The survey gathered feedback from over 350 members of the Phenotypic Drug Discovery LinkedIn group on how the group can better serve their needs such as through discussion forums, networking opportunities, and sharing of practical implementation techniques. The responses provided insights into both the achievements and obstacles encountered when using phenotypic approaches for target identification, siRNA screening, and drug discovery including issues around reproducibility, validation of hits, and difficulty identifying molecular targets. Overall, the surveys aimed to understand how the group could improve and provide a useful overview of the field despite the low response rate typical for online surveys.
Computer aided drug design (CADD) uses computer modeling to help design and discover new drug molecules. It involves designing molecules that are complementary in shape and charge to bind to a biomolecular target like a protein. This can help drugs activate or inhibit the target to produce therapeutic effects. CADD is not a direct route to new drugs but provides information to guide and coordinate drug discovery experiments in a more efficient manner. It is hoped CADD can help save time and money in the drug development process.
Tacey E.K. White has over 25 years of experience in pharmaceutical safety assessment and drug development. She currently works as a senior consultant, advising on nonclinical safety strategies throughout drug development. Previously, she held roles at Exponent, Covance, and GlaxoSmithKline, where she designed and directed developmental and reproductive toxicity and juvenile toxicity studies to support regulatory submissions. She has deep expertise in areas like developmental toxicity, juvenile toxicity, and pregnancy and lactation labeling.
The document provides an overview and review of scientific trends and publications in translational bioinformatics from approximately the last 14 months. It discusses several key papers related to topics like clinical genomics, drugs, genetic basis of disease, and emerging data sources. The author evaluated over 100 papers and selected around 50 final papers to highlight, discussing 32 of them briefly across 8 topic areas. The goal was to provide a "snapshot" of important progress and opportunities in the field.
- Telemonitoring for heart failure patients has been shown to reduce mortality rates by up to 36% and decrease hospitalization rates in studies such as TEN-HMS and the Cochrane review.
- The Hull model of telemonitoring in the UK involves a comprehensive system of care including home monitoring devices, community kiosks, and support from nurses and specialist clinics to closely manage heart failure patients.
- Further research and investment in telemonitoring technologies could help shift care from crisis management to proactive health maintenance and empowering patients to better self-manage their condition.
Here are some insights and case studies from 4 of the speakers who will be at QSP Congress. We asked them 4 questions and compiled them into one document. They give real personal opinions on some of the topics that are so far defining the adoption and application of systems pharmacology.
AACR 2018 Ask the Expert talk on NCI's Provocative Questions InitiativesNorbert Tavares, Ph.D.
Ask the Expert presentation on NCI's Provocative Questions Initiative, presented by Norbert Tavares, Ph.D. at the annual American Association for Cancer Research (AACR) conference at the National Cancer Institutes (NCI) booth on 4/6/2018.
The document summarizes a webinar presentation about accessing shelved pharmaceutical compounds through the CTSA Pharmaceutical Assets Portal. It provides background on the goals of the portal, which is to improve information exchange between pharmaceutical companies and academic researchers regarding drugs discontinued in clinical trials that could be candidates for drug repositioning. It describes some initial achievements and collaborations of the portal project. It also discusses the Clinical and Translational Science Awards program and how the portal was inspired by examples of drug repositioning.
CHI's Immunogenicity and Bioassay Summit 2015James Prudhomme
This document summarizes an upcoming conference on immunogenicity assessment and clinical relevance for biopharmaceutical products. The conference will take place November 17-18, 2015 in Baltimore, MD and will include keynote speakers from the FDA and industry. It will feature sessions on regulatory expectations, preclinical studies and risk assessment, different assay formats and technologies, and challenges with immunogenicity assessment. Short courses on related topics will also be offered. The document provides an agenda with session topics, speaker names and affiliations, and descriptions of presentation topics.
Computer aided drug design (CADD) uses computer modeling to help design and discover new drug molecules. It involves designing molecules that are complementary in shape and charge to bind to a biomolecular target like a protein. This can help drugs activate or inhibit the target to produce therapeutic effects. CADD is not a direct route to new drugs but provides information to guide and coordinate drug discovery experiments in a more efficient manner. It is hoped CADD can help save time and money in the drug development process.
Tacey E.K. White has over 25 years of experience in pharmaceutical safety assessment and drug development. She currently works as a senior consultant, advising on nonclinical safety strategies throughout drug development. Previously, she held roles at Exponent, Covance, and GlaxoSmithKline, where she designed and directed developmental and reproductive toxicity and juvenile toxicity studies to support regulatory submissions. She has deep expertise in areas like developmental toxicity, juvenile toxicity, and pregnancy and lactation labeling.
The document provides an overview and review of scientific trends and publications in translational bioinformatics from approximately the last 14 months. It discusses several key papers related to topics like clinical genomics, drugs, genetic basis of disease, and emerging data sources. The author evaluated over 100 papers and selected around 50 final papers to highlight, discussing 32 of them briefly across 8 topic areas. The goal was to provide a "snapshot" of important progress and opportunities in the field.
- Telemonitoring for heart failure patients has been shown to reduce mortality rates by up to 36% and decrease hospitalization rates in studies such as TEN-HMS and the Cochrane review.
- The Hull model of telemonitoring in the UK involves a comprehensive system of care including home monitoring devices, community kiosks, and support from nurses and specialist clinics to closely manage heart failure patients.
- Further research and investment in telemonitoring technologies could help shift care from crisis management to proactive health maintenance and empowering patients to better self-manage their condition.
Here are some insights and case studies from 4 of the speakers who will be at QSP Congress. We asked them 4 questions and compiled them into one document. They give real personal opinions on some of the topics that are so far defining the adoption and application of systems pharmacology.
AACR 2018 Ask the Expert talk on NCI's Provocative Questions InitiativesNorbert Tavares, Ph.D.
Ask the Expert presentation on NCI's Provocative Questions Initiative, presented by Norbert Tavares, Ph.D. at the annual American Association for Cancer Research (AACR) conference at the National Cancer Institutes (NCI) booth on 4/6/2018.
The document summarizes a webinar presentation about accessing shelved pharmaceutical compounds through the CTSA Pharmaceutical Assets Portal. It provides background on the goals of the portal, which is to improve information exchange between pharmaceutical companies and academic researchers regarding drugs discontinued in clinical trials that could be candidates for drug repositioning. It describes some initial achievements and collaborations of the portal project. It also discusses the Clinical and Translational Science Awards program and how the portal was inspired by examples of drug repositioning.
CHI's Immunogenicity and Bioassay Summit 2015James Prudhomme
This document summarizes an upcoming conference on immunogenicity assessment and clinical relevance for biopharmaceutical products. The conference will take place November 17-18, 2015 in Baltimore, MD and will include keynote speakers from the FDA and industry. It will feature sessions on regulatory expectations, preclinical studies and risk assessment, different assay formats and technologies, and challenges with immunogenicity assessment. Short courses on related topics will also be offered. The document provides an agenda with session topics, speaker names and affiliations, and descriptions of presentation topics.
Developing the Reimbursement Story 2016-03-10Lyssa Friedman
The document discusses strategies for developing a reimbursement case for molecular diagnostic tests early in development. It emphasizes designing analytic and clinical validity studies to demonstrate test accuracy and association with clinical conditions. Clinical utility studies should show how test results impact patient management, outcomes, and healthcare costs. Randomized controlled trials provide the strongest evidence but alternative study designs like prospective observational studies and decision modeling may also support reimbursement. The goal is to generate evidence of a test's medical necessity from the intended patient population to achieve coverage and payment.
The document summarizes Andy Pope's presentation on lead discovery and hit identification approaches at GSK. It discusses current hit identification methods like high-throughput screening (HTS) and encoded library technologies. HTS involves screening large libraries of up to 2 million compounds but has limitations due to costs and inability to screen under different conditions. Encoded library technologies address these limitations by allowing synthesis and screening of much larger virtual libraries of over 1 billion compounds under various conditions using DNA-encoded small molecules. The document emphasizes the importance of compound quality and hit qualification methods to identify true hits from screening assays.
Introduction to Discovery Partnerships with Academia (DPAc)Andrew Pope
This document provides an introduction to GSK's Discovery Partnerships with Academia (DPAc) model. Some key points:
- DPAc allows academic researchers to partner with GSK scientists to translate innovative research into new medicines, with shared investment, ownership, and rewards if successful.
- It focuses on drug discovery from early screening through to candidate clinical compounds.
- GSK provides access to its drug discovery and development capabilities to help progress projects.
- There are currently several active DPAc partnerships in Europe and North America focused on various disease areas.
An overview of scope and eligibility for funding, including lessons learnt from the first call - with a chance to ask questions.
Presented by Laura Ajram on 4th May 2020.
This document discusses secondary data analysis and provides examples of large federal health surveys that can be used for secondary analysis, including NHANES and NHIS. It outlines strengths and limitations of secondary data analysis. Complex survey design must be accounted for, including statistical weighting, clustering, and stratification. Several statistical software programs are designed for analyzing complex survey data. The document concludes with a hypothetical case study using NHIS and EPA air pollution exposure data to study the relationship between acrolein levels and childhood asthma episodes.
Root cause Analysis (RCA) & Corrective and Preventive action (CAPA) in MRCT d...Bhaswat Chakraborty
This presentation describes Identification & differentiation of Protocol deviation & violation; Different methods of RCA & best suitable method for Multiregional Clinical Trial; CAPA management and CAPA application to other trial sites/CRO/SMO/ Country that is involved in same trial (Strategic Management and application of CAPA in MRCT)
Christopher Brawley has over 7 years of experience in clinical trial management and coordination. He is currently a Clinical Trial Manager at Natera Inc. where he is responsible for implementing large clinical trials according to study protocols. Previously he held clinical trial management roles at Gilead Sciences and Stanford University with responsibilities including developing study documents, training staff, monitoring trials, and generating reports. He has a BS in Molecular Biology from the University of Illinois.
Where do recent small molecule clinical development candidates come from?Jonas Boström
Presentation given at the ACS meeting in San Diego 2019.
JMedChem publication available here: https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.8b00675
Michael Ward has over 15 years of experience in biomedical research and drug development. He currently works as a Senior Clinical Science Specialist at Genentech, where he helps develop clinical trial protocols and analyzes data from Alzheimer's disease studies. Prior to this role, he worked as a Senior Manager leading statistical analysis teams. Dr. Ward has extensive experience across multiple disciplines including neuropsychology, bioinformatics, data management, and clinical research.
Move Your Research Out of the Ivory Tower and Impact Health: Translating Earl...CTSI at UCSF
This presentation highlights how the UCSF Clinical and Translational Science Institute (CTSI) enhances and facilitates early-stage research efforts at UCSF and UCSF/industry partnerships - to develop new treatments, diagnostics and prevention.
We are defining the problem too narrowly. Our paradigm of pharmaceutical quality sifted long-ago. We have harmonized on a regulatory methodology for QbD (e.g., ICH Q8). However, with the prevailing ontological gaps (for example as illustrated in the continuing challenges posed with the current FDA’s Inactive Ingredient Database) - How good are the scientific explanations in regulatory submissions? Is quality risk-assessment - metaphysical or an epistemological category?
Researching information needs and beliefs of patients, professionals and the ...EUPATI
"Researching information needs and beliefs of patients, professionals and the public regarding medicines development", presentation held by Bella Starling on 6 March 2013 at DIA EuroMeeting
This document provides an overview of artificial intelligence in drug discovery. It discusses three main challenges: 1) determining the best data to use for training models, 2) obtaining well-characterized patient data to pair molecular mechanisms with clinical indications, and 3) the lack of skilled AI researchers in big pharma. It also reviews the competitive landscape and growth of companies selling patient data and those applying AI in healthcare. Examples of AI applications discussed include using deep learning to predict drug approval and quantum molecular dynamics simulations.
Aug2013 reference material selection and design working groupGenomeInABottle
The document summarizes discussions from a working group meeting regarding the selection and design of reference materials for genome sequencing. It was attended by approximately 25 people from federal agencies, clinical labs, and technology companies. Options discussed included plasmids with cancer mutations from NCI, tumor-normal cell line pairs, and cell lines from HorizonDx and Acrometrix that contain engineered variants. The working group aims to define testing protocols to evaluate reference material performance across labs and assess their ability to characterize sequencing platforms and tests.
Visioning the Next Decade: NIPTE-FDA CollaborationAjaz Hussain
NIPTE Seminar at US FDA, 16 March 2016.
QBR as an Organizing Principle for the Proposed NIPTE Center of Excellence for Pharmaceutical Formulations (CEPF)
SearchLeeds, Kelvin Newman 'The Trope Factory' Branded3
Kelvin Newman is the Founder of Rough Agenda, a company that arranges specialist digital marketing events including BrightonSEO. In 2014 Kelvin was voted by econsultancy as the most influential individual in digital and in 2013 won the Search Personality award at the UK Search Awards.
Ten Podcasts to Help You Design Better Softwareohellojames
This document recommends 10 podcasts to help with designing better software, including UXHH Radio, UIE Brain Sparks, The Big Web Show, Sitepoint, Design Guy, This Week in Tech, Tech Weekly, On the Media, 99% Invisible, and Radiolab. It thanks the reader in multiple languages and provides links to additional slides and the author's Twitter handle with the hashtag #10pdbs.
Developing the Reimbursement Story 2016-03-10Lyssa Friedman
The document discusses strategies for developing a reimbursement case for molecular diagnostic tests early in development. It emphasizes designing analytic and clinical validity studies to demonstrate test accuracy and association with clinical conditions. Clinical utility studies should show how test results impact patient management, outcomes, and healthcare costs. Randomized controlled trials provide the strongest evidence but alternative study designs like prospective observational studies and decision modeling may also support reimbursement. The goal is to generate evidence of a test's medical necessity from the intended patient population to achieve coverage and payment.
The document summarizes Andy Pope's presentation on lead discovery and hit identification approaches at GSK. It discusses current hit identification methods like high-throughput screening (HTS) and encoded library technologies. HTS involves screening large libraries of up to 2 million compounds but has limitations due to costs and inability to screen under different conditions. Encoded library technologies address these limitations by allowing synthesis and screening of much larger virtual libraries of over 1 billion compounds under various conditions using DNA-encoded small molecules. The document emphasizes the importance of compound quality and hit qualification methods to identify true hits from screening assays.
Introduction to Discovery Partnerships with Academia (DPAc)Andrew Pope
This document provides an introduction to GSK's Discovery Partnerships with Academia (DPAc) model. Some key points:
- DPAc allows academic researchers to partner with GSK scientists to translate innovative research into new medicines, with shared investment, ownership, and rewards if successful.
- It focuses on drug discovery from early screening through to candidate clinical compounds.
- GSK provides access to its drug discovery and development capabilities to help progress projects.
- There are currently several active DPAc partnerships in Europe and North America focused on various disease areas.
An overview of scope and eligibility for funding, including lessons learnt from the first call - with a chance to ask questions.
Presented by Laura Ajram on 4th May 2020.
This document discusses secondary data analysis and provides examples of large federal health surveys that can be used for secondary analysis, including NHANES and NHIS. It outlines strengths and limitations of secondary data analysis. Complex survey design must be accounted for, including statistical weighting, clustering, and stratification. Several statistical software programs are designed for analyzing complex survey data. The document concludes with a hypothetical case study using NHIS and EPA air pollution exposure data to study the relationship between acrolein levels and childhood asthma episodes.
Root cause Analysis (RCA) & Corrective and Preventive action (CAPA) in MRCT d...Bhaswat Chakraborty
This presentation describes Identification & differentiation of Protocol deviation & violation; Different methods of RCA & best suitable method for Multiregional Clinical Trial; CAPA management and CAPA application to other trial sites/CRO/SMO/ Country that is involved in same trial (Strategic Management and application of CAPA in MRCT)
Christopher Brawley has over 7 years of experience in clinical trial management and coordination. He is currently a Clinical Trial Manager at Natera Inc. where he is responsible for implementing large clinical trials according to study protocols. Previously he held clinical trial management roles at Gilead Sciences and Stanford University with responsibilities including developing study documents, training staff, monitoring trials, and generating reports. He has a BS in Molecular Biology from the University of Illinois.
Where do recent small molecule clinical development candidates come from?Jonas Boström
Presentation given at the ACS meeting in San Diego 2019.
JMedChem publication available here: https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.8b00675
Michael Ward has over 15 years of experience in biomedical research and drug development. He currently works as a Senior Clinical Science Specialist at Genentech, where he helps develop clinical trial protocols and analyzes data from Alzheimer's disease studies. Prior to this role, he worked as a Senior Manager leading statistical analysis teams. Dr. Ward has extensive experience across multiple disciplines including neuropsychology, bioinformatics, data management, and clinical research.
Move Your Research Out of the Ivory Tower and Impact Health: Translating Earl...CTSI at UCSF
This presentation highlights how the UCSF Clinical and Translational Science Institute (CTSI) enhances and facilitates early-stage research efforts at UCSF and UCSF/industry partnerships - to develop new treatments, diagnostics and prevention.
We are defining the problem too narrowly. Our paradigm of pharmaceutical quality sifted long-ago. We have harmonized on a regulatory methodology for QbD (e.g., ICH Q8). However, with the prevailing ontological gaps (for example as illustrated in the continuing challenges posed with the current FDA’s Inactive Ingredient Database) - How good are the scientific explanations in regulatory submissions? Is quality risk-assessment - metaphysical or an epistemological category?
Researching information needs and beliefs of patients, professionals and the ...EUPATI
"Researching information needs and beliefs of patients, professionals and the public regarding medicines development", presentation held by Bella Starling on 6 March 2013 at DIA EuroMeeting
This document provides an overview of artificial intelligence in drug discovery. It discusses three main challenges: 1) determining the best data to use for training models, 2) obtaining well-characterized patient data to pair molecular mechanisms with clinical indications, and 3) the lack of skilled AI researchers in big pharma. It also reviews the competitive landscape and growth of companies selling patient data and those applying AI in healthcare. Examples of AI applications discussed include using deep learning to predict drug approval and quantum molecular dynamics simulations.
Aug2013 reference material selection and design working groupGenomeInABottle
The document summarizes discussions from a working group meeting regarding the selection and design of reference materials for genome sequencing. It was attended by approximately 25 people from federal agencies, clinical labs, and technology companies. Options discussed included plasmids with cancer mutations from NCI, tumor-normal cell line pairs, and cell lines from HorizonDx and Acrometrix that contain engineered variants. The working group aims to define testing protocols to evaluate reference material performance across labs and assess their ability to characterize sequencing platforms and tests.
Visioning the Next Decade: NIPTE-FDA CollaborationAjaz Hussain
NIPTE Seminar at US FDA, 16 March 2016.
QBR as an Organizing Principle for the Proposed NIPTE Center of Excellence for Pharmaceutical Formulations (CEPF)
SearchLeeds, Kelvin Newman 'The Trope Factory' Branded3
Kelvin Newman is the Founder of Rough Agenda, a company that arranges specialist digital marketing events including BrightonSEO. In 2014 Kelvin was voted by econsultancy as the most influential individual in digital and in 2013 won the Search Personality award at the UK Search Awards.
Ten Podcasts to Help You Design Better Softwareohellojames
This document recommends 10 podcasts to help with designing better software, including UXHH Radio, UIE Brain Sparks, The Big Web Show, Sitepoint, Design Guy, This Week in Tech, Tech Weekly, On the Media, 99% Invisible, and Radiolab. It thanks the reader in multiple languages and provides links to additional slides and the author's Twitter handle with the hashtag #10pdbs.
Ringkasan dokumen tersebut adalah sebagai berikut:
Dokumen tersebut memberikan rekomendasi tentang ciri-ciri slide presentasi yang baik, yang meliputi fokus pada satu ide per slide, penggunaan visual yang sederhana dan mudah dipahami, serta penyampaian pesan secara terstruktur dan konsisten dari awal hingga akhir presentasi.
The document discusses Microsoft's Management Data Warehouse (MDW) which allows for monitoring of SQL Server performance on the cheap. It provides built-in reports for disk usage, query statistics, and server statistics collected every 6 hours, 60 seconds, and 10 seconds respectively. The MDW uses two SQL jobs, one to collect data and store it temporarily and another to upload it. It can operate in cached or non-cached mode, with cached being heavier on performance. The presentation demonstrates the MDW and provides tips like not changing the table structure and creating smaller collector sets to stagger uploads.
SearchLeeds, Mel Hyde 'How to maximise potential from an ongoing shift in dev...Branded3
Group Head of Paid Search, Mel Hyde discusses how to maximise potential from an ongoing shift in device usage. Mel is responsible for ensuring the right strategy is applied to Branded3’s PPC client accounts and that all accounts deliver performance, efficiency and growth. With a truly integrated approach to our client’s digital campaigns.
The document discusses 12 image development strategies that can be used in the planning and sketching process to create images. The strategies are selection, viewpoint, juxtaposition, simplification, positive/negative space, elaboration, distortion, personification, magnification, fragmentation, metamorphosis, and multiplication. Using these strategies gives direction and can help minimize mistakes when developing images.
SearchLeeds, Ian Harris 'Content confusion: What is the point of your content...Branded3
This document discusses different types of content marketing and how to measure their effectiveness. It outlines customer engagement content, which aims to engage potential customers at different stages of buying, and viral content, which aims to engage a large audience. Customer engagement content should be relevant, drive sign-ups and engagement, while viral content targets trending topics that will widely share. Both should be measured using metrics like traffic, social shares, and links gained. While content can attract visitors, direct search and organic brand traffic typically drive more conversions. The goal of content should ultimately be driving profitable customer action.
Stephen Kenwright - London Affiliates ConferenceBranded3
Stephen Kenwright, Director or Search at Branded3 looks and 'Strategic keyword research and analysis' in his presentation for the London Affiliates Conference: http://www.igbaffiliate.com/events/london-affiliate-conference
Quantative Systems Pharmacology - A brief intro.pptxDrMathanKumar
1) Quantitative and Systems Pharmacology (QSP) is an emerging approach in drug discovery that uses mathematical models of biological systems to better understand how drugs modulate cellular networks and impact human physiology.
2) QSP aims to address the high failure rate of clinical drug development by providing a more complete understanding of drug mechanisms of action and accounting for variability between patients.
3) QSP combines computational and experimental methods to develop systems-level models using ordinary differential equations that can predict therapeutic effectiveness, dosing regimens, and identify best biomarker targets.
Facilitating Advanced Drug Development and Evaluation Using CRISPR-Cas9 Techn...Chi-Ping Day
This document discusses using CRISPR/Cas9 technology to facilitate advanced drug development. It describes drug development as a process of disease modeling that involves: 1) Identifying the dysfunctional system that causes the disease, 2) Generating hypotheses for target identification, 3) Validating targets by testing hypotheses, 4) Evaluating outcomes, and 5) Reconfiguring the system. CRISPR/Cas9 offers advantages like reducing confounding effects through specific gene editing and versatile screening/validation strategies. Remaining issues include off-targets, potential DNA damage, immune response, and efficiency.
This document outlines the steps involved in conducting a systematic review and meta-analysis on the prevalence of elder abuse. It discusses how 52 studies from around the world were analyzed using comprehensive meta-analysis software. The key findings were that the pooled prevalence of elder abuse was 15.7%. While systematic reviews have strengths like being comprehensive and transparent, they also have limitations such as reliance on the quality of primary studies and risk of publication bias.
The document summarizes key themes from a webinar on developing medical policies and coverage guidelines for next generation sequencing in oncology. It discusses the challenges of evaluating genomic tests and gaining insurance coverage. Recommendations include requiring laboratories to obtain accreditation for analytic validity, covering small gene panels when clinical utility is established, and facilitating data collection to support coverage of larger tests and off-label drug use. The webinar included perspectives from various stakeholders on addressing these issues.
- Discover new methods for managing clinical next-gen data with insights from Pfizer, Boston Children’s Hospital and AstraZeneca
- Uncover and critique the latest technologies out there for you to use in clinical trials. Mayo Clinic, Merck and Harvard Medical School let you into their trade secrets
- Hear the genomics strategies that Roche, Millennium and Regeneron are using for discovery and validation of clinically actionable biomarkers
-Bristol-Myers Squibb, Takeda and Partners Healthcare the role that NGS can play when implementing an effective strategy in the lab to speed up CDx development
- Learn how to integrate molecular details into medical decision making, with fresh data from Washington University School of Medicine and Genzyme
Critical appraisal presentation by mohamed taha 2Cairo University
This document discusses how to critically appraise a research article. It provides 10 questions to ask when appraising an article, including whether the study question is relevant, if the study design was appropriate, and if the data supports the conclusions. As an example, it summarizes a study that examined the relationship between serum cholesterol levels and exposure to violence in suicide attempters. The study addressed relevant questions, utilized an appropriate cohort study design, and its conclusions were reasonably supported by the collected data.
Bioinformatics role in Pharmaceutical industriesMuzna Kashaf
Bioinformatics plays a key role in the pharmaceutical industry by enabling target identification of diseases, rational drug design, compound refinement, and other processes. It facilitates identifying target diseases and compounds, detecting molecular bases of diseases, designing drugs, refining compounds, and testing drug solubility and effects. Bioinformatics supports various stages of drug development including formulation, crystallization determination, polymer modeling, and testing before human use. Its integration into the pharmaceutical industry supports drug discovery, healthcare advances, and realizing the promises of projects like the Human Genome Project.
We can aid decision making from the pre-clinical to the clinical setting, supporting line of sight to the clinic, by identifying and translating crucial biomarker approaches into the real world.
This document summarizes a project aiming to develop a comprehensive open-access database of cutaneous neurofibroma (cNF) expression and mutation data to facilitate systems biology analysis. The project has assembled an initial cNF dataset and conducted exploratory analyses to better understand cNF biology. Challenges include the need for more data to power studies given tumor heterogeneity. Next steps involve expanding the dataset by integrating additional public and project-generated cNF data to guide future research and therapeutic development.
Acmg secondary findings open forum 3 28-12 finalerikanature
The document summarizes a meeting of the American College of Medical Genetics (ACMG) Open Forum on secondary findings from clinical sequencing. It introduces the Secondary Findings in Clinical Sequencing Workgroup, which was formed to develop guidelines on reporting secondary findings from whole exome and whole genome sequencing. The workgroup aims to provide preliminary recommendations to the ACMG in May 2012 and publish final guidelines in June 2012. The workgroup seeks feedback from the community on their approach and will revise their recommendations accordingly.
This document describes the Continuous Update Project, a novel approach developed by the World Cancer Research Fund to systematically review mechanistic evidence on diet, nutrition, physical activity and cancer. The approach involves conducting systematic reviews and meta-analyses of both epidemiological and mechanistic studies to make judgements on causal relationships. It emphasizes reproducibility, predefined criteria, and reviews evidence separately from making judgements. The goal is to help identify causal links between exposures and cancer outcomes.
Translation research aims to bridge the gap between basic science and clinical applications by developing new medical treatments and ensuring they reach patients. It has two parts: T1 translates new knowledge from basic research into clinical tests and applications; T2 translates clinical findings into practice. Successful translation requires multidisciplinary teams with expertise in both basic and clinical research. Challenges include coordinating large research efforts and overcoming barriers to implementing new practices. National research institutions have established translation centers and programs to facilitate collaboration between scientists and speed the delivery of new treatments to improve human health.
This document provides an overview of how to conduct a systematic review. It begins by defining what a systematic review is and why they are important for evidence-based practice. It then outlines the key steps in conducting a systematic review, including formulating an answerable question using PICO(T), performing a comprehensive literature search, selecting studies and extracting data in an unbiased manner, critically appraising the evidence, and synthesizing the data. The document emphasizes that systematic reviews need to follow a structured, systematic process and make all methods explicit to minimize bias. It also discusses challenges that can arise in systematic reviews like database, publication, and language biases.
This document outlines a project to develop a standardized methodology for conducting systematic reviews of mechanistic cancer studies. The goal is to enable more rigorous synthesis of evidence from animal and cell line studies on how dietary factors may influence cancer risk. An international team of experts will hold workshops to design a comprehensive search strategy, quality assessment criteria, and data extraction methods. These will be tested by reviewing evidence on potential mechanisms linking milk consumption to prostate cancer risk, such as effects on hormone and growth factor levels. The resulting review methodology template will provide guidance for systematically evaluating mechanistic evidence across study types.
This document discusses lessons learned from analyzing data from the MIMIC database. It makes the following key points:
1) While causality cannot be proven with observational data, large datasets like MIMIC can still provide useful insights, especially when multiple studies find consistent results.
2) Single-center databases are limited; collaborating and sharing data across centers expands what can be learned.
3) Reliable research requires transparent and continuous peer review as well as open sharing of data, methods, and findings.
4) Bringing together different experts in data-driven "datathons" can help ensure robust and impactful analyses.
Generic non-biological complex drugs DIA CMC Workshop 2017Ajaz Hussain
#DIACMC17
Assigned title for the talk by the organizers:“The need of conducting clinical study for assuring safety and efficacy, as well as a lack of immunogenicity for generic NBCDs”
SUMMARY
Integrated analytical, product and process development to reduce uncertainty in ‘pharmaceutical equivalence’ is the foundation on which confidence in generic drugs rests
Need to leverage the context: RLD “Prescribe-ability” and lot-lot “Switchability” is acceptable
The “sameness” mindset (as opposed to an “equivalence” mindset) poses challenges to evidence ‘synthesis” (not “piece meal” check the box ) in ANDA submissions
Integrated evidence must a priori account for posed/anticipated “legal challenges” intrinsic to the US system
Clinical assessment of Therapeutic Equivalence of generic product intended (i.e., designed) to be equivalent to RLD should only be needed in rare circumstances
When there is a need to provide assurance to non-scientists stakeholders
Currently the FDA’s GADUFA Research and efforts by many in the sector are predominantly focused on developing a “test of bioequivalence”
For most complex products such a test, in and of itself, may be insufficient to ensure therapeutic equivalence over generic product life-cycle
The document discusses two scientific journals - the Journal of Laboratory Automation (JALA) and the Journal of Biomolecular Screening (JBS). It provides information on their editors, impact factors, indexing in databases, scientific advisors and editorial boards. The goal of both journals is to publish research applying technological advances to scientific exploration and discovery of new therapeutics. Authors are encouraged to submit their work to these peer-reviewed, MEDLINE-indexed journals.
Webinar: Oncology Trial Recruitment: Challenging Indications and Challenging ...Medpace
Medpace experts discuss how to overcome oncology recruitment challenges for clinical trials for specific populations, indications, and challenging studies.
The document provides an overview of clinical trials and the drug development process. It discusses the importance of clinical trials in translating basic research into new treatments. There are different types of clinical trials such as treatment, prevention, and diagnostic trials. The drug development process involves drug discovery, pre-clinical animal testing, and 4 phases of clinical trials in humans to test safety, efficacy, and get regulatory approval. Phase 1 trials involve few participants to test safety, while Phase 2 and 3 trials have larger numbers of participants to further evaluate safety and efficacy. Phase 4 trials monitor safety after market approval. Randomization and blinding are important trial design elements to reduce bias.
- Neusentis is a regenerative medicine subsidiary of Pfizer focused on developing cell-based therapies.
- Their portfolio includes collaborations on stem cell-derived retinal pigment epithelial (RPE) cells to treat macular degeneration, and allogenic adult multipotent stem cells to treat inflammatory bowel disease.
- Major challenges for developing and commercializing cell therapies include cell biology and manufacturing complexities, rigorous clinical trial design and supply logistics, and demonstrating a clear business case for pricing and reimbursement.
Similar to 9 28-2012 surveys phenotypic drug discovery sig (20)
2. About the Survey
The Phenotypic Drug Discovery LinkedIN group has grown to over 350 members
since its start in Mid May and is composed of a diverse population representing
scientists, service/technology providers, and bio-entrepreneurs. With the help
of Lynn Valastyan and Francis Willard two surveys were developed to provide
general information about the PDD SIG membership in general and to better
estimate the use and impact of phenotypic approaches by scientists.
Survey responses have hit a plateau so it is probably time to publicize the
complete results of both surveys. The data from the survey cannot be
statistically significant with less than 10% of the PDD SIG membership
responding. Although the response was initially disappointing, Nan Hallock
(Director of Publishing for SLAS) indicated that surveys were like letters to the
editors….not too many people actively participate, but many are interested.
Hopefully members of the PDD SIG will find the results interesting…..
Jonathan Lee
September 28, 2012
10. How can the Phenotypic Drug Discovery SIG
LinkedIn site better serve your needs?
• Discussion forum is very helpful to follow progress in the area
• Networking and leads to capital investors.
• Keep the discussion going
• Exchange ideas and promote concept
• Understand hurdles identified by others. Sharing of practical
implementation techniques. Progression of phenotypic-based projectsinto
the clinic.
• By somehow getting more coal-face medchemists to join in!
• I was impressed with excellent discussions posted by finest scientists in
the field. Adding presentations that highlight the PSA if any would be
interesting.
• The set of very good and relevant topics that were raised up recently. It
provided very useful sharing of information and stimulated interesting
discussion.
• A section or catalog of PSA resources, e.g. service providers, pre-
competitive consortia, academic core labs, would be helpful.
11. How can the Phenotypic Drug Discovery SIG
LinkedIn site better serve your needs?
• The discussions on the site are extremely useful to me as a young
scientist in academia. The site would be better if we had some sort
of member directory so that we may more easily find people of
certain expertise and network (if one wishes to be involved in such
a network).
• Monthly or weekly compilation of all relevant papers in the area of
PDD
• Provide catalogue of available phenotypic capabilities and assays
with contact names
• It's too late to serve my personal needs, but for the needs of many
others, it we should discuss new business models (including funding
sources) to reintegrate PDD into mainstream drug discovery. This
may not seem natural for the primarily scientific bent of this
group, but if scientists don't get more savvy and assertive in the
business, satisfactory change can not occur.
21. What significant achievements and or obstacles have
been encountered when using phenotypic approaches
for target identification or si/shRNA screening?
• Uniformity across the board for acceptable bioassays. Harmonization of
protocols for PSA in target discovery and validation.
• The quality of libraries have been questionable (especially Qiagen). Off
target effects are troublesome and require several individual oligos per
gene. The cellular response is variable and population-based analysis is
required. Transfecting some cell types can be challenging. There is no real
negative control in siRNA screens, since all oligo will have some sort of
effect. Obtaining a good base line is difficult, probably the best is the
mode or median of the entire library screen omitting positive controls.
• reproducible results
• Not all responses are direct effects - both mechanistic and siRNA
nonspecificity issues.
• Obstacle: disconnect between mammalian cells and yeast genetic screens
for small molecule TID.
• Translation os siRNA results into shRNA results for stable cell generation in
target validation studies
22. • Achievements: always found known genes in the list of potential functional genes.
Obstacles: -Very low confirmation rate for the whole list of genes in functional screen.
-Never sure that the siRNA against target will work and demonstrate effect significant
to produce detectable phenotype. - Problem with the selection of the hits from the
list to follow up on.
• Obstacle: relative cost and need for larger collaborations Acheivement: proof of
concept on modification of a key pathway cells/tissues specifically mimicking human
disease phenotypes.
• We are just starting target identification work, however a strategy using genetic
methods are already in place.
• Challenges: library preperation and throughput across assays formats, Validation of
hits. Achievement validated novel targets identified.
• Target identification in phenotypic settings is not a trivial exercise - there's always
concern that interactions seen are not actually those which are relevant to the
observed phenotype.
• Achievements: many novel, useful targets or pathways discovered. Useless targets
eliminated. Novel compound-target pairings discovered that were developed into
biological probes and new screens that couldn't have been developed any other way.
Obstacles: 1, managerial/investor resistance to starting program without predefined
target(s) and screen(s) specifically directed at the predefined target(s); 2,
managerial/investor resistance to doing what looks to them like "just tool
development
23. What significant achievements and or obstacles have been
encountered when using phenotypic approaches for drug
discovery?
• Achievement- whole cell activity obtained Obstacle- deciphering of biological target has been cumbersome for
biology colleagues.
• Acceptance for peer-review funding. If you have specific NIH study sections that are interested in promoting PSA,
it will be much appreciated.
• Processing time for a thorough image analysis is challenging, requires powerful computer clusters. Statistical
analysis of objects within populations is challenging from a computational point of view as files comprising
several billion lines need to be processed. This requires computers with either large RAM or much free disk space
for temp files. Visualisation of data is complex (how to display population distributions of various phenotypes?).
Statistic methods to derive probabilities of phenotypes and test of population results.
• just getting started, target deconvoltion is currently our largest concern
• Acheivement = small molecule with novel MOA Obstacle = chemist
• Hard task to convince managers that PSA could be valuable and successfull for finding drugs with new MOA.
Mentalities are still target oriented !
• Identifying the molecular target. Of course, there is not agreement if this is necessary, but it is very helpful for
publication in a highend journal (this is a University).
• Identified 4 compounds from Prestwick library as non-DA symptomatic augmentation therapy for Parkinson's
disease
• Achievements: identification of small molecules with cellular activity producing desired pheontype made cell
target validation and in vivo relevance more convincing, plus delivered valid tool compounds and cellular
systems to feed into the DD program. Obstacles: The chemical matter used in the the phenotype screen was not
of good drug discovery quality (i.e. chemotypes unsuitable for development) necessitating a follow up to
discover better chemcial matter against the target. This was because as an academic group we did not have
access to good pharma collections but rather just the (cheap) off the shelf combichem library.
24. • Achievements: new target and biology were found for anti-TB drug discovery. New scaffolds in characterization for
HCV drug discovery. Two completed successful phenotypic siRNA screening discovered new functional genes.
Obstacles: secondary assays are not ready after primary assay is done mostly because potential mechanisms and
targets are not known
• Obstacle: timing and throughput issues; longer learn and confirm med. chem. cycle AChievement: bettwr
understanding of pre-ADME issues and enablement of a proof of concept and proof of relevance in patient derived
tissues i.e. a clinical trial in a test-tube on modulation of the disease phenotype.
• Assays of sufficient quantitative quality have been set up so as to perform SAR using phenotypic assays
• Achievements: Identified molecules which modulated in vitro and in vivo biology and easily differentiated from
standard of care. Identified cellular processes not previously associated with therapeutic biology. Demonstrated
that phenotypic assays can provide evidence of compound SAR, can successfully utilize chemoinformatics mining
methods, and can be statistically validated. Phenotypic assays can be as operationally robust as biochemical assays
yet interrogate multiple molecular targets in a native context and without preconceptions of target validation.
Obstacles: Compound drug-ability and metabolism issues encountered (like biochemical approaches). Compound
prioritization can be difficult. Phenotypic approaches may lead to unexpected findings relevant to the biology
resulting in flow scheme modification and timeline delays.
• Obstacles: Flat in vitro SAR; Low hit rate; High hit rate; Lack of a experience/strategy/knowledge for prosecuting
hits. Target-directed mindsets that are inherently biased against PDD- both in bench scientists and the
management. Overselling of the concept by senior management. Achievements: novel mechanistically
differentiated compounds for therapeutically relevant assays. Often the comparable 'target-based' projects have
major druggability issues.
• Challenges: Implementation of informatics workflows to collate multiparametric high-content data. Throuput for
screening compound and combinations across multiple assay formats/cell models. Development of bespoke image
analysis algorithms to extract quantitative data from novel (3D, co-culture) assay formats.
• Target identification can be difficult to do rapidly, which puts pressure on the team as a whole.
• Achievements: discovering novel chemical scaffolds with a desirable balance of pharmacological properties acting
on previously undiscovered or intractable targets. Obstacles: 1, managerial/investor resistance to advancing leads
without a defined or fashionable mechanism of action. 2, managerial/investor resistance to starting programs not
predicated on screening against fashionable target(s).