Table 2.

Trial Design Strategies for Precision Medicine in Sepsis and Acute Respiratory Distress Syndrome

Approach	Brief Description
Adaptive trial designs	Incorporate prospectively planned modification of one or more aspects of trial design (e.g., sample size, dose, treatments, or study endpoints) based on adaptive analyses
Adaptive enrichment	Modification of eligibility criteria to target participants likely to benefit and/or exclude participants unlikely to benefit
Biomarker-guided adaptive design	Stratification of participants based on biomarker level with planned modifications based on treatment response within groups
Biomarker-threshold adaptive design	Biomarker may predict response to treatment but optimal threshold to guide treatment is not known and is established within the trial
Response adaptive randomization	Prior analyses suggest efficacy within several potential subgroups that are examined within the trial with allocation into subgroups changed on the basis of interim analyses
Platform trial	Multiple interventions are tested within a single trial framework against a single control arm for a single condition. Therapeutic arms are added or dropped from the trial based on interim analyses
Seamless phase 2/3 trials	Rapid transition of a promising phase 2 to a larger phase 3 study facilitating cost-efficient scaling for effective therapies
Perpetual trial	Trial framework is established for a condition and new therapies are continually being added or dropped in perpetuity
Integration with the electronic health record	Trial procedures including screening, randomization, and deployment of interventions are integrated with the electronic health record, improving efficiency and potentially generalizability