Pharmacometrics is the science of using mathematical and statistical methods to characterize and predict the pharmacokinetic and pharmacodynamic behavior of drugs. It aims to improve decision making in drug development and pharmacotherapy. Pharmacometric models integrate pharmacokinetic and pharmacodynamic models to describe the relationship between drug concentration, effect, and patient characteristics. Population pharmacometric modeling is useful for characterizing variability in these parameters between individuals.
Genetic polymorphism in drug transport and drug targets.pavithra vinayak
Genetic polymorphism in drug transport and targets.--pharmacogenetics
DRUG TRANSPORTER
Two types of transporter :
•ATP binding Cassette (ABC) – Found in ABCB, ABCD and ABCG family. Associated with multidrug resistance (MDR) of tumor cells causing treatment failure in cancer.
•Solute Carrier (SLC) – Transport varieties of solute include both charged or uncharged
P-glycoprotein
• ATP binding cassette subfamily B member- 1 (ABCB 1)
• Multidrug resistance protein 1 (MDR1)
• Transport various molecules, including xenobiotic, across cell membrane
• Extensively distributed and expressed throughout the body
Mechanism of Pglycoprotein
Substrate bind to P-gp form the inner leaflet of the membrane
ATP binds at the inner side of the protein
ATP is hydrolyzed to produce ADP and energy
Genetic polymorphism in drug transport and drug targets.pavithra vinayak
Genetic polymorphism in drug transport and targets.--pharmacogenetics
DRUG TRANSPORTER
Two types of transporter :
•ATP binding Cassette (ABC) – Found in ABCB, ABCD and ABCG family. Associated with multidrug resistance (MDR) of tumor cells causing treatment failure in cancer.
•Solute Carrier (SLC) – Transport varieties of solute include both charged or uncharged
P-glycoprotein
• ATP binding cassette subfamily B member- 1 (ABCB 1)
• Multidrug resistance protein 1 (MDR1)
• Transport various molecules, including xenobiotic, across cell membrane
• Extensively distributed and expressed throughout the body
Mechanism of Pglycoprotein
Substrate bind to P-gp form the inner leaflet of the membrane
ATP binds at the inner side of the protein
ATP is hydrolyzed to produce ADP and energy
Definition and scope of Pharmacoepidemiology ABUBAKRANSARI2
In these slides I shared the information of definition and scope of pharmacoepidemiology. Types of studies - cohort studies, cross-sectional studies etc.
breif notes on what is pharmacoepidemiology, why do we need pharmacoepidemiology, whats is its aim and its main applications, advantages and disadvantages
Toxicological Approach to Drug DiscoverySuhas Reddy C
For better understanding of students. This will give you a detailed explanation of Toxicological approach. Contact me through comment section if you need any assistance in understating
Population pharmacokinetics is the study of the sources and correlates of variability in drug concentrations among individuals who are the target patient population receiving clinically relevant doses of a drug of interest
Bayesian theory in population pharmacokinetics--
1) INTRODUCTION TO BAYESIAN THEORY
2)BAYESIAN PROBABILITY TO DOSING OF DRUGS
3)APPLICATIONS AND USES OF BAYESIAN THEORY IN APPLIED PHARMACOKINETICS:
therapeutic drug monitoring and clinical pharmacokinetics-fifth pharm d notes
conversion from INTRAVENOUS TO ORAL DOSING----- design of dosage regimenpavithra vinayak
conversion from INTRAVENOUS TO ORAL DOSING----- TYPES OF IV TO PO THERAPY CONVERSIONS: MEDICATIONS INCLUDED IN AN IV TO PO CONVERSION PROGRAM: SELECTION OF PATIENTS FOR IV TO PO THERAPY CONVERSION: design of dosage regimen--clinical pharmacokinetics and therapeutic drug monitoring-- fifth pharm D notes
Nomograms and tabulations in design of dosage regimens pavithra vinayak
Nomograms and tabulations in the design of dosage regimens --- NOMOGRAM IN UREMIC PATIENTS: NOMOGRAM FOR RELATIONSHIP BETWEEN CREATININE CLEARANCE AND ELIMINATION RATE CONSTANT FOR FOUR DRUGS clinical pharmacokinetics and therapeutic drug monitoring ---fifth PharmD notes
Pharmacological Approach to Drug DiscoverySuhas Reddy C
For better understanding of students. This will give you a detailed explanation of Pharmacological approach. Contact me through comment section if you need any assistance in understating
Spontenous adr reporting in india
PASSIVE survillence system, data assement
data aciqsition, data interpretation, what all information required in ADR form, WHEN TO REPORT
BLUE CARD,YELLOW CARD, WHO CODES
The presentation gives you a bird eye's view regarding basics of PK-PD modeling, its applications, types, limitations and various softwares used for the same.
Definition and scope of Pharmacoepidemiology ABUBAKRANSARI2
In these slides I shared the information of definition and scope of pharmacoepidemiology. Types of studies - cohort studies, cross-sectional studies etc.
breif notes on what is pharmacoepidemiology, why do we need pharmacoepidemiology, whats is its aim and its main applications, advantages and disadvantages
Toxicological Approach to Drug DiscoverySuhas Reddy C
For better understanding of students. This will give you a detailed explanation of Toxicological approach. Contact me through comment section if you need any assistance in understating
Population pharmacokinetics is the study of the sources and correlates of variability in drug concentrations among individuals who are the target patient population receiving clinically relevant doses of a drug of interest
Bayesian theory in population pharmacokinetics--
1) INTRODUCTION TO BAYESIAN THEORY
2)BAYESIAN PROBABILITY TO DOSING OF DRUGS
3)APPLICATIONS AND USES OF BAYESIAN THEORY IN APPLIED PHARMACOKINETICS:
therapeutic drug monitoring and clinical pharmacokinetics-fifth pharm d notes
conversion from INTRAVENOUS TO ORAL DOSING----- design of dosage regimenpavithra vinayak
conversion from INTRAVENOUS TO ORAL DOSING----- TYPES OF IV TO PO THERAPY CONVERSIONS: MEDICATIONS INCLUDED IN AN IV TO PO CONVERSION PROGRAM: SELECTION OF PATIENTS FOR IV TO PO THERAPY CONVERSION: design of dosage regimen--clinical pharmacokinetics and therapeutic drug monitoring-- fifth pharm D notes
Nomograms and tabulations in design of dosage regimens pavithra vinayak
Nomograms and tabulations in the design of dosage regimens --- NOMOGRAM IN UREMIC PATIENTS: NOMOGRAM FOR RELATIONSHIP BETWEEN CREATININE CLEARANCE AND ELIMINATION RATE CONSTANT FOR FOUR DRUGS clinical pharmacokinetics and therapeutic drug monitoring ---fifth PharmD notes
Pharmacological Approach to Drug DiscoverySuhas Reddy C
For better understanding of students. This will give you a detailed explanation of Pharmacological approach. Contact me through comment section if you need any assistance in understating
Spontenous adr reporting in india
PASSIVE survillence system, data assement
data aciqsition, data interpretation, what all information required in ADR form, WHEN TO REPORT
BLUE CARD,YELLOW CARD, WHO CODES
The presentation gives you a bird eye's view regarding basics of PK-PD modeling, its applications, types, limitations and various softwares used for the same.
Modelo de UDI "Nos vamos de visita cultural" 1º ESOalvaroge
El principal producto esperado, objeto de desarrollo de esta unidad integrada es la participación activa del alumnado desde un enfoque multidisciplinar que ponga de manifiesto la adquisición de las competencias clave a través de un proyecto de guía cultural de su ciudad que se contextualiza con el de principio de la etapa pero que bien podría servir como fuente de aprendizaje para situaciones futuras en la vida del alumnado.
PAREXEL Early Phase Clinical Research Services experts discuss developing trends in drug development including adaptive trials design, real-world data and biomarkers.
Drug discovery is a
process which aims
at identifying a
compound
therapeutically useful
in curing and treating
disease
Target identification is process of
identifying the direct molecular
target(protein, nucleic acid, or
small molecule).
Identifying the biological of the
disease and the potential targets
for involvement ,is the first step in
the discovery of a medicine
Regulatory consideration for biosimilars by fdaGopal Agrawal
Need for biosimilars
First to approve guidelines for biosimilars
Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product (as per FDA)
Review on Bioanalytical Method Development in Human Plasmaijtsrd
Bioanalytical methods are widely used to quantitate drugs and their metabolites in plasma matrices and this method are applied to study in the areas of human clinical and nonhuman study. Bioanalytical methods employed for the quantitative estimation of drugs and their metabolites plays an important role in estimation and interpretation of bioequivalence, pharmacokinetic, and toxicokinetic studies. The major bioanalytical role is method development, method validation, and sample analysis. Techniques such as high pressure liquid chromatography HPLC and liquid chromatography coupled with double mass spectrometry LCMS MS can be used for bioanalytical studies. Mayuri Gavhane | Dr. Ravindra Patil | Tejaswini Kande "Review on Bioanalytical Method Development in Human Plasma" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-6 | Issue-7 , December 2022, URL: https://www.ijtsrd.com/papers/ijtsrd52578.pdf Paper URL: https://www.ijtsrd.com/chemistry/analytical-chemistry/52578/review-on-bioanalytical-method-development-in-human-plasma/mayuri-gavhane
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.
The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
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
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.
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.
CRISPR-Cas9, a revolutionary gene-editing tool, holds immense potential to reshape medicine, agriculture, and our understanding of life. But like any powerful tool, it comes with ethical considerations.
Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
The Promise: CRISPR offers exciting possibilities:
Gene Therapy: Correcting genetic diseases like cystic fibrosis.
Agriculture: Engineering crops resistant to pests and harsh environments.
Research: Studying gene function to unlock new knowledge.
The Peril: Ethical concerns demand attention:
Off-target Effects: Unintended DNA edits can have unforeseen consequences.
Eugenics: Misusing CRISPR for designer babies raises social and ethical questions.
Equity: High costs could limit access to this potentially life-saving technology.
The Path Forward: Responsible development is crucial:
International Collaboration: Clear guidelines are needed for research and human trials.
Public Education: Open discussions ensure informed decisions about CRISPR.
Prioritize Safety and Ethics: Safety and ethical principles must be paramount.
CRISPR offers a powerful tool for a better future, but responsible development and addressing ethical concerns are essential. By prioritizing safety, fostering open dialogue, and ensuring equitable access, we can harness CRISPR's power for the benefit of all. (2998 characters)
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.
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.
2. INTRODUCTION
Pharmacometrics- “measuring pharmacology”
Defined as science of quantitative pharmacology
Relationship between
Exposure – Pharmacokinetics
Response – Pharmacodynamics
Both desired and undesired effects
Individual patient characteristics
3. HISTORY
Pharmacometrics first appeared in the literature in
1982 in the Journal of Pharmacokinetics and
Biopharmaceutics
Pharmacokinetics : F. H. Dost in 1953
Pharmacodynamics : Dungilson in 1848
Derendorf et al.
4. DEFINITION
Science of developing and applying mathematical
and statistical methods to:
a. Characterize, understand and predict a drug’s
pharmacokinetic and pharmacodynamic behavior
b. Quantify uncertainty of information about that
behavior
c. Rationalize data-driven decision making in the
drug development process & pharmacotherapy
5. FDA DEFINITION
Pharmacometrics is an emerging science
Defined as the science that quantifies drug, disease
and trial information to aid efficient drug
development and/or regulatory decisions
6. PHARMACOMETRICS STAFF
Multidisciplinary team consisting of :
Quantitative clinical pharmacologists
Statisticians
Engineers
Data management experts
Clinicians
7. OBJECTIVES OF PHARMACOMETRIC WORK:
1. Primary focus :decision to approve & label the drug
product
2. Provides advice on trial design decisions
3. Research is conducted to create new knowledge basis o
n the unique data & literature -
to inform better regulatory and drug development
decisions
8. CORNERSTONE OF PHARMACOMETRICS
MODELING refers to the development of a
mathematical representation of an entity, system
or process.
PM model will improve both drug development and
support rational pharmacotherapy.
SIMULATION refers to the procedure of solving
the mathematical equations on a computer that
resulted from model development.
To provide a convincing objective evidence of a
proposed study design.
9. TYPES OF MODELS :
1. Drug models
Typical focus of PM
Referred as PK/PD relationship, concentration-effect,
dose-response
2. Disease models
describe the relationship between biomarkers and
clinical outcomes, time course & placebo
3. Trial models
describe the inclusion/exclusion criteria, patient dis-
continuation and adherence.
10. WHAT IS PK/PD MODELING
PK/PD modeling is a scientific mathematical tool
which integrates PK model to that of PD model.
PK model - describes the time course of drug
concentration in the plasma or blood.
PD model - describes the relationship between drug
concentration at site of action & effect.
Result is summation of Pharmacodynamics and
pharmacokinetics effect.
11. POPULATION PK/PD MODELLING
This includes the search for covariates such as patient weight,
age, renal function & disease status which contribute to
interindividual variability, affecting PK/PD relationship.
It is a useful tool during drug development.
OBJECTIVE : Characterisation of interindividual variability
in PK/PD parameters.
The detection and quantification of covariate effects may
influence the dosage regimen design.
12. BIOMARKERS
NIH (National Institute of Health) defines biomarkers as
an indicator of a biological state.
It is a characteristic that is measured and evaluated as an
indicator of normal biological processes, pathogenic
processes or pharmacologic responses to a therapeutic
intervention.
Detection of biomarker
Quantitative
a link between quantity of the marker and disease .
Qualitative
a link between existence of a marker and disease.
An Ideal Marker should have great sensitivity, specificity
and accuracy in reflecting total disease burden. A tumor
marker should be prognostic of outcome and treatment.
13. CLASSIFICATION OF BIOMARKERS
ANTECEDENT BIOMARKERS : Identifying the risk of developing
an illness. e.g. amyloidal plaques start forming before the
symptoms
SCREENING BIOMARKERS: Screening for subclinical disease.
E.g. abnormal lipid profile is a screening marker of heart disease.
DIAGNOSTIC BIOMARKERS: Recognizing overt disease. E.g.
Diagnostic kits for various diseases.
STAGING BIOMARKERS : Categorizing disease severity.
PROGNOSTIC BIOMARKERS: Predicting future disease course,
including recurrence and response to therapy and monitoring
efficacy of therapy.
14. APPLICATIONS OF BIOMARKERS
• Use in early-phase clinical trials to establish “proof of
concept”.
• Diagnostic tools for identifying patients with a specific
disease.
• As tools for characterizing or staging disease processes.
• As an indicator of disease progress.
• For predicting and monitoring the clinical response to
therapeutic intervention.
15. CLINICAL TRIAL SIMULATION
Simulation of a clinical trial can provide a
data set that will resemble the results of an
actual trial.
Multiple replications of a clinical trial
simulation can be used to make statistical
inferences
Estimate the power of the trial
Predicting p-value
Estimate the expected % of the population that
should fall within a predefined therapeutic range
16. CLINICAL DRUG DEVELOPMENT:
In clinical drug development, PK/PD modeling and
simulation can potentially impact both internal and
regulatory decisions.
Drug Development process
Discovery (3years)
Preclinical (3.5 years)
Phase 1 (1 year)
Phase 2 (2 years)
Phase 3 (3 years)
Thus it takes a molecule around 12-13 years to come
into market where it further faces the challenge of Phase 4
trials.
17.
18. PHASE 1:
Phase 1 starts with dose escalating studies in normal
volunteers with rigorous sampling. In addition, one may
establish an initial dose–concentration–effect relationship
that offers the opportunity to predict and assess drug
tolerance and safety in early clinical development.
Quantitative dose–concentration–effect relationships
generated from PK/PD modeling in Phase1 can be utilized in
Phase 2 study design.
PK/PD modeling is an important tool in assessing drug-
drug interaction potential.
Dosage form improvements often occur based on the PK
properties of the drug candidate.
19. Phase 2 trials are typically divided into two stages, each with
some specific objectives.
Phase 2A : is to test the efficacy hypothesis of a drug
candidate, demonstrating the proof of concept.
Phase 2B : is to develop the concentration–response
relationship in efficacy and safety by exploring a large
range of doses in the target patient population.
The PK/PD relationship that has evolved from the
preclinical phase up to Phase 2B is used to assist in
designing the Phase 3 trial.
Phase 2:
20. PHASE 3:
OBJECTIVE:
To provide confirmatory evidence that demonstrates
an acceptable benefit/risk in a large target patient
population.
This period provides the ideal condition for final
characterization of the PK/PD in patients as well as for
explaining the sources of interindividual variability in
response, using population PK/PD approaches.
21. NDA REVIEW:
PK/PD modeling plays an important role during the NDA
submission and review phase by integrating information
from the preclinical and development phases.
Existence of a well defined PK/PD model furthermore
enables the reviewer to perform PK/PD simulations for
various scenarios.
This ability helps the reviewer gain a deeper
understanding of the compound and provides a
quantitative basis for dose selection.
Thus, PK/PD modeling can facilitate the NDA review
process and help resolve regulatory issues.
22. POST MARKETING PHASE:
Post-marketing strategy, population modeling
approaches can provide the clinician with relevant
information regarding dose individualization by:
Characterizing the variability associated with PK
and PD.
Identifying subpopulations with special needs.
PHASE 4:
23. TRAIL MODEL
Optimize design of Phase 2 to phase 4 human trials
(set inclusion and exclusion criteria, give statistically
significant results by accounting for variation in
compliance and inter-patient variability.
Help in making in-licensing decisions based on
predictions of effectiveness.
Optimize target selection for a therapeutic indication.
Formulating strategies for competitive differentiation of
novel drugs based on predicted effectiveness in clinical
and post market populations.
24. SOFTWARES USED IN PK/PD MODELING
•WinNonlin
•NONMEM
•XLMEM
•Boomer
• JGuiB (Java Graphic User Interface for Boomer)
•TOPFIT
•ADAPT II
•BIOPAK
•MULTI
25. PHARMACOMETRICS AND
REGULATORY AGENCIES
FDA has promoted the role of pharmacometrics in
the drug approval process
through its approach to review of applications and
by publishing its “guidances.”
FDA has gained expertise in pharmacometrics from
self-training within and by recruitment of new highly
skilled personnel
value of pharmacometrics continues to be
evaluated at the FDA.
26. FDA PHARMACOMETRICS 2020 STRATEGIC G
OALS
Train 20 Pharmacometricians
Technical track
Disease track
Drug development track
Implement 15 Standard Templates
Develop disease specific data & analysis standards
Expect industry to follow
Develop 5 Disease models
Create public disease model library
27. CONTD..
International Harmonization
Share expertise between global regulatory bodies
Integrated Quantitative Clinical Pharmacology
Summary
All NDAs should have exposureresponse analysis
Design by Simulation: 100% Pediatric Written
Requests
Leverage prior knowledge to design Pediatrics
Written Request trials
28. CONCLUSION
Pharmacometrics has improved the effectiveness of the drug
development process.
It is relatively fast and inexpensive as compared to cost of
actual clinical trials.
It can provide insight into both efficacy and cost effectiveness,
even with limited data.
Project team members from various disciplines utilize the CTS
to explore a series of scenarios, from different trial designs, to
alternative ways of analyzing the generated data.
It has great need of improved dosing strategy selection for the
avoidance of adverse events.