Phase 0 approaches, including microdosing, are early-stage clinical trials that test very low, subtherapeutic doses of new drugs in humans to gather safety and pharmacological data before larger studies. Traditionally used to assess pharmacokinetics, these methods now also help understand a drug's mechanism of action and pharmacodynamics. Phase 0 trials can improve the selection of drug candidates for further development, making the process safer, cheaper, quicker, and more informed. While challenges like extrapolating results to therapeutic doses and managing development timelines remain, the authors suggest that phase 0 approaches should be considered for most drug development scenarios.
Microdosing—administering a minute, subpharmacologic dose—can now be used with ultrasensitive analytical methods to characterize the pharmacokinetics (PK) of compounds in humans early in drug development. This approach may help select drug candidates before investigational new drug (IND) applications, but its usefulness depends on how well microdose PK predicts PK at therapeutic doses. A critical assessment of published clinical data examines this predictive value. The review considers microdosing alone and combined with other innovative methods, both before and during clinical development, as a way to improve the efficiency and informativeness of drug development.