Academic Curriculum

Overview

The research fellowship program in Pediatric Clinical Pharmacology at Children's Mercy Kansas City provides didactic education in both translational and clinical research.

The overarching goals of this program are to provide each trainee with:

A firm conceptual understanding of research methods that are considered to represent the fundamentals of pediatric clinical/developmental pharmacology.
Direct application of knowledge, skills and critical abilities to identify problems and design effective plans to conduct the research necessary to solve them.
The ability to effectively communicate through scientific writing and grant proposal development information to be gained and information attained through their research endeavors.
An ability to effectively organize a career development plan that will insure a successful transition to independent research support.
Values consistent with the ethical conduct of science, a commitment to lifelong learning and the education of others as part of a professional career.

Core didactics

Principles of Clinical Pharmacology is a general clinical pharmacology course (30 hr total) sponsored by the NIH Clinical Center. This weekly lecture series covers the fundamentals of clinical pharmacology as a translational scientific discipline which spans the continuum of drug discovery through therapeutic use. Faculty for this course include NIH staff and distinguished scientists from the pharmaceutical industry, FDA and academic institutions. The most recent lectures will be viewed online and the companion text will be purchased for each trainee. Fellows will take a 10-question self-assessment test prepared by the course facilitator) for each lecture and will convene with the facilitator, or a faculty member, to discuss each topic area.

Developmental Pharmacology is covered by the NIH T32 Pediatric Clinical Pharmacology webinar series. This weekly series address the fundamentals of clinical pharmacology, including drug metabolism and transport, assessment of drug effects, pharmacotherapy, and pediatric drug formulations from a pediatric perspective. The course is taught by faculty from leading academic institutions (including Children’s Mercy), the NIH, and the FDA.

Introduction to Pharmacokinetics/Pharmacodynamics over a 3-month time frame, provides trainees with a comprehensive, functional understanding of the processes (physiologic and mathematical) used to quantitate drug disposition (e.g. drug liberation, absorption, distribution, metabolism, excretion) and response.

Applied Pharmacokinetics I and II represent two experiential, trainee-paced courses that introduce fellows to both classical and population-based approaches for analyzing PK/PD data. Applied PK I focuses on bedside or clinical PK applications and is entirely case-based. Applied PK II is also case-based, examining larger PK-PD datasets derived from investigator initiated and industry sponsored studies. Software applications introduced in this course include Kinetica, Phoenix, WinNonLin, NONMEM, and Simcyp.

Survey in Pharmacogenomics provides trainees with a conceptual and factual basis regarding the role of pharmacogenomics as a determinant of drug disposition and action. The course consists of two modules; the first focuses on genomic determinants of PK and PD, the role of pharmacogenomics in pediatric drug development and relevant contemporary bioethical issues, the second provides a comprehensive overview of the tools and technologies that are currently used to support research in the field and contemporary issues in genomic research (e.g. epigenetics, epistasis, applied statistical genetics). This module also introduces trainees to the emerging field of translational bioinformatics where computational and biostatistical methods are integrated to explore genomic data which can define the expression of disease and its response to treatments. Concepts germane to the field such as GWAS and DNA sequence analysis, SNP and haplotype analysis, next-generation DNA sequencing, meta-analysis of “-omics” (genomics, proteomics, metabolomics) data, expression quantitative trait loci analysis and the generation of data-driven hypothesis are covered. The experiential portion of this course will consist of six guided laboratory experiences (3 hr each) intended to provide “hands-on” training in techniques germane to PG (e.g., PCR-RFLP, qPCR, sequencing, microarray). A separate “hands-on” application introduces trainees to commonly used bio-computing tools.

Adverse Drug Reactions occur in 5-10% of children have a documented adverse drug reactions (ADR), and interpretation of ADRs is critical to clinical pharmacology and prescribing decisions. At Children's Mercy, a hospital wide pharmacovigilance program actively identifies and uses a standardize approach to gather clinical data related to the ADR, classify the ADR type and severity, standardize documentation in the electronic medical record and provide education to families and medical teams. All fellows will be expected to participate in the T32 ADR short course, a didactic and interactive course represented by a series of three 1-hour lectures offered over a 3-month period. The course is designed to provide trainees with fundamental, basic instruction on pediatric adverse drug reactions. The goals of the course are to: 1) educate fellows on ADR phenotypes 2) introduce the concept of ADR causality assessment tools 3) provide opportunities for ADR interpretation and documentation in clinical cases 4) practice using national pharmacovigilance datasets (FDA adverse event reporting system, NHS YellowCard system).

Pharmacoepidemiology is a mini-series is intended to provide trainees with a conceptual, working understanding of applied pharmacoepidemiology research from the conceptual (honing pharmacoepidemiological research questions, identifying data sources, and study designs) to the operational (data management, regulatory data compliance, measurement of medication use and outcomes, addressing sources of bias). Course objectives aim to ensure fellows 1) Understand fundamental principles of epidemiologic and statistical methods related to pharmacoepidemiology research; 2) Identify strategies for measuring medication use and outcomes in secondary data sources 3) Recognize potential sources of bias in pharmacoepidemiologic studies and common strategies for minimizing bias, and 4) Evaluate the quality and generalizability of pharmacoepidemiology scientific literature.

Research Study Methods are addressed in a series of two 5-lecture workshops, Qualitative Research Skills (offered in odd years) and Formative Research Skills (offered in even years). Collectively, these courses address; designing qualitative and formative studies, defining interventions, conducting in-depth interviews/focus groups, analyzing data, writing for publication and alternative methods of dissemination, and applying findings to interventions. Nested in these two offerings include attention to reproducibility and rigor, clinical/biological relevance to study design, resource authentication, and faithful and transparent reporting.

Translational Team Science is a workshop intended to introduce trainees to transdisciplinary research with an emphasis on drug and biomarker discovery and development. The format for the course includes 2 full days and 1 half-day with didactic and one-on-one lectures encompassing: The Science of Translation in NCI Cancer Centers; Managing Multidisciplinary, Multiorganizational Teams; Business Plan Development; Intellectual Property Development; Biotech Company Formation; SBIR Programs; Regulator Science; Target to Preclinical Proof of Principle; Role of Chief Medical, Scientific, and Regulatory Officers; Preclinical Proof of Principle to Clinical Proof of Concept; Early Phase Clinical Trial Considerations; Clinical Proof of Concept to NDA; NDA Submission to Launch; and Sales, Marketing, and Distribution. The goals of the course are to: 1) develop trainees understanding of team science, 2) advance trainees understanding of the translation science process, 3) enhance trainees theoretical and practical skills in design and implementation of a multidisciplinary translational project and 4) help trainees discover resources to support their own translational science projects. The workshop will be taught by nationally recognized experts representing all disciplines required to translate laboratory discoveries to the bedside.

Other local instruction

Clinical Pharmacology & Therapeutics Journal and Book Club is a monthly presentation of timely, relevant peer reviewed publications in the field of pediatric clinical pharmacology is delivered in a virtual blackboard style format via Microsoft Yammer. Each month a trainee and a faculty discussant are expected to post/summarize a chosen article, generate discussion topics/polling questions, serve as interactive moderators of discussions, and provide a summary of the discussion at the end of the 2-week review and comment period. The purpose is to facilitate current knowledge acquisition and data interpretation while providing a practicum for teaching communication skills. The virtual format mitigates the challenges of traditional in person journal clubs by 1) increasing broader participation, 2) providing ample time and flexibility to investigate supporting literature, and 3) improving broader dissemination with digitally archived discussions. Twice yearly the journal club will be replaced by a book club designed to take a deeper dive into areas of scientific and professional relevance. Participants will be provided the book 2-3 months in advance and asked to engage in a virtual dialogue about their impressions.

Clinical Pharmacology Case Conference is a weekly conference involving faculty, fellows, residents, students and subspecialists reviews interesting case from the inpatient Clinical Pharmacology consultation service and discusses patients scheduled for the Individualized Personalized Therapeutics clinic. Though open participation is welcome throughout the fellowship, only fellows in their third year are required to participate.

Laboratory Research Conference is a monthly meeting provides an opportunity to review research being conducted in the laboratories of the Division of Clinical Pharmacology. These seminars, jointly presented by faculty, research associates, and fellows, are intended to share information and to solicit comments/recommendations regarding the significance of research findings and hypothesis generation.

Grant Writing Boot Camp. In addition to the 1-on-1 mentorship provided by Clinical Pharmacology faculty, fellows are required to participate in a day-long Boot Camp organized by the GME office. Fellows having completed the course are eligible to apply for competitive, intramural Fellowship Research Awards.

Office of Faculty Development has offerings that fellows can self-select from OFD mini-sessions and half-day workshops that are offered monthly around topics related to developing as a successful faculty member in an academic medical setting. Offerings change on an annual basis but always include information on teaching scholarship, performance improvement, personal and career development.

Advanced degree offerings

Master of Science. All trainees entering the program who do not have a graduate degree (MS or PhD) in a biomedical science have the option to enroll in one of two Master’s programs at KUMC or UMKC. It is anticipated that trainees will spend 2 to 2.5 years completing degree requirements. This extended period may be required to accommodate the schedule for the required core didactic clinical pharmacology offerings from the program at Children's Mercy and the external rotations.

Elective rotations

Simcyp/Certara Corporation
Trainees will initially participate in one of several workshops offered by Certara, followed by an intensive onsite rotation. Using a hands-on approach, this rotation would introduce the trainee to the strategies by which existing in vitro and in vivo data are evaluated for inclusion in modeling tools and involve them in the process of identifying, vetting, and prioritizing data to refine these models. They should leave this rotation with; 1) a solid conceptual understanding of the principles of modeling and simulation along with the strengths and limitations inherent to PBPK-based modeling and simulation tools, 2) the knowledge of how to apply, and validate, PBPK-based modeling and simulation to virtual sets of children for the purposes of clinical trial design, and 3) an introduction on how to explore PBPK-driven approaches to generate hypothesis about drug disposition pathways when existing physiologic data are unavailable.

Office of Clinical Pharmacology, Center for Drug Evaluation and Research, FDA (Gil Burckart, PharmD)
Trainees will have an opportunity to join the Pediatric Clinical Pharmacology group led by Dr. Burckart under the competitive ORISE program. The experience is a 2-month commitment, and activities include review of IND, NDA and Phase II/III Pediatric plans submitted to the FDA with any pediatric studies planned, followed by attendance at the weekly Pediatric Review Committee (PeRC) meetings where the projects are discussed with representatives from the individual Divisions (e.g. GI, Neuro, Onc). Trainees will have the opportunity to work with the Office of Pediatric Clinical Pharmacology to discuss neonatal studies, and pharmacokinetic and pharmacodynamic studies with the specialty divisions. Trainees will be expected to prepare and deliver a presentation to members of the Office of Clinical Pharmacology on topic related to their area of expertise.

Pharmacogenomics KnowledgeBase (Russ Altman, MD, PhD and Teri Klein, PhD)
Under the supervision Drs. Klein and Altman, trainees may elect to spend one month at the Pharmacogenomics Knowledge Base (PharmGKB) at Stanford University. Trainees will be exposed to the curation process that has been developed, as well as the role of PharmGKB in the development of the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. To individualize the experience, the trainees have an opportunity to work on VIP gene summaries or pathways for drug response of interest to them, which are potentially postable on the site and publishable as summaries in Pharmacogenetics & Genomics.

Mayo Clinic Adult Pharmacology (Liewei Wang, MD, PhD and Richard Weinshilboum, MD)
Under the supervision of Drs. Wang and Weinshilboum, co-PIs for Mayo’s Clinical Pharmacology T32 Training Grant (GM08685), trainees have the option of visiting the Mayo Clinic and gaining exposure to specialized, adult focused Clinical Pharmacology experiences that complement and supplement the pediatric training opportunities provided by the local program. The oncology efforts within the Mayo program include cancer therapy and clinical trials as well as the development of anti-tumor agents. Other areas include epidemiology, signal transduction and vaccine research, and specialty-related areas include machine learning-based predictors of antidepressant response, inflammatory bowel disease, neuropharmacology, pharmacology of the vasculature, in addition to drug metabolism and pharmacogenomics from an adult perspective.

Formulary Management
Interested fellows will be introduced to the process of promoting rational and appropriate pediatric medication use through two opportunities. Within the context of a health care delivery organization, fellows will undertake a participatory experience with the institutions Pharmacy & Therapeutics Committee. Fellows will receive an initial didactic session followed by participation in two meetings. Meeting dates will be selected where discussion is anticipated to be centered around the therapeutic class most closely related to the fellow’s medical subspecialty. Fellows that are interested in gaining experience from the perspective of a health care management organization will join Drs. McLaughlin and Wagner at a quarterly meeting of the Advisory Council on Rare Disease and Personalized Medicine for Missouri Health Net Division at the state capital.

Didactic Offerings	Subspecialty Year 2/Clinical Pharmacology Year 1				Subspecialty Year 3/Clinical Pharmacology Year 2				Clinical Instructor/Clinical Pharmacology Year 3
	July-Sept.	Oct.-Dec.	Jan.-March	April-June	July-Sept.	Oct.-Dec.	Jan.-March	April-June	July-Sept.	Oct.-Dec.	Jan.-March	April-June
	NIH Clinical Pharmacology Course (self-study)				NIH T32 Pediatric Clinical Pharmacology (webinar)				NIH T32 Pediatric Clinical Pharmacology (webinar)
		Rxgenetics/Rxgenomics		Rxgenetics II /Rxgenomics		Intro to PK/PD	Applied PK I		Applied PK II		Pharmacoepidemiology
	Research Bioethics		Qualitative Research Skills		IRB Fellowship		Formative Research Skills		Adverse Drug Reactions		Translational Team Science
	Biostatistics Repeating Lecture Series (opt-out w/ enrollment in Masters program)
	Virtual/Book Journal Club
	Children's Mercy Fellows Core Curriculum/GME Workshops/OFD Workshops/Grand Rounds/Academic Scholarship Conference
Academic Development	Identify Mentors	Initiate MC Curriculum		Annual Evaluation		Prepare Grant Submission		Annual Evaluation	Appt. as Clinical Instructor	Complete MS Curriculum	External Rotation	Final Evaluation
	Develop Research Plan	Initiate Research						Prelim Review of Data	Complete Research and Prepare for Presentation		Develop and Submit K23 or K99/00
	Develop Clinical Translational Research Plan	Draft Clinical Protocol	Prepare IRB Submission	Initiate Clinical Protocol								Analyze/Present Clinical Data