able. We recognize, further, that the section includes safeguards with respect to any drug whose use in such patients it authorizes: that the drug be under investigation in a controlled clinical trial under an IND, that the sponsor be pursuing marketing approval with due diligence, and that FDA be unable to conclude that the drug clearly does not provide a therapeutic benefit. These safeguards, separately and together, however, do not require that there be any rational basis for qualified experts to conclude that the drug may provide a therapeutic benefit, even to the limited patient population at grave risk. We agree that, for investigational drugs to treat the patient populations within the scope of the section 312.34, proof of effectiveness sufficient for new drug approval or even strong evidence of effectiveness-should not be required. What we urge is a requirement of medical and scientific rationality-a requirement of some scientific evidence on the basis of which an expert could rationally conclude that the drug may be effective in the intended_patient population. In the preamble to the final IND regulations, FDA observed, "Of course, there should be some evidence to support the reasonableness of a drug's administration for its investigational use." 52 Fed. Reg. 8802 (Mar. 19, 1987). The same general principle should also apply to any treatment use of an investigational drug, including treatment use in patients suffering from an immediately life-threatening disease. The evidence need not be conclusive. It may be only preliminary or suggestive. It should, however, be sufficient to support a reasonable scientific conclusion of possible effectiveness. Such positive evidence could be obtained in a variety of ways, including from clinical trials outside the United States, from animal data, perhaps in some circumstances from in vitro data. It could also be obtained from clinical experience, where the circumstances surrounding the experience provide sufficient indicia that it has scientific value. We believe that this approach was intended in the proposed regulation, and that our suggestion would merely make that intention explicit. The preamble to the proposal states that the treatment IND would be used for "promising" investigational drugs, and that "all data available" will be used by FDA to determine whether a treatment IND is justified. We support this approach and believe it will improve the ÎND/NDA system, drug development, and public health in this country. Finally, we want to call attention to the interplay of proposed section 312.34 and proposed section 312.7(d). We have no general objection to the sale of drugs administered under an IND. If there were no requirement for some rational basis for believing an investigational drug may be effective, however, the permission to sell it pursuant to section 312.7(d) could provide an unintended opportunity for the marketing of governmentally legitimized quack drugs to those suffering from immediately life-threatening diseases for which no satisfactory treatment is available. For these reasons, we recommend that the proposed regulations be revised to provide that FDA may deny a treatment IND for an immediately life-threatening illness if the available scientific evidence, taken as a whole, fails to provide a reasonable basis for con cluding that the drug may be effective for its intended use in its intended patient population. Respectfully submitted. [The prepared statement of Mr. Cooper follows:] April 29, 1987 Dockets Management Branch (HFA-305) Food and Drug Administration Room 462 5600 Fishers Lane Rockville, Maryland 20857 Re: Docket No. 82N-0394 Investigational New Drug, We support the treatment use of investigational drugs in the kinds of circumstances described in proposed S 312.34, and we endorse the agency's undertaking to set forth in regulations the standards and criteria for such use. We also believe that, in all but one respect, the standards and criteria proposed are generally sound. We do strongly urge, however, that $ 312.34(b)(3)(i), which sets forth the standard of effectiveness for use of a drug to treat an immediately life-threatening illness for which there is no satisfactory treatment, be changed to require a rational basis for believing that the drug may be effective. This change would make the regulation consistent with Dockets Management Branch the preamble and would prevent the unintended possibility that worthless drugs could be marketed to victims of life-threatening illnesses. In United States v. Rutherford, 442 U.S. 544 (1979), the Supreme Court unanimously rejected the claim that the terms "safety" and "effectiveness" have no reasonable application to "terminally ill" cancer patients. If noted that the Federal Food, Drug and Cosmetic Act makes no special provision for drugs used to treat terminally ill patients. 442 U.S. at 551. The specific holding of Rutherford is that all persons are to be protected by the NDA requirement, but the clear rationale of the Supreme Court's decision supports the judgment that all should beprotected by the IND requirements as well. We believe that this is a proper and necessary role for FDA. We recognize that § 312.34 deals with a special class of patients: those suffering from an immediately life-threatening disease, for which no satisfactory alternative drug or other therapy is available. We recognize, further, that the section includes safeguards with respect to any drug whose use in such patients it authorizes: that the drug be under investigation in a controlled clinical trial under an IND, that the sponsor be pursuing marketing approval with due diligence, and that FDA be Dockets Management Branch unable to conclude that the drug clearly does not provide a therapeutic benefit. These safeguards, separately and together, however, do not require that there be any rational basis for qualified experts to conclude that the drug may provide a therapeutic benefit, even to the limited patient population at grave risk. We agree that, for investigational drugs to treat the patient populations within the scope of § 312.34, proof of effectiveness sufficient for new drug approval or even strolig should not be required. What we -- a evidence of effectiveness urge is a requirement of medical and scientific rationality requirement of some scientific evidence on the basis of which an expert could rationally conclude that the drug may be effective in the intended patient population. In the Preamble to the final IND regulations, FDA observed: "Of course, there should be some evidence to support the reasonableness of a drug's administration for its investigational use." 52 Fed. Reg. 8802 (Mar. 19, 1987). The same general principle should also apply to any treatment use of an investigational drug, including treatment use in patients suffering from an immediately life-threatening disease. The evidence need not be conclusive; it may be only preliminary or |