Predictors of increased melphalan exposure correlate with overall survival, nonrelapse mortality, and toxicities in patients undergoing reduced-intensity allogeneic stem cell transplantation with fludarabine and melphalan.

The reduced-intensity conditioning regimen, fludarabine and melphalan 140 mg/m2 (FM140), is widely adopted in practice. Pharmacokinetic studies report 10-fold interpatient variability in melphalan exposure. We identified low hemoglobin (Hb) and/or creatinine clearance (CrCl), determinants of melphalan pharmacokinetic, as strong predictors of outcomes after high-dose melphalan and autologous transplant. We hypothesized that these variables could predict for outcomes after FM140. Overall survival was shorter in patients with a lower Hb (113 vs. 2536 days; p = 0.004), due to an increased rate of nonrelapse mortality (NRM) (p = 0.0005). Overall survival was also worse in patients with lower CrCl (75 vs. 317 days; p = 0.003), with a significantly worse nonrelapse mortality (p = 0.0023). In a multivariate analysis, a higher Hb and CrCl predicted for better overall survival (p = 0.017). In patients with a lower Hb, the median duration of hospitalization (p = 0.02) and the mean duration of diarrhea (p = 0.008) were longer. In patients with a lower CrCl, the median duration of hospitalization (p = 0.06) and the mean duration of diarrhea (p = 0.0009) longer, and the rate of infection was higher (p = 0.02). We show for the first time that Hb and CrCl represent important determinants of outcomes after FM140, suggesting that pharmacokinetic-directed dosing may be beneficial in achieving optimal outcomes.

Optimizing Clinical Reasoning Assessments With Analytic and Holistic Ratings: Examining the Validity, Reliability, and Cost of a Simplified Patient Note Scoring Procedure.

PURPOSE: Post-standardized patient (SP) encounter patient notes used to assess students' clinical reasoning represent a significant time burden for faculty who traditionally score them. To reduce this burden, the authors previously reported a complex faculty-developed scoring method to assess patient notes rated by nonclinicians. The current study explored whether a simplified scoring procedure for nonclinician raters could further optimize patient note assessments by reducing time, cost, and creating additional opportunities for formative feedback. METHOD: Ten nonclinician raters scored patient notes of 141 students across 5 SP cases by identifying case-specific patient note checklist items. The authors identified the bottom quintile of students using the proportion of correct items identified in the note (percent-scores) and case-specific faculty-generated scoring formulas (formula-scores). Five faculty raters scored a subset of notes from low, borderline, and high-performing students (n = 30 students) using a global rating scale. The authors performed analyses to gather validity evidence for percent-scores (i.e., relationship to other variables), investigate its reliability (i.e., generalizability study), and evaluate its costs (i.e., faculty time). RESULTS: Nonclinician percent- and formula-scores were highly correlated ( r = .88) and identified similar lists of low-performing students. Both methods demonstrated good agreement for pass-fail determinations with each other (Kappa = .68) and with faculty global ratings (Kappa percent =.61; Kappa formula =.66). The G-coefficient of percent-scores was .52, with 38% of variability attributed to checklist items nested in cases. Using percent-scores saved an estimated $746 per SP case (including 6 hours of faculty time) in development costs over formula-scores. CONCLUSIONS: Nonclinician percent-scores reliably identified low-performing students without the need for complex faculty-developed scoring formulas. Combining nonclinician analytic and faculty holistic ratings can reduce the time and cost of patient note scoring and afford faculty more time to coach at-risk students and provide targeted assessment input for high-stakes summative exams.

Can Nonclinician Raters Be Trained to Assess Clinical Reasoning in Postencounter Patient Notes?

PURPOSE: Clinical reasoning is often assessed through patient notes (PNs) following standardized patient (SP) encounters. While nonclinicians can score PNs using analytic tools such as checklists, these do not sufficiently encompass the holistic judgments of clinician faculty. To better model faculty judgments, the authors developed checklists with faculty-specified scoring formulas embedded in spreadsheets and studied the resulting interrater reliability (IRR) of nonclinician raters (SPs and medics) and student pass/fail status. METHOD: In Study 1, nonclinician and faculty raters rescored PNs of 55 third-year medical students across 5 cases of the 2017 Graduation Competency Examination (GCE) to determine IRR. In Study 2, nonclinician raters scored all notes of the 5-case 2018 GCE (178 students). Faculty rescored all notes of failing students and could modify formula-derived scores if faculty felt appropriate. Faculty also rescored and corrected scores of additional notes for a total of 90 notes (3 cases, including failing notes). RESULTS: Mean overall percent exact agreement between nonclinician and faculty ratings was 87% (weighted kappa, 0.86) and 83% (weighted kappa, 0.88) for Study 1 and Study 2, respectively. SP and medic IRRs did not differ significantly. Four students failed the note section in 2018; 3 passed after faculty corrections. Few corrections were made to nonfailing students' notes. CONCLUSIONS: Nonclinician PN raters using checklists and scoring rules may provide a feasible alternative to faculty raters for low-stakes assessments and for the bulk of well-performing students. Faculty effort can be targeted strategically at rescoring notes of low-performing students and providing more detailed feedback.