Qualitative interviews to support development of a patient-reported companion measure to the Glucocorticoid Toxicity Index.

INTRODUCTION: Glucocorticoids (GCs) are associated with multiple toxicities that have substantial impact on patients. We conducted qualitative interviews with patients to identify the toxicities that are most relevant from their perspective, with the goal of creating a patient-reported companion measure to the Glucocorticoid Toxicity Index (GTI), a clinician-facing instrument. METHODS: Thirty-one patients with recent or current GC use participated in concept elicitation interviews. Participants received GC treatment for myasthenia gravis, chronic inflammatory demyelinating polyradiculoneuropathy, vasculitis, or systemic lupus erythematosus. Transcripts were coded following a thematic analysis approach. RESULTS: Participants reported more than 100 toxicities they believed to be associated with their GC medications. Common toxicities included weight gain (87%), increased appetite (84%), insomnia/sleep problems (77%), cognitive impairment/brain fog (71%), easy bruising (68%), anxiety (65%), irritability/short temper (65%), and osteoporosis (39%). These toxicities often centered on self-esteem, neuropsychiatric effects, skin toxicities, and musculoskeletal function. They can be categorized into domains such emphasizing neuropsychiatric, metabolic/endocrine, musculoskeletal, and dermatological effects, highlighting aspects of GC toxicity that patients are uniquely positioned to appreciate and report. CONCLUSION: Our results confirm that the toxicities associated with GCs are pervasive and diverse, with substantial impact on patients' lives. These data will be used to inform the development of a patient-reported outcome measure assessing GC toxicity. This patient-reported instrument will be designed to complement the clinician-reported GTI, facilitating a more detailed understanding of the nuances of change in GC toxicity.

Efgartigimod improved health-related quality of life in generalized myasthenia gravis: results from a randomized, double-blind, placebo-controlled, phase 3 study (ADAPT).

There are substantial disease and health-related quality-of-life (HRQoL) burdens for many patients with myasthenia gravis (MG), especially for those whose disease symptoms are not well controlled. HRQoL measures such as the Myasthenia Gravis Quality of Life 15-item revised (MG-QOL15r) and EuroQoL 5-Dimensions 5-Levels (EQ-5D-5L) are vital for evaluating the clinical benefit of therapeutic interventions in patients with MG, as they assess the burden of disease and the effectiveness of treatment, as perceived by patients. The phase 3 ADAPT study (NCT03669588) demonstrated that efgartigimod-a novel neonatal Fc receptor inhibitor-was well tolerated and that acetylcholine receptor antibody-positive (AChR-Ab+) participants who received efgartigimod had statistically significant improvements in MG-specific clinical scale scores. The ancillary data reported here, which cover an additional treatment cycle, show that these participants had similar significant improvements in HRQoL measures, the MG-QOL15r and EQ-5D-5L utility and visual analog scales, and that these improvements were maintained in the second treatment cycle. Positive effects on HRQoL were rapid, seen as early as the first week of treatment in both treatment cycles, and maintained for up to 4 weeks in the follow-up-only portion of treatment cycles. The pattern of improvements in HRQoL paralleled changes in immunoglobulin G level, and correlational analyses show that improvements were consistent across HRQoL measures and with clinical efficacy measures in the ADAPT study. The substantial and durable improvements in HRQoL end points in this study demonstrate the broader benefit of treatment with efgartigimod beyond relief of immediate signs and symptoms of gMG.

Utilization of MG-ADL in myasthenia gravis clinical research and care.

The Myasthenia Gravis Activities of Living (MG-ADL) scale is an 8-item patient-reported scale that measures myasthenia gravis (MG) symptoms and functional status. The objective of the current review is to summarize the psychometric properties of the MG-ADL and published evidence of MG-ADL use. A targeted literature review for published studies of the MG-ADL was conducted using a database and gray literature search. A total of 48 publications and 35 clinical trials were included. Studies indicated that the MG-ADL is a reliable and valid measure that has been used as an outcome in clinical trials and observational studies to measure MG symptoms and response to treatment. While most often used as a secondary endpoint in clinical trials, its use as a primary endpoint has increased in recent years. The most common MG-ADL endpoint is change in MG-ADL score from baseline, although there has been an increase in the analysis of a responder threshold using the MG-ADL. A new concept of minimal symptom expression (MSE) has emerged more recently. Duration of treatment effect is another important construct that is being increasingly evaluated using the MG-ADL. The use of the MG-ADL as a primary endpoint in clinical trials and in responder threshold analyses to indicate treatment improvement has increased in recent years. MSE using the MG-ADL shows promise in helping to determine success of treatment and may be the aspirational goal of MG treatment for the future once validated, particularly given the evolving treatment landscape in MG.

Estimating health state utilities associated with a rare disease: familial chylomicronemia syndrome (FCS).

Aims: Familial chylomicronemia syndrome (FCS) is a rare genetic disorder with no currently approved therapies. Treatments are in development, and cost-utility analyses will be needed to examine their value. These models will require health state utilities representing FCS. Therefore, the purpose of this study was to estimate utilities for FCS and an associated episode of acute pancreatitis (AP).Methods: Because it is not feasible to gather a large enough sample of patients with this extremely rare condition to complete standardized preference-based measures, vignette-based methods were used to estimate utilities. In time trade-off interviews, general population participants in the UK and Canada valued health state vignettes drafted based on literature review, clinician input, and interviews with patients. Four health states described variations of FCS. A fifth health state, describing AP, was added to one of the other health states to evaluate its impact on utility.Results: A total of 308 participants provided utility data (208 UK; 100 Canada). Mean utilities for FCS health states ranged from 0.46 to 0.83, with higher triglycerides, more severe symptoms, and a history of AP associated with lower utility values. The disutility (i.e. utility decrease) of AP ranged from -0.17 to -0.25, with variations depending on the health state to which it was added. Utility means were similar in the UK and Canada.Conclusions: The vignette-based approach is useful for estimating utilities of a rare disease. The health state utilities derived in this study would be useful in models examining cost-effectiveness of treatments for FCS.

Quantifying neurologic disease using biosensor measurements in-clinic and in free-living settings in multiple sclerosis.

Technological advances in passive digital phenotyping present the opportunity to quantify neurological diseases using new approaches that may complement clinical assessments. Here, we studied multiple sclerosis (MS) as a model neurological disease for investigating physiometric and environmental signals. The objective of this study was to assess the feasibility and correlation of wearable biosensors with traditional clinical measures of disability both in clinic and in free-living in MS patients. This is a single site observational cohort study conducted at an academic neurological center specializing in MS. A cohort of 25 MS patients with varying disability scores were recruited. Patients were monitored in clinic while wearing biosensors at nine body locations at three separate visits. Biosensor-derived features including aspects of gait (stance time, turn angle, mean turn velocity) and balance were collected, along with standardized disability scores assessed by a neurologist. Participants also wore up to three sensors on the wrist, ankle, and sternum for 8 weeks as they went about their daily lives. The primary outcomes were feasibility, adherence, as well as correlation of biosensor-derived metrics with traditional neurologist-assessed clinical measures of disability. We used machine-learning algorithms to extract multiple features of motion and dexterity and correlated these measures with more traditional measures of neurological disability, including the expanded disability status scale (EDSS) and the MS functional composite-4 (MSFC-4). In free-living, sleep measures were additionally collected. Twenty-three subjects completed the first two of three in-clinic study visits and the 8-week free-living biosensor period. Several biosensor-derived features significantly correlated with EDSS and MSFC-4 scores derived at visit two, including mobility stance time with MSFC-4 z-score (Spearman correlation -0.546; p = 0.0070), several aspects of turning including turn angle (0.437; p = 0.0372), and maximum angular velocity (0.653; p = 0.0007). Similar correlations were observed at subsequent clinic visits, and in the free-living setting. We also found other passively collected signals, including measures of sleep, that correlated with disease severity. These findings demonstrate the feasibility of applying passive biosensor measurement techniques to monitor disability in MS patients both in clinic and in the free-living setting.

Multiple Sclerosis Performance Test: Technical Development and Usability.

INTRODUCTION: In the clinic, the assessment of patients with multiple sclerosis (MS) is typically qualitative and non-standardized. OBJECTIVES: To describe the MS Performance Test (MSPT), an iPad Air® 2 (Apple, Cupertino, CA, USA)-based neurological assessment platform allowing patients to input relevant information without the aid of a medical technician, creating a longitudinal, clinically meaningful, digital medical record. To report results from human factor (HF) and usability studies, and the initial large-scale implementation in a practice setting. METHODS: The HF study examined use-error patterns in small groups of MS patients and healthy controls (n = 14), the usability study assessed the effectiveness of patient interaction with the tool by patients with a range of MS disability (n = 60) in a clinical setting, and the implementation study deployed the MSPT across a diverse population of patients (n = 1000) in a large MS center for routine clinical care. RESULTS: MSPT assessments were completed by all users in the HF study; minor changes to design were recommended. In the usability study, 73% of patients with MS completed the MSPT, with an average administration time of 32 min; 85% described their experience with the tool as satisfactory. In the initial implementation for routine care, 84% of patients with MS completed the MSPT, with an average administration time of 28 min. CONCLUSION: Patients with MS with varying disability levels completed the MSPT with minimal or no supervision, resulting in comprehensive, efficient, standardized, quantitative, clinically meaningful data collection as part of routine medical care, thus allowing for large-scale, real-world evidence generation. FUNDING: Biogen. TRIAL REGISTRATION: NCT02664324.

Movement measurements at home for multiple sclerosis: walking speed measured by a novel ambient measurement system.

BACKGROUND: Gait disturbance is a major contributor to clinical disability in multiple sclerosis (MS). A sensor was developed to assess walking speed at home for people with MS using infrared technology in real-time without the use of wearables. OBJECTIVE: To develop continuous in-home outcome measures to assess gait in adults with MS. METHODS: Movement measurements were collected continuously for 8 months from six people with MS. Average walking speed and peak walking speed were calculated from movement data, then analyzed for variability over time, by room (location), and over the course of the day. In-home continuous gait outcomes and variability were correlated with standard in-clinic gait outcomes. RESULTS: Measured in-home average walking speed of participants ranged from 0.33 m/s to 0.96 m/s and peak walking speed ranged from 0.89 m/s to 1.51 m/s. Mean total within-participant coefficient of variation for daily average walking speed and peak walking speed were 10.75% and 10.93%, respectively. Average walking speed demonstrated a moderately strong correlation with baseline Timed 25-Foot Walk (rs = 0.714, P = 0.111). CONCLUSION: New non-wearable technology provides reliable and continuous in-home assessment of walking speed.

Validation of an ambient measurement system (AMS) for walking speed.

Walking speed is an important indicator of worsening in a variety of neurological and neuromuscular diseases, yet typically is measured only infrequently and in a clinical setting. Passive measurement of walking speed at home could provide valuable information to track the progression of many neuromuscular conditions. The purpose of this study was to validate the measurement of walking speed by a shelf-top ambient measurement system (AMS) that can be placed in a patient's home. Twenty-eight healthy adults (16 male, 12 female) were asked to walk three pre-defined routes two times each (total of 168 traversals). For each traversal, walking speed was measured simultaneously by five sources: two independent AMSs and three human timers with stopwatches. Measurements across the five sources were compared by generalised estimating equations (GEE). Correlation coefficients compared pairwise for walking speeds across the two AMSs, three human timers, and three routes all exceeded 0.86 (p < .0001), and for AMS-to-AMS exceeded 0.92 (p < .0001). Aggregated across all routes, there was no significant difference in measured walking speeds between the two AMSs (p = .596). There was a statistically significant difference between the AMSs and human timers of 8.5 cm/s (p < .0001), which is comparable to differences reported for other non-worn sensors. The tested AMS demonstrated the ability to automatically measure walking speeds comparable to manual observation and recording, which is the current standard for assessing walking speed in a clinical setting. The AMS may be used to detect changes in walking speed in community settings.

Qualitative Research on Fatigue Associated with Depression: Content Validity of the Fatigue Associated with Depression Questionnaire (FAsD-V2).

BACKGROUND: Fatigue is one of the most common symptoms of major depressive disorder (MDD). The Fatigue Associated with Depression Questionnaire (FAsD) was developed to assess fatigue and its impact in patients with MDD. The current article presents the qualitative research conducted to develop and examine the content validity of the FAsD and FASD-Version 2 (FAsD-V2). METHODS: Three phases of qualitative research were conducted with patients recruited from a geographically diverse range of clinics in the US. Phase I included concept elicitation focus groups, followed by cognitive interviews. Phase II employed similar techniques in a more targeted sample. Phase III included cognitive interviews to examine whether minor edits made after Phase II altered comprehensibility of the instrument. Concept elicitation focused on patients' perceptions of fatigue and its impact. Cognitive interviews focused on comprehension, clarity, relevance, and comprehensiveness of the instrument. Data were collected using semi-structured discussion guides. Thematic analyses were conducted and saturation was examined. RESULTS: A total of 98 patients with MDD were included. Patients' statements during concept elicitation in phases I and II supported item development and content. Cognitive interviews supported the relevance of the instrument in the target population, and patients consistently demonstrated a good understanding of the instructions, items, response options, and recall period. Minor changes to instructions for the FAsD-V2 did not affect interpretation of the instrument. CONCLUSIONS: This qualitative research supports the content validity of the FAsD and FAsD-V2. These results add to previous quantitative psychometric analysis suggesting the FAsD-V2 is a useful tool for assessing fatigue and its impact in patients with MDD.

Responder definition of the Multiple Sclerosis Impact Scale physical impact subscale for patients with physical worsening.

BACKGROUND: The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was developed to examine the impact of multiple sclerosis (MS) on physical and psychological functioning from a patient's perspective. OBJECTIVE: To determine the responder definition (RD) of the MSIS-29 physical impact subscale (PHYS) in a group of patients with relapsing-remitting MS (RRMS) participating in a clinical trial. METHODS: Data from the SELECT trial comparing daclizumab high-yield process with placebo in patients with RRMS were used. Physical function was evaluated in SELECT using three patient-reported outcomes measures and the Expanded Disability Status Scale (EDSS). Anchor- and distribution-based methods were used to identify an RD for the MSIS-29. RESULTS: Results across the anchor-based approach suggested MSIS-29 PHYS RD values of 6.91 (mean), 7.14 (median) and 7.50 (mode). Distribution-based RD estimates ranged from 6.24 to 10.40. An RD of 7.50 was selected as the most appropriate threshold for physical worsening based on corresponding changes in the EDSS (primary anchor of interest). CONCLUSION: These findings indicate that a ≥7.50 point worsening on the MSIS-29 PHYS is a reasonable and practical threshold for identifying patients with RRMS who have experienced a clinically significant change in the physical impact of MS.

The Fatigue Associated with Depression Questionnaire (FAsD): responsiveness and responder definition.

PURPOSE: The Fatigue Associated with Depression Questionnaire (FAsD) was developed to assess fatigue and its impact among patients with depression. The purpose of this study was to examine the questionnaire's responsiveness to change and identify a responder definition for interpretation of treatment-related changes. METHODS: Data were collected at baseline and at 6 weeks from patients with depression starting treatment with a new antidepressant. RESULTS: Of the 96 participants, 55.2% were women, with a mean age of 43.4 years. The total score and both subscales demonstrated statistically significant change with moderate to large effect sizes (absolute values ≥ 0.76). FAsD change scores were significantly correlated with change on the Brief Fatigue Inventory (r ≥ 0.73; p < 0.001). FAsD mean change scores discriminated among patient subgroups differing by degree of improvement in patient- and clinician-reported fatigue and depression. Responder definition for the two subscales and total score (0.67, 0.57, 0.62) was estimated primarily based on mean change among patients who reported a small but important improvement in fatigue. DISCUSSION: The FAsD was responsive to change, and the responder definition may be used when interpreting treatment-related change. Results add to previous findings suggesting the FAsD is a useful measure of fatigue among patients with depression.

Validation of a patient interview for assessing reasons for antipsychotic discontinuation and continuation.

INTRODUCTION: The Reasons for Antipsychotic Discontinuation Interview (RAD-I) was developed to assess patients' perceptions of reasons for discontinuing or continuing an antipsychotic. The current study examined reliability and validity of domain scores representing three factors contributing to these treatment decisions: treatment benefits, adverse events, and distal reasons other than direct effects of the medication. METHODS: Data were collected from patients with schizophrenia or schizoaffective disorder and their treating clinicians. For approximately 25% of patients, a second rater completed the RAD-I for assessment of inter-rater reliability. RESULTS: All patients (n = 121; 81 discontinuation, 40 continuation) reported at least one reason for discontinuation or continuation (mean = 2.8 reasons for discontinuation; 3.4 for continuation). Inter-rater reliability was supported (kappas = 0.63-1.0). Validity of the discontinuation domain scores was supported by associations with symptom measures (the Positive and Negative Syndrome Scale for Schizophrenia, the Clinical Global Impression - Schizophrenia Scale; r = 0.30 to 0.51; all P < 0.01), patients' primary reasons for discontinuation, and adverse events. However, the continuation domain scores were not significantly associated with these other indicators. DISCUSSION: Results support the reliability, convergent validity, and known-groups validity of the RAD-I for assessing patients' reasons for antipsychotic discontinuation. Further research is needed to examine validity of the RAD-I continuation section.

Validation of a clinician questionnaire to assess reasons for antipsychotic discontinuation and continuation among patients with schizophrenia.

The Reasons for Antipsychotic Discontinuation Questionnaire (RAD-Q) was designed to assess clinicians' perceptions of reasons for antipsychotic discontinuation or continuation. The current study examined psychometric properties of this instrument and patterns of antipsychotic discontinuation. The sample of 121 patients (81 discontinuation, 40 continuation) with schizophrenia or schizoaffective disorder was 66.9% male, with a mean age of 41.6 years. Treating clinicians reported a mean of 4.1 reasons for discontinuation and 7.5 reasons for continuation. RAD-Q domain scores were derived to quantify the impact of three factors on the decision to discontinue or continue: treatment benefits, adverse events, and distal reasons other than direct effects of the medication. Analysis of inter-rater reliability indicated an acceptable degree of agreement between clinicians (weighted Kappa for discontinuation scores=0.70-0.78). Correlations with symptom measures (Clinical Global Impression-Schizophrenia Scale (CGI-SCH), Positive and Negative Syndrome Scale (PANSS)) supported convergent validity of the benefits domain score (r=0.28-0.47; all p<0.05). Domain scores discriminated among groups of patients differing in clinician and patient-reported clinical variables. Results suggest that the RAD-Q is a useful detailed measure of reasons for antipsychotic discontinuation and continuation. Findings indicate that clinicians usually report multiple reasons for discontinuation, rather than a single reason for each patient.

Reasons for continuing or discontinuing olanzapine in the treatment of schizophrenia from the perspectives of patients and clinicians.

BACKGROUND: The aim of this study was to assess the reasons for discontinuing or continuing olanzapine in patients with schizophrenia, from the perspectives of the patients and their clinicians. METHODS: The Reasons for Antipsychotic Discontinuation/Continuation (RAD) is a pair of questionnaires assessing these reasons from the perspectives of patients and their clinicians. Outpatients with schizophrenia (n = 199) who were not acutely ill participated in a 22-week open-label study of olanzapine from November 2006 to September 2008. Reasons for continuing or discontinuing olanzapine (on a five-point scale), along with the single most important reason and the top primary reasons, were identified. Concordance between reasons given by patients and clinicians was assessed. RESULTS: The top primary reasons for continuing olanzapine were patients' perceptions of improvement, improvement of positive symptoms, and improved functioning. The study discontinuation rate was low (30.2%), and only a subset of patients who discontinued reported reasons for medication discontinuation. The top primary reasons for discontinuing olanzapine were insufficient improvement or worsening of positive symptoms, adverse events, and insufficient improvement or worsening of negative symptoms. Ratings given by patients and clinicians were highly concordant. CONCLUSION: The main reason for continuing or discontinuing olanzapine appears to be medication efficacy, especially for positive symptoms. Reasons for medication discontinuation differ somewhat from reasons for continuation, with a high level of concordance between patient and clinician responses.

Cost of post-traumatic stress disorder vs major depressive disorder among patients covered by medicaid or private insurance.

OBJECTIVE: To compare healthcare costs and resource utilization among patients with post-traumatic stress disorder (PTSD) vs control subjects with major depressive disorder (MDD) in populations covered by Medicaid or private insurance. STUDY DESIGN: Retrospective analysis of Medicaid and private insurance administrative claims data. METHODS: Patients with at least 2 PTSD diagnoses during or after 1999, and at least 1 PTSD diagnosis during or after 2003, were identified from deidentified Medicaid claims from Florida, Missouri, and New Jersey (1999-2007) and from a privately insured claims database (1999-2008). Patients had continuous eligibility 6 months before (baseline) and 12 months after (study period) the index date and were aged 18 to 64 years. Potential control subjects having MDD without PTSD diagnosis were identified using similar selection criteria. Control subjects with MDD were matched to patients with PTSD on age, sex, state or region, employment status (private insurance only), index year, and race/ethnicity (Medicaid only). Study period per-patient utilization and costs, calculated as reimbursements to providers for medical services and prescription drugs, were compared using univariate and multivariate analyses. RESULTS: Patients with PTSD had higher rates of other mental health disorders (eg, anxiety and bipolar disorder) and higher mental health-related resource use and costs than control subjects with MDD in both Medicaid and privately insured populations. The mean study period total direct healthcare costs were higher for patients with PTSD than for control subjects with MDD ($18,753 vs $17,990 for Medicaid and $10,960 vs $10,024 for private insurance, P <.05 for both). The difference in total direct costs was driven by higher mental health-related resource use for patients with PTSD. CONCLUSION: Patients having PTSD had 4.2% to 9.3% higher mean annual per-patient healthcare costs compared with matched control subjects having MDD among patients covered by Medicaid or private insurance.

Development and validation of a patient-report measure of fatigue associated with depression.

INTRODUCTION: Among researchers and clinicians who treat depression, there is growing interest in treatment of specific residual symptoms such as fatigue. However, there is no available measure that provides a detailed assessment of fatigue associated with depression. Thus, the purpose of the current study was to develop and validate a patient-reported outcome measure designed to assess depression-related fatigue and its impact. METHODS: The Fatigue Associated with Depression Questionnaire (FAsD) was developed based on literature review, clinician interviews, and focus groups and cognitive debriefing interviews with patients. Then, a draft questionnaire was administered to a sample of patients with depression. Statistical analysis first focused on item reduction and subscale identification, followed by psychometric evaluation of the FAsD. RESULTS: The per protocol sample (n = 317) was primarily female (68.1%), with a mean age of 47.0 years. Based on item performance and exploratory factor analysis, three items were dropped from the draft FAsD, yielding a final 13-item questionnaire with two subscales (experience and impact). The FAsD demonstrated good internal consistency reliability (Cronbach's alphas ≥ 0.88) and test-retest reliability (intraclass correlation coefficients ≥ 0.78). The FAsD demonstrated construct validity through strong correlations with measures assessing fatigue/energy and symptoms of depression. The FAsD also discriminated among groups of participants differentiated by clinician ratings of global severity of depression (CGI-S). LIMITATIONS: Limitations include heterogeneity of current treatments received by the sample, as well as lack of knowledge regarding the extent to which FAsD scores were influenced by patients' treatments rather than the depression itself. CONCLUSIONS: In this initial psychometric evaluation, the FAsD demonstrated good reliability, validity, and factor structure. This questionnaire may be a useful tool for evaluating treatment interventions that focus specifically on fatigue associated with depression.

Development of a clinician questionnaire and patient interview to assess reasons for antipsychotic discontinuation.

Time to treatment discontinuation and rates of discontinuation are commonly used when evaluating effectiveness of antipsychotic medication. However, less is known about reasons for discontinuation. The purpose of this study was to develop two measures of reasons for discontinuation or continuation of antipsychotics for the treatment of schizophrenia. Based on literature review, a patient interview pilot study, and expert panel input, two measures were drafted: the clinician-reported Reasons for Antipsychotic Discontinuation/Continuation Questionnaire (RAD-Q) and the patient-reported Reasons for Antipsychotic Discontinuation/Continuation Interview (RAD-I). Patients and clinicians completed the draft measures and structured cognitive debriefing interviews. For the draft instruments, reasons for discontinuation/continuation were divided into 3 categories: therapeutic benefits (positive symptoms, negative symptoms, mood, cognition, functional status), adverse events, and reasons other than direct effects of the medication (e.g., cost, inadequate social support). In cognitive debriefings, 10 clinicians and 15 patients indicated that the RAD-Q and RAD-I were clear, easy to complete, and comprehensive. Clinicians and patients suggested minor revisions, and the instruments were revised accordingly. The RAD-Q and RAD-I appear to be useful instruments for assessing reasons for antipsychotic discontinuation and continuation. The next step is a psychometric evaluation of the measures in a larger sample.

Reasons for discontinuation and continuation of antipsychotics in the treatment of schizophrenia from patient and clinician perspectives.

OBJECTIVE: To identify reasons for discontinuation and continuation of antipsychotic medications in the treatment of schizophrenia from the patients' and their clinicians' perspectives. RESEARCH DESIGN AND METHODS: Two measures were previously developed to assess the Reasons for Antipsychotic Discontinuation/Continuation (RAD), one from the patient's perspective and another from the clinician's perspective. These measures were administered to acutely ill schizophrenia patients enrolled in a 12-week study of antipsychotic medications (N = 596) and to their clinicians. The RAD was assessed at baseline and at endpoint. Reasons were rated on a 5-point scale from 'primary reason' to 'not a reason.' The single most important reason was also identified. The 'single most important reason' and the 'primary reasons' for discontinuing the drug used prior to enrollment, and for discontinuing or continuing the study drug were identified. Levels of concordance between patients' and clinicians' reasons were assessed. CLINICAL TRIAL REGISTRATION: The data source for this study is a clinical trial registered at www.clinicaltrials.gov (NCT00337662). MAIN OUTCOME MEASURES: Reasons for Antipsychotic Discontinuation/Continuation (RAD). RESULTS: Patients and clinicians identified several reasons for medication discontinuation and continuation (2.3 to 6.3 reasons, on average). The top 'single most important' reason for discontinuing the drug used prior to enrollment and for discontinuing the study drug was 'positive symptoms not sufficiently improved or made worse,' followed by 'medication-related adverse events.' The most frequent 'single most important' reason for medication continuation was 'improved positive symptoms,' followed by 'patient's perception of improvement,' and 'functional improvement.' A high level of concordance was observed between patients' and clinicians' ratings. CONCLUSIONS: Medication efficacy appears to be the core driver of medication discontinuation and continuation, especially with regard to positive symptoms. There was a high level of concordance between patients' and clinicians' perspectives. Limitations include the study requirement that patients be at least moderately ill and experiencing acute psychotic exacerbation, a potential selection bias in the readiness to respond to measures, and small sample sizes for some analyses. Further research is needed to replicate findings in patients who are not acutely ill.

Antipsychotic adherence, switching, and health care service utilization among Medicaid recipients with schizophrenia.

OBJECTIVE: To evaluate health care resource utilization in patients with schizophrenia who continued newly prescribed antipsychotic medications, compared with those switching to different treatments. METHODS: Adults with schizophrenia in the California Medicaid (MediCal) database who initiated treatment with index medications in 1998-2001, were classified as having: 1) abandoned antipsychotic medications; 2) switched to another medication; or 3) continued with the index antipsychotic, for up to 6 months after the index date. RESULTS: Of 2300 patients meeting eligibility criteria, 1382 (60.1%) continued index medications, 480 (20.9%) switched, and 438 (19.0%) abandoned antipsychotic treatment. Utilization in several resource categories occurred significantly more frequently among patients whose regimens were switched (vs those continuing index medications). These included using psychiatric (24.2% vs 14.5%; P < 0.001) or nonpsychiatric (31.5% vs 24.3%; P < 0.05) emergency services; being admitted to a hospital (10.6% vs 7.4%; P < 0.05); making nonpsychiatric outpatient hospital visits (43.3% vs 36.4%; P < 0.05) or nonpsychiatric physician visits (62.7% vs 56.4%; P < 0.05); and using other outpatient psychiatric (53.3% vs 40.7%; P < 0.001) or nonpsychiatric (82.7% vs 74.6%; P < 0.001) services. CONCLUSIONS: Switching antipsychotic medications is associated with significantly increased health care resource utilization (vs continuing treatment).

Development of the burden of prior authorization of psychotherapeutics (BoPAP) scale to assess the effects of prior authorization among Texas Medicaid providers.

This study describes an instrument to measure the perceived effects of prior authorization on quality of care among Texas Medicaid patients with severe mental illness. A questionnaire was mailed to 1,650 prescribers of psychiatric medications and 226 responses were used for analyses (17.5% response rate). Factor analysis revealed a 3-factor, 25-item instrument (BoPAP scale). Overall, prescribers reported a moderate burden of PA (BoPAP Mean = 3.90 +/- 0.52, possible range = 1-5). They perceived a high burden (4.49 +/- 0.57) on "administrative issues," a moderate burden (3.93 +/- 0.66) on "patient care processes/outcomes" and the lowest burden (3.30 +/- 0.74) on "system/societal costs." BoPAP scores differed based on provider characteristics, indicating evidence of discriminant validity.