Ants Hole Publishing

Introduction
Background
Findings and Conclusions
Recommendations
Appendix

IV. STAFF RECOMMENDATIONS

FDA Should Deny The DOD Request For A "Blanket Waiver" To Use Investigational Drugs Without Informed Consent In Case Of War Or Threat Of War

If investigational drugs are deemed necessary for protection or treatment, a waiver of informed consent should be sought only on a case-by- case basis. While the military might order individuals to take an investigational drug or use an investigational device if it is clearly safe and potentially efficacious, under no circumstances should the DOD fail to inform individuals about the known short-term and long-term risks prior to its administration.

In 1990, DOD applied to FDA for a waiver of informed consent, claiming they would provide warnings orally and in writing regarding the risks of pyridostigmine, even though they would not give soldiers the choice of whether or not to take it. According to reports from various sources, including DOD's own study, DOD did not fulfill its promise. In addition, DOD personnel apparently distributed these drugs to civilians without any warnings. These failures and broken promises should be sufficient to persuade FDA to reject the DOD request for a blanket waiver, and should be taken into consideration any time DOD applies for a waiver of informed consent. In addition, FDA should investigate these problems and work with DOD to prevent similar problems in the future. 

In addition, third-party or "deferred" consent should not be considered unless the individual receiving the drug is physically or mentally incompetent to make an informed decision on his/her behalf. If the DOD fails to obtain the necessary waivers, or fails to adequately inform those receiving the investigational products, DOD should be required to provide a written explanation to the appropriate congressional committees.

FDA Should Reject IND and NDA Applications From DOD That Do Not Include Data On Women, And Long-Term Followup Data

When DOD submits an IND (investigational new drug) application or NDA (new drug application) to FDA for any product that they plan to use, they should always be required to include women in their research, since it is likely that the product will be used by women. On the basis of that requirement, FDA should reject the currently pending NDA for pyridostigmine's use as an antidote enhancer, which was submitted to FDA in early 1994.

At a Senate briefing in November 1994, Dr. Ruth Merkatz, FDA's Associate Commissioner for Women's Health, stated that FDA will always require data on women in future drug approval applications, if the product under review is intended for use by women. However, Dr. Merkatz was not specific about whether this policy would apply to DOD.

In addition to data on women, it is increasingly clear that drugs can have long-term adverse reactions that are not immediately obvious. Given the responsibility of the Federal Government to provide medical care to veterans who were harmed during military service, DOD and FDA need to ensure that the VA and the public are aware of any potential long-term adverse reactions of any medical products that are given to military personnel.

In the case of pyridostigmine, a drug that DOD wants to have the authority to use in future conflicts in the Persian Gulf and elsewhere, FDA should immediately urge DOD to conduct the kinds of research that is needed to prove its safety for future military use, including research on its potentially toxic effects when combined with insecticides and other chemical agents that are commonly used by military personnel.

Congress Should Authorize A Centralized Database For All Federally Funded Experiments That Utilize Human Subjects

Currently, the U.S. Department of Agriculture maintains a database which can identify the number of research grants awarded for studying various species, such as beef and dairy cattle, poultry, sheep, swine, and others. (Note 166) However, a database which identifies the types of human subjects does not exist.

Congress should authorize a database which would provide crucial information on federally funded research utilizing human subjects. Included in this database should be the amount of Federal dollars spent on various research efforts and the type of human subjects utilized, such as women, minorities, children, prisoners, military personnel, and others.

Annual reports from the data collected should be provided to Congress. Such information would enable legislators to understand better the use of human subjects in federally sponsored research.

Congress Should Mandate All Federal Agencies To Declassify Most Documents On Research Involving Human Subjects

Information involving human subjects in military research, which remains classified for purported reasons of national security, needs to be reevaluated and declassified whenever possible. All Federal agencies should scrutinize classified information and make information available which might benefit individuals who participated in such research.

Congress Should Reestablish A National Commission For The Protection of Human Subjects Without Term Limits, Which Has The Authority To Investigate Potential Violations of Human Subjects' Right In Federally Funded Research

A National Commission should standardize Federal regulations (45 CFR 46), and consider adding military personnel as a vulnerable population. Policies for the conduct of research in war or for the purposes of national security should receive greater public debate. No existing regulations governing military personnel should be finalized without such public dialogue.

Congress should provide authorization and appropriations for the National Commission, and require annual reports on potential violations of human subjects' rights. The administrative body of the Commission should consist of nine members, three appointed by the majority party in Congress, three appointed by the minority party in Congress, and three appointed by the executive branch.

The VA and DoD Should Implement Regular Site Visits To Review The Performance Of IRBs

DOD and VA authorized site visits should include an evaluation of military and VA research onsite, and a random sample review of actual research and medical records, interviews with human subjects, and signed consent forms to assure investigator compliance. A mechanism should be in place whereby human subjects can express concern over perceived or actual violations of the informed consent contract. This mechanism should allow human subjects to register complaints to a regulatory agency and the National Commission, rather than solely the investigator of the research project. All military personnel and veterans involved in research should receive a copy of the "Experimental Subject's Bill of Rights." (Note 167)

The Feres Doctrine Should Not Be Applied For Military Personnel Who Are Harmed By Inappropriate Human Experimentation When Informed Consent Has Not Been Given

The U.S. Supreme Court has interpreted the Feres Doctrine to mean that soldiers "injured in the course of activity incident to service" may not sue the Government for compensation. (Note 168) However, when inappropriate experimentation has resulted in suffering for military personnel, this interpretation stands in violation of established ethical standards, including the Nuremberg Code, the Declaration of Helsinki, and the "Common Rule." Congress should not apply the Feres Doctrine for military personnel who are harmed by inappropriate experimentation when informed consent has not been given.

The U.S. Supreme Court mentioned the Nuremberg Code in United States v. Stanley in 1987. James Stanley, an Army serviceman, volunteered to test the effectiveness of protective clothing and equipment against chemical warfare in February 1958. (Note 169) In the process, he unknowingly received LSD as part of an Army study to determine the effects of the drug on humans. Although Stanley suffered from periods of incoherence and memory loss for years, he only learned in 1975 that he had participated in the LSD study when the Army solicited his cooperation in a followup study. Having been denied compensation for injury by the Army, Stanley filed under the Federal Tort Claims Act. Justice Antonin Scalia wrote the opinion for the Court, split 5 to 4. (Note 170) Justice Scalia wrote that permitting Stanley to sue the Army would disrupt the Army itself and "would call into question military discipline and decision-making." However, Justice Sandra Day O'Connor, writing for herself as one of the dissenting judges, stated that the Feres doctrine bar

"surely cannot insulate defendants from liability for deliberate and calculated exposure of otherwise healthy military personnel to medical experimentation without their consent, outside of any combat, combat training, or military exigency..." (Note 171)
Justice O'Connor also commented on the Nuremberg Code in her writing, stating that voluntary consent of the human subject is absolutely essential, even for the U.S. military. It was, after all, the U.S. military who played an instrumental role in the criminal prosecution of the Nazi officials who experimented with human beings during World War II.