Table 2.
Determination of grade 1 threshold based on ‘Combined method’ use and application to NEJM normal range
| Usable healthy young male data [11] | ‘Combined method’ derived threshold Grade 1 limit: data expressed as relative to upper or lower | Usable general application | |||||
|---|---|---|---|---|---|---|---|
| Laboratory parameter | Units | Normal range Upper and lower limit of normal range* | Spontaneous Variation Limit to define grade 1 Limit Decrease: – Increase: +† | Limit of NR | NEJM normal range 2004 [12] | Derived threshold value Grade 1 limit | Suggested corrected value adapted to healthy young male |
| ALT | IU l−1 | 10–58 | +10 | 1.2*ULNR | 0–35 | 42 | |
| AST | IU l−1 | 10–43 | +9 | 1.2*ULNR | 0–35 | 42 | |
| Bilirubin‡ | µmol l−1 | 5–27 | +12 | 1.3*ULNR | 5–17 (f) | 22 | 35 |
| Alkaline. phosphatases | IU l−1 | 46–117 | +16 | 1.1*ULNR | 30–120 | 132 | |
| Creatinine | µmol l−1 | 78–113 | +15 | 1.1*ULNR | <133 (f) | 146 | 125 |
| Potassium | mmol l−1 | 3.5–4.9 | −0.2 | (−0.95*LLNR) | 3.5–5 | 3.3 | |
| No data§ | 1.05 ULNR | 5.2 | |||||
| Glucose | mmol l−1 | 3.8–5.9 | −0.4 | (−0.9*LLNR) | 4.2**–6.4 | 3.8 | 3.4 |
| Haemoglobin (male) | g dl−1 | 13.4–17.5 male | −0.8 | (−0.95*LLNR) | 13.5–17.5 male | 12.5 | |
| PMN – white people | 109 l−1 | 1.7–6.5 | −0.5 | (−0.7*LLNR) | 1.8–7.7 | 1.3 | |
| +1.8 | 1.3*ULNR | 10 | |||||
| Eosinophils | 109 l−1 | <or = 0.480 | +0.15 | 1.3*ULNR | No data | 0.6 | |
| Platelets | 109 l−1 | 153–324 | −20 | (−0.85*LLNR) | 150–350 | 130 | |
| CPK (male) | IU l−1 | 53–400 | +72 | 1.2*ULNR | 60–400 | 480 | |
| aPTT | s | 28–43 | +5 | 1.1*ULNR | 22–35 | 38.5 | |
| ECG¶ | |||||||
| PR interval | ms | 120–196 | −21 | (−0.8*LLNR) | No data | No data | 100 ms |
| +23 | 1.1*ULNR | No data | No data | 220 ms | |||
| QTcB interval | ms | 357–425 | +42 | 1.1*ULNR | No data | No data | 460 ms |
| QTcF interval | ms | 261–422 | +42 | 1.1*ULNR | No data | No data | 460 ms |
| Vital signs¶ | |||||||
| Supine heart rate | beats min–1 | 44–82 | −20 | not applicable | No data | NO data | Not applicable |
| +18 | 1.2*ULNR | No data | No data | 100 beats min–1 | |||
| Supine systolic blood pressure | mmHg | 102–146 | −25 | not applicable | No data | No data | Not applicable |
| +18 | 1.1*ULNR | No data | No data | 160 mmHg | |||
| Supine diastolic blood pressure | mmHg | 53–84 | −15 | not applicable | No data | No data | Not applicable |
| +11 | 1.1*ULNR | No data | No data | 90 mmHg | |||
Young male healthy subject data. Normal range values determined by non-parametric procedure (2.5–97.5% of the distribution of data) [11].
Young male healthy subject data. Spontaneous variation limits (changes) determined by the 2.5–97.5% interval of variation in phase I conditions [11].
27 µmol l−1 is also the accepted limit of inclusion [11].
No robust available data due to haemolysis bias on potassium values.
Un-published data from the same healthy male population (same clinical pharmacology unit, see ref. [11].).
NR of general population without relevance to healthy young male subjects. Note:It is recommended that each clinical pharmacology unit defines its own normal ranges and changes based on their own population.