Using Smartphone Sensors for Ataxia Trials: Consensus Guidance by the Ataxia Global Initiative Working Group on Digital-Motor Biomarkers.

Smartphone sensors are used increasingly in the assessment of ataxias. To date, there is no specific consensus guidance regarding a priority set of smartphone sensor measurements, or standard assessment criteria that are appropriate for clinical trials. As part of the Ataxia Global Initiative Digital-Motor Biomarkers Working Group (AGI WG4), aimed at evaluating key ataxia clinical domains (gait/posture, upper limb, speech and oculomotor assessments), we provide consensus guidance for use of internal smartphone sensors to assess key domains. Guidance was developed by means of a literature review and a two stage Delphi study conducted by an Expert panel, which surveyed members of AGI WG4, representing clinical, research, industry and patient-led experts, and consensus meetings by the Expert panel to agree on standard criteria and map current literature to these criteria. Seven publications were identified that investigated ataxias using internal smartphone sensors. The Delphi 1 survey ascertained current practice, and systems in use or under development. Wide variations in smartphones sensor use for assessing ataxia were identified. The Delphi 2 survey identified seven measures that were strongly endorsed as priorities in assessing 3/4 domains, namely gait/posture, upper limb, and speech performance. The Expert panel recommended 15 standard criteria to be fulfilled in studies. Evaluation of current literature revealed that none of the studies met all criteria, with most being early-phase validation studies. Our guidance highlights the importance of consensus, identifies priority measures and standard criteria, and will encourage further research into the use of internal smartphone sensors to measure ataxia digital-motor biomarkers.

Frequently Used Patient-Reported Outcome Measures of General Physical Function Were Highly Correlated With a Multitask Performance Outcome Test Battery.

OBJECTIVES: This study aimed to determine the relationship between frequently used patient-reported outcome (PRO) measures and a multitask performance outcome (PerfO) measure of general physical function (PF) and to examine the association of these measures with depressive mood, pain, and age. METHODS: Frequently used PRO measures of general PF (Patient-Reported Outcomes Measurement Information System [PROMIS] PF item bank, PROMIS PF Short Form 20a, Short Form 36 Physical Function Scale) and a PerfO test battery, namely, the Physical Performance Test (PPT), were administered to 78 adult patients from 3 inpatient clinics (cardiology and angiology, rheumatology and clinical immunology, and psychosomatic medicine) at Charité - Universitätsmedizin Berlin. Pearson correlations were used to investigate the associations between PRO measures and the PPT. To explore the predictive value of age, depressive symptoms, and pain intensity, we conducted multiple linear regression analysis for each PF measure. RESULTS: We found strong linear relationships between PRO measures and PPT sum scores. Correlations between PPT sum scores and PROMIS PF T-scores were r > 0.75. For all PRO and PerfO measures, age was a predictor of general PF whereas depressive mood was not found to be a relevant predictor. Moreover, pain intensity was found to be a significant predictor of PRO measures but not for PPT sum scores. CONCLUSIONS: Our findings suggest that frequently used PRO measures and a multitask PerfO measure of general PF can be used to measure a common PF construct. Nevertheless, PF scores based on PRO measures should ideally be controlled for self-rated pain intensity.

Good practices for the translation, cultural adaptation, and linguistic validation of clinician-reported outcome, observer-reported outcome, and performance outcome measures.

Within current literature and practice, the category of patient-reported outcome (PRO) measures has been expanded into the broader category of clinical outcome assessments (COAs), which includes the subcategory of PRO, as well as clinician-reported outcome (ClinRO), observer-reported outcome (ObsRO), and performance outcome (PerfO) measure subcategories. However, despite this conceptual expansion, recommendations associated with translation, cultural adaptation, and linguistic validation of COAs remain focused on PRO measures, which has created a gap in specific process recommendations for the remaining types. This lack of recommendations has led to inconsistent approaches being implemented, leading to uncertainty in the scientific community regarding suitable methods. To address this gap, the ISOQOL Translation and Cultural Adaptation Special Interest Group (TCA-SIG) has developed recommendations specific to each of the three COA types currently lacking such documentation to support a standardized approach to their translation, cultural adaptation, and linguistic validation. The recommended process utilized to translate ObsRO, ClinRO and PerfO measures from one language to another aligns closely with the industry standard process for PRO measures. The substantial differences between respondent categories across COA types require targeted approaches to the cognitive interviewing procedures utilized within the linguistic validation process, including the use of patients for patient-facing text in ClinRO measures, and the need to interview the targeted observers for ObsROs measures.

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.

The MSOAC approach to developing performance outcomes to measure and monitor multiple sclerosis disability.

BACKGROUND: The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability. OBJECTIVES: (1) To assess the current literature and available data on functional performance outcome measures (PerfOs) and (2) to determine suitability of using PerfOs to quantify MS disability in MS clinical trials. METHODS: (1) Identify disability dimensions common in MS; (2) conduct a comprehensive literature review of measures for those dimensions; (3) develop an MS Clinical Data Interchange Standards Consortium (CDISC) data standard; (4) create a database of standardized, pooled clinical trial data; (5) analyze the pooled data to assess psychometric properties of candidate measures; and (6) work with regulatory agencies to use the measures as primary or secondary outcomes in MS clinical trials. CONCLUSION: Considerable data exist supporting measures of the functional domains ambulation, manual dexterity, vision, and cognition. A CDISC standard for MS ( http://www.cdisc.org/therapeutic#MS ) was published, allowing pooling of clinical trial data. MSOAC member organizations contributed clinical data from 16 trials, including 14,370 subjects. Data from placebo-arm subjects are available to qualified researchers. This integrated, standardized dataset is being analyzed to support qualification of disability endpoints by regulatory agencies.