Randomized controlled trial presentation

RANDOMIZED CONTROL TRIAL
PRESENTOR
DR. POORVA SHARMA
MDS 1ST
YEAR
PRECEPTOR
DR. SUMIT MALHOTRA

CONTENT
• INTRODUCTION
• SAMPLING
• SAMPLE SIZE
• EPIDERMIOLOGIC METHODS
• AIM
• STEPS IN RCT
• BIAS
• BLINDING
• STUDY DESIGNS IN RCT
• TYPES OF RCT
• PHASES OF RCT
• CONSORT GUIDELINES

INTRODUCTION
The word epidemiology is derived from the Greek word,
epidemic.
Epi=upon
Demos=people
Logos = science.
John M. Last (1988) defined epidemiology as “The study
of the distribution and determinants of health-related states
or events in specified population and the application of this
study to the control of health problems”.

SAMPLING
• The process of selecting number of individuals for a study in such a way that the
individuals represent the larger group from which they were selected and statistical
inference based on sample results may be attributed only to the population
sampled.
• Sampling is a process in which a predetermined number of observations are taken from a
larger population.
John M last, Miguel Porta . A dictionary of
epidemiology. 6th
edition. Oxford University Press.2014
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SAMPLING
METHODS
PROBABILITY
Simple
Random
Cluster
Systematic Stratified
NON-
PROBABILITY
Quota
Judgment
Convenience Snowball
CLASSIFICATION OF SAMPLING METHODS
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SAMPLE SIZE
• Bigger the sample, higher will be the precision of the estimates of the sample.
• An optimum size of the sample is to be considered, keeping in mind the following factors-
a. an approximate idea of the estimate of the characteristics under study and its variability
from unit to unit in the population. This may be obtained from previous investigations or
through pilot survey to be conducted immediately before the start of the actual
investigation.
b. knowledge about the characteristic under study.
c. the probability level within which the desired precision is to be maintained.
d. the availability of experimental material, resources and other practical consideration.
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• For instance, if a field survey is conducted to estimate the prevalence rate of a disease,
the sample size is calculated by the formula,
where‘n”isthesamplesize,‘p’ istheapproximateprevalencerateofthedisease,‘q’is1-qandListhe
permissibleerrorintheestimationofp.
• Ifthesamplesizeistoosmall,thereisaconsiderableriskthatthestudymaynotbesufficientlypowerful
todetectadifferencebetweenthegroups,ifatruedifferenceexists.
• Thestudywould,therefore,beworthless.
n= 4pq/L2
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Randomized controlled trial presentation

AIM OF THE EXPERIMENTAL EPIDEMIOLOGY
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Select suitable population
( Reference or target population)
Select suitable sample
( Experimental or study population)
Make necessary
exclusions
Those not eligible
those who do not wish
to give consent
Randomize
Experimental Group Control Group
Manipulation and follow up
ASSESSMENT
Select suitable sample
( Experimental or study population)
Make necessary
exclusions

THE PROTOCOL
It specifies the-
¥ Aims and objectives of the study,
¥ Criteria for the selection of study and control group,
¥ The procedures for allocation of subjects into study and control groups,
¥ Treatment to be applied
¥ Standardization of working procedures and schedules, upto the stage of
evaluation of outcome the study.
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BASIC STEPS IN CONDUCTING A RCT

• The protocol aims at preventing bias and to reduce the sources of error in the study.
• Once the protocol has been evolved, it should be strictly adhered throughout the study
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SELECTING REFERENCE AND
EXPERIMENTAL POPULATIONS
a). Reference or target population :
¥ It is the population to which the finding of the trail, if found successful,
are expected to be applicable.
(e.g., a drug, a vaccine or other procedure)
b). Experimental or study population :
¥ Is derived from the reference population.
¥ Actual population that participates in the experimental study.
¥ Ideally, it should be randomly chosen from the reference population.
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The participants or volunteers must fulfill the following three criteria:
1. They must give “informed consent”, i.e. they must agree to participate in the trial
after having been fully informed about the purpose, procedures and possible dangers
of the trial.
2. They should be representative of the population to which they belong; and
3. They should be qualified or eligible for the trial. i.e. let us suppose, we are testing the
effectiveness of a new drug for the treatment of periodontitis. If the volunteers are not
having periodontal disease, we will then say, they are not eligible or qualified for the
trial.
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RANDOMIZATION
Randomization is a statistical procedure by which the
participants are allocated into groups usually called
“Study” and “control” groups, to receive or not receive
an experimental preventive or therapeutic procedure, or
intervention.
Randomization is an attempt to eliminate “bias” and
allow for comparability.
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By random allocation, every individual gets an equal chance
of being allocated into either group.
It is crucial that both the groups should be alike with regards
to certain variables or characteristics. (age, sex etc.)
Randomization is done only after the participant has entered
the study i.e. after being qualified for the trial.
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MANIPULATION
The next step is to intervene or manipulate the study
(experimental) group by the deliberate application or
withdrawal or reduction of the suspected causal factor (e.g.,
this may be a drug, vaccine, dietary component, habit, etc) as
laid down in the protocol.
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FOLLOW UP
This implies examination of the experimental and control group subjects at defined intervals
of time, in a standard manner, with equal intensity, under the same given circumstances, in
the same time frame till final assessment of outcome.
The follow-up may be short or may require many years depending upon the study
undertaken.
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ASSESSMENT
The final step is assessment of the outcome of the trial in terms of :
A. Positive results: that is benefits of the experimental measure such as
reduced incidence or severity of the disease, cost to the health service
or other appropriate outcome in the study and control groups.
B. Negative results: that is , severity and frequency of side effects and
complication, if any ,including death.
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STRENGTHS OF RCT
• Effective method to control selection bias
• Able to directly estimate risk
• Controls confounding bias without adjustment
• Allows comparison of multiple outcomes
• Similar distribution of baseline characteristics in comparison groups
• Fulfills the basic assumption of statistical hypothesis tests
• Protection against confounders, both known and unknown
• Similar distribution of baseline characteristics in comparison groups

WEAKNESS OF RCT
• Not suitable for rare outcomes
• Not suitable for outcomes requiring long or extensive follow-up
• Adherence/withdrawal issues
• Limitations of external validity
• Complex, Expensive, time consuming, sometimes ethically questionable

IMPORTANCE OF RANDOMIZATION IN
RANDOMIZED CONTROLLED TRIAL
• Randomization is the random allocation of treatment, which means all
participants have the same chance of being assigned to each of the study groups.
• The allocation, therefore, is not determined by the investigators, the clinicians, or
other study participants.
• The basic benefits of randomization include-
Eliminates selection bias. Balances arms with respect to prognostic variables

(known and unknown). Forms basis for statistical tests, a basis for an assumption-

free statistical test of the equality of treatments

BIAS
Bias on the part of the participants, who may subjectively feel better or
report improvement if they knew they were receiving a new form of
treatment.
Observers bias, i.e. the investigator measuring the outcome of a
therapeutical trial may be influenced if he knows beforehand the particular
procedure or therapy to which the patient has been subjected to.
Bias in evaluation, that is, the investigator may subconsciously give a
favorable report of the outcome of the trial.
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BLINDING
Single blind trial : The trial is so planned that the
participant is not aware whether he belongs to the study
group or control group.
For eg- All patients receive scaling and root planing
(SRP). One group also receives a local antibiotic gel (e.g.,
doxycycline), and the other receives a placebo gel.
Blinding: The patient does not know if the gel applied is
active or a placebo, but the clinician applying it knows.
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• Double blind trial : The trial is so planned that neither the
doctor nor the participant is aware of the group allocation
and the treatment received.
For eg- Group A receives chlorhexidine 0.12%; Group B
receives a placebo mouthwash with identical taste, color, and
packaging.
• Neither the patient nor the clinician assessing plaque index
and gingival index knows the allocation.
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 Triple blind trial : This goes one step further.
The participant, the investigator and the person
analyzing the data are all “blind”.
For eg- To evaluate the effectiveness of SRP alone versus
SRP + adjunctive local doxycycline gel in chronic
periodontitis.
• Patients receive SRP in all quadrants.
• In selected sites, either doxycycline gel or placebo gel
is applied.
• Neither the patient, the periodontist performing SRP,
nor the examiner measuring probing depth and clinical
attachment loss knows which gel was used
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STUDY DESIGNS IN RCT
Concurrent parallel study designs
In this situation comparison are made between 2
randomly assigned groups, one group exposed to
specific treatment, and the other group not
exposed.
Patient remain in the study group or the control
group for the duration of the investigation.
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SCHEMATIC DIAGRAM OF THE
CONCURRENT PARALLEL DESIGN
PATIENTS
EXPOSED TO
SPECIFIC TREATMENT
UNEXPOSED TO
SPECIFIC TREATMENT
COMPARE
OUTCOME
OBSERVATIONS
TIME
RANDOM
ASSIGNMENT

CROSS OVER TYPE OF STUDY DESIGN
With this type of study design, each patient serves as his own control. As
before, the patients are randomly assigned to a study group and control
group.
The study group receives the treatment under consideration & the control
group receives some alternate form of active treatment or placebo.
The two group are observed over time.
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Then the patient in each group are taken off their medication or placebo to allow for the
elimination of the medication from the body and for the possibility of any crossover effects.
After this period of medication (the length of this interval is determined by the pharmacologic
properties of the drug being tested), the two groups are switched.
Those who received the treatment under study are changed to the control group therapy or
placebo, and vice versa.
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TYPES OF RANDOMZIED
CONTROLLED TRIALS [RCT]
1. Clinical trials
2. Preventive trial
3. Risk group trial
4. Cessation experiment
5. Trial of etiological events
6. Evaluation of health services
7. Community intervention trials (CITs)
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Clinical Trials
For the most part, “clinical trials” have been concerned with evaluating
therapeutic agents, mainly drugs. e.g., include evaluation of NSAID’s in
reducing inflammation in patient with periodontitis.
Many ethical administrative and technical problems are involved in the
conduct of clinical trials.

Types of Clinical Trials-
• A. PROPHYLACTIC TRIALS- Example : Immunization
• B. THERAPEUTIC TRIALS- Example : Drug Treatment, Surgical procedure
• C. SAFETY TRIALS- Example : Side effects of Oral Contraceptives and injectables
• D. RISK FACTOR TRIALS- Example : Smoking
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Phases of Clinical Trials-
• PHASE I CLINICAL TRIAL
• PHASE II CLINICAL TRIAL
• PHASE III CLINICAL TRIAL
• PHASE IV CLINICAL TRIAL
• PHASE V CLINICAL TRIAL (Recently added)
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• Before pharmaceutical companies start clinical trials on a drug, they conduct
extensive pre-clinical studies.
• These involve in-vitro and in-vivo (animal) experiments using wide-ranging
doses of the study drug to obtain preliminary efficacy, toxicity and
pharmacokinetic information.
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PHASE 0
• Phase 0, is a recent designation for exploratory, first-in-human trials,
also known as human micro dosing studies.
• Defective features of Phase 0 trials include the administration of single
sub therapeutic doses of the study drug to a small number of subjects
(10-15) to gather preliminary data on the agent’s pharmacodynamics
(what the drug does to the body) and pharmacokinetics (what the body
does to the drugs).
• Phase 0 study does not give data on safety or efficacy of a drug
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PHASE Ⅰ
• Phase trials are the first stage of testing in human subjects.
Ⅰ
• Nominally a small group of 20 to 100 healthy volunteers will be recruited.
• This phase is designed to assess the safety tolerability pharmacokinetics and
pharmacodynamics of a drug.
• These trials are often conducted in a clinical trial clinic where the subjects
occupy what are called research beds and can be observed by full time staff.
• Phase trials normally include dose-ranging also called dose escalation studies,
Ⅰ
so that not only the best and safest dose can be found but also to discover the
point at which a compound is too poisonous to administer.
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PHASE Ⅱ
• Once a dose or range of doses is determined, the next goal is to evaluate
whether the drug has any biological activity or effect.
• Phase trials are performed on larger groups (100-300) and are designed to
Ⅱ
assess the effectiveness and safety of a drug
• Phase studies are sometimes divided into phase A and phase B.
Ⅱ Ⅱ Ⅱ
• Phase A is specifically designed to assess dosing requirements (how much
Ⅱ
dose should be given)
• Phase B is specifically designed to study efficacy (how well the dose
Ⅱ
works at the prescribed doses)
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PHASE Ⅲ
• Phase studies are randomised controlled (300-3000 or more) multi-centre
Ⅲ
trials on large patient groups and are aimed at assessing how effective the drug is
in comparison with current gold standard treatment.
• Because of the size and comparability long duration, phase trials are the most
Ⅲ
expensive, time-consuming and difficult trials to design and run.
• Most drugs undergoing phase clinical trials can be marketed under FDA
Ⅲ
norms with proper recommendations and guidelines through a New Drug
Application in (NDA) containing all pre-clinical and clinical data
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PHASE Ⅳ
• Phase trial is also known as post marketing surveillance trial.
Ⅳ
• Phase trial involves the safety surveillance and ongoing technical support
Ⅳ
of a drug after it receives permission to be sold.
• The safety surveillance is designed to detect any rare or long term adverse
effects over a much larger patient population and longer time period than was
possible during phase to clinical trials.
Ⅰ Ⅲ
PHASE Ⅴ
• Phase assumes to signify the integration of a new helical
Ⅴ
treatment in two widespread public health practise.
• It is a growing term used in the literature to refer to comparative
effectiveness research and community based research.
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Preventive Trials
Implies- trials of primary preventive measures.
- trials of vaccines and chemo–prophylactic drugs.
The basic principle of experimental design are also applicable to these
trials.
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• Analysis of a preventive trial must result in a clear statement about-
a) The benefit the community will derive from the measure
b) The risks involved and
c) The cost to the health service in terms of money, men, and material resources.
• Since preventive trial involves larger number of subjects and sometimes a
longer time span to obtain results, there may be a greater number of practical
problem in their organization and execution.

Risk Factor Trials
A type of preventive trials is the trial of risk factors in which the
investigator intervenes to interrupt the usual sequence in the
development of disease for those individuals who have “risk
factor“ for developing the disease; often this involves risk factor
modification.
Concept of risk factor gave a new dimension to epidemiological
research.
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For Example-
MAJOR RISK
FACTOR FOR
CORONARY HEART
DISEASE
ELEVATED BLOOD CHOLESTEROL
SMOKING
HYPERTENSION
SEDENTARY HABITS
FOUR POSSIBLE
INTERVENTION FOR
CORONARY HEART
DISEASE
REDUCTION OF BLOOD CHOLESTEROL
CESSATION OF SMOKING
CONTROL OF HYPERTENSION
PROMOTION OF PHYSICAL ACTIVITIES

CESSATION EXPERIMENTS
Another type of preventive trial is the cessation experiment.
In this type of study, an attempt is made to evaluate the
termination of a habit (or removal of suspected agent) which
is considered to be causally related to a disease. if such
action is followed by a significant reduction in the disease,
the hypothesis of cause is greatly strengthened.
The familiar example is cigarette smoking and lung cancer.
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Trial of Etiological
Events
• One of the aim of experimental epidemiology is to confirm or refuse
an etiological hypothesis.
• Since most diseases are fatal, disabling or unpleasant, human
experiments to confirm an etiological hypothesis are rarely possible.
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Evaluation of Health Services
• RCTs have been extended to assess the effectiveness and efficiency of health
services.
• The necessity of the choice arises from the fact that resources are limited, and
priorities must be set for the implementation of a large number of activities,
which could contribute to the welfare of the society.
• These studies are also labelled as the “health services research” studies.
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Community Intervention Trials (CITS)
• They are usually carried out in hospitals, or clinics, and are usually at a patient group with
specific health conditions.
• However, randomized experiments are also sometimes done in the community.
• The classic example of a community intervention trial would be that of testing a vaccine.
• Some communities will be randomly assigned to receive the vaccine, while other
communities will either not be vaccinated, or will be vaccinated with a placebo.
• In these types of studies, the major difference from the RCT is that the randomization is done
on communities rather than individuals.
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• Very often, blinding is not possible in these types of studies, and contamination
and co-interventions become serious problems.
• Contamination occurs when individuals from one of the experimental groups
receive the intervention from the other experimental groups.
• Co-intervention occurs when other interventions, either unknown to the
investigators of this trial or otherwise, are simultaneously introduced, in which
case comparison of results from the two randomized groups will no longer be a
reflection of the intervention under trial.
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CONSORT (CONSOLIDATED STANDARDS OF REPORTING TRIALS) GUIDELINES
• Randomized controlled trials, when appropriately designed, conducted and reported
represent the gold standard in evaluating health-care interventions. However,
randomized trials can yield biased results if they lack appropriate methodology.
• Consort guidelines are used to assess a trial accurately. Inadequate reporting had led to
the development of the original CONSORT (Consolidated Standards of Reporting
Trials) statement in 1965 and its revision 5 years later.

Hopewell S, Chan AW, Collins GS,
Hróbjartsson A, Moher D, Schulz KF,
Tunn R, Aggarwal R, Berkwits M,
Berlin JA, Bhandari N. CONSORT
2025 statement: updated guideline for
reporting randomised trials. The
Lancet. 2025 May 3;405(10489):1633-
40.

CONCLUSION
• Experimental epidemiology is a branch of epidemiology that focuses on the study of disease
patterns and causes through experimental methods, such as controlled trials or interventions.
The goal is to establish cause-and-effect relationships between exposures (e.g., behaviors,
environmental factors, or interventions) and outcomes (e.g., disease, health events).
• Unlike observational epidemiology, where researchers simply observe and analyze natural
patterns, in experimental epidemiology, researchers can manipulate exposures (e.g.,
administering a drug or changing an environment) and then observe the outcomes. The
findings are often used to establish the effectiveness of health interventions, public health
policies, or other preventive measures.

REFERENCES
• Soben peter. Essentials of Preventive and Community Dentistry, 7th
Edition.
• Suvarna V Biradar, Divya S, Experimental Epidemiology – A Review, Asian
Journal of Pharmaceutical Technology & Innovation, 6 (27); 10-35, 2018.
• Hopewell S, Chan AW, Collins GS, Hróbjartsson A, Moher D, Schulz KF, Tunn
R, Aggarwal R, Berkwits M, Berlin JA, Bhandari N. CONSORT 2025 statement:
updated guideline for reporting randomised trials. The Lancet. 2025 May
3;405(10489):1633-40.
• Pannuti CM, Costa FO, Souza NV, Retamal-Valdes B, Costa AA, Susin C, Feres
M. Randomized clinical trials in periodontology: focus on outcomes selection.
Brazilian Oral Research. 2021 Sep 24;35(Supp 2):e100.
• Zabor EC, Kaizer AM, Hobbs BP. Randomized controlled trials. Chest. 2020 Jul
1;158(1):S79-87.

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