MASTERMIND: Bringing Microbial Diagnostics to the Clinic

Abstract

New diagnostics are urgently needed to address emerging antimicrobial resistance. The Antibacterial Resistance Leadership Group proposes a strategy called MASTERMIND (Master Protocol for Evaluating Multiple Infection Diagnostics) for advancement of infectious diseases diagnostics. The goal of this strategy is to generate the data necessary to support US Food and Drug Administration clearance of new diagnostic tests by promoting research that might not have otherwise been feasible with conventional trial designs. MASTERMIND uses a single subject's sample(s) to evaluate multiple diagnostic tests at the same time, providing efficiencies of specimen collection and characterization. MASTERMIND also offers central trial organization, standardization of methods and definitions, and common comparators.

Keywords: communicable diseases; molecular diagnostic techniques; reference standards..

Figure 1.

Conventional vs MASTERMIND diagnostic study. When multiple similar diagnostics are being evaluated independently, the necessary resources (subjects, costs, effort) are multiplied. In a MASTERMIND design, many of these resources are shared, while maintaining independence of study outcomes.

Figure 2.

Opportunities for a MASTERMIND design pertaining to bloodstream infections. There are 3 active areas of development: direct-from-blood pathogen detection, rapid pathogen identification from positive blood culture bottles, and rapid antibacterial susceptibility testing. A MASTERMIND study could evaluate diagnostics at any step in the culture processing pathway.

Figure 3.

MASTERMIND design for one diagnostic focus area. In this conceptualized scheme, a single patient would support the evaluation of multiple tests that focus on the same diagnostic task. In this scenario, each test can be compared to a composite comparator comprised of the routine clinical test and the other investigational platforms.

Figure 4.

MASTERMIND design for multiple diagnostic focus areas. In this conceptualized scheme, a single patient’s sample would support the evaluation of multiple tests that focus on different diagnostic tasks. Only 1 investigational platform is depicted for each step, although >1 could be evaluated, provided additional platforms are available and sample is not limiting. When there is only 1 test in each domain, the standard clinical assay could serve as the comparator assay.