TABLE 2.
Examples of challenges in generalizing the usefulness of a surrogate marker that is qualified in one context to other contexts1
| Intervention | Intermediate biomarker | Outcome |
| Different interventions, same outcome | ||
| Statins | Reductions LDL cholesterol2 | Lower CHD risk |
| HRTs (estrogen plus progestin and estrogen alone) | Reductions LDL cholesterol3 | No overall effect on CHD risk |
| Different forms of HRT intervention, same outcome, 50- to 59-y-old women | ||
| Estrogen plus progestin | Reductions LDL cholesterol | CHD: 1.34 (0.82, 2.19)4 |
| Estrogen alone | Reductions LDL cholesterol | CHD: 0.60 (0.35, 1.04) |
| Different age groups, same intervention, same outcome (global index) | ||
| Estrogen alone, age, y | ||
| 50–59 | Reductions LDL cholesterol | 0.84 (0.66, 1.07) |
| 60–69 | Reductions LDL cholesterol | 0.99 (0.85, 1.15) |
| 70–70 | Reductions LDL cholesterol | 1.17 (0.99, 1.39) |
| Different outcomes, same intervention | ||
| Estrogen plus progestin | Reductions LDL cholesterol | CHD: 1.18 (0.95, 1.45)Stroke: 1.37 (1.07, 1.76)Pulmonary embolism: 1.98 (1.36, 2.87)Colorectal cancer: 0.62 (0.43, 0.89)Hip fracture: 0.67 (0.47, 0.95)Global index: 1.12 (1.02, 1.24) |
1
From reference 17. CHD, coronary heart disease (defined as nonfatal myocardial infarction or coronary death); HRT, hormone replacement therapy.
2
LDL cholesterol is a qualified surrogate marker for statin interventions and their effects on CHD and cardiovascular disease outcomes.
3
On the basis of evidence in the Women’s Health Initiative, LDL cholesterol does not meet the criteria as a qualified surrogate marker for the outcomes evaluated via HRT interventions.
4
HR; 95% CI in parentheses (all such values).