Dataset Information

Using Electronic Health Records to Derive Control Arms for Early Phase Single-Arm Lung Cancer Trials: Proof-of-Concept in Randomized Controlled Trials.

ABSTRACT: Oncology drug development increasingly relies on single-arm clinical trials. External controls (ECs) derived from electronic health record (EHR) databases may provide additional context. Patients from a US-based oncology EHR database were aligned with patients from randomized controlled trials (RCTs) and trial-specific eligibility criteria were applied to the EHR dataset. Overall survival (OS) in the EC-derived control arm was compared with OS in the RCT experimental arm. The primary outcome was OS, defined as time from randomization or treatment initiation (EHR) to death. Cox regression models were used to obtain effect estimates using EHR data. EC-derived hazard ratio estimates aligned closely with those from the corresponding RCT with one exception. Comparing log HRs among all RCT and EC results gave a Pearson correlation coefficient of 0.86. Properly selected control arms from contemporaneous EHR data could be used to put single-arm trials of OS in advanced non-small cell lung cancer into context.

SUBMITTER: Carrigan G

PROVIDER: S-EPMC7006884 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Using Electronic Health Records to Derive Control Arms for Early Phase Single-Arm Lung Cancer Trials: Proof-of-Concept in Randomized Controlled Trials.

Carrigan Gillis G Whipple Samuel S Capra William B WB Taylor Michael D MD Brown Jeffrey S JS Lu Michael M Arnieri Brandon B Copping Ryan R Rothman Kenneth J KJ

Clinical pharmacology and therapeutics 20191011 2

Oncology drug development increasingly relies on single-arm clinical trials. External controls (ECs) derived from electronic health record (EHR) databases may provide additional context. Patients from a US-based oncology EHR database were aligned with patients from randomized controlled trials (RCTs) and trial-specific eligibility criteria were applied to the EHR dataset. Overall survival (OS) in the EC-derived control arm was compared with OS in the RCT experimental arm. The primary outcome was ...[more]

PMID: 31350853

Similar Datasets

Project description:This paper concerns the feasibility of x-ray differential phase contrast (DPC) tomosynthesis imaging using a grating-based DPC benchtop experimental system, which is equipped with a commercial digital flat-panel detector and a medical-grade rotating-anode x-ray tube. An extensive system characterization was performed to quantify its imaging performance.The major components of the benchtop system include a diagnostic x-ray tube with a 1.0 mm nominal focal spot size, a flat-panel detector with 96 μm pixel pitch, a sample stage that rotates within a limited angular span of ± 30°, and a Talbot-Lau interferometer with three x-ray gratings. A total of 21 projection views acquired with 3° increments were used to reconstruct three sets of tomosynthetic image volumes, including the conventional absorption contrast tomosynthesis image volume (AC-tomo) reconstructed using the filtered-backprojection (FBP) algorithm with the ramp kernel, the phase contrast tomosynthesis image volume (PC-tomo) reconstructed using FBP with a Hilbert kernel, and the differential phase contrast tomosynthesis image volume (DPC-tomo) reconstructed using the shift-and-add algorithm. Three inhouse physical phantoms containing tissue-surrogate materials were used to characterize the signal linearity, the signal difference-to-noise ratio (SDNR), the three-dimensional noise power spectrum (3D NPS), and the through-plane artifact spread function (ASF).While DPC-tomo highlights edges and interfaces in the image object, PC-tomo removes the differential nature of the DPC projection data and its pixel values are linearly related to the decrement of the real part of the x-ray refractive index. The SDNR values of polyoxymethylene in water and polystyrene in oil are 1.5 and 1.0, respectively, in AC-tomo, and the values were improved to 3.0 and 2.0, respectively, in PC-tomo. PC-tomo and AC-tomo demonstrate equivalent ASF, but their noise characteristics quantified by the 3D NPS were found to be different due to the difference in the tomosynthesis image reconstruction algorithms.It is feasible to simultaneously generate x-ray differential phase contrast, phase contrast, and absorption contrast tomosynthesis images using a grating-based data acquisition setup. The method shows promise in improving the visibility of several low-density materials and therefore merits further investigation.

Project description:IntroductionTight glycemic control (TGC) has shown benefits but has been difficult to achieve consistently. STAR (Stochastic TARgeted) is a flexible, model-based TGC approach directly accounting for intra- and inter- patient variability with a stochastically derived maximum 5% risk of blood glucose (BG) < 4.0 mmol/L. This research assesses the safety, efficacy, and clinical burden of a STAR TGC controller modulating both insulin and nutrition inputs in pilot trials.MethodsSeven patients covering 660 hours. Insulin and nutrition interventions are given 1-3 hourly as chosen by the nurse to allow them to manage workload. Interventions are calculated by using clinically validated computer models of human metabolism and its variability in critical illness to maximize the overlap of the model-predicted (5-95th percentile) range of BG outcomes with the 4.0-6.5 mmol/L band while ensuring a maximum 5% risk of BG < 4.0 mmol/L. Carbohydrate intake (all sources) was selected to maximize intake up to 100% of SCCM/ACCP goal (25 kg/kcal/h). Maximum insulin doses and dose changes were limited for safety. Measurements were made with glucometers. Results are compared to those for the SPRINT study, which reduced mortality 25-40% for length of stay ?3 days. Written informed consent was obtained for all patients, and approval was granted by the NZ Upper South A Regional Ethics Committee.ResultsA total of 402 measurements were taken over 660 hours (~14/day), because nurses showed a preference for 2-hourly measurements. Median [interquartile range, (IQR)] cohort BG was 5.9 mmol/L [5.2-6.8]. Overall, 63.2%, 75.9%, and 89.8% of measurements were in the 4.0-6.5, 4.0-7.0, and 4.0-8.0 mmol/L bands. There were no hypoglycemic events (BG < 2.2 mmol/L), and the minimum BG was 3.5 mmol/L with 4.5% < 4.4 mmol/L. Per patient, the median [IQR] hours of TGC was 92 h [29-113] using 53 [19-62] measurements (median, ~13/day). Median [IQR] results: BG, 5.9 mmol/L [5.8-6.3]; carbohydrate nutrition, 6.8 g/h [5.5-8.7] (~70% goal feed median); insulin, 2.5 U/h [0.1-5.1]. All patients achieved BG < 6.1 mmol/L. These results match or exceed SPRINT and clinical workload is reduced more than 20%.ConclusionsSTAR TGC modulating insulin and nutrition inputs provided very tight control with minimal variability by managing intra- and inter- patient variability. Performance and safety exceed that of SPRINT, which reduced mortality and cost in the Christchurch ICU. The use of glucometers did not appear to impact the quality of TGC. Finally, clinical workload was self-managed and reduced 20% compared with SPRINT.

Dataset Information

Using Electronic Health Records to Derive Control Arms for Early Phase Single-Arm Lung Cancer Trials: Proof-of-Concept in Randomized Controlled Trials.

Publications

Using Electronic Health Records to Derive Control Arms for Early Phase Single-Arm Lung Cancer Trials: Proof-of-Concept in Randomized Controlled Trials.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets