Specialty drug coverage varies between health plans' medical and pharmacy benefit policies.

BACKGROUND: In an effort to control drug spending, health plans are increasingly shifting specialty drugs from their medical benefit to the pharmacy benefit. One consequence of this trend is that some health plans have both a medical and a pharmacy coverage policy for the same drug. OBJECTIVE: To examine how frequently health plans issue medical and pharmacy benefit policies for the same specialty drug and to evaluate the concordance between plans' medical and pharmacy policies when plans issue both policy types. METHODS: We identified specialty drug coverage policies from the Tufts Medical Center Specialty Drug Evidence and Coverage Database, which includes policies issued by 17 of the largest US commercial health plans. Policies were current as of August 2020. We determined plans that issued both medical and pharmacy policies. Next, we identified drugs with "medical-pharmacy policy pairs," ie, drugs for which a plan issued both a medical and a pharmacy policy. For these pairs, we compared the plan's policies while accounting for the following coverage criteria: patient subgroups (patients must meet certain clinical criteria), prescriber requirements (a specialist must prescribe the drug), and step therapy protocols (patients must first fail alternative treatments). We considered medical-pharmacy policy pairs to be discordant if coverage criteria differed, eg, the medical policy included a prescriber requirement but the pharmacy policy did not. RESULTS: Eight plans issued separate medical and pharmacy benefit coverage policies for the same specialty drug and indication. Among these 8 plans, we identified 1,619 medical-pharmacy policy pairs. Eighty-six percent of pairs were concordant (1,386/1,619), and 14% were discordant (233/1,619). Discordance was most often due to differences in plans' application of step therapy protocols (184/233), followed by prescriber requirements (52/233) and patient subgroups (25/233). Forty pairs were discordant in multiple ways. Of discordant pairs, medical policies were more restrictive 41% (96/233) of the time; pharmacy policies were more restrictive 54% (125/233) of the time; 5% of the time (12/233), the medical policy was more restrictive in some ways, but the pharmacy policy was more restrictive in others. Overall, plans imposed coverage restrictions in their medical and pharmacy policies with similar frequencies. CONCLUSIONS: Commercial health plans' medical and pharmacy coverage policies for the same specialty drugs tended to be concordant, although we found coverage criteria to be discordant 14% of the time. Medical and pharmacy policies that are inconsistent in their coverage criteria and restrictions complicate, and potentially hinder, patients' access to specialty drugs. DISCLOSURES: Drs Kauf, O'Sullivan, and Strand were employees of Alkermes, Inc., when the study was conducted and may own stock in the company. Mx Levine, Mr Panzer, and Dr Chambers have no conflicts of interest to disclose. This research study was supported by Alkermes, Inc.

Unmet needs with antipsychotic treatment in schizophrenia and bipolar I disorder: patient perspectives from qualitative focus groups.

BACKGROUND: Schizophrenia (SZ) and bipolar I disorder (BD-I) are chronic mental health disorders often treated with antipsychotic medications. This qualitative study sought to better understand disease burden and treatment experiences with oral antipsychotic medications in participants living with SZ or BD-I. METHODS: Six 90-min focus groups were conducted with participants diagnosed with SZ or BD-I. Trained moderators facilitated discussions using a semistructured guide. Participants described symptoms, impacts of disease, and experiences with oral antipsychotic medications, whether favourable or unfavourable. RESULTS: Among participants with SZ (n = 15; 3 groups, 5 per group), 53% were male and 33% were white, with a mean of 18.6 years since diagnosis. Of participants with BD-I (n = 24; 3 groups, 8 per group), 33% were male and 42% were white, with a mean of 13.0 years since diagnosis. Participants described numerous symptoms of their illnesses that impacted relationships and daily life, including effects on emotional health, the ability to work, and encounters with law enforcement. Previous antipsychotic medications were deemed effective by 14/15 (93%) participants with SZ and 12/16 (75%) participants with BD-I. Most participants with SZ (13/15; 87%) or with BD-I (16/24; 67%) reported discontinuing their antipsychotic medication at some point. Side effects were a common reason for discontinuing or switching medications for participants with SZ (8/15; 53%) and for those with BD-I (11/24; 46%). The most common side effects reported in both cohorts were weight gain, drowsiness, sexual problems, and neurologic symptoms. Side effects negatively affected quality of life, leading to serious health problems and issues with self-esteem. CONCLUSIONS: People living with SZ or BD-I cited a range of favourable and unfavourable experiences with oral antipsychotic medications. Most participants reported that their antipsychotics were effective at controlling their symptoms, but multiple side effects impacted their quality of life, caused additional serious health problems, and often led to discontinuation of or switching antipsychotics. Findings from this study contribute to a better understanding of patients' experiences with antipsychotics and highlight a need for new medications with favourable benefit/risk profiles.

Changes in Clinical Management of Patients with Schizophrenia Treated with Long-Acting Injectable Antipsychotics (LAIs), Including Telepsychiatry Use, During the COVID-19 Pandemic.

Purpose: The COVID-19 pandemic substantially impacted care of patients with schizophrenia treated with long-acting injectable antipsychotics (LAIs). This study (OASIS-MAPS) examined how clinical sites adapted operations and used telepsychiatry to maintain standard of care for these patients during the pandemic. Methods: Two online surveys (initial: October-November 2020, N = 35; follow-up: July-September 2021, N = 21) were completed by a principal investigator (PI) or PI-appointed designee at sites participating in the OASIS study (NCT03919994). Survey responses were analyzed descriptively. Results: At the time of the initial survey, all 35 participating sites were using variants of telepsychiatry, with 20 sites adopting it after the pandemic started. Most sites reported no negative impacts of the pandemic on medication adherence, although approximately 20% of sites reported decreased adherence for LAIs. Twelve sites (34%) reported switching patients with schizophrenia from LAIs to oral antipsychotic medications, while 11 sites (31%) reported switching patients from shorter to longer injection interval LAIs during the pandemic. Most sites did not experience difficulties in implementing or expanding telepsychiatry services, although lower reimbursement rate for telepsychiatry and patients' lack of access to and training on relevant technologies were the most frequently reported barriers. Conclusion: Changes made by sites after the pandemic onset were viewed by almost all participants as satisfactory for maintaining standard of care. Almost all participants thought that the use of telepsychiatry services would continue after the pandemic in a hybrid manner combining telepsychiatry and office visits. Ensuring that patients have equitable access to telepsychiatry will be important in the post-pandemic future.

Impaired insight in schizophrenia: impact on patient-reported and physician-reported outcome measures in a randomized controlled trial.

BACKGROUND: Impaired insight poses a challenge in the treatment of patients with schizophrenia because of its potential to jeopardize therapeutic engagement and medication adherence. This study explored how insight impairment, graded from none to extreme, is related to patient-reported mental health status, depression, and neurocognition in schizophrenia. METHODS: In a post hoc analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study (NCT00014001), insight was measured using the Positive and Negative Syndrome Scale (PANSS) Item G12 (lack of insight). Additional assessments for this analysis included the 12-Item Short-Form Health Survey (SF-12) Mental Component Summary (MCS), physician- and patient-reported Clinical Global Impression-Severity (CGI-S), MATRICS Consensus Cognitive Battery, and Calgary Depression Scale for Schizophrenia. Relationships between patient-reported outcomes and PANSS total and Item G12 ratings were evaluated. RESULTS: Among 1431 CATIE study participants in this analysis, increasingly impaired insight at baseline was significantly associated with better patient-reported quality of life (QoL), lower baseline depression, and greater divergence between physician- and patient-reported illness severity. Patients with more severely impaired insight reported milder illness compared with physician reports, particularly those with moderate-severe to extreme impairment (PANSS Item G12 rating ≥ 5), approximately 10% (138/1431) of CATIE participants. For the 90% of patients with PANSS Item G12 ratings < 5, patient-reported QoL decreased with increasing symptoms. SF-12 MCS scores were linearly related to baseline PANSS total score only in patients with PANSS total score < 90 (moderately ill or better), and better symptom scores were associated with higher QoL. No significant relationship between insight and neurocognition was observed. CONCLUSIONS: In the small subgroup (10%) of CATIE study patients with schizophrenia and PANSS Item G12 ratings ≥5, moderate-severe-severe/extreme insight impairment was associated with significantly more positive perception of QoL and illness severity by the patient versus the treating physician. This was not observed in the remaining 90% of patients with normal to moderately impaired insight, suggesting that poor insight as a threat to the validity of self-report is uncommon.

Systematic Review of Real-World Treatment Patterns of Oral Antipsychotics and Associated Economic Burden in Patients with Schizophrenia in the United States.

BACKGROUND: Schizophrenia is a chronic mental disorder associated with substantial morbidity and mortality affecting 0.25-1.6% of adults in the USA. Antipsychotic treatment is the standard of care for schizophrenia, but real-world treatment patterns and associated costs have not been systematically reviewed. OBJECTIVE: We conducted a systematic review to summarize treatment patterns and associated costs related to oral antipsychotic treatment of patients with schizophrenia in the USA. DATA SOURCES: We searched Medline (via PubMed) and Embase to identify relevant observational studies published from January 1, 2008, to June 1, 2018; costs were converted to 2018 US dollars. STUDY ELIGIBILITY: Observational, real-world studies reporting on patterns of treatment and/or associated costs for adult patients with schizophrenia treated with oral antipsychotics in the USA were included. RESULTS: Eighty-one studies were identified. Frequently prescribed oral second-generation antipsychotics were olanzapine (up to 50.9%), risperidone (up to 40.0%), and quetiapine (up to 30.7%). Suboptimal adherence was common across studies. Antipsychotic switching occurred in about half of patients, while antipsychotic combination therapy occurred in nearly 30%; all were associated with increased medication-related costs. Mean annual direct medical costs differed by treatment, with reported costs of $17,115 to $26,138 for patients treated with olanzapine, $18,395 for risperidone, and $17,656 to $28,101 for quetiapine. LIMITATIONS: This systematic review is limited by the variations in definitions of schizophrenia-related clinical terms used between studies and by the inclusion of studies focused on only the US health care system. CONCLUSIONS: In the treatment of schizophrenia, suboptimal adherence, antipsychotic switching, and antipsychotic augmentation were all associated with high costs of care in comparison to patients who were adherent and did not require antipsychotic switching or augmentation. These findings illustrate the need for the development of new treatments that address efficacy and adherence challenges of currently available therapies.

Schizophrenia is a debilitating mental disorder that affects up to 1.6% of adults in the USA. Antipsychotic medications reduce symptoms of the disease, but many patients with schizophrenia are not fully adherent or choose to discontinue treatment entirely, increasing their risk of hospitalization. In others, efforts to achieve better symptom control or to avoid intolerable side effects may result in switching antipsychotic medications or adding additional medications, leading to higher medical treatment costs. The magnitude of these cost increases is unclear. This study sought to assess medical costs associated with antipsychotic treatment adherence, switching, and adding additional antipsychotics. We reviewed 81 studies published from January 2008 through June 2018 examining treatment adherence in patients with schizophrenia. We calculated rates of adherence, switching, and adding antipsychotics, as well as associated medical costs. Overall adherence to antipsychotic treatment was less than 50%, with up to 50% of patients switching medications and up to 29% adding an additional antipsychotic medication to their current treatment. Patients who were not treatment adherent incurred annual medical costs of $10,316 compared with $5723 in patients who were adherent. The costs of immediate or delayed switching of antipsychotic medications ranged from $21,922 to $28,232, while costs of adding an additional antipsychotic ranged from $24,045 to $29,344. These data suggest that suboptimal medication adherence, along with high rates of patient discontinuation and medication switching, lead to higher treatment costs in the management of patients with schizophrenia.

Weight gain and comorbidities associated with oral second-generation antipsychotics: analysis of real-world data for patients with schizophrenia or bipolar I disorder.

BACKGROUND: Many second-generation antipsychotics (SGAs) are associated with weight gain and cardiometabolic effects. Antipsychotic-associated weight gain is linked to treatment interruptions, potentially increasing risk of relapse and hospitalization. This retrospective study assessed clinically significant weight gain (CSWG), treatment interruptions, and development of cardiometabolic conditions in patients with schizophrenia (SZ) or bipolar I disorder (BD-I) following initiation of oral SGAs with moderate to high weight gain risk. METHODS: Patients with no prior use of moderate to high weight gain risk oral SGAs were identified from patient-level medical/pharmacy claims and electronic medical records (January 2013-February 2020; OM1 Real-World Data Cloud). Those with ≥ 1 weight measurement in both the 12 months preceding and 3 months after SGA initiation (index date) were analyzed for continuous changes in weight, CSWG (≥ 7% and ≥ 10% increases from baseline), treatment interruptions (switches/discontinuations), and development of cardiometabolic conditions. RESULTS: Median follow-up times in the SZ (n = 8174) and BD-I (n = 9142) cohorts were 153.4 and 159.4 weeks, respectively; 45.5% and 50.7% were obese at baseline. Mean (SD) percent weight increase during treatment was 3.3% (7.2) and 3.7% (7.0) for patients with SZ and BD-I, respectively, and was highest for underweight/normal weight patients (SZ: 4.8% [8.1]; BD-I: 5.5% [8.7]). More than 96% had treatment interruptions during follow-up, primarily discontinuations. CSWG and treatment interruptions occurred within a median of 13 and 14 weeks after treatment initiation, respectively. Of patients with CSWG and treatment interruptions, approximately 75% did not return to baseline weight during follow-up. Among those without baseline cardiometabolic conditions, 14.7% and 11.3% of patients with SZ or BD-I, respectively, developed ≥ 1 condition over 12 months post-index. Incidence was generally highest among those who were overweight/obese at baseline and those who experienced CSWG. CONCLUSIONS: In this analysis of real-world data, both weight gain and treatment interruptions occurred early in treatment for patients with SZ or BD-I. Treatment-associated weight gain persisted despite switching or discontinuing index treatment. Additionally, cardiometabolic morbidity increased within 12 months of treatment initiation. Patients with SZ or BD-I are at greater risk than the general population for cardiometabolic conditions; weight gain associated with SGAs may exacerbate these health risks.

Real-World Outcomes and Costs Following 6 Months of Treatment with the Long-Acting Injectable (LAI) Aripiprazole Lauroxil for the Treatment of Schizophrenia.

BACKGROUND: Continuous antipsychotic therapy is recommended as part of long-term maintenance treatment of schizophrenia, and gaps in antipsychotic treatment have been associated with increased risks of relapse and rehospitalization. Because the use of long-acting injectable (LAI) antipsychotics may reduce the likelihood of undetected medication gaps, initiating an LAI medication may affect resource utilization and costs. The LAI aripiprazole lauroxil (AL) was approved in the United States (US) in 2015 for the treatment of schizophrenia in adults. OBJECTIVE: The objective of this retrospective observational cohort study was to examine treatment patterns, resource utilization, and costs following initiation of AL for the treatment of schizophrenia in adults. METHODS: A retrospective analysis of Medicaid claims data identified a cohort of patients (N = 485) starting AL shortly after Food and Drug Administration approval in October 2015. Treatment patterns, resource utilization, and costs were compared 6 months before and after treatment initiation. Subgroup analyses were conducted based on the type of antipsychotic (LAI, oral, or none) received before initiation of AL. RESULTS: Over 6 months of follow-up, patients received an average of 4.6 injections out of a maximum of six (77%). After initiating AL, all-cause inpatient admissions decreased by 22.4%; other significant reductions were observed in mental health-related admissions and emergency room (ER) visits. All-cause inpatient costs decreased by an average of US$2836 per patient (p < 0.05) in the 6-month post-AL period, whereas outpatient pharmacy costs increased by US$4121 (p < 0.05), resulting in no significant difference in overall costs between the pre- and post-AL periods. The subgroup of patients who had been prescribed an oral antipsychotic before starting AL had significant reductions in proportion of patients with inpatient and ER visits and costs, but also reported a significant increase in pharmacy costs. CONCLUSIONS: AL was associated with a significant reduction in inpatient costs and an increase in outpatient pharmacy costs, resulting in no changes in total healthcare costs over 6 months. The adherence rate and reductions in inpatient use may indicate the potential for greater clinical stability among patients initiated on AL compared with their previous treatment.

Long-term effect of aripiprazole lauroxil on health-related quality of life in patients with schizophrenia.

BACKGROUND: This post hoc analysis of clinical trial data evaluated long-term, self-reported mental and physical health-related quality of life (HRQoL) scores in schizophrenia patients receiving aripiprazole lauroxil (AL), an atypical long-acting injectable (LAI) antipsychotic approved for the treatment of schizophrenia in adults. METHODS: The study population included 291 stable schizophrenia outpatients enrolled in 2 consecutive long-term safety studies of AL given every 4 weeks for up to 124 weeks. HRQoL was measured using the SF-36v2® Health Survey (SF-36v2) over the course of the follow-up. The primary outcome was change in SF-36v2 mental component summary (MCS) and physical component summary (PCS) scores from baseline to 124 weeks. To contextualize these scores, descriptive analyses were conducted to compare the scores with available scores for the general population as well as for other populations with chronic medical (ie, hypertension and type 2 diabetes) or psychiatric (ie, depression) conditions. RESULTS: Results from this post hoc analysis indicated that the mean MCS score for patients continuing AL improved significantly from baseline over 124 weeks (P < .05, all timepoints), while mean PCS score showed little change over 124 weeks. At baseline, patients had lower (worse) MCS scores than the normed general population, but by week 124, patients had MCS scores comparable to those in the general population. This pattern of change was not observed with PCS scores. Comparison of study MCS scores with those associated with other diseases showed that this schizophrenia cohort had lower scores than those with chronic medical conditions but higher scores than those with depression. PCS scores were higher in the study population than published scores for all reference populations at baseline and week 124. CONCLUSIONS: In this post hoc analysis, outpatients with schizophrenia who continued the LAI antipsychotic AL showed gradual and sustained improvement in self-reported mental HRQoL over several years of follow-up, whereas self-reported physical HRQoL did not change. By the end of follow-up, mental health scores of study patients with schizophrenia were comparable to those of the general population and better than those of patients with depression. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01626456 [trial registration date: June 15, 2012] and NCT01895452 [trial registration date: July 5, 2013]).

Real-World Patterns of Utilization and Costs Associated with Second-Generation Oral Antipsychotic Medication for the Treatment of Bipolar Disorder: A Literature Review.

OBJECTIVE: Treatment with second-generation antipsychotics (SGAs) for bipolar disorder, including bipolar I disorder (BD-I), is common. This review evaluated real-world utilization patterns with oral SGAs in the United States (US) for bipolar disorder (and BD-I specifically when reported) and economic burden associated with these patterns. METHODS: Structured, systematic searches of MEDLINE®, EMBASE®, and National Health Service Economic Evaluation Database identified primary research studies (published 2008-2018) describing real-world SGA use in adults with bipolar disorder/BD-I. RESULTS: Among 769 studies screened, 39 met inclusion criteria. Most studies (72%) were analyses of commercial or Medicare/Medicaid claims databases. Patient-related (eg, demographic, comorbidities) and disease-related (eg, mania, psychosis) factors were associated with prescribed SGA. Suboptimal utilization patterns (ie, nonadherence, nonpersistence, treatment gaps, medication switching, and discontinuation) were common for patients treated with SGAs. Also common were SGAs prescribed with another psychotropic medication and SGA combination treatment (use of ≥2 SGAs concurrently). Suboptimal adherence and SGA combination treatment were both associated with increased health care resource use (HCRU); suboptimal adherence was associated with higher total direct medical and indirect costs. LIMITATIONS: Different definitions for populations and concepts limited between-study comparisons. Focusing on SGAs limits contextualizing findings within the broader treatment landscape (eg, lithium, anticonvulsants). Given the nature of claims data, prescribing rationale (eg, acute episodes vs maintenance) and factors influencing observed utilization patterns could not be fully derived. CONCLUSION: Despite increased use of SGAs to treat bipolar disorder over the last decade, reports of suboptimal utilization patterns of SGAs (eg, nonadherence, nonpersistence) were common as was combination treatment. Patterns of SGA use associated with additional HCRU and/or costs were suboptimal adherence and SGA combination treatment; economic consequences associated with other utilization patterns (eg, nonpersistence) were unclear. Strategies to improve SGA treatment continuity, particularly adherence, may improve clinical and economic outcomes among people living with bipolar disorder.

Antipsychotic Treatment Experiences of People with Schizophrenia: Patient Perspectives from an Online Survey.

BACKGROUND: This survey examined the experiences of people living with schizophrenia who have used oral antipsychotics (APs). METHODS: Adults with self-reported physician-diagnosed schizophrenia (N=200), who were members of an online research participation panel and reported taking one or more oral APs within the last year, completed a cross-sectional online survey that focused on direct report of their experiences regarding APs (eg, symptoms, side effects, adherence). Descriptive analyses were conducted for the total survey sample and for subgroups defined a priori by experience with specific, prevalent side effects. RESULTS: The mean age of the sample was 41.9 (SD=11.0) years, 50% of participants were female, and 32% were nonwhite. Overall ratings were positive for medication effectiveness and convenience but negative for side effects. While most participants reported that APs improved schizophrenia symptoms (92%), 27% reported APs as having done "more harm than good." Almost all participants (98%) reported experiencing side effects of APs, with the most common being anxiety (88%), feeling drowsy/tired (86%), and trouble concentrating (85%). Side effects frequently cited as either "extremely" or "very" bothersome were weight gain (56%), sexual dysfunction (55%), and trouble concentrating (54%). Over 80% reported that side effects had negatively impacted their work and social functioning (eg, social activities or family/romantic relationships). Since initiating treatment, 56% of respondents had stopped taking APs at some point (65% of these due to side effects). Side effects commonly reported as having led to stopping AP treatment were "feeling like a 'zombie'" (22%), feeling drowsy/tired (21%), and weight gain (20%). CONCLUSION: Most participants reported improvements in schizophrenia symptoms associated with the use of APs. However, most participants also reported experiencing numerous bothersome side effects that negatively impacted their work, social functioning, and treatment adherence. Results highlight the unmet need for new APs with favorable benefit-risk profiles.

The Economic Burden of Bipolar Disorder in the United States: A Systematic Literature Review.

Bipolar disorder (BD) is a mood disorder with subtypes characterized by episodes of mania, hypomania, and/or depression. BD is associated with substantial economic burden, and the bipolar I disorder (BD-I) subtype is associated with high medical costs. This review further evaluated the economic burden of BD and BD-I in the United States (US), describing health-care resource utilization (HCRU) and sources of direct medical and indirect costs. Data were obtained from systematic searches of MEDLINE®, EMBASE®, and National Health Service Economic Evaluation Database. Citations were screened to identify primary research studies (published 2008-2018) on the economic burden of BD/BD-I or its treatment in real-world settings. Reported costs were converted to 2018 US dollars. Of identified abstracts (N=4111), 56 studies were included. The estimated total annual national economic burden of BD/BD-I was more than $195 billion, with approximately 25% attributed to direct medical costs. Individuals with BD/BD-I used health-care services more frequently and had higher direct medical costs than matched individuals without the disease. Drivers of higher direct costs included frequent psychiatric interventions, presence of comorbid medical/psychiatric conditions, and both suboptimal medication adherence and clinical management. Indirect costs (eg, unemployment, lost work productivity for patients/caregivers) accounted for 72-80% of the national economic burden of BD/BD-I. Different definitions for study populations and cost categories limited comparisons of economic outcomes. This review builds on existing literature describing the economic burden of BD and confirmed cost drivers of BD/BD-I. Improved clinical management of BD/BD-I and associated comorbidities, together with better medication adherence, may reduce health-care costs and improve patient outcomes.

Risk factors and costs associated with 30-day readmissions following alcohol-related hospitalizations in the United States from 2010 to 2015.

Patients with alcohol-related diagnoses at initial hospitalization are at high risk of 30-day readmission. Understanding risk factors for 30-day readmission among these patients may help to identify those who would benefit from efforts to reduce risk of readmission. The Nationwide Readmissions Database was used to estimate 30-day all-cause readmissions among United States patients with an alcohol-related index hospitalization and to evaluate risk factors and costs associated with these readmissions. Included patients were 18 years of age or older at initial hospitalization, had an alcohol-related primary diagnosis (based on ICD-9-CM codes), and were discharged between 2010 and 2015. They were followed for 30 days after initial hospitalization within the calendar year to identify all-cause readmissions. A logistic regression analysis assessed the association between risk factors and 30-day readmission. Average costs of initial admissions and readmissions were estimated. Among 113,931,723 adult index hospitalizations, 1,124,228 had alcohol-related diagnoses. Patients had a mean age of 49 years, 73% were male, and 45% had public insurance coverage. The annual rate of 30-day readmissions among patients with index alcohol-related hospitalizations increased from 119 readmissions per 1000 admissions in 2010 to 140 per 1000 in 2015, while the rate of readmissions among patients with all-cause hospitalizations declined from 103 to 98 per 1000. The regression analysis suggested that age, male sex, comorbid conditions, discharge against medical advice, admission to large and teaching hospitals, and Medicaid vs. non-Medicaid payment were all risk factors for 30-day readmission. Mean costs of initial alcohol-related hospitalizations were greater among those with a 30-day readmission than without a 30-day readmission, and the mean cost of 30-day readmission was even greater. Mitigating the upward trend in rates of readmission following alcohol-related initial hospitalizations may be addressed through better identification of high-risk patients who are admitted with an alcohol-related diagnosis and greater use of existing evidence-based psychosocial and pharmacotherapy treatment methods.

Antipsychotic treatment experiences of people with bipolar I disorder: patient perspectives from an online survey.

BACKGROUND: Oral antipsychotic (AP) medications are frequently prescribed to people with bipolar I disorder (BD-I). A cross-sectional online survey examined the experiences of people living with BD-I with a history of recent AP use. METHODS: Adults with self-reported physician-diagnosed BD-I (N = 200) who received oral APs during the prior year completed a survey on AP-related experiences, including side effects and their perceived burden on social functioning, adherence, and work. Items also assessed preferences for trade-offs (balancing symptom management and side effects) when considering a hypothetical new AP. The perceived impact of specific, prevalent side effects on adherence, work, and preferences for a hypothetical AP were also examined. Analyses were descriptive. RESULTS: The survey sample had a mean age of 43.2 (SD = 12.4) years, was 60% female, and 31% nonwhite. Almost all participants (98%) had experienced AP side effects. Common self-reported side effects were feeling drowsy or tired (83%), lack of emotion (79%), anxiety (79%), dry mouth (76%), and weight gain (76%). Weight gain was cited as the most bothersome side effect, rated by most participants (68%) as "very" or "extremely bothersome." Nearly half of participants (49%) reported that AP side effects negatively impacted their job performance; almost all (92%) reported that side effects - most commonly anxiety and lack of emotion - negatively impacted social relationships (e.g., family or romantic partners). The most commonly-reported reason for stopping AP use was dislike of side effects (48%). Side effects most likely to lead to stopping or taking less of AP treatment included "feeling like a 'zombie'" (29%), feeling drowsy or tired (25%), and weight gain (24%). When considering a hypothetical new AP, the most common side effects participants wanted to avoid included AP-induced anxiety (50%), weight gain (48%), and "feeling like a 'zombie'" (47%). CONCLUSIONS: Side effects of APs were both common and bothersome, and impacted social functioning, adherence, and work. Findings highlight the prevailing unmet need for new APs with more favorable benefit-risk profiles.

Economic Burden of Treatment-Resistant Depression on the U.S. Health Care System.

BACKGROUND: Treatment-resistant depression (TRD), defined as episodes of depression that do not respond to ≥ 2 lines of adequate depression therapy, is associated with a high economic burden. Although the economic burden of TRD is reported elsewhere, its exact magnitude and current value is uncertain due to differences in methodology in TRD identification. OBJECTIVE: To compare all-cause health care resource utilization (HCRU) and associated health care payments among patients with TRD and those with depression but without TRD, using administrative claims data. METHODS: This retrospective cohort study used data from the Truven Health MarketScan Commercial and Medicare Supplemental Databases (October 1, 2008-September 30, 2016). All patients were aged ≥ 18 years, newly diagnosed with depression (≥ 1 inpatient admission or ≥ 2 outpatient visits with a primary or secondary depression diagnosis), and newly treated with depression therapy. The population included patients with and without TRD. Patients with TRD were defined as having been treated with ≥ 3 courses of depression therapy within a 360-day period (initiation of the third course served as the TRD index date), while patients without TRD (non-TRD) were defined as having been treated with 2 courses of depression therapy. TRD and non-TRD cohorts were matched using propensity scores. Using the TRD index date of their matched TRD pair, non-TRD patients were assigned a simulated index date following second-line therapy. Eligible TRD and non-TRD patients were continuously enrolled from a 12-month baseline period before the first course of therapy through a 12-month follow-up period beginning with the TRD index date and simulated index date, respectively. Annual all-cause HCRU and associated payments (2016 U.S. dollars) were assessed in aggregate and by place of service during the follow-up period and were compared between the matched cohorts using nonparametric Wilcoxon signed-rank tests. RESULTS: The matched analysis included 800 patients in each cohort. For both cohorts, the mean age of patients was 39 years, and 60% were female. All clinical characteristics and all-cause HCRU were comparable at baseline. Compared with non-TRD patients, TRD patients had a significantly higher mean number of all-cause emergency department (ED) visits (0.29 vs. 0.24), outpatient visits (18.0 vs. 13.4), and prescriptions (30.0 vs. 24.0; all P < 0.05) during the 12-month follow-up period. The TRD cohort also had significantly higher mean total all-cause health care payments ($9,890 vs. $6,848; P < 0.001) and mean payments by place of service (ED: $518 vs. $408; outpatient: $3,603 vs. $2,585; pharmacy: $2,613 vs. $1,837; all P < 0.05) compared with the non-TRD cohort. CONCLUSIONS: In relation to propensity score-matched non-TRD patients, TRD patients used significantly more resources (ED visits, outpatient visits, and number of prescriptions) and had significantly higher overall health care payments. These results serve to highlight the unmet need in patients with TRD, suggesting that improved and more effective management of these patients may help reduce the economic burden of disease. DISCLOSURES: This study was funded by Alkermes. Sussman and Menzin, employees of Boston Health Economics, were paid consultants, and Olfson, an employee of Columbia University Irving Medical Center, was an unpaid consultant to Alkermes in connection with the study and development of this research article. O'Sullivan and Shah are employees of the study sponsor. Results from this analysis were first presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting in Boston, MA, on April 23-26, 2018.

Cystic fibrosis in young children: A review of disease manifestation, progression, and response to early treatment.

BACKGROUND: Studies have described illness associated with cystic fibrosis (CF) early in life, but there is no comprehensive accounting of the prevalence and ages of disease manifestation and progression described in individual studies. METHODS: We searched for peer-reviewed English-language studies of the health of children ≤6years old with CF (published 1990-2014). Structural abnormalities and dysfunction of the digestive and respiratory systems were summarized across relevant studies by system and age group. RESULTS: Primary studies (125 total) from 22 countries described abnormalities, dysfunction, and disease progression in infancy and early childhood. Improved health was consistently observed in association with diagnosis via newborn screening compared with cohorts diagnosed later by symptomatic presentation. CONCLUSIONS: The peer-reviewed literature is remarkably consistent: CF-associated growth impairment and airway abnormalities are reported at birth, and disease progression is reported in infancy and throughout childhood. Earlier access to routine CF management is associated with improved subsequent health status.

Can bundled payment improve quality and efficiency of care for patients with hip fractures?

The current Medicare reimbursement for hip fractures lacks accountability and promotes cost cutting. A bundled payment system-analogous to the Medicare Acute Care Episodes Demonstration for Orthopedic and Cardiovascular Surgery-may help curtail costs, foster communication among health care providers, and improve their accountability for patient outcomes. In hip fracture care, bundled payment may spur development of multidisciplinary best practice guidelines, quality assessment, and reporting, and result in benchmarking and best practices sharing. However, its implementation may face challenges: the need for quality assessment criteria and risk adjustment methods and possible risks of pushing costs outside of Medicare boundaries.

Budget impact analysis of antiepileptic drugs for Lennox-Gastaut syndrome.

BACKGROUND: In October 2011, clobazam was FDA-approved for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS), a debilitating childhood epilepsy characterized by drop attacks, for patients 2 years and older. OBJECTIVE: To assess the budget impact of adding clobazam to an antiepileptic drug (AED) portfolio containing topiramate, lamotrigine, and rufinamide in a hypothetical, 100,000-member commercially insured health plan. METHODS: Patient characteristics and AED efficacy (decrease in drop-seizure frequency) were modeled with clinical data. Medical costs were derived from administrative claims data from a large U.S. managed health plan, with the assumption that 2.3% of drop seizures required medical care. Two-year budget impact was measured. Results were expressed as the overall difference in costs (medical and pharmacy) to a health plan and cost per member per month (PMPM) after addition of clobazam. Analyses of alternative scenarios were performed. RESULTS: With the assumption that 0.04% of the plan population had LGS, adding clobazam to the formulary resulted in cost savings of $98,059 in year 1 and $131,690 in year 2 (savings of $0.08 and $0.11 PMPM, respectively). Analyses of alternative scenarios with lower seizure rates upon discontinuation or greater long-term efficacy for lamotrigine and topiramate did not substantially alter conclusions. The assumption that fewer drop seizures required medical care resulted in a savings of approximately $5,000 per year with clobazam, which suggested that medically attended drop seizures drive costs. CONCLUSIONS: Medically attended drop seizures are a major cost driver for LGS patients. Adding clobazam to a health plan formulary can have a positive overall budget impact through decreased medical costs associated with drop seizures.

Cost effectiveness of a gene expression score and myocardial perfusion imaging for diagnosis of coronary artery disease.

BACKGROUND: Over 3 million patients annually present with symptoms suggestive of obstructive coronary artery disease (oCAD) in the United States (US), but a cardiac etiology is found in as few as 10% of cases. Usual care may include advanced cardiac testing with myocardial perfusion imaging (MPI), with attendant radiation risks and increased costs of care. We estimated the cost effectiveness of CAD diagnostic strategies including "no test," a gene expression score (GES) test, MPI, and sequential strategies combining GES and MPI. METHODS: We developed a Markov-based decision analysis model to simulate outcomes and costs in patients presenting to clinicians with symptoms suggestive of oCAD in the US. We estimated quality-adjusted life years (QALYs), total costs, and incremental cost-effectiveness ratios (ICERs) for each strategy. RESULTS: In our base case, the 2-threshold GES strategy is the most cost-effective strategy at a threshold of $100,000 per QALY gained, with an ICER of approximately $72,000 per QALY gained relative to no testing. Myocardial perfusion imaging alone and the 1-threshold strategy are weakly dominated. In sensitivity analysis, ICERs fall as the probability of oCAD increases from the base case value of 15%. The ranking of ICERs among strategies is sensitive to test costs, including the time cost for testing. The analysis reveals ways to improve on prespecified GES thresholds. CONCLUSIONS: Diagnostic testing for oCAD with a novel GES strategy in a 2-threshold model is cost effective by conventional standards. This diagnostic approach is more efficient than usual care of MPI alone or a 1-threshold GES strategy in most scenarios.

Cost-effectiveness analysis of antiepileptic drugs in the treatment of Lennox-Gastaut syndrome.

An economic model evaluated the costs and outcomes of adjunctive clobazam therapy for Lennox-Gastaut syndrome (LGS) compared with adjunctive lamotrigine, rufinamide, and topiramate. Clinical data were used to estimate baseline frequency and the percentage of drop-seizure reductions over 3 months (all comparators) and 2 years (rufinamide). Claims data from a large US health care plan were employed to estimate costs. After 3 months, 21.5% of those receiving clobazam were drop-seizure-free. Over a 3-month horizon, clobazam was more effective and less expensive than comparators, with the assumption that >0.77% of drop seizures required medical care. Below this threshold, topiramate was less costly than clobazam. With the base-case assumption that 2.3% of drop seizures were medically attended, costs for patients receiving clobazam totaled $30,147 versus $34,223-$35,378 for comparators. Clobazam was more efficacious and less costly than rufinamide over a 2-year horizon. The percentage of medically attended drop seizures was a driver of results. Clobazam treatment may be cost-saving.

Cost effectiveness of targeted high-dose atorvastatin therapy following genotype testing in patients with acute coronary syndrome.

BACKGROUND: Results from the PROVE IT trial suggest that patients with acute coronary syndrome (ACS) treated with atorvastatin 80 mg/day (A80) have significantly lower rates of cardiovascular events compared with patients treated with pravastatin 40 mg/day (P40). In a genetic post hoc substudy of the PROVE IT trial, the rate of event reduction was greater in carriers of the Trp719Arg variant in kinesin family member 6 protein (KIF6) than in noncarriers. We assessed the cost effectiveness of testing for the KIF6 variant followed by targeted statin therapy (KIF6 Testing) versus not testing patients (No Test) and treating them with P40 or A80 in the USA from a payer perspective. METHODS: A Markov model was developed in which 2-year event rates from PROVE IT were extrapolated over a lifetime horizon. Costs and utilities were derived from published literature. All costs were in 2010 US dollars except the cost of A80, which was in 2012 US dollars because the generic formulation was available in 2012. Expected costs and quality-adjusted life-years (QALYs) were estimated for each strategy over a lifetime horizon. RESULTS: Lifetime costs were US$31,700; US$37,100 and US$41,300 for No Test P40, KIF6 Testing and No Test A80 strategies, respectively. The No Test A80 strategy was associated with more QALYs (9.71) than the KIF6 Testing (9.69) and No Test P40 (9.57) strategies. No Test A80 had an incremental cost-effectiveness ratio (ICER) of US$232,100 per QALY gained compared with KIF6 Testing. KIF6 Testing had an ICER of US$45,300 per QALY compared with No Test P40. CONCLUSIONS: Testing ACS patients for KIF6 carrier status may be a cost-effective strategy at commonly accepted thresholds. Treating all patients with A80 is more expensive than treating patients on the basis of KIF6 results, but the modest gain in QALYs is achieved at a cost/QALY that is generally considered unacceptable compared with the KIF6 Testing strategy. Compared with treating all patients with P40, the KIF6 Testing strategy had an ICER below US$50,000 per QALY. The conclusions from this study are sensitive to the price of generic A80 and the effect on adherence of knowing KIF6 carrier status. The results were based on a post hoc substudy of the PROVE IT trial, which was not designed to test the effectiveness of KIF6 testing.