Table 1.

Design components needed for a late recurrence trial.

Design Component	Description	Examples, Challenges
Method to identify patients at risk	Molecular Tumor Assay	eg. Gene-expression assays (see Table 2 ), other tumor genomic characteristics
	Minimal Residual Disease Assay	eg. Tumor informed (“bespoke”) or agnostic ctDNA assays; circulating tumor cells. Sensitivity of various approaches are incompletely characterized. Relationship between assay positivity and standard radiographic imaging is unknown.
Intervention	Pharmaceutical or other intervention demonstrated to reduce both the MRD biomarker and recurrence	eg. endocrine, targeted or immunotherapy. Tolerability or toxicity may be limiting for many potential interventions
Endpoints	Clinical endpoint upon which to base success of the intervention	eg. metastasis-free survival. Most relevant to the goal of the trial but not accepted FDA endpoint for drug registration. Long follow-up may be required.
Patient Reported Outcomes (PRO)	Instruments that assess impact of identifying MRD on quality of life	eg. Global QOL, CTCAE-PRO.