International initiative for harmonization of cerebrospinal fluid diagnostic comments in Alzheimer's disease
Bibliographic record
Abstract
Abstract Background The quantification of cerebrospinal fluid (CSF) biomarkers (Abeta peptides [Ab1‐40 and Ab1‐42], tau protein and its phosphorylated form phospho‐tau) is progressively implemented in laboratories as an aid for the multidisciplinary diagnosis of Alzheimer disease (AD), DeKosky ST, Alz dementia, 2011, PMID: 21322828 . However, no consensus has been defined among the different laboratories involved to adapt the conclusions/comments to the level of quantified CSF biomarkers. As a result, although the analytical methods for such quantification may be similar across the laboratories involved in this clinical task, the conclusions transmitted to the physician in charge (neurologist or psychiatrist) may be quite different. Harmonization of this report is thus necessary so patients’ care and research stratification can be similar wherever the analysis is performed. Method A total of 34 laboratories (involved in CSF biomarkers measurement) across the world accepted to be part of our project of diagnostic’s comments harmonization (represented countries: Austria, Belgium, Canada, France, Germany, Italy, Netherland, Poland, Spain, Sweden, United Kingdom, USA). As a first step, we defined the 9 most typical biochemical profiles, according to the level of CSF biomarkers and their combination. For each profile, each laboratory was asked to provide us with the comments/conclusions given in routine clinical practice. We then collected and pooled all the comments in a common file, so that the laboratories could, as a second step, choose and order three of these comments (for each biochemical profile defined), according to their reliability in clinical practice. Result We are currently analysing the second step‐answers of the laboratories, in order to define a consensual pattern of comments and conclusions that could be implemented in all the laboratories involved in the biochemical diagnosis of AD. Obtained data will be presented. Conclusion The discrepancies of the comments for AD biochemical diagnosis across laboratories worldwide can be confusing and it is of strong importance to harmonize them (according to the level of quantified biomarkers and other information likely available such as the age, APOE genotype...). Our initiative will likely provide such harmonized pattern of comments/conclusions, thus ensuring equal care of patients across the different diagnostic centres.
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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 | 0.321 | 0.259 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.004 |
| Bibliometrics | 0.017 | 0.016 |
| Science and technology studies | 0.003 | 0.004 |
| Scholarly communication | 0.007 | 0.004 |
| Open science | 0.011 | 0.014 |
| Research integrity | 0.004 | 0.004 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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".