 Be familiar with the types of research study designs  Be aware of the advantages, disadvantages, and uses of the various research design types  Recognize a study design from published study abstracts used as a class exercise

 Two main categories: 1.Observational:  Studies in which subjects are observed 2.Experimental:  Studies in which the effect of an intervention is observed

 Case Series  Case-Control  Cross Sectional  Cohort

 Case Series ◦ What are they?  Author describes some interesting or intriguing observations that occurred to a small number of patients ◦ Characteristics:  The simplest design  Descriptive  Lead to hypotheses subsequently investigated by other types (Case-Control, Cross-Sectional or Cohort study)  Generally over short period of time  Generally no controls

 Case-Control ◦ Retrospective ◦ Question answered: “What happened?” ◦ Matching needed for controls ◦ Might be difficult to differentiate from Case Series (Both are after the fact)  Ask if the goal was to describe a phenomenon, if description is the goal  Case Series

Example: association between smoking and lung cancer. People with lung cancer are enrolled to form the case group, and people without lung cancer are identified as controls. Researchers then look back in time to ascertain each person's exposure status (smoking history), (retrospective design). Investigators compare the frequency of smoking exposure in the case group with that in the control group, and calculate a measure of association.

 Cross Sectional ◦ AKA Surveys, epidemiologic or prevalence studies ◦ What are they?  Analyzes data collected on a group of subjects at one time ◦ Question answered: “What is happening now?” ◦ Short time

 Possible uses of Cross Sectional studies: ◦ Diagnosing or staging a disease ◦ Evaluating different methods of doing the same thing  e.g. Examining the relationship between histology slides and MRI findings of diseased carotid arteries ◦ Establishing norms  e.g. Establishing normal lab values from normal subjects ◦ Surveys  May use preexisting validated surveys  To learn what people think  Sometimes combined with interviews

 Cohort ◦ Question answered: “what will happen?” ◦ Prospective/forward ◦ e.g. Framingham study of cardiovascular disease: Started in 1948, 6000 citizens participated, followed for 20 years (study in 1970 by Gordon and Kannel) ◦ Possible uses:  Typical cohort study  Outcome assessment (patient outcomes: economic, functional, satisfaction,..)  Historical Cohort studies/AKA Retrospective cohort: Relies on prospective records collected (If accurate) – still forward in time in the past

Notion of time

Case SeriesCase-ControlCross SectionalCohort Longitudinal Studies

 AKA Clinical Trials (Involve humans)  Easier to identify (usually explicitly stated in the abstract)  Two main categories of clinical trials: 1.Controlled trials 2.Uncontrolled trials

Controlled trials – Experimental drug or procedure compared with another, with a placebo, or with the standard procedure – Greater validity

 Trials with independent concurrent controls ◦ Double or single blind ◦ Best is randomized assignment ◦ Same point in time ◦ These include:  RCT:  The epitome of all research designs  Provides the strongest evidence of concluding causation  Best insurance that results are due to the intervention  Nonrandomized trials:  Assignment not randomized  Opened to biases  Trials with self controls ◦ Subject to bias (Hawthorne effect) ◦ Can do crossover study (with washout period in between)  Trials with external control ◦ Uses the results of another investigator’s research as a comparison ◦ Historical controls can also be used: for disease with no cures yet

 The Hawthorne effect (also referred to as the observer effect) is a type of reactivity in which individuals improve an aspect of their behavior in response to their awareness of being observed.  washout period: A period in a clinical study during which subjects receive no treatment for the indication under study and the effects of a previous treatment are eliminated.

Uncontrolled trials  Investigator’s experience with the new drug or procedure is described but not formally compared with another one  More likely to be used for interventions that are procedures rather than drug

Controlled trialsUncontrolled trials Self controls Independent concurrent controls External controls RCTNon-randomized

Best Worst

Lancet 2002; 359: 57-61

 Advantages: ◦ RCT is the gold standard or reference  Disadvantages: ◦ Expensive ◦ Long duration

 Advantages: ◦ Design of choice for studying cause of a disease, course, risk factors  Disadvantages: ◦ Cannot be used to prove causation ◦ Long studies can be costly ◦ Vulnerable to patient attrition, migration

 Advantages: ◦ Quickest ◦ Least expensive ◦ Good for rare diseases and diseases that take long time ◦ Good for investigation of a preliminary hypothesis ◦ Time factor research  Disadvantages: ◦ Large biases ◦ Difficult to find matching controls

 Advantages: ◦ Best for:  Determining status of a disease  Prevalence of disease  Evaluation of diagnostic procedures ◦ Relatively quick and inexpensive  Disadvantages: ◦ Provide only a snapshot in time

 Advantages: ◦ Easy to write ◦ May be extremely useful to investigators looking for causes of the observation  Disadvantages: ◦ Subject to many biases in patient selection ◦ Should be viewed as hypothesis generating, not conclusive

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