Respiratory diagnostics are further complicated by the absence of a perfect gold standard. Culture is difficult or insensitive for some pathogens and unavailable for others (eg, human metapneumovirus, parainfluenzavirus type 4, rhinovirus group C, or Pneumocystis jiroveci). Serologic tests are often not available and usually require paired serum specimens for accurate results. Statistical methods to adjust for such alloyed gold standards, such as discrepant analysis, have been frequently employed, but they can be susceptible to significant bias [50] . Comparative evaluations of respiratory diagnostic assays must also take into account variations in which panel of pathogens is selected, which genetic sequences are targeted, what specimen sources are used [3, 51] , and even what methods are used for nucleic acid extraction [52] . The US Food and Drug Administration has recently published industry guidance that may encourage additional work in this area [53] .