Application of estimand framework to the design and analysis of multi-regional clinical trials.

With the increasing globalization of drug development and the publication of the International Council for Harmonisation (ICH) E17 guideline (ICH International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use 2017), multi-regional clinical trials (MRCTs) have become a preferred option to accelerate the availability of new medical products by design, execution and simultaneous submission under one protocol. MRCTs, with the participation of all major regions including countries from both developed and emerging markets, surely make new drug development more efficient. Even though the proposed estimand framework (ICH E9 (R1) (2019), came later in 2019 and was not mentioned in ICH E17, the application of the estimand framework has the potential to enhance the design, execution, and analysis in MRCTs. Defining an estimand within the regional context in MRCTs is an important issue that requires careful consideration. Given that consistency evaluation of treatment effects across regions is critical in MRCTs, the utilization of the estimand framework for regional consistency evaluation is also worth discussion. This paper aims to address these two questions. The five attributes of the estimand definition are discussed within a multi-regional context. It is imperative to thoroughly consider regional intrinsic/extrinsic factors when planning the estimand and estimation of MRCTs. A holistic approach is summarized to conduct consistency evaluation. When a regional inconsistency is observed, the possible reasons need to be further explored under five attributes of the estimand framework. Two real case studies are discussed to illustrate the application of the estimand framework in the consistency evaluation.

Evaluation of quality consistency between dispensing granules and traditional decoction of Bombyx batryticatus based on peptidomics and in silico simulations.

The application of traditional Chinese medicine dispensing granules is becoming increasingly prevalent. However, the consistency of dispensing granules with traditional decoction remains controversial. In this study, the consistency of peptide composition and pharmacodynamics between dispensing granules and traditional decoction of Bombyx batryticatus (BB) were assessed. A peptidomics method based on LC-tandem mass spectrometry technology was used to evaluate peptide composition similarity between BB traditional decoction and dispensing granules. The results revealed notable differences in peptide sequences between the two dosage forms, with only 8.55% of peptides shared between them. To evaluate the potential pharmacodynamic effects of the two dosage forms on epilepsy, virtual screening was used to identify potential active peptides, including blood-brain barrier permeability, toxicity prediction, and molecular docking. BB traditional decoction demonstrated a higher number and greater abundance of potential active peptides than BB dispensing granules, suggesting that BB traditional decoction may have a more favorable effect in treating epilepsy compared with BB dispensing granules. Moreover, molecular docking and molecular dynamics simulation studies confirmed the mechanism of action of active peptides to γ-aminobutyric acid transporter 1 (GAT-1). This study provides a scientific basis for the evaluation of quality consistency between BB traditional decoction and dispensing granules.

In vivo and in vitro chemical composition and biological activity of traditional vs. dispensing granule decoctions of Coptidis Rhizoma: A comparative study.

Coptidis Rhizoma (CR) holds significant clinical importance. In this study, we conducted a comparative analysis of CR's dispensing granule decoction (DGD) and traditional decoction (TD) to establish a comprehensive evaluation method for the quality of DGD. We selected nine batches of DGD (three from each of manufacturers A, B and C) and 10 batches of decoction pieces for analysis. We determined the content of representative components using high-performance liquid chromatography and assessed the content of blood components in vivo post-administration using ultra-performance liquid chromatography-mass spectrometry. The antibacterial activity was measured using the drug-sensitive tablet method. To evaluate the overall consistency of DGD and TD, we employed the CRITIC method and Grey relational analysis method. Our CRITIC results indicated no significant difference between the CRITIC scores of DGD-B and TD, with DGD-B exhibiting the highest consistency and overall quality. However, DGD-A and DGD-C showed variations in CRITIC scores compared with TD. After equivalent correction, the quality of DGD-A and DGD-C approached that of TD. Furthermore, our Grey relational analysis results supported the findings of the CRITIC method. This study offers a novel approach to evaluate the consistency between DGD and TD, providing insights into improving the quality of DGD.

Integrating multi-index determination coupled with hierarchical cluster analysis to evaluate the quality consistency of PVE30, an anti-HSV "glycoprotein" macromolecule of Prunellae Spica.

INTRODUCTION: Prunellae Spica (PS), derived from the dried fruit spikes of Prunella vulgaris L., is a traditional Chinese medicinal herb. Our previous studies found that PVE30, a water-extracting ethanol-precipitating "glycoprotein" macromolecule of PS, was a potential anti-herpes simplex virus (HSV) candidate. However, due to the complex structure and diverse bioactivity of the "glycoprotein", ensuring its quality consistency across different batches of PVE30 becomes particularly challenging. This poses a significant hurdle for new drug development based on PVE30. OBJECTIVE: Our study aimed to integrate multi-index determination coupled with hierarchical cluster analysis (HCA) to holistically profile the quality consistency of "glycoprotein" in PVE30. METHODS: High-performance gel permeation chromatography with refractive index detector (HPGPC-RID) was used to characterise the molecular weight (Mw) distribution, HPLC-PDA was used to quantitatively analyse the composed monosaccharides and amino acids, and UV-VIS was used to quantify the contents of polysaccharides and proteins. Qualitative and quantitative consistency was analysed for each single index in 16 batches of PVE30, and a 16 × 38 data matrix, coupled with HCA, was used to evaluate the holistic quality consistency of PVE30. RESULTS: The newly developed and validated methods were exclusive, linear, precise, accurate, and stable enough to quantify multi-indexes in PVE30. Single-index analysis revealed that 16 batches of PVE30 were qualitatively consistent in Mw distribution, polysaccharides and proteins, and the composition of composed monosaccharides and amino acids but quantitatively inconsistent in the relative contents of some "glycoprotein" macromolecules, as well as the composed monosaccharides/amino acids. HCA showed that the holistic quality of PVE30 was inconsistent, the inconsistency was uncorrelated with the regions where PS was commercially collected, and the contents of 17 amino acids and 2 monosaccharides contributed most to the holistic quality inconsistency. CONCLUSION: Multi-index determination coupled with HCA was successful in evaluating the quality consistency of PVE30, and the significant difference in quantitative indices was not caused by the origin of PS. The cultivating basis should be confirmed for PVE30-based new drug development.

[Development of Sample Size Formulas for Least Square Regression-Based Consistency Evaluation of Quantitative Indicators].

Objective To develop and verify the sample size formulas for quantitative data consistency evaluation based on the least square regression method. Methods According to the principle of least square regression-based quantitative consistency evaluation,statistical inference,and formula derivation,we developed the formulas for calculating sample size based on regression constant and regression coefficient.Furthermore,the accuracy of the formulas was verified by the data of three examples,and the results were compared with those of the sample size formula established based on the Bland-Altman(BA)method. Results The sample size formulas for regression-based quantitative consistency evaluation were deduced,and the accuracy of the formulas was verified by three examples.In addition,the results obtained with this formula had differences compared with those of the sample size formula established based on the BA method.Furthermore,consistent conclusions could be obtained by regression analysis and BA analysis with the sample size calculated with the regression method.However,with the sample size calculated based on the BA method,the consistency conclusion of regression analysis and BA analysis was sometimes not valid. Conclusion A sample size formula for quantitative consistency evaluation based on the regression method was proposed for the first time,which provided methodological support for the research in this field.

[Consistency evaluation of multidimensional quality attributes of Atractylodis Macrocephalae Rhizoma by fusion of multi-source information].

The quality control of Chinese medicinal decoction pieces is one of the key tasks in the traditional Chinese medicine industry. In this study, multi-source information fusion was employed to fuse the data from near-infrared spectroscopy, electronic tongues, and other tests and establish an overall quality consistency evaluation method for Atractylodis Macrocephalae Rhizoma, which provided methodological support for the overall quality evaluation of Atractylodis Macrocephalae Rhizoma. The near-infrared spectroscopy information was measured in both static and dynamic states for 23 batches of Atractylodis Macrocephalae Rhizoma samples from different sources, and the electronic tongue sensory information, moisture content, and leachate content were measured. The overall quality of Atractylodis Macrocephalae Rhizoma was evaluated by multi-source information fusion. The results showed that the near-infrared spectroscopy information of 16122103, 801000509, 801000352, 701003656, HX21L01, and 160956 was different from that of other batches of Atractylodis Macrocephalae Rhizoma powder in the static state, and 701003298, 16122103, 701003656, 701003107, 801000229, and 18090404 were the different batches in the dynamic state. The moisture content showed no significant difference between batches. The leachate content in the batch 801000509 was different from that in other batches. The electronic tongue sensory information of 150721004, 151237, 160703004, HX21M01, HX21K04, HX21K01, and 601003516 was different from that of other batches. Furthermore, data layer fusion was employed to analyze the overall quality of Atractylodis Macrocephalae Rhizoma. Four batches, 150721004, HX21M01, HX21K04, and HX21K01, showed the parameters exceeding the 95% control limits and differed from the other samples in terms of the overall quality. This study integrated the information of moisture, near-infrared spectroscopy, and other sources to evaluate the quality consistency among 23 batches of Atractylodis Macrocephalae Rhizoma samples, which provides a reference for the quality consistency evaluation of Chinese medicinal decoction pieces.

Quality consistency evaluation of chemical composition and pharmacology of Shaoyao-Gancao decoction dispensing granules and traditional decoction.

Dispensing granules of Chinese medicine (DGCM) have emerged as a more convenient alternative to traditional decoction (TD) of Chinese medicine, gaining popularity in recent years. However, the debate surrounding the consistency of DGCM compared to TD remains unresolved. In this study, three batches of Baishao and Gancao DGCM were obtained from manufacturers A, B, and C, and 15 batches of crude drugs were procured from hospital pharmacies for the preparation of dispensing granule decoction (DGD) and TD of Shaoyao-Gancao decoction (SGD). The HPLC-UV method was employed to determine the levels of gallic acid, paeoniflorin, albiflorin, liquiritin, liquiritin apioside, isoliquiritin apioside, isoliquiritin, glycyrrhizic acid, and isoliquiritigenin. The analgesic and antispasmodic effects were assessed using the hot plate and acetic acid writhing test in mice. To evaluate the consistency of chemical constituents and pharmacological effects between the two decoctions, the Criteria Importance Though Intercriteria Correlation (CRITIC) method combined with chemometrics was employed. Grey relation analysis (GRA) was used to assess the comprehensive quality consistency of the two decoctions. The CRITIC results revealed certain differences in chemical constituents and pharmacological effects between the selected DGCM and TD. Notably, DGD-A/C exhibited a significant difference from TD (p > 0.05), whereas DGD-B demonstrated no significant difference from TD (p > 0.05). The GRA analysis demonstrated that the overall quality consistency between DGD-B and TD was the highest among the three manufacturers. This study presents a method for evaluating the quality consistency of DGCM and TD of SGD, offering novel insights into the evaluation of consistency between DGCM and TD.

Comparison of area measurement methods in the routine assessment of diabetic foot ulcers-A consistency analysis method.

BACKGROUND: Ulcer area is a critical parameter in diabetic foot ulcer assessment but existing methods have deficiencies for routine measurement. AIM: We hypothesized that the Image J-based Computer Analysis method has a high level of agreement with the commonly used Maximum Length and Width and the Transparent Dressing-based Square Grid methods and aimed to test the consistency and verify the feasibility of the Image J-based Computer Analysis method in the routine assessment of ulcers. METHODS: Outpatient attendees with diabetic foot ulcers at the Department of Endocrinology of Sun Yat-sen Memorial Hospital were enrolled between October 2020 and October 2021. The three methods sequentially assessed the area of 65 included ulcers. Results were analysed using one-way analysis of variance and Bland-Altman plots to perform consistency analysis. RESULTS: The mean ± standard deviation ulcer area measured using the three methods were 14.79 ± 5.39, 14.35 ± 5.26, and 14.30 ± 5.26 cm2 , respectively. The measurement differences among the three groups or between any two were not statistically significant. Bland-Altman plots showed good consistency between the Image J-based Computer Analysis and the other two methods. CONCLUSION: The Image J-based Computer Analysis method can be interchanged with the other methods to assess ulcer areas. It is freely accessible, accurate and home-operable, thus worth consideration by nurses for routine ulcer area assessment.

Simultaneous Evaluation of Dissolution and Absorption Study of Compound Danshen Tablets and Capsules Based on Cellular Electrical Sensing Model.

This study explores the dissolution mechanism and absorption process of compound Danshen tablets (CDTs) and compound Danshen capsules (CDCs) in vitro. Taking the cell index as the evaluation index of dissolution and absorption of multi-component solid preparations of CDTs and CDCs, it breaks through the idea of traditional research. We used real-time cell-based assay (RTCA) to provide a new idea and method for the consistency evaluation of traditional Chinese medicine (TCM) compound preparations. The drug dissolution and absorption simulation system (DDASS) was established to obtain the dissolution and absorption samples of compound Danshen solid preparations at different time points. The cell index (CI) of the sample to H9C2 cells was detected by RTCA technology, and the dissolution and absorption percentage were calculated based on this index to obtain the dissolution and absorption kinetics model. Meanwhile, one batch of tablets and one batch of capsules (batch numbers ZKC1816 and 202101001) were selected to conduct the overall animal pharmacodynamic experiment to verify the feasibility of drug effect evaluation with cell index as an indicator. The best fitting model of dissolution curves of each batch of CDTs and CDCs is the Weibull model. There was a good correlation (r > 0.86) between the dissolution-absorption-pharmacodynamic curve. Based on RTCA technology, we have established the comprehensive evaluation method for cell biology of compound Danshen solid preparations in line with the overall concept of TCM and a synchronous evaluation system of dissolution and absorption in vitro of new TCM compound solid preparations.

[Fingerprint of Shenmai Injection based on ~1H-NMR technique].

Shenmai Injection is a Chinese medicinal injection prepared from Ginseng Radix et Rhizoma Rubra and Ophiopogonis Radix, which is widely used in clinical practice for the treatment and adjuvant therapy of cardiovascular diseases with significant pharmacological effects. Proton nuclear magnetic resonance spectroscopy(~1H-NMR) has the advantages of simple and nondestructive sample pretreatment, fast analysis, abundant chemical information, quantification and no need to follow the standard curve. It is widely used in the analysis and research of complex mixtures of traditional Chinese medicine, clinical blood and urine samples. In this study, the ~1H-NMR fingerprint of Shenmai Injection was established. Thirty-two chemical components were identified, including seven amino acids, eight small molecular organic acids, one alkaloid, four sugars, two nucleosides, seven saponins, and three other components. Pearson's correlation coefficient and multivariate analysis of variance(principal component analysis combined with hierarchical cluster analysis) were applied based on the ~1H-NMR fingerprint to evaluate the quality consistency. The results showed high-quality consistency of 82 batches of Shenmai Injection. This study confirms that the ~1H-NMR fingerprint has great potential in the application of quality control of Chinese medicinal injection.

Clinical evaluation of a laboratory-developed test using clone E1L3N for the detection of PD-L1 expression status in non-small cell lung cancer.

BACKGROUND: Programmed death ligand 1 (PD-L1) has been used as a diagnostic marker to identify patients that will benefit from immune checkpoint inhibitors in non-small cell lung cancer (NSCLC). Immunohistochemistry with E1L3N clone is one of the most widely used and inexpensive laboratory-developed tests for PD-L1, but still need to be compared and validated with standard methods for clinical application. METHODS: We investigated the performance of E1L3N clone for PD-L1 testing in 299 tumor tissues of NSCLC patients and its comparability with FDA-approved 22C3 clone. RESULTS: The results show that the negative coincidence rate, weak positive coincidence rate, and positive coincidence rate were 97.4%, 92.2%, and 97.6% using the E1L3N assay relative to the 22C3 assay, respectively. An overall agreement of 96.3% was achieved between these two assays. We also found that the overall concordances were 97.8% and 93.9% for PD-L1 detection in large and small specimens, respectively, and no significant difference was obtained between these two assays (p = 0.076). In addition, the expression of PD-L1 was not detected in tumor tissues of benign lung disease using both the E1L3N and 22C3 assays. CONCLUSION: E1L3N can be used as a reliable alternative antibody clone to evaluate PD-L1 expression status for NSCLC patients.

Consistency evaluation between dispensing granule and traditional decoction from Coptidis Rhizoma by using an integrated quality-based strategy.

INTRODUCTION: Dispensing granule, an innovative product of traditional Chinese medicine decoction, is widely practiced in clinic. As a prerequisite to support the clinical medication, quality consistency between dispensing granule and traditional decoction need to be evaluated. Furthermore, a generally applicable strategy for consistency evaluation of dispensing granule is needed. OBJECTIVE: In this study, we aimed to propose an integrated quality-based strategy to assess consistency between dispensing granule and traditional decoction taking Coptidis Rhizoma (CR) as a case study. METHODOLOGY: For chemical consistency evaluation, efficacy-related Coptis alkaloids were quantified with high-performance liquid chromatography (HPLC). The "Mean ± 3SD" of analyte contents in traditional decoction was considered as the criterion of consistency. And, as auxiliary analysis, principal component analysis (PCA) was employed for data visualisation. For biological consistency evaluation, two one-side t-tests and 90% confidence intervals of the geometric mean ratio of antibacterial zone diameter and 50% inhibitory concentration (IC50 ) of α-glucosidase inhibition were calculated. The scope of 80.00% to 125.00% was taken as in vitro bioequivalence interval. It was considered internally consistent with traditional decoction when the chemical and biological indices of dispensing granule fulfilled the preset criteria simultaneously. RESULTS: Eight out of 20 batches of CR dispensing granule were demonstrated consistent with traditional decoction in chemistry and biological activities. CONCLUSIONS: A generally applicable strategy was recommended that integrates chemical and biological characteristics for consistency evaluation of dispensing granule.

Establishment and validation of the quantitative analysis of multi-components by single marker for the quality control of Qishen Yiqi dripping pills by high-performance liquid chromatography with charged aerosol detection.

INTRODUCTION: Charged aerosol detection (CAD) has the merits of high sensitivity, high universality and response uniformity. The strategy that combines the quantitative analysis of multi-components by single marker (QAMS) with CAD has certain advantages for the quantification of multi-components. However, relevant research was limited. OBJECTIVES: To comprehensively investigate the crucial factors that affect the performance of the HPLC-CAD-QAMS approach and validate the credibility and feasibility of the method. METHODOLOGY: Multiple components of Qishen Yiqi dripping pills (QSYQ) were assayed using the high-performance liquid chromatography (HPLC)-CAD-QAMS approach. Some factors that affect the sensitivity and accuracy of the approach were sufficiently studied. After the method verification, principal component analysis (PCA) was applied to evaluate the quality consistency of three types of samples: normal samples, expired samples and negative samples. RESULTS: A HPLC-CAD-QAMS method was successfully developed for the multi-component determination of QSYQ. First, chromatographic conditions were optimised by a definitive screening design, and the optimised ranges of operating parameters were obtained with a Monte Carlo simulation method. Next, a new method to select the internal reference standards was successfully introduced based on the heatmap of Pearson correlation coefficients of the response factors. Then, the multi-point method was selected to calculate the relative correction factors, and a robustness test was conducted with Plackett-Burman design. Finally, the PCA was proved to be effective for the quality consistency evaluation of different samples. CONCLUSION: The developed HPLC-CAD-QAMS method can be a reliable and superior means for the multi-component quantitative analysis of QSYQ.

[Determination of five saponins in Xuesaitong Dropping Pills by micellar electrokinetic chromatography and evaluation method of between-batch consistency].

The present study determined five saponins in Xuesaitong Dropping Pills(XDP) by micellar electrokinetic chromatography(MEKC), and evaluated between-batch consistency by MEKC fingerprints and similarity analysis. A background buffer was composed of 20 mmol·L~(-1) sodium tetraborate-20 mmol·L~(-1) boric acid solution(pH 8.5), 55 mmol·L~(-1) sodium dodecyl sulfate(SDS), 23 mmol·L~(-1) ß-cyclodextrin, and 13% isopropyl alcohol. All separations were performed at 25 ℃,20 kV and the detection wavelength was set at 203 nm. The separation channel was a fused silica capillary with a dimension of 75 µm I.D. and a total length of 50.2 cm(effective length of 40.0 cm). The contents of notoginsenoside R_1, and ginsenosides Rg_1, Re, Rb_1, Rd were determined with their quality control ranges set. The fingerprints of XDP were established and the between-batch consistency was evaluated by similarity analysis. The contents of five saponins from the 19 batches of XDP were stable in the fixed ranges. Statistical analysis was carried out on the results of multiple batches of samples, and the specific quality control ranges were recommended as follows: notoginsenoside R_1 21.92-34.16 mg·g~(-1), ginsenosides Rg_1 83.54-131.78 mg·g~(-1), ginsenosides Re 13.58-19.82 mg·g~(-1), ginsenosides Rb_1 89.40-129.90 mg·g~(-1), and ginsenosides Rd 22.34-35.67 mg·g~(-1). Eleven characteristic peaks were identified in the fingerprints. Five peaks, notoginsenoside R_1 and ginsenosides Rg_1, Re, Rb_1, Rd, were identified with reference standards. The similarities of the 19 batches of samples were all above 0.988, indicating good between-batch consistency. This method is green and simple, and can be used for the quantitative determination and quality evaluation of XDP. It can also provide references for the quality control of other Chinese medicinal dripping pills.

Homogeneity score test of AC1 statistics and estimation of common AC1 in multiple or stratified inter-rater agreement studies.

BACKGROUND: Cohen's κ coefficient is often used as an index to measure the agreement of inter-rater determinations. However, κ varies greatly depending on the marginal distribution of the target population and overestimates the probability of agreement occurring by chance. To overcome these limitations, an alternative and more stable agreement coefficient was proposed, referred to as Gwet's AC1. When it is desired to combine results from multiple agreement studies, such as in a meta-analysis, or to perform stratified analysis with subject covariates that affect agreement, it is of interest to compare several agreement coefficients and present a common agreement index. A homogeneity test of κ was developed; however, there are no reports on homogeneity tests for AC1 or on an estimator of common AC1. In this article, a homogeneity score test for AC1 is therefore derived, in the case of two raters with binary outcomes from K independent strata and its performance is investigated. An estimation of the common AC1 between strata and its confidence intervals is also discussed. METHODS: Two homogeneity tests are provided: a score test and a goodness-of-fit test. In this study, the confidence intervals are derived by asymptotic, Fisher's Z transformation and profile variance methods. Monte Carlo simulation studies were conducted to examine the validity of the proposed methods. An example using clinical data is also provided. RESULTS: Type I error rates of the proposed score test were close to the nominal level when conducting simulations with small and moderate sample sizes. The confidence intervals based on Fisher's Z transformation and the profile variance method provided coverage levels close to nominal over a wide range of parameter combination. CONCLUSIONS: The method proposed in this study is considered to be useful for summarizing evaluations of consistency performed in multiple or stratified inter-rater agreement studies, for meta-analysis of reports from multiple groups and for stratified analysis.

Quality consistency evaluation of commercial transfer factor injections by chromatographic fingerprint combined with multivariate statistical analysis.

The current quality control methods relying mainly on chromogenic reaction can hardly ensure the quality and safety of the biochemical drug with complex chemical composition. Therefore, a chromatographic fingerprint method was developed for the quality evaluation of a multicomponent biochemical drug, transfer factor injection. High-performance liquid chromatography fingerprint was measured by using a C18 column (250 × 4.6 mm, 5 µm) with a mobile phase composed of 0.1% trifluoroacetic acid-water and 0.085% trifluoroacetic acid-acetonitrile under gradient elution. The developed method was validated and was subsequently applied to 57 batches of commercial products which were sampled by National Drug Assessment Program. High-resolution mass spectrometry analysis was performed on characteristic peaks of fingerprints, and a series of amino acids, nucleosides, and deoxynucleosides were identified. In the fingerprint assessments, principal component analysis and Hotelling T2 analysis yielded the best results. The results generally indicated that there was a significant difference among products of batch-to-batch or from different manufacturers. Abnormal samples and its discriminatory components were also explored. In summary, the established fingerprinting method with multivariate statistical analysis could offer an efficient, reliable, and practical approach for quality consistency evaluation of transfer factor injection, providing a reference for the quality control of other multicomponent biochemical drugs.

A consistency evaluation of signal-to-noise ratio in the quality assessment of human brain magnetic resonance images.

BACKGROUND: Quality assessment of medical images is highly related to the quality assurance, image interpretation and decision making. As to magnetic resonance (MR) images, signal-to-noise ratio (SNR) is routinely used as a quality indicator, while little knowledge is known of its consistency regarding different observers. METHODS: In total, 192, 88, 76 and 55 brain images are acquired using T2*, T1, T2 and contrast-enhanced T1 (T1C) weighted MR imaging sequences, respectively. To each imaging protocol, the consistency of SNR measurement is verified between and within two observers, and white matter (WM) and cerebral spinal fluid (CSF) are alternately used as the tissue region of interest (TOI) for SNR measurement. The procedure is repeated on another day within 30 days. At first, overlapped voxels in TOIs are quantified with Dice index. Then, test-retest reliability is assessed in terms of intra-class correlation coefficient (ICC). After that, four models (BIQI, BLIINDS-II, BRISQUE and NIQE) primarily used for the quality assessment of natural images are borrowed to predict the quality of MR images. And in the end, the correlation between SNR values and predicted results is analyzed. RESULTS: To the same TOI in each MR imaging sequence, less than 6% voxels are overlapped between manual delineations. In the quality estimation of MR images, statistical analysis indicates no significant difference between observers (Wilcoxon rank sum test, p w ≥ 0.11; paired-sample t test, p p ≥ 0.26), and good to very good intra- and inter-observer reliability are found (ICC, p icc ≥ 0.74). Furthermore, Pearson correlation coefficient (r p ) suggests that SNRwm correlates strongly with BIQI, BLIINDS-II and BRISQUE in T2* (r p ≥ 0.78), BRISQUE and NIQE in T1 (r p ≥ 0.77), BLIINDS-II in T2 (r p ≥ 0.68) and BRISQUE and NIQE in T1C (r p ≥ 0.62) weighted MR images, while SNRcsf correlates strongly with BLIINDS-II in T2* (r p ≥ 0.63) and in T2 (r p ≥ 0.64) weighted MR images. CONCLUSIONS: The consistency of SNR measurement is validated regarding various observers and MR imaging protocols. When SNR measurement performs as the quality indicator of MR images, BRISQUE and BLIINDS-II can be conditionally used for the automated quality estimation of human brain MR images.

Novel strategy for quality consistency evaluation of Chinese medicine "YIQING" tablet that combines the simultaneous quantification and screening of ten bioactive constituents.

The UV characteristics for different categories compounds in complex traditional Chinese medicines and herbal preparations usually vary. Thus, to achieve the integral analysis of multiwavelength fingerprint characteristics, we introduced a novel strategy of multiwavelength total fusion profiling. The simultaneous separation and quantification of multiple components by reversed-phase high-performance liquid chromatography coupled with diode array detection was developed in an effective, accurate, and reliable way. Furthermore, a 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging assay was set up to detect and screen the bioactivity of similar-structure constituents (aloe-emodin, rhein, emodin, chrysophanol, baicalein, wogonin, baicalin, wogonoside, berberine hydrochloride, and jatrorrhizine hydrochloride). Moreover, the high-performance liquid chromatography DPPH assay was developed to monitor the relationship between the biological activity and the spatial structure, the number of hydroxyl groups, the concentration of the analytes in samples. The result of qualitative classification for 15 batches of "YIQING" tablets using principle component analysis was consistent with the quantitative fingerprint assessment using the average linear quantitative fingerprint method. Therefore, chemometrics, multiwavelength total fusion profiling in conjunction with average linear quantitative fingerprint method and antioxidant activity can control the quality of traditional Chinese medicines/herbal preparations comprehensively and practically.

A Consistency Evaluation and Calibration Method for Piezoelectric Transmitters.

Array transducer and transducer combination technologies are evolving rapidly. While adapting transmitter combination technologies, the parameter consistencies between each transmitter are extremely important because they can determine a combined effort directly. This study presents a consistency evaluation and calibration method for piezoelectric transmitters by using impedance analyzers. Firstly, electronic parameters of transmitters that can be measured by impedance analyzers are introduced. A variety of transmitter acoustic energies that are caused by these parameter differences are then analyzed and certified and, thereafter, transmitter consistency is evaluated. Lastly, based on the evaluations, consistency can be calibrated by changing the corresponding excitation voltage. Acoustic experiments show that this method accurately evaluates and calibrates transducer consistencies, and is easy to realize.

Correlation and consistency between two detection methods for serum 25 hydroxyvitamin D levels in human venous blood and capillary blood.

Introduction: The study assessed the correlation and concordance of 25-hydroxyvitamin D [25(OH)D] levels in capillary and venous plasma collected simultaneously after vitamin D3 supplementation in 42 healthy adults. They were randomly divided into three groups by random number table method. Group A took 1,000 IU vitamin D3 daily, group B took 10,000 IU vitamin D3 every 10 days, and group C took 30,000 IU vitamin D3 every 30 days until the end of the 12th month. Venous blood serum 25(OH)D level was detected by chemiluminescence immunoassay (CLIA) and mass spectrometry (LC-MS) at day 1, day 14, day 28, month 6, and month 12 respectively, the capillary blood serum 25(OH)D level was detected by chemiluminescence immunoassay (CLIA) at the same time. Pearson correlation analysis and linear regression analysis were employed to investigate the relationship and transformation equation between the findings of the two samples and the results obtained from different detection methods within the same sample. The Bland-Altman method, Kappa analysis, and receiver operating characteristic (ROC) curve were utilized for assessing consistency, sensitivity, and specificity. Results: The three groups all reached a stable peak at 6 months, and the average levels of the three groups were 49.21, 42.50 and 43.025 nmol/L, respectively. The average levels of group A were higher than those of group B and group C (P < 0.001). The mean values of serum 25(OH)D measured by LC-MS and CLIA in 42 healthy adults were 45.32 nmol/L and 49.88 nmol/L, respectively, and the mean values of 25(OH)D measured by LC-MS in capillary blood were 52.03 nmol/L, and the difference was statistically significant (P < 0.001). Pearson correlation analysis showed that the linear fitting formula of scatter data was as follows: venous 25(OH)D concentration (nmol/L) = 1.105 * capillary 25(OH)D concentration -7.532 nmol/L, R2 = 0.625. Good agreement was observed between venous and corrected capillary 25(OH)D levels in clinical diagnosis (Kappa value 0.75). The adjusted serum 25(OH)D in capillary blood had a high clinical predictive value. Conclusions: The agreement between the two methods is good when the measured 25(OH)D level is higher. Standardized capillary blood chemiluminescence method can be used for 25(OH)D detection.