Association Between Persistence with Oral Atypical Antipsychotic Medications and Hospital and Emergency Department Utilization in Medicaid Patients with Schizophrenia.

Purpose: To examine 1-year persistence with oral atypical antipsychotics (OAAPs) for Medicaid patients with schizophrenia and assess the association between OAAP persistence and hospital and emergency department (ED) resource utilization. Patients and Methods: Using 2016-2020 multi-state Medicaid claims data, this retrospective study followed patients diagnosed with schizophrenia for 12 months after initiating OAAP therapy. Patients started on an OAAP with no evidence of antipsychotic use in the previous 6 months were included if they had a diagnosis of schizophrenia, were not dually enrolled in Medicaid and Medicare, did not switch to a long-acting injectable antipsychotic, and were continuously eligible 6 months before and 12 months after the initial OAAP prescription (index date). OAAP persistence was measured allowing for a <60-day gap. All-cause and schizophrenia-related inpatient and emergency department (ED) resource utilization during the follow-up period were compared between OAAP persistent and non-persistent groups. Results: The study sample of 13,007 had an average age of 39.1 years and 57.0% were male. Patients were persistent with their index OAAP for 135 days on average and 73.1% had a ≥60-day gap in antipsychotic therapy post-index. While 32.8% and 28.6% of patients who did not persist with their index OAAP restarted the index OAAP or switched to a different OAAP medication later in the year, respectively, a larger proportion (38.6%) had no further OAAP prescriptions. After adjustment for demographic and clinical variables, compared to non-persistent patients, persisting with OAAPs was significantly associated with fewer all-cause and schizophrenia-related hospitalizations (Incidence Rate Ratio [IRR]=0.742, p<0.001; IRR=0.823, p<0.001; respectively) and ED visits (IRR=0.759, p<0.001; IRR=0.773, p<0.001; respectively). Conclusion: Non-persistence with OAAP medication is common among patients with schizophrenia and associated with negative outcomes including increased utilization of hospital and ED resources. Patient-centered interventions that improve antipsychotic persistence should be implemented to facilitate optimal outcomes in this population.

One-Year Medication Treatment Patterns, Healthcare Resource Utilization, and Expenditures for Medicaid Patients with Schizophrenia Starting Oral Atypical Antipsychotic Medication.

Oral atypical antipsychotic (OAAP) medications are the most commonly prescribed treatment for the management of schizophrenia symptoms. This retrospective study, using Medicaid claims data (2016-2020), followed patients for 12 months after initiating OAAP therapy. Study outcomes included OAAP adherence, switching, augmentation, healthcare resource utilization (HRU), and expenditures. All-cause and schizophrenia-related HRU and expenditures were compared between adherent and nonadherent cohorts. Among 13,007 included patients (39.1 ± 12.8 years of age, 57.0% male, 36.1% Black, 31.8% White, 9.7% Hispanic), 25.7% were adherent to OAAPs (proportion of days covered [PDC] ≥ 0.8). During the 1-year follow-up period, Black individuals were in possession of an OAAP for an average of 166 days compared to 198 and 202 days for White and Hispanic patients, respectively. Approximately 16% of patients switched OAAP medications and 3.2% augmented therapy with an OAAP added to their index medication. Nearly 40% of patients were hospitalized during follow-up and 68.4% had emergency department (ED) visits. A greater proportion of nonadherent patients had all-cause inpatient (41.7% vs. 34.1%, p < 0.001) and ED visits (71.7% vs. 58.8%, p < 0.001) compared to adherent patients. Annual total healthcare expenditures were $21,020 per patient; $3481 higher for adherent versus nonadherent patients. Inpatient expenditures comprised 44.6% and 30.6% of total expenditures for nonadherent and adherent patients, respectively. Hospitalized patients' total expenditures were $23,261 higher compared to those without a hospitalization. Adherence to OAAP medication is suboptimal and associated with increased utilization of costly hospital and ED resources. Efforts to improve therapies and increase medication adherence could improve clinical and economic outcomes among individuals with schizophrenia.

Treatment Patterns and Healthcare Resource Use in Medicare Beneficiaries with Parkinson's Disease.

Background: Studies on real-world treatment patterns and long-term economic burden of Parkinson's disease (PD) have been limited. Objective: To assess treatment patterns, healthcare resource utilization (HRU), and costs associated with PD symptoms and treatment-related adverse events (AEs) among Medicare beneficiaries in the United States. Methods: A 100% Medicare Fee-For-Service data (2006-2020) of patients with PD were analyzed. PD treatment patterns were described for the subset of patients who had no previously observed PD treatments or diagnoses (ie, the incident cohort). HRU and healthcare costs associated with PD symptoms were assessed for all patients with PD (ie, the overall cohort) and that associated with treatment-related AEs were assessed for the subset of patients who received PD treatments after PD diagnosis (ie, the active treatment cohort), using longitudinal models with repeated measures. Results: Overall, 318,582 patients were included (mean age at PD diagnosis: 77.4 years; 53.3% female). Among patients in the incident cohort (N=214,829), 51.1% initiated levodopa monotherapy and 5.9% initiated dopamine agonists (DAs) monotherapy as first-line treatment. The proportion of incident patients treated with DAs and other PD therapies generally increased from post-diagnosis years 1 to 10. The median time from diagnosis to PD treatment initiation was 2.0 months; the median time to treatment discontinuation was the longest with levodopa (18.7 months), followed by DAs (9.5 months). In the overall cohort, PD symptoms, especially motor symptoms and severe motor symptoms, were associated with significantly higher rates of HRU and costs. In the active treatment cohort (N=234,298), treatment-related AEs were associated with significantly higher rates of HRU and medical costs. Conclusion: While levodopa is still the mainstay of PD management, considerable heterogeneity exists in real-world treatment patterns. Overall, PD symptoms and AEs were associated with significantly higher HRU and healthcare costs, suggesting unmet medical needs for PD treatments with better tolerability profiles.

Work Loss and Direct and Indirect Costs Associated with Parkinson's Disease.

Purpose: To examine work loss and indirect costs during the three-year periods prior to and following initial diagnosis of Parkinson's disease (PD) in patients and in spouses of PD patients, as well as direct costs of healthcare. Patients and Methods: This is a retrospective, observational cohort study using the MarketScan Commercial and Health and Productivity Management databases. Results: A total of 286 employed PD patients and 153 employed spouses met all diagnostic and enrollment criteria for short-term disability (STD) analysis (PD Patient cohort and Caregiving Spouse cohort). The proportion of PD patients having a STD claim increased from roughly 5% and plateaued at around 12-14% starting in the year prior to first diagnosis of PD. The mean number of days lost from work due to STD per year increased from 1.4 days in the 3rd year prior to diagnosis to 8.6 days in the 3rd year after diagnosis (corresponding to an increase in indirect costs from $174 to $1104). STD use for spouses of patients with PD was lowest in the year after their spouses were diagnosed and then rose dramatically in the 2nd and 3rd years after the spouse's diagnosis. Total all-cause direct health-care costs increased during the years leading up to PD diagnosis and were highest in the years following diagnosis, with PD-related costs contributing ~20-30% of the total. Conclusion: PD has both a significant direct and indirect financial burden on patients and their spouses when analyzed for 3 years before and after diagnosis.

Dopamine agonist monotherapy utilization in patients with Parkinson's disease.

Objectives: To characterize patients with Parkinson's disease (PD) who initiated dopamine agonist (DA) monotherapy, describe medication utilization and provider types, and estimate medication adherence and discontinuation rates. Methods: Retrospective study identified patients with PD in the Optum Research Database and included those with ≥1 claim for DA or levodopa between 09/01/2012 and 12/31/2018, ≥2 PD diagnoses, commercial or Medicare Advantage Part D (MAPD) insurance, ≥40 years old, and continuous medical and pharmacy coverage ≥12 months before and after index date. A subset of patients receiving DA monotherapy was selected for this analysis. Variables were analyzed descriptively. Adherence was measured with medication possession ratio (MPR) and proportion of days covered (PDC); defined as ≥0.80. Results: Patients (N = 642) had mean (SD) age of 70.2 (9.9) years, 70.6 % had MAPD coverage, and 61.7 % were male. Neurologists prescribed 64.6 % of DA monotherapy, and 56.9 % of patients had ≥2 PD diagnoses before or on the index date. Index therapy was discontinued by 44.1 % of patients, and 55.9 % persisted for 12 months without change. Mean (SD) time to discontinuation was 102 (79) days. Mean (SD) MPR for patients (n = 562) with ≥2 fills was 0.84 (0.2); 70.3 % were MPR adherent. Mean (SD) PDC for all 642 patients was 0.66 (0.3); 50.5 % were PDC adherent. Conclusion: Adherence and continuation of therapy were suboptimal, which could translate into poor patient outcomes. Future studies could provide insights on the impact of low adherence and persistence with DA monotherapy.

Exploring access to care from the perspective of patients with breast cancer: A qualitative study.

OBJECTIVES: Patients face a myriad of personal and system-based challenges in accessing breast cancer care, but less is known about access as expressed and experienced by patients themselves. The objective of this qualitative study was to further explore the breadth of issues related to access from the perspective of patients with breast cancer across their care journey. METHODS: Twelve women participated in 1-h semi-structured interviews and 48 women participated in 2-h focus groups at six oncology practices in 2018. Grounded theory was used to analyze the data. RESULTS: Six primary themes emerged concerning access to care: information, psychosocial support, health insurance, financial resources, timeliness, and emotions. CONCLUSIONS: This study identified six core dimensions of access to care. Access encompassed not only gaining entrée to care services-in the traditional sense of access-but also the continuing support needed to effectively use those services throughout the cancer care journey. Future strategies aimed at improving access to breast cancer care should attend to these ongoing patient-centric and system-based issues which are mostly amenable to change.

Levodopa treatment patterns in Parkinson's disease: A retrospective chart review.

BACKGROUND: Medication regimens for Parkinson's disease (PD) may change as the disease progresses, symptoms fluctuate, or medication-related adverse events occur. This study evaluated treatment trends by observation year for patients initially receiving monotherapy with levodopa and a peripheral dopa decarboxylase inhibitor (PDDI). METHODS: In this retrospective chart review, therapy changes were evaluated for patients across the US diagnosed with PD on or before 6/30/2014 who initially received levodopa-PDDI monotherapy. Index date was the first clinic visit. Post-index was any time between the first 31 days after index and study end (6/30/2019). Index Hoehn-Yahr (H-Y) score and medication changes were also analyzed by index low (<400 mg/day) or high (≥400 mg/day) levodopa doses in the levodopa-PDDI combinations. RESULTS: In the levodopa-PDDI cohort (n = 95), there were 0.39 dose escalations, 0.16 dose reductions, 0.12 discontinuations, 0.19 therapy switches, and 0.24 add-ons per patient per year during the study. Most dose escalations or add-ons occurred within the first 6 months post-index. Of those who ever stopped levodopa-PDDI (n = 34), 31 (91%) restarted within the study period. Most (83%) patients who restarted levodopa-PDDI did so in the same year as stopping treatment. Index low dose users were associated with lower H-Y scores, were more inclined to escalate their dose, and were less inclined to reduce their dose in the first 2 years of treatment than index high dose users. CONCLUSIONS: Prescribers and patients tend to experiment with levodopa-PDDI treatment. Although many patients appeared to stop levodopa-PDDI after an initial course of treatment, most subsequently restarted treatment.

Natural history and patterns of treatment change in Parkinson's disease: A retrospective chart review.

BACKGROUND: Parkinson's disease (PD) management seeks to balance the benefits and harms of current medications and evolves as the disease progresses. The natural history of PD and associated patterns of treatment change were analyzed to identify unmet needs in treatment of PD symptoms. METHODS: Medical charts of patients from clinics across the US diagnosed on or before June 30th, 2014 were retrospectively reviewed. Index date was the first clinic visit, and the post-index period was through study end (June 30th, 2019). Outcomes included the frequency of therapy changes in the post-index period, reasons for therapy change, and adverse events (AE). RESULTS: Patients (n = 203) at index were receiving levodopa-peripheral dopa decarboxylase inhibitor (PDDI) monotherapy (47%), dopaminergic agonist (DA) monotherapy (15%), monoamine oxidase B inhibitor (MAOBI) monotherapy (14%), or combination therapies. The percentage of patients in Hoehn-Yahr disease Stage 1-2 was 52% at index and 20% by the end of the study. Frequencies of motor, non-motor, and neuropsychiatric symptoms increased during the enrollment. Levodopa-PDDI monotherapy and levodopa-PDDI + MAOBI had the lowest rates of therapy changes. Symptom relapse was the most common reason for dose escalation, add-on, and dose reduction, whereas AEs were the most common reason for discontinuation and switching. Dose escalation, add-on, and forward switch were most likely to occur in the first 6 months of treatment. CONCLUSIONS: Therapy changes during the study period reflected the challenging and evolving management of PD as the disease progresses. New or add-on symptomatic treatments are needed that are well-tolerated and able to control PD symptoms.

An assessment of Parkinson's disease medication treatment patterns in the Medicaid population.

INTRODUCTION: Most Parkinson's disease (PD) medication adherence studies have focused on patients with commercial or Medicare health insurance coverage. However, less is known regarding medication treatment patterns within the Medicaid population. METHODS: This retrospective cohort study utilized 2011-2019 administrative healthcare claims from 7 state Medicaid programs. We compared newly diagnosed patients with PD started on either levodopa or a dopamine agonist (DA). Baseline comorbidities were compared. Outcomes were assessed during a 12-month post-index observation period, and included total medication days, proportion of days covered (PDC), adherence status, persistence to initiating PD medication, and time to non-persistence of initiating PD medication. RESULTS: Our study sample of 805 Medicaid patients had an average age of 54.1 years, with 52.0% being female. Levodopa was the predominant PD medication at initiation (75.4%). Roughly half of patients had a baseline depressive disorder and nearly 40% had an anxiety disorder. Levodopa patients had a significantly higher PDC compared to DA patients (0.621 vs. 0.546, p = 0.007). An adjusted logistic regression model showed no significant difference in the number of adherent patients between the two groups (p = 0.058). An adjusted Cox proportional hazards model controlling for demographic and baseline variables showed a 26% lower risk of non-persistence for levodopa patients versus DA patients (HR 0.740, CI 0.597-0.917, p = 0.006). CONCLUSIONS: Adherence and persistence rates were suboptimal following initiation of either levodopa or DA medication for patients with PD in Medicaid programs, though rates were better for those initiated on levodopa.

Parkinson disease among patients treated for benign prostatic hyperplasia with α1 adrenergic receptor antagonists.

BACKGROUNDRecently the α1 adrenergic receptor antagonist terazosin was shown to activate PGK1, a possible target for the mitochondrial deficits in Parkinson disease related to its function as the initial enzyme in ATP synthesis during glycolysis. An epidemiological study of terazosin users showed a lower incidence of Parkinson disease when compared with users of tamsulosin, an α1 adrenergic receptor antagonist of a different class that does not activate PGK1. However, prior research on tamsulosin has suggested that it may in fact potentiate neurodegeneration, raising the question of whether it is an appropriate control group.METHODSTo address this question, we undertook an epidemiological study on Parkinson disease occurrence rate in 113,450 individuals from the United States with 5 or more years of follow-up. Patients were classified as tamsulosin users (n = 45,380), terazosin/alfuzosin/doxazosin users (n = 22,690), or controls matched for age, sex, and Charlson comorbidity index score (n = 45,380).RESULTSIncidence of Parkinson disease in tamsulosin users was 1.53%, which was significantly higher than that in both terazosin/alfuzosin/doxazosin users (1.10%, P < 0.0001) and matched controls (1.01%, P < 0.0001). Terazosin/alfuzosin/doxazosin users did not differ in Parkinson disease risk from matched controls (P = 0.29).CONCLUSIONThese results suggest that zosins may not confer a protective effect against Parkinson disease, but rather that tamsulosin may in some way potentiate Parkinson disease progression.FUNDINGThis work was supported by Cerevel Therapeutics.

Evaluation of access to care issues in patients with breast cancer.

AIMS: System-level efforts have been deployed to improve oncology care and access while reducing utilization and costs. Understanding the nature of access to care from the perspective of patients themselves is an unmet need. This study examined access to care in a population of women with breast cancer and its relationship to overall patient satisfaction. MATERIALS AND METHODS: Patients with breast cancer from six oncology clinics in five states completed a survey during routine office visits. Access to care (higher scores indicated increasing access barriers), overall patient satisfaction, and patient demographic/clinical characteristics were measured. The relationships between access (composite and factor scores) and satisfaction were assessed using multivariable analyses controlling for age (the only significant characteristic from bivariate analyses). RESULTS: A total of 180 patients completed the survey. Factor analysis of access to care items revealed an 8-factor measure - Insurance, Health System, Emotional, Holistic Treatment, Family Support, Knowledge/Understanding, Information Quality, and Financial Support - with high reliability (Composite: Cronbach alpha = 0.93; Factors: Cronbach alpha range = 0.85-0.91). Access composite score was moderately low (mean = 1.90), indicating an overall low level of access barriers, and overall patient satisfaction was high (mean = 4.59). The composite score (p < .001) and the Health System and Knowledge/Understanding factors (p < .01) were significant and negative predictors of overall satisfaction. LIMITATIONS: Study sites were high functioning clinics and all, but one, are Oncology Care Model practices. Thus, the scope of access to care issues for patients of under-resourced clinics might not be well addressed. CONCLUSIONS: Access to care overall and by factor was significantly predictive of patient satisfaction with care. In addition, access to care factors varied across several demographic and clinical characteristics. Future strategies that address access to care challenges should consider these modifiable, patient-centric, and system-based issues.

Drug Treatment Value in a Changing Oncology Landscape: A Literature and Provider Perspective.

BACKGROUND: The U.S. health care system's transition to a value-based reimbursement model holds important implications for medical innovation, care delivery, and value-based assessments of therapeutic interventions. This transition has been especially noteworthy in oncology, with substantial ongoing changes to payer reimbursement and the provider landscape, as well as the introduction of value frameworks to guide drug treatment decision making. The implications of these changes for provider assessments of drug value and evidence needs remain unclear. OBJECTIVES: To understand provider perspectives on drug value assessment and the utility of existing oncology value frameworks by identifying (a) key value-based trends in the evolving oncology landscape, (b) provider definitions of drug value, (c) the role of existing value frameworks in provider decision making, and (d) future provider evidence needs for making value-based treatment decisions. METHODS: We conducted a literature review to identify existing oncology value frameworks and definitions of drug treatment value in oncology. Using a structured discussion guide informed by this literature review, we conducted 12 telephone-based in-depth interviews in November and December 2017 with U.S. oncology providers involved in organizational drug treatment and formulary decision making within their practices. Responses to interview questions were analyzed and reported as averages and percentages across participants. RESULTS: Of 293 publications identified by keyword searches, 35 relevant articles were identified. Among these, the literature review identified no common definition for providers to assess drug value. Interview research participants described large ongoing changes in the oncology provider landscape, with economic pressures from payers as the foremost leading factor. Although 5 value frameworks were found in the literature, interviews found that in practice few providers consider these value frameworks to be key influences when evaluating treatment or formulary decisions. Furthermore, while 83% of participants' organizations employed some form of internal clinical pathways, only the minority (25%) with pathways integrated in their electronic medical record (EMR) systems saw these pathways as significantly affecting clinicians' drug treatment decision making. To aid the ongoing shift from volume-based to value-based care, we found that, rather than value frameworks, providers are looking for patient-level tools to make more appropriate drug decisions. CONCLUSIONS: Payer reimbursement pressures are leading to radical changes in the oncology provider landscape, and there is a need for improved guidance for providers in assessing drug value. In particular, this study identifies the need for a timely and multifaceted summary of information required to assess the value of alternative treatment options for a given patient. Manufacturers also need to make significant strides to help generate and improve the dissemination of evidence to support the value of their therapies. DISCLOSURES: Funding for this work was provided by Novartis Pharmaceuticals. The study sponsor was involved in study design, data interpretation, and data review. All authors contributed to the development of the manuscript and maintained control over the final content. Sasane, Howe, Wong, and Zacker were employees of Novartis at the time of this study. Frois, Jarvis, and Grice are or have been employed by Analysis Group, which received a grant from Novartis for this research. At the time of this study, Analysis Group received funding from multiple manufacturers with oncology products in their portfolio during this time period, including, but not limited to, Astellas and Genentech.

Associations Between Treatment Satisfaction, Medication Beliefs, and Adherence to Disease-Modifying Therapies in Patients with Multiple Sclerosis.

BACKGROUND: Adherence to disease-modifying therapy (DMT) remains problematic for many patients with multiple sclerosis (MS). An improved understanding of factors affecting DMT adherence may inform effective interventions. This study examined associations between treatment satisfaction, medication beliefs, and DMT adherence. METHODS: A survey was mailed in 2016 to 600 adult patients with relapsing-remitting MS taking an injectable or oral DMT. Patients were sampled from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. The survey measured self-reported DMT adherence (doses taken divided by doses prescribed during previous 2-week period-adherence ≥0.80), DMT satisfaction using the Treatment Satisfaction Questionnaire for Medication version II, medication beliefs using the Beliefs About Medicines Questionnaire, and demographic and clinical covariates. Relationships between variables were examined using multivariate logistic regression. RESULTS: Final analyses included 489 usable surveys. Mean ± SD participant age was 60.5 ± 8.3 years. Most respondents were white (93.8%), female (86.6%), taking an injectable DMT (66.9%), and adherent to DMT (92.8%). Significant predictors of DMT adherence were age (odds ratio [OR], 1.086; 95% CI, 1.020-1.158; P = .011), type of DMT (oral vs. injectable; OR, 23.350; 95% CI, 2.254-241.892; P = .008), and DMT experience (naive vs. experienced; OR, 2.831; 95% CI, 1.018-7.878; P = .046). CONCLUSIONS: In patients with MS sampled from a patient registry, treatment satisfaction and medication beliefs were not significantly associated with DMT adherence. Based on significant predictors, younger patients, patients taking injectable DMTs, and patients with previous experience with another DMT(s) are at higher risk for nonadherence. Future research is warranted to assess relationships between variables in more diverse MS populations.

Outcomes-Based Contracting Experience: Research Findings from U.S. and European Stakeholders.

BACKGROUND: Outcomes-based contracts (OBCs), a type of risk-sharing arrangement (RSA), have emerged as a promising avenue for payers to engage with pharmaceutical manufacturers to share risk and improve patient access to medicines via evaluation of real-world outcomes. OBJECTIVE: To assess the level of recent OBC activity and stakeholder perceptions of these arrangements, as well as the outlook for future OBC activity from a payer and manufacturer perspective in the United States and EU-5 (France, Germany, Italy, Spain, and the United Kingdom). METHODS: Using a structured questionnaire, interviews were conducted with 27 experts, including 14 U.S. payers, 5 EU-5 national payers, and 8 manufacturer pricing/market access executives (4 U.S., 4 EU-5). We also used the University of Washington's Performance Based Risk-Sharing (PBRS) database and other targeted publicly available information. RESULTS: Publicly disclosed information on OBCs understates the level of OBC activity, since many arrangements are confidential. Overall, U.S. and EU-5 interviewees generally expected that 2 to 3 times more OBCs would be implemented in the next 5 years than in the previous 5 years. Key drivers included the introduction of a national OBC framework in Spain, potentially a similar framework in the United Kingdom, a growing sickness fund activity in Germany, and a U.S. movement towards accountable care. Motivation for OBCs varied markedly across markets and stakeholders, with operational feasibility noted as a significant hurdle in the United States and France. Along with improving health outcomes, cost and financial risk reduction were the primary OBC motivators for payers, while potential access or reimbursement gains were key factors for manufacturers. CONCLUSIONS: Using direct input from U.S. and EU-5 payer and pharmaceutical manufacturer decision makers, this research suggests that high OBC growth is expected in the EU-5 and, to a more moderate extent, in the United States, particularly if clear, simpler OBC frameworks can be developed. DISCLOSURES: This study was funded by Novartis Pharmaceuticals. Novartis employees were involved in all aspects of this study. Vegesna and Sasane are employed by and own stock in Novartis. Nazareth and Ko were employees of Novartis at the time of this study. Frois, Demean, Carpenter, and Wu are or have been employed by Analysis Group, which received a grant from Novartis for this research. Navarro received consulting fees from Novartis for his involvement in this research. Study concept and design were contributed by Sasane, Frois, Nazareth, and Wu. Navarro, Demean, and Frois took the lead in data collection, assisted by Carpenter, Ko, and Nazareth. Data interpretation was provided by Frois, Carpenter, Nazareth, and Ko, along with Sasane, Demean, Wu, and Navarro. The manuscript was written by Frois, Demean, Nazareth, and Ko, along with Sasane, Carpenter, Wu, and Navarro, and revised by Frois, Ko, and Vegesna, along with Sasane, Nazareth, Wu, and Navarro.

Estimating minimal important differences for several scales assessing function and quality of life in patients with attention-deficit/hyperactivity disorder.

OBJECTIVE: Defining minimal important difference (MID) is critical to interpreting patient-reported outcomes data and treatment efficacy in clinical trials. This study estimates the MID for the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) and the Child Health and Illness Profile-Parent Report (CHIP-CE-PRF76) among parents of young people with attention-deficit/hyperactivity disorder (ADHD) in the UK. METHODS: Parents of children (6-12 years; n=100) and adolescents (13-17 years; n=117) with ADHD completed a socio-demographic form, the CHIP-CE-PRF76, the WFIRS-P, and the Pediatric Quality of Life scale at baseline and 4 weeks later. At follow-up, a subset of parents completed anchor questions measuring change in the child/adolescent from baseline. MIDs were estimated using anchor-based and distribution-based methods, and separately for children and adolescents. RESULTS: The MID estimates for overall change in the WFIRS-P total score ranged from 11.31 (standard error of measurement) to 13.47 (anchor) for the total sample. The range of MID estimates for the CHIP-CE-PRF76 varied by domain: 6.80-7.41 (satisfaction), 6.18-7.34 (comfort), 5.60-6.72 (resilience), 6.06-7.57 (risk avoidance), and 4.00-5.63 (achievement) for the total sample. Overall, MID estimates for WFIRS-P MID and CHIP-CE-PRF76 were slightly higher for adolescents than for children. CONCLUSION: This study estimated MIDs for these instruments using several methods. The observed convergence of the MID estimates increases confidence in their reliability and could assist clinicians and decision makers in deriving meaningful interpretations of observed changes in the WFIRS-P and CHIP-CE in clinical trials and practice.

Increasing Patient Involvement in Drug Development.

BACKGROUND: To ensure the creation of treatments that maximize value at the lowest cost, all aspects of the health care system need to align with patient needs and preferences. Despite growing efforts to engage patients in research and regulatory activities, the pharmaceutical industry has yet to maximize patient involvement in the drug development process. OBJECTIVE: To gain a better understanding of the present state of patient involvement in drug development. METHODS: Through a semistructured interview methodology, we sought to identify opportunities, barriers, and examples of patient involvement in the drug development process. Telephone interviews were conducted with six senior leaders of evidence generation within the pharmaceutical industry and four patients. These interviews were supplemented with interviews with a research funder, a regulator, a patient advocacy group, and a caregiver. RESULTS: Although our interviewees spoke of the potential benefits of aligning research around the needs of patients, there were few examples they could share to suggest this was occurring at scale. A number of barriers were identified including the added burden associated with adverse event reporting, concerns about patient representativeness or their ability to participate in drug development conversations, and the costs in time and resources involved relative to returns on investment. CONCLUSIONS: As health care systems continue to evolve and establish patients as the primary stakeholder in their health care decision making, the pharmaceutical industry will need to be innovative to demonstrate the value of their products relative to the outcomes experienced by patients. Pharmaceutical companies should recognize the value of involving patients across the entire product life cycle and work to transform present perceptions and practices throughout their organizations.

The real-world patient experience of fingolimod and dimethyl fumarate for multiple sclerosis.

BACKGROUND: Oral disease-modifying therapies offer equivalent or superior efficacy and greater convenience versus injectable options. OBJECTIVES: To compare patient-reported experiences of fingolimod and dimethyl fumarate. METHODS: Adult relapsing-remitting multiple sclerosis patients treated with fingolimod or dimethyl fumarate were recruited from an online patient community and completed an online survey about treatment side effects, discontinuation, and satisfaction. RESULTS: 281 patients in four groups completed the survey: currently receiving fingolimod (CF, N = 61), currently receiving dimethyl fumarate (CDMF, N = 129), discontinued fingolimod (DF, N = 32) and discontinued dimethyl fumarate (DDMF, N = 59). Reasons for treatment switch were to take oral treatment (CF: 63.3 %, CDMF: 61.8 %), side effects of prior medication (CF: 67.3 %, CDMF: 44.1 %) and lack of effectiveness of prior medication (CF: 38.8 %, CDMF: 31.4 %). Main reasons for discontinuation were side effects (DF: 46.9 %, DDMF: 67.8 %) and lack of effectiveness (DF: 25.0 %, DDMF: 15.3 %). CDMF patients had an increased risk of abdominal pain, flushing, diarrhea, and nausea. Treatment satisfaction was highest among CF patients followed by CDMF, DF, and then DDMF patients. CONCLUSIONS: Discontinuation was driven by experience of side effects. Patients currently taking dimethyl fumarate were more likely to experience a side effect versus patients currently taking fingolimod. Examination of the relationship between tolerability and adherence/persistence is needed.

Persistency, medication prescribing patterns, and medical resource use associated with multiple sclerosis patients receiving oral disease-modifying therapies: a retrospective medical record review.

BACKGROUND: In the US, the approved multiple sclerosis (MS) oral disease-modifying therapies (ODMTs) are fingolimod (FTY), teriflunomide (TFN), and dimethyl fumarate (DMF). FTY and TFN are recommended with once-daily doses with no up-titration, whereas DMF treatment is recommended twice-daily (BID) and is initiated with a 7-day starter dose of 120 mg BID before up-titration to the maintenance dose of 240 mg BID. Limited information exists regarding real-world ODMT prescribing patterns to aid physician/patient decision-making. METHODS: Eligible patients for this retrospective medical record review were ≥18 years, had one visit related to ODMT initiation (index visit), and ≥1 visit within 12 months before and after the index visit. Primary objectives were to assess post-index ODMT persistency (i.e., discontinuation), prescribing patterns (medication switching, dose up-titrations, dose reduction, re-starts, and add-ons) and medical resource utilization (office-visits, MRI procedures, and mobility indicators) at distinct time windows of 3, 6, 9, and 12 months. Chi-square or Wilcoxon Rank Sum tests were used for 3-way ODMT group comparisons. RESULTS: Medical records of 293 MS-diagnosed patients using ODMTs were abstracted from 19 US-based neurology clinics between December 31, 2010 and June 30, 2014 (FTY: 101; DMF: 133; TFN: 59). Persistency rates among ODMT groups were similar. MS-related medication switching, dose reduction, re-starts, and add-ons were infrequently observed and were similar across ODMT groups. Of DMF patients with a confirmed starting dose of 120 mg BID with ≥12 months follow-up (n = 26), the percentage who were prescribed dose up-titrations to the recommended maintenance DMF dose was 23.1 % at 1-3 months, 26.9 % at 4-6 months, 42.3 % at 7-9 months, and 0 % at 10-12 months. There were no significant differences at any time window among the ODMT groups in the number of office visits or percent of patients receiving MRIs. Mobility indicator patterns (proportion of patients with abnormal gait, wheelchair use, etc.) were consistent over time. CONCLUSIONS: There was no difference in persistency, prescribing patterns (medication switching, dose reduction, re-starts, and add-ons) or medical resource utilization (office-visits, MRI procedures, and mobility indicators) among the ODMTs. However, in a small sub-group of patients, delays of up to 9 months in DMF dose-up titration to the recommended maintenance dose were observed.

Determinants of high cost in multiple sclerosis patients: a claims and chart review study.

OBJECTIVE: To identify factors associated with high cost multiple sclerosis (MS) patients using integrated administrative claims and medical charts data. METHODS: This study identified newly diagnosed MS patients (≥18 years) in a large United States managed care claims database between 1 January 2007 and 30 April 2011 using the ICD-9-CM code (340.xx). Mean annualized MS-related costs higher than the third quartile were categorized as high cost, lower than the first quartile as low, and the rest as medium. Patients were compared across cohorts with descriptive and inferential statistics. Baseline high cost factors were identified with multivariable logistic regression models. RESULTS: Administrative claims (n = 4342) and medical chart records (n = 400) data was evaluated. Mean (SD) annualized MS-related costs were $6313 ($14,177) for patients overall and $18,398 ($24,483) for high cost patients. Inpatient costs accounted for the largest proportion (49.69%) of MS-related costs among high cost patients. MS relapses and MS-related comorbidities were more prevalent in the high cost patients. In the multivariable analyses, patients with baseline use of antidepressants or corticosteroids, baseline muscle weakness, and initial treatment from a non-neurologist were likelier to be high cost MS patients. LIMITATIONS: MS-related clinical information was not completely available from medical chart data. The specificity of true MS-related costs may have been limited and the definition of the cost-based cohort segmentations was arbitrary. CONCLUSIONS: Overall, baseline use of MS-related medications, the presence of baseline MS-related comorbidities, MS relapses, and MS-related hospitalizations were significantly associated with high cost patients. Future comparative effectiveness studies of currently approved disease modifying therapies for MS may help to identify best strategies for individual patients to minimize clinical events that are associated with high disease related costs.

Burden of illness among patients with fragile X syndrome (FXS): a Medicaid perspective.

BACKGROUND: Fragile X syndrome (FXS) is an inherited intellectual disability that imposes a substantial clinical and humanistic burden on patients and caregivers. This study aimed to quantify the incremental burden of illness following FXS diagnosis in Medicaid populations. METHODS: A retrospective matched-cohort study was conducted using FL, NJ, MO, IA, and KS Medicaid claims (1997-2012). Patients with FXS were matched 1:5 to a comparison group without FXS, based on age, gender, state, and continuous Medicaid coverage. Healthcare resource utilization and costs were compared among cohorts over 1 year following first diagnosis. RESULTS: Overall, 697 patients with FXS were matched to 3485 non-FXS patients. Median age was 12.0 years; 82% were male. Newly diagnosed FXS patients were younger (median age: 7.0 years). During the follow-up, patients with FXS had significantly higher medication use, medical procedure use, medical specialist visits, and associated costs than the non-FXS comparison group. One-fourth of FXS patients filled prescriptions for stimulants, antipsychotics, or anticonvulsants; 25% of patients with FXS had speech and language therapy and 39% had physical therapy (versus 9%, 4% and 8%, respectively, for the comparison group). At least 44% of FXS patients visited a neurologist, cardiologist, otolaryngologist, or gastroenterologist; 92% of patients with FXS had an outpatient visit, 35% had an emergency room visit, and 34% used home services (compared to 31%-32%, 64%, 27%, and 10%, respectively, for the comparison group) (all p < 0.05). Patients with FXS had an incremental annual total healthcare cost of $33,409 (2012$) per person relative to the comparison group, while newly diagnosed FXS patients had incremental total annual healthcare costs of $17,617 (2012$) per person. CONCLUSIONS: Both established and newly diagnosed FXS were associated with significantly increased use of multiple medications and medical services, and increased healthcare costs. Treatments that could help reduce this disease burden are urgently needed.