Bay 94-9027 Can be Accurately Measured across Regions with Appropriate One-Stage Assay Reagent Use
Bibliographic record
Abstract
Abstract Introduction: Differences in coagulation assay reagents may lead to variable results for some extended-half-life (EHL) recombinant factor VIII (rFVIII) products, with the potential to adversely affect patient care. Laboratories assessing EHL-rFVIII activity can choose from many available one-stage assay and chromogenic assay reagents. A field study was conducted to evaluate the ability of clinical laboratories to accurately measure FVIII activity in plasma samples spiked with BAY 94-9027, an EHL rFVIII, when using diverse assay reagents and when guided in the choice of reagent. In a regional subanalysis, BAY 94-9027 field study results from clinical laboratories in the United States and Canada were compared with those from Europe and Israel. Methods: In this 2-part study, a broad range of laboratories in the United States, Canada, Europe (Austria, Germany, Italy, Romania, Spain, Switzerland, United Kingdom), and Israel were provided samples containing defined concentrations of BAY 94-9027 or an unmodified rFVIII (antihemophilic factor [recombinant] plasma/albumin-free method [rAHF-PFM]) as a control. In part 1, each laboratory measured FVIII activity using their routine methods (one-stage assay, chromogenic assay, or both); laboratories that had ≥2 routine one-stage assays were asked to perform sample testing with one of the less commonly used assays in the laboratory to ensure that part 1 captured both the prevalence and heterogeneity of one-stage assays used in the geographic regions studied. In part 2, laboratories used one-stage assays with SynthASil and Pathromtin SL reagents provided by Bayer; SynthASil and Pathromtin SL have previously been shown to accurately measure BAY 94-9027 and full-length rFVIII products. The field study data were analyzed to identify the most commonly used reagents in the 2 regions (United States/Canada and Europe/Israel) and to assess if regional differences resulted in differences in accuracy of FVIII activity measurement. Results: 52 laboratories (US/Canada, n=25; Europe/Israel, n=27) participated in the field study. The one-stage reagent SynthASil was commonly used in all countries (n=15) in part 1, but differences were seen in the frequency of use of other reagents. PTT-A (n=6) and Actin FSL (n=5) were frequently used in the US/Canada and Actin FS (n=6) and Pathromtin SL (n=6) in Europe/Israel. Regional differences in the choice of assay, with US/Canada more likely to use assays that did not accurately measure BAY 94-9027, affected the ability of laboratories to accurately measure FVIII activity in the spiked samples (Figure). In part 1 of the study, regional differences in median recovery of BAY 94-9027 were seen among laboratories when using their own in-house one-stage assays. These differences were not seen in part 2 of the study when laboratories used provided reagents (SynthASil and Pathromtin SL), despite using the same instrumentation as used in part 1. Regional differences in part 1 might have been exacerbated by use of less common, and potentially inappropriate, one-stage assay reagents, affecting the accuracy of BAY 94-9027 measurement. Chromogenic assay use was more common in Europe/Israel (n=11) than US/Canada (n=5). No regional differences in chromogenic assay results were observed. Conclusions: Most clinical laboratories were able to accurately measure BAY 94-9027 activity using their in-house assays. However, regional differences in the accurate measurement of BAY 94-9027 activity were influenced by regional choice of one-stage reagents used in part 1 of the study; the activity and accuracy differences were eliminated when all laboratories used the same provided one-stage reagents with their in-house instruments (part 2 of study). Therefore, standardization of laboratory procedures and use of newer, more accurate one-stage assay reagents should improve measurement of FVIII activity with EHL products. Figure. Figure. Disclosures Castellone: Bayer: Membership on an entity's Board of Directors or advisory committees; Wilmer-Hale: Consultancy. Church:Bayer: Employment. Leong:Bayer: Employment. Kitchen:Bayer: Consultancy, Other: travel reimbursement, Speakers Bureau.
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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 | 0.006 | 0.009 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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".