Career Development Statement

Danny BenjaminProfessor, Duke University

Grant Review 2001• The proposed research, in my opinion, is weak and not well thought out.

• No discussion is given to the sequencing or timing of these events, which seems a key element in exploring the value of using growth failure to monitor the course of treatment and disease. It is not clear that the proposed analyses will reflect the course of disease in these patients.

• A second major concern is that the proposed prospective study, while providing valuable practical experience for the investigator, adds little to the research aims of the proposal. As described, it is not clear that the proposed analysis will provide useful information on using growth failure to monitor HIV disease progression.

• Unfortunately even if he is able to develop the models he proposes, it is hard to accept the premise that assessments of growth failure will have the requisite precision to be a clinically reliable tool in the parts of the globe where it may be needed. The major significance of this work might be to assist a young clinical investigator to get a leg up on a career in research.

• While this effort may prove to be a useful exercise for a young investigator learning to flex his analytic muscles, its clinical utility may be somewhat limited.

• Finally, he develops the model among American children, whom he acknowledges will not need this tool since testing is available, rather than in Africa where testing costs would be prohibitive. Unfortunately, the course of pediatric HIV disease, and even more tellingly, the normal growth curves of the population may be so distinct from that of American children as to render the model useless. The dramatic difference between Africa and America in the contribution of malnutrition to growth abnormalities would render any comparisons between those sites in regard to the link between growth and ARV failure suspect, at best.

• The details of the recruitment, follow-up and protocols applied to the cohort he will assemble are never provided in sufficient detail to be assessed.

Review 2001 K23

• This application will provide the funding and mentoring necessary to assist a young investigator get started on a research career. The project that he will pursue will teach him valuable lessons in regard to methodology and use of data sets, but the actual significance of the science may not rank as well as the training it will provide.

• Because of the serious concerns about the analytic approach, the utility of this prospective study is unclear, would recommend that it and the research nurse be omitted from the proposal.

Grant Review 2004 U10• PPRU• The application is very responsive to the RFA. • This is a well written and comprehensive application. It describes a very promising

partnership between investigators in Duke University and a parallel group at UNC. • This is an important application which has the capacity to extend the strength of

the PPRU network.• Dr. Benjamin is an MD-PhD who completed a doctorate in 2003 in epidemiology

and will provide important support to the team in population science and biostatistics, while also committing to integrate the PPUR with the Duke Clinical Research Institute. The assembly of this team is, in itself, an ambitious project but the team shows wide scope and considerable expertise in the conduct of collaborative clinical research. There is ample experience in PK/PD analysis and study design.

• Taking the personnel as a whole there exists an extensive knowledge base for the conduct of collaborative clinical research, especially the design and analysis of randomized Phase I-III pediatric drug trials.

Grant Review 2007 R01

• These investigators are outstanding. Included are the principal investigators of almost every clinical trial performed in the field of fluconazole therapy to eradicate or prevent invasive candidiasis in the very low birth weight new born. This is a great strength of the application

• The trial is well conceived and the control of the trial will be handled by professionals from the Duke Clinical Research Institute…. There is much strength for this trial.

• The PI has an extensive track record in the field of managing fungal infections. He has been associated with at least two preliminary trials that have established the hypothesis for this project. He has an extensive CV with over 70 peer-reviewed publications and has extensive experience with successfully completed multi-center clinical trials. He has been a leader in the Neonatal Research Network and in the Pediatric Pharmacology Research Unit.

• The study is extremely well designed by an experienced investigator who has developed a multicenter network for the study. There is significant value of this study as it would help develop a proper treatment guideline. The success and risks are both high for this very expensive project.

• Overall, this is an extremely well crafted study with close to perfect written description of the protocol.

• No major weaknesses in the overall concept and study procedures study could be identified.

• Drs. Benjamin, Wade and Kaufman have conducted the seminal preliminary studies in this field and are best suited to conduct this study. Furthermore, the experience of Dr. Benjamin as an FDA advisor has been of critical help in the design of this study.

What NIH Asks• 6.A. Candidate Information and Career Development Plan• Candidate’s Background:• Describe the candidate's commitment to an academic career in Patient-Oriented

Research (POR. Include a description of all of the candidate's professional responsibilities in the grantee institution and elsewhere and show their relation to the proposed activities on the career award.

• Present evidence of the candidate's ability to interact and collaborate with other scientists.

• Describe prior training and how it relates to the objectives and long-term career plans of the candidate.

• Describe the candidate's research efforts to this point in his/her research career, including any publications, prior research interests and experience.

• Provide evidence of the candidate's potential to develop into an independent investigator.

• Include a statement that the candidate will commit at least 9 person-months (75% of full-time professional effort) to the POR program and related career development activities. The mentor or department chair must agree and provide a statement in the application documenting that this percent of the candidate’s time will be protected.

• 2. Candidate• My overarching career goal is to advance public health by integrating physiology

and pharmacology into approaches for designing, conducting, and interpreting early-phase trials in critically ill children. This approach will enhance our understanding of how critical illness influences drug disposition and action in the developing child. The skills I will acquire through this proposal are essential to accomplish this goal and will enable me to develop a successful career as an independent, extramurally funded clinician scientist bridging critical care medicine and pediatric clinical pharmacology.

• • History of research focused on understanding complex systems. After college, I

spent 3 years conducting ecological research and managing the Aquatic Biology Laboratory at the J.W. Jones Ecological Research Center (Figure 1). My work focused on understanding the complex interactions between the physical environment and its flora and fauna, and led to publications in peer-reviewed journals.1, 2 I subsequently attended medical school at the University of North Carolina at Chapel Hill (UNC) and then completed training in pediatrics and pediatric critical care medicine at Duke University Medical Center. As both a pediatric resident and critical care fellow, I began to explore the complex physiologic derangements of disease in critically ill children.3 In particular, I became interested in extracorporeal life support (ECMO) and the sophisticated modeling necessary to understand the interaction between the child and extracorporeal circuit.

• Clinical pharmacology in critically ill children. During my 1st year as a clinical critical care fellow, I worked closely with my mentor, Dr. Daniel K. Benjamin, Jr., to develop clinical research skills including grant writing, trial design, data management, statistical analysis, and manuscript writing. These efforts resulted in several first-author publications.3-6 Concomitantly, I developed a growing interest in clinical pharmacology with a focus on the impact of ECMO on drug disposition and dosing in critically ill children.

• During my 2nd and 3rd years of fellowship, I focused my research efforts on understanding and describing the complex relationships between child, drug, and the extracorporeal circuit. I am supported in my research by a T32 training grant (5T32HD043029-09), which enabled me to design a clinical trial evaluating the pharmacokinetics (PK) and pharmacodynamics (PD) of fluconazole prophylaxis in children supported with ECMO. I secured Institutional Review Board (IRB) approval from Duke University (#22822), submitted an Investigational New Drug application (IND #108314) to the Food and Drug Administration (FDA), and registered the trial with clinicaltrials.gov (NCT01169402). I also successfully competed for a Thrasher Foundation Early Career Award to complete enrollment of the infant and older cohorts. I recently completed enrollment for the infant cohort, presented these results at a national meeting,7 and published the findings.8 Data from this study will be submitted to the FDA for consideration of amended product labeling. In addition, I collaborated with other investigators to describe the PK and safety of daptomycin,9 moxifloxacin,10 and meropenem11 in critically ill children and described outcomes following sepsis in the intensive care unit.12-14

• In 2011, I joined the Pediatric Trials Network (PTN) team (PI: Benjamin) to gain exposure to senior mentors in clinical pharmacology, several of whom are advisors on this proposal. My specific roles in the PTN are to: 1) work with senior investigators on a protocol to evaluate the PK/PD of methadone in critically ill children; 2) design (with my mentors) the analysis plan of a study describing the PK of clindamycin in obese children; and 3) lead (with my mentors) a pharmaco-epidemiology project to assemble a PK database of drugs used in special populations. Through my involvement in these ongoing projects, I have become familiar with the organizational aspects of clinical investigations and gained an appreciation for the important role of a priori PK modeling and simulation to inform clinical trial design.

• • Advanced training in pharmaceutical sciences. In the 2nd year of my fellowship and concurrent with the work above, I began a PhD program

in pharmaceutical sciences with a concentration in pharmacotherapy and experimental therapeutics at the UNC Eshelman School of Pharmacy. I am currently a trainee in the Duke-UNC Clinical Pharmacology Training Program and have completed the second year of my graduate coursework. Under the guidance of Dr. Kim Brouwer of UNC, I am acquiring skills in clinical pharmacology and advanced PK/PD modeling. With oversight from my mentors, I am currently evaluating the population PK of fluconazole in children supported with ECMO, preliminary results of which are presented in this proposal.

• • In July 2012, I will join the faculty at Duke University Medical Center and Duke Clinical Research Institute (DCRI) as an assistant professor of

pediatrics with appointments in the Divisions of Critical Care Medicine and Quantitative Sciences. I have developed this K23 proposal so that I might continue my career development and, in particular, my continued acquisition of the knowledge and skills needed for an academic career in the field of pediatric clinical pharmacology. This award will enable me to build upon the research foundation I have developed thus far with expert, multi-dimensional mentorship that is second to none. Upon completing the career development and research plan articulated in my K23 proposal, I will be exceptionally well-positioned to transition to an independent investigator of clinical pharmacology in critically ill children.

Tell it Quick

What NIH Asks

• Career Goals and Objectives:• Describe a systematic plan: (1) that shows a logical

progression from prior research and training experiences to the training and research experiences that will occur during the career award period and then to independent investigator status; (2) that justifies the need for further career development to become an independent investigator; and (3) that utilizes the relevant research and educational resources of the institution.

Tell it Quick

• Career Development/Training Activities:• The candidate and the mentor are jointly responsible for the preparation of the career development

plan. A timeline is often helpful. The sponsor/mentor may form an advisory committee to assist with the development of the program of study or to monitor the candidate's progress through the career development program.

• The didactic (if any) and the research aspects of the plan must be designed to develop the necessary knowledge and research skills in scientific areas relevant to the candidate's career goals. The candidate must demonstrate they have received training or will participate in courses such as: data management, epidemiology, study design(including statistics), hypothesis development, drug development, etc., as well as the legal and ethical issues associated with research on human subjects.

• Describe the professional responsibilities/activities including other research projects) beyond the minimum required 75% effort commitment to the K23 award. Explain how these responsibilities/activities will help ensure career progression to achieve independence as an investigator conducting patient-oriented research.

• Training in the Responsible Conduct of Research:• Document prior instruction in or propose plans to receive instruction in the responsible conduct of

research in terms of subject matter and duration of instruction. Applications without plans for instruction in the responsible conduct of research will be considered incomplete

• Although the NIH does not establish specific curricula: conflict of interest, responsible authorship, policies for handling misconduct, policies regarding the use of human and animal subjects, and data management.

• Applicants must follow the application instructions found in PHS 398 Career Development Award Supplemental form Section 7.5.1, and refer to the NIH web site http://www.nih.gov/sigs/bioethics/researchethics.html) for additional guidance.

• 4. Career Development/Training Activities during Mentored Award Period• Outlined below are career development activities that will enable me to become an independent

investigator and leader in the field of pediatric clinical pharmacology. The multidisciplinary educational plan includes training in advanced pharmacology, statistical analysis, clinical trial design, and sophisticated modeling and simulation techniques (Table 2, Figure 2). The didactic coursework, the clinical trial experiences outlined in this application, the research environment at Duke University and the UNC Eshelman School of Pharmacy, and the expert mentoring provided by my internal and external advisory panels will provide an ideal context for my career development. This experience will allow me to develop sophisticated modeling skills that can be applied to the design and implementation of clinical trials in critically ill children (Table 1).

• • 4.1 Advanced coursework in experimental pharmaceutics: Table 2 outlines the coursework completed and

anticipated at the UNC Eshelman School of Pharmacy and the UNC Gillings School of Public Health. • In addition to the didactic coursework, I will present my research at national clinical pharmacology

meetings. I will continue to participate in formal conferences conducted by the Department of Pediatrics, the Division of Pediatric Critical Care, UNC Eshelman School of Pharmacy, and the DCRI. These conferences will include weekly research group meetings at Duke and UNC; pediatric departmental grand rounds; pediatric critical care, Eshelman School of Pharmacy, and DCRI research conferences; monthly research ethics conferences; and departmental faculty research conferences.

CommunicationsPresentation of results, K23 AIMs 1-3Grand rounds (Benjamin)Duke/DCRI research conferences (Benjamin,

Cheifetz)UNC research conferences (Brouwer)National ConferencesWriting course (Gopen)Manuscript preparation (Benjamin, Brouwer)

Ethics and RegulatoryResearch ethics (Duke, UNC-Chapel

Hill)Regulatory training (Benjamin)FDA appointmentIRB and IND training (DCRI)

PharmacologyAnalysis of K23 Aims 1-3PhD in pharmaceutical sciencesEx vivo drug disposition (Brouwer, Cheifetz)PBPK Modeling (Brouwer, Barrett)Drug trial design (Benjamin, Brouwer,

Capparelli, Kearns, Barrett)

Clinical ResearchK23 Aims 2-3Antifungal PK trial (Benjamin)Clinical trial operations and management

(DCRI)Training in epidemiology and biostatistics

(UNC-Chapel Hill)

Kevin Watt, MD

• 4.2 Pharmacology: I will acquire pharmacology skills throughout the duration of the proposal. In the first 2 years of the proposal, my training will focus on acquiring PK/PD modeling skills in the laboratory of Dr. Kim Brouwer in the UNC Eshelman School of Pharmacy as part of my PhD studies. Dr. Brouwer’s expertise in PK modeling using isolated perfused liver studies will translate easily to my studies of antifungal disposition in isolated ex vivo ECMO circuits (AIM 1). By measuring the rate and amount of adsorption of drugs to the isolated ex vivo ECMO circuit, I will generate data that will inform PBPK models in critically ill children on ECMO described in AIMs 2 and 3. I will acquire sophisticated PBPK skills through a combination of structured activities and work with Dr. Jeffrey Barrett, a leader in the emerging field of pediatric pharmacometrics. PBPK models offer advantages over traditional PK modeling in that they are more mechanistic in their orientation and consider organ-specific factors of drug disposition in estimating drug concentrations at the site of action. I will receive formal training in PBPK at the UNC Eshelman School of Pharmacy and at PBPK software modeling workshops. As a graduate student at UNC, I will have access to the expertise in PBPK modeling of the Hamner Institute and will attend trainings in PBPK modeling at the Hamner led by Harvey Clewell and Melvin Anderson. In addition, I will work closely with Dr. Barrett and enhance my skills by spending 2 weeks each year at his Laboratory for Applied PK/PD at the Children’s Hospital of Philadelphia.

• I will develop advanced skills in population PK/PD modeling to optimize antifungal dosing and understand the sources of variability at the population level. I will obtain formal training in population PK/PD methodologies through the Eshelman School of Pharmacy, as well as the advanced software training (NONMEM) required to perform these analyses. I will enhance my skills by meeting monthly with Dr. Edmund Capparelli of the University of California, San Diego (UCSD), who has a joint appointment at the DCRI and spends ~1 week per month at Duke. I will gain experience in designing and implementing pediatric PK studies, designing optimal PK sampling strategies, and modeling population PK and PD data. I will use the population PK/PD methodology as a complement to PBPK models to evaluate adequacy of model predictions.

• • 4.3 Clinical research: Dr. Benjamin will supervise my professional development in clinical research. In the research proposal (AIM 3), I outline prospective PK

trials for which I will be the principal investigator (PI), leading the research team and gaining further expertise in informed consent, data collection, data analysis, and manuscript preparation. In every aspect of this research, I will work closely with Dr. Benjamin and with internationally recognized pediatric pharmacologists and critical care specialists. I will capitalize on my access to the Pediatric Trials Network to learn the operations, data management, and regulatory processes of successful clinical trials. These interactions will allow me to develop a comprehensive understanding of the scientific and practical aspects of organizing and conducting single- and multicenter studies.

• • 4.4 Drug development and regulatory skill set: I will obtain experience in the regulatory process associated with human drug trials. I will submit an IND

application and associated annual reports to the FDA. I will work with the Office of Drug Development to resolve conflicts arising from clinical trials. The K23 mechanism will be instrumental in developing this regulatory skill set because I will be responsible for holding the IND and for reporting to the FDA on the proposed prospective PK study of micafungin outlined in the research plan (AIM 3). I will receive formal training in IND filing and institutional management from the experienced regulatory team at DCRI. I will also gain regulatory experience by becoming a special government employee within the Office of Pediatric Therapeutics at the FDA. I will have dedicated office space, a laptop computer, and access to the electronic file rooms of the FDA in Rockville, MD. I will also work closely with the pharmacometrics group within the Office of Clinical Pharmacology at the FDA—an experience that will add to my education with regard to the evaluation of PK/PD and PBPK models used to support regulatory dossiers and, in particular, the use of data for the purpose of pediatric labeling.

• • 4.5 Communications: I will develop my communication skills by presenting research updates regularly at divisional and departmental grand rounds, DCRI

research conferences, and the Department of Pediatrics research conferences. My primary mentors (Drs. Benjamin, Brouwer) will supervise and provide feedback on my performance during research presentations. To improve my oral presentation skills, I will participate in the communications program offered by the DCRI, which involves recording presentations for later review and feedback. I will also continue to present research studies at national meetings, and I will participate in the Duke-sponsored workshop aimed at improving scientific and manuscript writing skills.

• 4.6 Mentorship team: I have assembled an experienced mentorship team (Figure 3) with extensive clinical research expertise, mastery of sophisticated clinical pharmacology research methods, and a history of successful junior faculty mentorship. The team has collaborated on 8 NIH-sponsored grants and contracts.

• • Primary mentor, Daniel K. Benjamin, Jr., MD, PhD, MPH, professor of pediatrics, Duke University, adjunct professor of pharmacy at UNC, and

associate director of DCRI, the world’s largest academic research organization. Dr. Benjamin is the PI for the NICHD-sponsored PTN (HHSN267200700051C) and for 4 additional federal grants including 2 R01s (5R01FD003519-04, 5R01HD057956-04) and a K24 (5K24HD058735-04) for mentorship. Drs. Benjamin and Brouwer are co-PIs of a joint Duke-UNC Clinical Pharmacology T32 sponsored by NIGMS (1T32GM086330-02). For the past 3 years, I have met weekly with Dr. Benjamin for mentorship on all of my research projects; I will continue to meet weekly with him during the course of this proposal. Working with Dr. Benjamin, I will gain the necessary experience in trial operations and project development for AIMs 1, 2, and 3. In addition, Dr. Benjamin leads a weekly clinical research meeting consisting of faculty, fellows, and medical students participating in clinical research projects at the DCRI. These meetings review progress of current research and planning of abstracts and manuscripts. We also review skills in manuscript writing, statistical analysis, and data management.

• Co-mentor, Kim L. R. Brouwer, PharmD, PhD, the William R. Kenan Jr. Distinguished Professor and chair of the Division of Pharmacotherapy and Experimental Therapeutics at the UNC Eshelman School of Pharmacy. Dr. Brouwer directs an NIH-funded research program in drug transport and PK (5R01GM041935-19, 3R01GM041935-19S1). For the past year, I have established a relationship with Dr. Brouwer through my active participation in her weekly laboratory research meetings. Dr. Brouwer will supervise my dissertation research in PBPK (AIMs 1, 2, and 3). I will meet with her weekly for interpretation of results and instruction in PBPK modeling. Dr. Brouwer has mentored 32 clinical pharmacology/PK/PD research fellows and served as major advisor for 28 doctoral students. She has mentored me during the implementation and analysis of the fluconazole ECMO PK trial. 8

• Ira M. Cheifetz, MD, will serve on my internal advisory committee. He is a professor with tenure at Duke University, division chief of pediatric critical care, and director of the Duke ECMO program, the 4th largest ECMO program in the world. Dr. Cheifetz has extensive experience in ECMO research and is mentoring me in the design of ECMO trials (AIMs 1 and 3). I will meet weekly with him to review my progress. Dr. Cheifetz has mentored me throughout my fellowship in pediatric critical care.

• • The external advisory committee will include members with expertise in pediatric clinical pharmacology and PK/PD modeling. The entire committee

will meet quarterly; 2 of those meetings will be in person at the annual Pediatric Academic Society meeting and at the DCRI. Edmund Capparelli, PharmD, will chair the committee. He is a clinical professor of pediatrics and has broad experience in pediatric pharmacology through 16 years as the director/co-director of the NICHD-supported UCSD Pediatric Pharmacology Research Unit (PPRU) and more recently as the director of the NICHD-sponsored PTN Pharmacometric Core. Dr. Capparelli is an expert in the field of pediatric PK/PD modeling, especially population PK (AIMs 2 and 3). He has a joint appointment as faculty at the DCRI, and half of his effort is dedicated to mentoring fellows and junior faculty. I will meet with Dr. Capparelli monthly at the DCRI. I collaborated with Dr. Capparelli in the fluconazole ECMO PK trial.8 Gregory L. Kearns, PharmD, PhD, is the Marion Merrell Dow/Missouri Chair in Pediatric Medical Research at the University of Missouri-Kansas City and the Children’s Mercy Hospital, where he also serves as the chief scientific officer. He is an international leader in pediatric clinical pharmacology. He serves as director of the PPRU at Children’s Mercy Hospital and as chair for the PTN Clinical Pharmacology Core. He will provide guidance on clinical pharmacology, clinical trial design, and PK/PD analysis. I will meet with Dr. Kearns quarterly. Jeffrey Barrett, PhD, FCP, is a research associate professor of pediatrics and the director of the Laboratory for Applied PK/PD and PPRU within the Division of Clinical Pharmacology and Therapeutics at the Children’s Hospital of Philadelphia. Dr. Barrett has expertise in investigating sources of variation in PK/PD with modeling and simulation strategies to develop rational dosing guidance for children. He will mentor me in PBPK model development and validation (AIMs 2 and 3). In addition to quarterly meetings, I will communicate with him weekly and on an as-needed basis during PBPK model development. I will spend 2 weeks each year at Dr. Barrett’s Laboratory for Applied PK/PD in Philadelphia, where I will be trained in sophisticated PK/PD modeling. I have established a mentorship relationship with Dr. Barrett through my participation in the PTN.

Tell it Quick

Internal Advisory Committee

Weekly Meetings

External Advisory Committee

Monthly/Quarterly Meetings

MentorDaniel K. Benjamin, Jr,

MD, MPH, PhDClinical trials

Co-MentorKim L. R. Brouwer,

PharmD, PhD Pharmacology

Ira M. Cheifetz, MDECMO ex vivo studies

Edmund Capparelli, PharmD

Pediatric PK Modeling

Greg Kearns, PharmD, PhD Pharmacology

PI: Kevin Watt,

MDJeff Barrett, PhD, FCP

Pediatric PBPK

Protected Time, Timeline

Internal Advisory Committee

Weekly Meetings

External Advisory Committee

Monthly/Quarterly MeetingsMentor

Daniel K. Benjamin, Jr, MD, MPH, PhD

Clinical trials

Co-MentorKim L. R. Brouwer,

PharmD, PhD Pharmacology

Ira M. Cheifetz, MDECMO ex vivo studies

Edmund Capparelli, PharmD

Pediatric PK Modeling

Greg Kearns, PharmD, PhD Pharmacology

PI: Kevin Watt,

MD

Jeff Barrett, PhD, FCPPediatric PBPK

CommunicationsPresentation of results, K23 AIMs 1-3Grand rounds (Benjamin)Duke/DCRI research conferences

(Benjamin, Cheifetz)UNC research conferences (Brouwer)

National ConferencesWriting course

(Gopen)Manuscript preparation (Benjamin,

Brouwer)

Ethics and RegulatoryResearch ethics (Duke, UNC-Chapel

Hill)Regulatory training (Benjamin)FDA appointmentIRB and IND training (DCRI)

PharmacologyAnalysis of K23 Aims 1-3PhD in pharmaceutical sciencesEx vivo drug disposition (Brouwer,

Cheifetz)PBPK Modeling (Brouwer, Barrett)Drug trial design (Benjamin, Brouwer,

Capparelli, Kearns, Barrett)

Clinical ResearchK23 Aims 2-3Antifungal PK trial (Benjamin)Clinical trial operations and

management (DCRI)Training in epidemiology and

biostatistics (UNC-Chapel Hill)

Pharmacokinetics of drugs in ECMO8

Ecological Research  Basic coursework-

statistics and epidemiology

Medical School/Residency Faculty

1995-1998 2002-2009 2009-2012 2012-present

Thrasher Early Career Award

Organic matter dynamics in forested wetlands1,2

Fellowship

PhD Pharmaceutical Sciences

Lab management

Clinical pharmacology in critically ill children

Clinical pharmacology research4-6,9-14

Special Circumstances• My overarching career goal is to advance public health by contributing strategies for making more rapid and efficient

improvements to drug safety and dosing in infants. To make a successful shift of career focus from neonatal epidemiology to neonatal clinical pharmacology, I will need the protected time and new research skills provided by this career development award. These new skills in neonatal pharmacology will enable me to perform rigorous, independent, extramurally funded research.

• I attended the University of Virginia Medical School where Dr. Daniel K. Benjamin, Jr., then a pediatric resident, encouraged me to pursue a pediatric residency. After graduating at the top of my class at the University of Virginia, I completed a pediatric residency and neonatal-perinatal fellowship at The University of North Carolina at Chapel Hill (UNC). During fellowship, I completed a Master’s of Public Health in Epidemiology at UNC. I then accepted a faculty appointment at UNC in the Division of Neonatal/Perinatal Medicine. My first five years on faculty included two clinical years in the NICU and three research years during which I completed and published 13 hypothesis driven, peer-reviewed, clinically focused research projects all of which facilitated my developing skills in biostatistics and epidemiology. In 2009, I became the UNC satellite site PI of the NICHD Neonatal Research Network (Duke is primary site, Goldberg, PI).

• My interest in clinical pharmacology began in 2006, when my division chief, Dr. Carl Bose, became the PI for an industry funded Phase II safety trial of a synthetic surfactant and asked me to be the site PI at UNC. I observed how little was known about appropriate drug dosing for infants and realized that I had substantial deficits in my knowledge of pharmacokinetics/pharmacodynamics (PK/PD) and drug development.

• Dr. Benjamin as mentor and Duke/UNC collaboration: The Duke and UNC campuses are only 9 miles apart; this proximity has allowed me to maintain contact with Dr. Benjamin since medical school. While I was a fellow in neonatology and an epidemiology student at UNC, Dr. Benjamin was on the faculty at Duke and completing a PhD in epidemiology at UNC. Dr. Benjamin now has a joint appointment at the School of Pharmacy at UNC where I have collaborated with him on 6 NIH and industry-sponsored clinical pharmacology projects and three manuscripts, including projects completed as part of the NICHD-sponsored Pediatric Pharmacology Research Unit (PPRU, PI Benjamin). In 2007, I joined his team conducting the NICHD-sponsored trial evaluating the PK of meropenem in young infants (HHSN267200700051C; PI: Benjamin). I participated as a member of the Safety and Steering Committees. Through my involvement in this study, I became familiar with the organizational aspects of clinical studies and gained an appreciation for the important role of a priori PK modeling in clinical trial design.

• During the past three years, I developed a growing interest in pediatric drug development but realized that in order to master the skills required for research in this area, I needed more experience with drug development and formal training in pharmaceutical sciences. To gain clinical experience with drug development, I began working with Dr. Benjamin in his ongoing NICHD-funded pivotal trial of fluconazole in infants to increase my understanding of issues related to PK/PD. This will form the platform for AIM 1 of the proposed research for which I will first develop skills in PK/PD and predict optimal dosing and sampling times of fluconazole. I will validate these predictions in a dual center fluconazole PK trial in infants in AIM 2. I will use the knowledge from AIMs 1 and 2 for AIM 3: to design and conduct a multi-site PK study of rifampin.

Other Thoughts

• Mind of reviewer• Sit in on reviews• Review work in the group• Ice Cream