Tools, Technologies and Training for Healthcare Laboratories

Quality Requirements

Biological Variation in Patients with Disease

Dr. Carmen Ricos and her colleagues have generously allowed us to post a new database on Biologic Variation within subjects with disease. The previous databases have relied on data from healthy patients. See how the variation changes when you examine patients with different disease states.

Within-subject biological variation in disease

June 2009

We are pleased to present a new published data set from Dr. Carmen Ricos and her colleagues. This set of biologic variation data is unique in that it represents the biologic variation not from healthy individuals, but from patients with various diseases.

The original paper appeared as Carmen Ricos, Natalia Iglesias, Jose-Vicente Garcia-Lario, Margarita Simon, Fernando Cava, Amparo Hernandez, Carmen Perich, Joanna Minchinela, Virtudes Alvarez, Maria-Vicenta Domenench, Carlos-Victor Jimenez, Carmen Biosca, and Raquel Tena, Within-subject biological variation in disease: collated data and clinical consquences, Ann Clin Biochem 2007:44:343-352

A note on abbreviations:

Matrix: specimen type
S: Serum
P: Plasma
B: Whole Blood
U: Urine		 Column 3 CVI:
within-subject biological variation
in healthy patients		 Column 4 CVI:
within-subject biological variation
in patients with disease		 n: number of subjects studies
d: period of time covered in days s: number of samples obotained for each subject Disease: name of the disease in study Ref: Reference number
(see list below

 

 

Analytes A

Analyte Matrix CVI (%)
Healthy
(median)		 CVI (%)
Disease		 n d s Disease Reference Mean Units
?-Fetoprotein S 12 12 30 180 3 Colon neoplasm 10 2.86 ug/L
?-Fetoprotein S   35 40 180 3-10 Hepatic disease, no cirrhosis 10 4.07 ug/mL
?-Fetoprotein S   38 85 180 3-10 Hepatocellular carcinoma 10 3.97 ug/L
?-Fetoprotein S   40 45 108 3-8 Cirrhosis 10 3.83 ug/L
Alanine aminopeptidase S 4.1 4.3 20 28 7 Chronic liver disease 29 1.39 ukat/L
ALT S 24 11 20 28 7 Chronic liver disease 29 2.04 ukat/L
ALT S   13 27 56 8 Type I- DM 27 0.52 ukat/L
ALT S   25 9 2 11 Impaired renal function 23 0.21 ukat/L
Albumin S 3.1 2.8 16 56 8 Type I-DM 27 44 g/L
Albumin S   2.9 8 21 8 Chronic renal failure 28 41 g/L
Albumin S   3.3 20 28 7 Chronic liver disease 29 39 g/L
Albumin S   4.3 9 2 11 Impaired renal function 23 39.1 g/L
Albumin S   6.7 20 4 19 Acute myocardial infarction 22 37.1 g/L
Albumin, first morning U 36 42 47 21 3 Type I-DM 39 350 mg/L
Albumin, first morning U   61 16 21-28 10 Diabetic subjects 33 14 mg/L
Albumin/creatinine ratio U NA 39 16 21-28 10 Diabetic subjects 33 1.25 mg/mmol
ALP S 6.4 6.4 8 84 8 Chronic renal failure 28 3.21 ukat/L
ALP S   6.6 20 28 7 Chronic liver disease 29 7.5 ukat/L
ALP S   12.4 15 72 5 Paget disease 17 9.8 ukat/L
ALP bone isoform S 6.2 4.9 15 72 5 Paget disease 17 136 ug/L
Amino-terminal proBNP P NA 8.6 37 1 6 Stable chronic heart failure 20 570 ng/L
Amino-terminal proBNP P   20 37 5 5 Stable chronic heart failure 20 570 ng/L
Amino-terminal proBNP P   35 37 42 15 Stable chronic heart failure 20 570 ng/L
Amylase S 12 8.2 17 21 8 Chronic renal failure 28 110 U/L
Amylase S   8.4 20 28 7 Chronic liver disease 29 8.7 U/L
Amylase S   11.1 27 56 8 Type I- DM 27 4.58 U/L
Amylase (total) first morning U NA 35 47 21 3 Type I- DM 39 4.58 ukat/L
Amylase (pancreatic) first morning U NA 38 47 21 3 Type I- DM 39 2.90 ukat/L
Amylase Saliva NA 51 47 21 3 Type I- DM 39 1.60 ukat/L
Apo-A1 S 6.5 7.1 143 70 3 Lipid disorders 36 1.50 g/L
Apo-B S 6.9 6.4 143 70 3 Lipid disorders 36 1.71 g/L
AST S 12 10.6 20 28 7 Chronic liver disease 29 1.76 ukat/L
AST S   12.3 37 56 8 Type I- DM 27 0.48 ukat/L

Analytes B-C

Analyte Matrix CVI (%)
Healthy
(median)		 CVI (%)
Disease		 n d s Disease Reference Mean Units
Bicarbonate S 4.8 7.9 20 4 19.5 Acute myocardial infarction 22 19.5 mmol/L
BNP P NA 8.2 37 1 6 Stable chronic heart failure 20 135 ng/L
BNP P   24 37 5 s Stable chronic heart failure 20 135 ng/L
BNP P   40 37 42 15 Stable chronic heart failure 20 135 ng/L
CA 125 S 29 21.8 12 120 4 Non small cell lung carcinoma 43 NA NA
CA 125 S   36.0 24 1095 5 Resected lung neoplasm (not oat cell) 36 10.6 U/L
CA 125 S   46.2 41 1095 7 Resected ovarian neoplasm 35 8.8 U/L
CA 15.3 S 6.2 7.0 50 30 3 Radically resected breast cancer 24 16 U/mL
CA 15.3 S   11.2 33 2010 11 Breast cancer (resected) 32 NA NA
CA 15.3 S   16.7 170 90 NA Breast cancer 25 16.2 U/mL
CA 19.9 S 16 24.5 41 1095 7 Resected ovarian neoplasm 35 8.8 U/L
CA 19.9 s   24.5 24 1095 7 Resected lung neoplams (not oat cell) 35 13.2 U/L
Calcium S 1.9 1.3 8 84 8 Chronic renal failure 28 2.34 mmol/L
Calcium S   1.6 14 56 8 Hyptertension 30 2.34 mmol/L
Calcium S   2.8 9 84 11 Chronic renal failure 28 2.23 mmol/L
Calcium S   4.8 20 4 19.5 Acute Myocardial infarction 22 2.25 mmol/L
Calcium S   6.7 9 2 11 Impaired renal function 23 2.4 mmol/L
Calcium/creatinine ratio, 2h U NA 33 46 2 2 Inpatients Metabolic bone disease 45 0.31 mmol/mmol
Calcium/creatinine ratio, 2h U   39 20 30-90 2 Outpatients Osteoporosis (only) 45 0.48 mmol/mmol
Calcium/creatinine ratio, 2h. U   41 20 2 2 Inpatients Osteoporosis (only) 45 0.31 mmol/mmol
Calcium/creatinine ratio, 2h U   44 46 30-90 2 Outpatients Metabolic bone disease 45 0.39 mmol/mmol
CEA S 13 9.8 92 30 3 Radically resected breast cancer 24 NA NA
CEA S   10.6 12 120 4 Non small cell lung carcinoma 43 NA NA
CEA S   12.4 31 900 3 to 7 Colon neoplasm 21 1,80 ug/L
CEA S   16.2 420 90 >3 Radically resected breast cancer 24 NA NA
CEA S   19.1 32 901 4 to 7 Breast cancer (no evidence of disease) 21 1.40 ug/L
CEA S   23.6 24 1095 5 Resected lung neoplasm (not oat cell) 35 1.77 mg/L
CEA S   26.9 170 90 NA Breast cancer (operated) 25 1.60 ug/L
CEA S   27.0 33 2010 11 Breast cancer 32 NA NA
CEA S   44.9 33 1095 7 Resected colorectal neoplasm 35 1.99 mg/L
Chloride S 1.2 1.1 14 56 8 Hypertension 30 105 mmol/L
Chloride S   1.1 9 2 11 Impaired renal function 23 104 mmol/L
Chloride S   1.8 41 90 8 Renal post-transplantation 18 108.6 mmol/L
Chloride S   1.8 8 21 8 Chronic renal failure 28 110 mmol/L
Chloride S   1.9 27 56 8 Type I- DM 27 100 mmol/L
Chloride S   2.2 20 4 20 Acute myocardial infarction 22 102.7 mmol/L
Chloride S   3.2 10 28 7 Chronic liver disease 29 103 mmol/L
Cholesterol S 6.0 4.7 35 28 4 Mild hypercholesterolemia 41 6.0 mmol/L
Cholesterol S   5.0 128 70 3 Lipid disorders 35 6.1 mmol/L
Cholesterol S   5.2 20 28 7 Chronic liver disease 29 5.0 mmmol/L
Cholesterol S   7.0 14 56 8 Hyptertension 30 6.0 mmol/L
Cholesterol S   7.2 27 56 8 Type I- DM 27 5.6 mmol/L
Cholinesterase S 7.0 7.1 20 28 7 Chronic liver disease 29 103 ukat/L
Creatine kinase S 23 43 9 2 11 Impaired renal function 23 75.2 U/L
Creatinine S 4.3 5.3 17 21 8 Chronic renal failure 28 483 umol/L
Creatinine S   5.9 27 56 8 Type I- DM 27 73 umol/L
Creatinine S   6.4 9 2 11 Impaired renal function 23 190 umol/L
Creatinine S   6.5 11 56 8 Type I- DM 27 64 umol/L
Creatinine S   11.5 41 90 8 Renal post-transplantation 18 148 umol/L
Creatinine S   13.0 54 540 9 Children chronic kidney disease 40 52 umol/L
Creatinine S   13.4 20 4 19.5 Acute myocardial infarction 22 85 umol/L
Creatinine, first morning U NA 34 47 21 3 Type I- DM 39 10.1 mmol/L
CTx S 9.6 12.4 15 365 5 Paget 17 5976 pmol/L
CTX/creatinine ratio, 2h U NA 24 15 365 5 Paget 17 484 ug/mmol
Cyfra 21.1 S 22 21.8 12 120 4 Non small cell lung carcinoma 43 NA NA
Cystatin C S NA 12 54 540 9 Children chronic kidney disease 40 2.81 mg/L
alpha-ALA/creatinine ratio U 20 20 15 70 10 Acute intermittent porphyria 16 6.9 umol/mmol
alpha-ALA/creatinine ratio U   20 15 720 15 Acute intermittent porphyria 16 6.7 umol/mmol

Analytes F through N

Analyte Matrix CVI (%)
Healthy
(median)		 CVI (%)
Disease		 n d s Disease Reference Mean Units
FT4 S 7.6 5.7 12 0.33 5 Primary hypothyroidism 19 NA NA
FT3 S 7.9 8.7 12 0.33 5 Primary hypothyroidism 19 NA NA
GGT S 14 4.7 20 28 7 Chronic liver disease 29 6.8 ukat/L
GGT S   9.9 27 56 8 Type I- DM 27 0.37 ukat/L
Glucose S 5.7 27.4 9 2 11 Impaired renal function 23 5.1 mmol/L
HDL Cholesterol S 7.1 7.1 128 70 3 Lipid disorders 36 1.36 mmol/L
HDL Cholesterol S   7.7 27 56 8 Type I- DM 27 1.53 mmol/L
HDL Cholesterol S   8.7 14 56 8 Hyptertension 30 1.07 mmol/L
HDL Cholesterol S   9.5 17 21 8 Chronic renal failure 28 1.00 mmol/L
Hemoglobin B 2.8 2.3 14 56 8 Hypertension 30 9.8 mmol/L
Hemoglobin B   2.9 27 56 8 Type I- DM 27 10.1 mmol/L
Hemoglobin B   4.2 20 28 7 Chronic liver disease 29 8.9 mmol/L
Hemoglobin A1c B 1.9 4.3 47 720-1260 4-7 Type II- DM 42 6.5 %
Hemoglobin A1c B   8.8 214 365 4 Type I- DM 34 11.7 %
Hydroxyproline/creatinine ratio, 2h U 26 33.8 20 30-90 2 Osteoporosis (only) 45 30 umol/mmol
Hydroxyproline/creatinine ratio, 2h U   40.6 46 30-90 2 Metabolic bone disease 45 37 umol/mmol
Hydroxyproline/creatinine ratio, second U 13 18.7 15 365 5 Paget's disease 17 200 nmol/mg
LDL- Cholesterol S 8.3 6.6 35 28 4 Mild hypercholesterolemia 41 4.30 mmol/L
LDL- Cholesterol S   7.8 128 70 3 Lipid disorders 36 4.12 mmol/L
LDL- Cholesterol S   9.5 85 365 4 Coronoary artery disease 37 NA NA
Lipoprotein (a) S 8.5 26.2 12 360 4 Type I- DM 26 25 mg/dL
Lipoprotein (a) S   23.3 24 360 4 Type I- DM 26 >40 mg/dL
Lipoprotein (a) S   42.3 13 360 4 Type I- DM 26 15 mg/dL
Lipoprotein (a) S   42.3 21 360 4 Type I- DM 26 <10 mg/dL
MCA S 10.1 14.9 33 2010 11 Resected breast cancer 32 NA NA
NAG, first morning U NA 58 47 21 3 Type I- DM 39 48 nkat/L
NTx/creatinine ratio, 2h U 17 15.8 15 365 5 Paget 17 248 nmol

Analytes P

Analyte Matrix CVI (%)
Healthy
(median)		 CVI (%)
Disease		 n d s Disease Reference Mean Units
PBG, first morning U 15 18.0 15 70 10 Acute intermittent porphyria 16 5.0 umol/mmol
PBG, first morning U   25.0 15 720 15 Acute intermittent porphyria 16 5.0 umol/mmol
Potassium S 4.8 4.5 14 56 8 Hyptertension 30 4.36 mmol/L
Potassium S   4.8 16 56 8 Type I- DM 27 4.65 mmol/L
Potassium S   5.1 17 21 8 Chronic renal failure 28 4.98 mmol/L
Potassium S   7.0 11 56 8 Type I- DM 27 4.81 mmol/L
Potassium S   7.1 41 90 8 Renal post-transplantation 18 4.46 mmol/L
Potassium S   7.7 20 28 7 Chronic liver disease 29 4.50 mmol/L
Potassium S   12.4 20 4 19.5 Acute myocardial infarction 22 3.68 mmol/L
Potassium S   13.3 9 2 11 Impaired renal function 23 4.5 mmol/L
Procollagen (Type I N-terminal) S 6.8 10.0 15 72 5 Paget 17 176 ug/L
PAP S NA 34 15 4 8 Prostate cancer 36 6.7 U/L
PAP S   34 15 4 8 Prostate cancer 38 0.8 U/L
PAP S   34 15 4 8 Prostate cancer 38 0.3 U/L
PSA (total) S 18.1 14 5 4 8 Prostate cancer 38 40.3 ug/L
PSA (total) S   14 5 4 8 Prostate cancer 38 10.8 ug/L
PSA (total) S   14 5 4 8 Prostate cancer 38 3.2 ug/L
PSA (total) S   20 890 90-960 2-10 Prostate cancer 15 0.1-20 ug/L
Protein, total S 2.7 3.3 17 21 8 Chronic renal failure 28 74 g/L
Protein, total S   4.1 27 56 8 Type I- DM 27 73 g/L
Protein, total S   4.2 20 28 7 Chronic liver failure 29 78 g/L

Analytes S through Z

Analyte Matrix CVI (%)
Healthy
(median)		 CVI (%)
Disease		 n d s Disease Reference Mean Units
SCC S 39 39 24 1095 5 Lung neoplasm (not oat cell) 35 1.01 mg/L
Sodium S 0.7 0.6 14 56 8 Hypertension 30 143 mmol/L
Sodium S   0.7 17 21 8 Chronic renal failure 28 142 mmol/L
Sodium S   0.8 27 56 8 Type I- DM 27 140 mmol/L
Sodium S   0.8 9 2 11 Impaired renal function 23 142 mmol/L
Sodium S   0.9 20 28 7 Chronic liver disease 29 140 mmol/L
Sodium S   1.0 8 21 11 Chronic renal failure 28 143.4 mmol/L
Sodium S   1.1 41 90 8 Renal post-transplantation 18 141 mmol/L
Sodium S   1.5 20 4 19.5 Acute myocardial infarction 22 139.8 mmol/L
Sweat chloride Sweat 15 7.3 20 35 5 Cystic fibrosis 44 120 mmol/L
T3 S 8.7 8.4 13 56 8 Pregnancy 31 2.96 nmol/L
T3 S   8.7 12 0.33 5 Primary hypothyroidism 19 NA NA
T4 S 4.9 4.9 12 0.33 5 Primary hypothyroidism 19 NA NA
T4 S   7.3 13 56 8 Pregnancy 31 108 nmol/L
TSH S 29 29 24 1095 5 Lung neoplasm (not oat cell) 35 61 U/L
TPA S 36 36 24 1095 5 Lung neoplasm (not oat cell) 35 47 U/L
TPS S 36 36 24 1095 5 Lung neoplasm (not oat cell) 35 47 U/L
Triglycerides S 20.9 7.7 11 56 8 Type I- DM 27 2.4 mmol/L
Triglycerides S   15.4 17 21 8 Chronic renal failure 28 3.59 mmol/L
Triglycerides S   17.8 128 70 3 Lipid disorders 35 1.46 mmol/L
Triglycerides S   19.6 35 28 4 Mild hypercholesterolemia 41 1.41 mmol/L
Triglycerides S   20.0 16 56 8 Type I- DM 27 1.88 mmol/L
Triglycerides S   21.8 14 56 8 Hypertension 30 2.88 mmol/L
Urate S 8.6 10.1 17 21 8 Chronic renal failure 28 477 umol/L
Urate S   10.3 27 56 8 Type I- DM 27 276 umol/L
Urate S   13.2 41 90 8 Renal post-transplantation 18 415 umol/L
Urea S 12.3 6.5 9 2 11 Impaired renal function 23 13.2 mmol/L
Urea S   11.7 17 21 8 Chronic renal failure 28 21 mmol/L
Urea S   13.0 16 56 8 Type I-DM 27 5.9 mmol/L
Urea S   15.3 41 90 8 Renal post-transplantation 18 NA NA
Urea S   15.6 11 56 8 Type I- DM 27 5.26 mmol/L
Urea S   18.3 20 4 20 Acute myocardial infarction 22 5.31 mmol/L

References

  1. Fraser CG, Harris EK. Generation and application of data on biological variation in clinical chemistry. Crit Rev Clin Lab Sci 1989; 27: 409–37
  2. Fraser CG. Biological Variation: From Principles to Practice. Washington DC: AACC Press, 2001
  3. Kenny D, Fraser CG, Hyltoft Petersen P, Kallner A. Consensus Agreement. In: Hyltoft Petersen P, Fraser CG, Kallner A, Kenny D eds. Strategies to set global analytical quality specifications in laboratory medicine. Scand J Clin Lab Invest 1999; 59: 585
  4. Fraser CG. Are ‘scientific statements’ the scientific truth?. http:// www.westgard.com/guest23.htm (accessed 05 November 2006)
  5. Fraser CG. Inherent biological variation and reference values. Clin Chem Lab Med 2004; 42: 758–64
  6. Rico´s C, Cava F, Garci´a-Lario JV, et al. The reference change value: a proposal to interpret laboratory reports in serial testing based on biological variation. Scand J Clin Lab Invest 2004; 64: 175–84
  7. Iglesias N, Hyltoft Petersen P, Jensen E, Rico´s C, Joergensen P. Reference change values and power functions. Clin Chem Lab Med 2004; 42: 415–22
  8. Biosca C, Rico´s C, Lauzurica R, Galimany R. Reference change value concept combining two delta values to predict crises in renal posttransplantation. Clin Chem 2001; 47: 2146–8
  9. Biosca C, Rico´s C, Lauzurica R, Hyltoft Petersen P. Biological variation at long-term renal post-transplantation. Clin Chim Acta 2006; 368: 188–91
  10. Trape´ J, Botargues JM, Porta F, et al. Reference change value for a-fetoprotein and its application in early detection of hepatocellular carcinoma in patients with hepatic disease. Clin Chem 2003; 49: 1209–11
  11. Rico´s C, Alvarez V, Cava F, et al. Current databases on biological variation: pros, cons and progress. Scand J Clin Lab Invest 1999; 59: 491–500
  12. Sociedad Espan˜ ola de Bioqui´mica Cli´nica y Patologi´a Molecular. Comite´ de Garanti´a de la Calidad y Acreditacio´n de Laboratorios. Especificaciones de la calidad anali´tica en laboratorios con distintos niveles de recursos. Quim Clin 2000; 19: 219–36
  13. Rico´s C, Alvarez V, Cava F, et al. Biological variation database and quality specifications for imprecision, bias and total error. The 2006 update. https://westgard.com/guest32.htm (accessed 05 November 2006)
  14. Sociedad Espan˜ola de Bioqui´mica Cli´nica y Patologi´a Molecular. Comite´ de Garanti´a de la Calidad y Acreditacio´n de Laboratorios. Base de datos de variacio´n biolo´ gica, con las especificaciones de la calidad anali´tica (deseable, minima y optima). Actualizacio´n del an˜o 2006. f. http://www.seqc.es/bd/vb.htm (accessed 05 November 2006)
  15. Sole´tormos G, Semjonow A, Sibley PEC, et al. Biological variation of total prostate-specific antigen: a survey of published estimates and consequences for clinical practice. Clin Chem 2005; 51: 1342–51
  16. Aarsand AK, Hyltoft Petersen P, Sandberg S. Estimation and application of biological variation of urinary d-aminolevulinic acid and porphobilinogen in healthy individuals and in patients with acute intermittent porphyria. Clin Chem 2006; 52: 650–6
  17. Alvarez L, Rico´s C, Peris P, et al. Components of biological variation of biochemical markers of bone turnover in Paget’s bone disease. Bone 2000; 26: 571–6
  18. Biosca C, Rico´s C, Jime´nez CV, Lauzurica R, Galimany R. Are equally spaced specimens collection necessary to assess biological variation? Evidence from renal transplant recipients. Clin Chim Acta 2000; 301: 79–85
  19. Browning MCK, Bennet WM, Kirkcaldy AJ, Jung RT. Intraindividual variation of thyroxin, triiodothyronine and thyrotropin in treated hypothyroid patients: implications for monitoring replacement therapy. Clin Chem 1988; 34: 696–9
  20. Bruins S, Fokkema MR, Ro¨mer JWP, et al. High intraindividuial variation of brain natriuretic peptide (BNP) and amino-terminal proBNP in patients with stable chronic heart failure. Clin Chem 2004; 50: 2052–8
  21. Escriche C, Molina R, Filella X, Ballesta AM. In: Molina R, Ballesta AM (eds). Biology and clinical usefulness of tumor markers. The biological variability of tumor markers in the monitorization of patients with breast and colon cancer with no evidence of the disease. Vol I. Barcelona 1999
  22. Fraser CG, Hearne CR. Components of variance of some plasma constituents in patients with myocardial infarction. Ann Clin Biochem 1982; 19: 431–4
  23. Fraser CG, Williams P. Short-term biological variation of plasma analytes in renal disease. Clin Chem 1983; 29: 508–10
  24. Gion M, Cappelli G, Mione R, et al. Variability of tumor markers in the follow-up of patients radically resected for breast cancer. Tumor Biol 1993; 14: 325–33
  25. Gion M, Cappelli G, Mione R, et al. Evaluation of critical differences of CEA and CA 15.3 levels in serial samples from patients operated for breast cancer. Int J Biol Markers 1994; 9: 135–9
  26. Herna´ndez C, Francisco G, Chaco´n P, Mesa J, Simo´ R. Biological variation of Lipoprotein(a) in a diabetic population. Analysis of the causes and clinical implications. Clin Chem Lab Med 2003; 41: 1075–80
  27. Ho¨ lzel WGE. Intra-individual variation of some analytes in serum of patients with insulin-dependent Diabetes Mellitus. Clin Chem 1987; 33: 57–61
  28. Ho¨ lzel WGE. Intra-individual variation of some analytes in serum of patients with chronic renal failure. Clin Chem 1987; 33: 670–3
  29. Ho¨ lzel WGE. Intra-individual variation of analytes in serum from patients with chronic liver diseases. Clin Chem 1987; 33: 1133–6
  30. Ho¨ lzel WGE. Influence of hypertension and antihypertensive drugs on the biological intra-individual variation of electrolytes and lipids in serum. Clin Chem 1988; 34: 1485–8
  31. Ho¨ lzel WG, Deschner W. Intra-individual variation of serum thyroxin and triiodothyronine in pregnancy. Clin Chem 1988; 34: 2063–5
  32. Ho¨ lzel WG, Beer R, Deschner W, Griesmacher A, Muller MM. Individual reference ranges of CA 15-3, MCA and CEA in recurrence of breast cancer. Scand J Clin Lab Invest Suppl 1995; 221: 93–101
  33. Howey JE, Browning MC, Fraser CG. Selecting the optimum specimen for assessing slight albuminuria, and a strategy for clinical investigation: novel uses of data on biological variation. Clin Chem 1987; 33: 2034–8
  34. Jorde R, Sundsfjordt J. Intra-individual variability and longitudinal changes in glycUmic control in patients with Type 1 diabetes mellitus. Diabetic Med 2000; 17: 451–6
  35. Mora Brugue´s J. Variabilitat intraindividual dels marcadors tumorals. Doctoral Thesis. Barcelona: Universitat de Barcelona, 1993
  36. Kafonek SD, Derby CA, Bachorik PS. Biological variability of lipoproteins and apolipoproteins in patients referred to a lipid clinic. Clin Chem 1992; 38: 864–72
  37. Muusze RG. Intra-individual-variability and retest-reliability of lipoproteins in serum of coronary artery disease patients. Ann Clin Biochem 1987; 24(Suppl. 2): 136
  38. Panteghini M, Pagani F, Bonora R. Pre-analytical and biological variability of prostatic acid phosphatase and prostate-specific antigen in serum from patients with prostatic pathology. Eur J Clin Chem Biochem 1992; 30: 135–9
  39. Pascual T, Gonza´lez-Revalderi´a J, De Paula M, Miravalles E. Biological variability of urinary constituents in patients with Type IDiabetes Mellitus. Quim Clin 1998; 17: 368–71
  40. Sambasivan AS, Lepage N, Filler G. Cystatin C intrapatient variability in children with chronic kidney disease is less than in serum creatinine. Clin Chem 2005; 51: 2215–6
  41. Schectman G, Patsches M, Sasse EA. Variability in cholesterol measurements: comparison of calculated and direct LDL cholesterol determinations. Clin Chem 1996; 42: 732–7
  42. Trape´ J, Aliart M, Brunet M, Dern E, Abadal E, Queralto´ JM. Reference change value for HbA1c in patients with Type 2 Diabetes Mellitus. Clin Chem Lab Med 2000; 38: 1283–7
  43. Trape´ J, Lo´pez L, Pe´rez de Olaguer J, Buxo´ J. Application of reference change value for Cyfra 21-1, CEA and CA 125 in the follow-up of patients with NSCLC treated with chemotherapy. Clin Chem Lab Med 2003; 41(Special Supplement): S 521
  44. Van der Merwe D, Ubbink JB, Delport R, Becker P, Dhatt GS, Hayward Vermaak WJ. Biological variation in sweat sodium chloride conductivity. Ann Clin Biochem 2002; 39: 39–43
  45. Vasikaran SD, McCloskey EV, Kahn S, Kanis JA. Intra-individual variation in fasting urinary calcium- and hydroxyproline-creatinine ratios measured in metabolic bone clinic patients as both outpatients and inpatients. Ann Clin Biochem 1994; 31: 272–6 Ann

Let us know what you're interested in!

Please use this form to request more information about.

Westgard Products and Services.

Invalid Input
Invalid Input
Invalid Input
Invalid Input