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Randomized Controlled
Trial
(RCT)
Kun A Susiloretni
Study design M
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Systematic
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Practice Guideline

Randomized Controlled Trial

Cohort Study

Case Control Study

Case Reports

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What is RCT?
A study design
• that randomly assigns participants into an
experimental group or a control group.
• the only expected difference between the control
and experimental groups in a randomized
controlled trial (RCT) is the outcome variable
being studied.

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What is RCT?
• Randomized controlled trials are the most reliable
method available for testing new treatments.
• Randomized: The researchers decide randomly
as to which participants in the trial receive the new
treatment and which receive a placebo, or fake
treatment.
• Controlled: The trial uses a control group for
comparison or reference. In the control group, the
participants do not receive the new treatment but
instead receive a placebo or reference treatment.

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Design

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Design

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Design
• Choice of Intervention
• Choice of Control
• Choosing outcome measurements
• Number of Outcome Variables
• Adverse Effects

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Design-Define Entry Criteria
Inclusion criteria
• should produce a sufficient number of enrollees
who have a high enough rate of the primary
outcome to achieve adequate power to find an
important effect on the outcome.

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Exclusion criteria

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RCT

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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

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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

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Randomization
• This is intended to ensure that all potential confounding
factors are divided equally among the groups that will
later be compared (structural equivalence).
• These factors are characteristics that may affect the
patients’ response to treatment, e.g., weight, age, and
sex.
• Only if the groups are structurally equivalent can any
differences in the results be attributed to a treatment
effect rather than the influence of confounders.
• If the confounders are known, structural equivalence of
the patient groups can be attained by stratified
randomization

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7 Deadly Sins in Research
Sins Committed Before Research
• Sin #1: The Curse of the Handicapped Literature
Review
• Sin #2: Inadequate Power
• Sin #3: Ignoring the Importance of Measurement

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7 Deadly Sins in Research
Sins Committed During Research
• Sin #4: Using the Wrong Statistical Tool – ignore
confounding factors
• Sin #5: Merciless Torture of Data and Other
Questionable Analysis Practices
Sins Committed After Research
• Sin #6: Slavery to the P Value
• Sin #7: Lack of Transparency in Reporting Results
and Maintaining Raw Data

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A well designed RCT
• The sample to be studied will be appropriate to the hypothesis
being tested so that any results are appropriately generalizable.
• There will be effective (concealed) randomization of the subjects
to the intervention/control groups (to eliminate selection bias and
minimize confounding variables).
• Both groups will be treated identically in all respects except for
the intervention being tested and to this end patients
• investigators will ideally be blinded to which group an individual is
assigned.
• The investigator assessing outcome will be blinded to treatment
allocation.
• Analysis focuses on testing the research question that initially led
to the trial, rather than “trawling” to find a significant difference.

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Population sampling
• The study sample must be representative of the target
population for the findings of the study to be
generalisable.
• Inclusion and exclusion criteria will determine who will
be studied from within the accessible population.
• The most appropriate sampling strategy is normally
consecutive sampling, although stratified sampling may
legitimately be required.
• A sample size calculation and pilot study will permit
appropriate planning in terms of time and money for the
recruitment phase of the main study.
• Follow CONSORT guidelines on population sampling

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Randomisation
• The random assignment of subjects into one of two groups is the
basis for establishing a causal interpretation for an intervention.
• Effective randomisation will minimise confounding variables that
exist at the time of randomisation.
• Randomisation must be concealed from the investigator.
• Blocked randomisation may be appropriate for smaller trials to
ensure equal numbers in each group.
• Stratified randomisation will ensure that a potential baseline
confounding variable is equally distributed between the two
groups.
• Analysis of results should occur based on the initial
randomisation, irrespective of what may subsequently actually
have happened to the subject (that is, “intention to treat
analysis”).

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Intervention and outcome
• Blinding at the stage of applying the intervention and
measuring the outcome is essential if bias (intentional or
otherwise) is to be avoided.
• The subject and the investigator should ideally be blinded
to the assignment (double blind), but even where this is not
possible, a blinded third party can measure outcome.
• Blinding is achieved by making the intervention and the
control appear similar in every respect.
• Blinding can break down for various reasons, but this can
be systematically assessed.
• Continuous outcome variables have the advantage over
dichotomous outcome variables of increasing the power of
a study, permitting a smaller sample size.
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Quality control
• An inadequate approach to quality control will lead to potentially
significant errors due to missing or inaccurate results.
• An operations manual will allow standardisation of all procedures
to be performed.
• To reduce interobserver variability in outcome measurement,
training can be provided to standardise procedures in accordance
with the operations manual.
• Data collection forms should be user friendly, self explanatory,
and clearly formatted, with only truly relevant data being collected.
• Subsequent data transfer onto a computerised database can be
safe guarded with various measures to reduce transcription errors.
• Protocol revisions after study has started should be avoided if at
all possible, but, if necessary, should be appropriately
documented and dated to permit separate analysis.

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Writing research report

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Introduction
• Scientific background and explanation of rationale
• Specific objectives or hypotheses

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Methods
Trial design
• Description of trial design (such as parallel, factorial) including
allocation ratio (such as eligibility criteria), with reasons
Participants
• Eligibility criteria for participants
• Settings and locations where the data were collected
Interventions
• The interventions for each group with sufficient details to allow
replication, including how and when they were actually administered
Outcomes
• Completely defined pre-specified primary and secondary outcome
measures, including how and when they were assessed
Sample size
• How sample size was determined

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Methods
Randomisation: Sequence generation
• Method used to generate the random allocation sequence
• Type of randomisation; (such as blocking and block size)
• Mechanism used to implement the random allocation sequence
(such as sequentially numbered containers), describing any steps
taken to conceal the sequence until interventions were assigned
Implementation
• Who generated the random allocation sequence, who enrolled
participants, and who assigned participants to interventions
Blinding
• If done, who was blinded after assignment to interventions
• (for example, participants, care providers, those assessing
outcomes)

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Methods
Statistical methods
• Statistical methods used to compare groups for
primary and secondary outcomes
• Methods for additional analyses, such as
subgroup analyses and adjusted analyses

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Results
Participant flow (a diagram is strongly recommended)
• For each group, the numbers of participants who were
randomly assigned, received intended treatment, and
were analysed for the primary outcome
• For each group, losses and exclusions after
randomisation, together with reasons
Recruitment
• Dates defining the periods of recruitment and follow-up
Baseline data
• A table showing baseline demographic and clinical
characteristics for each group

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Results
Numbers analysed
• For each group, number of participants (denominator) included in
• each analysis and whether the analysis was by original assigned groups
Outcomes and estimation
• For each primary and secondary outcome, results for each group, and
the estimated effect size and its precision (such as 95% confidence
interval)
• For binary outcomes, presentation of both absolute and relative effect
sizes is recommended
Ancillary analyses
• Results of any other analyses performed, including subgroup analyses
and adjusted analyses, distinguishing pre-specified from exploratory
Harms
• All important harms or unintended effects in each group (for specific
guidance see CONSORT for harms42)
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References
• Hulley, S. B., Cummings, S. R., Browner, W. S., Grady, D. G. &
Newman, T. B. 2013. Designing clinical research, Lippincott Williams
& Wilkins.
• Kendall, J. 2003. Designing a research project: randomised
controlled trials and their principles. Emergency medicine journal:
EMJ, 20, 164.
• Prado, E. L., Maleta, K., Ashorn, P., Ashorn, U., Vosti, S. A., Sadalaki,
J. & Dewey, K. G. 2016. Effects of maternal and child lipid-based
nutrient supplements on infant development: a randomized trial in
Malawi. The American Journal of Clinical Nutrition, 103, 784-793.
• Moher, D., Hopewell, S., Schulz, K. F., Montori, V., Gøtzsche, P. C.,
Devereaux, P. J., Elbourne, D., Egger, M. & Altman, D. G. 2012.
CONSORT 2010 explanation and elaboration: Updated guidelines for
reporting parallel group randomised trials. International Journal of
Surgery, 10, 28-55.

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