Improved estimation of population variance in stratified successive sampling using calibrated weights under non-response.

This paper introduces a new method to estimate the population variance of a study variable in stratified successive sampling over two occasions, while accounting for random non-response. The method uses a logarithmic type estimator and leverages information from a highly positively correlated auxiliary variable. The paper also presents calibrated weights for the new estimator and examines its properties through numerical and simulation studies. The results indicate that the suggested estimator is more effective than the standard estimator for estimating the population variance.

A general class of improved population variance estimators under non-sampling errors using calibrated weights in stratified sampling.

This paper proposes a new calibration estimator for population variance within a stratified two-phase sampling design. It takes into account random non-response and measurement errors, specifically applying this method to estimate the variance in Gas turbine exhaust pressure data. The study integrates additional information from two highly positively correlated auxiliary variables to develop a general class of estimators tailored for the stratified two-phase sampling scheme. The properties of these estimators, in terms of their biases and mean square errors, have been thoroughly examined and extensively analyzed through numerical and simulation studies. Furthermore, the calibrated weights of the strata are derived. The proposed estimators outperform the natural estimator of population variance. Finally, suitable recommendations have been made for survey statisticians intending to apply these findings to real-life problems.

Estimating the growth rate of infection during the early phase of a pandemic like COVID-19.

At the very outbreak of a pandemic, it is very important to be able to assess the spreading rate of the disease i.e., the rate of increase of infected people in a specific locality. Combating the pandemic situation critically depends on an early and correct prediction of, to what extent the disease may possibly grow within a short period of time. This paper attempts to estimate the spreading rate by counting the total number of infected persons at times. Adaptive clustering is especially suitable for forming clusters of infected persons distributed spatially in a locality and successive sampling is used to measure the growth in number of infected persons. We have formulated a 'chain ratio to regression type estimator of population total' in two occasions adaptive cluster successive sampling and studied the properties of the estimator. The efficacy of the proposed strategy is demonstrated through simulation technique as well as real life population which is followed by suitable recommendation.

Some Classes of Logarithmic-Type Imputation Techniques for Handling Missing Data.

In this manuscript, three new classes of log-type imputation techniques have been proposed to handle missing data when conducting surveys. The corresponding classes of point estimators have been derived for estimating the population mean. Their properties (Mean Square Errors and bias) have been studied. An extensive simulation study using data generated from normal, Poisson, and Gamma distributions, as well as real dataset, has been conducted to evaluate how the proposed estimator performs in comparison to several contemporary estimators. The results have been summarized, and discussion regarding real-life applications of the estimator follows.

An Exponential-Cum-Sine-Type Hybrid Imputation Technique for Missing Data.

In this study, a new exponential-cum-sine-type hybrid imputation technique has been proposed to handle missing data when conducting surveys. The properties of the corresponding point estimator for population mean have been examined in terms of bias and mean square errors. An extensive simulation study using data generated from normal, Poisson, and Gamma distributions has been conducted to evaluate how the proposed estimator performs in comparison to several contemporary estimators. The results have been summarized, and discussion regarding real-life applications of the estimator follows.

Global Versus Indian Perspective of Pioglitazone-induced Adverse Drug Reactions Including Bladder Cancer: A Comparative Retrospective Pharmacovigilance Analysis.

PURPOSE: In 2011, France and Germany banned pioglitazone due to a concomitant risk for bladder cancer. There has been continued debate about this topic. Therefore, we present a detailed analysis of data from individual case safety reports of pioglitazone use (PG-ICSRs) associated with bladder cancer reported worldwide and in India. METHODS: Data from PG-ICSRs reported by the National Coordination Centre's Pharmacovigilance Programme of India, as well as over 131 World Health Organization member countries in the Uppsala Monitoring Centre's VigiLyze pharmacovigilance database system, from January 1, 1967, to March 4, 2018, were collected. Comparisons between data from global and Indian PG-ICSRs were made by applying filters such as country, bladder cancer, age group, gender, time period, information component, and data mining. FINDINGS: Among the adverse drug reactions (ADRs) reported with pioglitazone use worldwide, bladder cancer and related terms were the most highly reported (43%). The most frequently co-reported concurrently used drug was metformin, which was included in 25% and 40% of overall and bladder cancer-specific PG-ICSRs, respectively. Suspected bladder cancer-specific pioglitazone-related reactions were reported in 27 countries, with 8548 serious and 1858 fatal cases and an information components value of 9.15. The Americas had the highest relative percentage of suspected bladder cancer in PG-ICSRs (53%), while the prevalence was much lower in India (2%). In both cohorts, men over the age of 45 years constituted the most highly reported population. IMPLICATIONS: India has a very low prevalence of reported overall and bladder cancer-specific pioglitazone-related ADRs compared to Europe and the Americas. Possible explanations for the difference in reporting rates include variance in genetic makeup, low BC risk factor, pioglitazone prescription at a lower therapeutic dose, greater use of chemopreventive spices in the diet, higher frequency of metformin as a concurrent drug, and under-reporting of ADRs.

Veterinary pharmacovigilance in India: A need of hour.

Veterinary pharmacovigilance (PV) is important for the Medicine which are used for treating disease in animals. It becomes more important when these animals are further used for producing food. Adverse drug reactions (ADRs) have a direct impact on animals and indirect impact on human beings, for example, through milk products, other animal producing food products. Currently, PV program of India is playing a vital role in assessing the safety of medicines in Indian Population. The safety of medicine in animals can be assessed by veterinary PV. The research institutes involved in animal research and veterinary hospitals can be considered as ADR monitoring centers to assess the safety of medicines on animals.

Best Practices for Improving the Quality of Individual Case Safety Reports in Pharmacovigilance.

BACKGROUND: The quality of individual case safety reports (ICSRs) plays a vital role in identifying new safety signals in pharmacovigilance. This article focuses on establishing a method for ensuring the quality data. OBJECTIVE: To develop an in-house method for assessing the documentation grading and completeness score of ICSRs. METHODS: In the proposed method, 16 parameters, from report title to case narrative, are adopted to assess the quality of ICSRs. The in-house method ensures the completeness of the data and enhances the quality of ICSRs. RESULTS: The in-house method was found effective in calculating the completeness score of ICSR ranges from 0.05 to 1. Indian ICSR completeness scores significantly improved after the implementation of the proposed method in the third quarter of 2013. In 2014 and until the third quarter of 2015, the score was found to be 0.91 and 0.93 out of 1, respectively. CONCLUSION: The higher quality ICSRs aids in more effective identification of new drug safety alerts and provides evidence-based information for regulating the drug safety.

Selection of appropriate analytical tools to determine the potency and bioactivity of antibiotics and antibiotic resistance.

Antibiotics are the chemotherapeutic agents that kill or inhibit the pathogenic microorganisms. Resistance of microorganism to antibiotics is a growing problem around the world due to indiscriminate and irrational use of antibiotics. In order to overcome the resistance problem and to safely use antibiotics, the correct measurement of potency and bioactivity of antibiotics is essential. Microbiological assay and high performance liquid chromatography (HPLC) method are used to quantify the potency of antibiotics. HPLC method is commonly used for the quantification of potency of antibiotics, but unable to determine the bioactivity; whereas microbiological assay estimates both potency and bioactivity of antibiotics. Additionally, bioassay is used to estimate the effective dose against antibiotic resistant microbes. Simultaneously, microbiological assay addresses the several parameters such as minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC), mutation prevention concentration (MPC) and critical concentration (Ccr) which are used to describe the potency in a more informative way. Microbiological assay is a simple, sensitive, precise and cost effective method which gives reproducible results similar to HPLC. However, the HPLC cannot be a complete substitute for microbiological assay and both methods have their own significance to obtain more realistic and precise results.

Selection of appropriate analytical tools to determine the potency and bioactivity of antibiotics and antibiotic resistance$ / 药物分析学报

Antibiotics are the chemotherapeutic agents that kill or inhibit the pathogenic microorganisms. Re-sistance of microorganism to antibiotics is a growing problem around the world due to indiscriminate and irrational use of antibiotics. In order to overcome the resistance problem and to safely use antibiotics, the correct measurement of potency and bioactivity of antibiotics is essential. Microbiological assay and high performance liquid chromatography (HPLC) method are used to quantify the potency of antibiotics. HPLC method is commonly used for the quantification of potency of antibiotics, but unable to determine the bioactivity; whereas microbiological assay estimates both potency and bioactivity of antibiotics. Additionally, bioassay is used to estimate the effective dose against antibiotic resistant microbes. Simultaneously, microbiological assay addresses the several parameters such as minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC), mutation prevention concentration (MPC) and critical concentration (Ccr) which are used to describe the potency in a more informative way. Microbiological assay is a simple, sensitive, precise and cost effective method which gives reproducible results similar to HPLC. However, the HPLC cannot be a complete substitute for microbiological assay and both methods have their own significance to obtain more realistic and precise results.

Status of documentation grading and completeness score for Indian individual case safety reports.

The quality of individual case safety reports (ICSRs) generated under Pharmacovigilance Programme of India (PvPI) plays a pivotal role in detecting a signal from Indian drug safety data. Currently, more than hundred thousand ICSRs were generated under PvPI and reported to Uppsala Monitoring Centre. The documentation grading and completeness score of Indian ICSRs were rapidly increasing, and the current score was 0.94 out of 1.0. Periodical training on emphasizing the quality ICSRs is need of the hour.

Quality by Design Approach for Simultaneous Estimation of Doxycycline Hyclate and Curcumin by RP-HPLC Method.

A simple, rapid, reliable, robust and optimized reversed phase high performance liquid chromatographic method for simultaneous estimation of doxycycline hyclate and curcumin was successfully developed and validated as per International Conference on Harmonization guidelines. The objective was achieved in terms of well separated peaks within 10 min on a Waters Sunfire C8 column with dimensions of 250×4.6 mm, particle size 5.0 µm using mobile phase consisting of 30 volumes of potassium dihydrogen phosphate buffer (50 mM) adjusted to pH 6.5±0.1 with triethylamine and 70 volumes of methanol at flow rate of 0.85 ml/min. The column effluents were monitored at 400 nm maintained at ambient column temperature (28(o)). The developed method was found linear over the concentration range of 200-700 µg/ml for doxycycline hyclate and 8-28 µg/ml for curcumin, the detection and quantitation limit was found to be 26.063 and 78.97 µg/ml for doxycycline hyclate; 0.795 and 2.13 µg/ml for curcumin, respectively. The developed method was optimized using Minitab software version 16 to meet the current quality by design requirements. The method validation was done for linearity, range, detection and quantitation limit, accuracy, precision, specificity, system suitability testing, and robustness.

Development and validation of microbial bioassay for quantification of Levofloxacin in pharmaceutical preparations.

The aim of this study was to develop and validate a simple, sensitive, precise and cost-effective one-level agar diffusion (5+1) bioassay for estimation of potency and bioactivity of Levofloxacin in pharmaceutical preparation which has not yet been reported in any pharmacopoeia. Among 16 microbial strains, Bacillus pumilus ATCC-14884 was selected as the most significant strain against Levofloxacin. Bioassay was optimized by investigating several factors such as buffer pH, inoculums concentration and reference standard concentration. Identification of Levofloxacin in commercial sample Levoflox tablet was done by FTIR spectroscopy. Mean potency recovery value for Levofloxacin in Levoflox tablet was estimated as 100.90%. A validated bioassay method showed linearity (r2=0.988), precision (Interday RSD=1.05%, between analyst RSD=1.02%) and accuracy (101.23%, RSD=0.72%). Bioassay was correlated with HPLC using same sample and estimated potencies were 100.90% and 99.37%, respectively. Results show that bioassay is a suitable method for estimation of potency and bioactivity of Levofloxacin pharmaceutical preparations.

Implementing the Principle of the 3 Rs Through the Indian Pharmacopoeia.

Quality and safety tests are required for regulatory approval of drugs and pharmaceuticals in the country to guarantee minimum safety standards, and most of these tests include animal usage. In the case of biological medicines, these safety and quality tests have to be performed on a batch-to-batch basis and require a large number of animals. Russell and Burch's 1959 principle of the 3 Rs- replacement, reduction, and refinement-is now being increasingly adopted worldwide, and various national and international pharmacopoeias have taken initiatives to safeguard animals. This article details the Indian Pharmacopoeia Commission's initiative to implement the 3 Rs through the Indian Pharmacopoeia. Explored are the deletion of animal tests, such as the abnormal toxicity test at final lot for biologicals; the replacement of in vivo methods by in vitro methods; the reduction in the number of animals used where deletion of the animal test is not possible; and the refinement of tests to cause minimal suffering to the animals. In Indian Pharmacopoeia 2014, pyrogen testing using rabbits has been replaced by the bacterial endotoxin test in the majority of biological monographs-keeping in view international trends and, especially for vaccine monographs, validated in vitro tests such as the bacterial endotoxin test as an alternative to the pyrogen test where justified and authorized. Steps are taken for introducing a single-dilution assay for the potency testing of diphtheria and tetanus vaccine (adsorbed) with the aim of minimizing number of animals used. The justified and authorized use of animals in drug manufacturing, analytic laboratories, and research will not only help in the expedited development/production of drugs but also be useful in protecting and promoting animal health.

Development and validation of microbial bioassay for quantification of Levofloxacin in pharmaceutical preparations / 药物分析学报

The aim of this study was to develop and validate a simple, sensitive, precise and cost-effective one-level agar diffusion (5t1) bioassay for estimation of potency and bioactivity of Levofloxacin in pharmaceutical preparation which has not yet been reported in any pharmacopoeia. Among 16 microbial strains, Bacillus pumilus ATCC-14884 was selected as the most significant strain against Levofloxacin. Bioassay was optimized by investigating several factors such as buffer pH, inoculums concentration and reference standard concentration. Identification of Levofloxacin in commercial sample Levoflox tablet was done by FTIR spectroscopy. Mean potency recovery value for Levofloxacin in Levoflox tablet was estimated as 100.90%. A validated bioassay method showed linearity (r2 ? 0.988), precision (Interday RSD ? 1.05%, between analyst RSD ? 1.02%) and accuracy (101.23%, RSD ? 0.72%). Bioassay was correlated with HPLC using same sample and estimated potencies were 100.90%and 99.37%, respectively. Results show that bioassay is a suitable method for estimation of potency and bioactivity of Levofloxacin pharmaceutical preparations.

Development and Validation of an RP-HPLC Method for Quantitative Estimation of Eslicarbazepine Acetate in Bulk Drug and Tablets.

A convenient, simple, accurate, precise and reproducible RP-HPLC method was developed and validated for the estimation of eslicarbazepine acetate in bulk drug and tablet dosage form. Objective was achieved under optimised chromatographic conditions on Dionex RP-HPLC system with Dionex C18 column (250×4.6 mm, 5 µm particle size) using mobile phase composed of methanol and ammonium acetate (0.005 M) in the ratio of 70:30 v/v. The separation was achieved using an isocratic elution method with a flow rate of 1.0 ml/ min at room temperature. The effluent was monitored at 230 nm using diode array detector. The retention time of eslicarbazepine acetate is found to be 4.9 min and the standard calibration plot was linear over a concentration range of 10-90 µg/ml with r(2)=0.9995. The limit of detection and quantification were found to be 3.144 and 9.52 µg/ml, respectively. The amount of eslicarbazepine acetate in bulk and tablet dosage form was found to be 99.19 and 97.88%, respectively. The method was validated statistically using the percent relative standard deviation and the values are found to be within the limits. The recovery studies were performed and the percentage recoveries were found to be 98.33± 0.5%.

Development and Validation of a RP-HPLC Method for Estimation of Prulifloxacin in Tablet Dosage Form.

A simple, precise, rapid, accurate and economic reverse phase high performance liquid chromatographic method has been developed for the estimation of prulifloxacin in tablet dosage form. The separation was achieved by using octadecylsilane column (C(18)) and KH(2)PO(4) buffer: acetonitrile adjusted to pH 7.3 with triethyl amine in proportion of 10:90 v/v as mobile phase, at a flow rate of 1.0 ml/min. The detection was carried out at 278 nm. The retention time of prulifloxacin was found to be 2.4 min. The limit of detection and limit of quantitation were found to be 0.14 µg/ml and 0.42 µg/ml respectively. The accuracy and reliability of the proposed method was ascertained by evaluating various validation parameters like linearity, precision, accuracy and specificity according to ICH guidelines. The proposed method provides an accurate and precise quality control tool for routine analysis of prulifloxacin in tablet dosage form.

Development and Validation of a RP-HPLC Method for Estimation of Montelukast Sodium in Bulk and in Tablet Dosage Form.

The present work describes a simple, precise and accurate HPLC method for estimation of montelukast sodium in bulk and in tablet dosage form. The separation was achieved by using octadecylsilane column (C18) and acetonitrile:1 mM sodium acetate adjusted to pH 6.3 with acetic acid in proportion of 90:10 v/v as mobile phase, at a flow rate of 1.5 ml/min. Detection was carried out at 285 nm. The retention time of montelukast sodium was found to be 3.4 min. The limit of detection was found 1.31 µg/ml and limit of quantification 3.97 µg/ml. The accuracy and reliability of the proposed method was ascertained by evaluating various validation parameters like linearity (1-100 µg/ml), precision, accuracy and specificity according to ICH guidelines. The proposed method provides an accurate and precise quality control tool for routine analysis of montelukast sodium in bulk and in tablet dosage form.

Development and Validation of a RP-Ultra performance liquid chromatographic Method for Quantification of Topotecan Hydrochloride in Bulk and Injection Dosage Form.

A simple, very fast, precise and accurate reverse phase ultra performance liquid chromatographic method was developed for the determination and validation of topotecan hydrochloride in bulk and injection dosage form. A Waters BEH C18, 50×2.1 mm, 1.7 µm particle size column in gradient mode was used with mobile phase comprising of 0.1% v/v orthophosphoric acid in water and acetonitrile. The analytical column was thermostated at 50° and flow rate was set at 0.4 ml per min, with photo diode array detection at 260 nm. The retention time of topotecan was found 1.38 min. The method was validated in terms of linearity, accuracy, precision and specificity. The calibration curve was found linear between 20 to 60 µg/ml. The limit of detection and limit of quantification were found 0.2353 and 0.7131 µg/ml, respectively. Percentage recoveries were obtained in the range of 98.91% and 99.17%. The proposed method is precise, accurate, selective and reproducible. The ultra performance liquid chromatographic assay procedure, which proved superior because of its greater sensitivity and relatively shorter (4 min) run time, should be an important tool for speedy future analysis of topotecan hydrochloride in bulk and its injection dosage form.