8/4/2017 Sample size calculation

Int J Ayurveda Res. 2010 Jan-Mar; 1(1): 55–57. PMCID: PMC2876926

Sample size calculation

Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Parel, Mumbai - 400 012, India
1
Department of Clinical Pharmacology, TNMC and BYL Nair Hospital, Mumbai Central, Mumbai - 400 008, India
Address for correspondence: Dr. Supriya S. Bhalerao, Department of Clinical Pharmacology, TNMC and BYL Nair Hospital, Mumbai
Central, Mumbai 400 001, India. E-mail: [email protected]

Copyright © International Journal of Ayurveda Research

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.

I
One of the pivotal aspects of planning a clinical study is the calculation of the sample size. It is naturally
neither practical nor feasible to study the whole population in any study. Hence, a set of participants is
selected from the population, which is less in number (size) but adequately represents the population from
which it is drawn so that true inferences about the population can be made from the results obtained. This
set of individuals is known as the “sample.”

In a statistical context, the “population” is defined as the complete set of people (e.g., Indians), the “target
population” is a subset of individuals with specific clinical and demographic characteristics in whom you
want to study your intervention (e.g., males, between ages 45 and 60, with blood pressure between 140
mmHg systolic and 90 mmHg diastolic), and “sample” is a further subset of the target population which
we would like to include in the study. Thus a “sample” is a portion, piece, or segment that is representative
of a whole.

Every individual in the chosen population should have an equal chance to be included in the sample.
Ideally, choice of one participant should not affect the chance of another's selection (hence we try to
select the sample randomly – thus, it is important to note that random sampling does not describe the
sample or its size as much as it describes how the sample is chosen).

The sample size, the topic of this article, is, simply put, the number of participants in a sample. It is a basic
statistical principle with which we define the sample size before we start a clinical study so as to avoid bias
in interpreting results. If we include very few subjects in a study, the results cannot be generalized to the
population as this sample will not represent the size of the target population. Further, the study then may
not be able to detect the difference between test groups, making the study unethical.

On the other hand, if we study more subjects than required, we put more individuals to the risk of the
intervention, also making the study unethical, and waste precious resources, including the researchers’
time.

The calculation of an adequate sample size thus becomes crucial in any clinical study and is the process by
which we calculate the optimum number of participants required to be able to arrive at ethically and

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scientifically valid results. This article describes the principles and methods used to calculate the sample
size.

Generally, the sample size for any study depends on the:[1]

Acceptable level of significance

Some more factors that can be considered while calculating the final sample size include the expected
drop-out rate, an unequal allocation ratio, and the objective and design of the study.[2]

L
Everyone is familiar with the “p” value. This is the “level of significance” and prior to starting a study we
set an acceptable value for this “p.” When we say, for example, we will accept a p<0.05 as significant, we
mean that we are ready to accept that the probability that the result is observed due to chance (and NOT
due to our intervention) is 5%. To put it in different words, we are willing to accept the detection of a
difference 5 out of 100 times when actually no difference exists (i.e., get a “false positive” result).
Conventionally, the p value of 5% (p = 0.05) or 1% (p = 0.01), which means 5% (or 1%) chance of
erroneously reporting a significant effect is accepted.

P
Sometimes, and exactly conversely, we may commit another type of error where we fail to detect a
difference when actually there is a difference. This is called the Type II error that detects a false negative
difference, as against the one mentioned above where we detect a false positive difference when no
difference actually exists or the Type I error. We must decide what is the false negative rate we are willing
to accept to make our study adequately powered to accept or reject our null hypothesis accurately.

This false negative rate is the proportion of positive instances that were erroneously reported as negative
and is referred to in statistics by the letter β. The “power” of the study then is equal to (1 –β) and is the
probability of failing to detect a difference when actually there is a difference. The power of a study
increases as the chances of committing a Type II error decrease.

Usually most studies accept a power of 80%. This means that we are accepting that one in five times (that
is 20%) we will miss a real difference. Sometimes for pivotal or large studies, the power is occasionally set
at 90% to reduce to 10% the possibility of a “false negative” result.

E
We can understand the concept of “effect size” from day-to-day examples. If the average weight loss
following one diet program is 20 kg and following another is 10 kg, the absolute effect size would be 10
kg. Similarly, one can claim that a specific teaching activity brings about a 10% improvement in
examination scores. Here 10 kg and 10% are indicators of the claimed effect size.

In statistics, the difference between the value of the variable in the control group and that in the test drug
group is known as effect size. This difference can be expressed as the absolute difference or the relative
difference, e.g., in the weight loss example above, if the weight loss in the control group is 10 kg and in the
test group it is 20 kg, the absolute effect size is 10 kg and the relative reduction with the test intervention is
10/20, or 50%.

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We can estimate the effect size based on previously reported or preclinical studies. It is important to note
that if the effect size is large between the study groups then the sample size required for the study is less
and if the effect size between the study groups is small, the sample size required is large. In the case of
observational studies, for example, if we want to find an association between smoking and lung cancer,
since earlier studies have shown that there is a large effect size, a smaller sample would be needed to prove
this effect. If on the other hand we want to find out the association between smoking and getting brain
tumor, where the “effect” is unknown or small, the sample size required to detect an association would be
larger.

U
The underlying event rate of the condition under study (prevalence rate) in the population is extremely
important while calculating the sample size. This unlike the level of significance and power is not selected
by convention. Rather, it is estimated from previously reported studies. Sometimes it so happens that after
a trial is initiated, the overall event rate proves to be unexpectedly low and the sample size may have to be
adjusted, with all statistical precautions.

S (SD )
Standard deviation is the measure of dispersion or variability in the data. While calculating the sample size
an investigator needs to anticipate the variation in the measures that are being studied. It is easy to
understand why we would require a smaller sample if the population is more homogenous and therefore
has a smaller variance or standard deviation. Suppose we are studying the effect of an intervention on the
weight and consider a population with weights ranging from 45 to 100 kg. Naturally the standard deviation
in this group will be great and we would need a larger sample size to detect a difference between
interventions, else the difference between the two groups would be masked by the inherent difference
between them because of the variance. If on the other hand, we were to take a sample from a population
with weights between 80 and 100 kg we would naturally get a tighter and more homogenous group, thus
reducing the standard deviation and therefore the sample size.

S
There are several methods used to calculate the sample size depending on the type of data or study design.
The sample size is calculated using the following formula:

2σ 2,
2(Z a + Z 1–β )
n =
2
Δ

where n is the required sample size. For

Zα, Z is a constant (set by convention according to the accepted α error and whether it is a one-sided or
two-sided effect) as shown below:

For Z1-,β,Z is a constant set by convention according to power of the study as shown below:

In the above-mentioned formula σ is the standard deviation (estimated) and Δ the difference in effect of
two interventions which is required (estimated effect size).

This gives the number of sample per arm in a controlled clinical trial.

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This issue of the Journal has an article describing the benefits of ayurvedic treatment AyTP in patients of
migraine in an open uncontrolled trial design.[3] If anyone wishes to confirm these results using a
randomized controlled trial design where the effect of the ayurvedic intervention will be compared to
standard of care in headache as measured by VAS how would we plan the sample size?

As seen above, we need the following values: Zα, Z1-β,σ, standard deviation (estimated), and Δ, the
difference in effect of two interventions. Let us assume we will accept a p<0.05 as acceptable and a study
with 80% power; using the above tables, we get the following values: Zα, is 1.96 (in this case we will be
using a two-tailed test because the results could be bidirectional). Z1-β, is 0.8416. The standard deviation
(based on the data in the published paper) would be approximately 0.7. For Δ, the paper describes that the
ayurvedic therapy has given a 35% effect. Previously it has been reported that sumatriptan at 50 mg
improves headache by 50%.[4] Thus, the effect size would be 15% (i.e., 0.15).

The sample size for the new study will be

2 2
2(1. 96 + 0. 8416) (0. 72)
n =
2
(0. 15)

= 362 per arm.

Calculating for a 10% drop-out rate one would need to complete approximately 400 patients per arm to be
able to say with any degree of confi dence whether a difference exists between the two treatments.

L
The sample size calculated using the above formula is based on some conventions (Type I and II errors)
and few assumptions (effect size and standard variation).

The sample size ALWAYS has to be calculated before initiating a study and as far as possible should not
be changed during the study course.

The sample size calculation is also then influenced by a few practical issues, e.g., administrative issues and
costs.

Footnotes
Source of Support: Nil

Conflict of Interest: None decleared

R
1. Kirby A, Gebski V, Keech AC. Determining the sample size in a clinical trial. Med J Aust.
2002;177:256–7. [PubMed: 12197821]

2. Larsen S, Osnes M, Eidsaunet W, Sandvik L. Factors influencing the sample size, exemplified by
studies on gastroduodenal tolerability of drugs. Scand J Gastroenterol. 1985;20:395–400.
[PubMed: 3875139]

3. Prakesh B, Babu SR, Sureshkumar K. Response of Ayurvedic therapy in the treatment of migraine
without aura. Int J Ayurveda Research. 2010;1:29–35.

4. Cady RK, Sheftell F, Lipton RB, O'Quinn S, Jones M, Putnam G, et al. Effect of early intervention with
sumatriptan on migraine pain: Retrospective analyses of data from three clinical trials. Clin Ther.
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8/4/2017 Sample size calculation

2000;22:1035–48. [PubMed: 11048903]

Figures and Tables

α-error 5% 1% 0.1%
2-sided 1.96 2.5758 3.2905
1-sided 1.65 2.33

Power 80% 85% 90% 95%

Articles from International Journal of Ayurveda Research are provided here courtesy of Wolters Kluwer --
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