1Cruz R +Cruz T +Cuevas J +Cunanan R

Introduction
Challenge to every research protocol:
It must specify a sample of subjects that:
o can be studied at an acceptable cost
in time and money
o is large enough to control random
error in generalizing the study
findings to the population
o is representative enough to control
systematic error in these inference;
How representative are they?
Basic terms and concepts
o Population complete set of people
with specified set of characteristics.
o Sample subset of the population,
selected so as to be representative
of the larger population.
o Target population the large set of
patients throughout the world to
which the results will be
generalized. Defined by clinical and
demographic characteristics.
o Accessible population the subset
of the target population that is
available for the study. Defined by
geographic and temporal
characteristics.

Reasons for Sampling
1. Samples can be studied more quickly than
populations.
2. A study of a sample is less expensive than
studying an entire population.
3. A study of an entire population is impossible
in most situations.
4. Sample results are often more accurate
than results based on a population.
5. If samples are properly selected, probability
methods can be used to estimate the error
in the resulting statistics.
6. Samples can be selected to reduce
heterogeneity.






RESEARCH QUESTION
(Truth in the Universe)


STEP # 1
Target Populations

Specify clinical and
Demographic
Characteristics

CRITERIA



Well suited to the
Research Question

STUDY
PLAN
(Truth in
the
Study)


STEP # 3
Intended
Sample

Design an
approach
to selecting
the
sample

CRITERIA



Representa
tive of
accessible
population
and easy to
do



STEP # 2
Accessible
Population

Specify
temporal
And
geographic
Characteris
tics

CRITERIA



Representa
tive of
target
populations
and easy
to
study

SPECIFICSPECIFI
CATION
SAMPLING
SAMPLING
Sampling Technique
Dr. BrizuelaSampling Techniques

2Cruz R +Cruz T +Cuevas J +Cunanan R





Specification
Establishing Inclusion Criteria

Inclusion criteria define the main
characteristics of the target and accessible
populations.



Designing Inclusion Criteria
Considerations Examples
Inclusion
criteria






Target
population

Specifying the
characteristics that
define populations
that are relevant to
the research question
and efficient for
study:

Demographic
characteristics

Clinical
characteristics
A 5 year trial of
calcium
supplementation for
preventing
osteoporosis might
specify that the
subjects be:

White females age
45 50

In good general
health:
no known life
threatening disease;
not taking long-term
corticosteroids


Establishing Exclusion Criteria
Exclusion criteria indicate subsets of
individuals who meet the eligibility criteria, but
are likely to interfere with the quality of the
data or the interpretation of the findings. Those
characteristics that can affect the results.

Designing Exclusion Criteria

Considerations Examples
Exclusion
criteria

Specifying subsets of
the population that will
not be studied because
of:




A high likelihood of
being lost to follow-up

An inability to provide
good data

Ethical barriers

The subjects refusal to
participate

A 5-year trial of
calcium
supplementation for
preventing
osteoporosis might
exclude subjects who
are:

Plan to move out of
state

Disoriented or having
language barriers

Kidney stone formers

Unwilling to accept
possibility of random
allocation to placebo
group



Designing Inclusion Criteria

Considerations Examples
Inclusion
criteria






Target
population








Accessible
population

Specifying the
characteristics that
define populations that
are relevant to the
research question and
efficient for study:


Demographic
characteristics

Clinical characteristics





Geographic
characteristics

Temporal
characteristics

A 5 year trial of
calcium
supplementation for
preventing
osteoporosis might
specify that the
subjects be:

White females age 45
50

In good general health:
no known life
threatening disease; not
taking long-term
corticosteroids

Patients attending the
medical clinic at the
investigators hospital
Between Jan 1 and Dec
31, 2006

Choosing an accessible population

Clinic based samples inexpensive and easy to
recruit, but selection factors that determine
who comes to the hospital or clinic may have an
important effect

3Cruz R +Cruz T +Cuevas J +Cunanan R
Population based samples particularly useful
for guiding public health and clinical practice in
the whole community, but chief disadvantage is
the expense and difficulty involved

Sampling

A. Probability Sampling
o uses a random process to guarantee that each
unit of the population has a specified chance of
selection

1.Simple Random sampling
-every subject has an equal probability of being
selected for the study.
- recommended way is to use a table of random
numbers or a computer generated list of
random numbers
-process of enumerating every unit of the
accessible population, and then selecting the
sample at random
-what are needed:
a. accurate listing of the population
b. mechanism to find and enroll those who are
chosen

2. Systematic Sampling
-involves selecting by a periodic process;
starting point is chosen at random
Example: get 200 sample from a population of
3400
-Procedure: Number all units 1 to 3400; divide
population with the number to be sampled
(3400/200 =17). Select any number between 1
to 17 to be the k. Then select every 17
th
subject
thereafter.
NOTE: should not be used when a cyclic
repetition is inherent in the sampling frame.
-e.g. not appropriate for selecting months of
the year in a study of the frequency of different
types of accidents, because some accidents
occur most often at certain times of the year

3. Stratified Random sampling
-involves dividing the population into subgroups
according to characteristics and taking a
random sample from each of these strata
-characteristics used to stratify should be
related to the measurement of interest
- in Medicine, commonly used strata include:
age, gender, severity of disease


4. Cluster Sampling
-process of taking a random sample of natural
groupings of individuals in the population; very
useful when the population is widely dispersed
and it is impractical or costly to list and sample
from all of its elements
- clusters are commonly based on geographic
areas or districts, so this approach is used more
often in epidemiologic research than in clinical
research


B. Nonprobability Sampling
-sampling method in which the probability that a
subject is selected is unknown

1.Consecutive Sampling
-involves taking every patient who meets the
selection criteria over a specified time interval
or number of patients; it amounts to taking the
complete accessible population over the
duration of the study
2. Convenience Sampling
- process of taking those members of the
accessible population who are easily available
at the time of study

3. Judgemental Sampling
- involves handpicking from the accessible
population those individuals judged most
appropriate for the study

Sample Size Computation

Sample Size:
Factors that affect the number of subjects required for
a study:
1. Whether the research design involves paired or
unpaired data
2. Whether beta error is considered in addition to
alpha error
3. Whether a large or small variance is anticipated
in the data set
4. Whether alpha level chosen is the usual (p value
0.05) or smaller

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5. Whether the desired difference between means
or proportions to be detected is fairly small or
extremely small



Pre-Test:
Answer with LARGE or SMALL:
What sample size would be needed if the
investigator wants the answer to be very close
to the true value (i.e., have very narrow
confidence level or a very small p value)?
What sample size would be needed if
anticipated variance is small?
What sample size would be needed if the
difference the investigator wants to detect is
extremely small?
Recall..
t = d
s
d


N
Where: d is the mean difference that was observed,
s
d
is the standard error of that mean difference, and
N is the sample size

Therefore:

N =(z

)
2
* (s)
2
(d)
2

Derivation of Basic Sample Size Formula

For sample sizes in commonly pursued medical research

1.) Before and after studies using paired t test with only
alpha (type I) error only

N =(z

)
2
* (s)
2
(d)
2

Example:
Study
Characteristic
s
Assumptions made by
Investigator
Type of Study
Data sets


Variable
Standard
deviation (s)
Variance (s
2
)
Data for alpha
(z

)

Difference to
be detected
(d)
Before and after study of
an anti-HPN drug
Pre-treatment and post-
treatment
observations in the same
group
of subjects
Systolic blood pressure
15 mm Hg
225 mm Hg
p =0.05; therefore, 95%
confidence
desired (two-tailed test);
Z

=1.96
10 mm Hg or larger
difference
between pre and post-
treatment blood pressure
values

N =(z

)
2
* (s)
2
(d)
2
=(1.96)
2
* (15)
2
(10)
2
=(3.84)*(225)
(100)
=864 =8.64 =9 subjects total
100

2. ) Studies with one experimental & one control group
using t test with only alpha (type I) error only


N =(z

)
2
* 2 * (s)
2

(d)
2


Example:

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Study
Characteristics
Assumptions made by
Investigator
Type of Study
Data sets


Variable

Standard
deviation (s)

Variance (s
2
)
Data for alpha
(z

)

Data for alpha
(Z

)

Difference to be
detected (d)
RCT of an anti-HPN drug
Observations in one
experimental group and one
control group

Systolic blood pressure

15 mm Hg

225 mm Hg
p =0.05; therefore, 95%
confidence desired (two-tailed
test); Z

=1.96

20%beta error; therefore, 80%
power desired (one-tailed test);
Z

=0.84


10 mm Hg or larger difference
between mean blood pressure

N =(z

)
2
* 2 * (s)
2
(d)
2
=(1.96)
2
* 2 * (15)
2
(10)
2
=(3.84)*2*(225)
(100)
=1728 = 17.28
100
=18 subjects per group * 2 grps =36 subjects




3.) Studies with t test with alpha (type I) & beta (type II)
errors


N =(z
+
z

)
2
* 2 * (s)
2

(d)
2

example:
Study
Characteristics
Assumptions made by
Investigator
Type of Study



Data sets

Variable



Variance, p (1-p)

Data for alpha
(z

)

Data for alpha
(z

)



Difference to be
RCT of a drug to reduce
the 5yr mortality in
patients with a
particular form of cancer
Observations in one
experimental group and
one control group
Success=5-yr survival
after Tx; Failure =death
within 5 yrs of Tx

p=0.55;therefore, (1-p) =
0.45
p =0.05; therefore, 95%
confidence desired (two-
tailed test); Z

=1.96
20%beta error;
therefore, 80%power
desired (one-tailed test);
Z

=0.84

0.1 or larger difference
bet the success
(survival) of the E grp
and that of the C grp)
N =(z
+
z

)
2
* 2 * (s)
2
(d)
2

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=(1.96+0.84)
2
*2* (15)
2
(10)
2
=(7.84)*2* (225)
100
=3528 =35.28
100
=36 subjects per grp * 2 grps =72 subjects

4.) Studies using a test of differences with alpha (type I)
& beta (type II) errors



N =(z
+
z

)
2
* 2 * p(1 - p)
2

(d)
2
exa,ple:
Study
Char.Characte
ristics
Assumptions made by Investigator

Type of Study



Data sets


Variable

Variance, p (1-p)


Data for alpha (z

)




Data for alpha (z

)



RCT of a drug to reduce the 5yr
mortality in patients with a
particular form of cancer

Observations in one experimental
group and one control group

Success=5-yr survival after Tx;
Failure=death within 5 yrs of Tx
p=0.55;therefore, (1-p) =0.45

p =0.05; therefore, 95%
confidence

desired (two-tailed test);
Z

=1.96;

20%beta error; therefore, 80%
power

desired (one-tailed test); Z

=0.84





N =(z
+
z

)
2
* 2 * p(1 - p)
(d)
2
=(1.96+0.84)
2
* 2 * (0.55)(0.45)
(0.1)
2

=(7.84)*2*(0.2475)
0.01
=3.88 = 388

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0.01
=388 subjects per grp * 2 grps =776
References:
1. Epidemiology, Biostatistics and Preventive Medicine
(J ekel)
2. Designing Clinical Research (Hulley and Cummings)
3. Research Methods in Health and Medicine (Sanchez)
4. Basic and Clinical Biostatistics (Dawson and Trapp)
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