Downloaded from jco. ascopubs. org on February 19, 2013. For personal use only. No other uses without permission. Copyright© 2010 American Society of Clinical Oncology. All rights reserved. launchatrial, 3 theredundantandineffectivepracticeofreviewbylocal institutional review boards of isolated adverse events, 4 and multiple andoftenduplicativereviewsbyagenciessuchastheNCI, theUSFood and Drug Administration, sponsors, and local and central institutional review boards. 5 An area of somewhat lesser focus has been on the increasing burdens involved in the conduct of clinical trials. The high cost of clinical trials, driven by their complexity, is a major impediment to their conduct. Simplifying the conduct of trials is the most effective way to control these costs. For many years some authors, primarily from Great Britain, have advocated for the concept of large, simple trials. 6 In such trials, a large number of patients are enrolled, with a limited collection of data (such as just unexpected serious adverse events [AEs] and all cause mortality), little or no local site monitoring, and broad eligibility criteria. The theory of such trials is that the large number of patients will overwhelm the variability induced by the so-called loose design. Indeed, some oncology trials have used this approach, 7 primarily when comparing widely used, accepted therapies in common cancers. Such trials are also appropriate for comparative effectiveness research. 8 In oncology drug development, it has become increasingly important to identify prognostic and predictive biomarkers, including genetic signatures, which can identify subsets of patients suitable for treatment. This requires tissue acquisition and processing that increases—not decreases—the complexity of trials. For this reason alone, large simple trials in the sense defined above have not been, and seem unlikely in the future, to be widely accepted as an approach to oncology drug development in the United States. However, it is important to distinguish between necessary complexity, including the scientific necessity for biologic sampling, from unnecessary complexity, including excessive AE reporting, on-site monitoring, and eligibility criteria, which characterize much of current oncology clinical trials practice today. It is becoming increasingly important to identify and eliminate unnecessary complexity wherever it exists. We feel that it is critical that clinical trialists pursue research in clinical trials methodology, defined as research into how to conduct clinical trials more quickly and efficiently.

Data from existing clinical trials provide a fertile ground for generating evidence regarding the benefits and drawbacks of current and proposed standards for the conduct of clinical trials. The report of Kaiser et al9 in this issue ofJournal of Clinical Oncologyprovides a good example of how this approach can be effective. Kaiser et al tackle the specific issue of the collection of AE data in clinical trials. This is an important topic, as previous studies have documented that the collection and reporting of AE data is one of the most burdensome aspects of workload for clinical research associates on phase III clinical trials. 10 In a retrospective analysis of 24 NCI-supported cooperative group clinical trials, Mahoney et al11 demonstrated that only 3% of adverse events were NCI Common Toxicity Criteria grade 3 or higher; thus the vast majority of reporting for AEs is for events that are unlikely to significantly impact clinical practice. Through a well-designed, prospectively specified analysis, Kaiser et al document that a substantial reduction in workload would be possible through the collection of detailed AE data on only a subset of patients enrolled onto a …