RESEARCH METHODOLOGY

&
BIOSTATISTICS

* Few jewels from ocean

1
 Definition of Research

“Research is a
systematized effort
to gain new knowledge”.

2
 Steps in Research (Holy 11)
1. Collect review of literature/Situation Analysis
2. Identify and prioritize health problems
3. Decide aims & objectives
4. Planning Methodology
5. Execution
6. Compilation, Classification & Presentation of
data
7. Analysis
8. Test of Significance/Test of Hypothesis
9. Inferences
10. Report Writing
11. Dissemination of Report

3
 Process of Concluding
8 7 6

Reporting Inferences Analysis

Data Collection
5

Execution

Execution
Research Problem
Define
1

for Pretest
Collection
Data
Review of Literature Methodology
4

2 3
Planning

4
 STEP-1

DEFINITION
OF THE
RESEARCH PROBLEM

5
 RESEARCH PROBLEM ?

Research Problem refers to some difficulty

which a researcher experiences and
wants to obtain a solution for the same.

i.e. a question or issue to be examined.

6
Process of Defining Problem
Analysis of the Situation

Identify & Prioritize Problems

Select & Define Problem

Statement of Research
Objectives

7
 CRITERIA OF SELECTION
The selection of one appropriate researchable
problem out of the identified problems requires
evaluation of certain criteria.

*Internal / Personal criteria – Researcher‟s

side

*External Criteria – Problem side factors

8
INTERNAL CRITERIA OF SELECTION

 Researcher‟s Interest,

 Researcher‟s Competence,

 Researcher‟s own Resource:

 Human Resource
 Money
 Material
 Time

9
EXTERNAL CRITERIA OF SELECTION

 Researchability of the problem,

 Importance and Urgency,
 Novelty of the Problem,
 Feasibility,
 Facilities,
 Social Relevance
 Public health Importance

Dr. Kusum Gaur 10

 DEFINE RESEARCH PROBLEM
(Title of the Research Topic)

Transforming the selected research problem into a

scientifically researchable statement.

Problem definition or Problem statement should

be clear, precise, self-explanatory and include:-

 What
 How
 When
 Where

11
 RESEARCH OBJECTIVES
(Objectives)
 Research Objectives are the statement of the
questions that is to be investigated with the goal of
answering the overall research problem.

 Research Objectives should be clear and achievable.

 Generally, they are written as statements, using the

word “to”
(For example, „to discover …‟, „to determine …‟, „to
establish …‟, „to find out -----‟, „to assess -----‟etc. )

Objectives should infer in the end of the study

12
 Hypothetical Research Question
 Problem:
PCR of Diabetes Mellitus is increasing very
fast during last five year

 Mission:
Reduce the incidence of heart disease

 Belief:
Meditation is good to reduce stress which
is an important precursor of DM

 Hypothesis
H- Meditation decreases the risk of DM

13
 Association of Garlic consumption with
coronary Artery Diseases

Aim: To Study the association of Meditation with

Diabetes Mellitus in patients attending at Medical
OPD of SMS Hospital, Jaipur (Raj) India.

Objectives:
1. To assess and compare the proportion of DM
cases in individuals doing regular meditation
and not doing meditation.

2. To find out the risk ratio

of DM in individuals not
doing meditation on doing regular meditation.
14
 STEP-2

REVIEW
OF
LITERATURE

15
Review of literature

What ?

Why ?

Where ?

16
 What ?
REVIEW OF LITERATURE

Literature Review is the documentation

of a published and unpublished work

from secondary sources of data

in the areas of specific interest to the researcher.

17
Why ? - PURPOSE OF REVIEW

To find out already investigated problems

and those that need further investigation.

 To formulate researchable hypothesis.

 To gain a background knowledge

 To identify data sources

 Tolearn how others structured their

reports. 18
 Where ?
SOURCES OF LITERATURE
 Books and Journals
 Databases
Bibliographic Databases
Abstract Databases
Full-Text Databases
 Govt. and NGO Records & Reports
 Internet
 On line journals: ww.articalbase.com …….
 E. Databases – Popline, Medline …….
 Research Dissertations / Thesis

19
 Step-3

Methodology

20
 Methodology
 Study Area : Location of study - Hospital, community etc.

 Study Period: Start to end of Study (maximum period

available for study should be defined)

 *Selection of Study Design

 * Selection of Study Population

 Pre-requisits of study: Study Tools, Terminologies,

Orientation trainings etc.

*will be taken separately

21
 Methodology……
• Study Tools for data collection: subjects, proforma,
examination, measurements, lab investigations
• Planning
 Data collection, compilation, data entry
 Data cleaning
 Analysis plan:
• Confidentiality
• Ethical clearance: Consent from
 Institutional Review Board
 Observational units

22
 Study Design

A study design is a specific plan or protocol

for conducting the study, which allows the
investigator to translate the conceptual
hypothesis into an operational one.

23
 Direction of Study
Backward Forward

Cross -sectional

Retrospective Prospective

4. Ambidirectional
24
 Decision Tree
Intervention Done
No Yes
Observational Study Experimental Study

Comparison Group Randomization

No Yes
No Yes
Descriptive Study Analytic Study
NRCT Study RCT Study

Direction of Study

E O E O
Cohort Study E = O Case-Control Study
Cross-Sectional Study

25
 Epidemiological Study Design
Observational Studies
 Descriptive Studies

Analytic
Cross-Sectional
Case-Control
Cohort

Experimental / Interventional studies

As per Control: RCT/NRCT
As per Blinding: Single /Double Blind
As per Design: Simple/Cross-over
As per Area: Field/Clinical/Lab 26
 Descriptive Studies

• Case reports
• Case series
• Population studies

27
 Descriptive Studies: Uses

• Hypothesis generating

• Suggesting associations

28
Descriptive Type of Obser vational Study

• Other Name Case-Series/Population

• Unit of Study Case/Individuals
• Study Question What is happening 
• Direction Of Inquiry
• Study Design
desired information
about cases/individuals is
collected

29
 Case-Series …….
Advantages
• Easy to do
• Excellent at identifying unusual situation
• Good for generating hypotheses

Disadvantages
• Generally short-term
• Investigators self-select (bias!)
• no controls

09/03/2010 30
Analytical Obser vational
Studies

• Cross-sectional

• Case-control

• Cohort

31
 Cross-sectional Study
• Data collected at a single point in time

• Describes associations

• Prevalence
A “Snapshot”

12/08/2012 Dr. Kusum Gaur 32 32

 Cross-Sectional Study
• Other Name Prevalence Study
• Unit of Study Individual
• Study Question What is happening 
• Direction of Inquiry
• Study Design Exposed
to Factor

Not
 Exposed
Diseased to Factor

Population Exposed to
 Factor
Non-
Disease Not
Exposed to
Factor 33
Objectives of a Cross-Sectional Study

To find out association

34
 Cross-sectional Study

SDaemfipnleed
ofPPoop
pu
ullaattiioonn

Regular Not doing meditation

Meditation

Prevalence of Prevalence of
DM DM

Time Frame = Present

12/08/2012 Dr. Kusum Gaur 35 35
 Cross-sectional Study
E.G. Out of 1000 population if 100 were doing meditation regularly &
out of that only 2 were having DM. Remaining 900 were not doing
meditation at all, out of that 220 were having DM.

+ DM -
Meditation

+ 2 98

- 220 680

12/08/2012 Dr. Kusum Gaur 36 36

 Cross-Sectional Study

• Strengths
– Quick
– Cheap

• Weaknesses
– Cannot establish cause-effect

09/03/2010 37
 Case-Control Studies
 Start with people who have disease(Cases)

 Match them with controls that do not have

disease (Match Confounding)

 Look back and assess exposures

38
 Controls
A control is a standard of comparison
(confounded with variability but without effect)

for

• Effects

• Variability

39
 Case-Control Study
• Other Name Retrospective Study
• Unit of Study Cases/Control
• Study Question What has happened 
• Direction of Inquiry= F O
• Study Design
Exposed
 Cases
Not
Exposed

Exposed

Control
Not
Exposed
40
Objective of a Case-Control Study

To find out association

To assess Risk Ratio

41
 Case-Control Study

Regular Meditation Cases

Patients with DM
No Meditation

Regular Meditation Controls

Persons w/o DM
No Meditation

Past Present
12/08/2012 Dr. Kusum Gaur 42 42
The logic of Case-Control Studies

Cases differ from controls only in having the

disease

If exposure does not predispose to having the

disease, then exposure should be equally
distributed between the cases and controls.

The extent of greater previous exposure among

the cases reflects the increased risk that exposure
confers
43
Case-Control Studies: Strengths

• Good for rare outcomes: cancer

• Can examine relation of exposures to disease
• Useful to generate hypothesis
• Fast
• Cheap
• Provides Odds Ratio

09/03/2010 44
Case-Control Studies: Weaknesses

• Cannot measure
– Incidence
– Prevalence
– Relative Risk
• Can only study one outcome
• High susceptibility to bias

09/03/2010 45
 Cohort Study

• Begin with disease-free individuals

• Classify patients as exposed/unexposed

• Record outcomes in both groups

• Compare outcomes using relative risk

46
 Cohort Study
• Other Name Prospective Study / Follow-up Study/Incidence Study
• Unit of Study Individual
• Study Question What is happening 
• Direction of Inquiry O
• F Study Design Diseased

•
Exposed to Not Non
Factor Diseased

Cohort
Cohort Diseased
Not
Exposed to
Factor
Non-Diseased

47
 Logic of Cohort
Study
Cohort is a group of persons sharing a
common characteristics

Differences in the rate at which exposed and

control subjects contract a disease is due to
the differences in exposure, since others are
known and similar.

48
 Cohort Study
 Prospective (usually)

 Controlled

 Can determine causes and incidence of

diseases as well as identify risk factors

 Generally expensive, time consuming and

difficult to carry out
49
 Steps for Cohort Study
 Identify geographically defined group
 Identify exposed subjects and not exposed
subjects
 Follow over a specific time
 Record the fraction in each group who
develop the condition of interest
 Compare these fractions using RR, AR or OR

50
Objectives of a Cohort Study

 To find out association

 To assess Risk Ratio

 To find out Relative Risk

 To find out Attributed Risk

51
 Prospective Cohort Study
DM
No Meditation
No DM

Cohort
DM
Regular
Meditation No DM

Present Future

52
 Cohort Strengths
Study:

• Can measure multiple outcomes

• Can adjust for confounding variables

• Can calculate Attributed Risk

09/03/2010 53
 Cohort Weaknesses
Study:
• Expensive

• Time consuming

• Cannot study rare outcomes

• Confounding variables

09/03/2010 54
 Measurements of association

Cohort Study Case Control Study

•Significance Test •Significance Test

•Relative Risk •OR
•Attributable Risk
•OR

55
 Measures of Association
Significance Test – to test significance of
difference in exposure between control and
Cases
Odds ratio - ratio of the odds of contracting
disease in given exposure
Relative Risk – Ratio between incidence
among exposed and incidence among non-
exposed
Attributed Risk – percentage of difference
between incidence among exposed and non-
exposed with incidence among exposed
RR or OR of 1 indicate no effect of exposure (equal odds) 56
 ‘Z’ Score of Exposure Rates
Cases control

Exposed a b
a x 100
Non- c d
Exposure Rates = in Cases exposed
(P2) a+c

b x 100
Exposure Rates = in Controls P2 – P1

(P1) b+d Z Score =

SEDP

P1Q 1 P 2 Q 2
09/03/2010
SEDP = ------------- + -------- 57
N1 N2
 ad
ODD‟s Ratio = Times
bc

Incidence among Exposed

RR = Times
Incidence among Non-Exposed

a/a+b a (c+d)
= =
c/c+d c (a+b)

09/03/2010 58
 Attributed Risk

(Incidence among Exposed - Incidence among Non-Exposed)

AR = x 100
Incidence among Exposed
a
Incidence among Exposed= x 100 a+b
c

Incidence among Non-Exposed= x 100

c+d

09/03/2010 59
 Experimental Studies

Clinical trials provide the “gold standard” of

determining the relationship between factor

and the event

60
Types of Experimental Study

As per Randomization:
• Randomized Control Trials (RCT)

• Concurrent Parallel Design (RCT)

• Sequential RCT Design

• RCT with External Control

• Non – Randomized Trials (NRCT)

61
Types of Experimental Study….

As per Design:
• Simple

• Cross-Over Study Design

As per Study Area:

• Field Trials

• Clinical Trials

• Lab. Trials 62
Quality of Experimental Study

• Randomization

• Blinding

• Control

• Cross-Over

63
 Controls in Clinical Trials
A clinical trial is a comparative, prospective
experiment conducted in human subjects

•Historical controls are better than no

controls

•Patients can serve as own controls -

This is usually beneficial as the
comparison removes patient differences
64
 Blinding
Good practice: factors that can affect
the evaluation of outcome should not be
permitted to influence the evaluation process

Single-blind
Patient or evaluator (either of one) is blinded as
to intervention

Double-blind design
Neither patient nor outcome evaluator knows Rx
to which patient was assigned

65
 Randomized Control Trials (RCT)

• Before and After Comparison

• Comparison with Placebo

• Comparison Of two medicine/procedure/tests

• Comparison Of > two medicine/procedure/tests

66
• Other Name
Experimental Study
Intervention Study
• Objective To know the effect of intervention
• Unit of Study Individual meeting entry criteria
• Study Question What is happening after intervention in
both groups 
• Direction of Inquiry I E
• Study Design 1(Intervention with Placebo) Positive
Outcome

Group 1/cases Intervention

Negative
Outcome

Positive
Outcome
Group
Placebo
2/control
Negative
Outcome

67
 Clinical Trial

R Treatment Outcomes
a Group
n
Study d
Population o
m

i z
Control Group Outcomes
e

68
 Inter vention Study - Design 2
(Comparison of Effect of Two Inter ventions)

Cases
Meeting
Entry criteria

Group - 1 Group -2

Intervention -1 Intervention Intervention - 2

Positive Negative Positive

Outcome Negative
Outcome Outcome Outcome

69
 Cross Over Design
Group -1 Cases Group-2
Meeting
Entry
criteria Intervention - 2
Intervention - 1

Positive Negative
Positive Negative Outcome
Outcome Outcome
Outcome

Group -1
Group -2 Crossover

Intervention -2
Intervention -1

Positive Negative
Positive Negative
Outcome
Outcome Outcome
Outcome

70
Other Types of Experimental Study

• Quincy Experimental Study

• Block Experimental Study

71
 Quincy Experimental Study

Cases
Meeting
Entry criteria

Group - 1 Group -2

Intervention Intervention No Intervention

Positive Negative Positive

Outcome Negative
Outcome Outcome Outcome

72
 Block Experimental Study

Cases
Meeting
Entry criteria

Group -3
Group - 1

Group -2

Intervention Intervention-3
Intervention -1 Intervention

Intervention-2

Positive Negative
Positive Negative
Outcome Outcome Outcome Outcome

Positive Negative
Outcome Outcome

73
Steps of Experimental Study
Drawing up a Protocol

Reference Population

Sample Population

Exclusions

Randomization

Experimental Group Control Group

Manipulation/Intervention

Follow - up

12/08/2012 AsDsr. e
Kus
sus
mmGae
urnt of Outcome 74
Ideal Study Design for established causality

Ethical Issues

75
STUDY QUESTIONS AND APPROPRIATE DESIGNS

Type of Question Appropriate Study Design

Burden of illness Field Surveys
- Prevalence Cross Sectional
- Incidence Survey Longitudinal

Causation, Risk & Prognosis survey

Case Control Study,
Cohort study, RCT

Treatment Efficacy Randomized Controlled study

Diagnostic Test Evaluation Randomized Controlled study

Cost Effectiveness Randomized Controlled study

76
 Hierarchy of Epidemiological Study Design

Establish Causality RCT

Cohort

Case Control

Cross-Sectional

Case Series

Generate Hypothesis Case Report

77
 Methodology
 Study Area : Location of study - Hospital, community
etc.

 Study Period: Start to end of Study (maximum period

available for study should be defined)

 *Selection of Study Design

 * Selection of Study Population

Sample Size
Sampling Technique

 Pre-requisits of study: Study Tools, Terminologies,

Orientation trainings etc.

78
Selection of study population

Whole Population

Sample Population

79
 What is Sample ?

• A sample is a small representative

segment of a population

• Inferences drawn from a sample are

expected to be applicable for the source
population

80
 Why do we need a sample?

To get inferences

applicable to universe

with minimum resources

81
 Sample – Qualities
Sample is a part of population but it is true
representative of whole.

Qualities

Adequate size

Appropriate sampling technique

82
 Factors on which SAMPLE SIZE depend:
• Population Factors
– Type of information available
• Type of study
– Type of Data
– Type of study design
– Type of sampling
– Type of Statistical Analysis for outcome needed
• Determined values of research by researcher
– Power
– Significance level

83
 Power: Ability to detect right answer

Alpha Error: Chance to miss right answer

84
Type of Data & level of Measurements

Qualitative – Counted Facts – Nominal Data

Measured as Numbers expressed as proportions

Quantitative- Measured Facts - Numerical Data

Measured as quantity & expressed as Mean
SD
*Ordinal Data – Rank Order Data
Measured as rank & expressed as Median Percentile

85
91
 Sample size for Qualitative data

Z 2 PQ 4 PQ
Sample Size= ------------------- -- = ---
---------------
L2 L2

P= Prevalence of disease
Q = 100-P
L = allowable error
Z= 1.96 ≈ 2 for 95% CL
for descriptive/case-series type of
09/03/2010 study design 86
92
 Sample size for Quantitative data

Z 2 SD 2 4 SD 2
Sample Size= -------------------
-- =----------------------
L2 L2

SD= Standard Deviation L =

allowable error
Z= 1.96 ≈ 2 for 95% CL
For Descriptive Studies only
09/03/2010 87
94
 Finite Correction
Sample Size – Finite Population (where the
population is less than 50,000)
SS
New SS =
( 1 + ( SS – 1 ))Pop

88
 How many controls?
n
k
2n  Here n0=No. of cases &
n = expected no. of cases

n 0
• k = 13 / (2*11 – 13) = 13 / 9 = 1.44
•kn0 = 1.44*11 ≈ 16 controls (and 11 cases)
– Same precision as 13 controls and 13 cases

89
 Sampling Design factors of sample size

Variance of Specified Sampling

Design Effect =
Variance of Simple Random Sampling

97
Sampling Technique effect on Sample Size
Sampling Technique Design Effect Size Multiplier

Simple Random Sampling 1

Systemic Random Sampling 1.2

Stratified Random Sampling 0.8

Cluster Random Sampling 2

98
 Conventionally accepted
Researcher’s Estimations

Alpha Error 0.05

Power 80%

Confidence Limit 95%

99
 Key Concepts: Sample size
• Sampling Design - larger sample for Custer

• Desired Power – more power for larger sample

• Allowable error – smaller error for larger sample

• Heterogeneity leads to have larger sample to

cover diversities

• Nature of Analysis – Complex multivariate

needs larger sample 93
100
Steps -Sample Size Estimation
• Stage 1- * Base Sample Size Calculation (n)

• Stage 2 – Sample Size with Design Effect (d)

=n*d

• Stage 3- Contingency Addition (e.g. 5%)

SS Estimation for study population
=(n*d)+5%of n

*Use appropriate equation for sample size

calculation
http://stat.ubc.ca/~rollin/stats/ssize/
94
101
95
96
E.G. Mean 1= 5, Mean 2 = 15 & SD = 14 inputting values

97
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12/08/2012 Dr. Kusum Gaur 107

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