The responsibility for monitoring the trials rests with the sponsor. NCI-Sponsored Trials Included Some Use of Tranquilizing Agents

Published reports of the three trials did not disclose the extent of tranquilizer use among study patients. Table 1 shows the number of patients receiving hydrazine sulfate and various antiemetic medications. Retrospective Analyses Found No Evidence of Adverse Effects From the Use of Allegedly Incompatible Drugs

Analyses of data from NCI-sponsored clinical trials found no evidence of adverse effects on survival associated with hydrazine sulfate and the use of tranquilizing agents as antiemetics and barbiturates. Before completion of NCI’s sponsored clinical trials, FDA approved more than 70 applications permitting the compassionate use of hydrazine sulfate. In its approvals, FDA staff requested that physicians caution their patients to avoid tranquilizers, barbiturates, and alcohol while taking hydrazine sulfate. NCI Did Not Ensure Collection of Data on the Use of Alleged Incompatible Agents

NCI contributed to the subsequent controversy surrounding these trials by not requiring better data collection and analysis of this issue. Although NCI officials were aware of the concerns surrounding the use of allegedly incompatible agents with hydrazine sulfate, they did not believe it was necessary to maintain research records during its trial regarding concurrent medications and possible alcohol use. CALGB’s Published Trial Results Did Not Accurately Describe Tranquilizer Use

A paper presenting the final results of the CALGB clinical trial did not clearly describe the use of tranquilizing agents by study patients. We believe the investigator erred in not reporting the widespread use of benzodiazepine tranquilizing agents. Although CALGB informed NCI that the use of concurrent medications would be captured on the patient research forms in accordance with the research plan, CALGB investigators did not uniformly record this information on the forms as originally intended. NCI criticized this lapse and ensured that a letter from the CALGB investigator was published that provided more complete and accurate information.
Why GAO Did This Study

Pursuant to a congressional request, GAO provided information on the National Cancer Institute (NCI)-sponsored clinical trials of the anticancer drug hydrazine sulfate, focusing on: (1) NCI protocol design and data management procedures; (2) how NCI and the trials' investigators dealt with the drug's potential incompatibility with certain agents; (3) the extent to which patients received these incompatible agents; and (4) how the investigators reported the issue.

What GAO Found

GAO found that: (1) the three large NCI-sponsored clinical trials showed that the drug did not prolong cancer patients' survival; (2) controversy surrounding the trials focused on trial participants' use of tranquilizers, barbiturates, and alcohol, which were allegedly incompatible with the drug; (3) clinical trial records showed that participants used tranquilizers under varying circumstances, particularly for relief from vomiting; (4) the investigators believed that it was unethical to withhold antiemetic medications from patients undergoing chemotherapy; (5) subsequent analyses of patients' use of concurrent medications did not invalidate NCI conclusions that the drug was ineffective; (6) the Food and Drug Administration (FDA) may have contributed to the confusion surrounding the trials due to its more conservative position on how the drug should be administered to some patients; (7) although FDA approved more than 70 applications permitting the use of hydrazine sulfate, it cautioned physicians about their patients' use of tranquilizing agents while on the drug; (8) there were lapses in recordkeeping and reporting because NCI did not require complete and accurate research records on the patients' use of tranquilizing agents during the trials; and (9) NCI-sponsored investigators only recently analyzed this issue, since published results did not accurately describe the widespread use of tranquilizers during the trials.