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RESEARCH METHODOLOGY

&
BIOSTATISTICS

* Few jewels from ocean

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Definition of Research

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

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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

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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

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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.

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Process of Defining Problem
Analysis of the Situation

Identify & Prioritize Problems

Select & Define Problem

Statement of Research
Objectives

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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

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INTERNAL CRITERIA OF SELECTION

 Researcher‟s Interest,

 Researcher‟s Competence,

 Researcher‟s own Resource:


 Human Resource
 Money
 Material
 Time

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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

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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

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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

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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.
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STEP-2

REVIEW
OF
LITERATURE

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Review of literature

What ?

Why ?

Where ?

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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.

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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

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Step-3

Methodology

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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

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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

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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.

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Direction of Study
Backward Forward

Cross -sectional

Retrospective Prospective

4. Ambidirectional
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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

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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

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Descriptive Studies: Uses

• Hypothesis generating

• Suggesting associations

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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

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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

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Analytical Obser vational
Studies

• Cross-sectional

• Case-control

• Cohort

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

• Describes associations

• Prevalence
A “Snapshot”

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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

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Cross-sectional Study

SDaemfipnleed
ofPPoop
pu
ullaattiioonn

Regular Not doing meditation


Meditation

Prevalence of Prevalence of
DM DM

Time Frame = Present


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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

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Cross-Sectional Study

• Strengths
– Quick
– Cheap

• Weaknesses
– Cannot establish cause-effect

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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

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

for

• Effects

• Variability

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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
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Objective of a Case-Control Study

To find out association

To assess Risk Ratio

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Case-Control Study

Regular Meditation Cases


Patients with DM
No Meditation

Regular Meditation Controls


Persons w/o DM
No Meditation

Past Present
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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
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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

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Case-Control Studies: Weaknesses

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

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Cohort Study

• Begin with disease-free individuals

• Classify patients as exposed/unexposed

• Record outcomes in both groups

• Compare outcomes using relative risk

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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

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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.

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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
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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

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Objectives of a Cohort Study

 To find out association

 To assess Risk Ratio

 To find out Relative Risk

 To find out Attributed Risk

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Prospective Cohort Study
DM
No Meditation
No DM

Cohort
DM
Regular
Meditation No DM

Present Future

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Cohort Strengths
Study:

• Can measure multiple outcomes

• Can adjust for confounding variables

• Can calculate Attributed Risk

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Cohort Weaknesses
Study:
• Expensive

• Time consuming

• Cannot study rare outcomes

• Confounding variables

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Measurements of association

Cohort Study Case Control Study

•Significance Test •Significance Test


•Relative Risk •OR
•Attributable Risk
•OR

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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
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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)

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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

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Experimental Studies

Clinical trials provide the “gold standard” of

determining the relationship between factor

and the event

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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)

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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

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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
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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

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Randomized Control Trials (RCT)

• Before and After Comparison

• Comparison with Placebo

• Comparison Of two medicine/procedure/tests

• Comparison Of > two medicine/procedure/tests

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• 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

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Clinical Trial

R Treatment Outcomes
a Group
n
Study d
Population o
m

i z
Control Group Outcomes
e

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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

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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

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Other Types of Experimental Study

• Quincy Experimental Study

• Block Experimental Study

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Quincy Experimental Study

Cases
Meeting
Entry criteria

Group - 1 Group -2

Intervention Intervention No Intervention

Positive Negative Positive


Outcome Negative
Outcome Outcome Outcome

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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

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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

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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

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Hierarchy of Epidemiological Study Design

Establish Causality RCT

Cohort

Case Control

Cross-Sectional

Case Series

Generate Hypothesis Case Report

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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.

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Selection of study population

Whole Population

Sample Population

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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

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Why do we need a sample?

To get inferences

applicable to universe

with minimum resources

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

Qualities

Adequate size

Appropriate sampling technique

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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

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Power: Ability to detect right answer

Alpha Error: Chance to miss right answer

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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

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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
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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
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Finite Correction
Sample Size – Finite Population (where the
population is less than 50,000)
SS
New SS =
( 1 + ( SS – 1 ))Pop

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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

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Sampling Design factors of sample size

Variance of Specified Sampling


Design Effect =
Variance of Simple Random Sampling

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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

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Conventionally accepted
Researcher’s Estimations

Alpha Error 0.05

Power 80%

Confidence Limit 95%

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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
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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/
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E.G. Mean 1= 5, Mean 2 = 15 & SD = 14 inputting values

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