The training program will be individualized based on the needs and experience of incoming Heme Scholars. During the first year, Scholars will pursue a Clinical Core Curriculum that involves inpatient and outpatient care of patients with specific non-malignant hematologic disorders. The Didactic Clinical Research Curriculum will teach the skills necessary for independent and ethical clinical research, with the option to earn a Masters of Science degree in Clinical Investigation. This curriculum draws on the strengths of Clinical Research Training Center (CRTC), and other Washington University degree granting programs in biostatistics, and epidemiology.
Clinical Core Curriculum
The one-year clinical core curriculum will expose Scholars to the management of patients with non-hematologic blood diseases in outpatient and inpatient settings, emphasizing the opportunities in the three selected major fields of ongoing clinical research at WUMC. By its very nature, hematology is multidisciplinary because hematologic diseases frequently affect multiple organ systems. Consequently, the care of inpatients and outpatients with hematologic diseases will necessarily involve specialties such as neurology, pulmonology, immunology, urology, neuroimaging, and nephrology through consultation.
The curriculum will be individualized and modified based on the experience, credentials, and abilities of Scholars. For example, Scholars entering directly after residency training could participate in an intensive year of clinical training with at least 8 months of clinical rotations, several clinic experiences, and a continuing clinic. In contrast, Scholars entering from later years of fellowship training or soon after faculty appointment - who may already be eligible for (Adult) Hematology, Pediatric Hematology-Oncology, or other relevant board examinations - would have a more limited schedule of clinical rotations targeted to their field of clinical research concentration. These Scholars may elect additional career development and training in areas of interest, such as bioinformatics, pharmacogenomics, epidemiologic methods, advanced biostatistics, survey research, or nutrition. Some of the relevant WUMC courses in these subject areas are listed.
To document their level of knowledge at the completion of the curriculum, Scholars will take an examination in non-malignant hematology, using instruments developed for existing fellowship training programs. If appropriate, additional instruction may be prescribed.
A typical curriculum for a Scholar with little prior non-malignant hematology training could include:
Sequential Inpatient, Clinical and Laboratory Rotations:
Consultative and inpatient pediatric and/or adult hematology (including hemostasis) (12 weeks)
Blood banking/transfusion medicine (4 weeks)
Hematopathology (4 weeks)
Clinical and laboratory electives (8 weeks)
Continuous/Simultaneous Outpatient Clinics and Conferences:
Outpatient clinics, including a continuing clinic relevant to clinical research interests (1/2 day per week) and selected elective clinics (48 weeks). The distribution of clinic experiences would be individualized.
Rounds and clinical conferences (2-3 hours/week)
Hematology Core Topics (about 20 sessions):
Lectures or mentored discussion groups on advanced topics relevant to clinical hematology research opportunities in the Program, and covering knowledge that is critical for the clinical hematologist.
Didactic Clinical Research Curriculum
The Didactic Clinical Research Curriculum includes coursework in topics critical to all clinical investigators, complementing the Clinical Core Curriculum that covers topics specific to non-malignant hematology. The one-year curriculum provides formal instruction in areas important for establishing an independent research program. Topics covered include the fundamentals of:
Observation and experimental research methods
Data collection and quality assurance
Responsible conduct of research
Presentation and publication
This curriculum is based on the Core Curriculum for Clinical Investigation (CCCI) that was developed under the Clinical and Translational Sciences Award (CTSA).
Courses meet in the late afternoon/early evening since past experience and input from young faculty indicates that this is the best time to attend courses.
The curriculum will be individualized to accommodate students with prior training in specific components (e.g., biostatistics), or to provide training in response to specific needs (e.g., bioinformatics, pharmacogenomics, epidemiologic methods, advanced biostatistics, survey research, or nutrition).
As part of their career development plan, Scholars may adapt their curriculum to meet requirements for a 14-credit, six-course Certificate of Completion. Additional components make up a 33-credit Mentored Training Program in Clinical Investigation that leads to a Master of Science degree in Clinical Investigation.
The standard curriculum for a Certificate of Completion of the Core Curriculum in Clinical Investigation consists of the following courses. Complete course descriptions, schedules and syllabi are available at the Clinical Research Training Center website.
Designing Outcomes and Clinical Research (Fall Semester-3 credits)
Introduction to Statistics for Clinical Investigation (Fall Semester-3 credits)
Intermediate Statistics for the Health Sciences (Spring Semester-3 credits)
Ethical and Legal Issues in Clinical Research (Fall & Spring Semesters-2 credits)
Scientific Writing and Publishing (Spring Semester-2 credits)
Grantsmanship (Fall Semester-3 credits)
Epidemiology for Clinical Research (Spring Semester-3 credits)
To earn a Masters of Science in Clinical Investigation, Scholars must take two electives related to their research interests and fulfill additional research credits. The research requirement is met by the Mentored Research Experience.
Scholars may want or need additional formal training in specific topics, which may be accommodated through course offerings from a variety of Schools, Departments or Divisions. A sampling is given below. Completion of the first four (summer) courses (11 credits) leads to a Certificate in Genetic Epidemiology under the Genetic Epidemiology Master of Science (GEMS) Program. Additional courses in probability and statistics (not listed below) are offered by the Department of Mathematics as part of the GEMS Program.
Statistical Computing with SAS (Division of Biostatistics #M21-503, 2 credits) Coursemaster: Karen Schwander Intensive hands-on summer training in SAS (Statistical Analysis System) during 7 full weekdays.
Biostatistics for Research Workers (Division of Biostatistics #M21-505, 3 credits) _Coursemasters: Treva Rice and Yun Ju Sung. Intensive two-week summer course designed for researchers who want to expand their knowledge of practical methods in statistics. Oriented toward statistical and epidemiological concepts, applications, practical hints and hands-on approach to data.
Fundamentals of Genetic Epidemiology _(Division of Biostatistics #M21-515, 3 credits) Coursemasters: Treva Rice and colleagues. Intensive 10 day summer course on causes of phenotypic variation, familial resemblance/aggregation, heritability (family, twin, and adoption designs), biometrical genetics, Hardy-Weinberg Equilibrium, major gene, segregation analysis, ascertainment, study designs, basic concepts in linkage and association analysis.
Introduction to Bioinformatics (Division of Biostatistics #M21-550, 3 credits) Coursemasters: Jingqin (Rosy) Luo and C. Charles Gu. This is an 11-day summer course with broad exposure to the basic concepts, methodology and application of bioinformatics to solve biological problems. Specifically, the students will learn the basics of online genomic/protein databases and database mining tools, and acquire understanding of mathematical algorithms in genome sequence analysis (alignment analysis, gene finding/predicting), and of the impact of recent developments in the DNA chip technology.
Epidemiology, Clinical Trials and Study Design Management _(Division of Biostatistics #M21-616, 3 credits) Coursemasters: J. Philip Miller and colleagues. Critical concepts and methods in epidemiology, including attributable risk, cohort studies, and case control studies; methods for analysis of clinical trials; study design issues, power analysis, study management issues (protocols, data entry, data flow, database management, QC), special considerations for multicenter studies, human studies, principles and issues in designing linkage and association studies, and ethical, legal, and social issues concerning human studies.
Computational Statistical Genetics (Division of Biostatistics #M21-621, 3 credits) Coursemasters: Michael Province and colleagues. Provides computational experience with statistical genetics methods and concepts, concentrating on the applications of genomics and SAS computing, efficient new bioinfomatic tools to interface with the latest, most important genetic epidemiological analysis software, as well as how to derive, design and implement statistical genetics models. Didactic instruction on haplotype estimation and modeling of relationship to phenotype, LD mapping, DNA pooling analysis methods, analysis approaches in pharmacogenomics, and epistasis (GxG) and GxE interactions; data mining methods, including clustering, recursive partitioning, boosting, and random forests; fundamentals of meta-analysis, importance sampling, permutation tests and empircal p-values, and the design of monte-carlo simulation experiments.
Human Linkage and Association Analysis _(Department of Genetics #M21-5482, 3 credits) Coursemasters: John Rice and colleagues. Meiosis, inheritance, Hardy Weinberg Equilibrium; Linkage analysis: definition, crossing over, map functions, phase, LOD scores, genetic heterogeneity, penetrance, phenocopies, liability classes and multipoint analysis; non-parametric linkage analysis (sibpairs and pedigrees) and practical aspects of preparing data; determination of power for mendelian and complex trait analysis; linkage disequilibrium analyses, allelic association (case control designs and family bases studies); quantitaive trait analysis: measured genotypes, variance components methods, epistasis and GxE interaction.
Introduction to Industry-Sponsored Clinical Trials. Coursemasters: David DeBrota, MD, Walter Offen, PhD, Greg Sides, MD, Alex Dmitrienko, MD, Robert Metcalf, MD, David Ceryak. This is a series of one-hour lectures by professionals from Lilly Research Laboratories, Eli Lilly & Company. Topics include data monitoring, clinical trial design, statistical concepts, drug development, and Good Clinical Practice (GCP).
Mentored Research Experience
Toward the end of the first year, each Scholar will begin a one or two year intensive Mentored Research Experience to generate publishable results and preliminary data for subsequent independent grant applications, facilitating the transition between fellowship training and faculty appointment. The program will focus on three major areas of non-malignant hematologic disease: (1) bone marrow failure syndromes, including paroxysmal nocturnal hemoglobinuria, aplastic anemia, congenital anemias, and myleodysplastic syndrome; (2) hemostatic and thrombotic disorders, including von Willebrand disease, thrombotic microangiopathy, and other congenital or acquired hemorrhagic or thrombotic syndromes; and (3) sickle cell disease and other hemoglobinopathies. These research projects will encompass pediatric, adolescent and adult subjects with non-malignant hematologic disorders.
This mentored research component draws on the superb clinical resources of Washington University-affiliated hospitals and centers including Barnes-Jewish Hospital, St. Louis Children's Hospital, the Center for Advanced Medicine, the Siteman Cancer Center, the Pediatric Patient-Oriented Research Unit (PORU), the General Clinical Research Center (GCRC), the Center for Clinical Studies, the Clinical Nutrition Research Unit (CNRU), the Multi Academic Clinical Research Organization (MACRO), and Volunteers for Health. The multidisciplinary scope of the program is reflected in the composition of the Program Faculty, which includes members of the Departments of Internal Medicine, Pediatrics, Pathology and Immunology, Obstetrics and Gynecology, Psychiatry, and Neurology.
The Mentored Research Experience will provide practical training in clinical research. Scholars will apply the skills learned or reinforced in the curriculum of the first year by designing a clinical research project in consultation with their Mentors, and writing a detailed project description for review by their Career Development Committee. If appropriate, they will write a clinical protocol and human studies consent forms, and guide them through IRB and protocol review board approval.
This research experience will integrate Scholars' didactic education with first-hand knowledge of clinical research. They will learn to develop a research question, generate a hypothesis, devise an appropriate and feasible study design, obtain approvals from regulatory bodies, ensure the protection and safety of subjects through informed consent and data safety monitoring, understand and deal with ethical issues to conduct responsible research, and develop data collection tools. They will learn methods of data collection (chart review, paper and web-based surveys, interviews, focus groups, electronic queries and use of preexisting datasets, merging data sets, data security), data analysis (univariate and multivariate analysis, survival analysis, graphical representations of data), and biostatistics (power and sample size calculations, cluster analysis ROC curves, how to interact with biostatisticians and epidemiologists). Successful research also requires successful communication of results, and Scholars will gain practical experience in scientific writing, presentation and teaching. The efficiency of this critical learning will be enhanced by intensive interaction of each Scholar with their Mentors, reinforced by oversight from their Career Development Committee.
Selection of Research Project, Mentors, and Career Development Committee
Upon entry into the Program, or early during the first year, Scholars will meet informally with Program Faculty of their choice to identify a potential research project and select two Mentors. With the guidance of the Mentors, each Scholar will write a concise research proposal, modeled on NIH K award applications, describing specific aims, background and significance, a detailed budget and research plan, and addressing as needed issues on human subjects, protocol design and approval procedures, data safety monitoring, and the use of vertebrate animals. The Program Director and Advisory Committee will evaluate the proposal and provide written comments, suggest revisions if necessary, and approve or suggest modifications in the budget, the choice of Mentors, and the composition of the Career Development Committee. Final decisions about the selection of Mentors and Career Development Committee will be made jointly by the Mentors, Scholars, Program Director and Advisory Committee. After approval, the Scholar will meet with the selected Career Development Committee to review the research proposal in detail.
Responsibilities of Mentors
Mentors will oversee the practical apprenticeship of their Scholars, day-to-day, as they learn the skills needed to conduct independent clinical research. If gaps are identified in a Scholar's knowledge or clinical research skills, Mentors will formulate plans to fill those gaps. Mentors will assess whether a Scholar's research project can generate publishable results and preliminary data for a grant application, within the time available.
Mentorship carries an obligation to promote the career of trainees. This will involve assistance with writing meeting abstracts and manuscripts; recommending Scholars to speak at meetings; supporting admission to professional societies, providing Scholars with opportunities to review manuscripts in their field; facilitating their attendance at national and international meetings; networking to access resources for their research.
The Mentored Research Experience is intended to produce a published manuscript and preliminary data for a grant application. If successful, therefore, most Scholars will be prepared to write a grant application toward the end of their training. A typical first grant proposal will be an individual K series career development award, or possibly an R01 award, and usually will request support to continue or extend the research performed during training. Prior to submission these grant applications will be reviewed and edited by both Mentors and by other members of the Scholar Development Committee.
As members of the Program Faculty, Mentors also will participate in developing, updating, enhancing, evaluating and revising the first-year curriculum.
Composition and Responsibilities of Career Development Committees
Career Development Committees will be customized to serve the needs of each Scholar. The will be composed of the two Mentors, plus three persons selected from the Program Faculty for expertise relevant to the research proposal. Career Development Committees may contain one or more members of the Advisory Committee, and will be chaired by a member other than a Mentor. The composition (2 Mentors, 3 others) and designation of Chair (non-Mentor) is intended to provide external viewpoints to balance those of the Mentors, and increase the multidisciplinary advice to the Scholar. The Committees will provide the kind of oversight and advocacy for the Scholar that a traditional thesis committee provides for Ph.D. degree candidates. The Committee will meet with the Scholar formally twice a year, and will provide feedback on the Scholar's development and on the research project. They will evaluate the Scholar's development of independence, scholarship, management ability, and collaboration skills. They will evaluate the Project for feasibility, soundness, scientific importance, value to the Scholar's career development, likelihood of generating publishable results within the time available, and adequacy of resources committed. They also will serve as a supplemental check on protocol design, human subjects assurances, informed consent, and other aspects of the responsible conduct of research. The Chair will prepare brief (one page) reports of meetings, identifying weakness and strengths in the interim results and proposed studies, and making recommendations for the prioritization of research goals.
Seminars & Other Activities
Physician-scientists must be outstanding learners and teachers to stay at the forefront of their chosen field. To facilitate continuous self-education, the Program will support journal clubs, seminars and symposia to enable Scholars and other WUMC physician-scientists to exchange information, to benefit from the intellectual resources of the larger scientific community, and to interact with outstanding visiting scientists. Such activities bridge the clinical and didactic curricula. Scholars interact with the larger community of physician-scientists through research seminars, journal clubs, retreats, and scientific meetings, examples of which are listed below. These activities are distinct from the Clinical Conferences and Rounds that are components of the Clinical Core Curriculum.
Hematology Research Seminars
The Division of Hematology hosts a (bi-weekly to monthly) seminar series in which WUMC faculty members and invited speakers from other institutions deliver seminars on their recent research. The multidisciplinary topics are wide ranging and include basic, translational patient-oriented and clinical research.
Research in Progress Seminars
This bi-monthly seminar series, alternating with Hematology Research Seminars, features two speakers who each present a 20 minute talk on their current and proposed research, allowing another 10 minutes for discussion. Participants include graduate students, postdoctoral fellows, and Scholars. The format offers an excellent training in how to prepare graphical materials, organize and deliver a scientific talk, and field questions. The setting also encourages useful interactions with other physician-scientists. Scholars can attend during their first "curriculum" year, and may choose to be added to the speaker rotation during their "research" years.
Multidisciplinary Clinical Research Seminars
This weekly seminar series is sponsored by the K12 Multidisciplinary Clinical Research Career Development Program. Heme Scholars will participate with other Scholars, Mentors and faculty to present current research and discuss clinical research methods.
Scholars' Practicum Retreat
Heme Scholars will join other K12 Multidisciplinary Clinical Research Scholars at Washington University in an all day retreat for Scholars, Mentors, and other Program Faculty. Scholars will present the results of their research to attendees, and contribute to wide ranging discussions of science. Additional presentations will cover topics relevant to career development including grant writing, managing a laboratory budget, conflict resolution in the workplace, collaborative research, and personnel recruitment and management. Participation in this retreat will facilitate multidisciplinary interactions and networking among physician-scientists at all stages of career development.
NIH Annual K12 Grantees Meeting
Heme Scholars, Mentors, and the Program Director will attend an annual K12 grantees' meeting in Bethesda, MD, hosted by the NHLBI Division of Blood Diseases and Resources. This meeting will facilitate interactions with participants in other K12 Clinical Hematology Research Career Development Programs, for the purposes of presenting their research results as a poster or talk, sharing information and making adjustments to improve the curriculum.
Scholars will have funding to attend and present their research at national and international scientific meetings.