This is the companion talk to one I posted yesterday. This is the Third of the talks that I gave in Asia back in May. Both this talk and the "Making Every Patient Count" presentation were part of a larger program at the DIA China Annual meeting.
Clinical Pharmacology in Orphan Drug DevelopmentE. Dennis Bashaw
This is the fourth talk that I gave in Asia back in May. It was presented at the Konect (Korea National Enterprise for Clinical Trials) 3rd symposia that was held in Seoul at Seoul National University.
Transalational Sciences and Clinical Pharmacology in Orphan Drug DevelopmentE. Dennis Bashaw
This document discusses challenges and solutions for developing orphan drugs and implementing precision medicine programs. It notes that orphan drug development faces resource constraints as trials require more patients than rare diseases have. However, using clinical pharmacology tools allows learning from small populations by incorporating biomarkers, modeling, and innovative designs. The future of drug development lies in going beyond traditional trials to involve patients more and continually learn from individual experiences. Quantitative tools during all stages of development can extract maximum knowledge from minimal data to improve understanding, approval chances, and labeling.
Clinical Pharmacology: Leveraging Science to Provide AccessE. Dennis Bashaw
1) The document discusses the paradigm shift in biomarker development from a "learn and confirm" model to an "identify, confirm, refine, and learn" model to continuously learn from clinical trials.
2) It outlines policies used by the FDA to incentivize orphan drug development, including expedited programs, marketing exclusivity, and fee reductions. International collaboration is important for developing policies tailored to individual countries.
3) Successful partnerships between the FDA, NIH, patient groups, and industry have helped advance rare disease drug development, including through biospecimen repositories and training programs.
This document discusses orphan drugs and rare disease drug development. It outlines the challenges in developing drugs for rare diseases, including small patient populations and lack of knowledge. The role of clinical pharmacology in drug development is described, including use of innovative analyses, trial designs, and knowledge management to help overcome challenges. Clinical pharmacology can point the way by applying lessons from oncology and pediatric drug models to the orphan drug context. Collaboration across different stakeholders is needed to develop safe and effective drugs for rare diseases.
Drug Information Association Clinical Forum Presentationdneasha
Pharmacoepidemiology studies were performed on YASMIN and CRESTOR to better understand safety risks in real-world use. For YASMIN, a large database study found no increased risks of hyperkalemia or blood clots compared to other oral contraceptives. For CRESTOR, a global program using multiple databases evaluated safety outcomes like rhabdomyolysis. Future directions may include using health databases and electronic records in large simple trials to efficiently answer safety questions.
Detection, reporting and monitoring of ad rs final pptSabeena Choudhary
Adverse drug reactions (ADRs) are important to monitor through pharmacovigilance programs. Spontaneous reporting of ADRs by healthcare professionals and patients allows detection of rare or delayed reactions not seen in clinical trials. Common causes of ADRs include medication errors, non-compliance, and drug interactions. Serious ADRs can lead to death, hospitalization, disability or congenital abnormalities. It is important for doctors, nurses and patients to recognize and report any suspected ADRs to their national pharmacovigilance center to monitor drug safety. Proper causality assessment is needed to determine the likelihood of an ADR being caused by a suspected medication.
The document discusses various methods used in pharmacovigilance including spontaneous reporting systems, case series, stimulated reporting, active surveillance methods like sentinel sites and drug event monitoring, use of registries, observational studies like cross-sectional, case-control and cohort studies, targeted clinical investigations and descriptive studies. It also outlines the key aims and shared responsibilities of pharmacovigilance among drug companies, regulatory authorities, doctors, pharmacists and nurses.
Pharmacovigilance is the monitoring of medicines to detect adverse effects and improve patient safety. The document discusses the importance of pharmacovigilance in identifying unknown risks, encouraging safe drug use, and preventing withdrawal of medicines from the market. It outlines how pharmacovigilance involves spontaneous reporting from healthcare professionals, analysis of safety data, and information sharing to improve clinical practice and drug regulation. Students can contribute through reporting adverse drug reactions, creating drug alerts and bulletins, and presenting information on pharmacovigilance.
Clinical Pharmacology in Orphan Drug DevelopmentE. Dennis Bashaw
This is the fourth talk that I gave in Asia back in May. It was presented at the Konect (Korea National Enterprise for Clinical Trials) 3rd symposia that was held in Seoul at Seoul National University.
Transalational Sciences and Clinical Pharmacology in Orphan Drug DevelopmentE. Dennis Bashaw
This document discusses challenges and solutions for developing orphan drugs and implementing precision medicine programs. It notes that orphan drug development faces resource constraints as trials require more patients than rare diseases have. However, using clinical pharmacology tools allows learning from small populations by incorporating biomarkers, modeling, and innovative designs. The future of drug development lies in going beyond traditional trials to involve patients more and continually learn from individual experiences. Quantitative tools during all stages of development can extract maximum knowledge from minimal data to improve understanding, approval chances, and labeling.
Clinical Pharmacology: Leveraging Science to Provide AccessE. Dennis Bashaw
1) The document discusses the paradigm shift in biomarker development from a "learn and confirm" model to an "identify, confirm, refine, and learn" model to continuously learn from clinical trials.
2) It outlines policies used by the FDA to incentivize orphan drug development, including expedited programs, marketing exclusivity, and fee reductions. International collaboration is important for developing policies tailored to individual countries.
3) Successful partnerships between the FDA, NIH, patient groups, and industry have helped advance rare disease drug development, including through biospecimen repositories and training programs.
This document discusses orphan drugs and rare disease drug development. It outlines the challenges in developing drugs for rare diseases, including small patient populations and lack of knowledge. The role of clinical pharmacology in drug development is described, including use of innovative analyses, trial designs, and knowledge management to help overcome challenges. Clinical pharmacology can point the way by applying lessons from oncology and pediatric drug models to the orphan drug context. Collaboration across different stakeholders is needed to develop safe and effective drugs for rare diseases.
Drug Information Association Clinical Forum Presentationdneasha
Pharmacoepidemiology studies were performed on YASMIN and CRESTOR to better understand safety risks in real-world use. For YASMIN, a large database study found no increased risks of hyperkalemia or blood clots compared to other oral contraceptives. For CRESTOR, a global program using multiple databases evaluated safety outcomes like rhabdomyolysis. Future directions may include using health databases and electronic records in large simple trials to efficiently answer safety questions.
Detection, reporting and monitoring of ad rs final pptSabeena Choudhary
Adverse drug reactions (ADRs) are important to monitor through pharmacovigilance programs. Spontaneous reporting of ADRs by healthcare professionals and patients allows detection of rare or delayed reactions not seen in clinical trials. Common causes of ADRs include medication errors, non-compliance, and drug interactions. Serious ADRs can lead to death, hospitalization, disability or congenital abnormalities. It is important for doctors, nurses and patients to recognize and report any suspected ADRs to their national pharmacovigilance center to monitor drug safety. Proper causality assessment is needed to determine the likelihood of an ADR being caused by a suspected medication.
The document discusses various methods used in pharmacovigilance including spontaneous reporting systems, case series, stimulated reporting, active surveillance methods like sentinel sites and drug event monitoring, use of registries, observational studies like cross-sectional, case-control and cohort studies, targeted clinical investigations and descriptive studies. It also outlines the key aims and shared responsibilities of pharmacovigilance among drug companies, regulatory authorities, doctors, pharmacists and nurses.
Pharmacovigilance is the monitoring of medicines to detect adverse effects and improve patient safety. The document discusses the importance of pharmacovigilance in identifying unknown risks, encouraging safe drug use, and preventing withdrawal of medicines from the market. It outlines how pharmacovigilance involves spontaneous reporting from healthcare professionals, analysis of safety data, and information sharing to improve clinical practice and drug regulation. Students can contribute through reporting adverse drug reactions, creating drug alerts and bulletins, and presenting information on pharmacovigilance.
Safety data is generated throughout the drug development and approval process, including pre-clinical trials, clinical trials, and post-approval monitoring. In pre-clinical trials, exploratory and regulatory toxicology studies provide safety data. Clinical trials involve monitoring adverse events and serious adverse events. Post-approval, safety is monitored through periodic safety update reports, spontaneous reporting, and other methods. Safety data informs the entire process from drug discovery through marketing.
Pharmacovigilance is the science of monitoring the effects of medicines after they have been licensed for use, in order to identify new safety hazards and assess risks and benefits. It aims to improve patient care and safety in relation to medicine use. The thalidomide disaster in the 1960s demonstrated the need for formal pharmacovigilance systems to detect adverse drug reactions. Spontaneous reporting by healthcare professionals and mandatory reporting by manufacturers are key methods for collecting information on adverse drug events. Reports are assessed for causality and contribute to the ongoing evaluation of medicines to ensure their safe and effective use.
Drug Safety & Pharmacovigilance - Introduction - Katalyst HLSKatalyst HLS
Introduction to Drug Safety & Pharmacovigilance in Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Contact:
"Katalyst Healthcares & Life Sciences"
South Plainfield, NJ, USA
info@KatalystHLS.com
Pharmacovigilance AND ADVERSE DRUG REACTIONS.
MONITORING REPORTING ROLE OF PHARMACIST.
CLASSIFICATION OF ADR. MECHANISM OF ADR
ROLE OF PHARMACIST IN MANAGING ADR. AUGMENTED, BIZZARE, CONTINOUS, DELAYED, END OF TREATMENT, ABCD, ABCDE.
Regulatory requirements for drug approval unit3Aman chourasia
New Drug Application (NDA) is an application submitted to the individual regulatory authority for authorization to market a new drug i.e. innovative product. To gain this permission a sponsor submits preclinical and clinical test data for analyzing the drug information, description of manufacturing trials.
Pharmacoepidemiology involves applying epidemiological methods to study drug use and effects in large populations. It is primarily concerned with post-marketing drug safety surveillance but also analyzes patterns of drug use and assesses effectiveness. Pharmacoepidemiological studies use large healthcare databases and are important for identifying adverse drug reactions, determining risk factors, and improving appropriate medication use. Common study designs include cohort studies, case-control studies, and randomized controlled trials. Pharmacoepidemiology plays a key role in drug regulation, marketing, clinical practice, and public health policy.
GCP: An international ethical and scientific quality standard for designing, conducting, recording and reporting clinical trials that involve the participation of human subjects.
PV: The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.
1) The process of bringing a new medicine from initial discovery to patient use (molecule to medicine) is a long, complex, and expensive process involving target identification, preclinical testing, clinical trials, and regulatory review and approval.
2) Preclinical testing involves evaluating a molecule's pharmacokinetics, pharmacodynamics, safety, and toxicity in cell and animal studies. Positive preclinical results allow filing an Investigational New Drug (IND) application to begin human clinical trials.
3) Clinical trials are conducted in four phases to evaluate a drug's safety, efficacy, side effects, and optimal dosing in humans. The entire development process from discovery to approval takes 8-12 years and costs over $1
This document provides definitions and information related to pharmacovigilance. It discusses adverse event reporting, international collaboration, and national drug regulatory authorities. Key aspects of pharmacovigilance include collecting, monitoring, and preventing adverse effects of pharmaceutical products to assure their safe use.
This document discusses pharmacovigilance, which involves monitoring the safety of drugs after they have been approved. It defines pharmacovigilance and explains why it is needed given limitations of clinical trials. It describes types of adverse drug reactions and how they are classified. It outlines the goals and processes of pharmacovigilance programs, including reporting adverse reactions, conducting causality assessments, and submitting periodic safety update reports. The overall aim is to ensure safe and effective use of medicines through continual monitoring and regulatory action.
This document discusses therapeutic drug monitoring (TDM) of biologics in inflammatory bowel disease (IBD). It provides an overview of the evolution of biologic agents for treating IBD from 1993 to present. Six biologic agents are currently approved for refractory IBD, including four anti-TNF agents and two anti-integrin agents. The document reviews guidelines for TDM from the American Gastroenterological Association, including recommended target trough concentrations for infliximab, adalimumab, and certolizumab pegol in patients with active IBD. It also discusses the rationale, methods, and algorithms for performing TDM to optimize treatment for patients with IBD.
Pharmacovigilance involves monitoring the safety of drugs at all stages, from development through post-marketing. It aims to detect, understand, and prevent adverse drug reactions through activities like adverse event reporting, drug monitoring, and studying medication errors and drug-related deaths. Pharmacovigilance is important for protecting public health as patterns of drug use change over time with globalization and advances in technology and medicine.
David Neasham Practical Use Pharmacoepi Drug Devguest41e570
This document summarizes a presentation on practical applications of pharmacoepidemiology in clinical drug development. It provides details on two case studies: a study of Yasmin, an oral contraceptive containing drospirenone, which found no increased risk of adverse events compared to other oral contraceptives. It also describes a large international study program of Crestor, a statin, which evaluated patient characteristics and safety outcomes across multiple databases.
Pharmacovigilance involves monitoring approved drugs to detect adverse effects, assess risks, prevent harm and promote safe use. It aims to improve public health by identifying unknown risks from case reports and studies. Several methods are used including spontaneous reporting, active surveillance and observational studies. Organizations like WHO and regulatory authorities play important roles in pharmacovigilance. The goal is continual assessment of benefit-risk profiles to optimize treatment outcomes.
Pharmacoepidemiology is the study of drug use in populations and the application of epidemiological methods to examine drug effects. It bridges clinical pharmacology and epidemiology. Pharmacoepidemiological research includes evaluating specific drug use, patterns of drug use, and drug-taking behaviors. Studies focus on prescribing trends, medication adherence, drug interactions, and adverse drug reactions. Data sources include medical records, health insurance claims, and national databases. Observational studies measure drug exposure and outcomes without intervention, while interventional studies actively change exposures. Descriptive studies describe disease occurrence, and case reports/series provide initial signals of drug effects. Cross-sectional studies examine drug use at a point in time, while cohort studies follow exposed and
This Presentation contains an introduction to clinical research.
* Basic definition of Clinical Research.
* Steps involved in clinical Research.
* Phases in Clinical Research.
* Types of clinical Trials.
pharmacovigilance, adverse effects, causality assessment,methods, who-umc method with case study, FOR DOWNLOAD PPT MAIL ME ON iamgauravchhabra@gmail.com
pharmacovigilance from pharmaceutical administration topic presented by konatham kumar reddy from chilkur balaaji college of pharmacy hyderabad telangana
UPDATED-Early Phase Drug Developmetn and Population PK and Its' ValueE. Dennis Bashaw
Presentation Given at Regional AAPS DDDI Meeting in Baltimore. Similar to previous talks BUT updated to include a discussion of BIA 10-2474 and extended discussion of risk
Safety data is generated throughout the drug development and approval process, including pre-clinical trials, clinical trials, and post-approval monitoring. In pre-clinical trials, exploratory and regulatory toxicology studies provide safety data. Clinical trials involve monitoring adverse events and serious adverse events. Post-approval, safety is monitored through periodic safety update reports, spontaneous reporting, and other methods. Safety data informs the entire process from drug discovery through marketing.
Pharmacovigilance is the science of monitoring the effects of medicines after they have been licensed for use, in order to identify new safety hazards and assess risks and benefits. It aims to improve patient care and safety in relation to medicine use. The thalidomide disaster in the 1960s demonstrated the need for formal pharmacovigilance systems to detect adverse drug reactions. Spontaneous reporting by healthcare professionals and mandatory reporting by manufacturers are key methods for collecting information on adverse drug events. Reports are assessed for causality and contribute to the ongoing evaluation of medicines to ensure their safe and effective use.
Drug Safety & Pharmacovigilance - Introduction - Katalyst HLSKatalyst HLS
Introduction to Drug Safety & Pharmacovigilance in Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Contact:
"Katalyst Healthcares & Life Sciences"
South Plainfield, NJ, USA
info@KatalystHLS.com
Pharmacovigilance AND ADVERSE DRUG REACTIONS.
MONITORING REPORTING ROLE OF PHARMACIST.
CLASSIFICATION OF ADR. MECHANISM OF ADR
ROLE OF PHARMACIST IN MANAGING ADR. AUGMENTED, BIZZARE, CONTINOUS, DELAYED, END OF TREATMENT, ABCD, ABCDE.
Regulatory requirements for drug approval unit3Aman chourasia
New Drug Application (NDA) is an application submitted to the individual regulatory authority for authorization to market a new drug i.e. innovative product. To gain this permission a sponsor submits preclinical and clinical test data for analyzing the drug information, description of manufacturing trials.
Pharmacoepidemiology involves applying epidemiological methods to study drug use and effects in large populations. It is primarily concerned with post-marketing drug safety surveillance but also analyzes patterns of drug use and assesses effectiveness. Pharmacoepidemiological studies use large healthcare databases and are important for identifying adverse drug reactions, determining risk factors, and improving appropriate medication use. Common study designs include cohort studies, case-control studies, and randomized controlled trials. Pharmacoepidemiology plays a key role in drug regulation, marketing, clinical practice, and public health policy.
GCP: An international ethical and scientific quality standard for designing, conducting, recording and reporting clinical trials that involve the participation of human subjects.
PV: The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.
1) The process of bringing a new medicine from initial discovery to patient use (molecule to medicine) is a long, complex, and expensive process involving target identification, preclinical testing, clinical trials, and regulatory review and approval.
2) Preclinical testing involves evaluating a molecule's pharmacokinetics, pharmacodynamics, safety, and toxicity in cell and animal studies. Positive preclinical results allow filing an Investigational New Drug (IND) application to begin human clinical trials.
3) Clinical trials are conducted in four phases to evaluate a drug's safety, efficacy, side effects, and optimal dosing in humans. The entire development process from discovery to approval takes 8-12 years and costs over $1
This document provides definitions and information related to pharmacovigilance. It discusses adverse event reporting, international collaboration, and national drug regulatory authorities. Key aspects of pharmacovigilance include collecting, monitoring, and preventing adverse effects of pharmaceutical products to assure their safe use.
This document discusses pharmacovigilance, which involves monitoring the safety of drugs after they have been approved. It defines pharmacovigilance and explains why it is needed given limitations of clinical trials. It describes types of adverse drug reactions and how they are classified. It outlines the goals and processes of pharmacovigilance programs, including reporting adverse reactions, conducting causality assessments, and submitting periodic safety update reports. The overall aim is to ensure safe and effective use of medicines through continual monitoring and regulatory action.
This document discusses therapeutic drug monitoring (TDM) of biologics in inflammatory bowel disease (IBD). It provides an overview of the evolution of biologic agents for treating IBD from 1993 to present. Six biologic agents are currently approved for refractory IBD, including four anti-TNF agents and two anti-integrin agents. The document reviews guidelines for TDM from the American Gastroenterological Association, including recommended target trough concentrations for infliximab, adalimumab, and certolizumab pegol in patients with active IBD. It also discusses the rationale, methods, and algorithms for performing TDM to optimize treatment for patients with IBD.
Pharmacovigilance involves monitoring the safety of drugs at all stages, from development through post-marketing. It aims to detect, understand, and prevent adverse drug reactions through activities like adverse event reporting, drug monitoring, and studying medication errors and drug-related deaths. Pharmacovigilance is important for protecting public health as patterns of drug use change over time with globalization and advances in technology and medicine.
David Neasham Practical Use Pharmacoepi Drug Devguest41e570
This document summarizes a presentation on practical applications of pharmacoepidemiology in clinical drug development. It provides details on two case studies: a study of Yasmin, an oral contraceptive containing drospirenone, which found no increased risk of adverse events compared to other oral contraceptives. It also describes a large international study program of Crestor, a statin, which evaluated patient characteristics and safety outcomes across multiple databases.
Pharmacovigilance involves monitoring approved drugs to detect adverse effects, assess risks, prevent harm and promote safe use. It aims to improve public health by identifying unknown risks from case reports and studies. Several methods are used including spontaneous reporting, active surveillance and observational studies. Organizations like WHO and regulatory authorities play important roles in pharmacovigilance. The goal is continual assessment of benefit-risk profiles to optimize treatment outcomes.
Pharmacoepidemiology is the study of drug use in populations and the application of epidemiological methods to examine drug effects. It bridges clinical pharmacology and epidemiology. Pharmacoepidemiological research includes evaluating specific drug use, patterns of drug use, and drug-taking behaviors. Studies focus on prescribing trends, medication adherence, drug interactions, and adverse drug reactions. Data sources include medical records, health insurance claims, and national databases. Observational studies measure drug exposure and outcomes without intervention, while interventional studies actively change exposures. Descriptive studies describe disease occurrence, and case reports/series provide initial signals of drug effects. Cross-sectional studies examine drug use at a point in time, while cohort studies follow exposed and
This Presentation contains an introduction to clinical research.
* Basic definition of Clinical Research.
* Steps involved in clinical Research.
* Phases in Clinical Research.
* Types of clinical Trials.
pharmacovigilance, adverse effects, causality assessment,methods, who-umc method with case study, FOR DOWNLOAD PPT MAIL ME ON iamgauravchhabra@gmail.com
pharmacovigilance from pharmaceutical administration topic presented by konatham kumar reddy from chilkur balaaji college of pharmacy hyderabad telangana
UPDATED-Early Phase Drug Developmetn and Population PK and Its' ValueE. Dennis Bashaw
Presentation Given at Regional AAPS DDDI Meeting in Baltimore. Similar to previous talks BUT updated to include a discussion of BIA 10-2474 and extended discussion of risk
DDS personalised medicines M.Pharma 1st Sem Pharmaceutics.pptxkushaltegginamani18
The document discusses personalized medicines and customized drug delivery systems. It defines personalized medicine as using genetic profiling and other individual patient characteristics to guide medical treatment. Customized drug delivery systems aim to optimize drug therapy for each patient by controlling dosage and delivery through technologies like bioelectronic medicines, 3D printing of pharmaceuticals, and telepharmacy.
1) The document describes the phases of clinical trials, from Phase I to Phase III. Phase I trials involve small numbers of patients and evaluate safety, Phase II evaluates efficacy and identifies groups likely to benefit, and Phase III further evaluates efficacy and safety in large randomized controlled trials.
2) The document provides examples of Phase I, II, and III clinical trial designs and goals. Phase III trials are typically multicenter, randomized controlled trials used to generate evidence for marketing approval of new drugs. Control groups are important to account for factors like natural disease progression.
3) Clinical trials progress from exploratory Phase I safety studies to definitive Phase III trials evaluating efficacy versus a control as the standard for regulatory approval of new interventions.
This document provides an overview of a proposed new drug called Regenozene to treat multiple sclerosis (MS) by inhibiting Death Receptor 6 (DR-6). The drug aims to promote remyelination of neurons in MS patients. If successful, Regenozene could potentially stop relapses and reverse disability from MS, addressing major unmet needs. The document outlines the pathogenesis of MS, Regenozene's proposed mechanism of action, target product profile, development plan through clinical trials and regulatory approval, manufacturing and intellectual property considerations, market analysis and financial projections. The virtual business model aims to minimize risk through partnerships while maintaining control over development.
The document discusses the importance of evaluating exposure-response relationships during Phase 2-3 clinical trials in order to select optimal doses, understand safety and efficacy results, and inform dosing recommendations for different patient populations. Conducting pharmacokinetic assessments and exposure-response analyses can help overcome barriers like late study design and data collection, and ensure patients receive the right drug, dose, and dosing instructions.
Early phase drug development and the fda roadmap final version 2axE. Dennis Bashaw
This is the slide deck used in my webinar that was presented on 2/1/2018 on the FDA Predictive Toxicology Roadmap. It was presented at a webinar hosted by BioIVT in my private capacity and is not an official statement of FDA policy
This document discusses Phase IV clinical trials, which are post-marketing studies conducted after a drug has been approved. Phase IV trials have several objectives, including assessing long-term risks and benefits of drug use in real-world populations. They can be mandated by regulatory authorities or initiated independently. Regulatory-mandated studies evaluate things like drug interactions, new formulations, or safety in special populations. Independent studies may utilize randomized controlled trial designs to compare drugs or surveillance methods to monitor drug use. Sample sizes are typically larger than Phase III trials to detect rare side effects.
Pharmacovigilance (PV) Companies: Ensuring Drug Safety in Personalized Treatm...ClinosolIndia
Pharmacovigilance, a critical component of the healthcare and pharmaceutical industry, plays a pivotal role in monitoring and ensuring the safety of drugs. As personalized treatment approaches gain prominence, the responsibilities of PV companies become even more significant. This article explores the key functions of pharmacovigilance companies in the context of personalized medicine, focusing on their role in ensuring drug safety and mitigating potential risks associated with tailored therapeutic interventions.
This document provides an overview of the drug development and clinical trial process. It discusses the various phases of drug discovery and development, including pre-clinical research (discovery and pharmacology) and clinical trials (Phase 1-3). Key points covered include the high costs and risks of drug development, clinical trial design and goals for each phase, pharmacokinetics/dynamics studies to understand drug behavior in the body, and factors like safety, efficacy, and regulatory approval. The overall process takes an average of 15 years and $2.6 billion to bring a new drug to market.
Bellus health corporate presentation baird conference september 6BellusHealth
- Roberto Bellini, President and CEO of BELLUS Health, presented at the Baird Global Healthcare Conference on their lead drug candidate BLU-5937 for chronic cough.
- BLU-5937 is a highly selective P2X3 antagonist that has shown in animal studies to reduce cough frequency equivalently to MK-7264 while avoiding its side effect of taste alteration.
- BELLUS is currently conducting a Phase 1 trial with data expected in Q4 2018 to select doses for future trials, with the goal of BLU-5937 becoming the best-in-class P2X3 antagonist for chronic cough.
A Little Bit of Everything, Quick & Snappy: Probiotics to Advances in the Car...PASaskatchewan
As pharmacists, you are rarely faced with a consistent patient population with similar problems and questions. More likely, each patient you interact with has unique and varied concerns that you must be ready to address in an instant. This session reflects the diversity of patients a pharmacist will face in day-to-day practice and covers a range of topics in a quick and snappy format. This session will cover the evidence as it relates to concurrent probiotic and antibiotic use, second line treatment for patients with type 2 diabetes, and explore new utilization strategies of using drugs traditionally used in the treatment of type 2 diabetes for patients with type 1 diabetes.
Presentation on drug development challenges and clinical trial optimization. Originally presented at DIA China May 2017. The companion slide set is here as well-Optimizing Clinical Trials with Advanced Tools
Thesis_PhD_Improving medication safety in the elderlyHA VO THI
The document discusses medication safety issues for elderly patients, noting that physiological changes with aging increase their risk of adverse drug reactions and interactions from polypharmacy. Polypharmacy, defined as using multiple medications, is common in elderly patients due to multiple chronic conditions but can increase problems with adherence and side effects. Improving medication safety for elderly patients requires addressing polypharmacy issues through individualized treatment reviews that consider life expectancy, treatment goals and targets.
ich guidelines for clinical trials, scientific approach ppt.pptxJyotshnaDevi4
The document outlines the ICH guidelines for conducting clinical trials. It describes the objectives to promote common understanding and evaluation of foreign clinical trial data. Clinical trials should follow scientific principles and protect subjects. Trials generally proceed through four phases, starting with small healthy volunteer studies (Phase I) to evaluate safety, followed by exploratory efficacy studies (Phase II), then confirmatory efficacy and dosing studies (Phase III), and finally post-marketing studies (Phase IV). Special populations like children, pregnant women, and those with organ impairment require unique consideration. Proper study design, conduct, analysis and reporting are emphasized.
Adapting Clinical Trials During a Global Pandemic: Lessons LearnedClinosolIndia
The COVID-19 pandemic has had a significant impact on clinical trials worldwide, requiring rapid adaptations to ensure patient safety, data integrity, and the continuity of research efforts. Several key lessons have been learned during this challenging time:
Flexibility and Adaptability: The pandemic highlighted the importance of flexibility in clinical trial design and operations. Researchers and regulatory bodies had to quickly adapt protocols to accommodate remote visits, decentralized approaches, and virtual assessments. Being able to modify protocols and implement alternative strategies allowed trials to continue while minimizing disruptions.
Remote Monitoring and Data Collection: Remote monitoring and data collection became crucial during the pandemic to ensure patient safety and collect data without in-person visits. Technologies such as wearable devices, telemedicine platforms, and electronic patient-reported outcomes (ePROs) played a significant role in enabling remote data collection and reducing the need for site visits.
Patient-Centric Approaches: The pandemic emphasized the importance of considering patients' needs and preferences. Remote visits, home healthcare services, and decentralized trial models were implemented to reduce the burden on patients and ensure their safety. Patient engagement and education became even more critical to maintain participation and retention in trials.
Regulatory Flexibility: Regulatory agencies recognized the need for flexibility during the pandemic and implemented measures to expedite trial approvals and amendments. They provided guidance on remote monitoring, virtual visits, and other alternative approaches, allowing researchers to adapt quickly while ensuring patient safety and data integrity.
Implementation of Pharmacogenomics in community pharmacies in Alberta:Percept...Dalia A. Hamdy
- Pharmacogenomics (PGx) utilizes DNA data to predict drug response and avoid side effects, leading to personalized therapy. Mutations in drug-metabolizing enzymes can impact drug metabolism and therapeutic outcomes.
- Benefits of PGx include increased medication effectiveness and reduced costs. However, barriers to implementation include lack of healthcare provider and patient education, insurance coverage, and legislation.
- A survey of 70 pharmacists, 105 pharmacy students, and 112 patients in Alberta found that while knowledge of PGx is limited, most agree it can improve care. Pharmacists and students want more education on using PGx for patient care.
This document outlines a Phase III clinical trial protocol to compare the efficacy and safety of a novel calcium channel blocker drug called Cardex to the drug Nifedipine in treating patients with stage 1 hypertension. The proposed randomized controlled trial would involve 600 patients across 15 centers in India. Patients would be randomly assigned to receive either Cardex or Nifedipine and their blood pressure and platelet aggregation would be measured at regular intervals over 18 months to assess the comparative efficacy, safety and pharmacokinetics of the two drugs. The protocol provides details on the study objectives, design, procedures, statistical analysis and ethical approval process.
This document discusses the importance and benefits of pharmacogenetic testing for physicians and their patients. It notes that pharmacogenetic testing can help physicians determine the right drug, dose, and timing for each individual patient to reduce adverse drug reactions and improve outcomes. Not utilizing this testing could open physicians up to legal liability issues. The document provides several case studies demonstrating how pharmacogenetic testing could have helped identify the right treatment for patients and avoided negative health consequences or legal risks for physicians. It also addresses the ease of testing, billing, and reimbursement to make the case for integrating pharmacogenetics into medical practice.
Similar to DIA China 2017 Optimizing Clinical Trials with Advanced Tools (20)
The document summarizes the history of dermal absorption assessment at the FDA. It discusses how prior to the 1990s, topical dermal drugs had little direct assessment of in vivo bioavailability and clinical efficacy trials were used instead. In the mid-1990s, the FDA began requiring "maximal use trials" (MUsT) to better understand absorption under conditions maximizing exposure. MUsTs became standard for new drug applications. The document then focuses on sunscreen absorption studies showing circulating levels and the FDA's own studies evaluating absorption of 7 ingredients under MUsT conditions. It concludes MUsTs provide important safety data but the FDA has not said sunscreens are unsafe.
Slides presented by me at the Korean-American Professional Association in Life Sciences (KAPAL) 5th Annual Meeting in Rockville, MD. Slides discuss the recent reorganization of the Center for Drug Evaluation and Research at the FDA
Dialog and Debate: Personalized Medicine in Topical TreatmentsE. Dennis Bashaw
This document discusses the importance of dermal absorption assessments and maximal use trials (MUsT) for topical drug products. It provides background on the evolution of bioavailability testing from pre-1990 approaches to the current standard of MUsT trials. A MUsT is designed to evaluate potential systemic absorption under maximum recommended use conditions and accumulate data on dermal therapeutic responses. Over 20 years, 66 MUsT trials have been conducted on NDAs involving over 1,500 patients. MUsTs are a key part of the FDA review process for both prescription and over-the-counter topical products to determine safety.
Regulatory aspects of bioequivalence iss xr4-revisedE. Dennis Bashaw
The document provides an overview of regulatory aspects of pharmacokinetics related to bioequivalence. It discusses key bioequivalence terminology including pharmaceutical equivalents, pharmaceutical alternatives, and therapeutic equivalents. It also outlines FDA regulations and guidance around bioequivalence testing, including acceptable study designs and criteria for determining bioequivalence. Specific topics covered include examples of bioequivalence studies for foods effects, orally administered locally acting drugs, and narrow therapeutic index drugs. The document emphasizes that bioequivalence evaluations are done on a case by case basis depending on the specific drug.
This document summarizes four case studies involving issues with bioanalytical method validation:
1) An analyst constructed standard curves inconsistently between assay runs, using a varying number of calibration standards.
2) An analytical method was used for multiple studies over many years without re-validation, despite changes in equipment and assay conditions.
3) Subject concentration-time curves showed implausible "U-shaped" profiles, indicating an unresolved analytical problem.
4) Hundreds of samples were rendered below the lower limit of quantification due to the laboratory failing to specify and follow procedures for sample acidification using hydrochloric acid.
The document emphasizes that proper standard operating procedures, ongoing method monitoring,
This document summarizes four case studies of issues encountered during bioanalytical method validation:
1) An analyst constructed standard curves inconsistently between assay runs, undermining the reliability of concentration values.
2) An assay was used for many years without re-validation despite changes in equipment affecting analyte retention times.
3) Some subjects showed non-physiological "U-shaped" concentration-time curves that were accepted without investigation.
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Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
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3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
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1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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Integrating Ayurveda into Parkinson’s Management: A Holistic Approach
DIA China 2017 Optimizing Clinical Trials with Advanced Tools
1. Optimizing Clinical Trials
with Advanced Tools
CAPT E. Dennis Bashaw, Pharm.D.
Dir. Division of Clinical Pharmacology-3
Office of Clinical Pharmacology
Office of Translational Sciences
US Food and Drug Administration
Session 901:STRATEGY OF CLINICAL DEVELOPMENT
2. 2
• The presentation today should not be
considered, in whole or in part as being
statements of policy or recommendation
by the US Food and Drug Administration.
• Throughout the talk, representative
examples of commercial products will be
mentioned. No commercial endorsement
is either implied or intended.
3. 3
Outline
• 21st Century Challenges in Drug
Development
• Beyond Classical PK/PD
• Case Studies
–Secukinumab
–Edoxaban
• Lessons Learned
• Conclusions and Closing Thoughts
7. 7
Updated Drug Development Cost Figures
J Health Econ. 2016 May;47:20-33. doi: 10.1016/j.jhealeco.2016.01.012
8. 8
The Cost of Research vs Ease of Conduct
High
Low
Single Center Randomized Trials
Low
Single Case
Reports
Cohort Studies
Case-Control Studies
Case Series
HighEase of conduct
Multi-Center Randomized Trials
Cost
9. 9
Why Replicate Trials?
• Guidance for Industry-Providing Clinical Evidence of
Effectiveness for Human Drugs and Biological Products
– Congress adopted the 1962 Drug Amendments, Section 505(d) of the Act uses
the plural form in defining “substantial evidence” as “adequate and well-
controlled investigations, including clinical investigations.” See also use of
“investigations” in section 505(b) of the Act, which lists the contents of a new
drug application. which included a provision requiring manufacturers of drug
products to establish a drug’s effectiveness by "substantial evidence." Substantial
evidence was defined in section505(d) of the Act as “evidence consisting of
adequate and well-controlled investigations, including clinical investigations, by
experts qualified by scientific training and experience to evaluate the
effectiveness of the drug involved, on the basis of which it could fairly and
responsibly be concluded by such experts that the drug will have the effect it
purports or is represented to have under the conditions of use prescribed,
recommended, or suggested in the labeling or proposed labeling thereof.”
10. 10
BEYOND CLASSICAL PK/PD
Patrick Muller and Mark Milton, “The Determination and Interpretation of the Therapeutic Index in Drug Development”
Nature Reviews Drug Discovery, 2012, vol. 11, pg 751-751
11. 11
The Triad of Drug Innovation
• Knowledge Management
– Leveraging information
• Biomarker Qualification
• Disease History
• Innovative Trial Designs
– Moving away from the “2 replicate trials” standard
• Innovative Analysis
– Pharmacometrics
• Modeling and Simulation
– Pharmcogenomics
• Patient Factors
– Pharmacovigilance
12. 12
Tools vs Utility
• In the last 20yrs, the term “precision medicine” has been
growing in the literature as a goal to real patient
individualization
• Ideally precision medicine should include not only patient care
but also encompass drug development
– Identify and include actionable information on patient
factors
– Empower the physician to use state of the art diagnostics
and biomarkers
Huang S-M, Temple R, Clin Pharmacol Ther. 2008
16. 16
Psoriasis and Inflammatory Cascade
• Psoriasis is a complex inflammatory disease that occurs in genetically susceptible
individuals. It is a common, immune-mediated disease, affecting 7.4 million
adults. In these patients there are many cytokines whose levels are elevated,
including TNF-α, IFN-γ, IL-6, IL-8, IL-12, IL-18, and IL-17.3 The IL-17 family consists
of subtypes A–F, with IL-17A having the most prominent role in host defense and
autoimmunity.
https://www.dovepress.com/long-term-safety-of-biologics-in-the-treatment-of-psoriasis-peer-reviewed-fulltext-article-PTT#F1
17. 17
Case 1: Secukinumab
• Human interleukin-17A antagonist indicated for the
treatment of moderate to severe plaque psoriasis in
adult patients who are candidates for systemic therapy
or phototherapy
– adults with psoriatic arthritis
– adults with active ankylosing spondylitis
• Dose-ranging in Phase II can help identify subgroups
who may benefit from altered dosing
19. 19
Phase II Study Results
• Subgroup analysis showed an increased benefit with
regardless of body weight, but highest response was
in patients with body weight <90 kg
• Results from this trial and other sources support
benefit of exploring a higher 300 mg dose in Phase III
Endpoint Placebo
Secukinumab
25 (x1) mg 25 (x3) mg 75 (x3) mg 150 (x3) mg
PASI 75 9% 3% 19% 57% 82%
IGA 0/1 9% 0% 12% 33% 48%
Papp et al, 2012
20. 20
Phase III Confirms Benefit of
Higher Dose
• A significant difference in efficacy between two weight strata was
observed.
• Difference between weight group within each dose is similar to the
difference between doses
• Dose can be optimized for best risk/benefit accordingly for each
weight group
Dose 150 mg 300 mg
Weight Group ≥ 90 kg
(N=215)
< 90 kg
(N=355)
≥ 90 kg
(N=209)
< 90 kg
(N=359)
PASI 75 132 (61%) 261 (74%) 152 (73%) 297 (83%)
IGA 0/1 98 (46%) 194 (55%) 119 (57%) 243 (68%)
http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DermatologicandOphthalmicDrugsAdvisoryCommittee/ucm404866.htm
21. 21
Case 1: Outcome
• Phase III trial results support safety and efficacy of
both doses
• Patients with higher body weight or those that are
non-responsive at the 300 mg dose may benefit from a
further increase in dosing
• Sponsor agreed to conduct a post-marketing study to
evaluate a higher dose
25. 25
Case 2: Edoxaban
• Indicated to reduce the risk of stroke and systemic embolism in
patients with non-valvular atrial fibrillation
– Also indicated for treatment of deep vein thrombosis and
pulmonary embolism
• Edoxaban inhibits free factor Xa and prothrombinase activity
and inhibits thrombin-induced platelet aggregation. Inhibition of
factor Xa in the coagulation cascade reduces thrombin
generation and thrombus formation.
• Anti-coagulant class associated with steep bleeding and stroke
dose and exposure-response curves
26. 26
Phase II Edoxaban: 30 and 60 mg
QD based on study in patients
with atrial fibrillation
Salazar et al., Thromb Haemost, 2012
Dose selection for Phase III based
on bleeding event rate
27. 27
Phase II Edoxaban: Doses selected to
achieve less bleeding than warfarin
Salazar et al., Thromb Haemost, 2012
28. 28
Dose Response Is Evident
For Stroke & Major Bleeding Events
mITT population,
on-treatment events
29. 29
Renal Clearance is the
Major Edoxaban Elimination Pathway
• 60% of systemic edoxaban cleared
by the kidneys
• AUC increased 32%, 74%, and
72% for mild, moderate, and
severe impairment
• Patients with moderate renal
impairment received a 50% dose
reduction in the Phase 3 ENGAGE
AF study
Applicant: CSR U-120, Table 11.2, Edoxaban 60 mg; CSR U-301, Tables 14.2.5.2, 14.5.3.24, Edoxaban 60 mg
ModerateMildNormal
Edoxaban Ctrough (ng/mL)
50% Dose Reduction
High Dose Arm
30. 30
Patients with Normal Renal Function
with 60 mg Edoxaban had a Higher Risk
for Stroke/SEE Relative to Warfarin
Applicant: CSR U-120, Table 11.2, Edoxaban 60 mg; CSR U-301, Tables 14.2.5.2, 14.5.3.24, Edoxaban 60 mg
Stroke/SEE
Renal Function Category Hazard Ratio (95% CI) Hazard Ratio (95% CI)
Edoxaban Better Warfarin Better
Major Bleeds
30
31. 31
Case 2: Outcome
• Concerns identified with stroke event rate in patients with
normal renal function
• Such subjects would have lower exposure given edoxaban’s
primary route of elimination
• Boxed warning included in labeling based on renal function >90
mL/min
33. 33
PD Knowledge Driven Development
https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/cardiovascularandrenaldrugsadvisorycommittee/ucm420704.pdf
Biomarker Well Understood
IND May 2007 NDA Jan 2014
Type “C” Sept 2013
Pre-NDA Mtg. Feb 2012
EOP2 Aug 2008
35. 35
Time for Development
• Although both Edoxaban and Secukinumab were developed by
different companies and were reviewed by different divisions at
the FDA they share at least two things in common:
– They both were approved in 7yrs from the time of initial IND
filing.
– They both leveraged information from biomarkers
• The clotting cascade for Edoxaban
• The discovery of IL-17’s role for Secukinumab
36. 36
36
Biomarkers and Modeling
Adapted from S. McCune, Dep Dir., Office of Translational Sciences, Pediatric Advisory Committee-Neonatal Subcommittee Mtg. March 2013
37. 37
Biomarkers Are the Present
and the Future
• Biomarkers
– Expand understanding of the disease and its progression
– Provide insight into FUTURE drug development
– Provide the potential for clinician based individualization
(i.e., bleeding time vs IL-17A)
– Provide a path forward to a more optimized drug
development program
– Provide opportunities for collaboration with regulatory
bodies
38. 38
FDA Partnership in Qualification
https://www.fda.gov/drugs/developmentapprovalprocess/drugdevelopmenttoolsqualificationprogram/
41. 41
The Future
• It is easy to say that we are on the edge of a revolution in drug
development
– We have ALWAYS been on the EDGE!
– Only the tools and our perspective of them have changed
• Patient factors are being recognized more and more as the key
to individualizing not only drug therapy but expectations of
therapy.
42. 42
Communicating the Future
• As new advances are made, they must be reflected both in
regulatory policy and in patient care
• While we rightly focus on the population, we must not lose sight
of the individual patient and the individual physician, nurse, and
pharmacist as well
– Biomarkers can allow us to link the patient, their genetics, the
ontology of the disease, and the healthcare system into a “holistic”
treatment approach
• Clinical Pharmacology can help identify populations and
broaden patient utility and safety
• Only by selecting the right biomarkers and identifying the
proper dose for the patient population can we make “every
patient count” as every patient is a teaching opportunity for us
43. 43
Combining the Workstreams
Biomarker Selection
Utilize in vitro and in
vivo systems to probe
and qualify biomarkers
PBPK Modeling
Build models based on
observed knowledge with a
“learn and confirm” strategy.
Classical PK/PD
Synthesize the
available PK/PD data
on Drug Metabolism
Develop
Actionable
Information
Informed labeling for the
prescriber
Pharmacogenomics
Utilize in vitro systems
to identify relevant
genetic factors to
enhance patient safety
and selection
Patient Selection
Understand the pathology
of the disease to select
the needed diversity in the
affected population
44. 44
Development of Safe and Effective
Drugs For ALL Requires a Team Effort
Academia
Industry
International
Collaboration
Patient
Advocacy
Regulatory
Science
Benefits
To All
Good Science is Everybody’s Business!
45. 45
Contact Information
CAPT Edward D. Bashaw, PharmD.
Director, Div. of Clinical Pharmacology-3
US FDA
10903 New Hampshire Ave
Building 51, Rm 3134
Edward.Bashaw@fda.hhs.gov
46. 46
Acknowledgements
• The Staff of the Division of Clinical
Pharmacology-3
• The Office of Clinical Pharmacology
• The Office of Translational Sciences
• The Drug Information Association-China