title: The changing face of phase 1 cancer clinical trials: new challenges in study requirements.
abstract: Phase 1 studies in cancer have changed in recent years. Now, with the advent of new, less toxic, targeted agents, more patients may be candidates for new drug studies earlier in the course of their disease. It is to the advantage of the members of the oncology community to know more regarding the details and requirements for participation in early-phase clinical trials so they can advocate for their patients and help them decide when such trials may be an appropriate choice. To examine the work intensity of early phase cancer clinical trials, the authors of this report compared the study requirements of phase 1 and 2 protocols. Five parameters were studied as a surrogate of study complexity-the number of physical examinations, vital sign determinations, electrocardiograms (ECGs), nonpharmacokinetic laboratory tests, and pharmacokinetic (PK) sampling-in the first 4 weeks of protocol in 90 studies (49 phase 1 studies and 41 phase 2 studies). From July 2004 through March 2007, there were 49 phase 1 trials in the phase 1 Program, 9 phase 2 studies that were conducted by physicians appointed in that program, and 32 phase 2 trials with accessible data in the Department of Thoracic/Head & Neck Medical Oncology. In the phase 1 trials versus the phase 2 trials, there were significantly more (P < .05) physical examinations (mean +/- standard error, 3.16 +/- 0.24 vs 2.22 +/- 0.13), vital sign determinations (5.63 +/- 0.61 vs 2.80 +/- 0.26), ECGs (4.36 +/- 1.16 vs 0.80 +/- 0.17), nonpharmacokinetic laboratory tests (18.08 +/- 1.31 vs 10.12 +/- 0.65), and PK sampling (15.14 +/- 1.79 vs 1.02 +/- 0.53). These values also differed significantly (P < .005 for each) when the median values were compared in nonparametric tests. Although both phase 1 and phase 2 trials had substantial study requirements, those for the phase 1 studies were significantly higher. The successful conduct of early-phase clinical trials requires significant research infrastructure.
authors.affiliation: Division of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Craft
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.forename: Xiudong
authors.initials: X
authors.lastname: Lei
authors.forename: Roy
authors.initials: R
authors.lastname: Herbst
authors.forename: Scott
authors.initials: S
authors.lastname: Lippman
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Karp
mesh_terms: D035843:Biomedical Research; D002985:Clinical Protocols / Q000592:standards; D017321:Clinical Trials, Phase I as Topic / Q000639:trends*; D017322:Clinical Trials, Phase II as Topic; D009369:Neoplasms; D018579:Patient Selection; D010808:Physical Examination; D012107:Research Design / Q000639:trends; D014481:United States