1. How to Write a Clinical Protocol
Rebecca Torguson, MPH
Director, Cardiovascular Research Operations
MedStar Cardiovascular Research network
MedStar Heart Institute

2. I/we have no real or apparent conflicts of interest to report.
Rebecca Torguson
I/we have no real or apparent conflicts of interest to report.

3. What is research?
Research is the systematic collection, analysis and interpretation of data to answer a certain question or solve a problem
Formation of the topicHypothesis
Conceptual definitions
Operational definition
Gathering of data
Analysis of data
Test,
revising of hypothesis
Conclusion,
iteration if necessary

4. The Research Question However, usually too general !
‘Research’ usually begins with a general question of interest to you, which may arise from
an observation within your area of work or interest
a prompt or issue in your field of study
prior research of relevance
However, usually too general !
Needs to be formulated into a specific question that can be investigated
Once the question is defined, a systematic approach to the investigation must follow (research)

5. First Steps
Gather your thoughts so you can clearly formulate them in the form of questions, aims, and hypotheses
Perform a literature research make sure your ideas were not studied and published already
Establish your investigational team
Design a research approach strategy
Secure budget and seek help for grant application writing

6. Research Protocol What is a Research Protocol?
A formal document specifying what the study hopes to achieve and how it is to be conducted
When should you write a Research Protocol?
For every research project, no matter how small or seemingly insignificant

7. Why Writing a Research protocol?
To clarify the research question
To compile existing knowledge
To formulate a hypothesis and objectives
To decide about a study design
To clarify ethical considerations (need for FDA approval, etc.)
To apply for funding
To have a guideline and tool for the research team
Study design – causal relationship between exposure and outcome is relevant
Ethical considerations - in new TB drugs I still need to cure the patients
Order is not relevant

8. The Research Team…
Ensure expertise in scientific, clinical, and methodological areas
Expertise in statistics, health economics behavioral sciences, qualitative research, trialists (for RCTs)
Add as Co-applicants / Collaborators
Partner Organizations, e.g. academic, health service providers, government agencies

9. Prinicpal Components of the Protocol
Adequate title
Introduction/rationale of the study
Objectives/hypothesis/endpoints
Methodology/ Intended Populations
Plan of analysis/ Statistical Approach
Timeline
Ethical considerations
Bibliography
Budget

10. Title of a research project
Accurate, short, concise
Descriptive: should make the main objective clear, should mention the target population
Key words: should contain key words for referencing

11. Specific Aims Objectives

12. Research Objectives
Define a GENERAL OBJECTIVE and derive SPECIFIC OBJECTIVES
The formulation of objectives will help to:
Focus the study (narrowing it down to essentials)
Avoid the collection of data which are not strictly necessary for understanding and solving the problem you have identified
Organize the study in clearly defined parts or phases

13. Research Hypothesis
Intervention, Observation, Control variable
Independent variable
Dependent variable
Make clear statements!
Describes the relationship between INDEPENDENT variables (risk factors, predisposing factors) and DEPENDENT variables (outcome)
Determines the type of data to be collected and the type of analysis to be conducted

14. Outcome of Interest Primary Endpoint Secondary Endpoints
– What is it?
– Can it be defined precisely?
– Can it be measured?
– How do you plan to measure / document it?
Secondary Endpoints
– Are there any?
– If yes, how many? (too many?)
– If no, should there be?

15. Study Design /Methods

16. Eligibility Criteria (Inclusion/ Exclusion)

17. Sample Size Estimation
For almost every type of study
Different inputs depending on study design
Well laid out in statistical texts
Trade off between power and practicality
Be prepared to abandon study if necessary
Get help!

18. Objective of Sample Size Estimation

19. Methodology Data quality control
Describe measures of data quality control:
Double data entry
Consistancy checking
Data monitor
Verfication procedures of source data
Interrater variability measurements (definition interpritiation)

20. Ethical considerations
One of the most important aspects of biomedical research!
Ask local IRB for advice as needed!
Important aspects to consider:
Data safety / confidentiality (need for CEC‘s and DSMB‘s)
Any possibly harm/ side effects/ consequences
Right of discontinuation at any time
Role of data safety and monitoring board (in trials)
Alternative treatments/ approaches (in trials)
Risk versus Benefits

21. Ethical considerations Informed consent
Outline how, when and where the patient will be consented!
Information form should contain:
Justification for research
Responsibilities (Who)
Outline of study
Risks
Insurance
Confidentiality (legal framework)
Volontary particpation
A separate consent form is required!
Simple language!

22. References/Bibliography
Use of standard referencing system:
Harvard style
Name and publication year in text
Alphabetical bibliography
Vancouver style
Numbered references
Continous referencing in text
Make use of software
Reference Manager
Endnote software
See also „A Pratical Guide for Health Researchers“

23. Budget The budget should be broken down by: Items Budget justification
Personnel
Consumables, equipment, supplies, communication, funds for patients, data processing
Budget justification
Jusitify the use of each item, considering the workplan of the study

24. Appendicies Case Record Forms (CRFs)
Questionaires
Patient information form (in required languages)
Consent form (in required languages)
Core Lab requirements (as applicable)
CV of investigators
Statistical analysis plan
Timelines: enrollment projections, follow up completion, manuscript submission
Clinicaltrials.gov registration

25. Practical hints for funding proposals
Discuss research proposal with your collaborators well in advance
Strictly follow guidelines for applicants
Application deadlines are strict
Demonstrate your expertise
Be realistic about the time things take
Ask your colleagues to read your proposal prior to submission
No typographical or other errors!

26. Consider the job of the reviewer …
has an interest in ranking the applications in an unbiased, fair, scientifically rigorous way, giving the best scores to those grants that are most likely to contribute to our body of knowledge.
may not be extremely familiar with all techniques. All parts of the grant must be clear and written in such a way that a non-expert can understand them.
may not know the applicant personally. It is the job of the applicant to convince the reviewer.
may not fully understand the significance of the research area without a clear, compelling argument presented in the application.
is capable of understanding and interpreting preliminary data if well-presented. 
must read 10 to 15 applications in great detail and form an opinion about all of them.
The successful proposal is clear and precise, is easy to read, has a detailed experimental design section, and is free of typographical and other errors.

27. Good Luck!