NOTE TO REPORTERS AND EDITORS ORI Reports Fabricated and/or Falsified Data for Three Patients on NCI-Sponsored Studies

The Federal Government's Office of Research Integrity (ORI) has reported findings of scientific misconduct on the part of a data manager who worked at hospitals conducting breast cancer treatment studies sponsored by the National Cancer Institute (NCI). ORI's findings appeared in the Federal Register on Feb. 4.

ORI found that the data manager fabricated and/or falsified data for three individual patients, one in each of three different clinical trials. "Each of these trials had a large number of patients and was conducted at many institutions," said Richard Ungerleider, M.D., chief of NCI's Clinical Investigations Branch. "The fabricated data, involving as it did just one patient on each trial, will not affect these trials' results."

The three studies were large, multicenter, randomized, controlled trials of chemotherapy treatments for breast cancer conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP), one of NCI's Clinical Trials Cooperative Groups.

The trials were:

NSABP B-09, adjuvant chemotherapy with and without tamoxifen (Nolvadex). This trial included 2,697 patients at 83 institutions; patients were accrued between 1977 and 1981.

NSABP B-12, adjuvant chemotherapy with and without doxorubicin (Adriamycin). This trial included 1,106 patients at 98 institutions; patients were accrued between 1981 and 1984.

NSABP B-22, adjuvant chemotherapy with high-dose, standard-dose, or intensified-dose cyclophosphamide. This trial included 2,305 patients at 198 institutions. Patients were accrued between 1989 and 1991.

The scientific misconduct in all three cases related to telephone contacts with patients. The data manager maintained contact with some of the patients who had participated in these trials at two Chicago-area hospitals. His contacts were made as part of the follow-up phase of the studies. ORI found that, for three patients, the data manager falsified and/or fabricated telephone contacts and information, including the patients' survival status.

NCI and the cooperative groups it sponsors to conduct clinical trials have a number of safeguards against scientific misconduct, including on-site auditing and quality-control systems. However, in a system that involves thousands of patients and investigators at hundreds of institutions, improprieties may sometimes occur, said NCI Director Richard Klausner, M.D. "We have a system in place to monitor these trials to assure the quality of the data that is collected, and if we find a problem, we have existing mechanisms to address it," he said.

Norman Wolmark, M.D., chairman of the NSABP, said that he hopes this finding does not erroneously cause women treated for breast cancer to question its effectiveness. "The NSABP has state-of-the-art procedures in place to monitor the women and men who participate in its clinical trials," he said. "The public should remain confident that these procedures work to protect them."

The problems with the data were discovered in 1996 by NSABP, which had added a retrospective component to its routine quality assurance program that audits information coming out of its studies. The new component used computer software to check various data points. Unexplainable discrepancies were reported by NSABP to NCI, which in turn notified ORI.

ORI requested formal investigations at the institutions in which the data manager had worked: Rush-Presbyterian-St. Luke's Medical Center, Chicago, and MacNeal Cancer Center, then affiliated with Northwestern University, Chicago. Based on the evidence and findings by Rush-Presbyterian and Northwestern, ORI found that the data manager had intentionally falsified and/or fabricated data for these three patients. As a result of these findings, ORI has instituted administrative actions which limit the data manager's participation in research funded by the U.S. Public Health Service.

The news section of NCI's clinical trials Web site (http://cancertrials.nci.nih.gov) contains this "Note to Reporters and Editors" with a link to the Federal Register notice. The online statement also contains a link to monitoring guidelines for NCI-sponsored clinical trials (Guidelines for Monitoring of Clinical Trials for Cooperative Groups and CCOP Research Bases) from NCI's Clinical Trials Monitoring Branch.