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

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

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

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

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

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

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

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

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?

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

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?

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

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”

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?

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?

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

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?

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

Research Questions

Research Question Expertise Mentors Collaborators Relevance Feasibility

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

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

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…

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

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

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

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

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).

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.

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

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?

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.