Speed of Adoption of Immune Checkpoint Inhibitors of Programmed Cell Death 1 Protein and Comparison of Patient Ages in Clinical Practice vs Pivotal Clinical Trials

Results from phase 2 and 3 trials in patients with advanced melanoma have shown significant improvements in the proportion of patients achieving an objective response and prolonged progression-free survival with the combination of nivolumab (an anti-PD-1 antibody) plus ipilimumab (an anti-CTLA-4 antibody) compared with ipilimumab alone. We report 2-year overall survival data from a randomised controlled trial assessing this treatment in previously untreated advanced melanoma.

The usual search for explanations and solutions for the research-practice gap tends to analyze ways to communicate evidence-based practice guidelines to practitioners more efficiently and effectively from the end of a scientific pipeline. This examination of the pipeline looks upstream for ways in which the research itself is rendered increasingly irrelevant to the circumstances of practice by the process of vetting the research before it can qualify for inclusion in systematic reviews and the practice guidelines derived from them. It suggests a 'fallacy of the pipeline' implicit in one-way conceptualizations of translation, dissemination and delivery of research to practitioners. Secondly, it identifies a 'fallacy of the empty vessel' implicit in the assumptions underlying common characterizations of the practitioner as a recipient of evidence-based guidelines. Remedies are proposed that put emphasis on participatory approaches and more practice-based production of the research and more attention to external validity in the peer review, funding, publication and systematic reviews of research in producing evidence-based guidelines.

To analyze the age-related enrollment of cancer patients onto registration trials of new drugs or new indications approved by the US Food and Drug Administration from 1995 to 2002. This study involved retrospective analyses of demographic data of cancer patients enrolled onto registration trials. The data on 28,766 cancer patients from 55 registration trials were analyzed according to age distributions of > or = 65, > or = 70, and > or = 75 years. The rates of enrollment in each age group for each cancer were compared with the corresponding rates in the US cancer population. The age distributions of the US cancer population were derived from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute for the period 1995 to 1999 based on the 2000 US Census. The proportions of the overall patient populations aged > or = 65, > or = 70, and > or = 75 years were 36%, 20%, and 9% compared with 60%, 46%, and 31%, respectively, in the US cancer population. Statistically significant under-representation of the elderly (P or = 70 years accounted for most of the under-representation. Elderly were under-represented in the registration trials of new cancer therapies. Various strategies may be needed to evaluate cancer therapies for the elderly in prospective clinical trials and to improve cancer care in the elderly population.