Different Types of Epidemiologic Studies Kamran Yazdani, MD MPH Department of Epidemiology and Biostatistics School of Public Health

CASP Critical Appraisal Skills Programme http://www. phru. nhs CASP Critical Appraisal Skills Programme http://www.phru.nhs.uk/Pages/PHD/resources.htm (Appraisal Tools)

CASP Major Points: Is the Objective CLEAR? Is the Method (Design & Analysis) APPROPRIATE? Dealing with: Selection Bias Information Bias Confounding Chance error Reporting (Analysis, Results) Interpreting (Association, Causation) Generalizability Consistency, Coherence SCREENING

http://www.strobe-statement.org/Checklist.html (Checklists) STROBE STrengthening the Reporting of OBservational studies in Epidemiology http://www.strobe-statement.org/Checklist.html (Checklists)

Epidemiology The study of the distribution and determinants of health-related states or events in specified populations, and the application of this study to control of health problems.

Aim of epidemiological studies To determine distribution of disease Descriptive Studies To examine determinants of a disease To judge whether a given exposure causes or prevents disease Analytical Studies

انواع مطالعات توصيفي: با هدف بررسي و توصيف يك وضعيت بدون آنكه قصد بررسي يك رابطه (آزمون فرضيه) را داشته باشيم تحليلي: با هدف بررسي يك رابطه ، اختلاف يا ارتباط (آزمون فرضيه) صورت مي پذيرد

Epidemiologic Design Strategies Descriptive studies case reports, case-series, cross-sectional Analytical studies Observational studies Cross-sectional Case-control studies Cohort studies Intervention studies Clinical trials Field trials Community trials Experimental (animals) Diagnostic Tests studies or Process Research

انواع مطالعات توصيفي تحليلي مشاهده اي گزارش مورد گزارش موارد كوهورت مداخله اي گزارش مورد گزارش موارد كوهورت كارآزمايي باليني اكولوژيك مورد شاهدي كارآزمايي ميداني مقطعي كارآزمايي اجتماعي

Advantages of Case Reports and Case series Allows for the description of new disease processes. Allows for the description of outcomes associated with rare diseases or rare features of any disease. To formulate hypotheses of the association

Disadvantages/Limitations of Case Report & Case Series Impossible to determine disease frequency. Cannot establish causality between exposures or risk factors and disease outcome.

Case Report example In 1961, a published case report of a 40 year-old woman who developed pulmonary embolism after beginning use oral contraceptive

Case Series example In Los Angeles, five young homosexuals men, previously healthy, were diagnosed with pneumocyst cariini pneumonia in a 6-month period (80-81)

Case Series example RESULTS: Twelve patients with histopathologically confirmed tumours detected after extraction of teeth were studied. There were 11 males and one female giving a male to female ratio of 11:1. They ranged in age from 15-85 years with a mean age of 53 years. Pain and swelling were the most common presenting complaints. The mandible was more often involved seven (58.3%) cases while five (41.7%) cases occurred in the maxilla. Squamous cell carcinoma (in 9 cases) was the most common malignant neoplasm among these patients.

Cross-sectional studies Cross-Sectional Studies measure existing disease and current exposure levels. They provide some indication of the relationship between the disease and exposure or non-exposure

Cross Sectional Studies (contd) Sample without knowledge of Exposure or Disease Sample at one point in time Mostly prevalence studies/surveys

Cross Sectional Studies (Advantages) Good design for hypothesis generation Can estimate overall and specific disease prevalence and sometimes rates Can estimate exposure proportions in the population Can study multiple exposures or multiple outcomes or diseases

Cross Sectional Studies (Advantages) Relatively easy, quick and inexpensive!!! Best suited to studying permanent factors (breed, sex, blood-type) to deal with TEMPORALITY. Often good first step for new study issue

Cross Sectional Studies (Disadvantages) Impractical for rare diseases Not a useful type of study for establishing causal relationships Confounding is difficult to control Problems with temporal sequence of data hard to decide when disease was actually acquired miss diseases still in latent period recall of previous exposure may be faulty

Cross Sectional Studies Disease Status Yes No Total Exposure Status Yes a b a +b No c d c +d a +c b +d N

Cross Sectional Studies Depression Yes No Total Yes 3 87 90 low SES No 14 75 89 17 162 179

Cross Sectional Studies Points need concern: Sampling Protocol (Quality Assurance & Control) Appropriate Analysis Appropriate and Fair Interpretation

Randomized Clinical Trials Population Outcome Inclu & Exclu New Treatment Improved Not improved Participants (Randomization) Comparison treatment Improved Not improved

Randomized Clinical Trials Cure Total Yes No A 13 87 100 Treatment 75 100 B 25 38 162 200

Cohort / Follow-up Studies Study population (Non-diseased) Exposed Non-exposed Disease + Disease -

Cohort study, at a glance Case control Cohort Study group Diseased/ healthy Exposed/ unexposed Measure of effect OR, AR Risk, RR,OR.AR temporal Hard to establish Easy to establish multiple exposures outcomes time Short Long cost inexpensive Expensive Population size small Large Information bias exposure Outcome Best when D rare E frequent E rare D frequent Problems Control selection Exposure information Unexposed selection change over time

جدول توافقي در مطالعه‌ي كوهورت Disease Status Yes No Total n1 Exposure Status Yes a b a +b No c d c +d n2 a +c b +d N

آيا مطالعه كوهورت هميشه تحليلي است؟

مطالعه كوهورت ـ انواع زمان حال مواجهه پي آمد مواجهه پي آمد مواجهه

Prospective vs. retrospective Cohort Studies Prospective Cohort Studies Time consuming, expensive More valid information on exposure Measurements on potential confounders Retrospective Cohort Studies Quick, cheap Appropriate to examine outcome with long latency periods Admission to exposure data Difficult to obtain information of exposure Risk of confounding

چه موقع مطالعه كوهورت مناسب‌تر است؟ شواهدي موجود باشد LOSS TO FOLLOW UP را بتوانيم كنترل كنيم مدت پي گيري نسبتاً كوتاه باشد بتوانيم كوهورت تاريخي انجام دهيم مواجهه نادر باشد

Selection of the Exposed Population Sample of the general population: Geographically area, special age groups, birth cohorts (Framingham Study) A group that is easy to identify: Nurses health study Special population (often occupational epidemiology): Rare and special exposure

Selection of the Comparison Population Internal Control Group Exposed and non-exposed in the same Study population (Framingham study, Nurses health study) Minimise the differences between exposed and non-exposed External Control Group Chosen in another group, another cohort (Occupational epidemiology: Asbestosis vs. cotton workers) The General Population

Bias Selection bias: Information bias Non-representativeness (unequal in e+ & e-) Non-response during data collection Losses to follow up Healthy worker effect Information bias Misclassification on exposure Misclassification on event

CASP questions

Case-control study Exposed Cases Non-exposed Study Population Exposed

Direction exposure outcome

Applications Diseases with long latency period For best use of time and money The best for rare diseases & useful for prevalent diseases Mutiple exposures

Case-control study, at a glance Cohort Study group Diseased/ healthy Exposed/ unexposed Measure of effect OR, AR Risk, RR,OR.AR temporal Hard to establish Easy to establish multiple exposures outcomes time Short Long cost inexpensive Expensive Population size small Large Information bias exposure Outcome Best when D rare E frequent E rare D frequent Problems Control selection Exposure information Unexposed selection change over time

BIASes Selection Information

Selection of cases Case definition is more important than other studies: Strict diagnostic criteria (high degree of caseness) Homogenous diseases (one well-defined outcome or health-related state)

Selection of cases Sources of cases Population Hospital (available, better dx, low inf bias, high sel bias) Registry … Are the cases representative of total population or a fraction of it?

Selection of cases Incident vs. Prevalent Selection & Information BIASes

Selection of controls Study base Deconfounding Comparable accuracy Sel bias Deconfounding confounding Comparable accuracy Info bias

Selection of controls سوال: آيا مي توان براي يك گروه بيمار كه از بيمارستان انتخاب شده اند، گروه كنترل را از جامعه گرفت؟

Types of controls Population controls Hospital controls Friend, RDD, neighbor controls Hospital controls Similar disease as controls

Hospital controls Similar study base Similar quality of information Convenience

Population controls Tax lists, vote lists, telephone directories,… RDD: Selection bias due to higher ses., families with more than phone lines and family size

Matching

Ratio of controls to cases Statistical considerations (increasing power) Unsuitable for very low or very high powers under equal sizes

Ratio of controls to cases Control to case ratio: up to 4-fold: case cont 1:1 200 200 1:2 150 300 1:3 133 400 1:4 125 500 1:5 120 600

جدول توافقي در مطالعه‌ي مورد ـ شاهدي Disease Status Yes No Total Exposure Status Yes a b a +b No c d c +d a +c n1 b +d n2 N

CASP questions

مقايسه RR و OR در مطالعه كوهورت OR مي تواند برآورد خوبي از RR باشد اگر: بيماري بروز بالايي نداشته باشد در مطالعه مورد شاهدي OR مي تواند برآورد خوبي از RR باشد اگر: موردها نماينده بيماران جامعه باشند شاهدها نماينده سالمهاي جامعه باشند

Comparing cohort and case control Study group Diseased/ healthy Exposed/ unexposed Measure of effect OR, AR Risk, RR,OR.AR temporal Hard to establish Easy to establish multiple exposures outcomes time Short Long cost inexpensive Expensive Population size small Large Information bias exposure Outcome Best when D rare E frequent E rare D frequent Problems Control selection Exposure information Unexposed selection change over time

Intuition and Logic in Research Dominant Mental Activity Intuition Feeling Judgement Experience Analysis Experiment Clinical trials Cohort Study Hi Case-control Study Cross-sectional Study Control over variance Case Report Case Series Qualitative Research Lo Potential for Misinterpretation Lo Hi