Professor Alain van Gool has had a mixed career in academia, pharmaceutical industry, and applied research focusing on biomarkers and personalized healthcare. He is currently the head of the Radboud Center for Proteomics, Glycomics and Metabolomics and coordinates biomarker research at the Radboud University Medical Center and TNO. The document discusses the evolving role of biomarkers from diagnosis to personalized healthcare and examples of biomarkers guiding treatment for melanoma and metabolic disease. It also presents examples of preclinical research models for studying metabolic disease and the effects of pharmaceutical, nutritional, and lifestyle interventions on conditions like atherosclerosis and obesity.
Pharmacology for Physiotherapy Book By Padmaja Udaykumar Second Edition.Khalid Ghaznavi
Pharmacology for Physiotherapy Book
By Padmaja Udaykumar Second Edition.
This consists of a complete book version. I hope this will be helpful for you.
“The Evolution of Pharmaceutical Biotechnology – Science, Strategies, Products, and Regulations”
Shows the latest developments in pharmaceutical biotechnology and provides a broad overview of biotherapeutic & biosimilar regulations globally and in the EU
Illustrates key pharmacovigilance considerations for biotherapeutic medicines “Pharmacovigilance Aspects of Biotherapeutic medicines:Nowadays and Perspectives”
Challenges and Considerations in Clinical Development of "Targeted Therapies"...Medpace
In this webinar, Medpace experts discuss key clinical, operational and laboratory considerations, lessons-learned, and best practices for accelerating the global development of safe and effective targeted therapeutics, using acute myeloid leukemia (AML) to highlight the complexities.
Pharmacology for Physiotherapy Book By Padmaja Udaykumar Second Edition.Khalid Ghaznavi
Pharmacology for Physiotherapy Book
By Padmaja Udaykumar Second Edition.
This consists of a complete book version. I hope this will be helpful for you.
“The Evolution of Pharmaceutical Biotechnology – Science, Strategies, Products, and Regulations”
Shows the latest developments in pharmaceutical biotechnology and provides a broad overview of biotherapeutic & biosimilar regulations globally and in the EU
Illustrates key pharmacovigilance considerations for biotherapeutic medicines “Pharmacovigilance Aspects of Biotherapeutic medicines:Nowadays and Perspectives”
Challenges and Considerations in Clinical Development of "Targeted Therapies"...Medpace
In this webinar, Medpace experts discuss key clinical, operational and laboratory considerations, lessons-learned, and best practices for accelerating the global development of safe and effective targeted therapeutics, using acute myeloid leukemia (AML) to highlight the complexities.
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..
Getting Ahead of the Evolving Landscape in RadiopharmaceuticalsMedpace
In this webinar devoted to radiopharmaceuticals, the featured speakers will explore the scientific, operational and regulatory considerations for radiopharmaceuticals. With a focus on oncology, they will discuss the current regulatory landscape and how this impacts overall development programs. The speakers will explore the challenges of conducting radiopharmaceutical trials, offering insights into trial start-up, site selection and operational aspects to seamlessly execute these studies as part of clinical development plans.
Sagar Lonial, MD, FACP, Shaji Kumar, MD, Robert Z. Orlowski, MD, PhD, and Nina Shah, MD, prepared useful practice aids pertaining to multiple myeloma for this CME/MOC activity titled "How I Think, How I Treat: Understanding Innovation in Multiple Myeloma—New Models for Attacking Disease Across the Clinical Spectrum". For the full presentation, complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/30sAs5I. CME/MOC credit will be available until July 16, 2021.
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, Pharmacogenetics and Pharmacokinetics Zohaib HUSSAIN
Introduction
With the information available about human genome and human proteome, it is now well understood that there are a lot of variations between individuals. These minor variations account for many differences like adverse drug reactions, which are responsible for many hospitalizations and casualties. The observed variable effect of drug is due to difference in sensitivity as some people need higher dose and some need lower dose to get similar therapeutic effect, but in some people drug has no therapeutic effects and in some it shows strong adverse reactions.
Instructions and advice on what investors should do after using advisor chat. This presentation includes evaluating your right advisor and whether or not to meet in person.
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..
Getting Ahead of the Evolving Landscape in RadiopharmaceuticalsMedpace
In this webinar devoted to radiopharmaceuticals, the featured speakers will explore the scientific, operational and regulatory considerations for radiopharmaceuticals. With a focus on oncology, they will discuss the current regulatory landscape and how this impacts overall development programs. The speakers will explore the challenges of conducting radiopharmaceutical trials, offering insights into trial start-up, site selection and operational aspects to seamlessly execute these studies as part of clinical development plans.
Sagar Lonial, MD, FACP, Shaji Kumar, MD, Robert Z. Orlowski, MD, PhD, and Nina Shah, MD, prepared useful practice aids pertaining to multiple myeloma for this CME/MOC activity titled "How I Think, How I Treat: Understanding Innovation in Multiple Myeloma—New Models for Attacking Disease Across the Clinical Spectrum". For the full presentation, complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/30sAs5I. CME/MOC credit will be available until July 16, 2021.
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, Pharmacogenetics and Pharmacokinetics Zohaib HUSSAIN
Introduction
With the information available about human genome and human proteome, it is now well understood that there are a lot of variations between individuals. These minor variations account for many differences like adverse drug reactions, which are responsible for many hospitalizations and casualties. The observed variable effect of drug is due to difference in sensitivity as some people need higher dose and some need lower dose to get similar therapeutic effect, but in some people drug has no therapeutic effects and in some it shows strong adverse reactions.
Instructions and advice on what investors should do after using advisor chat. This presentation includes evaluating your right advisor and whether or not to meet in person.
Targeted Threat (APT) Defense for Applications Featuring pxGrid: a deep diveCisco DevNet
A session in the DevNet Zone at Cisco Live, Berlin. Targeted Attacks, which the media refers to as APTs, are threats that must be addressed by any organization requiring networked computers to do business. In this session we will go over the run book techniques used by these threat actors and then go over strategies for mitigating those attacks. In this session we will focus on the concepts that developers of network applications need to be aware of to mitigate these styles of attacks and techniques to use. To finish off, we will delve into pxGrid and what it can offer to break these APT style attack playbooks. Backgrounder: We obtained knowledge of these run book techniques from trusted advisors, peers in the industry and from our own observations. Our own observations included information from our CSIRT, our security products in the field as well as our internal phishing awareness campaign. After studying these techniques we devised strategies to mitigate them. Those strategies were then tested and deployed throughout our ecosystem. The Cisco CSDL initiative and ACT2 chips will also be techniques and tools highlighted in this session.
DEVNET-1115 Learning@Cisco: Developers + IT Professional: The Future of the I...Cisco DevNet
The digitalization of the world is breaking walls between different job roles, and the IT workforce is now pushed beyond the traditional plan, configure, support cycle. New job roles are now available, that integrate new elements like data analysis and software development to enhance the potential of the IT infrastructure to deliver on critical industry business cases.
2016-02-18 Innovation for Health 2016 conference, Rotterdam Alain van GoolAlain van Gool
Lecture on personalized healthcare in a great session at the Innovation for Health 2016 conference, discussing opportunities and challenges with 800 scientists, enterpreneurs and care professionals.
The dynamic region in the world and ....here are some headlines
+ Internet users in APAC: 1.83 Billion
+ Social media users in APAC: 1.43 Billion
+ Mobile connections in APAC: 3.86 Billion
+ Mobile social media users in APAC: 1.36 Billion
+ APAC's share of total global population: 55%
+ APAC's share of global internet users: 50%
+ APAC's share of global social media users: 53%
+ APAC's share of global mobile connections: 49%
+ APAC's share of global social media users: 56%
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.
Day 2: Innovation to optimise therapeutic options for prevention and treatmen...KTN
The focus of this day is to explore unmet clinical needs in the effective treatment and therapy of patients with multiple long term conditions. Such patients have been historically excluded from clinical trials and also suffer from the burden of polypharmacy complications that affect quality of life. Innovation that supports a more holistic and personalised intervention, that applies patient stratification and pharmacogenomics, could dramatically improve health outcomes for diverse patient groups.
-What are Standards of Care and why does the Mito community need such standards?
-Review the MMS's Standards of Care for Mitochondrial Disease and how they were developed.
-Outline upcoming MMS projects.
iCAAD London 2019 - Antonio Metastasio - PERSONALISED MEDICINE IN THE TREATM...iCAADEvents
Personalised medicine is considered the next frontier of health care. The role of genetic testing in psychiatry and in addictions medicine, however, has been recently critically reviewed. Are genetic tests helpful in assessing and managing these conditions?
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.
2023-11-14 Biomarkers Europe 2023, Berlin, Alain van Gool.pdfAlain van Gool
Lecture at the Biomarkers Europe 2023 conference for an audience of pharma scientists and omics/data solution providers. I outlined several initiatives of potential interest and discussed development of our sensitive personalized clinical biomarker test for minimal residual disease monitoring in multiple myeloma.
2023-11-09 HealthRI Biobanking day_Amsterdam_Alain van Gool.pdfAlain van Gool
Examples of lessons learned in Omics-based biomarker studies from myself and colleagues in X-omics and EATRIS, for an audience of biobankers, researchers and diagnostic/clinical chemistry experts.
2023-04-20 EATRIS-Plus Summerschool, Lisbon, Alain van GoolAlain van Gool
Closing keynote lecture at the EATRIS-Plus summerschool on personalised medicine, outlining developments, opportunities, challenges and recommendations to do next in this exciting era of personalised medicine.
2022-11-23 DTL Future of data-driven life sciences, Utrecht, Alain van Gool.pdfAlain van Gool
A pitch on directions to improve experimental reproducibility, illustrated by examples of past experiences. I made the plee to move from 'Proudly invented here' to 'Proudly copyied from', to re-use each other's eperiences in successes and failures.
2022-10-12 The future of population health_Alain van Gool.pdfAlain van Gool
Lecture as part of a global streamed event across Japan, Europe, USA with amazing speakers on the future of population health, in which I shared stories of personalized health(care).
2022-09-08 ECPM Digital Biomarkers and AI, Basel, Alain van Gool.pdfAlain van Gool
Lecture for 150 pharma professionals to outline the potentials and things-to-do with digital biomarkers, as part of a ECPM training on digitization and AI in drug development.
2022-04-14 EuroMedLab, Munich, Alain van GoolAlain van Gool
Keynote lecture at the EuroMedLab 2021 providing an audience of clinical chemists and laboratory medicine scientists with advancements of multi-omics applications in personalized healthcare, and challenges that we need to solve as translational scientists.
2021 12-10 Amalia Science Day, Nijmegen, Alain van GoolAlain van Gool
Short lecture as part of a highly diverse science day of the Amalia Children's hospital, outlining a variety of innovations in our Radboudumc, where I could outline some of our breakthroughs in applying multi-omics in pediatric healthcare.
2021 06-14 EATRIS-Plus summer school, Alain van GoolAlain van Gool
Introductory lecture for the 100 participant summer school of the EATRIS-Plus project, outlining personalized medicine, biomarker and multi-omics strategies and use cases.
2021 03-25 11th World Clinical Biomarkers & Companion Diagnostics, Alain van ...Alain van Gool
Closing keynote of a 3-day conference on clinical biomarkers and companion diagnostics, organised by Hanson Wade, outlining the power of omics approaches in healthcare and translation of inovations to impact.
2020 09-07 European Center Pharmaceutical Medicine course Biomarkers, Basel, ...Alain van Gool
Tutorial lecture on biomarkers for pharmaceutical industry R&D professionals, outlining status, potential and challenges of biomarkers in pharma, clinic and society.
2020 08-28 SensUs Event 2020 keynote, Eindhoven, Alain van GoolAlain van Gool
Closing keynote for international students participating in the SensUs Event 2020, where they designed and created a novel sensor for drug level monitoring in epilepsy treatment. Lecture outlined innovations in biomarkers in personalized health(care).
2020 02-10 European Center Pharmaceutical Medicine course - biomarkers, Basel...Alain van Gool
Review of biomarkers in personalized healthcare covering pharmaceutical drug development, translational clinical research, digital biomarkers and innovation gaps. This lecture was given as part of an advanced and fantastic pharmaceutical sciences course provided by ECPM.
2019 10-14 2nd Int Congress on Precision Medicine, Munich, Alain van GoolAlain van Gool
Opening lecture at the 2nd International Congress on Precision Medicine in Munich, outlining progress in omics-based biomarkers for rare diseases, biomarker innovation gaps and multi-partner initiatives to bridge those gaps to applications. Also reviewed the highlights of our recently published Handbook of Biomarkers and Precision Medicine.
2019 09-23 COST CliniMARK summerschool, Spetses, Alain van GoolAlain van Gool
Opening lecture of the COST CliniMARK summer school 'Approaches for Biomarker Discovery and Validation'. Extensive introduction in biomarker approached used in pharmaceutical industry, academic research and clinical care, and society, combined with review of biomarker innovation gaps and outlook.
2019 06-19 Dutch association for clinical chemistry and laboratory medicine -...Alain van Gool
Sharing my views on how X-omics biomarker analyses through next gen sequencing and mass spectrometry will change the landscape of diagnostics and clinical chemistry in the near future.
CHAPTER 1 SEMESTER V - ROLE OF PEADIATRIC NURSE.pdfSachin Sharma
Pediatric nurses play a vital role in the health and well-being of children. Their responsibilities are wide-ranging, and their objectives can be categorized into several key areas:
1. Direct Patient Care:
Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
2. Health Promotion and Education:
Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
This includes tasks like:
Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
3. Collaboration and Advocacy:
Objective: Collaborate effectively with doctors, social workers, therapists, and other healthcare professionals to ensure coordinated care for children.
Objective: Advocate for the rights and best interests of their patients, especially when children cannot speak for themselves.
This includes tasks like:
Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
4. Professional Development and Research:
Objective: Stay up-to-date on the latest advancements in pediatric healthcare through continuing education and research.
Objective: Contribute to improving the quality of care for children by participating in research initiatives.
This includes tasks like:
Attending workshops and conferences on pediatric nursing.
Participating in clinical trials related to child health.
Implementing evidence-based practices into their daily routines.
By fulfilling these objectives, pediatric nurses play a crucial role in ensuring the optimal health and well-being of children throughout all stages of their development.
Struggling with intense fears that disrupt your life? At Renew Life Hypnosis, we offer specialized hypnosis to overcome fear. Phobias are exaggerated fears, often stemming from past traumas or learned behaviors. Hypnotherapy addresses these deep-seated fears by accessing the subconscious mind, helping you change your reactions to phobic triggers. Our expert therapists guide you into a state of deep relaxation, allowing you to transform your responses and reduce anxiety. Experience increased confidence and freedom from phobias with our personalized approach. Ready to live a fear-free life? Visit us at Renew Life Hypnosis..
Global launch of the Healthy Ageing and Prevention Index 2nd wave – alongside...ILC- UK
The Healthy Ageing and Prevention Index is an online tool created by ILC that ranks countries on six metrics including, life span, health span, work span, income, environmental performance, and happiness. The Index helps us understand how well countries have adapted to longevity and inform decision makers on what must be done to maximise the economic benefits that comes with living well for longer.
Alongside the 77th World Health Assembly in Geneva on 28 May 2024, we launched the second version of our Index, allowing us to track progress and give new insights into what needs to be done to keep populations healthier for longer.
The speakers included:
Professor Orazio Schillaci, Minister of Health, Italy
Dr Hans Groth, Chairman of the Board, World Demographic & Ageing Forum
Professor Ilona Kickbusch, Founder and Chair, Global Health Centre, Geneva Graduate Institute and co-chair, World Health Summit Council
Dr Natasha Azzopardi Muscat, Director, Country Health Policies and Systems Division, World Health Organisation EURO
Dr Marta Lomazzi, Executive Manager, World Federation of Public Health Associations
Dr Shyam Bishen, Head, Centre for Health and Healthcare and Member of the Executive Committee, World Economic Forum
Dr Karin Tegmark Wisell, Director General, Public Health Agency of Sweden
Medical Technology Tackles New Health Care Demand - Research Report - March 2...pchutichetpong
M Capital Group (“MCG”) predicts that with, against, despite, and even without the global pandemic, the medical technology (MedTech) industry shows signs of continuous healthy growth, driven by smaller, faster, and cheaper devices, growing demand for home-based applications, technological innovation, strategic acquisitions, investments, and SPAC listings. MCG predicts that this should reflects itself in annual growth of over 6%, well beyond 2028.
According to Chris Mouchabhani, Managing Partner at M Capital Group, “Despite all economic scenarios that one may consider, beyond overall economic shocks, medical technology should remain one of the most promising and robust sectors over the short to medium term and well beyond 2028.”
There is a movement towards home-based care for the elderly, next generation scanning and MRI devices, wearable technology, artificial intelligence incorporation, and online connectivity. Experts also see a focus on predictive, preventive, personalized, participatory, and precision medicine, with rising levels of integration of home care and technological innovation.
The average cost of treatment has been rising across the board, creating additional financial burdens to governments, healthcare providers and insurance companies. According to MCG, cost-per-inpatient-stay in the United States alone rose on average annually by over 13% between 2014 to 2021, leading MedTech to focus research efforts on optimized medical equipment at lower price points, whilst emphasizing portability and ease of use. Namely, 46% of the 1,008 medical technology companies in the 2021 MedTech Innovator (“MTI”) database are focusing on prevention, wellness, detection, or diagnosis, signaling a clear push for preventive care to also tackle costs.
In addition, there has also been a lasting impact on consumer and medical demand for home care, supported by the pandemic. Lockdowns, closure of care facilities, and healthcare systems subjected to capacity pressure, accelerated demand away from traditional inpatient care. Now, outpatient care solutions are driving industry production, with nearly 70% of recent diagnostics start-up companies producing products in areas such as ambulatory clinics, at-home care, and self-administered diagnostics.
One of the most developed cities of India, the city of Chennai is the capital of Tamilnadu and many people from different parts of India come here to earn their bread and butter. Being a metropolitan, the city is filled with towering building and beaches but the sad part as with almost every Indian city
Navigating the Health Insurance Market_ Understanding Trends and Options.pdfEnterprise Wired
From navigating policy options to staying informed about industry trends, this comprehensive guide explores everything you need to know about the health insurance market.
Navigating Challenges: Mental Health, Legislation, and the Prison System in B...Guillermo Rivera
This conference will delve into the intricate intersections between mental health, legal frameworks, and the prison system in Bolivia. It aims to provide a comprehensive overview of the current challenges faced by mental health professionals working within the legislative and correctional landscapes. Topics of discussion will include the prevalence and impact of mental health issues among the incarcerated population, the effectiveness of existing mental health policies and legislation, and potential reforms to enhance the mental health support system within prisons.
India Clinical Trials Market: Industry Size and Growth Trends [2030] Analyzed...Kumar Satyam
According to TechSci Research report, "India Clinical Trials Market- By Region, Competition, Forecast & Opportunities, 2030F," the India Clinical Trials Market was valued at USD 2.05 billion in 2024 and is projected to grow at a compound annual growth rate (CAGR) of 8.64% through 2030. The market is driven by a variety of factors, making India an attractive destination for pharmaceutical companies and researchers. India's vast and diverse patient population, cost-effective operational environment, and a large pool of skilled medical professionals contribute significantly to the market's growth. Additionally, increasing government support in streamlining regulations and the growing prevalence of lifestyle diseases further propel the clinical trials market.
Growing Prevalence of Lifestyle Diseases
The rising incidence of lifestyle diseases such as diabetes, cardiovascular diseases, and cancer is a major trend driving the clinical trials market in India. These conditions necessitate the development and testing of new treatment methods, creating a robust demand for clinical trials. The increasing burden of these diseases highlights the need for innovative therapies and underscores the importance of India as a key player in global clinical research.
Leading the Way in Nephrology: Dr. David Greene's Work with Stem Cells for Ki...Dr. David Greene Arizona
As we watch Dr. Greene's continued efforts and research in Arizona, it's clear that stem cell therapy holds a promising key to unlocking new doors in the treatment of kidney disease. With each study and trial, we step closer to a world where kidney disease is no longer a life sentence but a treatable condition, thanks to pioneers like Dr. David Greene.
CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
This content provides an overview of preventive pediatrics. It defines preventive pediatrics as preventing disease and promoting children's physical, mental, and social well-being to achieve positive health. It discusses antenatal, postnatal, and social preventive pediatrics. It also covers various child health programs like immunization, breastfeeding, ICDS, and the roles of organizations like WHO, UNICEF, and nurses in preventive pediatrics.
1. Biomarkers in personalized healthcare,
changing perspectives
Professor in Personalized Healthcare
Head Radboud Center for Proteomics, Glycomics
and Metabolomics
Coordinator Radboud Technology Centers
Head Biomarkers in Personalized Healthcare
Prof Alain van Gool
Seminar LGC Biosciences
Cambridge, UK
15 Oct 2014
2. My mixed perspectives in personalized health(care)
8 years academia (NL, UK)
(molecular mechanisms of disease)
13 years pharma (EU, USA, Asia)
(biomarkers, Omics)
3 years med school (NL)
(personalized healthcare, Omics, biomarkers)
3 years applied research institute (NL, EU)
(biomarkers, personalized health)
A person / citizen / family man
(adventures in EU, USA, Asia)
1991-1996 1996-1998 2009-2012
1999-2007 2007-2009 2009-2011
2011-now
2011-now
2
3. Radboud university medical center
• Nijmegen, The Netherlands
• Mission: “To have a significant impact on healthcare”
• Strategic focus on Personalized Healthcare through
“the patient as partner”
• Core activities:
• Patient care
• Research
• Education
• 11.000 colleagues
• 52 departments
• 3.300 students
• 1.000 beds
• First academic centre outside US to fully implement EPIC
4. TNO = Netherlands Organisation for Applied Scientific Research
Mission = to drive ideas to reach their full market value.
We partner with: Governmental & regulatory organisations Universities Pharma, chemical and food companies International consortia
Knowledge
development
Knowledge
application
Knowledge
exploitation
Develop fundamental knowledge
With
universities
With partners
With
customers
Embedded in the market
TNO
TNO companies
4
Non-for-profit research organisation ~3500 employees 19 sites in Netherlands, 18 countries global 7 main themes (ao Life Sciences)
5. Biomarkers in Personalized Healthcare
an evolving role
• From only diagnosis
• To Translational Medicine
• To Personalized/Stratified/Precision Medicine
• To Personalized Healthcare
• To Person-centered Health(care)
5
6. Diagnostic biomarkers in the early days
{Kumar and van Gool, RSC, 2013}
1506:
The urine wheel
Use color, smell and taste of
urine to diagnose disease and
decide best treatment
Ullrich Pinder
Epiphanie Medicorum
7. Biomarkers in Translational Medicine in pharma
• Translational medicine
Exposure
Mechanism
Efficacy
Safety
• Personalized medicine
Diagnosis
Prognosis
Response prediction
• Tools for data-driven decision making
Biologically relevant
Clinically accepted
Quantitative
Different analytes/types
Fit-for-purpose application
{Source: Van Gool et al, Drug Disc Today 2010}
7
8. Biomarker data-driven decisions
Target engagement? Effect on disease?
yes yes !
no no
• No need to test current
drug in large clinical trial
• Need to identify a more
potent drug
• Concept may still be
correct
• Concept was not correct
• Abandon approach
• Proof-of-Concept
• Proceed to full
clinical
development
“Stop early, stop cheap”
“More shots on goal”
8
{Kumar and van Gool, RSC, 2013}
9. Source: John Arrowsmith: Nature Reviews Drug Discovery 2011
• Success rates of clinical proof-of-concept have dropped from 28% to 18%
• Insufficient efficacy as the most frequent reason
• Targeted therapy through Personalized Medicine may be the solution
Promise of Personalized Medicine
Analysis of 108 failures in phase II
Reason for failure Therapeutic area
9
10. Biomarkers in Personalized Medicine
• Melanoma – targeted medicine
• Metabolic health – system medicine
10
12. Clinical efficacy of Vemurafenib
{Wagle et al, 2011, J Clin Oncol 29:3085}
Before Rx Vemurafenib, 15 weeks Vemurafenib, 23 weeks
• Strong initial effects vemurafenib
• Emerging drug resistancy
• Reccurence of aggressive tumors
12
13. Tumor tissue/biomarker heterogeneity
• BRAFV600D/E is driving mutation
• However, also no BRAFV600D/E
mutation found in regions of
primary melanomas
• Molecular heterogeneity in
diseased tissue
• Biomarker levels in tissue vary
• Biomarker levels in body fluids
will vary
• Major challenge for
(companion) diagnostics
{Source: Yancovitz, PLoS One 2012}
13
14. ‘Complicating’ factors in oncology therapy
Source: 11 Sept 2013 @de Volkskrant
• Biological clock
• Smoking
• Pharma-Nutrition
• Drug-drug interaction
• Alternative medicine
• Genetic factors
• …
Interview with Prof Ron Matthijssen, ErasmusMC, Rotterdam
14
16. Systems view on metabolic health and disease
β-cell
Pathology
gluc
Risk factor
{Source: Ben van Ommen, TNO}
Visceral
adiposity
LDL elevated
Glucose toxicity
Fatty liver
Gut
inflammation
endothelial inflammation
systemic Insulin resistance
Systemic inflammation
Hepatic IR
Adipose IR
Muscle metabolic inflexibility
adipose
inflammation
Microvascular
damage
Myocardial infactions
Heart failure
Cardiac dysfunction
Brain
disorders
Nephropathy
Atherosclerosis
β-cell failure
High cholesterol
High glucose
Hypertension
dyslipidemia
ectopic
lipid overload
Hepatic inflammation
Stroke
IBD
fibrosis
Retinopathy
Chronic Stress
Disruption circadian rhythm
Parasympathetic
tone
Sympathetic arousal
Gut activity
Inflammatory
response
Adrenalin
Heart rate
Heart rate variability
High cortisol
α-amylase
16
17. Systems view on metabolic health and disease
β-cell Pathology
gluc Risk factor
Visceral
adiposity
LDL elevated
Glucose toxicity
Fatty liver
Gut
inflammation
endothelial
inflammation
systemic
Insulin resistance
Systemic
inflammation
Hepatic IR
Adipose IR
Muscle metabolic
inflexibility
adipose
inflammation
Microvascular
damage
Myocardial
infactions
Heart
failure
Cardiac
dysfunction
Brain
disorders
Nephropathy
Atherosclerosis
β-cell failure
High cholesterol
High glucose
Hypertension
dyslipidemia
ectopic
lipid overload
Hepatic
inflammation
Stroke
IBD
fibrosis
Retinopathy
Chronic Stress
Disruption
circadian rhythm
Parasympathetic
tone
Sympathetic
arousal
Gut
activity
Inflammatory
response
Adrenalin
Heart rate
Heart rate
variability
High cortisol
α-amylase
{Nakatsuji, Metabolism 2009}
17
18. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Systems view on metabolic health and disease
β-cell
Pathology
gluc
Risk factor
therapy
Visceral adiposity
LDL elevated
Glucose toxicity
Fatty liver
Gut inflammation
endothelial inflammation
systemic Insulin resistance
Systemic
inflammation
Hepatic IR
Adipose IR
Muscle metabolic
inflexibility
adipose
inflammation
Microvascular damage
Myocardial infactions
Heart failure
Cardiac
dysfunction
Brain disorders
Nephropathy
Atherosclerosis
β-cell failure
High cholesterol
High glucose
Hypertension
dyslipidemia
ectopic lipid overload
Hepatic
inflammation
Stroke
IBD
fibrosis
Retinopathy
Physical inactivity
Caloric excess
Chronic Stress
Disruption
circadian rhythm
Parasympathetic
tone
Sympathetic
arousal
Worrying
Hurrying
Endorphins
Gut
activity
Sweet & fat foods
Sleep disturbance
Inflammatory
response
Adrenalin
Fear
Challenge stress
Heart rate
Heart rate
variability
High cortisol
α-amylase
Lipids, alcohol, fructose
Carnitine, choline
Stannols, fibre
Low glycemic index
Epicathechins
Anthocyanins
Soy
Quercetin, Se, Zn, …
Metformin
Vioxx
Salicylate
LXR agonist
Fenofibrate
Rosiglitazone
Pioglitazone
Sitagliptin
Glibenclamide
Atorvastatin
Omega3-fatty acids
Pharma
Nutrition
Lifestyle
18
19. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Challenging metabolic equilibrium by Pharma-Nutrition
Age-matched “healthy” control group
t=16 w (sampling)
t=9 w
t=0
Induction of Diabetes
intervention period
High-fat (HF) diet
High-fat diet “diseased” control group
Nutrition/Life style switch
HF + Drug 1
HF + Drug 2
HF + Drug 3
….
HF + Drug 10
19
20. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
clinical chemistry
System networks
Metabolome
Transcriptome
fluxes
Analysis: high throughput, multi organ, multi level High-end data mining and warehousing
Extensive histological and molecular phenotyping
20
21. TNO’s applied biomarker tool box
Widely used preclinical translational models
Pharma, nutrition and chemical industry, academia
Focus on etiology of disease and mechanism of action
Human studies
Experimental medicine through CRO’s
Microdosing
Validated analytical platforms
Metabolomics profiling and targeted analysis, with focus on
lipids, ceramids, cannabinoides
Genomics, transcriptomics, proteomics and imaging through
a wide network of selected partners
Clinical chemistry
Data analysis
Network biology for mechanistic understanding
Multiparameter statistics and chemometrics
PK/PD translational modelling
Comprehensive system dynamics modelling
Biomarker expertise
Best practise strategies and approaches
A wide network with biomarker academia and industry
Metabolic Syndrome
• Atherosclerosis
• Diabetes
• Obesity
• Vascular inflammation
• NASH, fibrosis
21
22. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Effects on total adipose tissue weight
Full reversal of obese phenotype by Nutrition switch, not by all drug treatments
T0901317 (LXR agonist) also reverses obese phenotype
22
23. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Effects on atherosclerosis
Still increased atherosclerosis in Nutrition switch group
T0901317 (LXR agonist) strongly induces atherosclerosis
23
24. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
{Nolan, Lancet 2011}
A sure need for systems medicine
•Multiple interactions and flexibilities in human system (tissues, cells, proteins)
•Blocking one pathway will shift equilibrium and create new problems
•System medicine approach needed for maximal effect
•High value of biomarkers but how to translate to combination therapy?
•Pharma-Nutrition?
24
25. EC DG for Research and Innovation
Alain van Gool
Brussels, 11 Sept 2012
Relating tissue pharmacology – biomarker - therapy
25
26. Translating knowledge to field labs
1. Implementation-plan ‘Personalized diagnosis of (pre)diabetic and their lifestyle treatment in Dutch Health care’.
2.Use of Oral Glucose Tolerance Test as a stratification biomarker for (pre)diabetic patients
3. Advice a tailored treatment (lifestyle and/or medical)
4. Monitor added value of stratification
5. Communicate results and lessons learned
Being implemented in
1st line care
(region Hillegom,
Netherlands)
Alliance “Expedition Sustainable Care, starting with diabetes”
27. Year 1
Applying lessons learned across fields
e.g. System Biology @TNO
Year 2
Year 3
28. Personalized interventions by Pharma-Nutrition
Ongoing: Shared Innovation Programs through public-private consortia
Higher efficacy / less side effects
28
30. Biomarkers in Personalized Healthcare
an evolving role
• From only diagnosis
• To Translational Medicine
• To Personalized/Stratified/Precision Medicine
• To Personalized Healthcare
• To Person-centered Health(care)
30
31. Personalized Healthcare, more than pathways only
Source: Barabási 2007 NEJM 357; 4}
• People are different
• Different networks and influences
• Different risk factors
• Different preferences
31
33. A changing world: Personalized Medicine@ USA
“The term "personalized
medicine" is often described as
providing "the right patient with
the right drug at the right dose at
the right time."
More broadly, "personalized
medicine" may be thought of as
the tailoring of medical treatment
to the individual characteristics,
needs, and preferences of a
patient during all stages of care,
including prevention, diagnosis,
treatment, and follow-up.”
(FDA, October 2013)
33
34. A changing world: Personalized Medicine @Europe
European Science Foundation
30 Nov 2012
Innovative Medicine Initiative 2
8 July 2013
EC Horizon2020
10 Dec 2013
34
35. Most important in Personalized Healthcare:
Include the patient as partner
35
36. Patient
Radboud
Personalized Healthcare
A significant impact
on healthcare
Molecule
Population
Personalized Healthcare @ Radboud university medical
center
36
37. Personalized Healthcare @ Radboudumc
People are different Stratification by multilevel diagnosis
+
Patient’s preference of treatment
Exchange experiences in
care communities
Select personalized therapy
Population
Man
Molecule
37
41. Human
samples
Plasma, CSF (urine)
Controls vs. patient
QTOF Mass Spectrometry
- Reverse phase liquid chromatography
- Positive and negative mode
- Features
XCMS
Alignment
Peak comparison
> 10,000 Features
Personalized metabolic diagnostics
Xanthine Uric acid
41
Full metabolite profile:
Highly suspected of
xanthinuria
42. Proteomics Glycomics Metabolomics
• Mass spectrometry – NMR based, 20 dedicated fte, + guest scientists
• Part of diagnostic laboratory (Department of Laboratory Medicine)
• Close interaction with Radboudumc scientists and external partners
Radboud Center for Proteomics, Glycomics & Metabolomics
Ron Wevers, Alain van Gool, Leo Kluijtmans, Dirk Lefeber et al
Research Biomarkers Diagnostics
43. Research Biomarkers Diagnostics
Integrated Translational Research and Diagnostic Laboratory, 200 fte, yearly budget ~ 28M
euro. Close interaction with Radboudumc scientists and external partners
Please visit: www.laboratorymedicine.nl
Specialities:
• Proteomics, glycomics, metabolomics
• Enzymatic assays
• Neurochemistry
• Cellulair immunotherapy
• Immunomonitoring
Areas of disease:
• Metabolic diseases
• Mitochondrial diseases
• Lysosomal /glycosylation disorders
• Neuroscience
• Nefrology
• Iron metabolism
• Autoimmunity
• Immunodeficiency
• Transplantation
In development:
• ~500 Biomarkers
• Early and late stage
• Analytical development
• Clinical validation
Assay formats:
• Immunoassay
• Turbidicity assays
• Flow cytometry
• DNA sequencing
• Mass spectrometry
• Experimental human (-ized)
invitro and invivo models for
inflamation and
immunosuppression
Validated assays*:
• ~ 1000 assays
• 3.000.000 tests/year
Areas of application:
• Personalized healthcare
• Diagnosis
• Prognosis
• Mechanism of disease
• Mechanism of drug action
Department of Laboratory Medicine
*CCKL accreditation/RvA/EFI
44. Genomics
Bioinformatics
Animal
studies Translational
neuroscience
Image-guided
treatment
Imaging
Microscopy
Biobank
Health
economics
Mass
Spectrometry
Radboudumc
Technology
Centers
Investigational
products
Clinical
EHR-based trials
research
Statistics
Human
physiology
Data
stewardship
Molecule
Flow
cytometry
(Aug 2014)
44
45. 45
• Proteins
• Metabolites
• Drugs
• PK-PD • Preclinical
• Clinical
• Behavioural
• Preclinical
• Animal facility
• Systematic review
• Cell analysis
• Sorting
• Pediatric
• Adult
• Phase 1, 2, 3, 4
• Vaccines
• Pharmaceutics
• Radio-isotopes
• Malaria parasites
• Management
• Analysis
• Sharing
• Cloud computing
• DNA
• RNA
• Internal
• External
• HTA
• Evidence-based
surgery
• Field lab
• Statistics
• Biological
• Structural
• Preclinical
• Clinical
• Economic
viability
• Decision
analysis
• Experimental design
• Biostatistical advice
• Electronic Health Records
• Big Data
• Best practice
• In vivo
• Functional
diagnostics
About 200 dedicated people working in 17 Technology Centers, ~1500 users (internal, external), ~130 consortia
www.radboudumc.nl/research/technologycenters/
(Aug 2014)
47. Biomarkers in Personalized Healthcare
• 12 families with liver disease and dilated cardiomyopathy (5-20 years)
• Initial clinical assessment didn’t yield clear cause of symptoms
• Specific sugar loss of serum transferrin identified via glycoproteomics
ChipCube-LC- Q-tof MS
• Outcome 1: Explanation of disease
• Outcome 2: Dietary intervention as succesful personalized therapy
• Outcome 3: Glycoprofile transferrin developed and applied as diagnostic test
• Genetic defect in glycosylation enzyme (PGM1) identified via exome sequencing
{Tegtmeyer et al, NEJM 370;6: 533 (2014)}
Genomics Glycomics Metabolomics
47
48. Need to change development process for Personalized
Healthcare therapies
• Randomized Clinical Trials won’t be good enough (= groups)
• n=1 clinical trial designs needed whereby:
• Multiple monitoring in same person
• Use different types of biodata (molecular, non-molecular)
• Normalize data per individual
• Combine separate data through meta-analysis
• Output:
• Responders vs non-responders
• Tight data per subgroup
• Clear conclusions on therapy
48
49. healthy disease disease +
treatment
Different trial outcomes in Personalized Healthcare
49
100%
Normalisation Subgroups
50. H2020 PHC1 application - L’Homme Machine: Exploiting Industrial Control Techniques for Personalized Health
Partners
Biobanks
Databank
Coordinator: prof Lutgarde Buydens,
51. Biomarkers in Personalized Healthcare
an evolving role
• From only diagnosis
• To Translational Medicine
• To Personalized/Stratified/Precision Medicine
• To Personalized Healthcare
• To Person-centered Health(care)
51
53. The future is nearly there …
53
Personalized advice
Action
Selfmonitor
Cloud
Lifestyle
Nutrition
Pharma
54. Biomarkers in Person-centered Health(care)
Patient
Caregiver
Insurer
Self-monitoring
Patient
Caregiver
Insurer
Participatory
research
Bas Bloem
Marten Munneke
et al
54
Central
data point
55. Biomarkers in Personalized Healthcare
an evolving role
• From only diagnosis
• To Translational Medicine
• To Personalized/Stratified/Precision Medicine
• To Personalized Healthcare
• To Person-centered Health(care)
55
56. However …
Knowledge and Innovation gap:
1. What to measure?
2. How much should it change?
3. What should be the follow-up for me?
56
57. Translation is key in Personalized Healthcare !
Personal profile data
Knowledge
Understanding
Decision
Action
57
58. Translation 1: Data to usable tests
• Imbalance between biomarker discovery, validation and application
• Many more biomarkers discovered than available as diagnostic test
Discovery Clinical
validation/confirmation
Diagnostic
test
Number of
biomarkers
Gap 1
Gap 2
Biomarker Innovation Gap
58
59. Some numbers
Data obtained from Thomson Reuters Integrity Biomarker Module
Eg Biomarkers in time: Prostate cancer
May 2011: 2,231 biomarkers
Nov 2012: 6,562 biomarkers
Oct 2013: 8,358 biomarkers
15 Oct 2014: 10,169 biomarkers with
32,093 biomarker uses
EU: CE marking
USA: LDT, 510(k), PMA
60. Reasons for biomarker innovation gap
• Not one integrated pipeline of biomarker R&D
• Publication pressure towards high impact papers
• Lack of interest and funding for confirmatory biomarker studies
• Hard to organize multi-lab studies
• Biology is complex on organism level
• Data cannot be reproduced
• Bias towards extreme results
• Biomarker variability
• …
{Source: John Ioannidis, JAMA 2011}
{Source: Khusru Asadullah, Nat Rev Drug Disc 2011}
60
61. Way forward: shared innovation network projects
Standardisation, harmonisation,
knowledge sharing needed in:
1. Assay development
2. Clinical validation
61
62. Shared Innovation Network models
(Next Generation Life Science)
(Source: Model TNO’s Holst Center)
Old New
62
64. Biomarker Development Center (Netherlands)
STW perspectief grant
Biomarker Development Center
Public-private partnership 4 years
Project grant €4.3M of which € 2.2M government,
and € 2.1M industry (€ 0.9M cash/ € 1.2M kind)
Close interactions with:
- Clinicians (biomarker application)
- Industry partners and stakeholders
- Patient stakeholder associations
Open for
partners !
64
65. Translation 2: Science to patient
“I’m afraid you’re
suffering from an
increased IL-1β and
an aberrant miR843
expression”
Adapted from:
65
?
67. Personalized Health(care) model
Homeostasis Allostasis Disease
Time
Disease
Health
Personalized
Intervention
of patients-like-me
Big Data
Risk profiles
of persons-like-me
Molecular
Non-molecular
Environment
…
Personal profile
Selfmonitoring
Adapted from Jan van der Greef (2013)
67
68. Person-centered Health(care)
Ways forward:
• Patients included
• Participation + collaboration
• Personal profiles
• System biology
• Health informatics
• Personal preferences
• Personalized therapies in
Lifestyle + Nutrition + Pharma
68
69. Acknowledgements
Lucien Engelen
Jan Kremer
Paul Smits
Maroeska Rovers
Nathalie Bovy
Ron Wevers
Jolein Gloerich
Hans Wessels
Dirk Lefeber
Leo Kluijtmans
Bas Bloem
Marten Munneke
and others
Lutgarde Buydens
Jasper Engel
Jeroen Jansen
Geert Postma
and others
Members of the
Radboud umc Personalized Healthcare Taskforce (2013)
Radboud umc Technology Centers (2014)
alain.vangool@tno.nl
alain.vangool@radboudumc.nl
www.linkedIn.com
Many external collaborators
Jan van der Greef
Ben van Ommen
Peter van Dijken
Bas Kremer
Lars Verschuren
Marijana Radonjic
Thomas Kelder
Robert Kleemann
Suzan Wopereis
Ton Rullmann
William van Dongen
and others
69