Quality Control of Busulfan Plasma Quantitation, Modeling, and Dosing: An Interlaboratory Proficiency Testing Program
Bibliographic record
Abstract
BACKGROUND: Personalizing busulfan doses to target a narrow plasma exposure has improved the efficacy and lowered the toxicity of busulfan-based conditioning regimens used in hematopoietic cell transplant. Regional regulations guide interlaboratory proficiency testing for busulfan concentration quantification and monitoring. To date, there have been no comparisons of the busulfan pharmacokinetic modeling and dose recommendation protocols used in these laboratories. Here, in collaboration with the Dutch Association for Quality Assessment in Therapeutic Drug Monitoring and Clinical Toxicology, a novel interlaboratory proficiency program for the quantitation in plasma, pharmacokinetic modeling, and dosing of busulfan was designed. The methods and results of the first 2 rounds of this proficiency testing are described herein. METHODS: A novel method was developed to stabilize busulfan in N,N-dimethylacetamide, which allowed shipping of the proficiency samples without dry ice. In each round, participating laboratories reported their results for 2 proficiency samples (one low and one high busulfan concentrations) and a theoretical case assessing their pharmacokinetic modeling and dose recommendations. All participants were blinded to the answers; descriptive statistics were used to evaluate their overall performance. The guidelines suggested that answers within ±15% for busulfan concentrations and ±10% for busulfan plasma exposure and dose recommendation were to be considered accurate. RESULTS: Of the 4 proficiency samples evaluated, between 67% and 85% of the busulfan quantitation results were accurate (ie, within 85%-115% of the reference value). The majority (88% round #1; 71% round #2) of the dose recommendation answers were correct. CONCLUSIONS: A proficiency testing program by which laboratories are alerted to inaccuracies in their quantitation, pharmacokinetic modeling, and dose recommendations for busulfan in hematopoietic cell transplant recipients was developed. These rounds of proficiency testing suggests that additional educational efforts and proficiency rounds are needed to ensure appropriate busulfan dosing.
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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".