CLASS SESSION 11 RANDOMIZED CONTROLLED TRIALS Epidemiology 503

CLASS SESSION 11 RANDOMIZED CONTROLLED TRIALS Epidemiology 503, Section 2

Announcements Exams expected back Wednesday New groups!

Why Perform Studies? Etiology or cause of disease Extent of disease in the community Natural history and prognosis Evaluate interventions Provide foundation for developing public policy

Objective of Epidemiologic Studies Causal? Factor (“exposure”) (social, behavioral, genetic, drug treatment, policy, etc. ) Does exposure CAUSE outcome? Health Outcome (health event, disease occurrence, death, relapse)

Hierarchy of Study Designs Observational Studies Ecologic Studies Generate Hypotheses Cross Sectional Studies Good place to start investigating a research question Case Control Studies Cohort Studies Experimen tal Studies Randomized Trials / Intervention Studies Establish Causality Gold standard for establishing causality

The Gold Standard of Study Designs Randomized-Controlled Trials (RCTs) � Randomly assign persons or groups to either receive or not receive the exposure Considered the ideal design for evaluating effectiveness and side effects of new interventions or treatments

Source Population Study Population / Defined Population RANDOMIZATION Exposed to factor Event No event Not exposed to factor Event No event

Source Population Study Population / Defined Population RANDOMIZATION New treatment Improved Not improved Current treatment Improved Not improved

9 Components of a Randomized Trial Randomization Blinding (Masking)

Randomization 10 Every participant has equal probability of being selected into the study arm Randomize AFTER participants are screened Makes control and treatment groups similar for factors known and unknown � Use statistical tools to compare means or proportions of these variables by group (ANOVA, Chi-Square test) Removes investigator bias in the allocation of participants

Blinding (Masking) 11 Single blinded trials � Subjects do not know which treatment group they are assigned to Double blinded trials � Subject and data observers (and analysts) are unaware of treatment assignment

Validity Results of a study are valid if they reflect the truth � Internal validity refers to the design, methods, analysis and results of an individual study. Did the study do what it intended to do? � External validity refers to whether internally valid findings are also applicable (generalizable) to people other than those included in an individual study.

Source Population External Validity: Generalization of study to larger source population Study Population RANDOMIZATION Internal Validity Exposed to factor Event No event Internal Validity: Ability to reach correct conclusion from study - Reliability of data - Compliance - Loss to follow-up Not exposed to factor Event No event

Important Note A study that is internally invalid cannot ever be externally valid because it is fundamentally flawed and will result in biased (i. e. , wrong) results

Measures of Association: Relative 15 Ratio of two measures of disease incidence � Risk Ratio (Relative Risk) CIexposed = CIunexposed � Rate a / (a + b) c / (c + d) Ratio IRexposed = IRunexposed a / Person Timeexp c / Person Timeunexp Exp > 1 Exposed/treated has more risk than unexposed/control = 1 Exposed/treated has same risk as unexposed/control < 1 Exposed/treated has less risk than unexposed/control Outcome + - + a b - c d Total TOTAL

16 Measures of Association: Difference of two measures of disease incidence � Risk Difference CIexposed – CIunexposed = [a/(a+b)] – [c/(c+d)] � Efficacy Outcome CIunexposed – CIexposed Exp + + a b CIunexposed Total c Total d TOTAL

The RCT as “gold standard” Advantages Strongest evidence for causality If blinded, less observer bias Disadvantages Not “real life” High cost Inappropriate or unethical for many questions Subject to poor compliance, loss to follow-up

Today. . . 18 In-class activity re: findings from DASH (Dietary Approaches to Stop Hypertension) Study on dietary patterns & blood pressure

Group 1 Group 2 Group 3 Group 4 Group 5 19 Cousineau, Cody ccousz Ma, Heyun heyunma Zhang, Shukai shukaiz Burr, Laura lburr De Jong, Maxwell mgdejong Empey, Margaux empeym Liang, Chen ccliang Dave, Ashka Group 6 Sheth, Alexandra assheth Kilian, Tess tkilian Parkinson, Patrick pparkins Serpuja, Gita gserpuja Pont, Cassidy casspont Yaros, Thomas tfyaros addave Zhu, Ziwei zwzhu Espana, Katherine kvespana Craig, Nathan nacraig Fan, Lingxiao lingxfan Compton, Emily eacompto Spicer, Rosanna rrspicer Gao, Chao gchao Metz, Liza lizamm Amin, Shivali shivali Davis, Ellen emdavi Ma, Ying yingma Hamilton, Shannon shanlham Mulenga, Lukonde lukondem Sidhar, Shubhum ssidhar Yue, Xubo maxyxb Brewer, Aubrey brewerau Cloeter, Elyse cloetere Flynn, Nicole flnicole Amaya, Kerent kerentam Robinson, Myshelle marobi Eck, Hannah eckh Enache, Emma enacheem Babcock, Alexandra Maccarthy ambab Urdahl, Nicole nurdahl Fucinari, Juliana Eva jfucinar Tierney, John jomckayt Shackelford, Mira mirasha Novoa, Alfredo novoa Fang, Fang ffa Sharp, Whitney sharpwe Higgins, Madeline mlucille Group 7 Group 8 Group 9 Group 10