Evidence in oncology - The Janeway Lecture 2000

PURPOSE The purpose of this address is to evaluate the types of evidence that have fashioned clinical decision making in oncology over the past century and to determine the appropriate weighting of evidence at the start of a new cent ury in the shaping of patient care, clinical research, and health policy. METHODS Three separate analytic approaches were used: (1) a review of publications that altered medical practice, (2) a consideration of the misperception tha t little progress has been made by looking at the relationship between 5-ye ar survival rates and national mortality rates, (3) an evaluation of the qu ality of data from clinical trials. RESULTS Published reports suggest that res ipsa loquitur was the dominant mindset o f researchers in the first half century and continuing into the second half century. However, recognition of the scarcity of dramatic improvements in outcome and the possibility of incremental improvements led to the mounting of prospective randomized comparative trials that could identify such incr emental improvements. Findings from these trials have profoundly altered pa tient care in the past quarter century. Data suggest that there is a sequen ce of events-increased survival rates in patients at research institutions followed by significant increases in survival rates nationally-followed by a reduction in annual mortality rates that do reflect improvements in treat ment. Phase III comparative clinical trials yield the highest quality data in onc ology. Meta-analysis of such data may be useful, but the most compelling da ta that alter medical practice come either from comparative clinical trials showing such significant differences in results as to necessitate their ea rly termination on ethical grounds or from replicated phase III trials. DISCUSSION The nature of evidence influencing clinical practice and research has chang ed greatly in the past century. Although res ipsa loquitur still pervades t he thinking of some oncologists, recognition of the incremental nature of p rogress is now the more dominant force in contemporary oncologic research. In addition, as molecular targets become the focus of therapeutic efforts, it will be especially important to proceed as quickly as possible to phase III comparative trials rather than to phase II studies.