[Show abstract][Hide abstract] ABSTRACT: In spite of the large number of nutrient-derived agents demonstrating promise as potential chemopreventive agents, most have failed to prove effectiveness in clinical trials. Critical requirements for moving nutrient-derived agents to recommendation for clinical use include adopting a systematic, molecular-mechanism based approach and utilizing the same ethical and rigorous methods such as are used to evaluate other pharmacological agents. Preliminary data on a mechanistic rationale for chemoprevention activity as observed from epidemiological, in vitro and preclinical studies, phase I data of safety in suitable cohorts, duration of intervention based on time to progression of preneoplastic disease to cancer and the use of a valid panel of biomarkers representing the hypothesized carcinogenesis pathway for measuring efficacy must inform the design of phase II clinical trials. The goal of this paper is to provide a model for evaluating a well characterized agent- Polyphenon E- in a phase II clinical trial of prostate cancer chemoprevention.
[Show abstract][Hide abstract] ABSTRACT: The goal of this report is to describe the on going strategies, successes, challenges and solutions for recruitment in this multi-center, phase II chemoprevention trial targeting men at high risk for prostate cancer.
We developed and implemented a multi-center clinical trial in institutions with supportive infrastructure, lead by a recruitment team of experienced and committed physicians and clinical trial staff, implementing multi-media and community outreach strategies to meet recruitment goals. Screening logs were reviewed to identify trends as well as patient, protocol and infrastructure -related barriers impacting accrual and revisions to protocol implemented.
Between January 2008 and February 2011 a total of 3547 individuals were prescreened with 94% (n=3092) determined to be ineligible based on diagnosis of cancer or benign biopsy results. Of these, 216 were considered eligible for further screening with 52% (n=113) declining to participate due to patient related factors and 14% (n=29) eliminated due to protocol-related criteria for exclusion. Ninety-four (94) subjects consented to participate with 34% of these subjects (n=74) meeting all eligibility criteria to be randomized to receive study agent or placebo. Across all sites, 99% of the recruitment of subjects in this clinical trial is via physician recruitment and referral with less than 1% responding to other recruitment strategies.
A contemporary approach to subject recruitment and frequent evaluation is needed to assure responsiveness to emerging challenges to accrual and the evolving scientific literature. A focus on investing on improving systems for physician recruitment may be key to meeting recruitment target in chemoprevention trials.
[Show abstract][Hide abstract] ABSTRACT: Practice variation in transplant physician management of immune suppression (IS) after allogeneic hematopoietic cell transplantation (HCT) is anticipated to have important consequences, but has not been characterized to date. We conducted a national survey of transplant physician members of the American Society for Blood and Marrow Transplantation to discern variation in IS management, characterize the burden of graft-versus-host disease (GVHD) emerging in the setting of IS taper, and describe the proportion of HCT recipients who successfully discontinue IS by 2 and 5 years post-HCT. There was marked heterogeneity in IS discontinuation practice, with variation in initiation of taper, sequence of agents tapered, frequency of changes, and strategy utilized. Twenty-five percent reported no consistent strategy in their usual practice. Confidence in therapeutic decision making was limited. The majority indicated that they could not predict who would develop GVHD on taper of IS, and reported a resultant burden of both acute and chronic GVHD (aGVHD, cGVHD) emerging or recurring in the setting of IS taper. HCT physicians projected rates of IS discontinuation that increased from 2 to 5 years post-HCT, and differed significantly according to donor relation and stem cell source utilized. The marked variation in practice, burden of GVHD emerging in the setting of IS taper, and limited confidence in therapeutic decision making all highlight shortcomings in an essential component of HCT physicians' scope of practice. These data argue for more rigorous study of IS management post-HCT so that evidence-based practice guidelines can be developed.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2011; 17(10):1528-36. DOI:10.1016/j.bbmt.2011.03.006 · 3.40 Impact Factor