How well are Phase 2 cancer trial publications supported by preclinical efficacy evidence?

Major ethics policies require that human studies be preceded by animal experiments. We probed the extent to which trials testing efficacy of cancer drugs cited preclinical efficacy studies testing the same drug and disease indication. Using a sample of Phase 2 trial publications for novel cancer monotherapies approved by Food and Drug Administration 2005-2007, we conducted a systematic analysis of citations to preclinical efficacy evidence within trial publications. Citations were classified based on whether they "matched" the drug and indication of the trial. Our sample included 179 Phase 2 publications published 2004-2016. At least one preclinical study was cited for 113 of 179 publications (63%); 56 (31%) cited matching preclinical studies, and 74 (41%) did not cite either matching preclinical or matching clinical trial evidence. When excluding evidence that would likely not have been available to investigators before trial launch, 45 trials (25%) cited matching preclinical studies; 91 (51%) did not cite any matched preclinical or clinical, preceding evidence. No relationship between citation of matching and preceding preclinical evidence and trial outcomes was observed (28.4% of nonpositive trials vs. 26.9% of positive trials, p ~ 1). This suggests that many Phase 2 trial publications do not cite matching preclinical efficacy studies. Limited citation either suggests its absence or its exclusion from a publication. To ensure trials rest on a sound ethical basis and that publications support valid inference, journal editors and referees might encourage more complete descriptions of preclinical evidence or, where appropriate, active disclosure of its absence.