TY  - JOUR
AB  - External controls (eControls) leverage historical data to create non-randomized control arms. The lack of randomization can result in confounding between the experimental and eControl cohorts. To balance potentially confounding variables between the cohorts, one of the proposed methods is to match on prognostic scores. Still, the performance of prognostic scores to construct eControls in oncology has not been analyzed yet. Using an electronic health record (EHR)-derived de-identified database, we constructed eControls using one of three methods: ROPRO, a state-of-the-art prognostic score, or either a propensity score composed of five (5Vars) or 27 covariates (ROPROvars). We compared the performance of these methods in estimating the overall survival (OS) hazard ratio (HR) of 11 recent advanced non-small-cell lung cancer. The ROPRO eControls had a lower OS HR error (median absolute deviation [MAD] [confidence interval {CI}] 0.072 [0.036, 0.185]), than the 5Vars (MAD [CI] 0.081 [0.025, 0.283]) and ROPROvars eControls (MAD [CI] 0.087 [0.054, 0.383]). Notably, the OS HR errors for all methods were even lower in the phase III studies. Moreover, the ROPRO eControl cohorts included, on average, more patients than the 5Vars (6.54%) and ROPROvars cohorts (11.7%). eControls matched with the prognostic score reproduced the controls more reliably than propensity scores composed of the underlying variables. Additionally, prognostic scores could allow eControls to be built on many prognostic variables without a significant increase in the variability of the propensity score, which would decrease the number of matched patients.
AU  - Loureiro, H.
AU  - Roller, A.*
AU  - Schneider, M.*
AU  - Talavera Lopez, C.N.
AU  - Becker, T.*
AU  - Bauer-Mehren, A.*
C1  - 68769
C2  - 54979
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
SP  - 333-341
TI  - Matching by OS prognostic score to construct external controls in lung cancer clinical trials.
JO  - Clin. Pharmacol. Ther.
VL  - 115
IS  - 2
PB  - Wiley
PY  - 2023
SN  - 0009-9236
ER  - 

TY  - JOUR
AB  - Inhibition of sodium-glucose cotransporter 2 (SGLT2) represents an emerging pharmaceutical approach for the treatment of heart failure. The mechanisms by which SGLT2 inhibitors reduce the risk of heart failure are not well understood. The objective of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in the SLC5A2 gene, encoding SGLT2, and heart failure, and to assess potential mediators of this association. Regression and mediation analyses were conducted with individual participant data of the UK Biobank (n = 416,737) and validated in the cardiovascular high-risk cohort of the LUdwigshafen RIsk and Cardiovascular Health study (LURIC; n = 3316). Two intronic SNPs associated with SLC5A2 expression were included in a genetic score, which was associated with lower risk of heart failure in UK Biobank (odds ratio 0.97, 95% confidence interval, 0.95−0.99, P = 0.016). This association was also present in participants without type 2 diabetes or coronary artery disease (CAD). The associations of the genetic score with HbA1c, high-density lipoprotein cholesterol, uric acid, systolic blood pressure, waist circumference, and body composition mediated 35% of the effect of the score on heart failure risk. No associations of the genetic SGLT2 score with atherosclerotic cardiovascular disease outcomes or markers of volume status were observed, which was confirmed in the LURIC study. Variations in the gene encoding SGLT2 were associated with the risk of prevalent or incident heart failure. This association was mediated by several mechanisms and did not depend on the presence of type 2 diabetes or previous CAD events.
AU  - Katzmann, J.L.*
AU  - Mason, A.M.*
AU  - März, W.*
AU  - Kleber, M.E.*
AU  - Niessner, A.*
AU  - Blüher, M.
AU  - Speer, T.*
AU  - Laufs, U.*
C1  - 61244
C2  - 50108
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
SP  - 149-158
TI  - Genetic variation in sodium-glucose cotransporter 2 and heart failure.
JO  - Clin. Pharmacol. Ther.
VL  - 110
IS  - 1
PB  - Wiley
PY  - 2021
SN  - 0009-9236
ER  -