Progress in therapeutics and prevention occurs because experimental testing has been feasible due to willingness of humans to enroll in clinical trials, including randomized controlled trials (RCTs). Many advances in oncology have been made through the unprecedented efforts to conduct RCTs by Co-operative groups (COGs), established in 1955 by the NCI (National Cancer Institute). However, if patients are going to accept enrollment into experimental clinical trials, thereby contributing to future advances in the war against cancer, they (and the public) should believe that the RCT system is fair and intact. In particular, the public should be confident that the estimated effects of healthcare interventions in RCTs are reliable, correct, and trustworthy. The first step toward building the public confidence in clinical research is to assure that trials' methodologic quality (defined as the extent to which all aspects of a study's design and conduct protect against systematic bias and random error) is not compromised. Poorly conducted and reported research seriously compromises the integrity of the research process, especially if biased results receive false credibility. The focus of this application is to perform in-depth critical appraisal of the quality of RCTs conducted by the NCI COGs, which, surprisingly, has never been done. The main importance of the quality assessment is that correct interpretation of data related to health outcomes and the effects of a given health care intervention can be masked by the methodological quality. In other words, depending on the assessment of quality of research we may conclude that an effective intervention is ineffective or that a harmful intervention is beneficial. The short-term goal of this proposal is to assess the research integrity of the COG RCTs by evaluating their quality. The long-term goal is to ensure reliable, high-quality research. Assessing the quality of COG research will help correct any identified deficiencies and in turn help preserve and protect the research integrity of the system of COG clinical trials in which the public has invested so much. It is also hoped that public confidence in COG research may further increase, which in turn will enable development of more rapid advances in the war against cancer.