Table 1.

Challenges and Potential Solutions for MASTERMIND Studies

	Challenges	Potential Solutions
Comparator method considerations	• There may be no available, good-quality comparator method, particularly for novel diagnostics	• Use a composite of tests, while excluding the one being evaluated
	• Tests used for the comparator method may themselves have poor performance characteristics	• Utilize only tests with a high level of preclinical validation or include clinical and laboratory components in the comparator, or apply clinical adjudication, or use an algorithmic approach
Industry commitment	• If a company withdraws, there are deleterious consequences to the remaining components of the protocol	• Ensure high-level commitment from participating companies through early and ongoing engagement
Statistical considerations	• Indeterminate/equivocal results	• Include alternative tests, clinical data, or short-term follow-up data to clarify the diagnosis
	• Variations in specimen quality due to repeated collections	• Randomize order of specimen collection
	• Operational bias	• Blind users of the investigational test to clinical information and comparator test result(s) and vice versa
	• Determination of sample size	• May need to be adjusted during study based on the prevalence of infection

Abbreviation: MASTERMIND, Master Protocol for Evaluating Multiple Infection Diagnostics.