Table 1. Examples of calculating clinical validity and population impact.
Example | Empirical data | Hypothetical data | ||
---|---|---|---|---|
Abacavir |
Simvastatin |
|||
Study | Mallal et al.9 | Mallal et al.9 | SEARCH collaborative group10 | Voora et al.11 |
Variant | HLA-B*5701 | HLA-B*5701 | SLCO1B1 c.521T>C (*5) | SLCO1B1 c.521T>C (*5) |
Risk genotype freq | 6.7% | 6.6% | 25% | 28% |
Adverse event | Clinically diagnosed abacavir hypersensitivity | Immunologically confirmed abacavir hypersensitivity | Severe myopathy | Any side effect |
Adverse event freq | 8.5% | 3.1% | 0.8% | 23% |
ORa | 30 | 1176b | 8.5 | 2.8 |
Sensitivity | 48% | 100% | 73% | 45% |
Specificity | 97% | 96% | 76% | 77% |
PPV | 60% | 47% | 2% | 37% |
NPV | 95% | 100% | 99.7% | 83% |
PAF | 44% | 100% | 64% | 24% |
NNT | 2 | 3 | 49 | 6 |
NNG | 27 | 33 | 195 | 19 |
Abbreviations: NNG, number needed to genotype; NNT, number needed to treat; NPV, negative predictive value; PAF, population attributable fraction; PPV, positive predictive value. Severe myopathy: muscle symptoms and creatine kinase level above 10 × upper limit of normal; any side effect: composite of any side effect, myalgia and/or creatine kinase level above 3 × upper limit of normal.
The odds ratios (OR) compare carriers versus non-carriers of HLA-B*5701 for abacavir and CC/CT versus TT genotype at SLCO1B1 rs4149056 for simvastatin.