This document provides an overview of randomized controlled trials (RCTs), including their purpose and design. It discusses key aspects of RCTs such as randomization, blinding, and assessing outcomes. It provides examples of simple two-arm and cross-over RCT designs. The document also summarizes a specific cluster RCT that evaluated the effects of various child development and nutrition interventions on outcomes measured in children from birth to age 2 years.

1. Dr Sridevi NH
MBBS (MD)
Community medicine
Chikmagalur

2.  Introduction
 Different study designs.
 The basic steps with an example
 Number needed to treat
 Types of RCTs
 Blinding and contamination
 Summary
 References

3.  The randomized controlled trial (RCT) is one of the
simplest, most powerful tools of research.
 The RCT is a study in which people are allocated ‘at
random’ to receive one of several interventions.
 The intervention is controlled by the investigator

4.  Interventions include varied actions such as preventive
strategies, diagnostic tests, screening programs, and
treatments.

7.  Simple, two arm RCT.
 Cross over RCT design.
 Factorial RCT design.

10. HWilliams & Wilkins, 2001 ulley et al. Designing Clinical Research. 2ndEdition.
Lippincott

11.  Drawing up a protocol
 Selecting reference and experimental populations
 Randomization
 Manipulation or intervention
 Follow up
 Assessment of outcome

12.  The protocol specifies the aims and objectives of the
study.
 Criteria for the selection of study and control groups,
sample size, procedure for allocation.
 The exposure variable, outcome variable, confounding
variable and co interventions should be defined clearly.
 Inclusion and exclusion criteria should be enumerated.
 The protocol aims at preventing bias and to reduce the
sources of error in the study.

13.  Objective: To evaluate effect of stand-alone Care for
Child Development, stand-alone Enhanced Nutrition,
and Combined Care for Child Development and
Enhanced Nutrition.
 All children aged birth to 2.5 months were enrolled and
followed to age 2 years.

14.  Reference/target population: population to which the
findings of the trial, if found successful, are expected to
be applicable.
 Experimental population: actual population that
participates in the experimental study.
◦ Representative of the population
◦ Qualified or eligible for the trial.
◦ Informed consent.

15.  Experimental population :children less than two years in
Naushero Feroze district of Sindh Province, Pakistan.
Reference population is children less than two years in
other places of Pakistan

16.  It is a statistical procedure.
 Assignment is predetermined
 Each individual has an equal chance of being allocated
to all groups
 Best way to allocate participants to different intervention
groups
 Ensures that the only difference between the two
intervention groups is the intervention

17.  Makes the Study and Control groups comparable
 Minimizes chance of confounding even against unknown
confounders
 Selection Bias minimized
 Facilitates blinding / masking of treatment from
participants and investigators

18.  Unrestricted randomization:
Simplest method – is tossing a coin, Use random
number tables, Can use computers to generate random
numbers.
 Restricted randomization
Also called block randomization or balanced
randomization

19.  Randomization is done in blocks – each block will have
equal number of subjects assigned to each group at the
end of the block

20.  Stratified randomization
 Block randomization may not protect against obtaining
different distributions of important risk factors for the
outcome in the study groups
 Used only when the results of the trial are thought to be
related to a particular factor
 Ensures that different subgroups are balanced between
treatment groups

21. Matched pair randomization:
It can be used when the experiment has only two
treatment conditions. Subjects are grouped into pairs
based on some variable and then are randomly
assigned to different intervention
Cluster randomization:
 All the methods can be applied to either individuals or
communities
 All individuals belonging to a specific group (village,
ethnic, school etc.) communities are allocated
intervention/placebo

22.  The Trial was a cluster randomized controlled trial.
 80 LHW catchment areas were selected for the study.
 Stand-alone Care for Child Development
 Stand-alone Enhanced Nutrition
 Combined Care for Child Development and Enhanced
Nutrition
 Control group

23.  Introduce the Intervention and Placebo Control
Modalities.
 Deliberate application or withdrawal or reduction of the
suspected causal factor as laid down in the protocol.

28.  Examination of both the group subjects at defined
intervals of time, under the same given circumstances, in
the same time frame till final assessment of outcome.
 Follow up may be short or may require many years
depending upon the study undertaken.

29.  The study team undertook in-depth assessments when
enrolled children were 6, 12, 18 and 24 months old.

30.  The incidence of positive and negative results is
rigorously compared in both the groups, if any
differences are found: tested for statistical significance.

31.  Child development:
 Measured at 12 and 24 months using the Bayley Scales
of Infant and Toddler Development
 Four scales were used:
◦ the cognitive scale,
◦ the communication scale,
◦ the motor scale and
◦ the social-emotional scale

32.  Child growth and nutrition status was measured by
data collectors using multiple tools.
 Anthropometry (length/height, weight, mid-upper-arm
circumference and head circumference) was taken at
baseline (when each child was enrolled) and when
children were 6, 12, 18 and 24 months old

35. Subject variation: participants may feel better or report
improvement if they knew they were receiving a new form
of treatment
Observer bias: Investigator measuring the outcome of a trial
may be influenced if he knows beforehand the particular
procedure to which the subject has been subjected
Bias in evaluation: Investigator may subconciously give a
favourable report of the outcome of the trial.

36. Number of patients that need to be treated/ receive
intervention in order to have an impact on one person
For example, if 80% of patients in the control group got better
and 90% of patients in a treatment group got better, the
absolute risk of not getting better if denied the more effective
treatment is 10%.
NNT = 1/ (IE - INE) (where IE and INE are measured as
proportions out of 1)
For every 10 patients who get this treatment, 1 more would get
better compared to the control group.

38.  Number of patients that need to be treated/ receive intervention
to in order to have one adverse outcome
 NNH = 1/ARI Absolute risk Increase
 Drug to decrease tumour size in colorectal cancer
 EER = 55/75=0.73 (Experimental Event Rate)
 CER=35/75=0.47 (Control Event Rate)
 ARI = 0.73 – 0.47 = 0.26
 NNH= 1/ ARR = 1/ 0.26 = 4
 Every four patients treated one will die

39.  Clinical trials: aspirin on cardiovascular mortality
 Preventive trials:vaccines and chemo prophylactic drugs
 Risk factor trials :on CHD
 Cessation experiments: cigarette smoking and lung
cancer
 Trial of etiological agents: oxygen for retrolental fibroplasia
 Evaluation of health services: domiciliary treatment for TB

40.  Single Blind – Participant does not know which
treatment received
 Double Blind – Doctor and Participant, both do not know
which treatment received
 Triple Blind – Person analyzing the data, Doctor and
Participant, all do not know which treatment received.

41.  Study participants do not receive their allocated
intervention / placebo
 Study participants receive the intervention even though
they were in control group
 Tends to weaken the observed association

42.  In summary, RCTs are quantitative comparative
controlled experiments in which a group of investigators
study two or more interventions in a series of individuals
who are randomly ‘allocated’ to receive them.

43. Thank you

44. 1. Park K. Randomized contolled trials . Parks text book of Preventive and
social medicine. 23rd edition. Jabalpur, M/S Banarsidas Bhanot Publishers.
January 2015 page 80-87
2. Leon Gordis. Epidemiology 4th edition. Elsevier. 2009 page 131-163.
3. Roger detels. Oxford textbook of public health. 5th edition. Oxford 2009
page 527-556
4. Textbook of public health and community medicine 1st edition 2009. AFMC
page 151-158
5. Hulley et al. Designing Clinical Research. 2ndEdition. Lippincott Williams
& Wilkins, 2001