Types of study designs Arash Najimi PhD. Candidate Department of health education & health promotion Isfahan University of Medical Sciences

Types of Studies Descriptive Studies Observational Analytic Studies Cross Sectional studies Ecologic studies Case Control studies Cohort studies Experimental Studies Randomized controlled trials

Hierarchy of Study Types Analytic Descriptive Case report Case series Survey Observational Cross sectional Ecologic Case-control Cohort studies Experimental Randomized controlled trials Field Trials Community Trials Strength of evidence for causality between a risk factor and outcome

Descriptive studies Getting a “lay of the land” Surveys (NHIS, MCBS) Describing a novel phenomena Case reports or case series

Descriptive studies Cannot establish causal relationships Still play an important role in describing trends and generating hypotheses about novel associations The start of HIV/AIDS research Squamous cell carcinoma in sexual partner of Kaposi sarcoma patient. Lancet. 1982 Jan 30;1(8266):286. New outbreak of oral tumors, malignancies and infectious diseases strikes young male homosexuals. CDA J. 1982 Mar;10(3):39-42. AIDS in the "gay" areas of San Francisco. Lancet. 1983 Apr 23;1(8330):923-4.

Analytic Studies Attempt to establish a causal link between a predictor/risk factor and an outcome. You are doing an analytic study if you have any of the following words in your research question: greater than, less than, causes, leads to, compared with, more likely than, associated with, related to, similar to, correlated with

Hierarchy of Study Types Analytic Descriptive Case report Case series Survey Observational Cross sectional Ecologic Case-control Cohort studies Experimental Randomized controlled trials Field Trials Community Trials Strength of evidence for causality between a risk factor and outcome

Cross-sectional Study: Pluses + Prevalence (not incidence) + Fast/Inexpensive - no waiting! + No loss to follow up + Associations can be studied

Cross-sectional study: minuses - Cannot determine causality Cigarette smoking Depression time

Cross-sectional study: minuses - Cannot determine causality - Cannot study rare outcomes

Case control studies Investigator works “backward” (from outcome to predictor) Sample chosen on the basis of outcome (cases), plus comparison group (controls)

Study multiple exposures in a Case-control Study B Exposed to A Not Exposed Disease No Disease

Case control studies Determines the strength of the association between each predictor variable and the presence or absence of disease Cannot yield estimates of incidence or prevalence of disease in the population (why?) Odds Ratio is statistics

Case-control Study: pluses + Rare outcome/Long latent period + Inexpensive and efficient: may be only feasible option + Establishes association (Odds ratio) + Useful for generating hypotheses (multiple risk factors can be explored)

Case-control study-minuses Causality still difficult to establish Selection bias (appropriate controls) Recall bias: sampling (retrospective) Cannot tell about incidence or prevalence

Cohort studies A cohort (follow-up, longitudinal) study is a comparative, observational study in which subjects are grouped by their exposure status, i.e., whether or not the subject was exposed to a suspected risk factor The subjects, exposed and unexposed to the risk factor, are followed forward in time to determine if one or more new outcomes (diseases) occur Subjects should not have outcome variable on entry The rates of disease incidence among the exposed and unexposed groups are determined and compared.

Study multiple outcomes in a cohort Study Exposed Not Exposed C B Develop Disease A Do not

Elements of a cohort study Selection of sample from population Measures predictor variables in sample Follow population for period of time Measure outcome variable Famous cohort studies Framingham Nurses’ Health Study Physicians’ Health Study Olmsted County, Minnesota

Prospective cohort study structure The present The future Top USMLE scorers Everyone else time

Strengths of cohort studies Know that predictor variable was present before outcome variable occurred (some evidence of causality) Directly measure incidence of a disease outcome Can study multiple outcomes of a single exposure (RR is measure of association)

Weaknesses of cohort studies Expensive and inefficient for studying rare outcomes Often need long follow-up period or a very large population Loss to follow-up can affect validity of findings

Other types of cohort studies Retrospective cohort Identification of cohort, measurement of predictor variables, follow-up and measurement of outcomes have all occurred in the past Much less costly than prospective cohorts Investigator has minimal control over study design

Other types of cohort studies Nested case-control study Case-control study embedded in a cohort study Controls are drawn randomly from study sample Case cohort Study

Hierarchy of Study Types Analytic Descriptive Case report Case series Survey Observational Cross sectional Ecologic Case-control Cohort studies Experimental Randomized controlled trials Field Trials Community Trials Strength of evidence for causality between a risk factor and outcome

Randomized controlled trials Investigator controls the predictor variable (intervention or treatment) Major advantage over observational studies is ability to demonstrate causality Randomization controls unmeasured confounding Only for mature research questions

Basic Trial Design Treatment Dx No Dx Control Dx No Dx Placebo Population Treatment Dx No Dx Randomization Sample Control Dx No Dx Placebo For example, select persons with high LDL-cholesterol from among patients presenting to the metabolic clinic at the SFVA and treat with lovastatin to see if this results in lower LDL cholesterol. Note can have an uncontrolled trial or time series design. These have no concurrent control group and can produce the wrong answer due to learning, regression to the mean or secular trends. Note, for example, that it is common to have a 30-50% improvement in depression scores, pain scores, hot flash scores. Can have a controlled trial without randomization. This addresses learning, regression to the mean and secular trends, but introduces the issue of baseline differences in the groups. This design is really no different from a double cohort study. Can have a randomized controlled trial without placebo (blinding). This allows (as will be discussed later) for co-intervention and biases outcome ascertainment. Also note that these three elements - treatment, randomization and blinding result in the major ethical concerns regarding randomized trials.

Steps in a randomized controlled trial Select participants Measure baseline variables Randomize Eliminates baseline confounding Types (simple, stratified, block)

Steps in a randomized controlled trial Blinding the intervention As important as randomization Follow subjects Measure outcome Clinically important measures Adverse events

Comparing Cohort Studies with Randomized Trials Interventional Study Observational Study Study group Study group Random Allocation No Allocation Cannot randomize people to receive a putatively harmful substance, such as a suspected carcinogen, the “exposure” in most randomized trials is a treatment or preventive measure Critical to interpreting study findings In a nonrandomized study, when we observe an association of an exposure with a disease, we are left with uncertainty as to whether the association may be a result of the fact that people were NOT randomized to the exposure; Perhaps it is not the exposure, but rather the factors that led people to be exposed, that are associated with the disease. E.g., If an increased risk of a disease is found in workers at a certain factory, and if workers at this factory tend to live in a certain area, the increased risk of disease could result from an exposure associated with their place of residence rather than with their occupation or place of work. Group A Group B Group A Group B

Hierarchy of Study Types Analytic Descriptive Case report Case series Survey Observational Cross sectional Ecologic Case-control Cohort studies Experimental Randomized controlled trials Field Trials Community Trials Strength of evidence for causality between a risk factor and outcome