study designs in epidemiology

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