This document sets out the methods to enable the earliest assessment of human case(s) of a novel or re-emerging respiratory pathogen with pandemic potential and their close contacts, specifically to guide development and early use of pathogen-specific diagnostic tests for clinical use and public health benefit. This FFX-Dx protocol provides guidance for the End User Validation and early use of the first diagnostic (Dx) test for Pathogen X in a rigorous but focused assessment of the First Few Pathogen X cases and contacts in a given country, as part of the Respiratory Investigations and Studies, Unity Studies initiative.