Increased delay from initial concern to diagnosis of autism spectrum disorder and associated health care resource utilization and cost among children aged younger than 6 years in the United States.

BACKGROUND: Prolonged delays between first caregiver concern and autism spectrum disorder (ASD) diagnosis have been reported, but associations between length of time to diagnosis (TTD) and health care resource utilization (HCRU) and costs have not been studied in a large sample of children with ASD. OBJECTIVE: To address these informational gaps in the ASD diagnostic pathway. METHODS: This retrospective, observational, single cohort analysis of Optum's administrative claims data from January 1, 2011, to December 31, 2020, included commercially insured children who had 2 or more claims for an ASD diagnosis (earliest diagnosis designated as the index date), were between the ages of older than 1.5 years and 6 years or younger at index date, and were continuously enrolled for up to 48 months before and for 12 months after the index date. Two cohorts (between the ages of older than 1.5 years and 3 years or younger and between the ages of older than 3 years and 6 years or younger at ASD diagnosis) were divided into shorter (less than median) and longer (greater than or equal to median) TTD around each cohort median TTD calculated from the first documented ASD-related concern to the earliest ASD diagnosis, because TTD may vary by age at diagnosis. This exploratory analysis compared all-cause and ASD-related HCRU and costs during a 12-month period preceding ASD diagnosis among children with shorter vs longer TTD. RESULTS: 8,954 children met selection criteria: 4,205 aged 3 years or younger and 4,749 aged older than 3 years at diagnosis, with median TTD of 9.5 and 22.1 months, respectively. In the year preceding ASD diagnosis, children with longer TTD in both age cohorts experienced a greater number of all-cause and ASD-related health care visits compared with those with shorter TTD (mean and median number of office or home visits were approximately 1.5- and 2-fold greater in longer vs shorter TTD groups; P < 0.0001). The mean all-cause medical cost per child in the year preceding ASD diagnosis was approximately 2-fold higher for those with longer vs shorter TTD ($5,268 vs $2,525 in the younger and $5,570 vs $2,265 in the older cohort; P < 0.0001 for both). Mean ASD-related costs were also higher across age cohorts for those with longer vs shorter TTD ($2,355 vs $859 in the younger and $2,351 vs $1,144 in the older cohort; P < 0.0001 for both). CONCLUSIONS: In the year prior to diagnosis, children with longer TTD experienced more frequent health care visits and greater cost burden in their diagnostic journey compared with children with shorter TTD. Novel diagnostic approaches that could accelerate TTD may reduce costs and HCRU for commercially insured children. DISCLOSURES: This study was funded by Cognoa, Inc. Optum received funding from Cognoa to conduct this study. Dr Salomon is an employee and holds stock options of Cognoa, Inc. Dr Campbell was an employee of Cognoa, Inc., at the time this study was conducted. Dr Duhig was an employee of Cognoa, Inc., at the time the study was conducted and holds stock options. Dr Vu, Ms Kruse, Mr Gaur, and Ms Gupta are employees and/or stockholders of Optum. Dr Tibrewal was an employee of Optum at the time the research for this study was conducted. Dr Taraman is an employee and holds stock options of Cognoa, Inc., receives consulting fees from Cognito Therapeutics, volunteers as a board member of the American Academy of Pediatrics California and Orange County Chapter, is a paid advisor for MI10 LLC, and owns stock options of NTX, Inc., and HandzIn.

The Peanut Allergy Burden Study: Real-world impact of peanut allergy on resource utilization and productivity.

BACKGROUND: There is limited research demonstrating the real-world economic burden of peanut allergy (PA) in the United States. The Peanut Allergy Burden Study (PABS) is a cross-sectional quantitative survey designed to determine the real-world experience of patients and caregivers with PA. The objective of the study was to understand the real-world utilization of PA-related healthcare resources and the impact of PA on productivity. METHODS: Participants completed an online survey to examine the real-world 12-month and lifetime healthcare utilization and past week productivity impact of PA in children (as reported by caregiver proxy), adolescents with PA, adults with PA, and caregivers of children with PA. RESULTS: Healthcare resource use over the past 12 months was frequent for adults (n = 153), adolescents (n = 102), and children (as reported by caregivers) (n = 382) with PA. Patients and caregivers reported the following rates of PA-related utilization in the past 12 months: at least 3 regular allergist appointments (28.8%-39.3%), unscheduled allergist appointments (15.6%-18.3%), general practitioner appointments (16.7%-24.2%), over-the-counter (OTC) medication usage (28.5%-35.7%), and epinephrine autoinjector usage (17.7%-26.2%). Additionally, over half of patients and caregivers reported ≥1 PA-related emergency department (ED)/urgent care visit (57.5%-59.9%), overnight hospital admission (36.3%-47.4%), IV epinephrine use (37.2%-52.3%), or intubation (26.2%-39.8%) over the past 12 months for PA. Healthcare resource use was high among all groups. Regarding productivity, PA significantly impacted household work, schoolwork, and employed work for patients and caregivers. PA-related reactions also impacted school attendance of children with PA. CONCLUSION: Many healthcare resources were utilized by patients with PA and there was a loss of productivity associated with PA for patients and caregivers. New treatments to prevent or lower the risk of PA reactions could potentially help reduce healthcare resource utilization and PA-related productivity loss among patients and their families, particularly for patients for whom avoidance as a treatment strategy has not been reliable.

The Peanut Allergy Burden Study: Impact on the quality of life of patients and caregivers.

BACKGROUND: Peanut allergy (PA) places significant burden on peanut-allergic individuals and their families, yet limited research in the United States has quantitatively examined the impact on peanut-allergic individuals and their families' health-related quality of life (HRQoL). The Peanut Allergy Burden Study (PABS) aimed to quantify the impact of PA on the general and disease-specific HRQoL of children, adolescents, and adults with PA, as well as caregivers of children with PA. METHODS: A cross-sectional survey design was employed to examine the real-world impact of PA in children, adolescents, and adults with PA, and caregivers of children with PA. RESULTS: Of 153 adult patients, 102 adolescents, and 382 caregivers of peanut-allergic children (n = 382), 6.8% and 24.8% of participants indicated being dissatisfied or somewhat dissatisfied, respectively, with current approaches to avoid or prevent PA reactions. Approximately two-thirds of patients and caregivers indicated that PA interferes at least somewhat with daily living. In terms of general HRQoL, adolescents, adult patients, and caregivers indicated that mental/psychosocial health was more problematic than physical health. PA patients and caregivers indicated worse HRQoL in all domains compared to healthy samples, and worse overall HRQoL, psychosocial, emotional, and social functioning than a sample of chronically ill patients. Results from the allergy-specific HRQoL measures showed that adolescents experienced greater impairment in overall HRQoL due to PA and in allergen avoidance and dietary restriction than adults. CONCLUSION: PA negatively affects the general and PA-specific HRQoL of both patients and caregivers. The high emotional and psychosocial burden, in particular, demonstrates significant unmet need for patients with PA and their caregivers. Future work on treatment and preventive options to improve HRQoL for PA patients, particularly adolescents and their families, is needed.

Impact of non-medical switching of prescription medications on health outcomes: an e-survey of high-volume medicare and medicaid physician providers.

BACKGROUND: Non-medical switching refers to a change in a stable patient's prescribed medication to a clinically distinct, non-generic, alternative for reasons other than poor clinical response, side-effects or non-adherence. OBJECTIVE: To assess the perceptions of high-volume Medicare and/or Medicaid physician providers regarding the impact non-medical switching has on their patients' medication-related outcomes and health-care utilization. METHODS: We performed an e-survey of high-volume Medicare and/or Medicaid physicians (spending >50% of their time caring for Medicare and/or Medicaid patients), practicing for >2 years but <30 years post-residency and/or fellowship; working in a general, internal, family medicine or specialist setting; spending ≥40% of their time providing direct care and having received ≥1 request for a non-medical switch in the past 12 months. Physicians were queried on 15-items to assess perceptions regarding the impact non-medical switching on medication-related outcomes and health-care utilization. RESULTS: Three-hundred and fifty physicians were included. Respondents reported they felt non-medical switching, to some degree, increased side-effects (54.0%), medication errors (56.0%) and medication abandonment (60.3%), and ~50% believed it increased patients' out-of-pocket costs. Few physicians (≤13.4% for each) felt non-medical switching had a positive impact on effectiveness, adherence or patients' or physicians' confidence in the quality-of-care provided. Non-office visit and prescriber-pharmacy contact were most frequently thought to increase due to non-medical switching. One-third of physicians felt office visits were very frequently/frequently increased, and ~ 1-in-5 respondents believed laboratory testing and additional medication use very frequently/frequently increased following a non-medical switch. About 1-in-10 physicians felt non-medical switching very frequently/frequently increased the utilization of emergency department or in-hospital care. CONCLUSION: This study suggests high-volume Medicare and/or Medicaid physician providers perceive multiple negative influences of non-medical switching on medication-related outcomes and health-care utilization.

Communication of Medication Nonmedical Switching Policies and Procedures by Insurance Companies: Results of an E-Survey.

PURPOSE: Nonmedical switching is defined as a change in a stable patient's prescribed medication to a clinically distinct, nongeneric alternative for reasons other than lack of clinical response, adverse effects, or poor adherence. Nonmedical switching often results from formulary changes implemented by insurers to lower medication costs. We sought to survey randomly sampled physicians to elicit their opinions regarding insurers' communication about nonmedical switching. METHODS: We performed an online, cross-sectional survey of licensed, practicing physicians who were >2 years but <30 years out of residency and/or fellowship, who practiced in an internal medicine, family medicine, or specialist setting, spent ≥10% of their work time providing direct patient care, and had received at least 1 request for a nonmedical switch for ≥1 patient in the prior 12 months. The survey was fielded from November to December 2018. We report weighted percent responses categorized from 5- or 7-point Likert scale questions. FINDINGS: E-mail invitations were sent to 13,117 randomly sampled physicians, and 1818 opened the e-mail and followed the embedded survey link to participate. Of these, 1010 total physicians (55.5%), 606 primary care and 404 specialists, who treated patients experiencing nonmedical switching in the prior 12 months completed the survey. A few physicians were notified about nonmedical switches by insurers; more frequently physicians learned about them from pharmacies serving their patients. Notification frequently occurred at or after a refill came due. Notification via electronic medical record or insurer letter was less frequent. Few thought that insurers clearly communicated information about alternative medications when a nonmedical switch was required, and most disagreed that insurers provided clear procedures, timelines, and methods to track challenges. Nearly all agreed that insurers should provide supporting documentation or rationale for nonmedical switches and specifics on alternatives. Respondents overwhelmingly agreed that steps to improve communication and physicians' and patients' ability to navigate nonmedical switches or challenge procedures should be implemented. IMPLICATIONS: This survey of primary care and speciality physicians suggests that physicians believe that insurers' current level of communication regarding nonmedical switching is suboptimal. Respondents suggested that insurers did not optimally communicate information about alternative medications when a nonmedical switch was required and did not provide clear procedures, timelines, and methods to track challenges. A preponderance of physicians agreed that steps to improve physician-insurer communication to aid in the navigation of nonmedical switch and to challenge procedures should be implemented. If not addressed, these identified nonmedical switch communication issues may have a negative effect on achieving the quadruple aim of enhancing patient experience, improving population health, reducing costs, and improving the work life of health care practitioners and their staff.

Specialist physician perspectives on non-medical switching of prescription medications.

Introduction: A non-medical switch is a change to a patient's medication regimen for reasons other than lack of clinical response, side-effects or poor adherence. Specialist physicians treat complex patients who may be vulnerable to non-medical switching. Objectives: To evaluate specialist physicians' perceptions regarding the frequency of non-medical switch requests, and the impact on their patients' outcomes and healthcare utilization. Methods: An online survey of randomly sampled physicians spending ≥10% of time providing patient care and having received ≥1 non-medical switch request during the prior 12-months. Results: Among 404 specialist physicians surveyed, non-medical switch requests were reported as very frequent or frequent by 35.0% of oncologists (for injectable cancer agents) and up to 80.3% of endocrinologists (for injectable anti-hyperglycemics). Respondents reported decreased medication effectiveness (25.0% of oncologists to 75.0% of dermatologists) and increased side-effects (32.5% of oncologists to 66.7% of psychiatrists). Most specialists reported very frequent or frequent increases in non-office visits (52.5% of oncologists to 75.3% of endocrinologists) and calls with pharmacies (57.5% of oncologists to 80.5% of rheumatologists) due to non-medical switching. Conclusions: Receipt of non-medical switching requests were common among specialist physicians. Non-medical switching may lead to negative effects on patient care and require increased healthcare utilization.

Physicians' perspectives regarding non-medical switching of prescription medications: Results of an internet e-survey.

BACKGROUND: Physicians are in an ideal position to describe the impact of medication non-medical switching (switching commonly due to formulary changes by insurer for reasons unrelated to patient health) on their practice dynamics and patient care. We sought to examine physicians' openness to requests for non-medical switching and their experiences and opinions regarding the impact of non-medical switching on their practice, staff and patients. METHODS: An online survey of randomly-sampled physicians spending ≥10% of time providing patient care and having received ≥1 non-medical switch request during the prior 12-months. The impact of non-medical switching on clinical decision-making process; professional experience with clinical practice, patient-physician relationship, insurance process; and perceived impact on practice, staff and patients were assessed. Weighted percent responses were calculated. RESULTS: We sampled 1,010 physicians (response rate = 55.5%). Many responded being frequently not amenable (26.0%) or had reservations (41.8%) to non-medical switch requests; with >50% indicating patient stability on current therapy and suboptimal alternatives as factors frequently influencing amenability. Physicians agreed non-medical switching can create ethical concerns (clinical judgement, autonomy, ability to treat per guidelines; 74.8%, 82.3%, 53.5%, respectively), while forcing them to take responsibility for insurers' decisions (81.1%) and diverting their clinical time (84.3%). Most indicated non-medical switching increased practice burden (administrative, non-billable interactions, additional staffing, non-office patient contact, calls to/from the pharmacy; 85.0%, 72.5%, 62.2%, 64.2%, 69.5%, respectively). Physicians felt insurer processes discouraged non-medical switch challenges (76.7%) and required inconvenient lengths-of-time (76.1%) speaking to insurer representatives without proper expertise (62.0%). They believed non-medical switching negatively impacted aspects of care (effectiveness, side-effects, medication adherence and abandonment, out-of-pocket costs, medication errors; 46.5%, 53.2%, 50.6%, 49.4%, 59.6%, 54.5%, respectively). CONCLUSIONS: Physicians were frequently not amenable or had reservations regarding non-medical switching. They noted ethical concerns due to non-medical switching. Most felt non-medical switches burdened their practice and negatively impacted care.

Six-Month Use of Droxidopa for Neurogenic Orthostatic Hypotension.

BACKGROUND: Droxidopa is approved for adult patients with symptomatic neurogenic orthostatic hypotension (nOH); there is limited information regarding effects on symptoms, outcomes, and quality of life (QOL) beyond two weeks of treatment. OBJECTIVE: Examine the real-world experience of patients taking droxidopa after six months of treatment. METHODS: This non-interventional, US-based, prospective cohort study utilized a pharmacy hub, identifying patients who recently started droxidopa for nOH treatment. Questionnaires for fall frequency and other patient-reported outcomes (PROs) were completed at baseline and one, three, and six months following droxidopa initiation. RESULTS: 179 enrolled patients completed baseline surveys. Droxidopa continuation rates were high at months one, three, and six (87%, 79%, and 75%, respectively). From baseline to month one, there was significant reduction in the proportion of patients reporting falling at least once (54.1% vs. 43.0%; P = 0.0039), with similar observations at month three (52.9% vs. 44.5%; P = 0.0588) and month six (51.4% vs. 40.0%; P = 0.0339). Significant improvements from baseline to month one were observed and maintained at months three and six for most PROs, including the Orthostatic Hypotension Symptom Assessment Item 1, Short Falls Efficacy Scale-International, Sheehan Disability Scale, Physical Component of the 8-item Short-Form Health Survey, and Patient Health Questionnaire-9. CONCLUSIONS: In this non-interventional prospective study, fewer nOH patients reported falling after one, three, and six months of droxidopa treatment. Further, improvements reported in nOH symptoms, physical function, and QOL measures were maintained for six months following treatment initiation. Results from randomized clinical trials are required to validate the findings.

Relapse prevention: a cost-effectiveness analysis of brexpiprazole treatment in adult patients with schizophrenia in the USA.

OBJECTIVE: This study used a decision-analytic framework to assess the cost-effectiveness of brexpiprazole vs comparator branded therapies for reducing relapses and hospitalizations among adults with schizophrenia from a US payer perspective. METHODS: An economic model was developed to assess patients with stable schizophrenia initiating treatment with brexpiprazole (1-4 mg), cariprazine (1-6 mg), or lurasidone (40-80 mg) over a 1-year period. After 6 months, patients remained on treatment or discontinued due to relapse, adverse events, or other reasons. Patients who discontinued due to relapse or adverse events were assumed to have switched to other therapy, and those who discontinued due to other reasons were assumed to have received no therapy. Primary outcomes were incremental cost per relapse avoided and hospitalization avoided, and the secondary outcome was cost per quality-adjusted life-year (QALY) gained. Sensitivity and scenario analyses were also conducted. RESULTS: Brexpiprazole was associated with the highest per-patient clinical effectiveness (avoided relapses 0.637, avoided hospitalizations 0.719, QALYs 0.707) among comparators, followed by cariprazine (avoided relapses 0.590, avoided hospitalizations 0.683, QALYs 0.683) and lurasidone (avoided relapses 0.400, avoided hospitalizations 0.536, QALYs 0.623). Annual per-patient health-care costs were lowest for brexpiprazole ($20,510), followed by cariprazine ($22,282) and lurasidone ($25,510). Brexpiprazole was the least costly and most effective treatment strategy for all outcomes. Results were sensitive to relapse rates and daily cost of brexpiprazole. Limitations include data principally obtained from drug-specific randomized withdrawal studies and lack of direct-comparison trials. CONCLUSION: This analysis evaluated brexpiprazole treatment for the reduction of schizophrenia relapses and hospitalizations over a 1-year period compared to other recently available branded antipsychotics, and excluded generic antipsychotic treatments. Brexpiprazole treatment may lead to clinical benefits and medical cost savings, and provides a cost-effective treatment option for patients relatively to other branded second-generation antipsychotics.

A Survey of Payer Perspectives on Cannabis Use Disorder.

BACKGROUND: Cannabis use disorder (CUD) as described/defined in DSM 5, is characterized by impaired control of marijuana use and related personal, health, and legal consequences. CUD is a serious public health problem, affecting nearly 6 million individuals in the United States. There are no FDA approved medications to treat this disorder. The lack of available treatment options contributes to uncertainties by drug sponsors about formulary and reimbursement decision-making for CUD pharmacotherapies. OBJECTIVE: To addresses this gap by presenting the first findings on managed care payers' perceptions of CUD treatments and clinical trial end points. METHODS: An online survey was conducted with 50 payers from managed care organizations. The survey inquired about perceptions of unmet need in CUD treatment, relevant clinical trial end points, disease knowledge, and likelihood of review of new pharmacotherapies. RESULTS: The majority of payers (62%) reported that they were at least moderately familiar with CUD treatment end points. Most (80%) rated the unmet need for new pharmacotherapies for CUD as at least moderately important. Payers rated the most important end points for clinical trials as abstinence and decreased resource utilization. Most participants said an FDA approved CUD treatment would be formally reviewed by payers within 6 months (58%) or a year (36%). CONCLUSIONS: Based on these findings, payers see an unmet need for CUD treatment. Furthermore, FDA-approved pharmacotherapies for CUD will likely be reviewed quickly by payers, especially if data are provided on the likelihood of achieving abstinence and reduced resource utilization.

The Current Status of Outcomes-Based Contracting for Manufacturers and Payers: An AMCP Membership Survey.

BACKGROUND: As the United States health care system shifts from traditional volume-based payments to value-based payments, outcomes-based contracts (OBCs) are gaining popularity among payers and manufacturers as a mechanism for the shift toward value. Under this model, stakeholders hope to align drug payment and value to real-world performance metrics (e.g., biomarkers and health care resource utilization). OBJECTIVE: To understand the experiences, perceptions, and needs of payers and manufacturers related to OBCs. METHODS: The Academy of Managed Care Pharmacy (AMCP) and Xcenda conducted an online survey with AMCP payer and manufacturer members. Participants were asked a series of questions regarding their use of OBCs, barriers to implementation, and elements required in establishing successful OBCs. The importance and urgency of specific impediments to successful OBC implementation were also assessed. RESULTS: The survey was fielded May 12, 2017, to June 7, 2017, yielding 65 responses (35 payers/30 manufacturers). While a minority of payers/manufacturers had at least 1 OBC in place (20%/33%), a majority had interest in future OBC use (71%/63%). Among those with at least 1 OBC in place, 86%/80% of payers/manufacturers had renewed at least 1 OBC in the past 5 years. All payers and 60% of manufacturers with OBCs included compliance measures. Improvement in clinical outcomes was also common (71%/70%) (e.g., reaching set laboratory values goals), and 71%/60% included avoidance of unnecessary medical resource use (e.g., hospitalization and emergency department visit). The barrier most frequently identified by payers in implementing OBCs was evidence that OBCs reduced pharmacy spending (60%), while manufacturers identified the inability to obtain accurate data/outcome measures (73%) as a major limiting factor. Payers/manufacturers endorsed the use of easily measurable outcomes (91%/100%) as most important in establishing successful OBCs. Manufacturers, and to a lesser extent payers, indicated that regulations and legal issues need to be addressed to make progress in OBC implementation (e.g., safe harbor for preapproval health care economic information [77%/46%] and exemption of OBCs for best-price requirements [83%/51%]). The only exception was the clarification of regulations for discussing information outside of an FDA-approved label, in which both manufacturers and payers indicated a very strong need (100%) to be addressed. CONCLUSIONS: Surveyed AMCP members are interested in OBCs and recognize their alignment to societal health goals and health care affordability, although actual use of these contracts has been somewhat limited to date. Results from this survey indicate that there is potential for OBC use to increase as barriers and limitations are addressed. DISCLOSURES: This research was sponsored by the Academy of Managed Care Pharmacy and Xcenda. Duhig, Kaufman, and Hughes are employed by Xcenda. Saha is employed by the Academy of Managed Care Pharmacy. Smith has nothing disclose. Study concept and design were contributed by Duhig, Kaufman, Saha, and Hughes. Kaufman and Hughes collected the data, and data interpretation was performed by all the authors. The manuscript was written by Saha, Smith, and Duhig, along with Kaufman and Hughes.

Nursing Home Use Across The Spectrum of Cognitive Decline: Merging Mayo Clinic Study of Aging With CMS MDS Assessments.

BACKGROUND/OBJECTIVES: Objective, complete estimates of nursing home (NH) use across the spectrum of cognitive decline are needed to help predict future care needs and inform economic models constructed to assess interventions to reduce care needs. DESIGN: Retrospective longitudinal study. SETTING: Olmsted County, MN. PARTICIPANTS: Mayo Clinic Study of Aging participants assessed as cognitively normal (CN), mild cognitive impairment (MCI), previously unrecognized dementia, or prevalent dementia (age = 70-89 years; N = 3,545). MEASUREMENTS: Participants were followed in Centers for Medicare and Medicaid Services (CMS) Minimum Data Set (MDS) NH records and in Rochester Epidemiology Project provider-linked medical records for 1-year after assessment of cognition for days of observation, NH use (yes/no), NH days, NH days/days of observation, and mortality. RESULTS: In the year after cognition was assessed, for persons categorized as CN, MCI, previously unrecognized dementia, and prevalent dementia respectively, the percentages who died were 1.0%, 2.6%, 4.2%, 21%; the percentages with any NH use were 3.8%, 8.7%, 19%, 40%; for persons with any NH use, median NH days were 27, 38, 120, 305, and median percentages of NH days/days of observation were 7.8%, 12%, 33%, 100%. The year after assessment, among persons with prevalent dementia and any NH use, >50% were a NH resident all days of observation. Pairwise comparisons revealed that each increase in cognitive impairment category exhibited significantly higher proportions with any NH use. One-year mortality was especially high for persons with prevalent dementia and any NH use (30% vs 13% for those with no NH use); 58% of all deaths among persons with prevalent dementia occurred while a NH resident. CONCLUSIONS: Findings suggest reductions in NH use could result from quality alternatives to NH admission, both among persons with MCI and persons with dementia, together with suitable options for end-of-life care among persons with prevalent dementia.

Use and cost comparison of clobazam to other antiepileptic drugs for treatment of Lennox-Gastaut syndrome.

Background: Lennox-Gastaut syndrome (LGS) is a severe form of childhood-onset epilepsy associated with serious injuries due to frequent and severe seizures. Of the antiepileptic drugs (AEDs) approved for LGS, clobazam is a more recent market entrant, having been approved in October 2011. Recent AED budget impact and cost-effectiveness analyses for LGS suggest that adding clobazam to a health plan formulary may result in decreased medical costs; however, research on clinical and economic outcomes and treatment patterns with these AED treatments in LGS is limited. Objectives: To compare the baseline characteristics and treatment patterns of new initiators of clobazam and other AEDs among LGS patients and compare healthcare utilization and costs before and after clobazam initiation among LGS patients. Methods: A retrospective study of probable LGS patients was conducted using the MarketScan® Commercial, Medicare Supplemental, and Medicaid databases (10/1/2010-3/31/2014). Results: In the Commercial/Medicare Supplemental population, clobazam users were younger, had fewer comorbidities, and more prior AED use than non-clobazam users. In the 12 months pre-treatment initiation, clobazam users had significantly more seizure-related inpatient stays and outpatient visits and higher total seizure-related (P < 0.001) and all-cause (P < 0.001) costs than non-clobazam users. Among clobazam users, when compared to the 12 months pre-clobazam initiation, seizure-related medical utilization and costs were lower in the 12 months post-clobazam initiation (P = 0.004). Total all-cause (P < 0.001) and seizure-related (P = 0.029) costs increased post-clobazam initiation mainly due to the increase in outpatient pharmacy costs. Similar results were observed in the Medicaid population. Conclusions: Baseline results suggest a prescribing preference for clobazam in severe LGS patients. Clobazam users had a reduction in seizure-related medical utilization and costs after clobazam initiation. The improvement in medical costs mostly offset the higher prescription costs following clobazam initiation.

Fall-related healthcare use and costs in neurogenic orthostatic hypotension with Parkinson's disease.

AIMS: To compare patient characteristics, rates, and costs of medically attended falls among patients with Parkinson's disease (PD) and probable PD plus neurogenic orthostatic hypotension (PD + nOH). MATERIALS AND METHODS: MarketScan Commercial and Medicare Supplemental databases (January 1, 2009-December 31, 2013) were used to identify PD and probable PD + nOH patients. The first medical or prescription claim suggesting these diagnoses served as the index date. Baseline characteristics and post-index all-cause and fall-related healthcare utilization and costs were compared between patient groups. RESULTS: A total of 17,421 PD and 281 PD + nOH patients were identified. Compared with PD patients, PD + nOH patients were older (77 vs 74 years; p < .0001) and had more comorbidities. Pre- and post-index date, more PD + nOH patients had a medically attended fall than PD patients (25% vs 20% [p = .0159] and 30% vs 21% [p = 0.0002], respectively). Fallers in both groups had similar numbers of medically attended falls 12-months pre-index (mean =1.9), but PD + nOH fallers had more falls post-index (2.5 vs 2.0; p = .0176). Compared with PD patients, more PD + nOH patients (all p < .01) had fall-related emergency department (ED) visits (18% vs 10%), hospitalizations (7% vs 3%), and non-office visit outpatient services (15% vs 10%). Adjusted total post-index medical costs for falls ($2,260 vs $1,049; p = .0002) and total all-cause costs ($31,260 vs $20,910; p < .0001) were higher for PD + nOH vs PD patients. LIMITATIONS: This study had some limitations. There is no ICD-9-CM diagnosis code for nOH, so a combination of PD and OH diagnoses (with confounding conditions excluded) served as a proxy for an nOH diagnosis. Also, the rate of falls and associated costs in these cohorts might be under-reported because only medically attended falls were evaluated. CONCLUSIONS: PD + nOH patients had a higher prevalence of pre-existing comorbidities and a higher rate of medically attended falls than those with PD alone, leading to increased costs of care.

Measures of outcome for stimulant trials: ACTTION recommendations and research agenda.

BACKGROUND: The development and approval of an efficacious pharmacotherapy for stimulant use disorders has been limited by the lack of a meaningful indicator of treatment success, other than sustained abstinence. METHODS: In March, 2015, a meeting sponsored by Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) was convened to discuss the current state of the evidence regarding meaningful outcome measures in clinical trials for stimulant use disorders. Attendees included members of academia, funding and regulatory agencies, pharmaceutical companies, and healthcare organizations. The goal was to establish a research agenda for the development of a meaningful outcome measure that may be used as an endpoint in clinical trials for stimulant use disorders. RESULTS AND CONCLUSIONS: Based on guidelines for the selection of clinical trial endpoints, the lessons learned from prior addiction clinical trials, and the process that led to identification of a meaningful indicator of treatment success for alcohol use disorders, several recommendations for future research were generated. These include a focus on the validation of patient reported outcome measures of functioning, the exploration of patterns of stimulant abstinence that may be associated with physical and/or psychosocial benefits, the role of urine testing for validating self-reported measures of stimulant abstinence, and the operational definitions for reduction-based measures in terms of frequency rather than quantity of stimulant use. These recommendations may be useful for secondary analyses of clinical trial data, and in the design of future clinical trials that may help establish a meaningful indicator of treatment success.

Development of a patient-reported outcome instrument to assess complex activities of daily living and interpersonal functioning in persons with mild cognitive impairment: The qualitative research phase.

INTRODUCTION: As drug development research efforts move toward studying patients earlier in the course of Alzheimer's disease (AD), it is important to incorporate the patient's perspective into measurement of outcomes. METHODS: This article summarizes the qualitative work of the Patient-Reported Outcome Consortium's Cognition Working Group in the development of a new self-reported outcome measure in persons with mild cognitive impairment (MCI) due to suspected AD, herein referred to as MCI. RESULTS: The draft measure captures the patient's voice for two functional domains, complex activities of daily living and interpersonal functioning. DISCUSSION: This work represents a series of initial steps in the development of this rating scale. The next steps are to conduct psychometric analysis and evaluate the role of insight.

Direct medical costs and source of cost differences across the spectrum of cognitive decline: a population-based study.

BACKGROUND: Objective cost estimates and source of cost differences are needed across the spectrum of cognition, including cognitively normal (CN), mild cognitive impairment (MCI), newly discovered dementia, and prevalent dementia. METHODS: Subjects were a subset of the Mayo Clinic Study of Aging stratified-random sampling of Olmsted County, MN, residents aged 70 to 89 years. A neurologist reviewed provider-linked medical records to identify prevalent dementia (review date = index). Remaining subjects were invited to participate in prospective clinical/neuropsychological assessments; participants were categorized as CN, MCI, or newly discovered dementia (assessment date = index). Costs for medical services/procedures 1-year pre-index (excluding indirect and long-term care costs) were estimated using line-item provider-linked administrative data. We estimated contributions of care-delivery site and comorbid conditions (including and excluding neuropsychiatric diagnoses) to between-category cost differences. RESULTS: Annual mean medical costs for CN, MCI, newly discovered dementia, and prevalent dementia were $6042, $6784, $9431, $11,678, respectively. Hospital inpatient costs contributed 70% of total costs for prevalent dementia and accounted for differences between CN and both prevalent and newly discovered dementia. Ambulatory costs accounted for differences between CN and MCI. Age-, sex-, education-adjusted differences reached significance for CN versus newly discovered and prevalent dementia and for MCI versus prevalent dementia. After considering all comorbid diagnoses, between-category differences were reduced (e.g., prevalent dementia minus MCI (from $4842 to $3575); newly discovered dementia minus CN (from $3578 to $711)). Following the exclusion of neuropsychiatric diagnoses from comorbidity adjustment, between-category differences tended to revert to greater differences. CONCLUSIONS: Cost estimates did not differ significantly between CN and MCI. Substantial differences between MCI and prevalent dementia reflected high inpatient costs for dementia and appear partly related to co-occurring mental disorders. Such comparisons can help inform models aimed at identifying where, when, and for which individuals proposed interventions might be cost-effective.

Factors predicting change in frequency of heavy drinking days among alcohol-dependent participants in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).

AIMS: To discover the predictors of change in the frequency of heavy drinking (HD) over a 4-year period in alcohol dependent (AD)-individuals identified in the general population, namely, among participants of the US National Epidemiologic Survey on Alcohol and Related Conditions interviewed at Wave 1 (2001-2002) and at Wave 2 (2004-2005). METHODS: The study cohort included subjects meeting DSM-IV criteria for AD in the past year at Wave 1 (n = 1484), who were present at Wave 2 (n = 1172) and had complete data on factors of interest (n = 1123). Frequency of HD was defined as the number of HD days (HDD) (≥5 drinks per day for men and ≥4 for women). Change in frequency of HDD from baseline (Wave 1) to ~3 years later (Wave 2) was determined. An analysis of covariance model (ANCOVA), adjusting for baseline HDD, was used to examine individual factors associated with change in frequency of HDD, while a multivariable regression model was employed to assess factors associated with change in frequency of HDD simultaneously. RESULTS: Overall, there was a decrease in mean (SE) HDD [from 119.4 (1.8) at Wave 1 to 82.5 (2.1) at Wave 2, P < 0.0001]. Compared with smokers, non-smokers had a mean (SE) HDD reduction of 13.4 (6.7), P < 0.05. AD criteria of tolerance was significantly associated (P < 0.05) with less reduction in HDD. Change in depression/dysthymia status was associated with greater reduction in HDD in the ANCOVA model, but not the fully adjusted multivariable model. CONCLUSION: Findings from this study suggest that smoking and AD criteria of tolerance are important factors for long-term follow-up of AD patients and they should influence the selection of the kinds of interventions required for AD patients to achieve maximal therapeutic benefit.

Targeted smoking cessation messages for adolescents.

PURPOSE: To develop and to conduct a preliminary evaluation of smoking cessation messages targeted for adolescents. METHOD: We (a) conducted a formative evaluation to identify the optimal content and presentation approach for adolescent-targeted smoking cessation messages, (b) developed two smoking cessation videos catering to adolescent smokers' message preferences, and (c) copy tested the videos to determine the optimal message frame (gain vs. loss) using a quasi-experimental crossover design. RESULTS: In the formative evaluation, adolescent smokers preferred peer-delivered cessation messages that emphasized long-term health consequences and some social and short-term health consequences of smoking. The information from the formative evaluation was used to create a gain- (emphasized the benefits of quitting and joining a smoking cessation program) and a loss-framed video (emphasized the cost of continuing to smoke and consequences of failing to join a smoking cessation program). The copy test of the videos indicated that adolescents found the messages clear and appealing. The gain-framed message was considered more novel than the loss-framed message and was preferred by most participants. Nonetheless, the loss-framed version resulted in more positive attitudes toward quitting than the gain-framed version. CONCLUSION: Little is known about how to construct effective smoking cessation messages tailored specifically for adolescent smokers. The study findings provide insight into adolescents' preferences for message content and presentation. Although considered less novel, providing loss-framed information may be most influential among adolescents. These findings have important implications for developing effective adolescent-targeted smoking cessation messages.