Randomized controlled trials (RCTs) are experimental studies that assess the effect of an intervention by comparing outcomes between those who receive the intervention and a control group. RCTs minimize bias by randomly assigning participants to groups and concealing group assignments. Key factors in RCTs include sufficient sample size, stratified randomization to balance groups, blinding participants and assessors, and accounting for attrition. RCTs allow for causal inferences but have disadvantages like difficulty with some ethical questions and dropout.

1. KNOWLEDGE FOR THE BENEFIT OF HUMANITYKNOWLEDGE FOR THE BENEFIT OF HUMANITY
PUBLIC HEALTH AND EPIDEMIOLOGY (HFS3063)
Epidemiological Study Designs:
RANDOMISED CONTROLLED TRIALS
Dr.Dr. MohdMohd RazifRazif ShahrilShahril
School of Nutrition & DieteticsSchool of Nutrition & Dietetics
Faculty of Health SciencesFaculty of Health Sciences
UniversitiUniversiti SultanSultan ZainalZainal AbidinAbidin
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2. Topic Learning Outcomes
By the end of this lecture, students should be able to;
• describe randomised controlled trial design.
• explain the advantages and disadvantages of
randomised controlled trial design.
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3. Randomized controlled trials (RCT)
• RCT or randomized clinical trials are experimental
studies where the effect of an intervention is assessed
by collecting data before and after an intervention.
• Used to compare an intervention with one or more other
intervention or with no intervention.
• Intervention are often clinical treatments but may also be
educational interventions (e.g. health promotion leaflets).
• Two main features of the RCT;
a) They are comparative
b) They are designed to minimize bias
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4. a) Comparative
• In RCT, an intervention is investigated by comparing one
group of people who receive the intervention with a
control group or control arm who do not.
• Control group receives usual or no treatment and their
outcome measure (or the change in measure from the
baseline) is compared with that of the intervention group.
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6. b) Minimizing bias in RCT
1) Allocation bias
2) Performance bias
3) Assessment bias
4) Attrition bias
5) Allocation concealment
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7. 1) Allocation bias
• Occurs when the measured treatment effect differs from
the true treatment effect because of how participants
were selected into the intervention or control group.
• In RCT, participants will be randomized to either an
intervention or control group at study entry.
• Randomization ensures that characteristics that might
affect the relationship between intervention and outcome
measures will be roughly equal across all arms of the
study
– minimizing potential bias
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8. 2) Performance bias
• Occurs when participants’ response to the treatment is
affected by knowledge of the group to which they are
assigned.
– They know which group they belongs to either intervention or
control.
• Performance bias might also occur when health
professionals administer treatment differently
between treatment arms.
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9. 3) Assessment bias
• Health professionals assessing the outcome of treatment
relative to alternative or placebo interventions may
record outcome measures biased by the knowledge of
the group assignments.
• Overestimation or underestimation of the effects on
an intervention is known as assessment bias.
• There might be a systematic difference in measuring
the outcomes between the two groups because of the
method of recording used
– E.g. control group is assigned to one practitioner and the
intervention group to another, or groups are assessed at different
times of the day.
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10. (cont.) 3) Assessment bias
• How to minimize the assessment bias?
– Use a standardized method of evaluation across both groups.
– Avoid using subjective measures to assess the effectiveness
of a treatment which are more prone to bias.
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11. 4) Attrition bias
• Also called as loss-to-follow-up bias.
• Occurs when patients drop out of the study from their
respective study group.
• If halfway through a study the treatment has been
successful, participants may drop out and information
about the success of the treatment is then lost.
• Participants in the control group might be unhappy with
their lack of progress and may drop out of the study in
order to seek alternative help.
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12. 5) Allocation concealment
• Bias will be minimized where the allocation schedule is
concealed of whom is assigned to which group.
• Blinding (or masking) helps prevent systematic
differences between comparison groups in prognosis or
responsiveness to treatments (allocation bias).
• Blinding of both participants and practitioners prevents
performance and assessment bias by ensuring
everybody (participants, treatment admin, those
measuring outcomes) do not know which treatment was
given.
• It is recommended RCT participants are blind to the
treatment they receive.
– Control group receives placebo
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13. Why carry out RCT?
• RCT are prospective longitudinal studies
– Allowing causal association between intervention and outcomes.
• The random selection of participants into each arm and
the controlled way in which trial is carried out mean that
all factors are considered equal.
• Other study design cannot infer causality.
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14. Important factors in RCT?
1) Sample size
2) Stratification
3) Trial design
4) Between group contamination
5) Ethical issues
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15. 1) Sample size
• Sample size dependent upon
– the power of the test
– what size of intervention impact is considered meaningful
– type of hypothesis the RCT is testing
• The smaller magnitude of difference between groups
that is to be detected and the greater the variability in
outcomes, the larger the sample size that will be
required.
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16. 2) Stratification
• Very large trials are likely to have a good balance of
patients within each arm.
• When samples are small, however, treatment groups
may be chance end up with different characteristics
– May affect the outcome trial
• Stratification is a way of ensuring the treatment groups
are balanced on characteristics that are likely to alter the
relationship between treatment and outcome.
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17. 3) Trial design
• There are two commonly used trial design to allocate
treatment and control regimens in RCT;
– Parallel design
– Crossover design
• In parallel design, different patients will be randomized in
each treatment group.
– There will be differences in characteristics of participants
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18. (cont.) 3) Trial design
• Crossover trials are another way of overcoming
differences in groups by keeping the patients as
matched as possible.
• Instead of having different patients in each treatment
group, patients receive first one treatment and then the
other, in random order, with a wash out period in
between.
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19. (cont.) 3) Trial design
• Within-patient differences are then compared in
crossover design.
• Each patient effectively becomes their own ‘test’ and
‘control’.
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20. 4) Between group contamination
• Educational interventions are prone to contamination
e.g. a member of the control arm is a friend of a patient
receiving the low fat diet advice intervention.
– Information will be passed between the two arms of trial and thus
alter results.
• Use cluster sampling so natural cluster such as
geographic areas are randomized rather than
individuals.
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21. 5) Ethical issues
• RCT is not always possible because of ethical issues
when assigning patients to study arms.
• If one group of patients receives treatment thought to be
effective, while another group does not, the ethics of a
trial may be brought into question.
• Similarly, there are some trials that cannot be carried out
because they may actively encourage unhealthy
practices e.g. smoking.
– People cannot be randomized into smoking and non-smoking
group.
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22. Analysis of data
• RCT are experiments set up to test hypotheses.
• Null hypotheses – the intervention will have no impact on
the outcome measure
– Outcome will be similar in both the test and control groups
• Alternative hypotheses – intervention will have
meaningful effect and statistically significant
• Statistical method (e.g.);
– Pre and post intervention differences = paired t-test
– Mean differences pre and post between two group =
independent t-test
– Mean differences pre and post between more than two groups =
ANOVA
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23. Advantages of RCT
• Ability to make causal inferences mean that RCT provide
the strongest empirical evidence of a treatment’s
efficacy.
• Randomization of participants to the test and control
arms and concealment of their allocation ensures that
allocation bias and confounding or unknown variables
are minimized.
• The study can be tailored to answer a specific question.
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24. Disadvantages of RCT
• High dropout when the intervention has undesirable
side-effects or there is little incentive to stay in the
control arm.
• Ethical consideration may mean that a research question
cannot be investigated using RCT design
• For a descriptive overview it may be cheaper and easier
to use an observational design.
• Prior knowledge is required for sample size calculation;
– the level of improvement that is clinically meaningful
– expected variation of improvement in the sample
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25. Recapitulate
In this lecture, you have been exposed to;
• definition of RCT
• how biases is minimized in RCT
• factors to be considered when carrying out RCT
• analysis of data for RCT
• advantages and disadvantages of RCT
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26. Thank YouThank You
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