The second category of evil consists of tragic or unfortunate events that cannot be remedied or prevented by any reasonable human behavior. The appropriate response to such events is to acknowledge their existence and to view them with fear and trembling, but to refrain from a regulatory reaction until an action that can prevent their future occurrence is clear. A good case in point is the lethal reaction to FIAU. At the time of this writing the IOM committee is aware of no test that could be done to anticipate such lethal reactions. Among the actions we recommend is the conduct of careful studies aimed at developing a test or series of tests that would identify other agents that could produce such reactions. If and when such a test becomes available, it should be considered a part of routine preclinical testing of new drugs.
The public's frequent tendency to rely on a regulatory response to tragedies of this type may be grounded in some incorrect assumptions. Some individuals appear to assume that all calamities are preventable. Therefore, when they occur it is further assumed that somebody must have been careless, negligent, or exploitative. Favorite targets for such accusations are the industrial sponsors, the investigators, and the regulatory agency. Such behavior by the sponsors is usually attributed to their presumed willingness to override all other values in the single-minded pursuit of corporate profit. Investigators are similarly accused of negligent behavior owing to their presumed overly-zealous pursuit of financial or academic rewards such as tenure and prestige (e.g., Twentieth Century Fund Task Force, 1984). Regulatory agencies are portrayed as inept or out of touch with the needs of the people, and individuals within the agencies are accused or suspected of conflicts of interest.
The committee wishes to call attention to two dangerous consequences of these assumptions. The tendency to "close the book" by indicating blame has the effect of reinforcing the erroneous public perception that new treatments can be developed and tested free of risks if only enough care is taken. As a result, once society is satisfied that it has identified the individual or group responsible for the tragic event and removed this danger from the drug development system, we can all feel free to return to business as usual.
A second danger is even more insidious. The failure of the public to appreciate the risks of research in the field of drug development compounded with a strong tendency to affix blame on those who carry out the trials when something goes wrong creates a risk for the future of clinical research. Young medical scientists cannot fail to notice that this situation presents grave risks to their personal reputations and careers. Skilled clinical investigators in the field of drug development are a valuable national resource who can reduce the burden of pain, illness, and premature death.
The committee has found nothing in its review to suggest that the tragedy was preventable given the heretofore unobserved and unanticipated late complication of the treatment. Furthermore, we find nothing to suggest that investigators were negligent in the conduct of the trials under review or that they were calloused or insensitive to the needs and conditions of the patients whom they studied.
The fact that we cannot at this time recommend a regulatory action that would absolutely prevent a recurrence of a tragic event of the sort caused by FIAU should not be a source of intimidation with respect to new drug development. Examination of the past record of experience with Phase I testing of new drugs shows that, in fields other than oncology,