6052 Background: Regulations require IND application review by the FDA prior to initiation of the clinical study. Deficiencies identified in the study protocol require communication between the FDA reviewers and the Sponsor for resolution. If the deficiencies are not adequately resolved, clinical hold and subsequent delay in the start of the clinical study results. To identify and analyze the commonly encountered IND application deficiencies, data from recent reviews were collected. Methods: Eight clinical reviewers analyzed the deficiencies that had been identified in 268 IND applications reviewed in the DDOP FDA from January 2003 to June 2005. All of the study protocol deficiencies leading to a clinical hold, or requiring resolution prior to study initiation were categorized as deficiencies pertaining to: patient eligibility; starting drug dose; study conduct (toxicity management, dose adjustment, stopping criteria); statistical or endpoints; non-clinical; and other issues. Results: 268 IND applications reviewed over a 30-month period by eight medical officers were analyzed. One hundred and twelve (42%) of the applications had no deficiencies; however, 156 (58%) had one (31%) or multiple (69%) deficiencies. Deficiencies pertained to study conduct/scheme (65%), dose (48%), patient eligibility (46%), others (31%), statistics or endpoints (15%), and non-clinical (4%) issues. In 141 (90%) of the deficient applications the deficiencies were adequately addressed by FDA reviewer-Sponsor communication and the trials could start as scheduled. Fifteen (10%) deficient trials were placed on clinical hold. Fourteen (93%) of these trials had multiple deficiencies that pertained to patient eligibility in 12 (80%), starting drug dose in 12 (80%), study conduct in 11 (73%), other in 7 (47%), and non-clinical and statistical issues in 2 (13%) each. Conclusions: Deficiencies were identified in 58% of the reviewed IND applications: 90% of these were resolved by FDA-Sponsor communication. Only 10% of deficient studies were placed on clinical hold; all except one had multiple deficiencies. The most common deficiencies leading to clinical hold pertained to eligibility of study population and proposed starting drug dose. No significant financial relationships to disclose.
Pharmacological and clinical study results of trastuzumab deruxtecan (T-DXd, ENHERTU®)
