CASE STUDY
The Evaluation of Global Data as a Harmonized Database
Situation
Establishment of Reference ranges for clinical laboratory analytes often begins with ranges determined by the manufacturer of the instrument/reagent. Labs often take those ranges and test the results obtained from @ 100 patients/subjects determined to be “normal” based on the laboratory’s specifications. At which point the appropriate statistical tool is used to determine how well the range fits that population.
Objective
One consideration that ACM-Pivotal wanted to assess was the difference when evaluating populations from separate subpopulations. Consideration of homogenous nature of the population subsets and the prevalent dietary differences in the regions served were of interest.
Table A: A study summary of a subset of safety assays with the overall study means and result ranges.
|
Test name
|
Visit #
|
#Obs
|
#Eval
|
Mean
|
Minimum
|
Maximum
|
Std Dev
|
|
BUN
|
SCR
|
1140
|
1139
|
15.73
|
4.00
|
75.00
|
7.11
|
|
CK
|
SCR
|
1143
|
1139
|
129.22
|
18.00
|
2419.00
|
127.69
|
|
Creatinine
|
SCR
|
1140
|
1139
|
0.93
|
0.30
|
4.40
|
0.30
|
|
HCT
|
SCR
|
1140
|
1129
|
41.37
|
25.00
|
56.50
|
4.58
|
|
HCB
|
SCR
|
1139
|
1130
|
13.81
|
7.40
|
18.80
|
1.60
|
|
Potassium
|
SCR
|
1153
|
1120
|
4.63
|
3.00
|
6.40
|
0.47
|
|
RBC
|
SCR
|
1141
|
1129
|
4.74
|
2.81
|
6.93
|
0.50
|
|
Uric Acid
|
SCR
|
1140
|
1137
|
5.14
|
1.50
|
15.10
|
1.52
|
|
WBC
|
SCR
|
1147
|
1130
|
7.91
|
2.80
|
19.36
|
2.04
|
Table B: The data summarized in Table A was then broken out by the standard regional areas in order to determine if there were any significant bias in the data between the different sub populations.
|
Test name
|
Region
|
Visit #
|
#Obs
|
#Eval
|
Mean
|
Min.
|
Max.
|
Std Dev
|
|
BUN
|
Europe
|
SCR
|
214
|
213
|
17.77
|
8.00
|
68.00
|
6.26
|
|
|
India
|
SCR
|
479
|
479
|
12.16
|
4.00
|
40.00
|
5.11
|
|
|
USA
|
SCR
|
447
|
447
|
18.60
|
5.00
|
75.00
|
7.65
|
|
CK
|
Europe
|
SCR
|
214
|
213
|
105.17
|
19.00
|
515.00
|
73.27
|
|
|
India
|
SCR
|
480
|
479
|
118.79
|
18.00
|
907.00
|
94.62
|
|
|
USA
|
SCR
|
449
|
447
|
151.84
|
24.00
|
2419.00
|
168.97
|
|
Creatinine
|
Europe
|
SCR
|
214
|
213
|
1.08
|
0.60
|
2.00
|
0.21
|
|
|
India
|
SCR
|
479
|
479
|
0.88
|
0.30
|
2.80
|
0.31
|
|
|
USA
|
SCR
|
447
|
447
|
0.90
|
0.50
|
4.40
|
0.31
|
|
HCT
|
Europe
|
SCR
|
214
|
212
|
41.14
|
28.20
|
53.20
|
3.99
|
|
|
India
|
SCR
|
481
|
474
|
40.22
|
25.00
|
53.80
|
4.73
|
|
|
USA
|
SCR
|
445
|
443
|
42.70
|
29.50
|
56.50
|
4.34
|
|
HGB
|
Europe
|
SCR
|
214
|
212
|
14.03
|
9.00
|
18.00
|
1.41
|
|
|
India
|
SCR
|
481
|
474
|
13.37
|
7.40
|
18.00
|
1.71
|
|
|
USA
|
SCR
|
444
|
444
|
14.17
|
8.60
|
18.80
|
1.45
|
|
Potassium
|
Europe
|
SCR
|
214
|
212
|
4.72
|
3.70
|
6.40
|
0.43
|
|
|
India
|
SCR
|
479
|
472
|
4.68
|
3.40
|
6.30
|
0.49
|
|
|
USA
|
SCR
|
460
|
436
|
4.51
|
3.00
|
6.10
|
0.45
|
|
RBC
|
Europe
|
SCR
|
214
|
212
|
4.88
|
3.60
|
6.36
|
0.48
|
|
|
India
|
SCR
|
481
|
474
|
4.67
|
2.8
|
6.93
|
0.52
|
|
|
USA
|
SCR
|
446
|
443
|
4.73
|
3.34
|
6.47
|
0.48
|
|
Uric Acid
|
Europe
|
SCR
|
214
|
213
|
5.29
|
2.60
|
12.50
|
1.55
|
|
|
India
|
SCR
|
479
|
477
|
4.97
|
1.80
|
15.10
|
1.42
|
|
|
USA
|
SCR
|
447
|
447
|
5.25
|
1.50
|
11.10
|
1.59
|
|
WBC
|
Europe
|
SCR
|
214
|
212
|
8.25
|
3.25
|
19.36
|
2.29
|
|
|
India
|
SCR
|
481
|
474
|
8.19
|
2.80
|
17.50
|
2.02
|
|
|
USA
|
SCR
|
452
|
444
|
7.44
|
3.00
|
16.60
|
1.84
|
Conclusion
The only assay to demonstrate a significant bias, while with in an established reference range used globally was BUN. This was attributed to the predominant regional vegetarian diet. Other assays that we anticipated to yield a significant bias were uric acid and hgb, yet none was noted.
