F01 Development of the huntington’s disease integrated staging system (HD-ISS)
Bibliographic record
Abstract
Background HD is an inherited autosomal dominant neurodegenerative disease. While there is biological certainty that individuals with a pathogenic expansion in the huntingtin gene (HTT) will develop the signs and symptoms of HD within a normal lifespan, this is not reflected in present terminology. Current staging methods do not address disease progression before an overt clinical phenotype, despite well-accepted biomarkers of neurodegeneration predating clinical diagnosis. Aims To propose a new HD framework, referred to as the HD-ISS, that comprises an HD biological research definition and evidence-based staging centered on prognostic biological, clinical, and functional landmarks. Methods This framework is the result of a formal consensus process by the HD-RSC’s Regulatory Science Forum (RSF), a working group of expert representatives from industry and academia. Observational data was employed to calculate ‘cut-offs’ using the extreme values in models of the control population to define the HD-ISS Stages and to evaluate the framework. Results The HD-ISS defines HD biologically as the presence of the expanded HTT gene. The HD-ISS landmarks demonstrate robust prognostic value to classify individuals into each Stage and data-driven landmark thresholds to define Stage boundaries that are not CAG-dependent. Individual study visits, participant Stage progression, and longitudinal models of Stage progression align with the natural history of HD and with increased CAG predicting accelerated transitions. Conclusions The RSF has developed a biological definition of HD and an evidence-based staging system that encompass the full course of the disease and are unconstrained by concepts such as ‘manifest’ or ‘pre-manifest.’ The HD-ISS is intended for research settings to allow clinical trials earlier in the disease course, and provides a new structure to anchor and harmonize clinical study populations. The immediate use of the HD-ISS will allow for further validation.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.048 | 0.061 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.005 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.004 | 0.004 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.033 | 0.016 |
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".