J009 PROOF-HD: changes in q-motor and cuhdrs show an alignment of objective measures and clinical scales, and the capability of q-motor to predict long-term clinical outcomes
Bibliographic record
Abstract
Background Q-Motor measures lack rater-bias and revealed higher sensitivity and consistency than clinical scales in several trials, but little is known about the relationship of treatment responses between Q-Motor and clinical scales. Observational studies and clinical trials show correlation between longitudinal worsening in the objective measures of Q-Motor and worsening in clinical progression as assessed by cUHDRS, TFC, and TMS. Objective To assess correlations between the benefit of pridopidine in Q-Motor and measures of clinical progression, and to determine the predictive value of early benefits in Q-Motor towards later improvements in measures of clinical progression and function. Methods In PROOF-HD, the primary Q-Motor tapping endpoint ‘Inter-Onset-Interval’ (IOI) was analyzed in the ‘finger-tapping’ (digitomotography) and ‘pronate/supinate-hand-tapping’ (dysdiadochomotography) tasks. Correlations between changes in IOI and changes in cUHDRS and TFC at weeks 26, 52, 65 and 78 were calculated. A causal inference model adjusting for natural disease progression and baseline characteristics was applied to assess the relationship of these changes with pridopidine treatment. In addition, we assessed whether early changes to 26 weeks correlate with changes to later visits up to week 78. Results Changes in IOI and the cUHDRS were correlated at all visits in finger-tapping [r=-0.26–-0.41, p<0.0001] and pronate/supinate-tapping [r=-0.17–-0.30, p=0.0038–p<0.0001]. Early Q-Motor improvements at 26 weeks were correlated to benefits in cUHDRS at later visits, up to week 78 in finger-tapping [r=-0.17–-0.23, p=0.0048–p=0.00018] and pronate-supinate-tapping [r=-0.12–-0.19, p=0.036–r=0.0057]. The causal-interference-model confirmed these findings with significant relationships detected for treatment induced changes at all visits for both tasks [all p<0.0001]. The model suggests that every 10 msec benefit of pridopidine in finger-tapping is associated with an average of 0.1 less decline in cUHDRS (p<0.0001). Similar observations were seen with the TFC. Conclusion The correlation of observed changes in Q-Motor measures and cUHDRS and TFC suggest an alignment of objective measures and clinical scales in the assessment of treatment effects in PROOF-HD up to week 78. Furthermore, Q-Motor effects at 26 weeks are highly predictive of changes in cUHDRS and TFC at later visits.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".