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BackgroundTardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with antipsychotic use. Data from RE-KINECT, a real-world study of antipsychotic-treated outpatients, were analyzed to assess the effects of possible TD on patient health and social functioning.MethodsAnalyses were conducted in Cohort 1 (patients with no abnormal involuntary movements) and Cohort 2 (patients with possible TD per clinician judgment). Assessments included: EuroQoL's EQ-5D-5L utility (health); Sheehan Disability Scale (SDS) total score (social functioning); patient- and clinician-rated severity of possible TD ("none", "some", "a lot"); and patient-rated impact of possible TD ("none", "some", "a lot"). Regression models were used to analyze the following: associations between higher (worse) severity/impact scores and lower (worse) EQ-5D-5L utility (indicated by negative regression coefficients); and associations between higher (worse) severity/impact scores and higher (worse) SDS total score (indicated by positive regression coefficients).ResultsIn Cohort 2 patients who were aware of their abnormal movements, patient-rated TD impact was highly and significantly associated with EQ-5D-5L utility (regression coefficient: - 0.023, P

IntroductionThe Alzheimer's Disease Composite Score (ADCOMS) is a tool developed to detect clinical progression and measure treatment effect in patients in early stages of Alzheimer's disease (AD). The psychometric properties of the ADCOMS have been established; however, the threshold for clinical meaningfulness has yet to be identified.MethodsAnchor-based, distribution-based, and ROC curve analyses were used to estimate clinically meaningful thresholds for change in ADCOMS for patients with mild cognitive impairment (MCI) and AD dementia. This study included data from three sources: the Alzheimer's Disease Neuroimaging Initiative (ADNI), the National Alzheimer's Coordinating Center (NACC), and a legacy dataset that included data from four sources: the placebo group from three MCI trials and an earlier data cut from ADNI. Results were stratified by disease severity (MCI vs. dementia) and APOE ε4 carrier status.ResultsA total of 5355 participants were included in the analysis. The ADCOMS was able to detect change for MCI and dementia patients who experienced a meaningful decline in cognition (as defined by the Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB]) between baseline and month 12. The following ADCOMS cut-offs were proposed: 0.05 for MCI and 0.10 for dementia.ConclusionsThe ADCOMS was previously established as a valid and reliable tool for use in clinical trials for MCI due to AD and dementia populations. By defining thresholds for clinically meaningful change of ADCOMS, this work is an important step in interpreting clinical findings and estimates of treatment effects in early stage AD trials.

Purpose/backgroundRE-KINECT (NCT03062033) was designed to assess the presence and impact of possible tardive dyskinesia (TD) in antipsychotic-treated outpatients.Methods/proceduresThe study included adults with 3 or more months of lifetime antipsychotic exposure and 1 or more psychiatric disorder. Based on clinician observation and assessment, patients were assigned to cohort 1 (without involuntary movements or with non-TD involuntary movements) or cohort 2 (with involuntary movements confirmed by clinician as possible TD). Baseline assessments included the following: patient characteristics; location/severity of involuntary movements; and impact of possible TD on health-related quality of life, including the EuroQoL 5-Dimensions 5-Level questionnaire.Findings/resultsOf 739 eligible patients, 204 (27.6%) had clinician-confirmed possible TD (cohort 2). Compared with cohort 1, patients in cohort 2 were significantly older (P < 0.0001), more likely to have schizophrenia or schizoaffective disorder (P < 0.0001) and longer lifetime exposure to antipsychotics (P < 0.0001), and less likely to be working or studying, based on clinician perception (P = 0.0010). Clinician- and patient-rated severity of possible TD movements was significantly correlated in each of 4 body regions (head/face, neck/trunk, upper extremities, lower extremities), for maximum severity in any region, and for total number of affected regions (P < 0.001 for all correlations). For the patient-rated EuroQoL 5-Dimensions 5-Level, the health state visual analog scale score was significantly lower (worse) in cohort 2 versus cohort 1 (66.8 vs 69.7; P = 0.0002), as was the utility index score (0.71 vs 0.76; P < 0.0175).Implications/conclusionsResults from this real-world population indicate that TD occurs frequently and can significantly reduce quality of life in patients with a psychiatric disorder.

Spasticity is common in multiple sclerosis (MS), often leading to functional limitations and disability. We developed a conceptual model of spasticity in MS integrating expert opinion, recent literature, and experiences of clinicians and people with MS spasticity. A conceptual model was developed based on a targeted literature review of articles published between 2014 and 2019, followed by input from clinicians, then input from participants with MS spasticity. Multidisciplinary experts on spasticity provided guidance at each step. Key concepts of the integrated spasticity conceptual model included: moderators; triggers; modifiers; treatment; objective manifestations; subjective experience; physical, functional, social, and emotional/psychological impacts; and long-term consequences. Participants with MS spasticity most frequently endorsed spasms, tightness, and pain as descriptors of spasticity. Some participants with MS spasticity had difficulty distinguishing spasticity from other MS symptoms (e.g. muscle weakness). Some triggers, emotional/psychological impacts, and long-term consequences of spasticity reported by participants with MS spasticity were not previously identified in the published literature. This conceptual model of spasticity, integrating published literature with the experience of clinicians, people with MS spasticity, and experts, demonstrates the complex, multidimensional nature of MS spasticity. This model may be used to improve clinician–patient dialogue, research, and patient care. Many people with multiple sclerosis (MS) have spasticity, generally in the lower limbs, but this symptom is complex and multidimensional and therefore difficult to characterize. MS spasticity may be influenced by moderators, triggers, modifiers, and treatment, all of which can affect objective measures and the subjective experience of spasticity. MS spasticity can have physical, functional, social, and emotional/psychological impacts as well as long-term consequences that can affect rehabilitation and ultimately reduce health-related quality of life for people with MS. Given that people with MS may view spasticity differently than their rehabilitation providers, providers should ask patients about their spasticity, including their moderators, triggers, modifiers, experience, impacts, long-term consequences, and effects on quality of life. This conceptual model provides a framework to improve clinician-patient dialogue, research, and rehabilitation for MS spasticity. [ABSTRACT FROM AUTHOR]

Patient reported outcomes provide the patient's perspective on the effectiveness of treatment. The draft Food and Drug Administration guidance on patient reported outcomes for labeling and promotional claims raises a number of method and measurement issues that require further clarification, including methods of determining responsiveness and minimal important differences. For clinical trials, instruments need to be based on a clear conceptual framework, have evidence supporting content validity and acceptable psychometric qualities. The measures must also have evidence documenting responsiveness and interpretation guidelines (i.e., minimal important difference) to be most useful as effectiveness endpoints in clinical trials. The recommended approach is to estimate the minimal important difference based on several anchor-based methods, with relevant clinical or patient-based indicators, and to examine various distribution-based estimates (i.e., effect size, standardized response mean, standard error of measurement) as supportive information, and then to triangulate on a single value or small range of values for the MID. Confidence in a specific MID value evolves over time and is confirmed by additional research evidence, including clinical trial experience. The MID may vary by population and context, and no one MID will be valid for all study applications involving a PRO instrument. Responsiveness and MID must be demonstrated and documented for the particular study population, and these measurement characteristics are needed for PRO labeling and promotional claims.

Background: RE-KINECT (NCT03062033), a real-world study of possible tardive dyskinesia (TD) in antipsychotic-treated patients, included a questionnaire to assess the effects of patients' abnormal involuntary movements on caregivers. Aims: To capture the experiences of caregivers who assisted individuals with abnormal involuntary movements that were confirmed by clinicians as being consistent with TD. Methods: Qualified (nonpaid) caregivers were invited to complete a questionnaire that included the following: caregivers' sociodemographic characteristics, their perceptions about the impact of abnormal involuntary movements on patients, and the impact of these movements on themselves (caregivers). Results: Of the 41 participating caregivers, 25 (61.0%) were women, 20 (48.8%) were employed full time or part time, and 35 (85.4%) were family members or friends. Based on responses from caregivers who noticed patients' abnormal involuntary movements and were caring for individuals who also noticed those movements, 48.0% of patients had "a lot" of severity in ≥1 body region and 76.0% had abnormal involuntary movements in ≥2 regions. Caregiver ratings were significantly correlated with patient ratings (but not with clinician ratings) for maximum severity of abnormal involuntary movements and the number of affected regions (both p <.05). Based on their own judgments and perceptions, caregivers reported that the patient's movements had "some" or "a lot" of impact on their (caregiver's) ability to continue usual activities (50.0%), be productive (58.3%), socialize (55.6%), or take care of self (50.0%). Conclusions: Caregivers as well as patients are negatively affected by TD, and the impact of TD on caregivers' lives should be considered when determining treatment options. [ABSTRACT FROM AUTHOR]

Objective: Tolerability and safety of treatments are important in oncology trials and should be informed by patient assessments. We identified the most relevant patient‐reported symptomatic adverse events (AEs) to measure in patients with non‐small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations. Methods: This study selected relevant symptomatic AEs from 78 AEs available in the Patient‐Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO‐CTCAE) measurement system. Initially, symptomatic AEs were selected based on literature and product labeling reviews, and then core sets of symptomatic AEs were identified by patient and clinician interviews. Qualitative and descriptive analyses were performed using the data collected from three iterative rounds of patient interviews. Results: During concept elicitation interviews involving 29 patients, 12 symptomatic AEs were identified and were then adapted into a 25‐item PRO‐CTCAE form for use in future clinical trials along with commonly used PRO measures. Cognitive interviews showed that the PRO‐CTCAE items were easy to answer and appropriate for assessing the patients' experience with symptomatic AEs. This study also assessed disease symptoms, impacts, and overall patient experience. Conclusions: The 25‐item PRO‐CTCAE form captures the most relevant symptomatic AEs in this patient population, and it is available for future studies. Baseline characterization of AEs associated with this distinct patient group contributes to our broader knowledge about NSCLC and through platforms like Project Patient Voice will expand our understanding of treatment tolerability and safety for NSCLC. Ultimately, this data collection will help inform decision‐making for patients, caregivers, healthcare providers, and regulators. [ABSTRACT FROM AUTHOR]