Randomized controlled trials (RCT) are prospective studies that measure the effectiveness of a new intervention or treatment.
Randomization reduces bias and provides a rigorous tool to examine cause-effect relationships between an intervention and outcome
Dr. A Sumathi - LINEARITY CONCEPT OF SIGNIFICANCE.pdf
The randomised controlled trial (RCT) .pptx
1. DEPARTMENT OF COMMUNITY MEDICINE
DATTA MEGHE MEDICAL COLLEGE, DMIHER, NAGPUR
TOPIC : RANDOMISED CONTROL TRIAL
1
Master of Public Health
PG activity – Seminar Presentation
Presented by
Priti bisane
MPH First Year
Semester- I
2. CONTENT
INTRODUCTION
HISTORY
ELEMENTS
TYPES OF RCT
STEP FOR CONDUCTING RCT
ADVANTAGES & DISTADVANTAGES
STRENGTH & LIMITATION
CONCLUSION
3. LEARNING OBJECTIVE
• Describe RCT
• Explain the history of RCT
• Enlist the types of RCT
• How the RCT is conducted
• Describe the advantages and disadvantages of RCT
• Explain the strength and limitation
4. Randomised controlled trial
An RCT is a type of study in which participants are randomly assigned to one
of two or more clinical interventions. The RCT is the most scientifically
rigorous method of hypothesis testing available, and is regarded as the gold
standard trial for evaluating the effectiveness of interventions.
5. Randomized Clinical Trial: History
The first fully controlled clinical trial was conducted by J.B. Amberson, B.T. McMahon and Pinner in
1931.
Twenty-four tuberculosis patients were either given treatment (a sodium-gold concoction called
sanocrysin) or were given no treatment at all.
A coin flip decided who received treatment and who did not;
The control group received injections of distilled water.
The findings were that the two groups had no significant difference in recovery, so sanocrysin was
discredited as a treatment for TB.
Statistician Sir Austin Bradford Hill introduced the idea of random numbers to assign patients in the
1940s—a process that is still used today.
6. Bias in intervention evaluation
Selection Bias – which occurs when the two groups being
studied differ systematically in some way
1. Performance bias refers to systematic differences between
groups that occur during the study. –
2. Detection bias refers to systematic differences in the way
outcomes are determined.
3. Attrition bias occurs when there are systematic differences
between groups in withdrawals from a study.
4. Reporting bias refers to systematic differences between
reported and unreported data.
7. A randomized clinical trial has four elements:
1.A treatment group and a control group. The treatment group receives an
experimental treatment. The control group might be given no treatment at all,
a placebo, or “treatment-as-usual.” The idea is that the control group gives the clinician
something to compare the experimental results to.
2.Randomization to allocate patients to one of the two groups. This randomization is
normally performed by a computer.
8. A randomized clinical trial has four elements:
3.Blinding means withholding which group each participant has been assigned to .
Prevent the patient or researcher from knowing what group they are assigned to.
In a blind trial, the participants don’t know what treatment they are receiving (which
may be a placebo.
Studies may use single , double or triple binding.
Single blinding
The participant are unaware
to which group they belong
9. Double blinding
The investigator or the participants
do not know the group allocation.
Triple blinding
None of the patients , investigator or
trial administer know
10. Quadruple blinding
Patient , investigator , trial , administrator and data analyser
blinded.
4 .An ethical reason for the trial.
11. Type of Randomized Controlled Trials:
1 Clinical trial
Concerned with evaluating therapeutic agent , mainly drugs
e.g. Evaluation of beta-blockers in reducing cardiovascular
mortality
2. Preventive Trials :-
- Trial of primary preventive measures eg . Vaccines
- Analysis of preventive trials must result in clear statement about
benefits to community , risk involved and cost to health
12. 3. Risk Factor Trials:-
Investigator intervenes to interrupt the usual sequence in the
development of disease for those individual who have risk factor
for developing the disease
4. Cessation Experiment :
- An attempt is made to evaluate the termination of a habit which
is considered to be casually related to disease
- - Cigarette smoking and lung cancer
13. 5. Trial of Etiological Agents:-
-To confirm or refute an etiological hypothesis
6. Evaluation of Health Services :-
-Domiciliary treatment of PTB was as effective as more costlier
hospital or sanatorium treatment
14. Phases of clinical Trials
I. Phase I Trial done on group of healthy individuals to know
safety, efficacy and side effects
II. Phase II carried in diseased group to know safety and efficacy
done in multiple centers.
15. III.Phase III carried in thousands of people to study safety, efficacy
and whether fit for manufacturing. Determine the effectiveness {
overall benefit /risk – cost assessment } of new therapies
relative to standard therapy
IV. Phase VI post – marketing study as the drug has already been
granted regulatory approval / license.
16. Drawing up a
Protocol
Selecting reference &
experimental
population
Randomization
Manipulation or
Intervention
Follow -up
Assessment of
Outcome
Steps of conducting a RCT
17. Design of a Randomized
Controlled Trial
SELECT SUITABLE
POPOULATION
SELECT SUITABLE SAMPLE
MAKE NECESSARY
EXCLUSIONS
RANDOMISE
EXPERIMENTA
L
GROUP
CONTROL
GROUP
MANIPULATION &
FOLLOW-UP
ASSESSMENT
18. 1 .The Protocol
-Rationale
- Aims and objective
- Research questions
- Design the study : selection of study and control groups
- Size of sample & allocation of subjects in both groups
- Treatments to be applied – when , where , how
- Standard of Operation {SOP}
- Ethics : Patient consent , confidentiality , adverse events
- Documentation
- Procedure
19. 2 . SELECTING REFERENCE AND EXPERIMENTAL POPULATIONS
A.Reference or target population – population to which the
findings of the trails , it found successful , are expected to be
applicable { e.g. drugs, vaccines , etc.}
B. Experimental or study population –
Actual population that participates in the experimental study
Derived from the reference population
Has same characteristics as the reference population
Must give informed consent
Should be qualified or eligible foe the trial
Effectiveness of drugs in treating anaemia – subjects should be
anaemic
Effectiveness of a vaccines against a disease – subject should not
be already immune
20. 3. RANDOMIZATION
- Heart of the control trial
- Procedure : Participants are allocated into study and control
groups
- Eliminates bias and allows comparability
- Both groups should be alike with regards to certain variables that
might affect the outcomes of the experiment
21. 4. MANIPULATION / INTERVENTION
Deliberate application or withdrawal or reduction of a suspend
casual factor
- It creates an independent variable {drugs vaccine, new
procedure} whose effect is measured in final outcome
constituting the dependent variable {incidence of disease ,
survival time , control of events etc}
22. 5. FOLLOW UP
-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
- Attrition :Inevitable losses to follow up {death, migration , loss
of interest}
23. 6.ASSESSMENT
-Positive results:-
- Reduced incidence or severity of disease
- Reduced cost to health service
- Appropriate outcome in the study
- Negative results :-
- Increased severity or frequently of side effects
- complications
- Death
24. Advantages
•Good randomization will "wash out" any population bias
•Easier to blind/mask than observational studies
•Results can be analyzed with well known statistical tools
•Populations of participating individuals are clearly identified
25. Disadvantages
•Expensive in terms of time and money
•Volunteer biases: the population that participates may not be
representative of the whole
•Loss to follow-up attributed to treatment
26. Strengths
1. Ability to evaluate causal relationships
2. High internal validity (the extent to which differences between
intervention and control groups can be attributed to the
intervention), due to minimized bias within the study
3. Investigator control over patient exposure
4. Prospective data collection, which allows for standardization of
exposure and outcome collection
5. Attempted balance, through randomization, between known and
unknown confounding factors between groups
.
27. Limitations
Higher cost than observational studies
Limited external validity and generalizability, due to strict inclusion
and exclusion criteria and application of interventions by protocol
Ethical considerations related to assigning patients to particular
care approaches
Generally shorter-duration follow-up than observational studies
Inefficiency of detection of rare or delayed outcomes, due to
smaller sample size and shorter-duration follow-up than
observational studies
28. CONCLUSION
The RCT is a valuable tool in various aspects of research in health care, from drug
safety and effectiveness to studies of health professional interventions. To
sufficiently isolate the impact of the intervention on the outcome, RCTs must be
thoughtfully designed and conducted and must involve team members with
expertise across all relevant clinical and methodological aspects.
30. Selection bias occurs when there are systematic differences between groups. For example, if groups are not comparable on key
demographic factors, then between-group differences in treatment outcomes cannot necessarily be attributed solely to the study
intervention. RCTs attempt to address selection bias by randomly assigning participants to groups – but it is still important to
assess whether randomization was done well enough to eliminate the influence of confounding variables.
Performance bias refers to systematic differences between groups that occur during the study. For example, if participants
know that they are in the active treatment rather than the control condition, this could create positive expectations that have an
impact on treatment outcome beyond that of the intervention itself. Ideally, participants and investigators should remain unaware
of which group participants are assigned to. Of note, this is more easily achieved in medication trials, where the medication and
the placebo appear identical, than in psychotherapy trials.
Detection bias refers to systematic differences in the way outcomes are determined. For example, if providers in a
psychotherapy trial are aware of the investigators' hypotheses, this knowledge could unconsciously influence the way they rate
participants' progress. It is crucial that psychotherapy RCTs address this by utilizing independent outcome assessors who are
blind to participants' assigned treatment groups and investigators' expectations.
Attrition bias occurs when there are systematic differences between groups in withdrawals from a study. It's common for
participants to drop out of a trial before or in the middle of treatment, and researchers who only include those who completed
the protocol in their final analyses are not presenting the full picture. Analyses should include all participants who were
randomized into the study (intention to treat analysis), and not only participants who completed some or all of the intervention.
Reporting bias refers to systematic differences between reported and unreported data. One example is publication bias, which
occurs because studies with positive results are more likely to be published, and tend to be published more quickly, than studies
with findings supporting the null hypothesis. At the investigator level, outcome reporting bias can also occur when researchers
only write about study outcomes that were in line with their hypotheses. Efforts to address this include requirements that RCT
protocols be published in journals or on trial registry websites, which allows for confirmation that all primary outcomes are
reported in study
