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. Author manuscript; available in PMC: 2013 Aug 1.
Published in final edited form as: Biomark Med. 2012 Oct;6(5):10.2217/bmm.12.57. doi: 10.2217/bmm.12.57

Table 2.

Pros and cons of different ways of allocating resources to perform a study using 100 tests.

Subjects (n) Tests per subject at different times Tests per sample Information on analytical imprecision (SDA and CVA) Information on within-subject biological variation (SDI and CVI) Equation for SE of sampled population Reduction of SE by this study design Reduced dispersion of test result to improve classification§
100 1 1 No No
(SDA2+SDI2+SDG2100)12
Most None
50 2 1 No Yes/limited
([SDA22+SDI22+SDG2]/50)12
Less Yes
50 1 2 Yes No
([SDA22+SDI2+SDG2]/50)12
Less Maybe
25 4 1 No Yes/limited
([SDA24+SDI24+SDG2]/25)12
Less Yes/best
25 2 2 Yes Yes
([SDA24+SDI22+SDG2]/25)12
Least Yes

It is assumed that 100 subjects are available and that performing duplicate measurements on individual samples and/or repeated measurements on individual subjects are options.

Analytical imprecision (SDA and CVA) can be estimated by taking the square root of the average variance of pairs of measurements, or other methods.

The sum of within-subject variation (SDI or CVI) and analytical imprecision (SDA or CVA) can be estimated by taking the square root of the average variance of pairs of measurements separated in time; CVI can only be accurately estimated if CVA is determined separately and subtracted from (CVI + CVA).

§

Dispersion (confidence interval) for an individual test result is a function of CVA and CVI. Averaging repeated results separated in time will always reduce dispersion; averaging replicate results from each sample will only reduce dispersion if the magnitude of CVA is similar to or greater than that of CVI. How much misclassification is reduced depends on other factors (see text).

CV: Coefficient of variation; SD: Standard deviation; SDG: Between-subject SD; SE: Standard error of the mean.