RANDOMIZED CONTROLLED TRIALS (RCT)

NISHATH NIHAR FINAL YEAR

CONTENTS:IntroductionHistoryDefinitionSteps in RCTBlindingTypes of RCTAdvantages and DisadvantagesUsesConclusionReferences

INTRODUCTION

In the last 35-40 years, determined efforts have been made to use scientific techniques to evaluate methods of treatment & prevention.

An important advance in this field is the development of RANDOMIZED CONTROLLED TRIALS

HISTORY In 1747, James Lind performed a human

experiment in which he added different substances to diet of 12 soldiers suffering from SCURVY

Oranges & lemons, cider, vinegar, sulphuric acid, salt water and garlic

Only the sailors given oranges & lemons recovered

DEFINITION“ 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 therapeutic procedure, maneuver or intervention”

-John M Last,2001

STEPS IN RCT1. Drawing up a protocol2. Selecting reference and experimental

population3. Randomization4. Manipulation5. Follow up6. Assessment of outcome

1. DRAWING UP A PROTOCOL• The protocol specifies the aims & objectives of

the study• Criteria for selection, size of sample,

procedures for allocation of study & control groups

• Standardization of working procedure, schedules & responsibility of people involved in trial

• The protocol should be strictly adhered to throughout the study

2. SELECTING REFERENCE AND EXPERIMENTAL POPULATION• Reference or target population: population to which

the findings of trial, if found successful are expected to be applicable(eg, drug vaccine )

• Experimental or study population: Actual population that participates in trials

• Randomly chosen from reference population Criteria- must give informed consent - belong to reference population - eligible for the trial

3. RANDOMIZATION Statistical procedure by which participants are

allocated into study & control groups, to receive or not to receive an experimental preventive or therapeutic procedure

It is done to eliminate “Bias” and allows comparability Individual gets an equal chance of being allocated into

either group

Randomization is best done using a “ Table of random numbers”

4. MANIPULATION Deliberate application or withdrawal or reduction of

the suspected casual factor( eg., drug vaccine , dietary component, habit etc) as laid down in the protocol

It creates an Independent variable.

5. FOLLOW UP Examination of experimental and control group

subjects at defined intervals of time, in a standard manner under the same given circumstances till final assessment of outcome.

ATTRITION: Some loses to follow up are inevitable due to factors like death, migration or loss of interest

6. ASSESSMENT POSITIVE RESULTS: Benefits such as reduced

incidence or severity of disease NEGATIVE RESULTS: severity and frequency of side

effects, complications , including death BIASa) Subject variationb) Observer biasc) Evaluation bias Eliminated by “ BLINDING”

BLINDING• Done to eliminate bias • Single blind trial- participant is not aware whether he

belongs to study or control group

DOUBLE BLIND TRIAL Neither the participant nor the investigator is aware

TRIPLE BLIND TRIALThe participant, investigator and person analyzing data all are Blind

TYPES IN RCTA.CLINICAL TRIALS: It is done various purposes like prophylactic trials (e.g immunization, contraception) therapeutic trials(e.g drug treatment, surgery) safety trials(eg side effects of Ocs)

B. PREVENTIVE TRIALS: Synonymous with primary prevention. e.g vaccine trials analysis must result in clear statement about risk involved, benefits to community, cost etc

C. RISK FACTOR TRIALS: Investigator intervenes to interrupt the usual sequence in the development of disease for individuals who have risk factor for developing a disease eg. Reduction in blood cholesterol, control of BP in preventing CHD.

D. CESSATION EXPERIMENTS: Attempt is made to evaluate the termination of a habit which is considered to be casually related to disease eg. Smoking and lung cancer

E. TRIAL OF ETIOLOGICAL AGENTS: it is done to confirm or refute an etiological hypothesis.

F. EVALUATION OF HEALTH SERVICES: Efficiency & effectiveness of treatmentEg in India domiciliary treatment of pulmonary TB was as effective as costlier hospital treatment.

ADVANTAGES:• Eliminates bias• Facilitates blinding• Results in evidence-based medicine

DISADVANTAGES:• Time and cost• Ethical issues

USES Community diagnosis Evaluation of health services Evaluation of individual risk Searching for causes and risk factors Syndrome identification

CONCLUSION RCT’s are the best way to test the safety and efficacy

of new treatment They are regarded as the “GOLD STANDARD” of

clinical testing in new medical interventions.

REFERENCES• K.PARK Textbook of preventive & social medicine,

22nd edition• SOBEN PETER, Essentials of public health dentistry,

5th edition• Wikipedia

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