Cost consequence analysis of Apathy in Dementia Methylphenidate Trial 2 (ADMET 2).
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ABSTRACT: Background
This paper used data from the Apathy in Dementia Methylphenidate Trial 2 (NCT02346201) to conduct a planned cost consequence analysis to investigate whether treatment of apathy with methylphenidate is economically attractive.Methods
A total of 167 patients with clinically significant apathy randomized to either methylphenidate or placebo were included. The Resource Utilization in Dementia Lite instrument assessed resource utilization for the past 30 days and the EuroQol five dimension five level questionnaire assessed health utility at baseline, 3 months, and 6 months. Resources were converted to costs using standard sources and reported in 2021 USD. A repeated measures analysis of variance compared change in costs and utility over time between the treatment and placebo groups. A binary logistic regression was used to assess cost predictors.Results
Costs were not significantly different between groups whether the cost of methylphenidate was excluded (F(2,330) = 0.626, ηp2 = 0.004, p = 0.535) or included (F(2,330) = 0.629, ηp2 = 0.004, p = 0.534). Utility improved with methylphenidate treatment as there was a group by time interaction (F(2,330) = 7.525, ηp2 = 0.044, p < 0.001).Discussion
Results from this study indicated that there was no evidence for a difference in resource utilization costs between methylphenidate and placebo treatment. However, utility improved significantly over the 6-month follow-up period. These results can aid in decision-making to improve quality of life in patients with Alzheimer's disease while considering the burden on the healthcare system.
SUBMITTER: Lanctot KL
PROVIDER: S-EPMC10579450 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
Publications
Cost consequence analysis of Apathy in Dementia Methylphenidate Trial 2 (ADMET 2).
Lanctôt Krista L KL Chen Clara C Mah Ethan E Kiss Alex A Li Abby A Shade Dave D Scherer Roberta W RW Vieira Danielle D Coulibaly Hamadou H Rosenberg Paul B PB Lerner Alan J AJ Padala Prasad R PR Brawman-Mintzer Olga O van Dyck Christopher H CH Porsteinsson Anton P AP Craft Suzanne S Levey Allan A Burke William J WJ Mintzer Jacobo J Herrmann Nathan N
International psychogeriatrics 20230417 11
<h4>Background</h4>This paper used data from the Apathy in Dementia Methylphenidate Trial 2 (NCT02346201) to conduct a planned cost consequence analysis to investigate whether treatment of apathy with methylphenidate is economically attractive.<h4>Methods</h4>A total of 167 patients with clinically significant apathy randomized to either methylphenidate or placebo were included. The Resource Utilization in Dementia Lite instrument assessed resource utilization for the past 30 days and the EuroQo ...[more]
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Project description:BackgroundAlzheimer's disease (AD) is characterized not only by cognitive and functional decline, but also often by the presence of neuropsychiatric symptoms. Apathy, which can be defined as a lack of motivation, is one of the most prevalent neuropsychiatric symptoms in AD and typically leads to a worse quality of life and greater burden for caregivers. Treatment options for apathy in AD are limited, but studies have examined the use of the amphetamine, methylphenidate. The Apathy in Dementia Methylphenidate Trial (ADMET) found that treatment of apathy in AD with methylphenidate was associated with significant improvement in apathy in two of three outcome measures, some evidence of improvement in global cognition, and minimal adverse events. However, the trial only enrolled 60 participants who were followed for only 6 weeks. A larger, longer-lasting trial is required to confirm these promising findings.MethodsThe Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) is a phase III, placebo-controlled, masked, 6-month, multi-center, randomized clinical trial targeted to enroll 200 participants with AD and apathy. Participants are randomly assigned 1:1 to 20 mg methylphenidate per day prepared as four over-encapsulated tablets or to matching placebo. The primary outcomes include (1) the mean difference in the Neuropsychiatric Inventory Apathy subscale scores measured as change from baseline to 6 months, and (2) the odds of having a given rating or better on the modified AD Cooperative Study Clinical Global Impression of Change ratings at month 6 compared with the baseline rating. Other outcomes include change in cognition, safety, and cost-effectiveness measured at monthly follow-up visits up to 6 months.DiscussionGiven the prevalence of apathy in AD and its impact on both patients and caregivers, an intervention to alleviate apathy would be of great benefit to society. ADMET 2 follows on the promising results from the original ADMET to evaluate the efficacy of methylphenidate as a treatment for apathy in AD. With a larger sample size and longer follow up, ADMET 2 is poised to confirm or refute the original ADMET findings.Trial registrationClinicalTrials.gov, NCT02346201 . Registered on 26 January 2015.
| S-EPMC5774109 | biostudies-literature
Project description:BackgroundDiagnostic criteria for apathy have been published but have yet to be evaluated in the context of clinical trials. The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) operationalized the diagnostic criteria for apathy (DCA) into a clinician-rated questionnaire informed by interviews with the patient and caregiver.ObjectiveThe goal of the present study was to compare the classification of apathy using the DCA with that using the Neuropsychiatric Inventory-apathy (NPI-apathy) subscale in ADMET 2. Comparisons between NPI-Apathy and Dementia Apathy Interview Rating (DAIR) scale, and DCA and DAIR were also explored.MethodsADMET 2 is a randomized, double-blind, placebo-controlled phase III trial examining the effects of 20 mg/day methylphenidate on symptoms of apathy over 6 months in patients with mild to moderate Alzheimer's disease (AD). Participants scoring at least 4 on the NPI-Apathy were recruited. This analysis focuses on cross-sectional correlations between baseline apathy scale scores using cross-tabulation.ResultsOf 180 participants, the median age was 76.5 years and they were predominantly white (92.8%) and male (66.1%). The mean (±standard deviation) scores were 7.7 ± 2.4 on the NPI-apathy, and 1.9 ± 0.5 on the DAIR. Of those with NPI-defined apathy, 169 (93.9%, 95% confidence interval [CI] 89.3%-96.9%) met DCA diagnostic criteria. The DCA and DAIR overlapped on apathy diagnosis for 169 participants (93.9%, 95% CI 89.3%-96.9%).ConclusionThe measurements used for the assessment of apathy in patients with AD had a high degree of overlap with the DCA. The NPI-apathy cut-off used to determine apathy in ADMET 2 selects those likely to meet DCA criteria.
| S-EPMC7704818 | biostudies-literature
Project description:ImportanceApathy, characterized by diminished will or initiative and one of the most prevalent neuropsychiatric symptoms in individuals with Alzheimer disease, is associated with significant caregiver burden, excess disability, increased medical costs, and mortality.ObjectiveTo measure whether methylphenidate compared with placebo decreases the severity of apathy in individuals with Alzheimer disease.Design, setting, and participantsThis multicenter randomized placebo-controlled clinical trial was conducted from August 2016 to July 2020 in 9 US clinics and 1 Canadian clinic specializing in dementia care. A total of 307 potential participants were screened. Of those, 52 did not pass screening and 55 were not eligible. Participants with Alzheimer disease, mild to moderate cognitive impairment, and frequent and/or severe apathy as measured by the Neuropsychiatric Inventory (NPI) were included.InterventionsTen milligrams of methylphenidate, twice daily, vs matching placebo.Main outcomes and measuresThe coprimary outcomes included (1) change from baseline to 6 months in the NPI apathy subscale or (2) improved rating on the Alzheimer's Disease Cooperative Study Clinical Global Impression of Change. Other outcomes include safety, change in cognition, and quality of life.ResultsOf 200 participants, 99 were assigned to methylphenidate and 101 to placebo. The median (interquartile range) age of study participants was 76 (71-81) years; 68 (34%) were female and 131 (66%) were male. A larger decrease was found from baseline to 6 months in the NPI apathy score in those receiving methylphenidate compared with placebo (mean difference, -1.25; 95% CI, -2.03 to -0.47; P = .002). The largest decrease in the NPI apathy score was observed in the first 100 days, with a significant hazard ratio for the proportion of participants with no apathy symptoms receiving methylphenidate compared with placebo (hazard ratio, 2.16; 95% CI, 1.19-3.91; P = .01). At 6 months, the odds ratio of having an improved rating on the Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for methylphenidate compared with placebo was 1.90 (95% CI, 0.95-3.84; P = .07). The difference in mean change from baseline to 6 months estimated using a longitudinal model was 1.43 (95% CI, 1.00-2.04; P = .048). Cognitive measures and quality of life were not significantly different between groups. Of the 17 serious adverse events that occurred during the study, none were related to the study drug. No significant differences in the safety profile were noted between treatment groups.Conclusions and relevanceThis study found methylphenidate to be a safe and efficacious medication to use in the treatment of apathy in Alzheimer disease.Trial registrationClinicalTrials.gov Identifier: NCT02346201.
| S-EPMC8477302 | biostudies-literature
Project description:ObjectivesAmong participants with Alzheimer's disease (AD) we estimated the minimal clinically important difference (MCID) in apathy symptom severity on three scales.DesignRetrospective anchor- and distribution-based analyses of change in apathy symptom scores.SettingApathy in Dementia Methylphenidate Trial (ADMET) and ADMET 2 randomized controlled trials conducted at three and ten clinics specialized in dementia care in United States and Canada, respectively.ParticipantsTwo hundred and sixty participants (60 ADMET, 200 ADMET 2) with clinically significant apathy in Alzheimer's disease.MeasurementsThe Clinical Global Impression of Change in Apathy scale was used as the anchor measure and the MCID on the Neuropsychiatric Inventory - Apathy (NPI-A), Dementia Apathy Interview and Rating (DAIR), and Apathy Evaluation Scale-Informant (AES-I) were estimated with linear mixed models across all study visits. The estimated thresholds were evaluated with performance metrics.ResultsAmong the MCID was a decrease of four points (95% CI: -4.0 to -4.8) on the NPI-A, 0.56 points (95% CI: -0.47 to -0.65) on the DAIR, and three points on the AES-I (95% CI: -0.9 to -5.4). Distribution-based analyses were largely consistent with the anchor-based analyses. The MCID across the three measures showed ∼60% accuracy. Sensitivity analyses found that MMSE scores and apathy severity at baseline influenced the estimated MCID.ConclusionsMCIDs for apathy on three scales will help evaluate treatment efficacy at the individual level. However, the modest correspondence between MCID and clinical impression of change suggests the need to consider other scales.
| S-EPMC11695175 | biostudies-literature
Project description:ObjectiveThe Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) found that methylphenidate was effective in treating apathy with a small-to-medium effect size but showed heterogeneity in response. We assessed clinical predictors of response to help determine individual likelihood of treatment benefit from methylphenidate.DesignUnivariate and multivariate analyses of 22 clinical predictors of response chosen a priori.SettingData from the ADMET 2 randomized, placebo controlled multi-center clinical trial.ParticipantsAlzheimer's disease patients with clinically significant apathy.MeasurementsApathy assessed with the Neuropsychiatric Inventory apathy domain (NPI-A).ResultsIn total, 177 participants (67% male, mean [SD] age 76.4 [7.9], mini-mental state examination 19.3 [4.8]) had 6-months follow up data. Six potential predictors met criteria for inclusion in multivariate modeling. Methylphenidate was more efficacious in participants without NPI anxiety (change in NPI-A -2.21, standard error [SE]:0.60) or agitation (-2.63, SE:0.68), prescribed cholinesterase inhibitors (ChEI) (-2.44, SE:0.62), between 52 and 72 years of age (-2.93, SE:1.05), had 73-80 mm Hg diastolic blood pressure (-2.43, SE: 1.03), and more functional impairment (-2.56, SE:1.16) as measured by the Alzheimer's Disease Cooperative Study Activities of Daily Living scale.ConclusionIndividuals who were not anxious or agitated, younger, prescribed a ChEI, with optimal (73-80 mm Hg) diastolic blood pressure, or having more impaired function were more likely to benefit from methylphenidate compared to placebo. Clinicians may preferentially consider methylphenidate for apathetic AD participants already prescribed a ChEI and without baseline anxiety or agitation.
| S-EPMC10765607 | biostudies-literature
Project description:ObjectiveIn a recent crossover trial, methylphenidate treatment decreased apathy in Alzheimer's disease. We further assessed this finding in the Apathy in Dementia Methylphenidate Trial (ADMET).MethodSix-week, randomized, double-blind, placebo-controlled multicenter trial enrolling Alzheimer's disease participants (NINCDS-ADRDA criteria) with apathy assigned to methylphenidate 20 mg daily or placebo, conducted from June 2010 to December 2011. Primary outcomes were change in Apathy Evaluation Scale (AES) score and modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGI-C). Secondary outcomes included change in Neuropsychiatric Inventory (NPI) apathy score, Mini-Mental State Examination (MMSE) score, and safety.Results60 participants were randomly assigned (29 methylphenidate, 31 placebo). At baseline, mean (SD) age = 76 (8) years, MMSE score = 20 (5), AES score = 51 (12), NPI total score = 16 (8), and 62% of the participants (n = 37) were female. After 6 weeks' treatment, mean (SD) change in AES score was -1.9 (1.5) for methylphenidate and 0.6 (1.4) for placebo (P = .23). Odds ratio for improvement in ADCS-CGI-C was 3.7 (95% CI, 1.3 to 10.8) (P = .02), with 21% of methylphenidate versus 3% of placebo rated as moderately or markedly improved. NPI apathy score improvement was 1.8 points (95% CI, 0.3 to 3.4) greater on methylphenidate than on placebo (P = .02). MMSE trended toward improvement on methylphenidate (P = .06). There were trends toward greater anxiety and weight loss > 2% in the methylphenidate-treated group.ConclusionsMethylphenidate treatment of apathy in Alzheimer's disease was associated with significant improvement in 2 of 3 efficacy outcomes and a trend toward improved global cognition with minimal adverse events, supporting the safety and efficacy of methylphenidate treatment for apathy in Alzheimer's disease.Trial registrationClinicalTrials.gov identifier: NCT01117181.
| S-EPMC3902018 | biostudies-literature
Project description:AIMS AND OBJECTIVES:The objective of this analysis was to clarify the concepts of apathy and passivity in the context of dementia by identifying distinguishing and overlapping attributes for both concepts simultaneously. BACKGROUND:Apathy is among the most common and persistent symptoms in dementia. The concept of apathy is often used interchangeably with passivity. Understanding similarities and differences between these concepts is of critical importance in clarifying clinical diagnostic criteria, developing consistent measurement in research and translating research evidence into nursing practice. DESIGN:A systematic literature search of multiple databases identified relevant articles for review. A modified combination of Haase et al.'s simultaneous concept analysis method and Morses' principle-based concept analysis using qualitative content and thematic analysis procedures was applied to identify overlapping and distinguishing attributes. METHODS:A search of PubMed, CINAHL and PsycINFO databases identified 176 articles meeting inclusion criteria. The concepts of apathy and passivity were characterised using a standardised manual to identify attributes of definitions (conceptual and operational), related conditions, functional, behavioural and neurobiological correlates, antecedents and consequences. Thematic analysis identified common themes across each category which were tabulated and entered into comparative matrices to identify overlapping and distinguishing features. RESULTS:There is considerable overlap across attributes of apathy and passivity. Apathy is distinguished as a clinical syndrome characterised by loss of motivation not due to emotional distress or cognitive impairment. Passivity is distinguished as a lack of interaction between the individual and environment in the context of cognitive impairment. CONCLUSION:In contrast to passivity, apathy is a more robustly defined concept focused on motivational limitations within the individual associated with specific neuroanatomical deficits. RELEVANCE TO CLINICAL PRACTICE:The identification of key distinguishing features of apathy and passivity in dementia is a critical first step in ensuring consistent measurement of each concept.
| S-EPMC6326867 | biostudies-literature
Project description:Physical inactivity has been identified as a leading risk factor for premature mortality globally, and adolescents, in particular, have low physical activity levels. Schools have been identified as a setting to tackle physical inactivity. Economic evidence of school-based physical activity programmes is limited, and the costs of these programmes are not always collected in full. This paper describes a micro-costing and cost-consequence analysis of the 'Girls Active' secondary school-based programme as part of a cluster randomised controlled trial (RCT). Micro-costing and cost-consequence analyses were conducted using bespoke cost diaries and questionnaires to collect programme delivery information. Outcomes for the cost-consequence analysis included health-related quality of life measured by the Child Health Utility-9D (CHU-9D), primary care General Practitioner (GP) and school-based (school nurse and school counsellor) service use as part of a cluster RCT of the 'Girls Active' programme. Overall, 1,752 secondary pupils were recruited and a complete case sample of 997 participants (Intervention n = 570, Control n = 427) was used for the cost-consequence analysis. The micro-costing analysis demonstrated that, depending upon how the programme was delivered, 'Girls Active' costs ranged from £1,054 (£2 per pupil, per school year) to £3,489 (£7 per pupil, per school year). The least costly option was to absorb 'Girls Active' strictly within curriculum hours. The analysis demonstrated no effect for the programme for the three main outcomes of interest (health-related quality of life, physical activity and service use).Micro-costing analyses demonstrated the costs of delivering the 'Girls Active' programme, addressing a gap in the United Kingdom (UK) literature regarding economic evidence from school-based physical activity programmes. This paper provides recommendations for those gathering cost and service use data in school settings to supplement validated and objective measures, furthering economic research in this field. Trial registration: -ISRCTN, ISRCTN10688342.
| S-EPMC6697369 | biostudies-literature
Project description:The neuropsychiatric syndrome of apathy is now recognized to be a common and disabling condition in Huntington's disease. However, the mechanisms underlying it are poorly understood. One way to investigate apathy is to use a theoretical framework of normal motivated behaviour, to determine where breakdown has occurred in people with this behavioural disruption. A fundamental computation underlying motivated, goal-directed behaviour across species is weighing up the costs and rewards associated with actions. Here, we asked whether people with apathy are more sensitive to costs of actions (physical effort and time delay), less sensitive to rewarding outcomes, or both. Based on the unique anatomical substrates associated with Huntington's disease pathology, we hypothesized that a general hypersensitivity to costs would underpin Huntington's disease apathy. Genetically confirmed carriers of the expanded Huntingtin gene (premanifest to mild motor manifest disease, n = 53) were compared to healthy controls (n = 38). Participants performed a physical effort-based decision-making task (Apple Gathering Task) and a delay discounting task (Money Choice Questionnaire). Choice data was analysed using linear regression and drift diffusion models that also accounted for the time taken to make decisions. Apathetic people with Huntington's disease accepted fewer offers overall on the Apple Gathering Task, specifically driven by increased sensitivity to physical effort costs, and not explained by motor severity, mood, cognition or medication. Drift diffusion modelling provided further evidence of effort hypersensitivity, with apathy associated with a faster drift rate towards rejecting offers as a function of varying effort. Increased delay sensitivity was also associated with apathy, both when analysing raw choice and drift rate, where there was moderate evidence of Huntington's disease apathy drifting faster towards the immediately available (low-cost) option. Furthermore, the effort and delay sensitivity parameters from these tasks were positively correlated. The results demonstrate a clear mechanism for apathy in Huntington's disease, cost hypersensitivity, which manifests in both the effort and time costs associated with actions towards rewarding goals. This suggests that Huntington's disease pathology may cause a domain-general disruption of cost processing, which is distinct from apathy occurrence in other brain disorders and may require different therapeutic approaches.
| S-EPMC11884755 | biostudies-literature
Project description:IntroductionWhile apathy is broadly defined as a loss of motivation, it is increasingly recognised as a multidimensional syndrome spanning executive, emotional, and initiation domains. Emotional apathy is purportedly driven by deficits in using socioemotional rewards to guide behaviour, yet the link between these symptoms and reward processing, and their common neural correlates, has not been directly examined.MethodsSixty-four patients (33 behavioural-variant frontotemporal dementia, 14 Alzheimer's disease, 8 semantic dementia, 6 progressive nonfluent aphasia, 3 logopenic progressive aphasia) were classified into high (HEA; n = 36) and low (LEA; n = 28) emotional apathy groups based on emotional apathy subscale scores on the Dimensional Apathy Scale. Patients and age-matched healthy controls (n = 27) performed an instrumental reward learning task where they learned to associate cues with either social or monetary outcomes.ResultsHEA patients showed impaired learning on both the social and monetary reward conditions, relative to LEA patients (p = 0.016) and controls (p = 0.005). Conversely, the LEA group did not differ from controls (p = 0.925). Importantly, multiple regression analyses indicated that social reward learning significantly predicted emotional apathy. Voxel-based morphometry analyses revealed that emotional apathy and social reward learning were both associated with orbitofrontal cortex, ventral striatum, and insula atrophy.DiscussionOur results demonstrate a unique link between impaired social reward learning and emotional apathy in dementia and reveal a shared neurobiological basis. Greater understanding of these neurocognitive mechanisms of reward processing will help improve the identification of emotional apathy in dementia and inform the development of novel interventions to address these symptoms.
| S-EPMC10049956 | biostudies-literature