Experimental Study Design

RCT

EXPERIMENTALEXPERIMENTAL Exposure manipulated by Investigator

DescriptiveAnalytic

Exposure NOT manipulated by InvestigatorOBSERVATIONALOBSERVATIONAL

• Cohort• Case-control

• Case-series• Cross-sectional• Ecological

Clinical trials

Study Designs

Expe

rimen

tal D

esig

n

timeStudy begins here (baseline point)

Studypopulation

Intervention

Control

outcome

no outcome

outcome

no outcome

baselinefuture

RANDOMIZATION

Types of trials

B lind ed N o t b lind ed

R a nd o m ised N o t ran d om ised

C o n tro lled N o t co n tro lled

T ria l

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

ObjectivesQuestions to be askedCriteria for selectionSize of sampleAllocation in study & control groupsTreatment to be givenStandardization of Procedures

Randomized Controlled Trials

Examples include: (aspirin & streptokinase), (simvastatin & vitamins)

ii. Selecting Reference

&

Experimental or StudyPopulation

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 resultBenefitsNegative 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. NaturalExperiments

3. Before & afterComparison 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

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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

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Design of a randomized controlled trialStudy

population

Selection by defined criteria

Non participants(do not meet

selection criteria

Potential participants

Invitation to participate

Non participants

Control

participants

Randomization

Treatment

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Designs Used in Experimental Studies

• Parallel Design• Cross Over Design

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Patients

Exposed to Specific R

Unexposed to Specific R

RandomAssignment

aa

Patients

Exposed to Specific R

Unexposed to Specific R

RandomAssignment

CompareCompareoutcomeoutcome

TimeTime

Time

CompareOutcome

Exposed and Unexposed to

R

Observation

Observation

b

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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

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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

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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)

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Selected Concepts

All except #2 apply to observational designs as well

1. Control group 2. Randomization 3. Admissibility criteria4. Outcome ascertainment5. Ethics

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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

Exposed Not exposed

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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

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Effects from inert interventions

Placebo effect – improvement associated with inert interventions

Placebo effects are a scientific mystery

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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.

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Element 2. Randomization

Randomization works by balancing extraneous determinants in the groups being compared, thus mitigating confounding

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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

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Polio Field Trial (1954)

Polio rates (per 100,000)Placebo 69Refusers 46Vaccinated 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) Dr. Jonas Salk, 1953

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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

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4. Outcome Ascertainment

• Outcome ascertainments must be valid

• Without valid outcome ascertainment, we have GIGO (garbage in, garbage out)

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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