Examining current practice for the analysis and reporting of harm outcomes in phase II and III pharmacology trials: exploring methods to facilitate improved detection of adverse drug reactions

Introduction Randomised controlled trials (RCTs) provide data to help establish the harm-profile of drugs but evidence suggests that this data is underutilised and analysis practices are suboptimal. Aims To develop and assess methods for the analysis and presentation of harm outcomes in phase II/III drug trials that can facilitate the detection of adverse drug reactions (ADRs) and enable communication of informative harm-profiles.Methods A systematic review looked at current practice for collection, analysis and reporting of harm outcomes and a scoping review to identify statistical methods proposed for their analysis was undertaken. A survey of clinical trial statisticians measured awareness of methods for the analysis of harm outcomes, barriers to their use and opinions on solutions to improve practice. Alternative strategies for analysis and presentation of harm outcomes were explored. Results The review of current practice confirmed that data on harm outcomes is not being fully utilised, providing evidence of inappropriate and inconsistent practices. The scoping review revealed a broad range of methods for the analysis of both prespecified and emerging harms. The survey confirmed sub-optimal practices and while there was a moderate level of awareness of alternative approaches, use was limited. Guidance and training on more appropriate methods was unanimously supported. Recommendation were devised via consensus to encourage trialists to use visualisations for analysing and reporting harm outcomes. Of the evaluated methods for the analysis of emerging harms none were appropriate in trials ≤5000 participants with some utility in specific scenarios, recommendations for use are provided. Conclusion Clinical trial statisticians agree that there is a need to improve how we analyse and report harm outcomes in RCTs. Efforts to date have focused on prespecified harm outcomes, with little thought given to emerging harms. Several solutions for immediate adoption are proposed but there remains the need for an easy to implement, objective, signal detection approach. Guidelines for best analysis practice that are endorsed by key stakeholders would also enable a more coherent and consistent path for change.Open Acces

Proceedings of the 119th Annual Meeting of the Iowa Academy of Science [Program, 2007]

https://scholarworks.uni.edu/ias_docs/1007/thumbnail.jp

MRI-guided non-invasive epicardial mapping in patients with implanted pacing devices

Developing patient-specific 3D heart models to non-invasively localize arrhythmic foci. My research focussed on the application of MRI and complex electrocardiography in patients with MRI conditional pacemaker systems

Liposomes generated from proliposomes for treatment of glioma using Momordica charantia extracts

Every year there is 2% increase in the reported cases of glioma. It is important to treat glioma from materials that are readily available in nature. One of the interesting properties of liposomes is their ability to target tumours and facilitate the cellular uptake of therapeutic agents compared to the agent alone. In this project, liposomes were prepared from SPC (Soy phosphatidylcholine) and HSPC (Hydrogenated soy phosphatidylcholine) phospholipids. Drug-free liposomes prepared by proliposomes were compared with the conventional method of producing liposomes. Conventional liposomes are biocompatible and biodegradable, however, they are physically and chemically unstable. The instability problems were avoided by formulating liposomes using the ethanol-based proliposome technology. In ethanol-based proliposome method, aqueous phase (e.g. water) was added to an ethanolic solution of phospholipid to generate liposomes. In this work, natural anticancer materials such as Paclitaxel (PTX) and Momordica charantia extracts (Whole fruit, Fruit alone and Seed alone) from Africa, China and India were incorporated in liposome formulations. These liposomes were analysed by investigating, the resultant size, size distribution and zeta potential of the vesicles. Either, the anticancer drug or extract of Momordica charantia was mixed with liposomes and checked for the efficacy of the anticancer-liposome formulations on the viability of glioma cell lines and the molecular mechanism of the cell death were also investigated. The results show that liposomes prepared by the conventional thin- film method were comparatively large in size as compared to liposomes generated from proliposomes. Liposomes generated from proliposomes (made from SPC or HSPC), when generated by hydration with Momordica charantia extracts (WF – Whole fruit, FA – Fruit alone or SA – Seed alone) from Africa, China or India respectively, or when prepared using PTX in the lipid phase had significantly larger size and wider size distribution as compared to drug free liposomes. Liposomes generated from proliposomes were neutral or negatively charged and were a mixture of oligolamellar and multilamellar vesicles regardless of formulation. Particle size and size distribution of HSPC liposomes were larger than SPC liposomes on inclusion of either Paclitaxel or Momordica charantia extracts. Liposome generated by proliposome method using the Momordica charantia extracts (FA, SA and WF) exerted cytotoxic effects against glioma cells 1321N1, Gos-3 and U87-MG at the higher concentrations with or without liposomes. Momordica charantia extracts showed either slight or no significant effect on the normal glial cells. The liposome formulations were more effective against glioma cells as compared to drug-free liposomes. FA extract of Momordica charantia was very effective with and without liposomes but less than PTX liposomes. The activities of caspase 3/7, caspase 9 and cytochrome c release were elevated in cancerous glial cell line indicating apoptosis via mitochondrial cell death or intrinsic pathway. In conclusion, the study showed that liposomes generated from proliposomes were appropriate to target cancerous glial cells by binding plant extracts Momordica charantia and PTX to SPC and HSPC phospholipids. The cell death was induced by apoptosis via mitochondrial cell death

Plant Hormones

Plant hormones are among the most essential biochemicals found in plants. Since Charles and Francis Darwin identified auxin action, several plant hormones have been discovered. These small signaling molecules regulate not only developmental and growth activities, but also stress responses throughout the plant’s life cycle. This book discusses recent advances, new perspectives, and applications of plant hormones. It is a useful resource for academics, scientists, students, and industry professionals