Circulating Tumor Cell Analysis: Technical and Statistical Considerations for Application to the Clinic

Table 1

Determination of database/sample size that will provide a given precision in rare event analysis.(𝐚)

Desired CV (%) →		1	5	10	20	40
r = no. of events of interest →		10000	400	100	25	6
When occurring at a frequency of		Total no. of events which must be collected(b)
(%)	1∶𝑛
10	10	10^5	4×10^3	10^3	2.5×10^2	6.3×10^1
1	100	10^6	4×10^4	10^4	2.5×10^3	6.3×10^2
0.1	1000	10^7	4×10^5	10^5	2.5×10^4	6.3×10^3
0.01	10,000	10^8	4×10^6	10^6	2.5×10^5	6.3×10^4
0.001	100,000	10^9	4×10^7	10^7	2.5×10^6	6.3×10^5
0.00001(c)	10,000,000	10^11	4×10^9	10^9	2.5×10^8	6.3×10^7

(a)For cell-based assays such as flow cytometry, a simple calculation can be used to determine the size of the database/sample that will provide a given precision: 𝑟=(100/CV)²; where 𝑟 is the number of events meeting the required criterion, and CV is the coefficient of variation of a known positive control. Modified from http://www.icms.qmul.ac.uk/flowcytometry/uses/rareeventanalysis/index.html, Queen Mary, University of London.
(b)With a WBC count in the low-normal range (∼5×10⁹/L), 10 mL of blood would contain ∼5×10⁷ events.
(c)Estimated frequency of CTCs in the peripheral blood of cancer patients.