Early clinical drug development has seen little change in 20 years despite a 40% failure rate due to poor drug metabolism and pharmacokinetics. A new method called microdosing allows investigational drugs to be tested in humans earlier, enabling smarter candidate selection. Microdosing relies on two ultrasensitive techniques: positron emission tomography (PET) for pharmacodynamic information and accelerator mass spectrometry (AMS) for pharmacokinetic information. This approach permits safer human studies and reduces the use of animals in preclinical toxicology.
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.