A Study of Practical Parameters and Their Relative Importance as Perceived by Various Stakeholders in Clinical Trials

A contract research organization (CRO) is a company which conducts a Good Clinical Practice (GCP) in clinical trial. There are literally hundreds of CROs worldwide employing a workforce of nearly 100,000 professionals. The project proposes the study of practical parameters and their relative importance as perceived by the various stakeholders in clinical trials. The survey was conducted in Bangalore and New Delhi. Primary market data was obtained by primary market research which included 80 clinical trial stakeholders by having a preliminary communication with them, followed by administering a questionnaire along with prior permission. There were 15 Sponsors/ CROs, 27 Investigators /Monitors and 38 Ethics committee members involved in the study. It was shown from the study that a clinical investigator involved in a clinical trial is responsible for ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations; for protecting the rights, safety, and welfare of the subjects under the investigator’s care; and for the control of drugs under investigation. It was also shown from the study that the sponsors of a clinical trial carry the ultimate responsibility for the initiation, management and financing of the clinical trial. The study has identified a specific training need at the level of the individual stakeholder to perform a particular job function and to identify the actual practical parameters in the Indian context important for the conduction of clinical trials (GCP) with respect to the different stakeholders, to determine the relative importance of these parameters as perceived by various stakeholders involved in clinical trials, and to identify the relative contributions of different stakeholders to the success/ satisfactory conduct of a clinical trial

The effect of prolonged simulated non- gravitational environment on mineral balance in the adult male, volume 1 Final report

Effect of prolonged bed rest with simulated weightlessness on mineral balance in male adult - Vol.

Advanced control strategies for bioprocess chromatography: Challenges and opportunities for intensified processes and next generation products

Recent advances in process analytical technologies and modelling techniques present opportunities to improve industrial chromatography control strategies to enhance process robustness, increase productivity and move towards real-time release testing. This paper provides a critical overview of batch and continuous industrial chromatography control systems for therapeutic protein purification. Firstly, the limitations of conventional industrial fractionation control strategies using in-line UV spectroscopy and on-line HPLC are outlined. Following this, an evaluation of monitoring and control techniques showing promise within research, process development and manufacturing is provided. These novel control strategies combine rapid in-line data capture (e.g. NIR, MALS and variable pathlength UV) with enhanced process understanding obtained from mechanistic and empirical modelling techniques. Finally, a summary of the future states of industrial chromatography control systems is proposed, including strategies to control buffer formulation, product fractionation, column switching and column fouling. The implementation of these control systems improves process capabilities to fulfil product quality criteria as processes are scaled, transferred and operated, thus fast tracking the delivery of new medicines to market

Prevention of bone mineral changes induced by bed rest: Modification by static compression simulating weight bearing, combined supplementation of oral calcium and phosphate, calcitonin injections, oscillating compression, the oral diophosphonatedisodium etidronate, and lower body negative pressure

The phenomenon of calcium loss during bed rest was found to be analogous to the loss of bone material which occurs in the hypogravic environment of space flight. Ways of preventing this occurrence are investigated. A group of healthy adult males underwent 24-30 weeks of continuous bed rest. Some of them were given an exercise program designed to resemble normal ambulatory activity; another subgroup was fed supplemental potassium phosphate. The results from a 12-week period of treatment were compared with those untreated bed rest periods. The potassium phosphate supplements prevented the hypercalciuria of bed rest, but fecal calcium tended to increase. The exercise program did not diminish the negative calcium balance. Neither treatment affected the heavy loss of mineral from the calcaneus. Several additional studies are developed to examine the problem further

Hormonal replacement therapy, prothrombotic mutations and the risk of venous thrombosis

Hormone replacement therapy (HRT) increases the risk of venous thrombosis. We investigated whether this risk is affected by carriership of hereditary prothrombotic abnormalities. Therefore, we determined the two most common prothrombotic mutations, factor V Leiden and prothrombin 20210A in women who participated in a case-control study on venous thrombosis. Relative risks were expressed as odds ratios (OR) with 95% confidence intervals (CI95). Among 7 7 women aged 45-64 years with a first venous thrombosis, 51% were receiving HRT at the time of thrombosis, compared with 24% of control women (OR = 3.3, CI95 1.8-5.8). Among the patients, 23% had a prothrombotic defect, versus 7% among the control women (OR = 3.8, CI95 1.7- 8.5). Women who had factor V Leiden and used HRT had a 15-fold increased risk (OR = 15.5, CI95 3.1-77), which exceeded the expected joint odds ratio of 6.1 (under an additive model). We conclude that the thrombotic risk of HRT may particularly affect women with prothrombotic mutations. Efforts to avoid HRT in women with increased risk of thrombosis are advisable

High-Throughput Raman Spectroscopy Combined with Innovate Data Analysis Workflow to Enhance Biopharmaceutical Process Development

Raman spectroscopy has the potential to revolutionise many aspects of biopharmaceutical process development. The widespread adoption of this promising technology has been hindered by the high cost associated with individual probes and the challenge of measuring low sample volumes. To address these issues, this paper investigates the potential of an emerging new high-throughput (HT) Raman spectroscopy microscope combined with a novel data analysis workflow to replace off-line analytics for upstream and downstream operations. On the upstream front, the case study involved the at-line monitoring of an HT micro-bioreactor system cultivating two mammalian cell cultures expressing two different therapeutic proteins. The spectra generated were analysed using a partial least squares (PLS) model. This enabled the successful prediction of the glucose, lactate, antibody, and viable cell density concentrations directly from the Raman spectra without reliance on multiple off-line analytical devices and using only a single low-volume sample (50–300 μL). However, upon the subsequent investigation of these models, only the glucose and lactate models appeared to be robust based upon their model coefficients containing the expected Raman vibrational signatures. On the downstream front, the HT Raman device was incorporated into the development of a cation exchange chromatography step for an Fc-fusion protein to compare different elution conditions. PLS models were derived from the spectra and were found to predict accurately monomer purity and concentration. The low molecular weight (LMW) and high molecular weight (HMW) species concentrations were found to be too low to be predicted accurately by the Raman device. However, the method enabled the classification of samples based on protein concentration and monomer purity, allowing a prioritisation and reduction in samples analysed using A280 UV absorbance and high-performance liquid chromatography (HPLC). The flexibility and highly configurable nature of this HT Raman spectroscopy microscope makes it an ideal tool for bioprocess research and development, and is a cost-effective solution based on its ability to support a large range of unit operations in both upstream and downstream process operations

Metabolic, inflammatory and haemostatic effects of a low-dose continuous combined HRT in women with type 2 diabetes: potentially safer with respect to vascular risk?

BACKGROUND Conventional hormone replacement therapy (HRT) containing conjugated equine oestrogen (CEE) and medroxyprogesterone acetate (MPA) increases triglyceride, C- reactive protein (CRP) and coagulation Factor VII concentrations, potentially explaining their increased coronary heart disease (CHD) and stroke risk. OBJECTIVE To assess the metabolic effects of a continuous combined HRT containing 1 mg oestradiol and 0.5 mg norethisterone or matching placebo. DESIGN Double-blind, randomized placebo-controlled trial. PATIENTS Fifty women with type 2 diabetes. MEASUREMENTS Classical and novel risk factors for vascular disease. RESULTS Triglyceride concentration was not altered (P = 0.31, change in active arm relative to placebo) and low-density lipoprotein (LDL) cholesterol concentration declined 13% (P = 0.018). IL-6 concentration (mean difference -1.42 pg/ml, 95% CI: -2.55 to - 0.29 IU/dl, P = 0.015), Factor VII (-32 IU/dl, -43 to -21 IU/l, P lt 0.001) and tissue plasminogen activator antigen (by 13%, P = 0.005) concentrations fell, but CRP was not significantly altered (P = 0.62). Fasting glucose (P = 0.026) also declined significantly, but there are no significant effects on HBA1c, Factor IX or APC resistance. CONCLUSIONS HRT containing 1 mg oestradiol and 0.5 mg norethisterone may avoid the adverse metabolic effects potentially implicated in the elevated CHD and stroke risk induced by conventional higher dose HRT. This type of preparation may therefore be more suitable than conventional HRT for women at elevated CHD risk such as those with type 2 diabetes. Large randomized controlled trials of such low dose preparations, powered for cardiovascular end points, are now needed

On arbitrages arising from honest times

In the context of a general continuous financial market model, we study whether the additional information associated with an honest time gives rise to arbitrage profits. By relying on the theory of progressive enlargement of filtrations, we explicitly show that no kind of arbitrage profit can ever be realised strictly before an honest time, while classical arbitrage opportunities can be realised exactly at an honest time as well as after an honest time. Moreover, stronger arbitrages of the first kind can only be obtained by trading as soon as an honest time occurs. We carefully study the behavior of local martingale deflators and consider no-arbitrage-type conditions weaker than NFLVR.Comment: 25 pages, revised versio

The surface temperatures of Earth: steps towards integrated understanding of variability and change

Surface temperature is a key aspect of weather and climate, but the term may refer to different quantities that play interconnected roles and are observed by different means. In a community-based activity in June 2012, the EarthTemp Network brought together 55 researchers from five continents to improve the interaction between scientific communities who focus on surface temperature in particular domains, to exploit the strengths of different observing systems and to better meet the needs of different communities. The workshop identified key needs for progress towards meeting scientific and societal requirements for surface temperature understanding and information, which are presented in this community paper. A "whole-Earth" perspective is required with more integrated, collaborative approaches to observing and understanding Earth's various surface temperatures. It is necessary to build understanding of the relationships between different surface temperatures, where presently inadequate, and undertake large-scale systematic intercomparisons. Datasets need to be easier to obtain and exploit for a wide constituency of users, with the differences and complementarities communicated in readily understood terms, and realistic and consistent uncertainty information provided. Steps were also recommended to curate and make available data that are presently inaccessible, develop new observing systems and build capacities to accelerate progress in the accuracy and usability of surface temperature datasets