One of the recommendations of the FDA Task Force is that all patients in Phase I or II trials of any new drugs should be monitored for 6 to 9 months after the cessation of therapy. The NIH subcommittee recommended that this recommendation should apply only when there are scientific reasons for suspecting the possibility of long-term or delayed toxicity.
The differences between the two sets of recommendations reflect a somewhat predictable difference in the relative weighing of risk and benefit by the two groups. A 6- to 9-month detailed follow-up on every patient in a Phase I study of an anti-cancer or anti-HIV drug will substantially increase the time and cost of new drug discovery. It will also very substantially increase the difficulty in establishing causal relationships. The net result is likely to be a trade-off in which a few drugs with dangerous toxicities are uncovered at the cost of stopping the development of at least some safe drugs that would have benefited large numbers of patients. The IOM committee recommends that the duration of follow-up be stated explicitly in each protocol along with a rationale. The IOM committee anticipates that because of the FIAU case, the potential for the delayed onset of toxicity after stopping therapy will influence follow-up protocol designs. There is a need to maintain flexibility in study design and tailor protocols for specific drugs to specific clinical situations.