Design issues in a randomized controlled trial of a pre-emptive versus empiric antifungal strategy for invasive aspergillosis in patients with high-risk hematologic malignancies

C. Orla Morrissey, Sharon C A Chen, Tania Christine Sorrell, Kenneth F Bradstock, Jeffrey Szer, Catriona L Halliday, Nicole M. Gilroy, Anthony P Schwarer, Monica A Slavin

Research output: Contribution to journalReview ArticleResearchpeer-review

14 Citations (Scopus)


Invasive aspergillosis (IA) is a major cause of mortality in patients with hematological malignancies, due largely to the inability of traditional culture and biopsy methods to make an early or accurate diagnosis. Diagnostic accuracy studies suggest that Aspergillus galactomannan (GM) enzyme immunoassay (ELISA) and Aspergillus PCR-based methods may overcome these limitations, but their impact on patient outcomes should be evaluated in a diagnostic randomized controlled trial (D-RCT). This article describes the methodology of a D-RCT which compares a new pre-emptive strategy (GM-ELISA- and Aspergillus PCR-driven antifungal therapy) with the standard fever-driven empiric antifungal treatment strategy. Issues including primary end-point and patient selection, duration of screening, choice of tests for the pre-emptive strategy, antifungal prophylaxis and bias control, which were considered in the design of the trial, are discussed. We suggest that the template presented herein is considered by researchers when evaluating the utility of new diagnostic tests ( number, NCT00163722).

Original languageEnglish
Pages (from-to)179-193
Number of pages15
JournalLeukemia and Lymphoma
Issue number2
Publication statusPublished - Feb 2011


  • Aspergillus
  • bias
  • clinical trial
  • Diagnostic tests
  • evaluation

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