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12<br />

Chapter | 1 Concepts <strong>of</strong> Normality in <strong>Clinical</strong> <strong>Biochemistry</strong><br />

tendency <strong>of</strong> the population can be obtained from the sample,<br />

such as the sample median and the sample mode. Also,<br />

sample-based estimates <strong>of</strong> the measures <strong>of</strong> dispersion or<br />

spread for the population can be obtained. The sample<br />

variance is computed as s 2 Σ ( x − i x ) 2 /( n 1), and the<br />

sample standard deviation, s , is obtained by taking the<br />

square root <strong>of</strong> s 2 . The descriptive statistics are called point<br />

estimates <strong>of</strong> the parameters and represent good approximations<br />

<strong>of</strong> the parameters. An alternative to the point estimate<br />

is the interval estimate , which takes into account the<br />

underlying probability distribution <strong>of</strong> the point estimate<br />

called the sampling distribution <strong>of</strong> the statistic.<br />

C . Sampling Distributions<br />

In actual practice, only a single sample is taken from a population<br />

and, on the basis <strong>of</strong> this sample, a single point estimate<br />

<strong>of</strong> the unknown population parameter is computed. If<br />

time and resources would permit repeated sampling <strong>of</strong> the<br />

population in the same manner—that is, with the same probability-based<br />

sampling design—one point estimate would<br />

be obtained for each sample obtained. The estimates would<br />

not be the same because the sample would contain different<br />

elements <strong>of</strong> the population. As the number <strong>of</strong> such repeated<br />

sampling operations increases, a more detailed description<br />

emerges <strong>of</strong> the distribution <strong>of</strong> possible point estimates<br />

that could be obtained by sampling the population.<br />

This is the sampling distribution <strong>of</strong> the statistic.<br />

Some fundamental facts relating to the sampling distribution<br />

<strong>of</strong> the sample mean follow: (1) The center <strong>of</strong> the<br />

sampling distribution <strong>of</strong> x − is equal to μ , the center <strong>of</strong> the<br />

underlying distribution <strong>of</strong> elements in the population. (2)<br />

The spread <strong>of</strong> the sampling distribution <strong>of</strong> x − is smaller than<br />

σ 2 , the spread <strong>of</strong> the underlying distribution <strong>of</strong> elements<br />

in the population. Specifically, the variance <strong>of</strong> the sampling<br />

distribution <strong>of</strong> x − (denoted σ 2 x<br />

− ) equals σ 2 /n , where n<br />

is the sample size. So increasing the sample size serves to<br />

increase the likelihood <strong>of</strong> obtaining an x − close to the center<br />

<strong>of</strong> the distribution because the spread <strong>of</strong> the sampling<br />

distribution is being reduced. (3) The central limit theorem<br />

(Daniel, 2005 ; Schork and Remington, 2000 ; Zar, 1999 )<br />

states that regardless <strong>of</strong> the underlying distribution <strong>of</strong> the<br />

population <strong>of</strong> elements from which the sample mean is<br />

based, if the sample size is reasonably large ( n 30), the<br />

sampling distribution <strong>of</strong> x − is approximated well by the<br />

Gaussian distribution. So x − drawn from any distribution has<br />

a sampling distribution that is approximately N (μ , σ 2 /n ) for<br />

n 30. If the distribution <strong>of</strong> the underlying population <strong>of</strong><br />

elements is Gaussian or approximated well by a Gaussian<br />

distribution, the sampling distribution <strong>of</strong> x − will be approximated<br />

well by the Gaussian distribution regardless <strong>of</strong> the<br />

sample size on which x − is based.<br />

Probabilities <strong>of</strong> the sampling distribution <strong>of</strong> x − , N ( μ ,<br />

σ 2 / n ), can be evaluated using the method described in<br />

Section II.B.<br />

Example 3<br />

Suppose the underlying population <strong>of</strong> elements is N (4,16)<br />

and a sample <strong>of</strong> size n 9 is drawn from this population<br />

using SRS. It is desired to find the probability <strong>of</strong> observing<br />

a sample mean less than 3.1 or greater than 6.2. In solving<br />

this problem, the relevant sampling distribution is specified:<br />

x − is N (4,16/9). Note that the sampling distribution <strong>of</strong> x −<br />

is Gaussian because the problem stated that the underlying<br />

population was Gaussian. (Otherwise the stated sample size<br />

would have needed to be 30 or larger to invoke the central<br />

limit theorem.) The probability <strong>of</strong> observing x − 3.1 in the<br />

distribution <strong>of</strong> x − is equivalent to the probability <strong>of</strong> observing<br />

z (3.1 4)/(4/3) 0.675 in the standard Gaussian distribution.<br />

Going to Table 1-2 , z 0.675 is approximately the<br />

75th percentile <strong>of</strong> the standard Gaussian distribution, and by<br />

symmetry z 0.675 is approximately the 25th percentile.<br />

Thus, the probability <strong>of</strong> observing a z value less than or equal<br />

to 0.675 is approximately 0.25. The probability <strong>of</strong> observing<br />

a sample mean greater than 6.2 is equivalent to the probability<br />

<strong>of</strong> observing z (6.2 4)/(4/3) 1.65. Table 1-2 gives<br />

the probability <strong>of</strong> observing a z 1.65 as approximately 0.95<br />

so the probability <strong>of</strong> observing a z 1.65 equals 1 0.95 or<br />

0.05. The desired probability <strong>of</strong> observing a sample mean<br />

less than 3.1 or greater than 6.2 is the sum <strong>of</strong> 0.25 and 0.05,<br />

which is 0.3 or 3 chances in 10.<br />

D . Constructing an Interval Estimate <strong>of</strong><br />

the Population Mean, μ<br />

This brief exposure to sampling distributions and their standardized<br />

forms provides the framework for generating an<br />

interval estimate for μ . Consider the probability statement<br />

Prob( 2 z 2) 0.9544. Because z ( x − μ )/(σ /√ n ),<br />

this probability statement is equivalent to the statement<br />

Prob( 2 ( x − μ )/(σ /√ n ) 2) 0.9544. Some standard<br />

algebraic manipulation <strong>of</strong> the inequality within the<br />

parentheses gives Prob(x − ( 2σ /√ n ) μ x − (2 σ /<br />

√ n )) 0.9544. This is the form <strong>of</strong> the confidence statement<br />

about the unknown parameter μ . With repeated<br />

sampling <strong>of</strong> the underlying population, 95.44% <strong>of</strong> the<br />

intervals constructed by adding and subtracting 2 σ / √ n to<br />

and from the sample mean would be expected to cover the<br />

true unknown value <strong>of</strong> μ . The quantities <strong>of</strong> x − 2 σ /√ n<br />

and x − 2 σ /√ n are called the lower and upper confidence<br />

limits , respectively, and the interval bounded below by<br />

x− 2 σ /√ n and above by x − 2 σ /√ n —that is, ( x − 2 σ /√ n ,<br />

x− 2 σ /√ n ) is the 95.44% confidence interval for μ . In<br />

practice, only one sample is taken from the population, and<br />

thus there is a 95.44% chance that the one interval estimate<br />

obtained will cover the true value <strong>of</strong> μ . Note that 95.44% or<br />

0.9544 is called the confidence level .<br />

The degree <strong>of</strong> confidence that is to be had is determined<br />

by the amount <strong>of</strong> error that is to be tolerated in the estimation<br />

procedure. For a 0.9544 level <strong>of</strong> confidence, the error rate is<br />

1 0.9544 0.0456. The error rate is designated by alpha, α .

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