 25,577 patients over 9 years were used to parameterize direct medical costs by H&Y stage. Patients were age 62, 61% male, and 50% H&Y1/50% H&Y2 at baseline. Costs and life-years were discounted at 3%. RESULTS: Based on the relative rate of change in ADL-UPDRS, rasagiline reduced progression rates by 76.1%. Rasagiline added $48,226 in drug costs over 25 years. Total direct costs (medical and pharmacy) for untreated patients were $264,389 and $148,736 for rasagiline treated patients; incremental direct costs were $115,653 in favor of rasagiline. Incremental life years gained were 1.97 in favor of rasagiline. At 10 years, the model associated rasagiline with a 45% reduction in patients who were in H&Y3, H&Y4 or H&Y5. Sensitivity analysis indicated that incremental costs varied between $31,146 and $130,888. CONCLUSIONS: Clinical trials results for rasagiline (1 mg/day) indicated that the change in relative progression rate versus placebo could yield substantial economic and clinical benefits over a 25 year horizon. PND28 MOBILITY, INDIRECT COSTS, AND HEALTH-RELATED QUALITY OF LIFE IN MULTIPLE SCLEROSIS Coleman CI1, Roberts MS2, Sidovar M3 1 University of Connecticut School of Pharmacy, Hartford, CT, USA, 2University of Connecticut/ Hartford Hospital Evidence-based Practice Center, Hartford, CT, USA, 3Acorda Therapeutics, Inc., Hawthorne, NY, USA

OBJECTIVES: The mobility impairment associated with multiple sclerosis (MS) may have an impact on employment status, work productivity, indirect costs, and health-related quality of life (HRQoL). We estimated indirect costs and HRQoL (utilities) of MS patients in the United States (US). METHODS: The North American Committee on Multiple Sclerosis (NARCOMS) registry was used to conduct a crosssectional study of participants who completed the biannual update and supplemental Spring 2010 surveys. Demographic, employment status, income, mobility impairment, and health utility data were collected from registry participants who agreed to participate in the Mobility Study. Mean annual indirect costs per participant in 2011 USD and mean utilities for the population and for cohorts reporting different levels of mobility impairment were estimated. The Patient Determined Disease Steps, NARCOM’s mobility Performance Scale score, and question 1 of the 12-item Multiple Sclerosis Walking Scale were used to define levels of mobility impairment. Indirect costs were estimated using the human capital approach and utilities using the EuroQol 5-Dimension. RESULTS: Analyses included 3433 to 3616 participants, depending on survey completeness. Most participants were women (80.1%), ⱖ40 years of age (80.7%), and had MS for ⱖ10 years (84.9%). A total of 20.3% of participants experienced a relapse in the past 6 months and 40.4% were receiving a disease-modifying drug; 32% were not working or attending school. Total indirect costs per participant per year were estimated to be $21,680⫾20,730. The largest relative increases in indirect costs occurred at earlier impairment stages, regardless of the mobility impairment measure used. Participants’ mean utility score (0.73⫾0.18) was lower than that of a similarly aged sample from the general US population (0.87). As with indirect costs, the largest declines in utility were seen at earlier mobility impairment stages. CONCLUSIONS: Mobility impairment may contribute to increases in indirect costs and declines in HRQoL in MS patients. PND29 RESOURCE UTILIZATION AND CAREGIVER BURDEN ASSOCIATED WITH FRAGILE X SYNDROME IN THE UNITED STATES Bailey D1, Raspa M1, Mitra D1, Sacco P2 1 RTI International, Research Triangle Park, NC, USA, 2Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

OBJECTIVES: To assess the nature and extent of burden experienced by caregivers of patients with Fragile X Syndrome (FXS) in the United States (US). METHODS: A total of 351 caregivers enrolled in a FXS survey research registry completed a webbased (93%) or phone-based (7%) survey that captured information on health care utilization, financial burden, employment status, paid and unpaid caregiver hours, and caregiver injuries and mental health. RESULTS: Respondents (293 with male child; 58 with female) were mostly female (91%), Caucasian (92%), and married (84%) with an average age of 50 years. Caregivers reported low hospitalization rates (2%) and Emergency Department visits (6%) over the past 12 months. The most commonly seen specialists were ophthalmologists (33%), psychiatrists (33%), developmental-behavioral pediatricians (28%), and neurologists (22%). 40% of males and 22% of females needed at least one of 11 common medical tests/procedures (e.g. CT scan, X-Ray). Nearly 19% of patients needed general anesthesia/sedation for a dental procedure. 66% were on at least one prescription medication for problems related to FXS. On average, parents spent nearly 9 hours/day caring for their

child. They also obtained 5 hours of paid support/day. During the past 30 days, the average caregiver and their spouse took 19 hours off from work to care for their child. More than 35% reported that someone in their family had quit working, 28% turned down a job or promotion, 54% changed work hours, and 26% changed jobs. Nearly 29% reported being injured by their child with FXS (16 injuries per year by male children; 4 injuries per year by female children). 35% of caregivers reported seeking treatment for depression or anxiety, and 28% took prescription medications to treat these symptoms. CONCLUSIONS: Caring for a child with FXS is associated with substantial caregiver burden and increased health care utilization. PND30 HEALTH CARE RESOURCE UTILIZATION AND QUALITY OF LIFE IN PATIENTS WITH OVERACTIVE BLADDER DUE TO NEUROGENIC DETRUSOR OVERACTIVITY IN THE UNITED KINGDOM: A DATABASE ANALYSIS Tang D1, Colayco D2, Piercy J3, Patel V2, Globe D2 1 The University of Arizona, Tucson, AZ, USA, 2Allergan, Inc., Irvine, CA, USA, 3Adelphi Real World, Macclesfield, Cheshire, UK

OBJECTIVES: To evaluate health care resource utilization (HRU) and health-related quality of life (HRQOL) between United Kingdom (UK) Neurogenic Detrusor Overactivity (NDO) patients with and without adequate response to anticholinergics. METHODS: A retrospective database analysis was conducted using the Adelphi OAB Disease Specific Programme, a multi-national, cross-sectional survey reported from both patients’ and physicians’ perspectives. The population for this analysis was limited to UK NDO patients with OAB with or without incontinence, excluding those with stress incontinence. Inadequate response to anticholinergics was defined by switching anticholinergics due to lack of efficacy or tolerability. HRU indicators included: 1) paid employment; 2) OAB-related hospitalization in the past 12 months; 3) ever having undergone OAB-related surgery; and 4) number of physician visits due to their bladder condition in the past three months. HRQOL was measured by the Incontinence Quality of Life Questionnaire (I-QOL) total score. Statistical differences were tested using Fisher’s exact test for dichotomous outcomes and Wilcoxon rank-sum test for continuous outcomes. RESULTS: The UK sample of patients with OAB or urinary incontinence was 1304 patients recruited by 122 physicians. A total of 40 NDO patients who filled out a self-completion questionnaire were identified, of whom 24 (60%) had inadequate response to anticholinergics. A significantly higher proportion of patients with inadequate response to anticholinergics underwent OAB-related surgeries (N(%): 11(46%) vs. 0(0%), p⬍0.01) versus patients with adequate response. In addition, patients with inadequate response had significantly more physician visits (mean(SD): 3.6(2.7) vs. 1.7(1.6), p⫽0.03) and a statistically and clinically lower I-QOL total score (mean(SD): 49(18) vs. 72(23), p⬍0.01). The proportion of patients on paid employment or have had OAB-related hospitalization did not significantly differ between the groups. CONCLUSIONS: Patients with inadequate response to anticholinergics were more likely to have greater health resource utilization and lower quality of life compared with patients with adequate response. NEUROLOGICAL DISORDERS – Patient-Reported Outcomes & Patient Preference Studies PND31 ASSESSING THE RELATIONSHIP BETWEEN THE NUMBER OF NURSING SUPPORT ENCOUNTERS AND MEDICATION POSSESSION RATIO IN RELAPSING REMITTING MULTIPLE SCLEROSIS PATIENTS RECEIVING GLATIRAMER ACETATE Jones J, Scheidt D, Kaushal R, Carroll CA Teva Pharmaceuticals, Kansas City, MO, USA

OBJECTIVES: To evaluate the relationship between the numbers of patient encounters over a two year period and medication possession ratio (MPR) in patients receiving services through a voluntary support program sponsored by the manufacturer of Glatiramer Acetate. METHODS: De-identified patient records were derived from a decision support system used for normal business operations. Patient records were included in the evaluation if they were 1) continuously enrolled in the program for a minimum of 24 months, and 2) received Glatiramer Acetate. Patients were grouped into four cohorts based upon the average number of encounters with the support services over the two year enrollment period. Chi-squared statistics were used to assess variation in categorical variable and Analysis of Variance (ANOVA) compared mean values for continuous variables. RESULTS: A total of 10,989 patients were continuously enrolled in the support program between the dates of September 2002 and August 2011. The mean age of the study population was 45 years with no difference in mean age observed across the four cohorts (p⫽ 0.09). The mean MPR for the study population was 0.85. Patients utilizing the support services once or twice during the two year study period had a lower MPR (0.84) than patients who utilized the services more frequently (0.87). CONCLUSIONS: Data from retail and specialty pharmacy services included within the Invision DataMart™ estimates a MPR for Glatiramer Acetate of 0.76 to 0.80. Nursing support services for multiple sclerosis enhance patient adherence by up to about 15% over that observed through retail or specialty pharmacy services alone. Costs of such service accrue to the sponsor while the benefit of improved compliance (i.e. lower medical expenditures) accrues to payers. PND32 POTENTIAL HUMANISTIC BENEFITS OF PEGYLATION IN THE TREATMENT OF MULTIPLE SCLEROSIS: A SYSTEMATIC REVIEW OF THE LITERATURE Becker RV Russell Becker Consulting, Chicago, IL, USA

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OBJECTIVES: PEGylated interferon beta-1a (PEG-IFN beta-1a) is being developed for the treatment of relapsing-remitting multiple sclerosis (MS). PEGylated drugs are commonly used in other therapeutic areas, including oncology and hepatitis, but none are currently approved for MS. This study was conducted to gain a better understanding of the published humanistic and patient quality of life benefits of PEGylated drugs currently available for the treatment of other diseases. METHODS: A comprehensive search of medical literature published between 1985 and 2010 was conducted using PubMed/MEDLINE and supplemental searches. Reviewed references were prospective or retrospective studies reporting the tolerability, healthrelated quality of life (HRQOL), convenience, compliance, and patient preferences associated with PEGylated drugs. Only studies comparing PEGylated drugs to their corresponding non-PEGylated counterparts in the same therapeutic area were included in the analysis. RESULTS: Fifty-nine articles and 12 conference abstracts were reviewed. Eleven PEGylated drugs were identified, 6 of which had corresponding non-PEGylated counterparts. All 6 of these PEGylated drugs were administered less frequently than their non-PEGylated counterparts yet exhibited similar or greater efficacy, along with greater patient convenience. PEGylated drugs were generally tolerated as well as or better than their non-PEGylated counterparts. In HRQOL studies, patients who received PEGylated drugs reported better HRQOL than those receiving non-PEGylated drugs across a broad spectrum of domains, as well as in global HRQOL scores. For studies measuring quality-adjusted life-years (QALYs), PEGylated drugs were reported to produce more QALYs than their nonPEGylated counterparts. While few studies have evaluated patient medication compliance and patient preference/satisfaction, the published results of these studies also favor PEGylated drugs. CONCLUSIONS: PEGylated drugs are reported to be tolerated at least as well as their non-PEGylated counterparts and to be associated with higher HRQOL and greater patient preference/satisfaction, convenience, and compliance. PEG-IFN beta-1a may offer similar benefits to patients with MS. PND33 IS EQ-5D A PROXY FOR SUBJECTIVE WELL-BEING? A STUDY OF THE RELATIONSHIP BETWEEN HEALTH AND HAPPINESS IN PARKINSON’S DISEASE PATIENTS De Vries J1, Cubi-Molla P1, Devlin NJ2 1 City University, London, UK, 2Office of Health Economics, London, UK

OBJECTIVES: In light of the apparent disconnect between traditional measures of societal well-being such as GDP and reported levels of happiness, governments globally are turning their attention to alternative subjective measures of well-being (SWB) to aid policy decisions. In the context of health, there is therefore growing interest in understanding how measures of health-related quality of life (HRQoL), widely used in health technology appraisal, relates to SWB, and whether SWB could provide a sound basis for resource allocation decisions in health and other sectors in the future. This pilot study investigates the relationship between HRQoL, as measured by EQ-5D, and SWB in Parkinson’s Disease (PD) and the extent to which patients’ self-reported health can be used to predict their subjective wellbeing. METHODS: A paper questionnaire including EQ-5D, four key SWB questions taken from the Office for National Statistics Integrated Household Survey in England and other demographic details was distributed to people with PD in the United Kingdom. Responses were used to estimate multiple regression models explaining SWB using each of the EQ-5D Index (using UK weights), EQ-5D dimensions and EQ-VAS and patient socio-demographic characteristics. RESULTS: A total of 276 questionnaires were distributed and 183 responses received. The EQ-5D Index was generally a weak predictor of SWB in terms of life satisfaction, life being worthwhile, and happiness (adjusted R2 from 0.13 - 0.26), but EQ-VAS performed better (adjusted R2 from 0.28-0.40). The EQ-5D anxiety/depression dimension was a reasonable predictor of anxiety (adjusted R2⫽0.34). CONCLUSIONS: The findings imply that EQ-VAS and some dimensions of the EQ-5D, together with key demographic data such as household status, could potentially be used to predict SWB e.g. via mapping. However further empirical research into the relationship between SWB and EQ-5D longitudinally, and in different disease areas, is required to corroborate these findings, and further standardisation of SWB measures is recommended. PND34 PATIENT PERCEPTIONS OF PROPHYLAXIS IN CHRONIC AND EPISODIC MIGRAINE Sanderson JC1, Devine EB1, Bloudek LM2, Varon SF2, Sullivan SD3 1 University of Washington, Seattle, WA, USA, 2Allergan, Inc., Irvine, CA, USA, 3University of Washington, Seattle, WA, USA

OBJECTIVES: To assess and report utilization and patient perceptions of migraine prophylaxis therapy in chronic migraine (CM) and episodic migraine (EM). METHODS: A web-based survey evaluating the burden of migraine was administered to 32,782 subjects from 6 countries. Responders (n⫽16,663) were eligible for the main questionnaire if they were ⱖ 18 years of age, reported at least 1 headache during the last 3 months, and reported symptoms meeting diagnostic criteria for migraine. Eligible responders (n⫽ 1,183) were classified as CM or EM, based on reported headache frequency (ⱖ15 and ⬍15 headache days per month, respectively). For four medication classes (antidepressants, antiepileptics, beta blockers and calcium channel blockers), subjects reporting current usage rated their overall satisfaction, perception of headache improvement and experience with adverse effects. RESULTS: Respondents (n⫽1,165) were predominantly female (75.0%) with a mean age of 43.6 ⫾ 12.2 years. 42.3% (n⫽493) of subjects were classified as CM. More CM subjects reported ever taking prophylaxis (CM vs. EM: 62.8% vs. 39.9%, p⬍0.001) and trying two or more prophylactic therapies (CM vs. EM: 46.0% vs. 22.8%, p⬍0.001). Adjusting for age and gender, EM subjects were more likely to agree or

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strongly agree that their headaches had improved and that they were satisfied with their prophylactic therapy (respectively: OR 2.1, p 0.001; OR 1.9, p 0.004). Adjusted multivariate analyses showed similar results, but statistical significance was maintained for headache improvement only (respectively: OR 2.0, p 0.026; OR 1.2, p 0.584). CONCLUSIONS: These findings support previous reports that most migraineurs, including many CM patients, have never tried prophylaxis. Though migraine type (chronic vs. episodic) appears to influence patient perceptions of prophylaxis, perceptions are multifactorial. PND35 FICTITIOUS PREFERENCES OR FELICITOUS RECODING? CONJOINT RESPONDENTS WHO MAKE SENSE OF NONSENSICAL QUESTIONS Yang JC, Johnson FR RTI Health Solutions, Research Triangle Park, NC, USA

OBJECTIVES: Well-defined attributes are a cornerstone of choice-format conjoint studies (discrete-choice experiments). However, little is known about how ill-defined attributes affect the quality of stated-choice data. The objective of this study was to evaluate choice responses when attribute levels in the choice options do not align with a respondent’s personal current reference condition. METHODS: A total of 193 US adults with self-reported epilepsy who reported taking antiepileptic drugs (AEDs) to treat their seizures completed a web-enabled, choice-format conjoint survey. Respondents responded to a series of choice questions to assess their willingness to add another AED to control their seizures. Consistent with endpoints measured in a clinical trial, the efficacy attribute was defined as a 100%, 75%, 50% or 25% reduction in the number of seizures relative to the respondent’s current reference condition: each respondent’s own number of seizures over the last 3 months. Other treatment outcomes included short-term and long-term side effects, difficulty urinating, weight change, dosing frequency, and personal cost of the add-on AED. RESULTS: Respondents’ current treatment generally achieved good seizure control. Only one-third of the respondents reported having any seizures and 20% reported having only 1 to 3 seizures. Nevertheless, aggregate preference estimates for the 100%, 75%, 50% or 25% seizure-reduction levels were correctly ordered, statistically different from each other (with one exception), and were of sensible magnitudes relative to other treatment outcomes. Statistical tests indicated that there was no difference in preferences between respondents with ⬍ 4 seizures and those with 4 or more seizures. CONCLUSIONS: We have no information about how patients with few or no seizures evaluated meaningless percentage reductions in their reference condition. Their reinterpretation of the attribute levels, however, resulted in the same preference estimates as those for whom the levels were consistent with their experience. Thus, our respondents may just fix our mistakes. PND36 STRUCTURED BENEFIT-RISK ASSESSMENT OF TRIPTAN TREATMENTS USING PATIENT-PREFERENCE DATA Gonzalez JM1, Hauber AB1, Levitan B2, Coplan P3 1 RTI Health Solutions, Research Triangle Park, NC, USA, 2Johnson & Johnson PRD, Titusville, NJ, USA, 3Purdue Pharma L.P., Stamford, CT, USA

OBJECTIVES: To demonstrate the use of trade-off preferences from a conjoint analysis in a structured framework for benefit-risk assessment of migraine treatments. METHODS: Efficacy and safety endpoints from a hypothetical clinical study of triptans in acute migraine were developed using the BRAT benefit-risk Framework to identify and define endpoints as treatment benefits or harms. This decision framework provides a foundation for selecting, organizing, understanding and summarizing evidence relevant to benefit-risk decisions. To assess the relative importance of these benefits and harms, we used a choice-format conjoint survey, also known as discrete-choice experiment, to elicit migraineurs’ preferences for clinical endpoints and to develop a set of importance weights for each endpoint. These importance weights were then used to weigh mock clinical evidence and demonstrate several means to assess the benefits and risks of triptans. We estimated several weighted measures of benefit-risk including incremental net clinical benefit, the probability that benefit exceeds harm, and maximum acceptable risk. RESULTS: A total of 201 self-reported migraineurs completed the conjoint-analysis survey. The most important outcome evaluated by migraineurs was the chance of dying from a myocardial infarction. The least important outcome was the chance that a migraine would return 24 hours after taking medication. Preferences for outcomes differed by gender. Weighted incremental net clinical benefit, the probability that benefit exceeds harm and maximum acceptable risk varied depending on patient subgroup. CONCLUSIONS: Stakeholders routinely need to make judgments about the relative value of benefits and risks associated with treatments. Preference information is typically not explicitly used to aid in the evaluation of clinical benefit and risk data. The use of preference information in the BRAT Framework can help decision makers assess clinical evidence using a structured approach. The use of a variety of weighted benefit-risk measures provided several perspectives by which decision makers can assess the decision. PND37 PREDICTORS OF POOR HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH EPILEPSY: INSIGHT FROM THE PATIENTSLIKEME® EPILEPSY COMMUNITY de la Loge C1, Dimova S1, Mueller K2, Durgin T3, Massagli MP4, Wicks P4 1 UCB Pharma, Brussels, Belgium, 2UCB Pharma, Monheim, Germany, 3UCB Pharma, Smyrna, GA, USA, 4PatientsLikeMe, Cambridge, MA, USA

OBJECTIVES: To identify predictors of poor health-related quality of life (HRQoL) in members of the free online PatientsLikeMe Epilepsy Community. METHODS: The PatientsLikeMe Epilepsy Community (launched January 2010) allows patients with epilepsy to record, monitor and share their socio-demographic and disease char-