Essential Tremor and Digital Biomarkers: A Scoping Review Using the TRACE Framework to Map Readiness for Clinical Trials and Routine Practice

[i] Studies are grouped by sensor modality and ordered chronologically within each group. TRACE tier assignments reflect the highest level of validation evidence achieved by each study. * Denotes Tier 3 (Ambulatory and Longitudinal Validation), defined as studies meeting all three criteria of calendar day separation, home or ambulatory data collection, and temporal performance evidence; ** Denotes Tier 4 (Clinical Trial Readiness), defined as a digital metric pre-specified as a primary or secondary endpoint in a registered clinical trial, or multi-site deployment across three or more independent sites with adherence and data completeness reporting. No study achieved Tier 5 (Economic and Implementation Readiness). ^† Denotes studies deploying sensors spanning two modality categories; listed under primary modality.

ET n refers to the number of Essential Tremor participants only; where studies enrolled mixed diagnostic cohorts, participants with other diagnoses are excluded from this count. The Clinical Anchor column records the validated clinical rating scale used as the reference standard for digital metric validation. None indicates no formal correlation with a validated clinical scale was reported. Informal estimate indicates that a clinician visual rating was used without a formally validated instrument. Where a scale was used solely for patient characterisation or group assignment without direct correlation against the digital metric, this is also recorded as None.

The Notes and Flags column records the following methodological designations. ET comparator: ET patients were recruited as a reference group for a study whose primary focus was another movement disorder, most commonly Parkinson’s disease; ET-specific digital biomarker performance was not a primary study aim. ET subgroup: ET patients were included within a larger mixed-diagnosis cohort without a dedicated ET-focused analysis. Tier 2+: a multi-visit or test-retest clinic design providing reliability, MDC, or longitudinal validation data across calendar-separated sessions without a home or ambulatory component; these studies are assigned Tier 2 in all analyses but represent the strongest candidates for Tier 3 promotion given the addition of a home deployment component. Tier 4 signal: a Tier 3 study that additionally demonstrates one or more operational features consistent with Tier 4 readiness, such as multi-site data collection or quantified adherence reporting, but does not meet the full Tier 4 threshold due to absence of a pre-registered endpoint or defined measurement context. Feasibility-grade Tier 3: all Tier 3 criteria are met but the ET sample size is fewer than 15, limiting the generalisability and statistical precision of the longitudinal and ambulatory evidence. Repeated-measures exception: the study was included despite an ET sample size below the standard eligibility threshold of ten participants based on a strong repeated-measures design providing substantial within-subject measurement. Therapeutic context: the device serves a primary therapeutic function; the digital biomarker is a secondary or co-primary endpoint rather than the sole purpose of the device. Contains Tier 1 component: the study includes both bench-level or phantom device validation and ET clinical patient data; the tier assigned reflects the highest tier achieved in the clinical component.

ET, Essential Tremor; TRACE, Technology Readiness and Clinical Evidence framework; IMU, inertial measurement unit; EMG, electromyography; TETRAS, Tremor Research Group Essential Tremor Rating Assessment Scale; FTM-TRS, Fahn-Tolosa-Marín Tremor Rating Scale; CRST, Clinical Rating Scale for Tremor; CRST-C, Clinical Rating Scale for Tremor Part C; MDS-UPDRS, Movement Disorder Society Unified Parkinson’s Disease Rating Scale; MDC, Minimum Detectable Change; NR, not reported; TAPS, Transcutaneous Afferent Patterned Stimulation; wTRS, Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET) tremor rating scale; TCRS, Tremor Clinical Rating Scale, a modified Fahn-Tolosa-Marin scale; FXTAS-RS, Fragile X-associated tremor/ataxia syndrome Rating Scale; BFRS, Bain & Findley Rating Scale; VTRS, Vocal Tremor Rating Scale; SARA, Scale for the assessment and rating of ataxia; QUEST-Voice, a 5-point patient-reported severity scale from the Quality of Life in Essential Tremor Questionnaire.

[i] For each modality, the highest TRACE validation tier achieved by any included study is reported alongside the best-evidenced device(s) or platform(s), the primary gap preventing trial integration, and the availability of minimum important difference and patient-reported outcome correlation data. Studies marked with † used sensors spanning two modalities and are listed under their primary modality; see Figure 2 for dual-counted modality totals. MID values reported in López-Blanco 2018, Elble 2017 and Rajan 2023 represent Minimum Detectable Changes or anchor-derived thresholds rather than formally derived Minimum Important Differences. ET, Essential Tremor; TRACE, Technology Readiness and Clinical Evidence framework; MID, Minimum Important Difference; PRO, Patient-Reported Outcome; MDC, Minimum Detectable Change; TAPS, Transcutaneous Afferent Patterned Stimulation; QUEST, Quality of Life in Essential Tremor Questionnaire; VHI, Voice Handicap Index; CRST-C, Clinical Rating Scale for Tremor Part C (patient self-report); IMU, inertial measurement unit; EMG, electromyography.