We specify a pre-registered protocol for Using publicly available trial-arm adverse-event line-listings, what fraction of AEs currently classified as grade >=3 under CTCAE v4 receive a different grade under CTCAE v5 at item-level mapping, and does the shift preferentially affect any organ system? using ClinicalTrials.
We specify a pre-registered protocol for When the same MIMIC-IV ICU admission records are analyzed using the KDIGO 2012 creatinine-only AKI definition versus the KDIGO creatinine-plus-urine-output definition, how different are the downstream associations between AKI exposure and long-term mortality? using MIMIC-IV v2.
We specify a pre-registered protocol for Applied to the same NHANES primary-care-representative slice, what fraction of adults receive a different 10-year CVD risk band (low/borderline/intermediate/high) under Framingham, Pooled Cohort Equations (PCE), and the 2023 AHA PREVENT equations? using NHANES 2017-2020 pre-pandemic continuous release, adults 40-75 with non-missing labs (total cholesterol, HDL, systolic BP, smoking, diabetes, eGFR, UACR).
We specify a pre-registered protocol for Among adult liver transplant candidates in a publicly-accessible registry slice, what fraction of patients receive a priority-band shift (change of >=5 points or change in priority category) between classical MELD, MELD-Na, and MELD 3.0, and is the shift systematic by sex and by sodium level?
We specify a pre-registered protocol for For proteins with experimentally-characterized disordered regions in DisProt, do AlphaFold2 (monomer), ESMFold, and OmegaFold produce concordant per-residue confidence scores (pLDDT or equivalent) on those disordered regions, and where they disagree, is the disagreement systematic by predictor? using DisProt v9+ curated disordered-region annotations intersected with UniProt sequences; pre-registered subset of 200 proteins with at least one disordered region >=30 residues.
We specify a pre-registered protocol for When DESeq2, edgeR, and limma-voom are applied with default settings to the same RNA-seq count matrix with an identical design formula, what fraction of genes receive discordant differential-expression calls (significant in one method but not another at FDR<0.05) and is this fraction sample-size dependent?
We specify a pre-registered protocol for Do CIBERSORT, CIBERSORTx, and quanTIseq, applied to the TCGA-BRCA RNA-seq matrix with identical inputs, agree on the tertile assignment of inferred neutrophil-to-lymphocyte ratio for individual patients? using TCGA-BRCA bulk RNA-seq expression matrix (FPKM or TPM) accessed from the GDC; patient-level barcodes and clinical file version pinned at pre-registration.
We specify a pre-registered protocol for Do Harmony, Scanorama, and scVI, applied to the same 10x Genomics PBMC 10k reference with an identical QC pipeline and a locked marker-gene reference, produce concordant cell-type labels at the top cluster level, and if not, at what fraction of cells do pairs disagree? using 10x Genomics PBMC 10k public dataset (combined from multiple publicly-released 10x PBMC runs), accessed via scanpy.
RAD-PNEUM-SBRT v1: We present a pre-validation composite scoring framework for grade >=2 radiation pneumonitis at 12 months in adult patients receiving thoracic SBRT for primary lung cancer or oligometastatic disease. Published literature reports grade >=2 RP 9-28% across SBRT series; lung V20 and mean lung dose remain strongest predictors [Barriger 2012; Palma 2013], with effect sizes for individual modifiers reported inconsistently across study designs and grading conventions.
FEBRIL-NEUT-MASCC v2: We present a pre-validation composite scoring framework for MASCC-style serious complication endpoint at 30 days in adult solid-tumour and selected haematologic-malignancy patients presenting with febrile neutropenia who are being triaged for outpatient vs inpatient management. Published literature reports MASCC score >=21 identifies low-risk with ~4-6% complication rate; original derivation Klastersky 2000; contemporary cohorts suggest item recalibration warranted [Klastersky 2000; Carmona-Bayonas 2015], with effect sizes for individual modifiers reported inconsistently across study designs and grading conventions.
POSTOP-VTE v1: We present a pre-validation composite scoring framework for symptomatic, imaging-confirmed VTE within 90 days in adult patients undergoing major abdominal surgery (open or laparoscopic) with LOS >=1 day. Published literature reports 90-day VTE incidence 1-5% depending on cancer status and procedure type [Bahl 2010; Merkow 2011], with effect sizes for individual modifiers reported inconsistently across study designs and grading conventions.
SEPSIS-MORT-72 v1: We present a pre-validation composite scoring framework for 72-hour all-cause mortality in adult ED patients meeting Sepsis-3 criteria at first measurement. Published literature reports 72-h mortality 5-15% in Sepsis-3 populations with strong lactate and SOFA gradients [Seymour 2016; Raith 2017], with effect sizes for individual modifiers reported inconsistently across study designs and grading conventions.
HEPARIN-HIT-4T v1: We present a pre-validation composite scoring framework for SRA-positive HIT (functional assay confirmation) in adult inpatients with suspected HIT in the 5-14 day window after heparin exposure. Published literature reports pre-test probability calibration of 4Ts: low (0-3) ~1%, intermediate (4-5) ~10%, high (6-8) ~34% for confirmed HIT [Cuker 2012; Linkins 2015], with effect sizes for individual modifiers reported inconsistently across study designs and grading conventions.
DOAC-BLEED-GFR v1: We present a pre-validation composite scoring framework for ISTH major bleeding at 12 months in adult patients with non-valvular atrial fibrillation or VTE on DOAC therapy with eGFR 15-59 mL/min/1.73m2.
METFORMIN-LACTATE v1: We present a pre-validation composite scoring framework for incident MALA within 12 months of the assessment window in adult patients with type 2 diabetes on metformin with eGFR 15-60 mL/min/1.73m2 being considered for continuation, dose-adjustment, or discontinuation.
CAR-T-CRS-GRADE v1: We present a pre-validation composite scoring framework for development of ASTCT grade >=3 CRS within 14 days of infusion in adult patients with relapsed/refractory B-cell lymphoma or leukaemia receiving commercial or investigational CD19 CAR-T products. Published literature reports grade >=3 CRS rates 10-50% depending on product and disease burden [Neelapu 2017; Schuster 2019; Maude 2018], with effect sizes for individual modifiers reported inconsistently across study designs and grading conventions.
We specify a pre-registered protocol for Does the ICI-HEPATITIS-RECHAL v1 Rechallenge Risk Score, derived on literature weights dominated by Western-cohort evidence, demonstrate adequate calibration-in-the-large (within +/-0.15) and C-statistic (>=0.
ICI-MYOCARDIT-RECHAL v1: We present a pre-validation composite scoring framework for recurrence of immune-related myocarditis (any grade) or new MACE attributed to ICI within 180 days of rechallenge in adult solid-tumour patients who survived an ICI-attributed myocarditis episode and are being considered for rechallenge. Published literature reports baseline incidence 0.
ICI-PNEUM-RECHAL v1: We present a pre-validation composite scoring framework for recurrence of grade >=2 immune-related pneumonitis within 180 days of rechallenge in adult solid-tumour patients with documented CTCAE grade >=3 immune-related pneumonitis who are being considered for rechallenge. Published literature reports pooled any-grade irAE recurrence 25-55% with pneumonitis-specific recurrence reported at 25-45% [Naidoo 2017; Delaunay 2017; Santini 2018], with effect sizes for individual modifiers reported inconsistently across study designs and grading conventions.
ICI-COLITIS-RECHAL v1: We present a pre-validation composite scoring framework for recurrence of grade >=2 immune-related colitis within 180 days of rechallenge in adult patients with solid tumours who experienced CTCAE grade >=3 immune-related colitis during first- or second-line ICI therapy and are being considered for rechallenge with any ICI. Published literature reports 30-55% any-grade irAE recurrence on rechallenge with same-organ recurrence concentrated at the upper end [Dolladille 2020; Abu-Sbeih 2019], with effect sizes for individual modifiers reported inconsistently across study designs and grading conventions.