1. Study Design: Making research pretty Adam P. Sima, PhD July 13, 2016

2. Defining a Research Question
Outline
Research Question Review
Prospective vs. Retrospective
Types of Study Design
Extra information

3. Research Questions Statement of the research focus
Generally one of 3 options
Estimation
Examples: prevalence; incidence
Change
Examples: Pre/Post; change over time
Relationship
Examples: Differences between groups; correlations

4. Research Question
The ability to answer a research question hinges on a number of factors*
Resources are key for a study
Patient enrollment/laboratory tests
Collaborator’s time/effort
Available resources can determine study design
*See extra slides for other factors

5. Study Design Not all study designs can be used for every situation.
Proper study design, paired with close attention to other factors, make for an easy evaluation of your research question
The ‘other factors’ will be discussed in subsequent lectures

6. Study Design Prospective vs. Retrospective
Prospective: Any study in which the data collector has control over which pieces of information are recorded.
Ex: Randomized controlled trials, epidemiologic studies
Retrospective: Any study that uses an extent data source and the data collector has no control over the information collected.
Ex: Chart reviews, administrative databases

7. Study Design Prospective Retrospective Expensive Planning intensive
Little or no bias
Little data management
No limit to information collected (w/in budget)
Causality (sometimes)
Inexpensive
Potentially flexible
High potential for bias
High potential for data management issues
Limited to variables available in database
Limited causal inference

8. Study Design Common study designs Clinical trials Cohort studies
Randomized controlled trials (RCTs)
Cohort studies
Cross-sectional
Case-control

9. Study Design Clinical Trials
Time-consuming; difficult to manage; potentially expensive; prospective
Phases
Phase I: Dose-finding (estimation)
Phase II: Efficacy (estimation, change, relationship)
Phase III: Confirmatory (RCT) (estimation, relationship)
Phase IV: Effectiveness (estimation, change, relationship)
Do a group of TBI patients using Drug X have less incidence of seizures than a control group?

10. Study Design
RCTs
Baseline versus Follow-up
Dropout
Treatment groups
Placebo or Standard-of-Care
Randomization
ALWAYS contact a biostatistician before planning a RCT

11. Study Design Cohort studies
Follow patients over time
Estimation, Change
Optimal for looking at change over time
‘Pre-/Post design’
Prospective or observational
Can estimate the incidence rate
Is there a change in the percentage abusing alcohol or drugs in patients with a TBI?

12. Study Design Prospective Cohort Enroll N subjects Issues:
Follow until end of study
Issues:
Dropout
Rare diseases

13. Study Design Retrospective Cohort Find N subjects Issues:
Measure outcomes that have already happened
Issues:
Same as prospective cohorts
“…existing data may be incomplete, inaccurate, or measured in ways that are not ideal for answering the research question”

14. Study Design Cross-sectional studies
All measurements are made at same time
The ‘anti-cohort’ study
Estimates prevalence
Very limited causal ability
What is the association between anxiety and depression in TBI patients?

15. Study Design Case-Control Studies
Definitions
Cases: Subjects with disease
Controls: Subjects without disease
Good for rare diseases
Match subjects on like factors
Matching can be a ‘black box’
Obtain a large amount of salient predictors
Then call a biostatistician
Controlling for a number of injury characteristics, is there a difference in the suicide rate between males and females for patients with a TBI?

16. Study Design Measuring population incidence/prevalence
Subjects drawn must be representative of a population
Advanced designs can be beneficial:
Less subjects (prospective)/more efficient use of data (observational)
More ethical study designs
Favors welfare of patients without compromising research fidelity

17. Activity In groups On your own See handout
How would you design a study to answer your research question if you had unlimited resources?
How would you design a study to answer your research question using only the resources available?
What are the main differences between the previous 2 questions, and how will you try to alleviate them in the design/data collection?

18. Study Design Resources
Research Innovator
Biostatistical Shared Resource
Cancer related projects only
Department of Biostatistics
Biostatistical Consulting Laboratory
Coming soon!
Home department resources

19. Research Questions

20. Research Question Expertise Mentors Collaborators Relevance
Feasibility

21. Research Question Sufficient knowledge of the subject matter
Expertise
Mentors
Collaborators
Relevance
Feasibility
Sufficient knowledge of the subject matter
Literature reviews
Experience

22. Research Question Mentors are important regardless of career stage
Expertise
Mentors
Collaborators
Relevance
Feasibility
Mentors are important regardless of career stage
Should help guide you through scientific, administrative, and political processes

23. Research Question
Expertise
Mentors
Collaborators
Relevance
Feasibility
Collaborators offer different expertise and skills to enhance the quality of research
Include researchers in other fields, bench scientists, biostatisticians, informaticists/data managers, coordinators, research assistants…

24. Research Question
Expertise
Mentors
Collaborators
Relevance
Feasibility
Good research questions should have clear clinical relevance
If not relevant, efforts will be taken away from more impactful activities

25. Research Question
Expertise
Mentors
Collaborators
Relevance
Feasibility
The research question needs to have a realistic chance of succeeding
Resources (time, personnel, supplies) need to be available
Study design must be appropriate for research question

26. Defining a Research Question
Research questions are dynamic
Change occurs as expertise, collaborator input, and resource availability becomes clearer
SEEK ASSISTANCE FROM RESEARCH TEAM EARLY AND OFTEN!!!!!
Including Biostatisticians

27. Defining a Research Question
Research Questions define the ‘who’, ‘how’, and ‘what’ of a research project.
Who: The general population of interest
How: The target variable of variable of interest
What: The purpose of the research

28. WHO General statement of the focus of the research
NOT inclusion/exclusion criteria
Related to the population of interest
BAD: The research will focus on seizures and gender.
GOOD: The research will focus on seizures and gender for subjects having a traumatic brain injury (TBI).

29. HOW Specific measurement used in assessing the research outcome
The outcome or response variable
BAD: The research will focus on seizures and gender in subjects having a TBI.
GOOD: The research will focus on the seizures 5-years post-injury and gender in subjects having a TBI.

30. WHAT Statement of what the research is going to focus
Generally one of 3 options
Estimation
Examples: prevalence; incidence
Change
Examples: Pre/Post; change over time
Relationship
Examples: Differences between groups; correlations

31. WHAT
BAD: The research will focus on the seizures 5-years post-injury and gender in subjects having a TBI.
GOOD (estimation): What is the incidence of seizures for males and females 5-years post-injury in subjects with a TBI?
GOOD (change): Did the rate of seizures increase between 1 and 5-years post-injury in subjects with a TBI, separately for males and females?
GOOD (relationship): Is the rate of seizures different for males and females different for subjects with a TBI 5-years post-injury?

32. Activity
On your own
Identify the ‘who’, ‘how’, and ‘what’ of your own research question.
If your research question does not have a ‘who’, ‘how’, and ‘what’, rewrite it.