International standard of Traditional Chinese Medicine techniques: the operating specifications for Chinese medicated bath (2022).

Chinese medicated bath is one of the external therapies in Traditional Chinese Medicine (TCM), which has been widely used clinically. The "International Standard of Traditional Chinese Medicine Techniques: The Operating Specifications for Chinese Medicated Bath" is drawn up by the Beijing University of Chinese Medicine Third Affiliated Hospital and Beijing University of Chinese Medicine Xiamen Hospital in collaboration with domestic TCM universities and hospitals. The specification includes definition, operating process, points for attention and contraindications. It is targeted to provide reference for TCM providers at home and abroad with TCM background in clinical decision-making.

The surveys on quality indicators for the total testing process in clinical laboratories of Fujian Province in China from 2018 to 2023.

OBJECTIVES: This study investigates the application of 15 Quality Indicators (QIs) in clinical laboratories in Fujian Province, China, from 2018 to 2023. It identifies the main causes of laboratory errors and explores issues in the application of QIs, providing a reference for establishing provincial state-of-the-art and operational quality specifications (QSs). METHODS: All clinical laboratories in Fujian Province were organized to submit general information and original QIs data through the online External Quality Assessment (EQA) system of the National Clinical Laboratory Center (NCCL) for a survey of 15 QIs. Data from 2018 to 2023 were downloaded for statistical analysis, and the current QSs for the 15 QIs in Fujian Province were compared and analyzed with those published by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Working Group on Laboratory Errors and Patient Safety (WG-LEPS). RESULTS: QIs data from 542 clinical laboratories were collected. The survey on data sources showed that the number of laboratories recording QIs data using Laboratory Information Systems (LIS) increased annually, but the growth was modest and the proportion was less than 50 %. Among the laboratories using LIS to record QIs data, 133 continuously participated in this survey for six years, reporting different QIs. Over the six years, all reported QIs showed significant improvement or at least remained stable. The best median Sigma (σ) metrics were for the percentage of critical values notification and timely critical values notification, reaching 6σ, followed by the percentage of incorrect laboratory reports, with σ metrics ranging from 4.9σ to 5.1σ. In contrast, the percentage of tests covered by internal quality control (IQC) (1.5σ-1.7σ) and inter-laboratory comparison (0.1σ) remained consistently low. Compared to the QSs published by IFCC WG-LEPS, the QSs for the 15 QIs in Fujian Province in 2023 were stricter or roughly equivalent, except for the percentage of incorrect laboratory reports (Fujian Province: 0-0.221, IFCC WG-LEPS: 0-0.03). CONCLUSIONS: 1. The application of QIs has significantly improved the quality of testing in clinical laboratories in Fujian Province, but the percentage of tests covered by IQC and inter-laboratory comparison remain low; 2. Effective application of QIs requires the establishment of comprehensive LIS, unified calculation standards, and other supporting measures.

The biological variation of insulin resistance markers: data from the European Biological Variation Study (EuBIVAS).

OBJECTIVES: An insulin resistant state is characteristic of patients with type 2 diabetes, polycystic ovary syndrome, and metabolic syndrome. Identification of insulin resistance (IR) is most readily achievable using formulae combining plasma insulin and glucose results. In this study, we have used data from the European Biological Variation Study (EuBIVAS) to examine the biological variability (BV) of IR using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and the Quantitative Insulin sensitivity Check Index (QUICKI). METHODS: Ninety EuBIVAS non-diabetic subjects (52F, 38M) from five countries had fasting HOMA-IR and QUICKI calculated from plasma glucose and insulin samples collected concurrently on 10 weekly occasions. The within-subject (CVI) and between-subject (CVG) BV estimates with 95 % CIs were obtained by CV-ANOVA after analysis of trends, variance homogeneity and outlier removal. RESULTS: The CVI of HOMA-IR was 26.7 % (95 % CI 25.5-28.3), driven largely by variability in plasma insulin and the CVI for QUICKI was 4.1 % (95 % CI 3.9-4.3), reflecting this formula's logarithmic transformation of glucose and insulin values. No differences in values or BV components were observed between subgroups of men or women below and above 50 years. CONCLUSIONS: The EuBIVAS, by utilising a rigorous experimental protocol, has produced robust BV estimates for two of the most commonly used markers of insulin resistance in non-diabetic subjects. This has shown that HOMA-IR, in particular, is highly variable in the same individual which limits the value of single measurements.

Basic regulatory science behind drug substance and drug product specifications of monoclonal antibodies and other protein therapeutics.

In this review, we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding in regulatory science and compliance. Pharmaceutical specifications comprise a list of important quality attributes for testing, references to use for test procedures, and appropriate acceptance criteria for the tests, and they are set up to ensure that when a drug product is administered to a patient, its intended therapeutic benefits and safety can be rendered appropriately. Conformance of drug substance or drug product to the specifications is achieved by testing an article according to the listed tests and analytical methods and obtaining test results that meet the acceptance criteria. Quality attributes are chosen to be tested based on their quality risk, and consideration should be given to the merit of the analytical methods which are associated with the acceptance criteria of the specifications. Acceptance criteria are set forth primarily based on efficacy and safety profiles, with an increasing attention noted for patient-centric specifications. Discussed in this work are related guidelines that support the biopharmaceutical specification setting, how to set the acceptance criteria, and examples of the quality attributes and the analytical methods from 60 articles and 23 pharmacopeial monographs. Outlooks are also explored on process analytical technologies and other orthogonal tools which are on-trend in biopharmaceutical characterization and quality control.

Analytical performance specifications for trace elements in biological fluids derived from six countries federated external quality assessment schemes over 10 years.

OBJECTIVES: This article defines analytical performance specifications (APS) for evaluating laboratory proficiency through an external quality assessment scheme. METHODS: Standard deviations for proficiency assessment were derived from Thompson's characteristic function applied to robust data calculated from participants' submissions in the Occupational and Environmental Laboratory Medicine (OELM) external quality assurance scheme for trace elements in serum, whole blood and urine. Characteristic function was based on two parameters: (1) ß - the average coefficient of variation (CV) at high sample concentrations; (2) α - the average standard deviation (SD) at low sample concentrations. APSs were defined as 1.65 standard deviations calculated by Thompson's approach. Comparison between OELM robust data and characteristic function were used to validate the model. RESULTS: Application of the characteristic function allowed calculated APS for 18 elements across three matrices. Some limitations were noted, particularly for elements (1) with no sample concentrations near analytical technique limit of detection; (2) exhibiting high robust CV at high concentration; (3) exhibiting high analytical variability such as whole blood Tl and urine Pb; (4) with an unbalanced number of robust SD above and under the characteristic function such as whole blood Mn and serum Al and Zn. CONCLUSIONS: The characteristic function was a useful means of deriving APS for trace elements in biological fluids where biological variation data or outcome studies were not available. However, OELM external quality assurance scheme data suggests that the characteristic functions are not appropriate for all elements.

How did we get here? Evolution of specifications grading in a required skills-based course series.

BACKGROUND AND PURPOSE: Specifications grading is a mastery-based grading approach to unlock student potential and empower students to focus on learning goals while receiving and acting on meaningful feedback. Within specifications grading, bundles are created to group assignments and assessments. Based on student achievement within each bundle, overall course grade is determined. This article describes the development and implementation of a specifications grading schema in a required skills-based course series, along with lessons learned. EDUCATIONAL ACTIVITY AND SETTING: In a longitudinal course series with both a didactic and lab component, specifications grading was utilized for determination of the overall course grade. Key components of the specifications grading schema were defined by assignment bundles. Assignment bundles aligned with knowledge and skills taught and assessed in each course and also included summative capstone assessments. Each bundle was assigned a numeric grade linked to a letter grade which determined the students' final grade in the course. FINDINGS: Following first course offerings, several changes to the specifications grading schema were made to improve tracking of assignments and activities, to improve consistency across courses, and to aid in final course grade determination. All quizzes were changed to optional, formative quizzes to encourage student accountability. Additional changes were made to the processes of capstone remediation and reassessment, which led to changes in language of the grading schema. SUMMARY: Developing and implementing specifications grading was a crucial first step in building a required skills-based course series, which led to further refinement and improvement for future course offerings.

What is high rumination?

OBJECTIVE: The current paper tries to illuminate the need for standard cutoff points. INTRODUCTION: rumination is considered to be a transdiagnostic process leading to a variety of consequences. But, what is prominent ruminative tendency? Are there agreed-upon specifications or cutoff points that distinguish between high and low tendency to ruminate? In an attempt to answer these questions, we reviewed 25 works that compared people characterized as high or low in rumination. We found numerous inconsistencies in the characterization criteria and a great variability in cutoff points. Most studies did not provide enough information about the cutoff criteria or values. METHOD: We examined a sample of 454 participants using the RRS (Ruminative Response Scale), from which we tried to identify standard cutoff points. RESULTS SHOWED: 1) distributions of RRS, brooding and reflective pondering; 2) most studies used median split, which might explain the differences among studies; 3) examination of standard scores for the various cutoffs presented big variability among the studies; and 4) women had higher scores of rumination and brooding than men. CONCLUSION: Our paper highlights the need for homogeneity in the field. It suggests addressing the RRS, brooding and reflective pondering distributions as references for future studies. We recommend specifying: cutoff criteria, cutoff values, range, means and standard deviations. Researchers should consider the specific population (i.e., men vs. women or clinical vs. non clinical) of interest and infer specific cutoff points accordingly. Importantly, researchers should consider the implications of their choice of cutoff points and apply their criterion accordingly.

Modelling the impact of bias in fecal immunochemical testing on long-term outcomes of colorectal cancer screening.

BACKGROUND: As the impact of unmanaged bias (i.e. systematic source of inaccuracy) in fecal immunochemical test (FIT) analytical performance on long-term colorectal cancer (CRC) outcomes is unknown, we assessed the impact bias in FIT performance in an ongoing FIT-based CRC screening program. METHODS: This study consisted of two parts: cross-sectional observational data analysis to estimate change in short-term outcomes and microsimulation modelling to estimate change in long-term outcomes assuming different levels of bias by assuming 15 % lower up to 15 % higher Hemoglobin detected in the stool compared to observed. Two scenarios were considered: bias occurring 1) one-time only, due to the occasional bias associated with the FIT kits used in 2020 and 2) consistently due to a constant bias associated with the FIT kits used from 2020 onwards. RESULTS: With a hypothetical bias of -15 % to +15 %, we observed a positivity rate ranging from 6.7 % to 7.8 %, and a detection rate for CRC between 0.65 % and 0.68 %. Single biases in FIT performance resulted in less than 0.1 % change in long-term CRC screening outcomes, while consistent biases resulted in a much larger change (up to 1.4 % in CRC cases and CRC-related deaths and up to 2.07 % in total costs). Detecting lower Hemoglobin concentrations resulted in a relatively larger change on long-term CRC outcomes in comparison to positive bias. CONCLUSIONS: Because of the substantial impact of consistent FIT bias, it is important to set evidence-based acceptance criteria of bias on long-term CRC screening outcomes and in particular, the introduction of an asymmetrical or upward shifted tolerance interval for FIT bias.

Predicting fat cover in beef cattle to make on-farm management decisions: a review of assessing fat and of modeling fat deposition.

Demands of domestic and foreign market specifications of carcass weight and fat cover, of beef cattle, have led to the development of cattle growth models that predict fat cover to assist on-farm managers make management decisions. The objectives of this paper are 4-fold: 1) conduct a brief review of the biological basis of adipose tissue accretion, 2) briefly review live and carcass assessments of beef cattle, and carcass grading systems used to develop quantitative compositional and quality indices, 3) review fat deposition models: Davis growth model (DGM), French National Institute for Agricultural Research growth model (IGM), Cornell Value Discovery System (CVDS), and BeefSpecs drafting tool (BeefSpecsDT), and 4) appraise the process of translating science and practical skills into research/decision support tools that assist the Beef industry improve profitability. The r2 for live and carcass animal assessments, using several techniques across a range of species and traits, ranged from 0.61 to 0.99 and from 0.52 to 0.99, respectively. Model evaluations of DGM and IGM were conducted using Salers heifers (n = 24) and Angus-Hereford steers (n = 15) from an existing publication and model evaluations of CVDS and BeefSpecsDT were conducted using Angus steers (n = 33) from a research trial where steers were grain finished for 101 d in a commercial feedlot. Evaluating the observed and predicted fat mass (FM) is the focus of this review. The FM mean bias for Salers heifers were 7.5 and 1.3 kg and the root mean square error of prediction (RMSEP) were 31.2 and 27.8 kg and for Angus-Hereford steers the mean bias were -4.0 and -10.5 kg and the RMSEP were 9.14 and 21.5 kg for DGM and IGM, respectively. The FM mean bias for Angus steers were -5.61 and -2.93 kg and the RMSEP were 12.3 and 13.4 kg for CVDS and BeefSpecsDT, respectively. The decomposition for bias, slope, and deviance were 21%, 12%, and 68% and 5%, 4%, and 91% for CVDS and BeefSpecsDT, respectively. The modeling efficiencies were 0.38 and 0.27 and the models were within a 20 kg level of tolerance 91% and 88% for CVDS and BeefSpecsDT, respectively. Fat deposition models reported in this review have the potential to assist the beef industry make on-farm management decisions on live cattle before slaughter and improve profitability. Modelers need to continually assess and improve their models but with a caveat of 1) striving to minimize inputs, and 2) choosing on-farm inputs that are readily available.

Study on quality control methods and pharmacodynamic material basis of different specifications of Corydalis Rhizoma produced in Zhejiang Province.

ETHNOPHARMACOLOGICAL RELEVANCE: The quality control methods of different specifications of Corydalis Rhizoma in Zhejiang China (ZJ CR) are the same, so the quality of each specification couldnot be guaranteed. To clarify the quality control methods and pharmacodynamic material basis of ZJ CR with different specifications could provide reference for the quality control of ZJ CR. AIM OF THE STUDY: The purpose of this study was to establish a quality control method for ZJ CR with different specifications and to screen out the pharmacodynamic material basis of ZJ CR with different specifications. MATERIALS AND METHODS: Firstly, according to the existing grading standards, the medicinal materials were divided into specifications, and the character indexes of ZJ CR with different specifications were established. The quality indexes were established by HPLC, network pharmacology and literature retrieval. The correlation between the trait indexes and quality indexes of ZJ CR with different specifications was analyzed, and the best quality control method was established. Further combined with the pharmacodynamic indexes of ZJ CR with different specifications, the pharmacodynamic material basis of ZJ CR with different specifications was screened out by spectrum-effect analysis. The correlation between trait indexes and pharmacodynamic indexes was analyzed to verify the rationality of grade standard. RESULTS: The three specifications of ZJ CR were CR (Diameter ≥1.1 cm), CR (Diameter <1.1 cm), and CR (No size distinction). Diameter, width, thickness, grain weight, volume and 50 g grain number could be used as the trait indexes of ZJ CR. Protopine (CR1), palmatine hydrochloride (CR2), berberine hydrochloride (CR3), dehydrocorydaline (CR4), tetrahydropalmatine (CR5), tetrahydroberberine (CR6), corydaline (CR7), stylopine (CR8) and isoimperatorin (CR9) were identified. Total components, core components (CR5, CR6, CR7 and CR8), alcohol-soluble extracts (ASE) could be used as quality indexes. The best quality control methods of the three specifications respectively were: the larger the diameter and grain weight, the smaller the number of 50 g grains; The larger the diameter, the smaller the volume, thickness, width and number of 50 g particles; The larger the grain weight and volume, the smaller the number of 50 g grains. The main analgesic components of the three specifications respectively were: CR1, CR2 and core components; CR2, CR4; CR8, CR9. The larger the diameter and the less the number of 50 g grains, the better the analgesic effect of ZJ CR, and the grade standard was reasonable. CONCLUSIONS: This study showed that the quality control methods and pharmacodynamic material basis of ZJ CR with different specifications were different, which may be caused by the differences in traits and the contribution of main active ingredients. This study constructed an evaluation model combining external traits, internal quality and overall efficacy, and provided theoretical support for the rationality of ZJ CR grade standard.

Applying the Milan models to setting analytical performance specifications - considering all the information.

Analytical performance specifications (APS) are used for decisions about the required analytical quality of pathology tests to meet clinical needs. The Milan models, based on clinical outcome, biological variation, or state of the art, were developed to provide a framework for setting APS. An approach has been proposed to assign each measurand to one of the models based on a defined clinical use, physiological control, or an absence of quality information about these factors. In this paper we propose that in addition to such assignment, available information from all models should be considered using a risk-based approach that considers the purpose and role of the actual test in a clinical pathway and its impact on medical decisions and clinical outcomes in addition to biological variation and the state-of-the-art. Consideration of APS already in use and the use of results in calculations may also need to be considered to determine the most appropriate APS for use in a specific setting.

Physiologically Based Biopharmaceutics Modeling (PBBM): Best Practices for Drug Product Quality, Regulatory and Industry Perspectives: 2023 Workshop Summary Report.

Physiologically based biopharmaceutics modeling (PBBM) is used to elevate drug product quality by providing a more accurate and holistic understanding of how drugs interact with the human body. These models are based on the integration of physiological, pharmacological, and pharmaceutical data to simulate and predict drug behavior in vivo. Effective utilization of PBBM requires a consistent approach to model development, verification, validation, and application. Currently, only one country has a draft guidance document for PBBM, whereas other major regulatory authorities have had limited experience with the review of PBBM. To address this gap, industry submitted confidential PBBM case studies to be reviewed by the regulatory agencies; software companies committed to training. PBBM cases were independently and collaboratively discussed by regulators, and academic colleagues participated in some of the discussions. Successful bioequivalence "safe space" industry case examples are also presented. Overall, six regulatory agencies were involved in the case study exercises, including ANVISA, FDA, Health Canada, MHRA, PMDA, and EMA (experts from Belgium, Germany, Norway, Portugal, Spain, and Sweden), and we believe this is the first time such a collaboration has taken place. The outcomes were presented at this workshop, together with a participant survey on the utility and experience with PBBM submissions, to discuss the best scientific practices for developing, validating, and applying PBBMs. The PBBM case studies enabled industry to receive constructive feedback from global regulators and highlighted clear direction for future PBBM submissions for regulatory consideration.

Using analytical performance specifications in a medical laboratory.

Analytical performance specifications (APS) are used for the quantitative assessment of assay analytical performance, with the aim of providing information appropriate for clinical care of patients. One of the major locations where APS are used is in the routine clinical laboratory. These may be used to assess and monitor assays in a range of settings including method selection, method verification or validation, external quality assurance, internal quality control and assessment of measurement uncertainty. The aspects of assays that may be assessed include imprecision, bias, selectivity, sample type, analyte stability and interferences. This paper reviews the practical use of APS in a routine clinical laboratory, using the laboratory I supervise as an example.

The role of analytical performance specifications in international guidelines and standards dealing with metrological traceability in laboratory medicine.

The goal of metrological traceability is to have equivalent results for a measurand in clinical samples (CSs) irrespective of the in-vitro diagnostic medical device (IVD-MD) used for measurements. The International Standards Organization standard 17511 defines requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples used with IVD-MDs. Each step in metrological traceability has an uncertainty associated with the value assigned to a material. The uncertainty at each step adds to the uncertainty from preceding steps such that the combined uncertainty gets larger at each step. The combined uncertainty for a CS result must fulfil an analytical performance specification (APS) for the maximum allowable uncertainty (umax CS). The umax CS can be partitioned among the steps in a metrological traceability calibration hierarachy to derive the APS for maximum allowable uncertainty at each step. Similarly, the criterion for maximum acceptable noncommutability bias can be derived from the umax CS. One of the challenges in determining if umax CS is fulfilled is determining the repeatability uncertainty (u Rw) from operating an IVD-MD within a clinical laboratory. Most of the current recommendations for estimating u Rw from internal quality control data do not use a sufficiently representative time interval to capture all relevant sources of variability in measurement results. Consequently, underestimation of u Rw is common and may compromise assessment of how well current IVD-MDs and their supporting calibration hierarchies meet the needs of clinical care providers.

Pairing a bioinformatics-focused course-based undergraduate research experience with specifications grading in an introductory biology classroom.

Introducing bioinformatics-focused concepts and skills in a biology classroom is difficult, especially in introductory biology classrooms. Course-based Undergraduate Research Experiences (CUREs) facilitate this process, introducing genomics and bioinformatics through authentic research experiences, but the many learning objectives needed in scientific research and communication, foundational biology concepts, and bioinformatics-focused concepts and skills can make the process challenging. Here, the pairing of specifications grading with a bioinformatics-focused CURE developed by the Genomics Education Partnership is described. The study examines how the course structure with specifications grading facilitated scaffolding of writing assignments, group work, and metacognitive activities; and describes the synergies between CUREs and specifications grading. CUREs require mastery of related concepts and skills for working through the research process, utilize common research practices of revision and iteration, and encourage a growth mindset to learning-all of which are heavily incentivized in assessment practices focused on specifications grading.

Technology for managing incontinence: What are the research priorities?

Incontinence and toileting difficulties can often be successfully addressed by treating their underlying causes. However, (complete) cure is not always possible and continence products to prevent or contain unresolved leakage or to facilitate toileting are in widespread use. Many people use them successfully but identifying the product(s) most likely to meet individual needs can be challenging and the recently published Seventh International Consultation on Incontinence includes a chapter which draws on the literature to provide evidence-based recommendations to help clinicians and product users to select appropriate products. This paper is based on the same evidence, but reviewed from the different perspective of those keen to identify unmet needs and develop improved products. For each of the main continence product categories it (i) outlines the design approach and key features of what is currently available; (ii) provides a generic functional design specification; (iii) reviews how well existing products meet the requirements of their main user groups; and (iv) suggests priorities for the attention of product designers. It also flags some core scientific problems which - if successfully addressed - would likely yield benefits in multiple incontinence product contexts.

Maintaining the quality of vaccines through the use of standards: Current challenges and future opportunities.

An international hybrid meeting held 21-22 June 2023 in Ottawa, Canada brought together regulators, scientists, and industry experts to discuss a set of principles and best practices in the development and implementation of standards. Although the use of international standards (ISs) and international units (IUs) has been an essential part of ensuring human and animal vaccine quality in the past decades, the types and uses of standards have expanded with technological advances in manufacture and testing of vaccines. The needs of stakeholders are evolving in response to the ever-increasing complexity, diversity, and number of vaccine products as well as increasing efforts to replace animal-based potency tests with in vitro assays that measure relevant quality attributes. As such, there must be a concomitant evolution in the design and implementation of both international and in-house standards. Concomitantly, greater harmonization of regulatory expectations must be achieved through collaboration with standard-setting organizations, national control laboratories and manufacturers. Stakeholders provided perspectives on challenges and several recommendations emerged as essential to advancing agreed upon objectives.