Submitting a Protocol for CTSI Support
Pediatric Protocols (Children's Hospital)
The goal of the Translational Research Units (TRUs) is to provide clinical research infrastructure for medical scientists who conduct patient-oriented research. The TRUs can be used by investigators who are supported by the NIH or other peer-reviewed research funding agencies. The TRU is also an appropriate site for pilot studies that may lead to future research support. Industry-sponsored studies may be conducted on the TRU provided they do not compromise investigator-initiated research projects. These studies may receive nursing and space support only, and will be charged an hourly fee of $45 for the use of the space and Pediatric TRU nursing staff.
There are 2 people you should contact prior to submitting a research protocol to the CTSI for support:
For help on study design and power analysis:
Dr. Pippa Simpson, the Pediatric TRU Biostatistician (955-5421, psimpson@mcw.edu)
or
Dr. Raymond Hoffmann, CTSI Biostatistician (456-8359/805-7327, hoffmann@mcw.edu)
For help with budget planning and study categorization:
Ms. Sherry Castillo, TRUs Administrative Director (805-7318, scastill@mcw.edu)
You may also wish to contact the TRUs Scientific Administrator/CTSI Global Navigator, Dr. Glenn Krakower (805-3802, gkrakowe@mcw.edu), for specific information on the CTSI itself, how the CTSI might help you in your research endeavors, and for specific information on putting together your CTSI application. And, you may want to contact the Research Subject Advocate (RSA), Ms. Keryl Jones (805-7321, kjones@mcw.edu), who can assist you with developing your Data Safety Monitoring Plan and consent/assent forms, and provide guidance with any safety or ethical issues. Please check our website links for overviews on CTSI Bionutition and Body Composition, Core Laboratory, Biostatistics, Biomedical Informatics, and fMRI. Prior to submitting your application, we encourage you to contact the appropriate Core Director(s) for more specific information about the services we can offer.
Submission Guidelines
Although not explicitly required, we recommend that you submit your application to the CTSI prior to the CHW IRB, in that the Scientific Review Committee may recommend changes to the consent form that will require subsequent re-review by the IRB.
Your submission packet should be assembled as follows:
- CTSI Request Summary Form link
- CHW/MCW HRRC Registration Form link
- CHW Consent Form link
- CHW Assent Form (if necessary) link
- 5-page protocol, including abstract, Minority and Utilization Tables link
- Data and Safety Monitoring Plan (DSMP) link
- NIH Biosketch for all investigators submitting their first application to the CTSI link
Please submit electronic copies of these documents to Dr. Glenn Krakower (gkrakowe@mcw.edu). Signed or stamped consent/assent forms and the DSMP may also be sent to:
Ms. Sherry Castillo, TRU Administrator
FMLH Pavilion LL
Tel: 805-7318 FAX: 805-7330
E-mail: scastill@mcw.edu
The submission deadline for the next meeting of the CTSI Scientific Review Committee is the 15th of each month. Incomplete submissions will be communicated directly to the PI.
The CTSI Protocol
The link below will provide you the forms and instructions you need to submit a GCRC application. Other links throughout this section will provide sample completed tables.
CTSI Protocol Template
CTSI Request Summary
This is the first two pages of the CTSI Protocol template. This form outlines all the requirements of the CTSI in terms of space, budget, and Core requirements. It also replaces sections G. Utilization Table and H. Other Support from the old GCRC Protocol Template.
Please list the anticipated numbers of Pediatric TRU inpatient and outpatient days for each year of your study (these numbers will be 0 for studies conducted in the clinic or other locations).
1. Please explain how the number of anticipated patient days is derived.
For example:
A total of 200 subjects will be seen over the 3-year course of this study. Each subject will be seen a total of 4 times in the TRU on an outpatient basis. [Thus, 800 patient visits are divided over 3 years, possibly listed as 300, 300, and 200 for years 1, 2, and 3, respectively]
2. For each Core service that will be requested, please describe in the right column the specific services required.
For example:
Research nurses are needed for vital signs and blood sampling and processing. Bionutritional support is needed to design and assist subjects with the 1200-calorie, 30g fat/day diets. The CTSI Core Laboratory will store plasma samples and perform assays for triglycerides and cholesterol concentrations. CTSI Biomedical Informatics support is requested to help establish the database and instruct in its usage.
Other Support
- Describe funds which support your research project; for example, NIH funding, non-federal organizational grants, MCW grants, CHW foundation awards, Department/Division funds, and any Pharmaceutical or Biotechnology company support);
- Please provide dollar amount and projected utilization of these funds;
- If this project receives other support, please include a copy of the contractual agreement, including the budget. The CTSI needs to document that there is no budgetary overlap in support of any items or procedures.
Data and Safety Monitoring Plan (DSMP)
All protocols submitted to the CTSI must have a completed DSMP. The template for this form, provided in .doc format, is given below.
The DSMP template requests the following information:
- Identities of individuals who will monitor
- Specific parameters to be monitored
- Fequency of the monitoring
- Compliance with the reporting of adverse events, anticipated and unanticipated, to the IRB, CTSI, external funding agency, and any applicable regulatory agency
- Plan for submitting DSMP reports
Most of the requested material for the eIRB protocol and the DSMP can easily be cut and pasted from the 5-page protocol. Please contact Keryl Jones, RSA (805-7321, kjones@mcw.edu) if you need any assistance.
DSMP
DSMP Sample
All MCW research studies deemed to be high risk, either by the investigator or the reviewing IRB, must receive oversight by a Data and Safety Monitoring Board (DSMB). The College has created distinct DSMBs in the areas of oncology, fMRI/adult physiology, and pediatrics. A protocol requiring a DSMB is assigned to the appropriate committee through an instrument inherent in eIRB.
The primary responsibilities of the DSMB are to periodically review and evaluate the accumulated study data for participant safety, study conduct, progress, and efficacy as appropriate. The DSMB is responsible for defining events and event triggers that would call for an unscheduled review, for defining guidelines to stop a protocol unmasking (unblinding), and defining voting procedures prior to initiating any data review. The DSMB concludes each review with a recommendation as to whether the study should continue without change, be modified, or be terminated.
Office of Research/HRPO
Consent Form
Each CTSI protocol has to be accompanied by a consent form, which in the case of CHW protocols should follow the HRRC guidelines. We have provided links to sample CHW consent and assent forms.
Your protocol and consent form must also have IRB approval. If your study is to be performed at the CTSI/Pediatric Satellite at CHW, it must also be submitted to the CHW IRB. To learn more about the Institutions Review Board, please click on the following:
Children's Hospital of Wisconsin Institutions Review Board (CHW IRB)
CHW Consent Form
CHW Assent Form
The 5-page Protocol
The format for the 5-page protocol is structured in a manner similar to that required for submitting grants to the NIH and should be thought of as a "Mini-R01".
NOTE: PARTS A-D SHOULD BE NO MORE THAN 5 PAGES
Abstract
Please complete a brief abstract on the third page of the CTSI protocol template.
A. HYPOTHESIS AND SPECIFIC AIMS
- List the broad, long-term objectives and specific aims to be accomplished
- Specifically state the hypothesis(es) to be tested
- State concisely and realistically the individual, short-term steps planned to test the hypothesis
For example:
- Specific Aim 1: To analyze treatment results in patients with (disease) in clinical improvement measured as a reduction in (variable)
- Specific Aim 2: To determine the change in (specific blood variable) with infusion of (agent) in patients with (disease)
B. BACKGROUND AND SIGNIFICANCE
- Briefly describe the background to this project, and provide references (to be listed sequentially in section F)
- Critically evaluate existing knowledge
- Specifically identify the gaps which the project is intended to fill
- State concisely the importance of the research of this project by relating the specific aims to the broad, long-term objectives, and to the relevance, understanding, prevention, or treatment of human disease
C. PROGRESS REPORT OR PRELIMINARY STUDIES
- Summarize the specific aims of your previous research (if any)
- Provide a succinct amount of your published or unpublished results or observations leading to the objectives of this proposal
- Discuss the importance of the findings
- Include in this section any references to publications relevant to the proposed research (include all references in section F)
D. RESEARCH DESIGN AND METHODS
Please structure this section as follows:
D1. Subjects
- Describe the characteristics of the subject population, including their anticipated number, age range, and health status
- List inclusion and exclusion criteria
D2. Study Design and Experimental Procedure
- Discuss the research design and procedures to be used to accomplish the specific aims
- Provide a timetable that matches the specific aims
- Include a flow diagram or table of the study design, if feasible
D3. Laboratory Analysis
- Briefly describe parameters to be analyzed and laboratory methods to be used
For example:
- A double-antibody, equilibrium radioimmunoassy (Linco Research, Inc., St. Charles MO) is used for the measurement of plasma insulin
- Triglycerides are determined spectrophotometrically. Triglyceride kits are obtained from Stanbio Laboratory, Inc. (San Antonio TX)
D4. Statistics and Data Analysis
- Justification of the sample size, with power analysis
- Experimental design or sampling scheme (i.e. the randomization scheme for allocating subjects to various treatment groups, discussions of a possible sequential design in the study because of ethical reasons)
- Description of the data analysis and what tests are being used
- Statement of whether the project is a pilot study or, for example, part of a multi-center trial
D5. Future Directions of your Research
E. RESEARCH PROTECTION OF HUMAN SUBJECTS
[Source: http://grants.nih.gov/grants/funding/phs398/section_1.html#researchp]
Address the following four subsections, using these subheadings:
1. RISKS TO THE SUBJECTS
Human Subjects Involvement and Characteristics:
Describe the proposed involvement of human subjects in the work outlined in the Research Design and Methods section. Describe the characteristics of the subject population, including their anticipated number, age range, and health status. Identify the criteria for inclusion or exclusion of any subpopulation. Explain the rationale for the involvement of special classes of subjects, such as fetuses, neonates, pregnant women, children, prisoners, institutionalized individuals, or others who may be considered vulnerable populations.
Sources of Materials:
Identify the sources of research material obtained from individually identifiable living human subjects in the form of specimens, records, or data. Indicate whether the material or data will be obtained specifically for research purposes or whether use will be made of existing specimens, records, or data.
Potential Risks:
Describe the potential risks to subjects (physical, psychological, social, legal, or other) and assess their likelihood and seriousness to the subjects. Where appropriate, describe alternative treatments and procedures, including the risks and benefits of the alternative treatments and procedures to participants in the proposed research.
If you plan to take blood for DNA analysis, please describe in your CTSI protocol, DSMP, and Consent form the procedures used to guarantee and maintain confidentiality, according to the guidelines of the Office of Research.
2. ADEQUACY OF PROTECTION AGAINST RISKS
Recruitment and Informed Consent:
Describe plans for the recruitment of subjects and the process for obtaining informed consent. Include a description of the circumstances under which consent will be sought and obtained, who will seek it, the nature of the information to be provided to prospective subjects, and the method of documenting consent. The informed consent document need not be submitted to the PHS unless requested.
Protection Against Risk:
Describe the planned procedures for protecting against or minimizing potential risks, including risks to confidentiality, and assess their likely effectiveness. Where appropriate, discuss plans for ensuring necessary medical or professional intervention in the event of adverse effects to the subjects. In studies that involve clinical trials (biomedical and behavioral intervention studies), describe the plan for data and safety monitoring of the research to ensure the safety of subjects.
3. POTENTIAL BENEFITS OF THE PROPOSED RESEARCH TO THE SUBJECTS AND OTHERS
Discuss the potential benefits of the research to the subjects and others. Discuss why the risks to subjects are reasonable in relation to the anticipated benefits to subjects and others.
4. IMPORTANCE OF THE KNOWLEDGE TO BE GAINED
Discuss the importance of the knowledge gained or to be gained as a result of the proposed research. Discuss why the risks to subjects are reasonable in relation to the importance of the knowledge that reasonably may be expected to result. Note: If a test article (investigational new drug, device, or biologic) is involved, name the test article and state whether the 30-day interval between submission of applicant certification to the Food and Drug Administration and its response has elapsed or has been waived and/or whether use of the test article has been withheld or restricted by the Food and Drug Administration.
TARGETED/PLANNED ENROLLMENT TABLES
Please list the total number of subjects anticipated to fall within each racial/ethnic group. If you don't know the racial/ethnic disease distribution of the disease you are studying, consult the GCRC Biostatistician, Dr. Raymond Hoffmann (456-8359 or hoffmann@mcw.edu) for assistance in obtaining these data. (link to Minorities Inclusion Table). Below the table, please explain why you are not including minorities, both genders, and both adults or children, as appropriate.
NOTE: As per the NCRR definition, children are defined as being below 21 years of age.
Gender and Minority Table example
F. BIBLIOGRAPHY
Please list the referenced papers in the order in which they appear in your text.
G. GCRC RESOURCE UTILIZATION TABLE
The following table (Excel 4.0 or higher format) can be downloaded from the GCRC Website to your Mac or PC by Clicking Here.
Please list the anticipated numbers of inpatient and outpatient days for each year of your study. For each Core that will be used, please place an X. Please make certain that the items checked off and the justifications match those given in the GCRC Request Summary.
Here's an example of a completed form:
GCRC Resource Utilization Table example, including the Justification
JUSTIFICATION
1. Please explain how the number of anticipated patient days is derived.
For example:
A total of 200 subjects will be seen over the 3-year course of this study. Each subject will be seen a total of 4 times in the GCRC on an outpatient basis. [Thus, 800 patient visits are divided over 3 years, possibly listed as 300, 300, and 200 for years 1, 2, and 3, respectively]
2. For each Core checked off, please describe the specific services required.
For example:
Research nurses are needed for vital signs and blood sampling and processing. The Core Laboratory will store plasma samples and perform assays for triglycerides and cholesterol concentrations. Informatics support is requested to help establish the database and instruct in its usage. Biostatistics support is requested for assistance with the power analysis and in statistical methodology.
H. OTHER SUPPORT
- Describe funds which support your research project; for example, NIH funding, non-federal organizational grants, MCW grants, CHW foundation awards, Department/Division funds, and any Pharmaceutical or Biotechnology company support)
- Please provide dollar amount and projected utilization of these funds
- If this project receives other support, please include a copy of the contractual agreement, including the budget. The GCRC needs to document that there is no budgetary overlap in support of any items or procedures
Review Process
Your proposal will be reviewed by members of the GCRC Research Review Committee, which meets the first Monday of each month. Review Criteria include the significance of your proposed research questions, clarity of hypothesis and specific aims, as well as appropriateness of design, methods, and statistical analysis. Other topics discussed include human research protection issues, the appropriateness of any exclusion of women, minorities, and children, the level of GCRC support as per guidelines established by the GCRC Advisory Committee, and the assigned patient category.
The GCRC Research Review Committee
The Program Director and the Administrative Director, in consultation with the principal investigator, assign a preliminary patient category to the study. Studies initiated by industry, designated as category D, are funded entirely by the industry via the principal investigator. These studies can request space, nursing, and bionutrition support only. All charges are paid by the GCRC grant for investigator-initiated research, designated category A, while B studies are investigator-initiated and involve patients receiving routine care. The GCRC covers only those charges directly related to the research aspect of B studies.
A primary and a secondary reviewer will also be assigned to your protocol prior to the meeting. They will evaluate your study on scientific merit and GCRC need using the NIH scoring system. You may be contacted by one of the reviewers in advance of the meeting to address specific questions, or possibly be invited to the Committee meeting to summarize the protocol and respond to the questions posed by the assigned reviewers and Committee members. After the presentation, you'll be excused, and the primary and secondary reviewers will present their evaluations to the Committee for discussion. Reviewer presentations are followed by further discussion among committee members prior to voting.
Members then vote on the following five possibilities: 1) Approval without revisions; 2) Approval with minor revisions, to be reviewed by either the original Committee reviewers (if they wish to see the revised protocol) or administratively; 3) Approval with major revisions, to be reviewed by all Committee members; 4) Table for additional information not available prior to review; or 5) Disapproval.
Shortly thereafter the Chairpersons communicate the Committee's decision to the principal investigator in a letter (disposition form) offering detailed suggestions for revisions, if required.
Once a Pediatrics protocol has been approved, it will next need to be evaluated by the CHW IRB. If it has gone the CHW IRB already, any revisions made in response to the GCRC Research Review Committee may need to be re-reviewed by the CHW IRB, even if they have already given approval. You will be notified when the GCRC has approved your protocol.