Browsing by Author "Stebbins, Glenn T"
Now showing 1 - 20 of 27
Results Per Page
Sort Options
Item Open Access A Unified Framework for Evidence-Based Diagnostic Criteria Programs in Movement Disorders.(Movement disorders : official journal of the Movement Disorder Society, 2023-07) Mestre, Tiago A; Fabbri, Margherita; Luo, Sheng; Stebbins, Glenn T; Goetz, Christopher G; Sampaio, CristinaItem Open Access Application of Longitudinal Item Response Theory Models to Modeling Parkinson's Disease Progression.(CPT: pharmacometrics & systems pharmacology, 2022-07-27) Zou, Haotian; Aggarwal, Varun; Stebbins, Glenn T; Müller, Martijn LTM; Cedarbaum, Jesse M; Pedata, Anne; Stephenson, Diane; Simuni, Tanya; Luo, ShengThe Movement Disorder Society revised version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts 2 and 3 reflect patient-reported functional impact and clinician-reported severity of motor signs of Parkinson's disease (PD), respectively. Total scores are common clinical outcomes but may obscure important time-based changes in items. We aim to analyze longitudinal disease progression based on MDS-UPRDS Parts 2 and 3 item-level responses over time and as functions of Hoehn & Yahr (H&Y) stages 1 and 2 for subjects with early PD. The longitudinal IRT modeling is a novel statistical method addressing limitations in traditional linear regression approaches such as ignoring varying item sensitivities and the sum score balancing out improvements and declines. We utilized a harmonized dataset consisting of six studies with 3,573 early PD subjects and 14,904 visits, and mean follow-up time of 2.5 year (±1.57). We applied both a unidimensional (each Part separately) and multidimensional (both Parts combined) longitudinal item response theory (IRT) models. We assessed the progression rates for both parts, anchored to baseline Hoehn & Yahr (H&Y) stages 1 and 2. Both the uni- and multidimensional longitudinal IRT models indicate significant worsening time effects in both Parts 2 and 3. Baseline H&Y stage 2 was associated with significantly higher baseline severities, but slower progression rates in both parts, as compared with stage 1. Patients with baseline H&Y stage 1 demonstrated slower progression in Part 2 severity compared to Part 3, while patients with baseline H&Y stage 2 progressed faster in Part 2 than Part 3. The multidimensional model had a superior fit compared to the unidimensional models and it had excellent model performance.Item Open Access Co-Existent Probable RBD and PD: Disease Progression, Medication Response, and Clinical Trial Implications(Movement Disorders Clinical Practice, 2023-01-01) Zou, Haotian; Guo, Yuanyuan; Goetz, Christopher G; Mestre, Tiago A; Stebbins, Glenn T; Al-Hajraf, Falah; Lawton, Michael; Hu, Michele; Luo, ShengItem Open Access Cross-Cultural Differences in Patient Perceptions of Dyskinesia in Parkinson's Disease.(Mov Disord, 2023-01-20) Kaasinen, Valtteri; Luo, Sheng; Martinez-Martin, Pablo; Goetz, Christopher G; Stebbins, Glenn TBACKGROUND: The prevalence of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) varies among geographical regions. Cultural differences in patient-based perceptions of LID have not been studied. OBJECTIVE: We compared patient and clinician evaluations of LID severity across multiple cultures in patients with PD. METHODS: The data set included the Unified Dyskinesia Rating (UDysRS) scores from 16 language translation programs (3566 patients). We defined the Perception Severity Index (PSI) as the ratio between normalized patient-based subjective ratings (UDysRS Part 1B) and normalized clinician examination (Parts 3 and 4) scores (Part 1B/Parts 3 + 4) and compared the PSI across languages. RESULTS: The mean PSI for the Chinese language (2.16) was higher than those of all other languages, whereas the ratio for the Korean language (0.73) was lower than those for Japanese, German, Turkish, Greek, Polish, and Finnish languages (corrected P values <0.05). CONCLUSIONS: Culture, as represented by language, affects the subjective perception of LID and needs to be considered in multinational clinical PD trials on dyskinesia. © 2023 International Parkinson and Movement Disorder Society.Item Open Access Dissecting the Domains of Parkinson's Disease: Insights from Longitudinal Item Response Theory Modeling.(Movement disorders : official journal of the Movement Disorder Society, 2022-09) Luo, Sheng; Zou, Haotian; Stebbins, Glenn T; Schwarzschild, Michael A; Macklin, Eric A; Chan, James; Oakes, David; Simuni, Tanya; Goetz, Christopher G; Parkinson Study Group SURE-PD3 InvestigatorsBackground
Longitudinal item response theory (IRT) models previously suggested that the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor examination has two salient domains, tremor and nontremor, that progress in time and in response to treatment differently.Objective
Apply longitudinal IRT modeling, separating tremor and nontremor domains, to reanalyze outcomes in the previously published clinical trial (Study of Urate Elevation in Parkinson's Disease, Phase 3) that showed no overall treatment effects.Methods
We applied unidimensional and multidimensional longitudinal IRT models to MDS-UPDRS motor examination items in 298 participants with Parkinson's disease from the Study of Urate Elevation in Parkinson's Disease, Phase 3 (placebo vs. inosine) study. We separated 10 tremor items from 23 nontremor items and used Bayesian inference to estimate progression rates and sensitivity to treatment in overall motor severity and tremor and nontremor domains.Results
The progression rate was faster in the tremor domain than the nontremor domain before levodopa treatment. Inosine treatment had no effect on either domain relative to placebo. Levodopa treatment was associated with greater slowing of progression in the tremor domain than the nontremor domain regardless of inosine exposure. Linear patterns of progression were observed. Despite different domain-specific progression patterns, tremor and nontremor severities at baseline and over time were significantly correlated.Conclusions
Longitudinal IRT analysis is a novel statistical method addressing limitations of traditional linear regression approaches. It is particularly useful because it can simultaneously monitor changes in different, but related, domains over time and in response to treatment interventions. We suggest that in neurological diseases with distinct impairment domains, clinical or anatomical, this application may identify patterns of change unappreciated by standard statistical methods. © 2022 International Parkinson and Movement Disorder Society.Item Open Access Expanded and Independent Spanish validation of the MDS ‐ Non Motor Rating Scale(Movement Disorders Clinical Practice) Cubo, Esther; Luo, Sheng; Martínez-Martín, Pablo; Stebbins, Glenn T; Lin, Jeffrey; Choi, Dongrak; García-Bustillo, Alvaro; Mir, Pablo; Santos-Garcia, Diego; Serrano-Dueñas, Marcos; Rodriguez-Violante, Mayela; Singer, Carlos; and the Spanish MDS‐NMS Validation Study GroupItem Open Access IPMDS-Sponsored Scale Translation Program: Process, Format, and Clinimetric Testing Plan for the MDS-UPDRS and UDysRS(Movement Disorders Clinical Practice, 2014-06-01) Goetz, Christopher G; Stebbins, Glenn T; Wang, Lu; LaPelle, Nancy R; Luo, Sheng; Tilley, Barbara CWe present the methodology and results of the clinimetric testing program for non-English translations of International Parkinson and Movement Disorder Society (MDS)–sponsored scales. The programs focus on the MDS revision of the UPDRS (MDS-UPDRS) and the Unified Dyskinesia Rating Scale (UDysRS). The original development teams of both the MDS-UPDRS and UDysRS envisioned official non-English translations and instituted a rigorous translation methodology. The formal process includes five core steps: (1) registration and start-up; (2) translation and independent back-translation; (3) cognitive pretesting to establish that the translation is clear and that it is comfortably administered to and completed by native-speaker raters and patients; (4) field testing in the native language using a large sample of Parkinson's disease patients; and (5) full clinimetric testing. To date, the MDS-UPDRS has 21 active language programs. Nine official translations are available, having completed all phases successfully, and the others are in different stages of development. For the UDysRS, 19 programs are active, with three official translations now available and the rest in development at different stages. Very few scales in neurology and none in movement disorders have fully validated translations, and this model may be adopted or modified by other scale programs to allow careful validation of translations. Having validated translations allows for maximal homogeneity of tools utilized in multicenter research or clinical trial programs.Item Open Access It Is as It Was: MDS-UPDRS Part III Scores Cannot Be Combined with Other Parts to Give a Valid Sum.(Movement disorders : official journal of the Movement Disorder Society, 2022-12) Goetz, Christopher G; Choi, Dongrak; Guo, Yuanyuan; Stebbins, Glenn T; Mestre, Tiago A; Luo, ShengBackground
Original clinimetric analyses by the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) developers did not confirm the validity of summing the scores of its parts. Recent studies used the summed score of Part III and other parts as efficacy outcomes.Objective
The aim of this study was to establish whether summing scores of MDS-UPDRS parts can be recommended.Methods
Using 7466 full MDS-UPDRS scores, we applied two-step factor analysis as in the original article to reassess the validity analysis with the threshold criterion set at comparative fit index ≥0.9.Results
All comparative fit indexes of any combination including Part III were lower than 0.90.Conclusions
Summing Part III MDS-UPDRS scores with other parts is not clinimetrically sound. The MDS-UPDRS is a validated four-part scale with corresponding individual part scores and needs to be used within the limits originally presented. © 2022 International Parkinson and Movement Disorder Society.Item Open Access Item Response Theory Analysis of the MDS-UPDRS Motor Examination: Tremor vs. Nontremor Items.(Movement disorders : official journal of the Movement Disorder Society, 2020-05-29) Tosin, Michelle Hyczy de Siqueira; Goetz, Christopher G; Luo, Sheng; Choi, Dongrak; Stebbins, Glenn TBACKGROUND:In PD, tremor severity behaves differently from other core motor features. However, the most commonly used assessment of overall motor severity, total MDS-UPDRS Motor Examination (Part 3) score, does not account for this distinction. OBJECTIVES:To investigate the Motor Examination (Part 3) using Item Response Theory approaches focusing on sample-independent strategies that assess how well items measure latent models of PD motor severity. METHODS:Data from 6,298 PD patients were analyzed with graded response model Item Response Theory approaches involving two analyses all 33 Part 3 items versus the 10 tremor items and 23 bradykinesia, rigidity, gait, and posture items considered separately. The strength of relationship between items and the latent measure of parkinsonian motor severity (discrimination parameter) and calculated thresholds (location parameters) were assessed using the mirt program implemented in R (R Foundation for Statistical Computing, Vienna, Austria). RESULTS:Analyzing all Part 3 items together, nontremor items demonstrated good discrimination parameters (mean = 1.83 ± 0.37) and range of thresholds (-1.73 to +4.42), but tremor items had poor discrimination (mean = 0.52 ± 0.76) and thresholds (-0.69 to 14.29). Segregating nontremor from tremor items in two independent analyses provided markedly improved discrimination and location parameters for both. CONCLUSIONS:MDS-UPDRS Part 3 tremor and nontremor items have very different relations to the construct of PD severity. Strongly improved clinimetric properties for Part 3 are obtained when tremor and nontremor items are considered separately. We suggest that evaluating PD motor severity, as an operationalized summary measure, is best attained through separate analyses with tremor and nontremor motor scores. © 2020 International Parkinson and Movement Disorder Society.Item Open Access MDS‐UPDRS Motor Examination retains its two‐domain profile in both ON and OFF(Movement Disorders Clinical Practice) Guo, Yuanyuan; Stebbins, Glenn T; Mestre, Tiago A; Goetz, Christopher G; Luo, ShengItem Open Access Missing Data in the Unified Dysksinesia Rating Scale (UDysRS).(Movement disorders clinical practice, 2018-09) Luo, Sheng; Ren, Xuehan; Han, Weilu; Goetz, Christopher G; Stebbins, Glenn TIdentify the number of allowable missing values still permitting valid surrogate score calculation for the Unified Dyskinesia Rating Scale (UDysRS). Missing data frequently occur in Parkinson's disease rating scales, and they compromise data validity, risking data exclusion from final analyses. Accessing the International Parkinson and Movement Disorder Society-sponsored UDysRS translation databases (3313 complete scores). We sequentially removed item scores, consistently or randomly from subjective and objective sections. Lin's Concordance Correlation Coefficient compared prorated scores with complete scores. We considered prorated scores valid when Coefficients exceeded 0.95. For consistently missing items, three from the subjective section and five from the objective section are allowable. For randomly missing items, seven from the subjective section and four from the objective section are permissible. We provide guidelines for constructing valid surrogate summary UDysRS scores with clear thresholds for retaining or rejecting scores based on missing values.Item Open Access Movement Disorder Society-Unified Parkinson's Disease Rating Scale Use in the Covid-19 Era.(Movement disorders : official journal of the Movement Disorder Society, 2020-04-22) Goetz, Christopher G; Stebbins, Glenn T; Luo, ShengItem Open Access Novel Approach to Movement Disorder Society–Unified Parkinson's Disease Rating Scale Monitoring in Clinical Trials: Longitudinal Item Response Theory Models(Movement Disorders Clinical Practice, 2021-01-01) Luo, Sheng; Zou, Haotian; Goetz, Christopher G; Choi, Dongrak; Oakes, David; Simuni, Tanya; Stebbins, Glenn TBackground: Although nontremor and tremor Part 3 Movement Disorder Society–Unified Parkinson's Disease Rating Scale items measure different impairment domains, their distinct progression and drug responsivity remain unstudied longitudinally. The total score may obscure important time-based and treatment-based changes occurring in the individual domains. Objective: Using the unique advantages of item response theory (IRT), we developed novel longitudinal unidimensional and multidimensional models to investigate nontremor and tremor changes occurring in an interventional Parkinson's disease (PD) study. Method: With unidimensional longitudinal IRT, we assessed the 33 Part 3 item data (22 nontremor and 10 tremor items) of 336 patients with early PD from the STEADY-PD III (Safety, Tolerability, and Efficacy Assessment of Isradipine for PD, placebo vs. isradipine) study. With multidimensional longitudinal IRT, we assessed the progression rates over time and treatment (in overall motor severity, nontremor, and tremor domains) using Markov Chain Monte Carlo implemented in Stan. Results: Regardless of treatment, patients showed significant but different time-based deterioration rates for total motor, nontremor, and tremor scores. Isradipine was associated with additional significant deterioration over placebo in total score and nontremor scores, but not in tremor score. Further highlighting the 2 separate latent domains, nontremor and tremor severity changes were positively but weakly correlated (correlation coefficient, 0.108). Conclusions: Longitudinal IRT analysis is a novel statistical method highly applicable to PD clinical trials. It addresses limitations of traditional linear regression approaches and previous IRT investigations that either applied cross-sectional IRT models to longitudinal data or failed to estimate all parameters simultaneously. It is particularly useful because it can separate nontremor and tremor changes both over time and in response to treatment interventions.Item Open Access Prognostic Modeling of Parkinson's Disease Progression Using Early Longitudinal Patterns of Change.(Movement disorders : official journal of the Movement Disorder Society, 2021-07-30) Ren, Xuehan; Lin, Jeffrey; Stebbins, Glenn T; Goetz, Christopher G; Luo, ShengBackground
Predicting Parkinson's disease (PD) progression may enable better adaptive and targeted treatment planning.Objective
Develop a prognostic model using multiple, easily acquired longitudinal measures to predict temporal clinical progression from Hoehn and Yahr (H&Y) stage 1 or 2 to stage 3 in early PD.Methods
Predictive longitudinal measures of PD progression were identified by the joint modeling method. Measures were extracted by multivariate functional principal component analysis methods and used as covariates in Cox proportional hazards models. The optimal model was developed from the Parkinson's Progression Marker Initiative (PPMI) data set and confirmed with external validation from the Longitudinal and Biomarker Study in PD (LABS-PD) study.Results
The proposed prognostic model with longitudinal information of selected clinical measures showed significant advantages in predicting PD temporal progression in comparison to a model with only baseline information (iAUC = 0.812 vs. 0.743). The modeling results allowed the development of a prognostic index for categorizing PD patients into low, mid, and high risk of progression to HY 3 that is offered to facilitate physician-patient discussion on prognosis.Conclusion
Incorporating longitudinal information of multiple clinical measures significantly enhances predictive performance of prognostic models. Furthermore, the proposed prognostic index enables clinicians to classify patients into different risk groups, which could be adaptively updated as new longitudinal information becomes available. Modeling of this type allows clinicians to utilize observational data sets that inform on disease natural history and specifically, for precision medicine, allows the insertion of a patient's clinical data to calculate prognostic estimates at the individual case level. © 2021 International Parkinson and Movement Disorder Society.Item Open Access Reply to: "The Framework for Diagnostic Criteria in Movement Disorders: The Value of Methodological Tools and Combined Criteria".(Movement disorders : official journal of the Movement Disorder Society, 2023-09) Mestre, Tiago A; Luo, Sheng; Stebbins, Glenn T; Sampaio, Cristina; Goetz, Christopher GItem Open Access Reply to: Comment on "Summing MDS-UPDRS Parts 1 + 2 (Non-motor and Motor Experience of Daily Living): The Patient's Voice".(Movement disorders : official journal of the Movement Disorder Society, 2023-08) Goetz, Christopher G; Zou, Haotian; Stebbins, Glenn T; Schrag, Anette; Mestre, Tiago A; Luo, ShengItem Open Access Resolving Missing Data from the Movement Disorder Society Unified Parkinson's Disease Rating Scale: Implications for Telemedicine.(Movement disorders : official journal of the Movement Disorder Society, 2022-06-18) Luo, Sheng; Goetz, Christopher G; Choi, Dongrak; Aggarwal, Sanket; Mestre, Tiago A; Stebbins, Glenn TBackground
Telemedicine has become standard in clinical care and research during the coronavirus disease 2019 pandemic. Remote administration of Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination) precludes ratings of all items, because Rigidity and Postural Stability (six scores) require in-person rating.Objective
The objective of this study was to determine imputation accuracy for total-sum and item-specific MDS-UPDRS Motor Examination scores in remote administration.Methods
We applied multivariate imputation by chained equations techniques in a cross-sectional dataset where patients had one MDS-UPDRS rating (International Translational Program, n = 8,588) and in a longitudinal dataset where patients had multiple ratings (Rush Program, n = 396). Successful imputation was stringently defined as (1) generalized Lin's concordance correlation coefficient >0.95, reflecting near-perfect agreement between total-sum score with complete data and surrogate score, calculated without patients' actual Rigidity and Postural Stability scores; and (2) perfect agreement for item-level scores for Rigidity and Postural Stability items.Results
For total-sum score when Rigidity and Postural Stability scores were withdrawn, using one or multiple visits, multivariate imputation by chained equations imputation reached near-perfect agreement with the original total-sum score. However, at the item level, the degree of perfect agreement between the surrogate and actual Rigidity items and Postural Stability scores always fell below threshold.Conclusions
The MDS-UPDRS Part III total-sum score, a key clinical outcome in research and in clinical practice, can be accurately imputed without the Rigidity and Postural Stability items that cannot be rated by telemedicine. No formula, however, allows for specific item-level imputation. When Rigidity and Postural Stability item scores are of key clinical or research interest, patients with PD must be scored in person. © 2022 International Parkinson and Movement Disorder Society.Item Open Access Successful use of the Unified Dyskinesia Rating Scale regardless of PD- or dyskinesia-duration.(Parkinsonism & related disorders, 2019-10) Ren, Xuehan; Lin, Jeffrey; Luo, Sheng; Goetz, Christopher G; Stebbins, Glenn T; Cubo, EstherOBJECTIVE:We assessed differential item functioning (DIF) in the Unified Dyskinesia Rating Scale (UDysRS) to evaluate bias risk from the duration of Parkinson's Disease (PD) and duration of dyskinesia. BACKGROUND:Assessing DIF is a core validation step for rating scales. If DIF is present for an item, interpretation must consider influences from the tested covariates. DIF can be uniform or non-uniform, depending on the consistency of influence from the given covariate across all levels of dyskinesia. METHODS:Using a large UDysRS database (N = 2313), uniform and non-uniform DIF related to the duration of PD and/duration of dyskinesia were tested. Unidimensionality of UDysRS was first confirmed using confirmatory factor analysis. DIF analysis was conducted using two independent latent models. DIF in an item was confirmed if both methods independently identified DIF at a significance level using Bonferroni correction. McFadden pseudo R^2 measured clinical relevancy of DIF magnitude (negligible, moderate, and large) for items identified with DIF, and items with DIF were considered clinically relevant if they exceeded a negligible designation. RESULTS:Most items did not show uniform or non-uniform DIF based on PD and dyskinesia duration in isolation or in combination. For all items where DIF was identified, the magnitude statistic was in the negligible range (McFadden pseudo R^2 < 0.035) and the combined impact of multiple identified DIF items on UDysRS likewise did not exceed the negligible designation. CONCLUSION:The absence of clinically relevant DIF suggests that the UDysRS can be applied across all patients regardless of their PD- or dyskinesia-duration.Item Open Access Summing MDS-UPDRS Parts 1 + 2 (Non-motor and Motor Experience of Daily Living): The Patient's Voice.(Movement disorders : official journal of the Movement Disorder Society, 2023-04) Zou, Haotian; Goetz, Christopher G; Stebbins, Glenn T; Schrag, Anette; Mestre, Tiago A; Luo, ShengItem Open Access Using Movement Disorder Society Unified Parkinson's Disease Rating Scale Parts 2 and 3 Simultaneously: Combining the Patient Voice with Clinician Ratings(Movement Disorders) Guo, Yuanyuan; Goetz, Christopher G; Stebbins, Glenn T; Mestre, Tiago A; Luo, Sheng