Representativeness, Generalizability, and Diffusion of Cancer Clinical Trial Treatments

Abstract

The path from initial development of an anti-cancer agent to diffusion of a new cancer therapy into the cancer treatment community relies, crucially, on clinical trials. In this dissertation, we investigated the representativeness, generalizability, and diffusion of cancer clinical trial treatments. Representativeness was examined using a national, online survey sample of 5,499 patients enrolled from 2007-2011. Income independently predicted clinical trial participation (p=.01) and cost concerns were much more evident among lower income patients (p<.001). We concluded that a better understanding of why income is a barrier may help identify ways to make clinical trials better available to all patients, and would increase the generalizability of clinical trial results across all income levels. To examine generalizability, we compared 5,190 trial patients from 21 SWOG studies from 1987-2007 to 69,187 corresponding non-trial controls selected from the Surveillance, Epidemiology, and End Results (SEER) program. The impact of trial participation on overall survival endured for only one year, and was therefore more likely to influence overall survival in poor prognosis studies (9/10) rather than good prognosis (0/11) studies (p<.0001). We concluded that the long term generalizability of standard arm outcomes improves confidence that trial treatment effects will translate to the real world setting, especially for good prognosis diseases. To examine diffusion, we analyzed docetaxel diffusion in metastatic prostate cancer patients diagnosed from 1995-2007 using the SEER-Medicare database. 6561 metastatic prostate cancer patients were identified; 1350 subsequently received chemotherapy (i.e. hormonal therapy failures). Diffusion was slower for socioeconomically disadvantaged patients. Eighty percent of docetaxel diffusion occurred prior to the release of phase III results showing superiority of docetaxel over standard-of-care in hormone-refractory prostate cancer. We concluded that efforts to increase the rate of diffusion of treatments among disadvantaged populations could lead to cancer population survival gains; also, diffusion prior to definitive phase III evidence suggests the widespread prevalence of off-label chemotherapy use. These results contribute to our understanding of the role of clinical trial results in the development of new treatments, and may help improve the speed and efficiency with which new cancer treatments are translated into clinical practice.