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Review of the Fialuridine (FIAU) Clinical Trials (1995) / Chapter Skim
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FDA-Proposed Changes to the Code of Federal Regulations
Pages 133-142

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From page 133...
... · Control groups should be used in safety studies when underlying disease likely to mimic drug toxicity. · Sponsors required to provide estimates of underlying mortality and morbidity rates for diseased populations.
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From page 134...
... Semiannual Reports · Current annual death and serious adverse experiences report to be supplemented by semiannual reports; semiannual report not to take place of annual report. · Report all deaths, serious adverse experiences, and study discontinuations due to adverse experiences, whether or not unexpected, and whether or not caused by the study drug.
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From page 135...
... · Failure to implement adequate safety monitoring to be grounds for clinical hold or termination of an IND. REVIEW OF ONGOING INVESTIGATIONS · Investigators required to submit safety data to sponsors to allow sponsors to comply with safety reporting requirements, i.e., semiannual reports.
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From page 136...
... A real-time form of monitoring and analysis requires real-time data flow and abandoning the case report form of data collection in favor of a contact or visit-driven form of data collection and flow. This is obviously no panacea, since the FlAU studies reviewed here all had formal or informal realtime monitoring systems as well as the mandated case report forms, but it is a change that would help insure that all investigators are as alert to developing problems as these FTAU investigators were.
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From page 137...
... Follow-up The IOM committee concurs with the view expressed in both the FDA and NIH reports arguing for follow-up beyond the formal close of a trial, especially for trials involving new compounds. It is reasonable to expect sponsors and investigators to maintain some minimal form of contact with patients (e.g., via mail or telephone and for a period of weeks or months)
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From page 138...
... A Statistical Analysis of Mortality in the FIAU/FlAC Trials Both the FDA and NTH reports speak of the desirability of following persons enrolled for a period of 6 months or longer following enrollment. The FDA report speaks, in addition, to the desirability of pretrial estimates of expected mortality in the patient populations from which the subjects are to be drawn, and combining information from related trials in deciding whether or not to continue development of a drug.
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From page 139...
... . Using hypothetical mortality rates ranging from 10 to 20 percent per year for the HIV-infected patients in the R89 trial and from 2 to 4 percent per year in the R91 and PPPC trials, the number of deaths "expected" in each group of patients was calculated and compared to the number of deaths actually observed.
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From page 140...
... . The proposed revised definition for serious adverse drug experience is An adverse drug experience occurring at any dose that is fatal or life-threatening, results in persistent or significant disability/incapacity; requires or prolongs inpatient hospitalization, necessitates medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure, or is a congenital anomaly.
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From page 141...
... That said, however, there is nothing, so far as the committee can ascertain, to stop a sponsor from waiving its right to confidentiality of data sets supplied to FDA or of making them available themselves to interested parties on an as needed basis. Furthermore, there is nothing to stop investigators undertaking trials frown publishing their results and, in the case of multicenter trials, insisting that the combined results be published as a condition for participation.
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From page 142...
... All that is needed is the collective will. Virtually all trials performed at major research institutions, regardless of the funding source, are subject to TRB review before implementation.
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Key Terms

  • fda report
  • safety reports
  • underlying disease
  • pppc trial
  • serious adverse

  • following enrollment
  • ongoing monitoring
  • trial involves
  • adverse experiences
  • nih reports

  • underlying mortality
  • safety reporting
  • semiannual reports
  • events observed
  • stopping rules

  • reports speak
  • safety summary
  • mortality rates
  • educated guesses
  • safety monitoring

  • report form
  • fda task
  • background morbidity
  • safety data
  • data flow

  • drug toxicity
  • force report
  • adverse drug
  • adverse events
  • data center


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