Reduce Measurement Variability Research Articles

Computerized Extraction of Electrocardiograms From Continuous 12‐Lead Holter Recordings Reduces Measurement Variability in a Thorough QT Study

Continuous Holter recordings are often used in thorough QT studies (TQTS), with multiple 10-second electrocardiograms (ECGs) visually selected around predesignated time points. The authors hypothesized that computer-automated ECG selection would reduce within-subject variability, improve study data precision, and increase study power. Using the moxifloxacin and placebo arms of a Holter-based crossover TQTS, the authors compared interval duration measurements (IDMs) from manually selected to computer-selected ECGs. All IDMs were made with a fully automated computer algorithm. Moxifloxacin-induced changes in baseline- and placebo-subtracted QT intervals were similar for manual and computer ECG selection. Mean 90% confidence intervals were narrower, and within-subject variability by mixed-model covariance was lower for computer-selected than for manual-selected ECGs. Computer ECG selection reduced the number of subjects needed to achieve 80% power by 40% to 50% over manual. Computer ECG selection returns accurate ddQTcF values with less measurement variability than manual ECG selection by a variety of metrics. This results in increased study power and reduces the number of subjects needed to achieve desired power, which represents a significant potential source cost savings in clinical drug trials.

Measurement of Drug in Small Particles from Aqueous Nasal Sprays by Andersen Cascade Impactor

To determine if cascade impactor (CI) measurement of drug in small particles from aqueous nasal sprays, described in FDA's 2003 draft Nasal Bioavailability/Bioequivalence Guidance, can be optimized to reduce measurement variability. To examine the influence of flow rate configurations and number of impactor stages on CI deposition and explore the importance of inlet volume. A total of eight assemblies and manual vs. automatic actuation were tested for deposition on the sum of all stages of the CI, and for Group 2 total drug mass per the Guidance. Mean deposition and variance about the mean were determined for each assembly. The path length for a spherical 1 l inlet was too short to allow adequate aerosol formation. Data variance was reduced by a factor of two or more by using an automatic actuator relative to manual actuation. Impactor assembly modification did not improve variance over the standard assembly. Use of a spherical inlet (≥ 2 l volume) and automatic actuation are recommended for comparative measurements of drug in small particles arising from aqueous nasal sprays. The standard (8-stage) 28.3 lpm CI flow rate configuration is recommended when using the Andersen Cascade Impactor (ACI), as no other assembly showed a distinct advantage.

A Six Sigma approach for R&D: measuring dissolved oxygen

A Six Sigma approach was applied to an R&D application with the goal of understanding and reducing measurement variability. Typically, Six Sigma is applied to a manufacturing process. Many aspects of processes and R&D applications are similar, e.g., input variables, measurements, and output values. In the current study, variables were identified, a gauge R&R test and Pareto analysis performed, and correction actions implemented to improve measurement variations. The gauge R&R study included an analysis of variances (ANOVA) using the Fisher test. The system under study was a new method to quantitate dissolved oxygen (DO) by colorimetry. Specifically, measurements were performed using a newly developed i–LAB® spectrometer. Various statistical and mathematical tools were employed to improve measurement variation, resulting in the standard deviation decreasing from 0.66 to 0.23. Additionally, the Six Sigma approach may be applied to other relevant R&D systems.

Evaluation of Retinal Nerve Fiber Layer Progression in Glaucoma: A Comparison between Spectral-Domain and Time-Domain Optical Coherence Tomography

To compare the performance of a spectral-domain optical coherence tomography (OCT) device and a time-domain OCT device to detect retinal nerve fiber layer (RNFL) progression in glaucoma patients. Prospective study. One hundred twenty-eight eyes of 81 glaucoma patients. Patients were followed up at 4-month intervals for at least 24 months for RNFL imaging and visual field examination. Both eyes were imaged by the Cirrus HD-OCT (Carl Zeiss Meditec, Inc., Dublin, CA) and the Stratus OCT (Carl Zeiss Meditec, Inc.) and underwent visual field testing at the same visit. Linear regression analyses between circumpapillary RNFL measurements (average, superior, and inferior RNFL thicknesses), visual field index (VFI), and follow-up time were performed. RNFL progression and RNFL improvement were identified when a significant negative or positive trend was detected, respectively. The agreement between the OCT instruments for progression detection was analyzed with κ statistics. Number of eyes with RNFL progression and improvement, agreement of progression detection between RNFL measurements and VFI, and rate of change of average RNFL thickness. Twenty-two eyes (19 patients) and 4 eyes (4 patients) had progression, and 0 and 5 eyes (5 patients) had improvement detected by the Cirrus HD-OCT and the Stratus OCT average RNFL measurements, respectively. The agreement for detection of RNFL progression was poor between the 2 OCT instruments (κ = 0.188, 0.027, and 0.267 for average, superior, and inferior RNFL thicknesses, respectively). The respective agreement between VFI and average RNFL thickness progression determined by the Cirrus HD-OCT and the Stratus OCT was 0.125 and 0.047. The rate of average RNFL thickness progression ranged between -1.52 μm/year and -5.03 μm/year for the Cirrus HD-OCT and between -2.22 μm/year and -7.60 μm/year for the Stratus OCT. The Cirrus HD-OCT outperformed the Stratus OCT in detecting more eyes with RNFL progression and fewer eyes with RNFL improvement. Because of reduced measurement variability, the Cirrus HD-OCT could detect changes in RNFL thickness sooner than the Stratus OCT. Proprietary or commercial disclosure may be found after the references.

A prospective study of telomere length measured by monochrome multiplex quantitative PCR and risk of lung cancer

Purpose Telomere length plays an important role in chromosomal stability and tumorigenesis, and its measurement in peripheral white blood cell DNA may be a predictor of the development of lung cancer. Experimental design Using a new method – monochrome multiplex quantitative PCR – which reduces measurement variability, we compared telomere length relative to standard DNA in white blood cell DNA in 229 incident male lung cancer cases and 229 matched controls within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of male smokers. Results Median (10th, 90th percentile) telomere length was 1.13 (0.86, 1.45) in cases and 1.08 (0.85, 1.38) in controls ( P = 0.038). Telomere length was inversely associated with pack-years of smoking (Spearman's correlation r = −0.16, P = 0.02) among controls. Compared to subjects with shorter telomere length (≤median), subjects with greater telomere length (>median) had a 1.6-fold (95% CI, 1.06–2.36) increased risk of lung cancer. There was a significant linear relationship between quartiles of telomere length and risk of lung cancer (odds ratios (95% confidence intervals) by quartile: 1.00, 0.98 (0.55–1.73), 1.62 (0.95–2.77), and 1.50 (0.84–2.68); P trend = 0.05). In addition, subgroup analysis showed that greater telomere length was associated with an increased risk of lung cancer among longer-term smokers (>38 years) (OR, 1.90; 95% CI, 1.00–3.59) but not among shorter-term smokers (≤38 years) (OR, 1.08; 95% CI, 0.56–2.11) ( P interaction = 0.01). Conclusions Our results suggest that greater telomere length may be associated with higher risk of lung cancer among male smokers.

Reliability of capturing foot parameters using digital scanning and the neutral suspension casting technique

BackgroundA clinical study was conducted to determine the intra and inter-rater reliability of digital scanning and the neutral suspension casting technique to measure six foot parameters. The neutral suspension casting technique is a commonly utilised method for obtaining a negative impression of the foot prior to orthotic fabrication. Digital scanning offers an alternative to the traditional plaster of Paris techniques.MethodsTwenty one healthy participants volunteered to take part in the study. Six casts and six digital scans were obtained from each participant by two raters of differing clinical experience. The foot parameters chosen for investigation were cast length (mm), forefoot width (mm), rearfoot width (mm), medial arch height (mm), lateral arch height (mm) and forefoot to rearfoot alignment (degrees). Intraclass correlation coefficients (ICC) with 95% confidence intervals (CI) were calculated to determine the intra and inter-rater reliability. Measurement error was assessed through the calculation of the standard error of the measurement (SEM) and smallest real difference (SRD).ResultsICC values for all foot parameters using digital scanning ranged between 0.81-0.99 for both intra and inter-rater reliability. For neutral suspension casting technique inter-rater reliability values ranged from 0.57-0.99 and intra-rater reliability values ranging from 0.36-0.99 for rater 1 and 0.49-0.99 for rater 2.ConclusionsThe findings of this study indicate that digital scanning is a reliable technique, irrespective of clinical experience, with reduced measurement variability in all foot parameters investigated when compared to neutral suspension casting.

A Comparison of Two Devices Used to Measure Golf Course Putting Green Speed

The Stimpmeter and Pelzmeter are two devices commonly used to measure putting green speed. The Stimpmeter was released in 1978 and the Pelzmeter followed approximately 25 years later. The Pelzmeter uses various technologies to potentially reduce measurement variability. However, it is unclear how similar these meters compare for measuring putting green speed. The objective of this research was to compare the measurement variability between the two devices when measuring putting green speed and to determine if they give similar results on the same putting surface. This study was conducted at four sites: the University of Arkansas (Fayetteville, AR); the University of Tennessee (Knoxville, TN); the University of Connecticut (Storrs, CT); and Michigan State University (East Lansing, MI). At each site, three evaluators used each device to measure putting green speed on plots with varying green speeds. There was a strong linear, one-to-one relationship between the Pelzmeter and the Stimpmeter when measuring putting green speed on the same turf. Measurement repeatability (as measured by standard deviation) among different evaluators was improved with the Pelzmeter at one of the four sites. There were no differences in measurement repeatability between the devices when a single evaluator repeatedly measured the same turf with the same device.

Reproducibility of Dynamic MR Imaging Pelvic Measurements: A Multi-institutional Study

To assess the reproducibility of bone and soft-tissue pelvimetry measurements obtained from dynamic magnetic resonance (MR) imaging studies in primiparous women across multiple centers. All subjects prospectively gave consent for participation in this institutional review board-approved, HIPAA-compliant study. At six clinical sites, standardized dynamic pelvic 1.5-T multiplanar T2-weighted MR imaging was performed in three groups of primiparous women at 6-12 months after birth: Group 1, vaginal delivery with anal sphincter tear (n = 93); group 2, vaginal delivery without anal sphincter tear (n = 79); and group 3, cesarean delivery without labor (n = 26). After standardized central training, blinded readers at separate clinical sites and a blinded expert central reader measured nine bone and 10 soft-tissue pelvimetry parameters. Subsequently, three readers underwent additional standardized training, and reread 20 MR imaging studies. Measurement variability was assessed by using intraclass correlation for agreement between the clinical site and central readers. Acceptable agreement was defined as an intraclass correlation coefficient (ICC) of at least 0.7. There was acceptable agreement (ICC range, 0.71-0.93) for eight of 19 MR imaging parameters at initial readings of 198 subjects. The remaining parameters had an ICC range of 0.13-0.66. Additional training reduced measurement variability: Twelve of 19 parameters had acceptable agreement (ICC range, 0.70-0.92). Correlations were greater for bone (ICC, >or=0.70 in five [initial readings] and eight of nine [rereadings] variables) than for soft-tissue measurements (ICC, >or=0.70 in three [initial readings] of 10 and four [rereadings] of 10 readings, respectively). Despite standardized central training, there is high variability of pelvic MR imaging measurements among readers, particularly for soft-tissue structures. Although slightly improved with additional training, measurement variability adversely affects the utility of many MR imaging measurements for multicenter pelvic floor disorder research.

Measuring atrophy in Alzheimer disease

Global brain atrophy rate calculated from serial MRI scans may be a surrogate marker of Alzheimer disease (AD) progression. Few studies have assessed atrophy in AD over short intervals. Thirty-eight patients with AD and 19 control subjects had MRI scans at baseline, 6 months, and 1 year. Ventricular change and whole-brain volume loss were calculated directly from the regions manually outlined on registered scans and using the automated (boundary shift integral [BSI]) technique. Sample sizes required to power placebo-controlled treatment trials over 6 months and 1 year were calculated using these techniques. Increased rates of ventricular expansion and whole-brain atrophy were seen in AD compared with control subjects at both 6 and 12 months using manual and automated techniques (p < 0.001). Using the BSI consistently reduced measurement variability especially for whole-brain change. In clinical trials, at 6 months, significantly fewer patients would be required using the ventricular BSI (VBSI) compared with the brain BSI (BBSI) (e.g., 165 vs 410 per arm to provide 90% power to detect a 20% reduction in rate of change). At 1 year, sample size estimates were smaller than at 6 months, and the advantage of using VBSI instead of BBSI was less marked. In short-interval studies, using the ventricular boundary shift integral instead of the brain boundary shift integral may allow for disease-modifying effects to be demonstrated using significantly smaller sample sizes. This potential benefit must be balanced against the possibility that ventricular volumes may be more likely to be affected by factors other than neurodegeneration.

CT angiographic measurement of the carotid artery: optimizing visualization by manipulating window and level settings and contrast material attenuation.

To evaluate a broad range of window and level settings for various contrast material attenuation coefficients and degrees of vascular stenosis to obtain the most accurate computed tomographic (CT) angiographic measurements. A total of 25, 480 measurements were made transversely (perpendicular to the lumen) and by means of maximum intensity projection (MIP) in a phantom with stenoses of 0%-100%, contrast material with attenuation coefficients of 150-350 HU, and 14 window and 13 level settings. Edge definition was also evaluated. There was an inherent relationship between the contrast material attenuation coefficient and the optimal window and level settings in the measurement of stenoses at both transverse and MIP CT angiography. This relationship between the contrast material attenuation coefficient D: and the optimal settings for window W: and level L: was represented by the following simple equations: W:/D: = [-2 x (L:/D:)] + 1.3, where -0.2 < L:/D: < 0.5, and W:/D: = [3.3 x (L:/D:)] - 1.3, where 0.5 < L:/D: < 1.0. With a vascular contrast material attenuation coefficient of 250-350 HU, the best transverse and MIP display settings for the window and level were 96 and 150 HU, respectively. The use of optimized window and level settings at CT angiography reduces measurement variability.

IMPROVEMENT OF A DIMENSIONAL MEASUREMENT PROCESS USING TAGUCHI ROBUST DESIGNS, by Chih-Young Lin, Chien-Long Hong, and Jiing-Yih Lai, Mechanical Engineering Department, National Central University, Chung-Li 320, Taiwan, Republic of China

Statistical process control (SPC) has been used extensively in industry for monitoring the product quality. The variations of measured product characteristics, however, come not only from the manufacturing process but also from the measurement process. Large measurement variability may cause errors in SPC results and, hence, lead to wrong interpretation of the product quality. The objective of this work was to conduct a robust design study to investigate the effects of measurement factors, which would lead to a reduction in the measurement variability. Repeatability and reproducibility studies verified the success of the proposed strategy. Process capability analyses confirmed the net effect of the reduced measurement variability on the product variability.

N-value and second derivative of the superconductor voltage-current characteristic

The authors studied the n-value (V varies as I/sup n/) and second derivative (d/sup 2/V/dI/sup 2/) of the voltage-current curve of high- and low-temperature superconductors and superconductor simulators. They used these parameters for diagnosing problems with sample heating and data acquisition, and as indicators of the superconducting-to-normal state transition. The superconductor simulator may be useful in testing the measurement system integrity and reducing measurement variability since its characteristics are highly repeatable. >

Automated Measurement of Flank Wear of Circuit Board Drills

The results of automated measurements of flank wear of drills used in circuit board drilling are presented. The measurement technique uses a machine vision system to increase measurement speed and reduce measurement variability. A flank area wear parameter is compared to the commonly used flank width wear measurement, and is shown to be more consistent, in agreement with similar work by T. I. Liu using multifaceted crankshaft drills.

Cryogenic Preconcentration-Direct FID Method for Measurement of Ambient NMOC: Refinement and Comparison with GC Speciation

A method for measuring total nonmethane organic compounds (NMOC) In the atmosphere has been refined to reduce measurement variability and evaluated for possible use In connection with the control of hydrocarbon emissions. The method, a simplification of the conventional gas chromatographlc (GC) speciation technique, uses cryogenic preconcentration and flame ionization detection but does not use a GC column. Tests to compare this simplified method to the GC speciation technique, using actual ambient air samples, were carried out. Test results showed that the sensitivity and precision of the simplified method approach those of the speciation technique. Other test results verified that the use of stainless steel sample canisters for collection and temporary storage of NMOC samples Is acceptable and contributes little additional variability to the method.