12 
and experience of each investigator. The tenth item requests an outline of 
any phase or phases of the planned investigations and a description of the 
Institutional Review Board (IRB). The eleventh item requests an agreement 
that the investiqator will notify the FDA if the investigation is discontinued 
and the reason for discontinuance. Items 12 through 16 deal with notification 
issues and environmental assessments. 
Dr. Ackerman said investigators must file an additional form (Attachment IV) 
with the FDA as part of an IND application. This form requests information on 
the principal investigators' Qualifications and experience, the requirements 
of the IRB, and the investigational plan. Item four specifically links the 
principal investigator to the sponsoring organization which is linked to the 
FDA and reouires that progress reports be made to the FDA at intervals of time 
not exceeding one year. Any adverse effect that may be regarded as caused by or 
probably caused by the new drug shall be reported to the sponsor promptly. If 
the adverse effect is alarming, it shall be reported immediately. Dr. Ackerman 
said promptly is defined as within seven to ten days and immediately by telephone 
call . 
Mr. Capron asked for the FDA definition of "adverse effect." Dr. Ackerman said 
the definition of adverse effect is in a constant state of evolution. One 
camp believes that any effect occurring within thirty days of administration 
of a druq should be reported. The other camp believes the only effects vhich 
need to be reported are those that could with a high degree of confidence be 
related to the drug. In practice in the beginning stages of a clinical trial, 
almost every effect is reported; as experience with the drug is qained, fewer 
observations are reported. 
Dr. Gorovitz asked how FDA defines adequacy and safety; some drugs are not 
safe but are used in desperate cases. Dr. Ackerman replied that adverse effects 
of a druq are evaluated on a risk/benefit basis. The cases can be highly 
soecif ic. 
Dr. Cook-Deegan asked what criteria trigger FDA involvement in the development 
of a drug. Dr. Ackerman said FDA can interact at several levels and can issue: 
regulations; guidelines binding in the leqal sense; or points to consider 
which are less binding and more of an exchange of views. The points to consider 
documents list FDA concerns and are generally documents in evolution. FDA is 
considering generating a points to consider document for human gene therapy. 
A number of triggers exist for initiating such an FDA action. For example, the 
number of individuals who are involved in the area is one such trigger; another 
trigger is the amount of controversy surrounding a procedure. 
Dr. Ackerman said the FDA attempts to anticipate problems but will not adept 
review procedures based on conjecture since such procedures may ultimately 
impede the review process. Although FDA would like to have seme basis for 
discussion, some experience is needed to develop a reasonable document. 
Dr. Motulsky asked how FDA would treat studies such as the National Institutes 
of Hea] th (NIH) study involving interleukin 2 (IL-2) activation of cancer 
patient T-cells. Dr. Ackerman replied that procedure involves an autologous 
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