Recent advances in clinical trial design considerations in Thera"nostics".

Theranostics in drug development is an evolving framework, known as combining 'thera' (a therapeutic drug) with 'nostics' (a diagnostic imaging drug) and with the latter being mostly used to select patient for evaluation of safety and efficacy of an investigational therapeutics. However, when a diagnostic imaging drug is still investigational, patient selection performance of a nostics imaging has not been demonstrated. Clinical trials conducted to assess the effect of an investigational therapeutics in a theranostics setting may focus only on the therapeutics development and not necessarily require definitive truth standard or reference standard to also assess patient selection performance of an investigational diagnostic imaging drug. We propose an In-Parallel with Leveraging development pathway in view of current practice of theranostics for a nostics imaging development. We rationalize minimum statistical metrics necessary for patient selection to allow for rigors of a nostics or diagnostics imaging drug development. We highlight tangible benefits with newer design considerations. We articulate potential indications of a nostics development including prognostic, predictive and treatment response monitoring in addition to patient selection. We further articulate potential additional clinical utilities of risk stratification and clinical management. To take full advantage and the likely payoff in the benefit of leveraging, a group sequential design or an adaptive design for the therapeutic trial is highly encouraged. Published by Elsevier Inc.