Systems of protocol review, quality assurance, and data audit.

The US National Cancer Institute (NCI) is the world's largest sponsor of clinical trials in cancer treatment and biology, and it is responsible for the reliability of data generated by means of its funding. The cooperative groups supported by the NCI consist of main academic institutions and smaller affiliates of these institutions. The size of these groups, their geographical dispersion, and the number of studies accruing patients at any one time make it a challenge to ensure that all requirements of institutional oversight, patient consent, protocol compliance, and data submission and quality are met. Each cooperative group has established various procedures for quality assurance. These include data coordinators at the data management center of the group, study chairs, and statisticians. In addition, each group has a committee of physician-investigators and clinical research associates who make periodic site visits to all member institutions to audit the on-site medical records of a sample of patients entered at that institution. The study records are compared with the medical records for all aspects of protocol management and data generation. In addition, adherence to requirements for consent-form signing and oversight by an institutional review board is assessed. Deviations from the study requirements are evaluated as being minor or major. A written report of the audit result is provided to both the NCI and the relevant administrative components of the cooperative group. The audit process has uncovered rare instances of scientific improprieties in these NCI-funded clinical trials, but more importantly it has educated investigators and support staff to improve adherence to research and data-collection requirements, which has resulted in greater reliability of study results.