Challenges of phase III trial design for novel treatments in diseases with no standard treatment: the AZA-001 myelodysplasia study model

Leuk Res. 2014 Feb;38(2):258-62. doi: 10.1016/j.leukres.2013.10.014. Epub 2013 Oct 27.


For cancers lacking standard treatments, comparing new agents with existing treatments is problematic. Here we discuss the study design from the AZA-001 trial, which compared azacitidine with 3 frequently used conventional care regimens (CCR) for higher-risk myelodysplastic syndromes. Before randomization, physicians preselected the most appropriate of 3 CCR for each patient, after thorough examination. Patients were then randomized to azacitidine or CCR. Patients randomized to CCR received their preselected treatment, thus including patients otherwise excluded as poor candidates for a single comparator. This design may serve as a template in other cancers lacking standard therapy.

Keywords: Azacitidine; CCR; Heterogenous; Novel treatment; Standard; Study design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / therapeutic use*
  • Azacitidine / therapeutic use*
  • Clinical Trials, Phase III as Topic / methods*
  • Clinical Trials, Phase III as Topic / standards
  • Drugs, Investigational / therapeutic use*
  • Humans
  • Multicenter Studies as Topic / methods
  • Myelodysplastic Syndromes / drug therapy*
  • Patient Selection
  • Randomized Controlled Trials as Topic / methods
  • Randomized Controlled Trials as Topic / standards
  • Research Design
  • Standard of Care


  • Antimetabolites, Antineoplastic
  • Drugs, Investigational
  • Azacitidine