Pharmacology
Program Information

Program Information

The expected duration of training is two-years with an optional third-year for selected fellows, and incorporates a core comprehensive training curriculum in the foundations of clinical pharmacology, pharmacogenetics, and pharmacometrics with a focus on individualized pediatric therapeutics. The program will implement a rigorous, highly structured, and mentored clinical scholar program in pharmacology-related research that is broad, cross disciplinary and focused on clinical pharmacology and experimental therapeutics. In addition to participation in the core program curriculum, enrollees will select an academic focus area related to pediatric pharmacology and predictive translational medicine for mentored career training. Current focus areas include clinical and developmental pharmacology, population PK/PD modeling and simulation, pharmacometrics, pediatric clinical trial design, pharmacogenetics and pharmacogenomics, and Bayesian approaches to precision dosing.

Program Content

Fellowship training includes a diverse set of experiences in research, clinical service, program development, teaching/mentorship, and consultation as outlined in the core training elements overview, goals and objectives and sample curriculum.

Mentoring Philosophy

Our training program is highly individualized. Based on dialogue with Program faculty, our training program is tailored to individual interests' and career development needs with respect to the balance of research and clinical care as well as specific content areas of focus. Fellows are expected to take initiative for their individual projects and training program in the context of close and collegial mentorship from faculty and are assigned a primary mentor in their focus area.

Program leaders and mentors are established senior investigators with National Institutes of Health-funded programs in pediatric clinical research. In close collaboration with his or her primary mentor, the program enrollee will focus in a specific area of novel drug development or individualized therapeutics including development of pharmacokinetic/pharmacogenetic assays and analysis, and/or development of biomarker assays for pharmacodynamic measurement and endpoints. It is anticipated that these activities will include a mentored development of a pediatric Phase I/II clinical study as well as training in the development and writing of extramural funding applications (e.g., NIH K-, and R-series grants).

Core Training Elements

Research training courses and curriculum (see sample curricula)

Introduction to Clinical Pharmacokinetics and Population Modeling
Applied Biostatistical and Epidemiological Methods
Good Clinical Practice (GCP)Training
Assortment of Modalities

Laboratory training sequence

Laboratory orientation (pharmacokinetics, pharmacogenetics, and pharmacodynamic/biomarker assay development)
Mentored translational laboratory research project

Clinical training rotations

Therapeutic Drug Monitoring Consultation Service
Genetic Pharmacology Service participation

Integrated Translational Research Program focus areas

Pharmacogenetics/genomics
Pharmacometrics, PK/PD modeling and simulation
Clinical Trial Simulation
Analytical pharmacology, drug metabolism and biomarker studies

The Cincinnati Children's Training Program in Clinical and Developmental Pharmacology includes optional additional elements to satisfy eligibility requirements for certification by the American Board of Clinical Pharmacology, Inc.

Rotations by Year

Year	Research Training Courses	Mentored Laboratory Research	Clinical Research Training Rotations	Total
1	7	4	1	12
2 and 3*	4	4	4	12

*Year 3 is optional and for selected fellows only

Goals and Objectives by Year of Training

YEAR 1

Master fundamentals of clinical pharmacokinetics, pharmacogenetics and biostatistics
Complete Good Clinical Practice (GCP) training
Develop proficiency with standard clinical trials procedures (SOPs), clinical protocol development, IRB submission and active management of Phase I/II clinical trials
Develop a mentored clinical translational Phase I/II research protocol with integrated pharmacokinetics/pharmacogenetics, pharmacodynamics/biomarkers and biostatistics for eventual IRB submission

YEAR 2 (AND OPTIONAL YEAR 3)

Attain proficiency in clinical trials management and procedures
Attain proficiency with biostatistics, literature evaluation, and lecture presentation
Develop in-depth understanding of application of clinical pharmacokinetics and Therapeutic Drug Monitoring (TDM) service
Develop application of clinical pharmacokinetics/pharmacogenetics and pharmacodynamics; potential development of PK and/or PD for clinical trials
Develop a mentored clinical translational Phase I/II research protocol with integrated pharmacokinetics/pharmacogenetics, pharmacodynamics and biostatistics and submit this protocol to the IRB
Clinical research trial submission for e.g. NIH R21 funding
Present abstract (e.g., of preliminary data) at an appropriate national meeting
Prepare/submit publication of own (clinical) research work

Sample Curriculum

Introduction to Clinical Pharmacokinetics and Population Modeling

(Cincinnati Children's Division of Clinical Pharmacology established course sequence)

Clinical Pharmacokinetics Sequence

a.   Introduction to pharmacokinetics
b. Mathematical material
c. One compartment IV bolus
d. Analysis of urine data
e. Intravenous infusion
f.    Routes of drug administration
g. Pharmacokinetics of oral administration
h.   Calculation of bioavailability parameters
i.     Bioavailability studies
j.    Physiological factors affecting oral absorption
k.   Physical-chemical factors affecting oral absorption
l.    Formulation factors
m. Multiple IV bolus dose administration
n.   Multiple oral dose administration
o.   Routes of excretion
p.   Metabolism
q.   Drug distribution
r.    Multi-compartment pharmacokinetic models
s.   Non-compartmental analysis
t.    Non-linear pharmacokinetic models
u.   Non-linear regression analysis of pharmacokinetic data
v.   Clinical applications of pharmacokinetics
w. Therapeutic drug monitoring
x.   Pediatric considerations
y.   Laboratory assignments

Population Modeling Sequence

a.   Introduction to population modeling
b.   Numerical integration
c.   Optimization
d.   Weighting schemes
e.   Software for population modeling – introduction to NONMEM
f.    Selection of the “best” model
g.   Clinical applications of population pharmacokinetic models
h.   Optimal sampling
i.    Bayesian analysis and population modeling
j.    Pharmacodynamic models
k.   Pharmacodynamic and physiologically-based pharmacokinetic models
l.    Principles of pharmacometrics
m. Use of population modeling techniques in clinical trial design and simulation

Applied Biostatistical and Epidemiological Methods

Scientific writing

Basic biostatistics

Clinical trials: biostatistical analyses overview

Clinical trials: trial designs based upon molecularly-targeted endpoints

Clinical trials: sample size determination

Introduction to STATA

Introduction to SAS

Statistical methods in epidemiology

Geographic information systems (GIS)

Analyzing sample survey data

Applied Longitudinal Data Analysis

Practice-based epidemiology

Applied regression analysis

Multiple comparison methods

Nutritional epidemiology

Introduction to microarray analysis

Applied logistic regression

Analysis of experimental data

Environmental epidemiology
Applied survival analysis

Good Clinical Practice (GCP) Training

(University of Cincinnati Program in Clinical Research)

1.Ethics of clinical trials
2.Regulatory issues
3.History, and principles of ICH
4.GMP and GCP
5.International clinical trials
6.IRBs
7.DSMBs
8.Informed consent and HIPAA elements
9.Investigational new drug development
10.Clinical trials implementation
11.CFR Part 312 requirements
12.Study documentation
13.Monitoring
14.Adverse experiences and reporting
15.Data privacy and protection
16.Patient recruitment
17.FDA inspection process/compliance

Modalities

The fellowship training program in Pediatric Clinical and Developmental Pharmacology is designed primarily to address the widely recognized shortage of well-trained pediatric physician scientists to conduct state of the art drug studies in neonates, children and adolescents. Through an assortment of modalities, such as didactic coursework, journal clubs, research rotations, and your own clinical research project, trainees experience the excitement of working at the laboratory-clinic interface and develop skills that prepare them to be independent researchers and mentors, and role models for future generations of pediatric clinical pharmacologists.

Fellow training will encompass a variety of complimentary modalities, including:

Mentored research
More than 75% of the fellowship will be dedicated to conducting clinical research projects
Fellows have a wide spectrum of research opportunities that are focused around a vigorous group of well-funded faculty.

Didactic coursework designed to provide basic skills in pharmacokinetics, pharmacodynamics, PK/PD modeling, and pharmacogenetics, clinical trial design, as well as ethical issues in clinical research:

Bi-monthly seminars and journal clubs focusing on the discipline of Clinical Pharmacology
Hands-on training in pharmacokinetic analysis
Clinical and Genetic Pharmacology Consult service
Therapeutic Drug Monitoring and Clinical Consultation
Shadowing in decision-making committees (e.g., Pharmacy and Therapeutics Committee, Institution Review Board)

Areas of particular research strength at Cincinnati Children's include:

Pharmacogenetic influences on pharmacokinetics and inter-individual response to drug therapy
Population pharmacokinetics and modeling
Clinical trial design and clinical trial simulation
Therapeutic Drug Management (TDM) and pharmacokinetically guided individualized therapeutics
Drug interactions based on human drug metabolism
Many therapeutic areas: organ transplantation, cancer, neurology, rheumatology, drug therapy during renal replacement therapy and psychiatry.

PharmacologyProgram Information