This document discusses the potential for personalized medicine through the use of omics technologies and biomarkers. It notes that while tailoring treatments based on genetic and molecular testing is not entirely new, recent advances in screening methods now enable more widespread biomarker discovery and patient stratification. However, it also cautions that associations found through such studies do not necessarily prove causality. The document explores examples of using biomarkers to stratify patients, like testing for EGFR mutations to identify lung cancer patients most likely to respond to targeted therapies. Overall it frames omics and biomarkers as evolutionizing rather than revolutionizing medicine by facilitating a more differentiated molecular understanding of diseases and their treatments.
2015 04-13 Pharma Nutrition 2015 Philadelphia Alain van GoolAlain van Gool
Keynote lecture at the Pharma-Nutrition 2015 conference, outline global paradigm shifts and activities in pharma, personalized healthcare and pharmanutrition combination therapies.
This document discusses the potential for rare diseases and orphan drugs to serve as models for biomarker-driven precision medicine and stratified therapies more broadly. It provides examples of how biomarkers have helped validate targets and predict responses in rare diseases like Muckle-Wells syndrome. Orphan diseases are seen as providing small patient populations, strong advocacy networks, and clinical trial models that could speed development of stratified medicines. However, regulators may be skeptical if stratification is used to avoid traditional clinical trials, and payers have concerns about costs if a stratified condition affects a large number of patients. Overall, lessons from rare diseases around biomarkers, clinical development, and policy/reimbursement could help advance the field of stratified medicine.
Personalized medicine involves the prescription of specific therapeutics best suited for an individual based on their genetic or proteomic profile. This talk discusses current approaches in drug discovery/development, the role of genetics in drug metabolism, and lawful/ethical issues surrounding the deployment of new health technology. I highlight some bioinformatic roles in the drug discovery process, and discuss the use of semantic web technologies for data integration and knowledge discovery..
Evaluation of comorbid autoimmune diseases among patients and family members enrolled in the Alopecia
Areata Registry, Biobank & Clinical Trials Network.
26 Oct 2017 Genetics and precision medicine Milano Cornel.pptAnimikh Ray
This document discusses precision and personalized medicine and the role of genetics and genomics. It defines precision medicine as tailoring medical treatment to an individual's characteristics, while personalized medicine separates patients into groups based on predicted disease risk or response. The document notes there is variability between individuals and considers factors like genetics, environment, and lifestyle. It discusses the increasing availability of DNA tests and need for prioritization due to limited budgets. Barriers to implementing genetics in medicine include lack of knowledge and guidelines. The document discusses criteria for prioritizing genetic tests and conditions, including evidence of benefit, available interventions, and health need. It provides examples of conditions that could be prioritized, like hereditary cancer syndromes and familial hypercholesterole
Recent Development in Pharmacogenomics
The summary discusses recent developments in pharmacogenomics including:
1) Recent drug label updates have incorporated genetic information to refine dosing for several drugs including warfarin, abacavir, and tetrabenazine based on CYP enzyme activity.
2) New targeted cancer therapies like crizotinib and vemurafenib have been approved for cancers with specific genetic mutations and require genetic testing to identify responders.
3) Research trends include large genome-wide association studies to identify genetic factors for diseases and drug responses while the FDA has released new guidances on pharmacogenomics.
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.
2015 04-13 Pharma Nutrition 2015 Philadelphia Alain van GoolAlain van Gool
Keynote lecture at the Pharma-Nutrition 2015 conference, outline global paradigm shifts and activities in pharma, personalized healthcare and pharmanutrition combination therapies.
This document discusses the potential for rare diseases and orphan drugs to serve as models for biomarker-driven precision medicine and stratified therapies more broadly. It provides examples of how biomarkers have helped validate targets and predict responses in rare diseases like Muckle-Wells syndrome. Orphan diseases are seen as providing small patient populations, strong advocacy networks, and clinical trial models that could speed development of stratified medicines. However, regulators may be skeptical if stratification is used to avoid traditional clinical trials, and payers have concerns about costs if a stratified condition affects a large number of patients. Overall, lessons from rare diseases around biomarkers, clinical development, and policy/reimbursement could help advance the field of stratified medicine.
Personalized medicine involves the prescription of specific therapeutics best suited for an individual based on their genetic or proteomic profile. This talk discusses current approaches in drug discovery/development, the role of genetics in drug metabolism, and lawful/ethical issues surrounding the deployment of new health technology. I highlight some bioinformatic roles in the drug discovery process, and discuss the use of semantic web technologies for data integration and knowledge discovery..
Evaluation of comorbid autoimmune diseases among patients and family members enrolled in the Alopecia
Areata Registry, Biobank & Clinical Trials Network.
26 Oct 2017 Genetics and precision medicine Milano Cornel.pptAnimikh Ray
This document discusses precision and personalized medicine and the role of genetics and genomics. It defines precision medicine as tailoring medical treatment to an individual's characteristics, while personalized medicine separates patients into groups based on predicted disease risk or response. The document notes there is variability between individuals and considers factors like genetics, environment, and lifestyle. It discusses the increasing availability of DNA tests and need for prioritization due to limited budgets. Barriers to implementing genetics in medicine include lack of knowledge and guidelines. The document discusses criteria for prioritizing genetic tests and conditions, including evidence of benefit, available interventions, and health need. It provides examples of conditions that could be prioritized, like hereditary cancer syndromes and familial hypercholesterole
Recent Development in Pharmacogenomics
The summary discusses recent developments in pharmacogenomics including:
1) Recent drug label updates have incorporated genetic information to refine dosing for several drugs including warfarin, abacavir, and tetrabenazine based on CYP enzyme activity.
2) New targeted cancer therapies like crizotinib and vemurafenib have been approved for cancers with specific genetic mutations and require genetic testing to identify responders.
3) Research trends include large genome-wide association studies to identify genetic factors for diseases and drug responses while the FDA has released new guidances on pharmacogenomics.
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.
Lessons learned in polygenic risk research | Grand Rapids, MI 2019Cecile Janssens
1. Fifteen years of polygenic risk research has shown that while polygenic risk scores can statistically significantly associate with complex diseases, the association does not necessarily predict disease risk well enough to be useful in healthcare.
2. To improve prediction, both data and models need to be improved to better reflect the underlying biological complexity. Additionally, predictive performance must be properly evaluated in the intended population and clinical utility determined.
3. Complex diseases are too complex and influenced by many factors to be perfectly predicted by current polygenic risk models. However, prediction does not need to be perfect to be useful, depending on the intended clinical application.
PDCD is an abbreviation for pyruvate dehydrogenase complex deficiency, a genetic mitochondrial disorder in children which is frequently associated with lactic acidosis and neurological/neuromuscular symptoms.
Personalised medicines -pharmacogentics and pharmacogenomicsAlakesh Bharali
This seminar basically introduces and explains the learner about what is personalised medicines, what is the need for it, how personalised medicines work. For this, the concept of pharmacogenetics and pharmacogenomics are considered. After going through the presentation, the learner will be able to understand about the concept of pharmacogentics and pharmacogenomics. Certain examples of personalised medicines are included in this seminar.Although personalised medicines are specific and helpful, ins spite of having lots of advantages , it also have some disadvantages which are also specified in this seminar.Although , we speak about personalised medicines, we never saw personalised medicines in our local market. So here is an approach given that , when will we see personalised medicines at the local pharmacy. Again, certain marketed products are also listed in the seminar.Also, the future of personalised medicines is depeicted in the seminar. How medicines will be in a an around 2050 is shown in the seminar. After going through the seminar, the learner would be able to understand about personalised medicines and all its aspects in detail.
Talk delivered at Warwick Biomedical Engineering Seminar series 27 November 2014. Develops a theme emerging from a review in 2010:
J Watkins, A Marsh, P C Taylor, D R J Singer
Therapeutic Delivery, 2010, 1, 651-665
"Continued adherence to a single-drug single-target paradigm will limit the ability of chemists to contribute to advances in personalized medicine, whether they be in discovery or delivery"
1) Personalized medicine aims to provide customized medical care tailored to individual patients based on their genes, proteins, and environment. This involves optimizing drug therapy based on a patient's predicted response and risk factors.
2) Customized drug delivery systems and 3D printing allow for personalized dosages forms and treatments. Telepharmacy uses technology to provide pharmacy services to remote areas.
3) Pharmacogenomics studies how a patient's genes affect their response to drugs to optimize treatment. It can help identify non-responders, avoid adverse events, and determine the proper drug dosage. Pharmacogenetic testing provides this genetic information.
This document discusses bridging system biology research to personalized healthcare. It summarizes:
1) System biology considers genetics, metabolism, mental state, and environment to yield personalized profiles for personalized healthcare solutions using lifestyle, food, and/or pharmaceutical interventions.
2) Personalized healthcare involves stratifying patients using multilevel diagnosis, respecting patient treatment preferences, and involving care communities.
3) Applying novel technologies in clinical care requires a balance of research/technology push to add useful biomarkers with considerations of daily practice needs and costs.
What is personalized medicine?
Why we need personalized medicine?
What’s Pharmacogenetics?
DNA polymorphism
Biomarkers
Today’s treatments with PM
Future insights
Challenges
What we still need to know more
Genomics, Personalized Medicine and Electronic Medical RecordsLyle Berkowitz, MD
We are now unlocking the secrets of health at a molecular level – which includes not only why some people get diseases, but also how to prevent or cure them. However, as Osler points out, knowing this information is only valuable in the context of making it available for the right patient at the right time.
This presentation provides a basic introduction to genomic or personalized medicine, and discusses how this information can and should be integrated into our electronic medical record systems.
These slides were originally presented at the HIMSS Annual Conference in February of 2007.
This document discusses precision psychiatry and the use of various "omics" technologies to advance precision medicine approaches in psychiatry. It outlines how genomics, pharmacogenomics, transcriptomics, and metabolomics can provide insights into the pathophysiology of mental illnesses and help determine individualized treatment approaches. Challenges include the complexity of gene-environment interactions, barriers to implementing pharmacogenomic testing in clinical practice, and the need for more work to develop multi-omics biomarkers that can predict disease risk and treatment response at the individual level.
The document discusses hypersensitivity reactions to chemotherapeutics and monoclonal antibodies. It begins by providing background on the history and development of chemotherapy. It then discusses the pathophysiology, risk factors, epidemiology, classification by immunological mechanism, and symptoms of acute and delayed hypersensitivity reactions. Key points include that the incidence of reactions to platinum salts is 12-17% and taxanes is 10-70%, and reactions can range from mild cutaneous symptoms to life-threatening anaphylaxis and involve various immune pathways.
Bias, confounding and causality in p'coepidemiological researchsamthamby79
A brief description of three issues (Bias, Confounding and Causality) commonly encountered while performing pharmacoepidemiological research. A big THANK YOU to Mr. Strom and Mr. Kimmel.
The document discusses biomarkers in oncology from cells to systems. It notes that while many biomarkers are discovered, few progress beyond initial publication to clinical validation and diagnostic tests. Reasons for this innovation gap include a lack of integrated biomarker research and development pipelines and challenges in organizing multi-lab validation studies. The talk emphasizes embracing novel omics technologies, considering tumor cells as part of a biological system, and focusing on biomarker validation to address this gap. It provides examples of using mRNA expression profiling and systems-level approaches to stratify and characterize tumors.
Genetic testing in neurology is becoming more common and offers potential for diagnosis confirmation and prognosis. The neurologist needs to be aware of testing indications, standards, and risks of inappropriate use. Genetic testing can be used for diagnostic, prenatal, predictive, carrier, and disease risk purposes, as well as pharmacogenetics. Providing counseling before and after testing is important to discuss implications and avoid misinterpretations of results.
EuroBioForum 2013 - Day 1 | Sergey SuchkovEuroBioForum
EuroBioForum 2013 2nd Annual Conference
27-28 May 2013 - Hilton Munich City, Munich, Germany
http://www.eurobioforum.eu/2013
=======================================
# NATIONAL PERSPECTIVES #
Russia:
Introduction into PPPM as a new paradigm of public health care service and an example of the ready-to-use Clinical Model in the Area of Medicine
Sergey Suchkov
Professor in Medicine and Immunology at Moscow State Medical & Dental University & I.M. Sechenov Moscow Medical Academy
=======================================
http://www.eurobioforum.eu
DiaGenomi Ltd. is a genetic testing company that offers several tests through their MyRISQ platform, including CardioRISQ. CardioRISQ is a cardiac risk assessment test that combines genetic testing for mutations in several genes related to cardiovascular disease with a lifestyle questionnaire. It provides a personalized assessment of cardiovascular disease risk. The test involves collecting a saliva sample for genetic analysis, completing an online lifestyle questionnaire, and receiving a medical report integrating this genetic and lifestyle data to provide a risk assessment and treatment plan tailored to the individual. DiaGenomi aims to improve prevention and management of disease through this holistic, personalized approach to genetic testing.
Reporting and monitoring adverse events with cancer treatment [final]Rosalynn Pangan
This document discusses reporting and monitoring of adverse events from cancer treatment. It begins with objectives of understanding adverse drug events, their importance, common events from cancer treatment, and FDA reporting processes. It then presents a case study of a patient who developed erythema and burning sensations on her hands and heels after her fifth chemotherapy session. Various topics are covered like defining adverse events, reactions, and serious reactions. Common adverse effects of chemotherapy like alopecia, nausea, and peripheral neuropathy are discussed. The importance of monitoring and reporting adverse events is emphasized to improve patient safety.
Pharmacogenetics and pharmacogenomics is an upcoming branch in therapeutics. Various pharmacogenomic tests are currently available to aid in actual clinical practice. It has shown to have promising results in personalized medicine It is my attempt to compile the basic concepts from various books, articles, and online journals. Please feel free to comment.
Pharmacogenomics is the study of how genes affect individual responses to drugs. It combines pharmacology and genomics to develop safe and effective personalized medications and dosages based on a person's genetic makeup. The goal is to improve treatment outcomes by predicting drug effectiveness and reducing adverse reactions. Challenges include implementing genetic tests in clinical practice and addressing cost, ethical and legal issues. Future applications include developing tailored drugs for many diseases and faster, more targeted clinical trials through biomarkers.
2015 01-06 Oudejaarssymposium Personalized Healthcare, GroningenAlain van Gool
Personalized healthcare is moving beyond just targeted medicine to become more patient-centered. Biomarkers are playing an evolving role, from diagnosis to translational medicine to personalized healthcare. Radboud University Medical Center aims to have a significant impact on healthcare through their focus on personalized healthcare and including the patient as a partner. Their integrated translational research and diagnostic laboratory develops biomarkers through various omics technologies for personalized diagnosis and treatment.
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.
Feeding plate for a newborn with Cleft Palate.pptxSatvikaPrasad
A feeding plate is a prosthetic device used for newborns with a cleft palate to assist in feeding and improve nutrition intake. From a prosthodontic perspective, this plate acts as a barrier between the oral and nasal cavities, facilitating effective sucking and swallowing by providing a more normal anatomical structure. It helps to prevent milk from entering the nasal passage, thereby reducing the risk of aspiration and enhancing the infant's ability to feed efficiently. The feeding plate also aids in the development of the oral muscles and can contribute to better growth and weight gain. Its custom fabrication and proper fitting by a prosthodontist are crucial for ensuring comfort and functionality, as well as for minimizing potential complications. Early intervention with a feeding plate can significantly improve the quality of life for both the infant and the parents.
Hypertension and it's role of physiotherapy in it.Vishal kr Thakur
This particular slides consist of- what is hypertension,what are it's causes and it's effect on body, risk factors, symptoms,complications, diagnosis and role of physiotherapy in it.
This slide is very helpful for physiotherapy students and also for other medical and healthcare students.
Here is summary of hypertension -
Hypertension, also known as high blood pressure, is a serious medical condition that occurs when blood pressure in the body's arteries is consistently too high. Blood pressure is the force of blood pushing against the walls of blood vessels as the heart pumps it. Hypertension can increase the risk of heart disease, brain disease, kidney disease, and premature death.
Lessons learned in polygenic risk research | Grand Rapids, MI 2019Cecile Janssens
1. Fifteen years of polygenic risk research has shown that while polygenic risk scores can statistically significantly associate with complex diseases, the association does not necessarily predict disease risk well enough to be useful in healthcare.
2. To improve prediction, both data and models need to be improved to better reflect the underlying biological complexity. Additionally, predictive performance must be properly evaluated in the intended population and clinical utility determined.
3. Complex diseases are too complex and influenced by many factors to be perfectly predicted by current polygenic risk models. However, prediction does not need to be perfect to be useful, depending on the intended clinical application.
PDCD is an abbreviation for pyruvate dehydrogenase complex deficiency, a genetic mitochondrial disorder in children which is frequently associated with lactic acidosis and neurological/neuromuscular symptoms.
Personalised medicines -pharmacogentics and pharmacogenomicsAlakesh Bharali
This seminar basically introduces and explains the learner about what is personalised medicines, what is the need for it, how personalised medicines work. For this, the concept of pharmacogenetics and pharmacogenomics are considered. After going through the presentation, the learner will be able to understand about the concept of pharmacogentics and pharmacogenomics. Certain examples of personalised medicines are included in this seminar.Although personalised medicines are specific and helpful, ins spite of having lots of advantages , it also have some disadvantages which are also specified in this seminar.Although , we speak about personalised medicines, we never saw personalised medicines in our local market. So here is an approach given that , when will we see personalised medicines at the local pharmacy. Again, certain marketed products are also listed in the seminar.Also, the future of personalised medicines is depeicted in the seminar. How medicines will be in a an around 2050 is shown in the seminar. After going through the seminar, the learner would be able to understand about personalised medicines and all its aspects in detail.
Talk delivered at Warwick Biomedical Engineering Seminar series 27 November 2014. Develops a theme emerging from a review in 2010:
J Watkins, A Marsh, P C Taylor, D R J Singer
Therapeutic Delivery, 2010, 1, 651-665
"Continued adherence to a single-drug single-target paradigm will limit the ability of chemists to contribute to advances in personalized medicine, whether they be in discovery or delivery"
1) Personalized medicine aims to provide customized medical care tailored to individual patients based on their genes, proteins, and environment. This involves optimizing drug therapy based on a patient's predicted response and risk factors.
2) Customized drug delivery systems and 3D printing allow for personalized dosages forms and treatments. Telepharmacy uses technology to provide pharmacy services to remote areas.
3) Pharmacogenomics studies how a patient's genes affect their response to drugs to optimize treatment. It can help identify non-responders, avoid adverse events, and determine the proper drug dosage. Pharmacogenetic testing provides this genetic information.
This document discusses bridging system biology research to personalized healthcare. It summarizes:
1) System biology considers genetics, metabolism, mental state, and environment to yield personalized profiles for personalized healthcare solutions using lifestyle, food, and/or pharmaceutical interventions.
2) Personalized healthcare involves stratifying patients using multilevel diagnosis, respecting patient treatment preferences, and involving care communities.
3) Applying novel technologies in clinical care requires a balance of research/technology push to add useful biomarkers with considerations of daily practice needs and costs.
What is personalized medicine?
Why we need personalized medicine?
What’s Pharmacogenetics?
DNA polymorphism
Biomarkers
Today’s treatments with PM
Future insights
Challenges
What we still need to know more
Genomics, Personalized Medicine and Electronic Medical RecordsLyle Berkowitz, MD
We are now unlocking the secrets of health at a molecular level – which includes not only why some people get diseases, but also how to prevent or cure them. However, as Osler points out, knowing this information is only valuable in the context of making it available for the right patient at the right time.
This presentation provides a basic introduction to genomic or personalized medicine, and discusses how this information can and should be integrated into our electronic medical record systems.
These slides were originally presented at the HIMSS Annual Conference in February of 2007.
This document discusses precision psychiatry and the use of various "omics" technologies to advance precision medicine approaches in psychiatry. It outlines how genomics, pharmacogenomics, transcriptomics, and metabolomics can provide insights into the pathophysiology of mental illnesses and help determine individualized treatment approaches. Challenges include the complexity of gene-environment interactions, barriers to implementing pharmacogenomic testing in clinical practice, and the need for more work to develop multi-omics biomarkers that can predict disease risk and treatment response at the individual level.
The document discusses hypersensitivity reactions to chemotherapeutics and monoclonal antibodies. It begins by providing background on the history and development of chemotherapy. It then discusses the pathophysiology, risk factors, epidemiology, classification by immunological mechanism, and symptoms of acute and delayed hypersensitivity reactions. Key points include that the incidence of reactions to platinum salts is 12-17% and taxanes is 10-70%, and reactions can range from mild cutaneous symptoms to life-threatening anaphylaxis and involve various immune pathways.
Bias, confounding and causality in p'coepidemiological researchsamthamby79
A brief description of three issues (Bias, Confounding and Causality) commonly encountered while performing pharmacoepidemiological research. A big THANK YOU to Mr. Strom and Mr. Kimmel.
The document discusses biomarkers in oncology from cells to systems. It notes that while many biomarkers are discovered, few progress beyond initial publication to clinical validation and diagnostic tests. Reasons for this innovation gap include a lack of integrated biomarker research and development pipelines and challenges in organizing multi-lab validation studies. The talk emphasizes embracing novel omics technologies, considering tumor cells as part of a biological system, and focusing on biomarker validation to address this gap. It provides examples of using mRNA expression profiling and systems-level approaches to stratify and characterize tumors.
Genetic testing in neurology is becoming more common and offers potential for diagnosis confirmation and prognosis. The neurologist needs to be aware of testing indications, standards, and risks of inappropriate use. Genetic testing can be used for diagnostic, prenatal, predictive, carrier, and disease risk purposes, as well as pharmacogenetics. Providing counseling before and after testing is important to discuss implications and avoid misinterpretations of results.
EuroBioForum 2013 - Day 1 | Sergey SuchkovEuroBioForum
EuroBioForum 2013 2nd Annual Conference
27-28 May 2013 - Hilton Munich City, Munich, Germany
http://www.eurobioforum.eu/2013
=======================================
# NATIONAL PERSPECTIVES #
Russia:
Introduction into PPPM as a new paradigm of public health care service and an example of the ready-to-use Clinical Model in the Area of Medicine
Sergey Suchkov
Professor in Medicine and Immunology at Moscow State Medical & Dental University & I.M. Sechenov Moscow Medical Academy
=======================================
http://www.eurobioforum.eu
DiaGenomi Ltd. is a genetic testing company that offers several tests through their MyRISQ platform, including CardioRISQ. CardioRISQ is a cardiac risk assessment test that combines genetic testing for mutations in several genes related to cardiovascular disease with a lifestyle questionnaire. It provides a personalized assessment of cardiovascular disease risk. The test involves collecting a saliva sample for genetic analysis, completing an online lifestyle questionnaire, and receiving a medical report integrating this genetic and lifestyle data to provide a risk assessment and treatment plan tailored to the individual. DiaGenomi aims to improve prevention and management of disease through this holistic, personalized approach to genetic testing.
Reporting and monitoring adverse events with cancer treatment [final]Rosalynn Pangan
This document discusses reporting and monitoring of adverse events from cancer treatment. It begins with objectives of understanding adverse drug events, their importance, common events from cancer treatment, and FDA reporting processes. It then presents a case study of a patient who developed erythema and burning sensations on her hands and heels after her fifth chemotherapy session. Various topics are covered like defining adverse events, reactions, and serious reactions. Common adverse effects of chemotherapy like alopecia, nausea, and peripheral neuropathy are discussed. The importance of monitoring and reporting adverse events is emphasized to improve patient safety.
Pharmacogenetics and pharmacogenomics is an upcoming branch in therapeutics. Various pharmacogenomic tests are currently available to aid in actual clinical practice. It has shown to have promising results in personalized medicine It is my attempt to compile the basic concepts from various books, articles, and online journals. Please feel free to comment.
Pharmacogenomics is the study of how genes affect individual responses to drugs. It combines pharmacology and genomics to develop safe and effective personalized medications and dosages based on a person's genetic makeup. The goal is to improve treatment outcomes by predicting drug effectiveness and reducing adverse reactions. Challenges include implementing genetic tests in clinical practice and addressing cost, ethical and legal issues. Future applications include developing tailored drugs for many diseases and faster, more targeted clinical trials through biomarkers.
2015 01-06 Oudejaarssymposium Personalized Healthcare, GroningenAlain van Gool
Personalized healthcare is moving beyond just targeted medicine to become more patient-centered. Biomarkers are playing an evolving role, from diagnosis to translational medicine to personalized healthcare. Radboud University Medical Center aims to have a significant impact on healthcare through their focus on personalized healthcare and including the patient as a partner. Their integrated translational research and diagnostic laboratory develops biomarkers through various omics technologies for personalized diagnosis and treatment.
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.
Feeding plate for a newborn with Cleft Palate.pptxSatvikaPrasad
A feeding plate is a prosthetic device used for newborns with a cleft palate to assist in feeding and improve nutrition intake. From a prosthodontic perspective, this plate acts as a barrier between the oral and nasal cavities, facilitating effective sucking and swallowing by providing a more normal anatomical structure. It helps to prevent milk from entering the nasal passage, thereby reducing the risk of aspiration and enhancing the infant's ability to feed efficiently. The feeding plate also aids in the development of the oral muscles and can contribute to better growth and weight gain. Its custom fabrication and proper fitting by a prosthodontist are crucial for ensuring comfort and functionality, as well as for minimizing potential complications. Early intervention with a feeding plate can significantly improve the quality of life for both the infant and the parents.
Hypertension and it's role of physiotherapy in it.Vishal kr Thakur
This particular slides consist of- what is hypertension,what are it's causes and it's effect on body, risk factors, symptoms,complications, diagnosis and role of physiotherapy in it.
This slide is very helpful for physiotherapy students and also for other medical and healthcare students.
Here is summary of hypertension -
Hypertension, also known as high blood pressure, is a serious medical condition that occurs when blood pressure in the body's arteries is consistently too high. Blood pressure is the force of blood pushing against the walls of blood vessels as the heart pumps it. Hypertension can increase the risk of heart disease, brain disease, kidney disease, and premature death.
PET CT beginners Guide covers some of the underrepresented topics in PET CTMiadAlsulami
This lecture briefly covers some of the underrepresented topics in Molecular imaging with cases , such as:
- Primary pleural tumors and pleural metastases.
- Distinguishing between MPM and Talc Pleurodesis.
- Urological tumors.
- The role of FDG PET in NET.
MBC Support Group for Black Women – Insights in Genetic Testing.pdfbkling
Christina Spears, breast cancer genetic counselor at the Ohio State University Comprehensive Cancer Center, joined us for the MBC Support Group for Black Women to discuss the importance of genetic testing in communities of color and answer pressing questions.
Unlocking the Secrets to Safe Patient Handling.pdfLift Ability
Furthermore, the time constraints and workload in healthcare settings can make it challenging for caregivers to prioritise safe patient handling Australia practices, leading to shortcuts and increased risks.
Michigan HealthTech Market Map 2024. Includes 7 categories: Policy Makers, Academic Innovation Centers, Digital Health Providers, Healthcare Providers, Payers / Insurance, Device Companies, Life Science Companies, Innovation Accelerators. Developed by the Michigan-Israel Business Accelerator
About this webinar: This talk will introduce what cancer rehabilitation is, where it fits into the cancer trajectory, and who can benefit from it. In addition, the current landscape of cancer rehabilitation in Canada will be discussed and the need for advocacy to increase access to this essential component of cancer care.
Rate Controlled Drug Delivery Systems, Activation Modulated Drug Delivery Systems, Mechanically activated, pH activated, Enzyme activated, Osmotic activated Drug Delivery Systems, Feedback regulated Drug Delivery Systems systems are discussed here.
Under Pressure : Kenneth Kruk's StrategyKenneth Kruk
Kenneth Kruk's story of transforming challenges into opportunities by leading successful medical record transitions and bridging scientific knowledge gaps during COVID-19.
KEY Points of Leicester travel clinic In London doc.docxNX Healthcare
In order to protect visitors' safety and wellbeing, Travel Clinic Leicester offers a wide range of travel-related health treatments, including individualized counseling and vaccines. Our team of medical experts specializes in getting people ready for international travel, with a particular emphasis on vaccines and health consultations to prevent travel-related illnesses. We provide a range of travel-related services, such as health concerns unique to a trip, prevention of malaria, and travel-related medical supplies. Our clinic is dedicated to providing top-notch care, keeping abreast of the most recent recommendations for vaccinations and travel health precautions. The goal of Travel Clinic Leicester is to keep you safe and well-rested no matter what kind of travel you choose—business, pleasure, or adventure.
Dr. David Greene R3 stem cell Breakthroughs: Stem Cell Therapy in CardiologyR3 Stem Cell
Dr. David Greene, founder and CEO of R3 Stem Cell, is at the forefront of groundbreaking research in the field of cardiology, focusing on the transformative potential of stem cell therapy. His latest work emphasizes innovative approaches to treating heart disease, aiming to repair damaged heart tissue and improve heart function through the use of advanced stem cell techniques. This research promises not only to enhance the quality of life for patients with chronic heart conditions but also to pave the way for new, more effective treatments. Dr. Greene's work is notable for its focus on safety, efficacy, and the potential to significantly reduce the need for invasive surgeries and long-term medication, positioning stem cell therapy as a key player in the future of cardiac care.
INFECTION OF THE BRAIN -ENCEPHALITIS ( PPT)blessyjannu21
Neurological system includes brain and spinal cord. It plays an important role in functioning of our body. Encephalitis is the inflammation of the brain. Causes include viral infections, infections from insect bites or an autoimmune reaction that affects the brain. It can be life-threatening or cause long-term complications. Treatment varies, but most people require hospitalization so they can receive intensive treatment, including life support.
1. Omics, Biomarkers, Personalized Medicine:
A New Era, or More of the Same?
Klaus Lindpaintner
Roche Genetics/Roche Center for Medical Genomics
2. 2
Differential drug efficacy
Same symptoms
Same findings
Same disease (?)
Same Drug….
Different Effects
?
Genetic Differences
Possible Reasons:
Non-Compliance…
Drug-drug interactions…
Chance…
Or….
3. 3
Pharmacotherapy: State-of-the-Art
Group Incomplete/absent efficacy
AT2-antag 10-25%
SSRI 10-25%
ACE -I 10-30%
Beta blockers 15-25%
Tricycl. AD 20-50%
HMGCoAR-I 30-70%
Beta-2-agonists 40-70%
• Inter-individual differences in drug efficacy
• Significant incidence of serious adverse effects
among elderly hospitalized patients (US)
Serious 6.7% 2 M cases
Lethal 0.3% 100,000 cases
JAMA 98;279:1200
4. 4
Pharmacogenetics and Personalized
Medicine
An altogether new concept?
• Knowledge of inter-individual differences wrt metabolism as old as
civilization: 6th century B.C. Pythagoras observes
that ingestion of fava beans is harmful to
some individuals yet innocuous to others
• Finding the optimal treatment for every patient is as
old as medicine: differential diagnosis
• Tailoring treatments to drug-specific test results is nothing new.
Example: antibiotics
• Gram-positive bacteria: e.g. penicillin derivatives
• Gram-negative bacteria: e.g. aminoglycosides
• M. tuberculosis: isoniazid/rifampin/pyrazinamide
5. 6
Bridging a Historical Divide
protein
RNA
DNA
protein
RNA
DNA
protein
RNA
DNA
protein
RNA
DNA
cell-biology cell-biology
drugs
tissue / organ physiology-pathology
clinical diagnosis
molecular diagnosis
6. 7
Pharmacogenetics, Pharmacogenomics
Glossary of Terms
• Pharmacogenetics:
• a concept to provide more patient/disease-specific health care*
• based on the effects of inherited (or acquired) genetic variants
• assessed primarily by sequence determination (or single gene expression)
• one drug – many genomes (patients)
• focus: patient variability
• Pharmacogenomics (1):
• a concept to provide more patient/disease-specific health care
• based on the effects acquired (or inherited) genetic variants
• assessed primarily by expression profiles (many mRNAs)
• one drug – many genomes (patients)
• focus: patient variability
• Pharmacogenomics (2):
• a tool for compound selection/drug discovery
• many drugs – one genome (inbred animal/chip)
• focus: compound variability
*as conceptualized by Motulsky (1957), Vogel (1959), Kalow (1962) and
endorsed in the 2003 Nuffield Council’s Report on Pharmacogenetics
7. 8
2 Major Classes of Pharmacogenetics –
Both Resulting in Patient Stratification
• Strictly affecting drug response – not predictive of disease risk:
“Differentiating people” (“classical” pgx: Archibald Garrod)
• Pharmacokinetics (not only M, but also AADE)
• Pharmacodynamics
• Has not had much impact
• Related to molecular subclass of clinical diagnosis:
“Differentiating disease” (“molecular differential diagnosis”)
• Inherently linked to disease mechanism/prognosis
• Likely increasing impact in indications where we begin to treat
causally – oncology, inflammatory disease
• Both are conceptually rather different (and arguably the second
should not be included) but have practically the same
consequence:
Patient stratification according to novel, DNA-based parameters
10. 11
Pharmacogenetics = molecular DD
Case Study: Herceptin®
Low HER2
High HER2
Bimodal response:
2/3 of patients: addition of Herceptin® to chemoRx
no benefit
1/3 of patients: addition of Herceptin® to chemoRx
50% survival time increased by factor 1.5 (20 29 weeks)
11. 12
Xeloda® (capcitabine)
Patient stratification based on enzyme patterns
S: susceptible
R: refractory
Xeloda susceptibility vs tumor TP/DPD
in 24 xenografts
(dThdPase/DPD)
TP/DPD
100
10
1
0.1
P = 0.0015
S R
Xeloda
5-DFUR 5-FU inactive
metabolites
TP DPD
TS
12. 13
Biomarkers
What’s new – and why now?
• Availability of powerful, highly parallel new screening
methods (omics) makes looking for new biomarkers a
reasonable proposition.
• Paradigm shift(?): maturation of these basic cell and
molecular biology tools makes them newly applicable
to later-stage R&D
• Opportunities: personalized medicine
• Challenges: technical, scientific (clinical-epidemiological)
economical, ethical
• CAVEAT 1:
Association ≠ Causality
• Good news and bad news
14. 15
health
outcome
Mutation
SNPs in other genes
Environment
intermediate
phenotype
health
outcome
intermediate
phenotype
Single Gene Disease
Deterministic … possible stigma
Heritability: h2 ≈ 1
16. 17
health
outcome
SNP
SNPs in other genes
Environment
intermediate
phenotype
health
outcome
intermediate
phenotype
Common Complex Disease
health
outcome
Mutation
SNPs in other genes
Environment
intermediate
phenotype health
outcome
intermediate
phenotype
Single Gene Disease
Probabilistic, not deterministic - no reason for stigma.
17. 18
Complex Common Disease:
Nature and Nurture
genes
environment
Hemo-
philia
CF
HD
MVA
GSW
Lung cancer
tobacco --- asbestos
P450
Stroke MI
AD Diabetes
Asthma
Colon,
breast
Cancer
P53, BRCA
nutrition
ApoE4
18. 19
Heritability estimates in CCD
Disorder or phenotype Heritability h2
Preeclampsia 0.2-0.35
NIDDM 0.26-0.50
Hypertension 0.28-0.73
Osteoarthritis 0.3-0.46
Stroke 0.32
Asthma 0.36-0.47
Obesity 0.4-0.7
Depression 0.41-0.66
Other dementia 0.43
Blood pressure 0.5
BMI 0.5-0.7
Rheumatoid arthritis 0.53-0.65
Death from heart disease 0.55
Coronary heart disease 0.56
IGT 0.61
SLE 0.66
Alzheimer’s (sporadic) 0.72
Protracted/recurrent otitis media 0.72
19. 20
Malignancy Heritability h2
Thyroid 0.53 (0.52–0.53)
Endocrine glands 0.28 (0.27–0.28)
Breast 0.25 (0.23–0.27)
Testis 0.25 (0.15–0.37)
Cervix invasive 0.22 (0.14–0.27)
Melanoma 0.21 (0.12–0.23)
Nervous system: age <15 years 0.13 (0.06–0.20)
Colon 0.13 (0.12–0.18)
Cervix in situ 0.13 (0.06–0.15)
Rectum 0.12 (0.08–0.13)
Nervous system 0.12 (0.10–0.18)
Non-Hodgkin lymphoma 0.10 (0.08–0.10)
Leukemia: age <15 years 0.09 (0.09–0.16)
Lung 0.08 (0.05–0.09)
Kidney 0.08 (0.07–0.09)
Urinary bladder 0.07 (0.02–0.11)
Leukemia 0.01 (0.00–0.01)
Stomach 0.01 (0.01–0.06)
Czene et al, Int J Cancer 99:260; 2002
Heritabilityestimates in cancer
20. 21
Medical Progress: Evolution or
Revolution?
…Genetics
Clinical expertise
Classical epidemiology
Differential diagnosis
Risk assessment - prevention
Historic Drivers of Medical Progress
More differentiated, molecular understanding of pathology and drug action
Clinical Disease Definition
Clinical Diagnosis
Molecular Disease Definition
Molecular Diagnosis
in-vitro Diagnostics
21. 22
Tuberculosis Heart Failure
Cancer
HER-2-negative (2/3) HER-2-positive (1/3)
Cytostatics Cytostatics + humMAb
Tuberculosis Heart Failure
Cancer
Antibacterials Cytostatics ACE Inhibitors
Consumption
Phlebotomy
Mean survival 3 yrs
Mean survival 7 yrs
Breast Ca
Colon Ca
Lung Ca
22. 23
Pharmacogenetics vs. other Markers
Ausefuldistinction?
* alteration germ-line in origin – heritable
DNA
mRNA
primary
protein
processed
protein,
small
molecule
response to
medicine
Normal
DNA*
mRNA*
primary
protein*
processed
protein,
small
molecule*
altered
response to
medicine*
Pharmaco-
genetics
DNA *
mRNA*
primary
protein*
processed
protein,
small
molecule*
altered
response to
medicine*
Pharmaco-
genomics
DNA
mRNA*
primary
protein*
processed
protein,
small
molecule*
altered
response to
medicine*
Pharmaco-
genomics
DNA
mRNA
primary
protein*
processed
protein,
small
molecule*
altered
response to
medicine*
Pharmaco-
proteomics
DNA
mRNA
primary
protein
processed
protein,
small
molecule*
altered
response to
medicine*
Pharmaco-
metabonomics
* alteration somatic – acquired (environment, life-style)
23. 24
Pharmacogenetics and beyond:
Biomarkers
• Key concept:
More targeted medicines (“personalized medicine”)
• More effective
• Safer
• More cost-effective (?)
• Based on a better understanding of inter-individual differences among
patients
• Inherited (the “classical” pharmacogenetics)
• Acquired (“flavors” of disease, underlying molecular heterogeneity of any
one clinical diagnosis: molecular differential diagnosis)
• Paradigm: carry out specific test that point to one or another medicine
as optimal for the patient before prescribing it.
What does not matter: Nature of test (DNA, RNA, protein, other)
What does matter: Information content
24. 25
Biomarker tests in medical practice
Twosetsofconsiderations
• Test performance
• Analytical performance – QC and accreditation of labs
• Clinical performance
• Clinical validity – retrospective/observation studies
• Clinical utility – prospective intervention trials
• Note: Prior probability: critical for test performance, esp.
screens (sensitivity/specificity, PPV/NPV)
• Nature of illness
• Serious (life-threatening) illness
Default: ”don’t withhold in error”;
If in doubt: “treat”
• Less serious illness
Default: “don’t treat in error”;
If in doubt: “don’t treat”
28. 29
Interpretation? Consequences?
• NEJM
• 8/9 responders + for mutation
• 7/7 non-responders – for mutation
• 2 of 25 untreated + for mutation
• Pre-testing will increase response rate to 100% among those
who test +
• Pre-testing will result in denial of treatment to 11% of who
would responders
• Pao et al, MSKCC (PNAS)
• 7/10 responders + for mutation
• 8/8 non-responders – for mutation
• 4/81 NSCLC smokers + for mutation
• 7/15 non-smoker, adeno-Ca + for mutation
• Pre-testing will result in denial of treatment to 30% of who
would be responders
29. 30
• Gefitinib (IRESSA) Response in Caucasians 10%
Prevalence of variants in Boston patients 2/25
(NEJM)
• Gefitinib (IRESSA) Response in Japanese 28%
Prevalence of variants in Japanese patients 26%
(Science)
• Erlotinib (TARCEVA) Monotherapy in NSCLS
EGFR Mutratoin prevalence 12%
Response Rate 42%
EGF-R variants and Drug Response
30. 31
Analytical Performance: Metrology
Aything butstraight-forward
• Precision
• Repeatability
under same conditions, precision in a series of measurement
in the same run; and
• Reproducibility
under different conditions, which are usually specified, e.g.
day-to-day or lab-to lab
• Trueness
• the closeness of agreement of an average value from a large
series of measurements with a "true value" or an accepted
reference value.
• Numerical value: bias
• Accuracy –
• referring to a single measurement and comprising both
random and systematic influences.
• Numerical value: total error of measurement.
31. 32
Biomarker tests in medical practice
Two sets of considerations
• Test performance
• Analytical performance – QC and accreditation of labs
• Clinical performance
• Clinical validity – retrospective/observation studies
• Clinical utility – prospective intervention trials
• Note: Prior probability: critical for test performance, esp.
screens (sensitivity/specificity, PPV/NPV)
• Nature of illness
• Serious (life-threatening) illness
Default: ”don’t withhold in error”;
If in doubt: “treat”
• Less serious illness
Default: “don’t treat in error”;
If in doubt: “don’t treat”
33. 34
unambiguous wt
wt vs. mut
wt vs. mut vs. artifact
wt?
wt vs. mut?
unambiguous known mut
known mut vs. new mut vs. both?
mut?
wt vs. mut vs. artifact?
known mut vs. new mut vs. both vs. indet?
unambiguous new mut
new mut?
wt?
known mut?
new mut?
unambiguous unknown
Analytical performance: EGFR sequencing
Sometimes,farfromit…
34. 35
EGFR mutation analysis analytical performance
Thedirty(notso)littlesecret
• Multiple complex variables:
• Tissue heterogeneity
• Limited sample quantity and quality (FFPE)
• LCDM/macro-dissection
• PCR-pre-amplification
• 4 exons x 2 amplification runs each
• How to deal with “drop-outs”?
• How to deal with non-replicated mutations – artifact or
quantitative manifestation of relative abundance of
mutation?
• None of current publications disclose this difficulty
• Own experience – using different “calling” algorithms:
• Algorithm 1: 6.1% (13 mut / 200 wt / 94 indeterminate)
• Algorithm 2: 7.5% (15 mut / 186 wt / 106 indeterminate)
• Algorithm 3: 9.9% (23 mut / 210 wt / 74 indeterminate)
36. 37
Biomarker tests in medical practice
Twosetsofconsiderations
• Test performance
• Analytical accuracy – QC and accreditation of labs
• Clinical performance
• Clin validity – retrospective/observation studies
• Clinical utility – prospective intervention trials
• Note: Prior probability: critical for test performance, esp.
screens (sensitivity/specificity, PPV/NPV)
• Nature of illness
• Serious (life-threatening) illness
Default: ”don’t withhold in error”;
If in doubt: “treat”
• Less serious illness
Default: “don’t treat in error”;
If in doubt: “don’t treat”
37. 38
Optimizing Sensitivity vs. Specificity
TargetProductProfileDefinitionisEssential
sensitivity
1-specificity
0% 100%
0%
100%
Note: Sliding the ROC-cutoff value may be more difficult with (categorical) genotype
data than with other (quantitative) biomarker data
38. 39
+ response - response
+ test true positive false positive
- test false negative true negative
Efficacy marker: High sensitivity
+ adverse event - adverse event
+ test true positive false positive
- test false negative true negative
Safety marker: High specificity
+ response - response
+ test true positive false positive
- test false negative true negative
Efficacy marker: High specificty
+ adverse event - adverse event
+ test true positive false positive
- test false negative true negative
Safety marker: High sensitivity
Less serious illness: don’t prescribe inappropriately
Serious illness: don’t withhold inappropriately
Biomarker performance
UpanddowntheROCcurve
39. 40
Case-in-point: Herceptin/HerCepTest
Thesearchfornewbiomarkers–anditsimplications
+ response - response
+Her2
test
20
true +
10
false +
30
66% response among
treated Her2+
- Her2
test
0
false -
70
true -
70
presumed 0% response
among Her2-
(NB: anecdotal data)
Sensitivity:
true+/(true+ + false-)
20/(20+0)=1
100% sensitive
Specificity:
true-/(true- + false+)
70/70+10=0.875
88% specific
100
+ response - response
+ new
BM test
16
true +
2
false +
18
88% response among
treated Her2+/BM+
- new
BM test
4
false -
8
true -
12
33% response among
Her2-/BM-
Sensitivity:
true+/(true+ + false-)
16/(16+4)=0.8
80% sensitive
Specificity:
true-/(true- + false+)
8/1+9=0.9
80% (98%*) specific
30
+ response - response
+ new BM
test
19
true +
5
false +
24
79% response among
treated Her2+/BM+
- new BM
test
1
false -
5
true -
7
16% response among
Her2-/BM-
Sensitivity:
true+/(true+ + false-)
19/(19+1)=0.95
95% sensitive
Specificity:
true-/(true- + false+)
5/5+5=.5
50% (94%*) specific
30
Status quo,
66% success rate
no potential responder denied Rx
Add-on-BM scenario 1
78% success rate
5% of would-be responders denied Rx
Add-on-BM scenario 2
88% success rate
20% of would-be responders denied Rx
*Specificity of combined Her2 and new BM tests
40. 41
Total Patients without
deficient TPMT-allele
Patients with one or two
deficient TPMT-alleles
Reference
n n % n %
25 20 80 5 20 Black et al. 1998
17 16 94 1 6 Naughton et al. 1999
7 4 57 3 43 Ishioka et al. 1999
15 14 93 1 7 Dubinsky et al. 2000
41 29 70 12 30 Colombel et al. 2000
8 6 75 2 25 Ando et al. 2001
Not all that glitters is gold: TPMT
Thiopurine-treated patients with adverse drug reactions
sensitivity
positive test predicts, but negative tests by no means excludes SAE
299 negative tests for every one positive test
41. 42
“Exhaustive pharmacogenetic research efforts have
narrowed your niche market down
to Harry Finkelstein of Newburg Heights here.”
Economic considerations
How far is segmentation of markets feasible?
42. 43
Emergence of sub-critically small
segments
A self-limited proposition
• Retrospectively:
Given biomedical variance, biomarker-defined
segments are unlikely to be recognizable unless they
represent a significant share of the overall patient
population.
• Prospectively:
Small segments known to exist will either not be
addressed for lack of business case, or under Orphan
Drug Guidelines
43. 44
The Tightening Reimbursement Climate
Biomarker strategies may be essential
Strategy Life-months Incr.
QALYs
Incr. Cost
UK £
Incr
Cost/QUALY
UK £
No test
Chemo-Rx alone
28.02 1.28 26,919 21,030
Positive HerCep Test
Chemo-Rx and Herceptin
29.30 1.36 33,376 24,541
No test
Chemo-Rx and Herceptin
29.41 1.37 49,211 35,920
Elkin et al; J Clin Oncol 2004; 22:854 ff
($/£ conv. rate 1/1/2003, not PPP-adjusted)
NB: National Institute for Clinical Excellence’s (NICE) threshold
for approving reimbursement through NHS believed to be
~UK £ 30,000 per QUALY (quality-adjusted life year)
44. 45
Biomarkers – likely outcome:
• The concept applies potentially to most compounds
• It will in fact, however, become reality only for some/few compounds…
but we will have to look at all to find the few!
• (We will likely see more examples of “pathology-related” biomarker-
based stratification (Herceptin-paradigm) that advance efficacy; and
most likely in oncology and inflammatory/autoimmune disease)
• Multifactorial algorithms likely to emerge, rather than simple, one-
variable models – but highly complex algorithms unlikely.
• Essential: Define Target-Product-Profile
• Key: Modesty, Realism, robust Optimism:
we will not have perfect medicines
BUT
we will have increasingly better medicines
45. 46
No 1-on-1 custom tailoring,
but towards a much better fit …
38 40
39 39½39¾
377/8
Remember: All medical decisions/knowledge are based on
group-derived (aggregate) data analysis.
“Data” on individuals (Harry Finkelstein) are anecdotal and
(largely) medically/clinically meaningless