Experimental Study Design RCT

EXPERIMENTAL Exposure manipulated by Investigator DescriptiveAnalytic Exposure NOT manipulated by Investigator OBSERVATIONAL Cohort Case-control Case-series Cross-sectional Ecological Clinical trials Study Designs

Experimental Design time Study begins here (baseline point ) Study population Intervention Control outcome no outcome outcome no outcome baseline future RANDOMIZATION

Types of trials

Randomized controlled trials (RCT) An epidemiological experiment in which subjects in a population are randomly allocated into groups, usually called study and control groups to receive and not receive an experimental preventive or therapetuic procedure, maneuver, or intervention John M.Last, 2001

EXPERIMENTAL STUDIES: Are of two types. Randomized Controlled Trials. Non Randomized Controlled Trials 1. Randomized Controlled Trials: Number one method of evaluation, basic steps are Drawing up a Protocol  Objectives  Questions to be asked  Criteria for selection  Size of sample  Allocation in study & control groups  Treatment to be given  Standardization of Procedures

Randomized Controlled Trials Examples include: (aspirin & streptokinase), (simvastatin & vitamins)

ii. Selecting Reference & Experimental or Study Population iii. Randomization REFERENCE POPULATION: It is the population to which the finding of trial is to be applied. STUDY POPULATION: Actual population that participates in the study and is derived from the reference population. Each person in reference population has equal chance of being included in study or Control group.

iv. Manipulation v. Follow Up vi. Assessment Deliberate application or withdrawal or reduction of suspected causal factor (vaccine, dietary component, habit). Examination of the experimental and control groups at a defined interval of time. Assessment of out comes in terms of  Positive resultBenefits  Negative result Side effects Both are compared in both groups.

NON-RANDOMIZED TRIALS When RCT is not possible on ethical, adm grounds  When preventive measures can be applied on community basis  When disease frequency is low and natural history is long  When cost and logistic is limited

NON-RANDOMIZED TRIALS TYPES: - 1.Un controlled Trials 2.Natural Experiments 3.Before & after Comparison Studies Trials with no comparison group. Experience of earlier untreated patients affected by the same disease Natural division into two groups e.g. smoker & nonsmoker, Migrants & natives, Religious and social groups. Without Control: Comparing the incidence of disease before and after introduction of a preventive measure. With Control: Preventive program is to be applied on entire community, another community is selected as control.

Experimental Study Examples Randomized clinical trial to determine if giving magnesium sulfate to pregnant women in preterm labor decreases the risk of their babies developing cerebral palsy Randomized community trial to determine if fluoridation of the public water supply decreases dental cavities

13 1.Randomized control trials/Clinical trials Parallel design Cross over design 2.Field trials 3.Community trials or Quasi study design Types Experimental Study Design

14 Design of a randomized controlled trial Study population Selection by defined criteria Non participants (do not meet selection criteria Potential participants Invitation to participate Non participants Control participants Randomization Treatment

15 Designs Used in Experimental Studies Parallel Design Cross Over Design

16 Patients Exposed to Specific R Unexposed to Specific R Random Assignment a Patients Exposed to Specific R Unexposed to Specific R Random Assignment Compareoutcome Time Time Compare Outcome Exposed and Unexposed to R Observation b

17 Advantages of Experimental Studies Exposure is under the control of investigator Randomization Blinding eliminates bias Control on time span Confounding factors can be controlled Best method to study causal relationship We can confirm or refute etiological hypothesis on evidence. Evaluate effectiveness and efficiency of Health services

18 Disadvantages of Experimental Studies Subject exclusion may limit ability to generalize findings to other patients. A long period of time is often required to reach a conclusion. A large number of participants may be required. Financial costs are typically high. Ethical concerns may arise. Subjects may not comply with treatment assignments. Exposure or treatment alternatives should be acceptable to both groups

19 Introduction Recall the definition of an experiment Trials - from the French trier (to try) Clinical trial – apply therapeutic interventions to sick individuals (e.g., chemotherapy trial) Field trial – apply preventive interventions to healthy individuals (e.g., vaccine trial) Community trial – apply interventions to aggregate units (e.g., fluoridation of public water)

20 Selected Concepts All except #2 apply to observational designs as well 1.Control group 2.Randomization 3.Admissibility criteria 4.Outcome ascertainment 5.Ethics

21 Element 1. Control Group The effects of an exposure can only be judged in comparison to what would happen in its absence The control group provides this comparison ExposedNot exposed

22 Illustration: “MRFIT” Multiple Risk Factor Intervention Trial Exposure: Health education vs. no special intervention Outcome: CVD Treatment group experienced dramatic declines in CVD But so did the control group Rates were declining in all groups in the 1970s Effect of the intervention was negligible

23 Effects from inert interventions Placebo effect – improvement associated with inert interventions Placebo effects are a scientific mystery

24 Hawthorne Effect subjects improve an aspect of their behavior being experimentally measured simply in response to the fact that they are being studied, not in response to any particular experimental manipulation.

25 Element 2. Randomization Randomization works by balancing extraneous determinants in the groups being compared, thus mitigating confounding

26 How randomization works Suppose you want to determine whether a particular diet (the exposure) is associated with improved weight gain in lab animals (outcome) Randomization encourages equal numbers of fast-growing rats in each group

27 Polio Field Trial (1954) Polio rates (per 100,000) Placebo 69 Refusers 46 Vaccinated 28 Note: Had refusers been used as the control group, the effects of the intervention would have been underrated (Am J Pub Health, 1957, 47: 283-7)Am J Pub Health, 1957, 47: Dr. Jonas Salk, 1953

28 3. Admissibility Criteria Restrict participants to those with uniform characteristics This too mitigates confounding Example: Excluding smokers from a study base would prevent confounding from smoking

29 4. Outcome Ascertainment Outcome ascertainments must be valid Without valid outcome ascertainment, we have GIGO (garbage in, garbage out)

30 5. Ethics – Respect for individuals – Beneficence – Justice – oversight – Informed consent

Unique Problems of Intervention Studies Ethics – Sufficient doubts to withold from half the population – Sufficient believes to expose half the population – Requires high scientific standards Feasibility – Widespread adaption of measures by community – Problems of finding sufficiently large eligible sample size Costs – Expensive

Summary Gold standard in epidemiological research Makes study groups comparable – Random allocation – Sufficient sample size Unique problems of ethics, feasibility and costs Ensure transparency of all trials