Journal Club Curriculum-Study designs

Objectives  Distinguish between the main types of research designs  Randomized control trials  Cohort studies  Case control studies  Cross-sectional studies  Identify the strengths and weaknesses of the main research designs

Categories of Research Experimental Observational

Randomized Control Trial  Experimental study design  Commonly used to compare treatment options or interventions  Study subjects are randomly assigned to an arm of the study (e.g., treatment or control group)  Usually accomplished via computer  Potential biases addressed through randomization, concealed allocation, blinding

Randomized control study (RCT)  Gives the best strength of association  Can be used to ‘prove’ that one intervention is better than another  Best if randomized and blinded to MD/ research staff, to statistician and to patient (triple blinded) which minimizes allocation bias  Expensive (the most expensive)  Best to compare treatment groups  Hard to accrue patients for rare diseases

Random Selection vs. Random Assignment  Random selection – population sorted into groups from which sample members are randomly chosen  Random assignment – study participants assigned to the treatment or control group using random procedure  May not be randomly selected  May be from a convenience sample of your patients

Defined Population RANDOMIZED New treatment Placebo or current treatment “ Control group ” Improved Not improved OUTCOME Improved Not improved OUTCOME

RCT Example  Post menopausal women selected from population and randomly assigned  Study group – receives HRT  Control group – receives placebo  Both groups observed prospectively to see who develops endometrial cancer  Compare rates of endometrial cancer in the two groups

Benefits of RCTs  Can study cause and effect  Control for confounders  Factors associated with both the treatment/intervention and outcome  Reduce bias – high internal validity  Provide strong evidence for effectiveness of treatment/intervention

Can’t Always Do RCT  Is it feasible?  Is it ethical?  Is blinding possible?  Or will the patient, and/or physician be aware of the intervention?

Limitations of RCTs  Tight inclusion and exclusion criteria necessary to achieve control  Study may not be generalizable – low external validity

Observational Studies  Used to study risk factors for disease and determinants of health  Including behavioral, socioeconomic and environmental determinants  Used to predict morbidity and mortality  Used when experimental studies not ethical

Cohort Study  A cohort is a group of people who share a common characteristic or experience within a defined period  It is an analysis of risk factors and follows a group of people who do not have the disease, and uses correlations to determine the risk of a subject developing the outcome of interest.

Cohort Study  Cohort studies are susceptible to bias by differential loss to follow-up, the lack of control over risk assignment and thus confounder symmetry, and the potential for zero time bias when the cohort is assembled.

Cohort Study  Prospective cohort – starting now, follow a group over time to see the effect of the risk factor (or an intervention) on disease  Retrospective cohort(or historical cohort) – collected data in past and now assess the effect of the risk factor/intervention on subsequent disease

Prospective Cohort PresentFuture

Retrospective Cohort PastPresent

Cohort Studies  Stronger association than case control or X-sectional  Needs well balanced groups ie comparable groups  Can determine a relative risk or risk ratio with prospective cohort study  Expensive

Cohort Studies  Can ‘prove’ an association  Examples: WHI, Nurse’s Health Study  Can be used to develop additional hypotheses to test

Cohort Example  Identify group of post menopausal women who have been prescribed HRT – study group  Identify similar group of post menopausal women who have not been prescribed HRT – control group  Follow both groups over time to see who develops endometrial cancer  Compare rates of endometrial cancer

Benefits of Cohort Studies  Temporality - can establish that the risk factor precedes the disease  Can study cause and effect  Can be used when RCTs unethical or unfeasible  Higher external validity – more generalizable to your patients

Case Control Study  Backward looking observational study design  Start with the outcomes and look backwards to see if the patient had the risk factor/intervention

Case control study  People with a disease (often, a specific diagnosis, perhaps lung cancer) are matched with people who do not have the disease (the 'controls'). Further data are then collected and the groups are compared to find out if other characteristics (perhaps a history of smoking) are also different between the two groups.  They have pointed the way to a number of important discoveries and advances, but their retrospective, non-randomized nature limits the strength of their conclusions  Appropriate for rare conditions particularly cancers

Case Control Study  Subject to selection, measurement and recall bias  Can infer an association but cannot prove  Inexpensive  Can calculate odd of developing disease (odds ratio)

Case Control

Case Control Example  Identify a group of post menopausal women who have recently been diagnosed with endometrial cancer – cases  Identify similar group of post menopausal women who have not been diagnosed with endometrial cancer – controls  Determine whether the women used HRT  Compare the odds that women who developed endometrial cancer used HRT with the odds that women who did not develop endometrial cancer used HRT

Benefits of Case Control Studies  Used to study rare events  Used when RCTs unethical and cohort studies unfeasible  Higher external validity than RCTs

Cross-sectional Study  Observational study design where data are collected at one point in time  Exposure and outcome estimated at the same point in time  Used for descriptive studies of populations  Used to study prevalence – proportion of the population with the condition or the disease

Cross Sectional Study  Cross-sectional data refers to data collected by observing many subjects (such as individuals, firms or countries/regions) at the same point of time.  Analysis of cross-sectional data usually consists of comparing the differences among the subjects.  Good for determining if a research question may be worthwhile to pursue  Inexpensive  Cannot determine risk or odds of developing a disease  Subject to selection bias and recall bias

Cross-sectional Study Example  Post menopausal women submit to an endometrial biopsy – findings classified as normal, hyperplasia or cancer  Biopsy results are compared to HRT use  Study identifies prevalence of endometrial cancer and hyperplasia in HRT users

Limitations of Observational Studies  Lower internal validity than RCTs – more susceptible to bias  May not allow for study of cause and effect  Level of evidence is lower