Table 2.
Selected Strategies to Enhance Clinical Trial Efficiency
| Strategy | Definition | Why This Strategy Improves Trial Efficiency | Examples |
|---|---|---|---|
| Prognostic enrichment | Identifying and focusing on high-risk patients | Studying patients with a high event rate increases the statistical power to detect a given level of relative risk reduction. | Norepinephrine dosage in septic shock (57) |
| PaO2/FiO2 ratio in ARDS (8, 58) | |||
| APACHE II score in septic shock (42) | |||
| Predictive enrichment | Identifying and focusing on patients who are more likely to respond to the therapy being studied | Biologic markers related to a therapy’s mechanism of action can be used to identify likely responders. | Response to corticotropin test for corticosteroids in septic shock (59) |
| IL-6 level for monoclonal anti–tumor necrosis factor in sepsis (50) | |||
| PaO2/FiO2 ratio for neuromuscular blockade in ARDS (8) | |||
| Direct lung injury for surfactant in ARDS (60) | |||
| PaO2/FiO2 ratio for prone positioning in ARDS (58) | |||
| Vitamin D level for vitamin D replacement in critically ill patients (61) | |||
| Plasma cell–free hemoglobin for acetaminophen in severe sepsis (62) | |||
| C-reactive protein level for corticosteroids in community-acquired pneumonia (51) | |||
| Adaptive randomization | Adjust trial enrollment on the basis of prespecified decision rules and early results of the trial | Randomization is adapted in order to answer trial question with the fewest people, minimizing the risk of harm and ensuring adequate power. | Anti-PDL1 in septic shock (53) |
| Risk-based subgroup analysis | Determine average treatment effect by quantile of baseline risk | This strategy helps clarify the expected benefit of treatment for patients on the basis of baseline risk, improving the application of clinical trial results to bedside practice. | Activated protein C in severe sepsis (63) |
| Pulmonary artery catheters in critically ill patients (64) | |||
| Route of enteral nutrition in critically ill patients (65) | |||
| Protocol-based early goal-directed therapy in sepsis shock (66) |
Definition of abbreviations: anti-PDL1 = antibody against programmed death-ligand 1; APACHE = Acute Physiology and Chronic Health Evaluation; ARDS = acute respiratory distress syndrome.