Clinical Research Proposal

							       Putting Together a
       Research Proposal
Tate Erlinger, MD, MPH
Director of Clinical Research
Office of Research Administration
Seton Family of Hospitals
Part I: Starting Out
Establish the Rationale
   A rationale for the choice of topic,
       Why is it important or useful within the concerns
        of the discipline in which you are writing?

       It is also sensible to indicate the limitations of
        your aims. In other words, don't promise what
        you can't possibly deliver.
Know the Literature in the Field
   A review of existing published work ("the
    literature") that relates to a topic.

   Tell how your proposed work will build on
    existing studies and yet explore new territory.
Outline your Approach
   An outline of your intended approach or
    methodology (with comparisons to existing
    published work), perhaps including costs,
    resources needed, and a timeline of when you
    hope to get things done
Part II:
Setting up a Specific Project
Where does clinical research start?
   Location
   Location
   Location



   Find a rich environment and a good mentor
   Take advantage of opportunities
A Research Project

             When?              How?




                     QUESTION

    Where?                             Who?



                      What?
Steps to Starting a Project?
1.   Why do you want to do a project?
2.   What is your question?
3.   Who should you ask for help?
4.   How might you approach the problem?
5.   Where is the study taking place?
6.   What is your time frame? (when?)
Why do you want to do a project?
   Interest in a topic
   Bolster your resume
   Exploring career paths
   Mandatory
   Other
Assemble a group
   Clinical Research is a group process…not an
    individual endeavor
   Identify a mentor/advisor
       Work together to build a team as your project
        progresses
What is the question?
   The MOST important part of the process
   How do you choose a question?
   How do you phrase the question?
   How does the question change as you start to
    look at what is feasible vs. what is optimal?
Choosing a Research Question
   Think of an area you are interested in and start
    READING
       Reviews
       Meta-analyses
       Editorials
   What are the conflicts in the field?
   What do experts say are the Gaps in
    knowledge?
Drafting a Question
   “The aim of this study is to…..”
       Determine the association between X and Y
       Determine the impact of intervention X on
        outcomes 1, 2 and 3.
       Etc.
   Be very specific
   Clearly articulate all the outcomes,
    interventions or variables of interest
 After the Question
    Go back to the
     literature
        Good recent reviews
        Good recent meta-
         analyses
    Create a data table


Author   Year      Study       Population   Outcomes Results Comments
                   Design
Revisit the Question
   After reviewing the literature more thoroughly
    has your question changed or been modified?
       No…keep going
       Yes…fine, collect a little more information
How, When, Where
   Once the question is posed, think about the
    “How, When, Where”
       In reality, you‟ve been considering this all along
Summary
   The question is the hardest and most
    important thing to define.
       Be specific
       Don‟t be afraid to refine
   Assemble a team, starting with an advisor
   Take the time to learn your field and gather
    data
   Have fun!
Setting up
   Decide on study design
       Cross-sectional (single point or period in time)
           Descriptive
           Exploratory associations
       Case-control
           Retrospective
           “prospective”
           Incident vs. prevalent cases
           Selection of cases / controls
       Prospective
           Random sample
           Convenience sample
           Duration of follow-up
           Measurement of exposures (multiple) / outcomes (multiple)
How large should the study be?
   Sample size / power calculations
       Underpowered studies are only useful for
        feasibility
       ALL studies should have an estimate of statistical
        power
           Use data from prior studies or pilot studies
   Various Methods used to calculate power or
    sample size…depends on study design and
    analytic techniques being used.
Collecting Data
   How will data be collected?
       Paper form (standardized)
       Spreadsheet
       Other?
   Who will collect the data?
   When will data be collected?
   What type of data will you collect?
What type of data?
   EXAMPLE: chart review
       Create data collection tool
       Avoid “free text” – difficult to analyze
       Multiple choice (or pre-defined choice) preferable
       Pilot the data collection tool first
           What were the problems?
           What was missed?
           Was there something that needs further clarification?
           Did you capture the data you were really after (valid)?
Data Storage
   Must transfer data from paper to electronic if
    not already done.
   Avoid multiple data manipulations if possible,
    e.g. transfers…better to start with electronic.
   Keep tight version control of data sets and
    ownership of data.
   Keep data secure, locked, on protected
    computer and/or locked drawer
Data Analysis
   Seek help if needed.
   “Cleaned” data set will be easiest to work
    with
   Analyze data according to Pre-defined plan
   DO NOT go „fishing‟
       Multiple comparisons problems
       Spurious results
Sections of the Proposal
   Title
   Investigators
   Abstract
   Specific Aims
   Background and Significance
   Experimental Design and Methods
   Preliminary Results (if applicable)
Title
   Type the entire protocol title. This title
    should match the one on the Request for
    Expedited Review and Request for Full Board
    Review Forms.
Investigators
   List the investigators as Principal
    Investigator, Co-Investigator, Collaborators,
    Coordinators, etc.
Abstract
   Include the hypothesis being tested, summary
    of the study aims and procedures,
    experimental design, and the significance of
    the research in layperson’s language.
Specific Aims
   Clearly state the hypotheses to be tested and
    the objectives or specific aims. Numbers and
    types of subjects and types of procedures
    should be specifically noted
Background and Significance
   Concise
   Demonstrate a knowledge of the field
   Cite relevant papers in the field
Background and Significance
   Provide details of clinical study design.
   Include an in-depth narrative of the methodology to
    be employed.
   Provide details of Statistical Considerations.
   This section must include a justification of the
    sample size and a statement regarding power based
    on one or more of the primary outcome measures,
    presumably ones for which there is some information
    about intra-individual variation
Preliminary Results:
   Be concise.
   If there are none, please state.
References
   NIH guidelines for preparing a proposal at:
    http://www.niaid.nih.gov/ncn/grants/write/ind
    ex.htm