Development Framework of Desirability of Outcome Ranking Endpoints for Use in Clinical Trials of Invasive Fungal Diseases.

BACKGROUND

Current Mycosis Study Group Education and Research Consortium (MSGERC) and European Confederation of Medical Mycology (ECMM) response criteria for clinical trials often fail to comprehensively assess outcomes of the total patient experience, prompting the need for innovative methodologies.

METHODS

Utilizing a modified Delphi process, members of MSGERC and ECMM were sent a series of surveys utilizing an online platform. Except for the first survey, participants' responses remained anonymous to the steering committee. The first survey was elaborated based on expert opinion, with each subsequent round building upon the responses from previous rounds. Agreement was predefined by consensus of the steering committee as majority support, set at >70% agreement, for each survey component.

RESULTS

For invasive candidiasis, a composite of treatment failure and infectious complications were included to elaborate a DOOR scale, with endpoints measured at 2 weeks after initiation of therapy. For invasive aspergillosis, a composite of treatment failure, presence of disease-attributable complications, and treatment-related adverse events were included to elaborate a DOOR scale, with endpoints measured at 6 weeks after initiation of therapy. For cryptococcosis, a composite of treatment failure and adverse events were included to elaborate a DOOR scale, with endpoints measured at 4 weeks after initiation of therapy. For mucormycosis, treatment failure and adverse events were included to elaborate a DOOR scale, with endpoints measured at 6 and 12 weeks after initiation of therapy.

CONCLUSIONS

Consensus endpoints were developed for invasive candidiasis, invasive aspergillosis, cryptococcosis, and mucormycosis for use in clinical trials.