Physician Toxicity Attribution In Phase I Trials: Evaluating The Effect Of Dose On The Frequency Of 11,909 Toxicities.

e17674 Background: Accurate classification of toxicity in Phase I trials as related or unrelated to study drug is critical. Attribution in Phase I has not been widely studied and assessing it is complicated by the lack of a gold standard. We examined dose-toxicity relationships as a function of physician-assigned attribution to evaluate for evidence of toxicity misattribution. Methods: Individual patient records from 1,156 patients enrolled to 38 Phase I studies between 2000-2010 were used. Dose was defined as percent of maximum dose administered on each study. Relationships between dose and patient-level toxicity were explored graphically and with logistic regression. All p-values were two-sided. Results: 11,909 unique toxicities were analyzed. A broad range of drug classes were represented. Only 4% and 12% of toxicities were assigned ‘definitely’ or ‘probably’ related, respectively. ‘Possibly’ related accounted for 30% of all toxicities. Using a simplified binomial attribution system, unrelated toxicity...