Should combat troops be given the option of refusing investigational drug treatment?

Food and Drug Law Journal

Volumn 52, Issue 4, 1997, Pages 377-400

  Ryan, Robyn Pforr ^a,b  

^a Washington law firm of Steptoe and Johnson   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

ATROPINE; BOTULINUM TOXOID; NERVE GAS; PRALIDOXIME; PYRIDOSTIGMINE; THALIDOMIDE; TOXOID; UNCLASSIFIED DRUG;

ARMY; ARTHRALGIA; BEHAVIOR; BOTULISM; DRUG SAFETY; ETHICS; FATIGUE; FOOD AND DRUG ADMINISTRATION; HEADACHE; HUMAN; HUMAN RIGHTS; INTOXICATION; LAW; LAW SUIT; ORAL DRUG ADMINISTRATION; PRURITUS; RESEARCH; REVIEW; WAR;

DRUGS, INVESTIGATIONAL; ETHICS, MEDICAL; HUMAN EXPERIMENTATION; HUMAN RIGHTS; HUMANS; INFORMED CONSENT; MILITARY PERSONNEL; PERSIAN GULF SYNDROME; PYRIDOSTIGMINE BROMIDE; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 0031448829     PISSN: 1064590X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (206)

1. Is Military Research Hazardous to Veterans' Health? Lessons Spanning Haifa Century, S. REP. NO. 97, 103d Cong., 2d Sess. 22-23 (1994).
2. Id.
3. Id.
4. Ed Bradley, The Pill; Illnesses Suffered by Persian Gulf War Veterans May Be Credited to Mandatory Medication Given by Pentagon to Counteract Effects of Nerve Gas, 60 MIN., Sept. 29, 1996, at *1, available in 1996 WL 8065000.
5. S. REP. NO. 97, supra note 1, at 22.
6. Id.; Bradley, supra note 4, at *2.
7. Bradley, supra note 4, at *2.
8. Id.
9. Interim Rule, 55 Fed. Reg. 52,817 (Dec. 21, 1990) (codified at 21 C.F.R. § 50.23 (1996)).
10. Id. at 52,817.
11. 55 Fed. Reg. 52,814-15 (Dec. 21, 1990) (letter from Ass't Sec'y of Defense, Health Affairs, to the Ass't Sec'y for Health, Dep't of Health & Human Servs. (Oct. 30, 1990)).
12. 55 Fed. Reg. at 52,816.
13. Informed Consent of Human Subjects, Exception from General Requirements, 21 C.F.R. § 50.23.
14. 55 Fed. Reg. at 52,814-15.
15. S. REP. NO. 97, supra note 1, at 20-21.
16. Id.; PRESIDENTIAL ADVISORY COMMITTEE ON GULF WAR VETERANS' ILLNESSES, INTERIM REPORT 21 (1996) (on file with author) [herein after INTERIM REPORT].
17. S. REP. NO. 97, supra note 1, at 22.
18. Id. at 46, 48, 51, 52.
19. In 1989, Judge William H. Webster, Director of the Central Intelligence Agency, testified before the Senate that at least 20 countries had chemical weapons and the trend toward chemical and biological warfare would continue "despite ongoing multilateral efforts to stop the [] proliferation." Hearings on Global Spread of Chemical and Biological Weapons Before the Senate Comm. on Governmental Affairs and Perm. Subcomm. on Investigations, 101st Cong., 1st Sess. 10 (1989) (cited in Doe v. Sullivan, 938 F.2d 1370, 1377 (D.C. Cir. 1991)). In 1991, the Secretary of Defense, Dick Cheney, also recognized that the proliferation of nuclear, chemical, and biological weapons and the missile technology for long-range delivery systems would make "regional conflict increasingly destructive and lethal." DICK CHENEY, ANNUAL REPORT OF THE SECRETARY OF DEFENSE TO THE PRESIDENT AND CONGRESS 3 (1991) (cited in Doe, 938 F.2d at 1377).
20. In 1989, Judge William H. Webster, Director of the Central Intelligence Agency, testified before the Senate that at least 20 countries had chemical weapons and the trend toward chemical and biological warfare would continue "despite ongoing multilateral efforts to stop the [] proliferation." Hearings on Global Spread of Chemical and Biological Weapons Before the Senate Comm. on Governmental Affairs and Perm. Subcomm. on Investigations, 101st Cong., 1st Sess. 10 (1989) (cited in Doe v. Sullivan, 938 F.2d 1370, 1377 (D.C. Cir. 1991)). In 1991, the Secretary of Defense, Dick Cheney, also recognized that the proliferation of nuclear, chemical, and biological weapons and the missile technology for long-range delivery systems would make "regional conflict increasingly destructive and lethal." DICK CHENEY, ANNUAL REPORT OF THE SECRETARY OF DEFENSE TO THE PRESIDENT AND CONGRESS 3 (1991) (cited in Doe, 938 F.2d at 1377).
21. Stuart L. Nightingale, Permitting the Use of Investigation al Agents for Prophylaxis/Treatment with Waiver of Informed Consent in Battlefield or Combat-Related Situations, statement at meeting of Presidential Advisory Committee Gulf War Veterans' Illnesses 9 (Jan. 12, 1996) [hereinafter Nightingale prepared statement] (on file with author). Despite the stated intentions of FDA officials, FDA is unlikely to make the Interim Rule permanent without a public comment period and, possibly, legislative hearings. The Presidential Advisory Committee on Gulf War Veterans' Illnesses, established by President Clinton, has recommended in its Interim Report that FDA first issue a Notice of Proposed Rule Making, revisiting several areas of change for the Rule, before making the Rule final. INTERIM REPORT, supra note 16, at 24. Additionally, the expected incoming new chairman of the Senate Veterans' Affairs Committee has expressed an interest in the issues surrounding the Rule, which may lead to increased legislative involvement in the Rule's fate. Interview with Jim Gottlieb, Minority Chief Counsel, Senate Comm. on Veterans' Affairs (Oct. 23, 1996).
22. INTERIM REPORT, supra note 16, at 21.
23. This paper does not discuss the government's tort liability for administering the drugs under this rule. See William Brook Lafferty, Comment, The Persian Gulf War Syndrome: Rethinking Government Tort Liability, 25 STETSON L. REV. 137 (1995) (discussion of tort liability for administering mandatory investigational drugs).
24. EDWARD SPIERS, CHEMICAL AND BIOLOGICAL WEAPONS: A STUDY OF PROLIFERATION 107-109, 110 (1994). As early as the late 1980s the United States was aware of Iraq's capability to use chemical warfare. Id. at 110. In April 1988, the Iraqis used chemical warfare in the recapture of the Al Fao peninsula. Id. Later Iraqi troops underscored its chemical warfare ability by publicly loading and then unloading chemical warfare from combat aircraft. Id.
25. Id. at 111-13.
26. Id. at 113.
27. 55 Fed. Reg. at 52,814.
28. Pub. L. No. 75-717, 52 Stat. 1040 (1938) (codified as amended 21 U.S.C. §§ 301 et seq. (1994)).
29. 21 U.S.C. § 355(a), (d).
30. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, 103D CONG., 2D SESS., IS MILITARY RESEARCH HAZARDOUS TO VETERANS' HEALTH? LESSONS FROM WORLD WAR II, THE PERSIAN GULF, AND TODAY 368 (1994) (justification for waiver of in formed consent for an investigational drug because of military combat exigencies).
31. S. REP. NO. 97, supra note 1, at 11.
32. Nightingale prepared statement, supra note 20, at 11.
33. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 30.
34. Id. at 127 (statement of Edward Martin, Acting Principal Ass't Sec'y of Defense, Health Affairs).
35. Nightingale prepared statement, supra note 20, at 15; S. REP. NO. 97, supra note 1, at 13.
36. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 266 (table providing the systemic reactions to botulinum pentavalent toxoid for the years 1970 through 1992).
37. Nightingale prepared statement, supra note 20, at 5.
38. 21 U.S.C. § 355(a)(i).
39. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 137 (statement of Dr. Robert J. Temple, Dir., Off. of Drug Evaluation, Center for Drug Evaluation and Research (CDER), FDA).
40. 21 C.F.R. § 50.23.
41. Id. 41 Id. Section 50.23 provides, in pertinent part: (a) The obtaining of informed consent shall be deemed feasible unless, before use of the test article. .., both the investigator and a physician who is not otherwise participating in the clinical investigation certify in writing all of the following: (1) The human subject is confronted by a life-threatening situation necessitating the use of the test article. (2) Informed consent cannot be obtained from the subject because of an inability to communicate with, or obtain legally effective consent from, the subject. (3) Time is not sufficient to obtain consent from the subject's legal representative. (4) There is available no alternative method of approved or generally recognized therapy that provides an equal or greater likelihood of saving the life of the subject. Id.
42. 55 Fed. Reg. at 52,815.
43. S. REP. NO. 97, supra note 1, at 20.
44. 55 Fed. Reg, at 52,815.
45. Id.
46. Id.
47. Id.
48. S. REP. NO. 97, supra note 1, at 20-21; STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 354 (minutes of Sept. 7, 1990 meeting between FDA and DOD). According to the meeting minutes, DOD officials notified FDA that, under its directive, the Secretary of Military Departments could dictate the use of unapproved FDA regulated products. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 354. "DOD's current position is that this is not their primary choice at this time." Id. According to the minutes of the Informed Consent Waiver Review Group on botulinum toxoid, FDA officials wanted DOD to provide additional information to pregnant women taking the botulinum toxoid vaccine. Minutes of Meeting of Informed Consent Waiver Review Group (Dec. 31, 1990) (on file with author). Without giving the reasons why, the minutes indicate that FDA ceded to DOD's resistance to this suggestion. Id.
49. 55 Fed. Reg. 52,817.
50. The Commissioner of Food and Drugs approved DOD's waiver requests for botulinum toxoid and pyridostigmine bromide on Dec. 31, 1990, and Jan. 8, 1991, respectively. INTERIM REPORT, supra note 16, at 21.
51. Doe v. Sullivan, 756 F. Supp. 12 (D.D.C. 1991) [hereinafter Doe I], aff'd, 938 F.2d 1370 (D.C. Cir. 1991) [hereinafter Doe II]. 52 Pub. L. No. 98-525, § 1401(c)(1), 98 Stat. 2492, 2615 (1985) (codified at 10 U.S.C § 980 (1994)).
52. Doe I, 756 F. Supp. at 14.
53. Id.; Doe II, 938 F.2d at 1386.
54. Doe I, 756 F. Supp. at 15.
55. Id. at 14, The court went on to state that, even if it found DOD's decision to be judicially reviewable, DOD's planned treatment did not violate the soldier's due process rights and the Interim Rule was within FDA's regulatory powers to enact. Id. at 16, 17. The court also held that administering such unapproved drugs to soldiers without their consent did not violate the DAA because DOD's administration of these drugs did not constitute research, and thus the Act was not applicable. Id. at 14.
56. Doe II, 93 8 F.2d at 1380. Then-Circuit Court Judge Ruth Bader Ginsburg wrote: We confront at this time not a dispute over military strategy or discipline, not one between soldiers and their superiors, but one over the scope of the authority Congress has entrusted to the FDA ... Doe's facial attack asks simply whether the law that governs FDA action permits the measure which that non-military agency has taken. Id. at 1380-81.
57. The court held that the authorizing statute was sufficiently ambiguous to allow for FDA's decision to carve out another exception to the informed consent requirement. Id. at 1382.
58. Id. at 1383. The court reasoned: The DAA, however, limits the authority of the Department of Defense, not the authority of the Food and Drug Commissioner. Although it might be argued that the DAA restricts the authority of the Assistant Secretary of Defense to make the request anticipated by Rule 23(d), it cannot he argued that the DAA restricts the Secretary of Health and Human Services from promulgating Rule 23(d). Id. at 1383.
59. Id. at 1383. The court conducted a balancing test, concluding that the government's interest in preventing unnecessary danger to troops and medical personnel and its interest in successfully completing the military mission were legitimate government concerns that outweighed the individual's interest in being free from experimental treatment without giving informed consent Id. at 1383.
60. Doe I, 756 F. Supp. at 14 n.2.
61. Nightingale prepared statement, supra note 20, at 9.
62. 55 Fed. Reg. at 52,817.
63. Id.
64. Id.
65. Id.
66. Id.
67. Id.
68. Id.
69. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 63 (statement of Chairman Sen. John D. Rockefeller IV).
70. Benjamin Weiser, Troops Won't Be Using Experimental Skin Drug; Contract for Chemical War Cream Canceled, WASH. POST, Feb. 7, 1991, at A26.
71. Id. Soldiers were to have carried the cream in small plastic bottles. Id. In the event of a chemical attack, the soldiers would have rubbed the cream in areas that might not be covered by gas masks, gloves, or chemical suits, such as the neck or wrist area. Id.
72. Id.
73. Id. Later, a federal grand jury charged a scientist who had been contracted by the Army to analyze the skin lotion with performing a fraudulent demonstration of an analysis of the skin cream before FDA. Scientist Charged With Lying to the FDA, BOSTON GLOBE, Nov. 21, 1991, at 65.
74. S. REP. NO. 97, supra note 1, at 28-34; Public Citizen, Petition to Repeal Interim Rule 16-19 (May 7, 1996) (on file with author) [hereinafter Public Citizen Petition].
75. Public Citizen Petition, supra note 75, at 20-22.
76. Nightingale prepared statement, supra note 20, at 11.
77. Id. DOD proposed treatment was 30 milligrams three times a day for seven days; in comparison myasthenia gravis patients were treated with doses of up to 1500 milligrams a day for many years. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 368. Several other North Atlantic Treaty Organization countries hold PB in reserve for us e as a pretreatment against nerve gas attack, including the United Kingdom, Germany, The Netherlands, Belgium, Canada, Israel, and Spain. Id. at 369.
78. Nightingale prepared statement, supra note 20, at 11. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 135 (statement of Dr. Robert J. Temple, Dir., Off. of Drug Evaluation, CDER, FDA).
79. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 104 (statement of Thomas J. Callender, M.D.) Dr. Callender criticized this finding of safety by analogy, saying that my asthenia patients have abnormal physiology that could account for differences in the safety of their treatment with PB from treatment of healthy patients. Id. He also stated that myasthenia patients receive other medications that could be protective of some of the side effects of PB. Id. Callender questioned the assumption that a lower dosage was necessarily safer, commenting that while large doses of insulin were safe for diabetics that even small doses of insulin can cause serious harm in nondiabetic patients. Id.
80. Id.; S. REP. NO. 97, supra note 1, at 12.
81. Public Citizen Petition, supra note 75, at 20-21; DEPARTMENT OF DEFENSE, DEPARTMENT OF DEFENSE COMMENTS ON PUBLIC CITIZEN LITIGATION GROUP'S PETITION TO REPEAL INTERIM RULE ON THE TREATMENT USE WITHOUT INFORMED CONSENT OF INVESTIGATIONAL NEW DRUGS IN MILITARY COMBAT EXIGENCIES 15 (1996) (on file with author) [hereinafter DOD RESPONSE TO PUBLIC CITIZEN PETITION].
82. Public Citizen Petition, supra note 75, at 20-21; DEPARTMENT OF DEFENSE, DEPARTMENT OF DEFENSE COMMENTS ON PUBLIC CITIZEN LITIGATION GROUP'S PETITION TO REPEAL INTERIM RULE ON THE TREATMENT USE WITHOUT INFORMED CONSENT OF INVESTIGATIONAL NEW DRUGS IN MILITARY COMBAT EXIGENCIES 15 (1996) (on file with author) [hereinafter DOD RESPONSE TO PUBLIC CITIZEN PETITION].
83. I. Koplovitz, L.W. Harris, D.R. Anderson, W.J. Lennox & J.R. Stewart, Reduction by Pyridostigmine Pretreatment of the Efficacy of Atropine and 2-PAM Treatment of Sarin and VX Poisoning in Rodents, 18 FUNDAMENTAL & APPLIED TOXICOLOGY 102-06 (1992).
84. Dana Priest, Poison Gas Exposure Estimate Is Growing; More Than 15,000 May Have Been Affected in Gulf Region, Pentagon Says, WASH. POST, Oct. 2, 1996, at A12. Bradley, supra note 4, at *5.
85. Nightingale prepared statement, supra note 20, at 14, 15. Under the pre-war IND protocols on PB and botulinum toxoid, DOD and the Center for Disease Control prepared annual reports for FDA on the safety and efficacy information about the drugs. Id.
86. Public Citizen Petition, supra note 82, at 21.
87. DOD RESPONSE TO PUBLIC CITIZEN PETITION, supra note 82, at 15 n.7.
88. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 385 (letter from Gregory P. Berezuk, Chief, Human Use Rev. and Reg. Affairs Off., Dep't of the Army, Off. of the Surgeon Gen., to Dir., Div. of Neuropharmacological Drug Prods., CDER, FDA (Jan. 17, 1991)).
89. S. REP. NO. 97, supra note 1, at 28-32.
90. Id. at 28. One doctor, a specialist in internal medicine as well as environmental and occupational toxicology, stated that the research indicated that there are sexual differences in responses to PB. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 100, 102 (statement by Dr. Callender). Dr. Callender stated that research that excluded women as subjects posed an unwarranted risk to women in combat zones. Id.
91. S. REP. NO. 97, supra note 1, at 29.
92. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 101 (Callender statement). Dr. Callender pointed out that long-term studies were essential because "it was well known that the ACHe [the enzyme acetylcholinesterase] inhibiting agents that cause permanent nerve damage typically take several weeks to months for the nerve damage to become evident." Id. at 101.
93. S. REP. NO. 97, supra note 1, at 29.
94. Id.
95. Public Citizen Petition, supra note 75, at 18; STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 102 (Callender statement); STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 147 (post-hearing answers provided by Dr. Edward Martin, Acting Principal Ass't Sec'y of Defense, DOD).
96. Philip Hilts, Chemical Mix May be Cause of Illnesses in Gulf War, N.Y. TIMES, Apr. 17, 1996, at A17.
97. Warren E. Leary, Gulf Illness May Reflect Multiple Exposures, Report Says, N.Y. TIMES, Jan. 9, 1997, at A18. The study, conducted by researchers from the University of Texas Southwestern Medical Center in Dallas, studied the effects of PB and pesticides on Navy combat construction engineers. Id.
98. S. REP. NO. 97, supra note 1, at 32.
99. David Brown, A Theory of Chemical Interactions, N.Y. TIMES, Jan. 2, 1997, at A10. The study, conducted by scientists at the Hebrew University in Jerusalem, studied the effects of PB ingestion by a group of laboratory mice under stressed conditions. "The stressed mice needed only one-hundredth of the dose given unstressed mice to show a similar amount of pyridostigmine 'activity' in brain tissue." Id. 100 STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 383 (letter from David Kessler, M.D., Comm'r of Food and Drugs, FDA, to Enrique Mendez, Jr., M.D., Ass't Sec'y for Defense, Health Affairs, DOD (Jan. 8, 1991)). In his testimony before the Presidential Advisory Committee on Gulf War Veterans' Illnesses, Dr. Stuart Nightingale, Assoc. Comm'r for Health Affairs, FDA, stated that "although informed consent was waived, giving as complete information as practicable to the troops was deemed a crucial ethical mandate and sine qua non for this distribution system to be approved." Nightingale prepared statement, supra note 20, at 8-9.
100. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 375-80 (citing DOD FIELD MANUAL 149, 151 (1990)); Nightingale prepared statement, supra note 20, at 4.
101. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 375-80 (citing DOD FIELD MANUAL 149, 151 (1990)); Nightingale prepared statement, supra note 20, at 4.
102. S. REP. NO. 97, supra note 1, at 36-37. According to a Senate survey of Persian Gulf military personnel, most stated they received no information, oral or written, about the drug and vaccine. Id. at 22.
103. Bradley, supra note 4, at *7.
104. Id.
105. Id.
106. R. Alta Charo, Prepared Statement for the Presidential Advisory Committee on Gulf War Illnesses Meeting 12 (Jan. 1996) [hereinafter Charo prepared statement].
107. Id. at 12.
108. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 122 (statement of Arthur L. Caplan, Ph.D., Ctr. for Bioethics, Univ. of Pa.); S. REP. NO. 97, supra note 1, at 22. During the war, a Stars and Stripes article reported on allegations in the United States about requiring troops to take "experimental vaccines." DOD RESPONSE TO PUBLIC CITIZEN PETITION, supra note 82, at 13. Additionally several troops believe that their children's birth defects may have been caused by their forced ingestion of PB. J.R. Moehringer, Gulf War's Legacy of Worry Grows, L.A. TIMES, Oct. 22, 1995, at A1. Perhaps this type of speculation, not supported as a potential side effect in any of the research literature, may have been avoided by informing the troops about what they were taking. FDA officials, who have the option of imposing sanctions on DOD for not complying with the IND requirements, told Senate officials in 1994 they would discuss the noncompliance with DOD. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 59 (testimony of Dr. Robert J. Temple, Dir., Off. of Drug Evaluation, CDER, FDA).
109. INTERIM REPORT, supra note 16, at 22; STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 94-95 (testimony of Chaplain Barry Walker); Public Citizen petition, supra note 75, at 12-15.
110. INTERIM REPORT, supra note 16, at 22.
111. Id. at 22.
112. DOD RESPONSE TO PUBLIC CITIZEN PETITION, supra note 82, at 1, 3-4.
113. 21 C.F.R. § 50.23.
114. 44 Fed. Reg. 47,713, 47,718 (Aug. 14, 1979).
115. JAY KATZ, EXPERIMENTATION WITH HUMAN BEINGS 523 (1973) ("lawyers, investigators, and courts often seem to overlook the fact that it lacks specific construction and remains and ill-defined concept"); PAUL S. APPELBAUM, CHARLES W. LIDZ & ALAN MEISEL, INFORMED CONSENT 3 (1987) (discussion of different concepts of informed consent and concept's "complex lineage").
116. JAY KATZ, EXPERIMENTATION WITH HUMAN BEINGS 523 (1973) ("lawyers, investigators, and courts often seem to overlook the fact that it lacks specific construction and remains and ill-defined concept"); PAUL S. APPELBAUM, CHARLES W. LIDZ & ALAN MEISEL, INFORMED CONSENT 3 (1987) (discussion of different concepts of informed consent and concept's "complex lineage").
117. KATZ, supra note 115, at 523-24; 44 Fed. Reg. at 47,718; APPELBAUM, supra note 115, at 22-23. See generally KATZ, supra note 115, at 540-608 (discussion of different social values supporting informed consent).
118. KATZ, supra note 115, at 523-24; 44 Fed. Reg. at 47,718; APPELBAUM, supra note 115, at 22-23. See generally KATZ, supra note 115, at 540-608 (discussion of different social values supporting informed consent).
119. KATZ, supra note 115, at 523-24; 44 Fed. Reg. at 47,718; APPELBAUM, supra note 115, at 22-23. See generally KATZ, supra note 115, at 540-608 (discussion of different social values supporting informed consent).
120. KATZ, supra note 115, at 523-24; 44 Fed. Reg. at 47,718; APPELBAUM, supra note 115, at 22-23. See generally KATZ, supra note 115, at 540-608 (discussion of different social values supporting informed consent).
121. KATZ, supra note 115, at 523-24; 44 Fed. Reg. at 47,718; APPELBAUM, supra note 115, at 22-23. See generally KATZ, supra note 115, at 540-608 (discussion of different social values supporting informed consent).
122. 44 Fed. Reg. at 47,718.
123. 44 Fed. Reg. at 47,713.
124. GEORGE J. ANNAS, LEONARD H. GLANTZ & BARBARA F. KATZ, INFORMED CONSENT TO HUMAN EXPERIMENTATION: THE SUBJECT'S DILEMMA 6-9 (1977) (discussion of origin and treatment of Nuremberg Code internationally and in U.S. courts).
125. Id. at 21.
126. See KATZ, supra note 115, at 305-06. See also 2 TRIALS OF WAR CRIMINALS BEFORE THE NUERNBERG MILITARY TRIBUNALS UNDER CONTROL COUNCIL LAW NO. 10, at 181-82 (1946-1949).
127. See KATZ, supra note 115, at 305-06. See also 2 TRIALS OF WAR CRIMINALS BEFORE THE NUERNBERG MILITARY TRIBUNALS UNDER CONTROL COUNCIL LAW NO. 10, at 181-82 (1946-1949).
128. ANNAS, GLANTZ & KATZ, supra note 120, at 7.
129. George J. Annas, Mengele's Birthmark: The Nuremberg Code in United States Courts, 7 J. CONTEMP. HEALTH L. & POL'Y 17, 24-25 (1991).
130. See KATZ, supra note 115, at 312. See also Human Experimentation: Code of Ethics of the World Medical Association: Declaration of Helsinki, 2 BRIT. MED. J. 177 (1964).
131. See KATZ, supra note 115, at 312. See also Human Experimentation: Code of Ethics of the World Medical Association: Declaration of Helsinki, 2 BRIT. MED. J. 177 (1964).
132. Id.
133. Id.
134. 44 Fed. Reg. at 47,713.
135. Id. It was only when the drug manufacturer applied for final approval that FDA reviewed how the research was conducted. Id. Until that point, FDA regulations required only that the drug be labeled "for investigational use only" and that the manufacturer keep records on how much drug was supplied and to whom. Id.
136. Id.
137. 44 Fed. Reg. at 47,714. Thalidomide is a sleeping pill that was given to patients in Europe and that caused women who took the pill during pregnancy to give birth to babies with severe birth defects. See 108 CONG. REC. 17,403-04 (1962) (reprinting News Release from FDA, U.S. Dep't of Health, Education, and Welfare (Aug. 23, 1962)).
138. 44 Fed. Reg. at 47,714. Thalidomide is a sleeping pill that was given to patients in Europe and that caused women who took the pill during pregnancy to give birth to babies with severe birth defects. See 108 CONG. REC. 17,403-04 (1962) (reprinting News Release from FDA, U.S. Dep't of Health, Education, and Welfare (Aug. 23, 1962)).
139. 108 CONG. REC. 17,403-04.
140. Id.
141. 108 CONG. REC. 17,397 (1962). Javits' proposed amendment initially did not require that consent be obtained, although Javits and others recommended that such consent be obtained. Id.
142. Id. Senator Carroll added: I have great confidence in our medical profession. I know the physician recognizes his ethical responsibility to the patient .... I know that in most cases the doctor is going to act in the interest of his patient. However, I repeat that I believe firmly every human being has a right to know whether he is being treated with experimental medicine. Id.
143. 44 Fed. Reg. at 47,714-15.
144. Id.
145. See Elliott J. Schuchardt, Distinguishing Between Research and Medical Practice During Operation Desert Storm, 49 FOOD & DRUG L.J. 271, 278-79 (1994).
146. Id.
147. The DAA provides that [f]unds appropriated to the Department of Defense may not be used for research involving a human being as an experimental subject unless -1) the informed consent of the subject is obtained in advance; or 2) in the case of research intended to be beneficial to the subject, the informed consent of the subject or a legal representative of the subject is obtained in advance. 10 U.S.C. § 980.
148. Id.
149. The Army Regulations provide that; [a]n Army member on active duty or active duty for training will usually be required to submit to medical care considered necessary to p reserve his life, alleviate undue suffering, or protect or maintain the health of others. A commanding officer may order the hospitalization of any member of his command or order him to submit to a medical examination when indicated. Army Reg. No. 600-20, ¶ 15-30 through 5-31 (Aug. 26, 1985) (cited in Capt Stephen E. Deardorff, Comment, Informed Consent Termination of Medical Treatment, and the Federal Tort Claims Act - A New Proposal for the Military Health Care System, 115 MIL. L. REV. 1, 68 n.338 (1987)).
150. Richard Delgado & Helen Leskovac, Informed Consent in Human Experimentation: Bridging the Gap Between Ethical Thought and Current Practice, 34 UCLA L. REV. 67 (1986); ANNAS, GLANTZ & KATZ, supra note 120, at 44; Charo prepared statement, supra note 106 at 2.
151. Richard Delgado & Helen Leskovac, Informed Consent in Human Experimentation: Bridging the Gap Between Ethical Thought and Current Practice, 34 UCLA L. REV. 67 (1986); ANNAS, GLANTZ & KATZ, supra note 120, at 44; Charo prepared statement, supra note 106 at 2.
152. Delgado, supra note 142, at 67.
153. Id.; ANNAS, GLANTZ & KATZ, supra note 120, at 44.
154. NATIONAL COMMISSION FOR THE PROTECTION OF HUMAN SUBJECTS OF BIOMEDICAL AND BEHAVIORAL RESEARCH, THE BELMONT REPORT: ETHICAL PRINCIPLES AND GUIDELINES FOR THE PROTECTION OF HUMAN SUBJECTS OF RESEARCH 2 (1979).
155. Id. at 3.
156. Id.
157. Id.
158. Id.
159. Id.
160. Id. "The general rule is that if there is any element of research in an activity, that activity should undergo review for the protection of human subjects." Id.
161. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 120-21 (Caplan statement).
162. Id. at 121.
163. Id. Caplan argues that the fact that both FDA and DOD viewed the treatment as research. The fact that both parti es believed that they needed to seek waivers from prevailing informed consent requirements is further evidence that the treatment constituted research. Id. Ironically, Caplan reaches his conclusion by focusing on the intent of the investi gators, while criticizing the Belmont Report's focus on investigators' intent. Id.
164. STAFF OF SENATE COMM. ON VETERANS' AFFAIRS, supra note 29, at 125 (Martin statement).
165. INTERIM REPORT, supra note 16, at 21.
166. Id.
167. S. REP. NO. 97, supra note 1, at 44; Charo prepared statement, supra note 106, at 2.
168. United States v. Stanley, 483 U.S. 669, 684 (1987).
169. Id. at 684.
170. Id. at 671.
171. Id.
172. Charo prepared statement, supra note 106, at 2.
173. DOD RESPONSE TO PUBLIC CITIZEN PETITION, supra note 82, at 1.
174. Id.
175. Id. at 10.
176. Id.
177. 55 Fed. Reg. at 52,815.
178. Doe I, 756 F. Supp. at 17. Edward D. Martin & Edmund G. Howe, Treating the Troops, 21 HASTINGS CTR. REP. 21, at *5, available on LEXIS, NEWS library, ASAPII file.
179. Doe I, 756 F. Supp. at 17. Edward D. Martin & Edmund G. Howe, Treating the Troops, 21 HASTINGS CTR. REP. 21, at *5, available on LEXIS, NEWS library, ASAPII file.
180. 55 Fed. Reg. at 52,815.
181. Id.
182. 21 C.F.R. § 50.23.
183. Charo prepared statement, supra note 106, at 10-11.
184. 46 Fed. Reg. 8943 (1981) (quoting GEORGE J. ANNAS, THE LAW OF INFORMED CONSENT TO HUMAN EXPERIMENTATION: AN INTRODUCTION WITH SPECIFIC REFERENCE TO THE HOSPITAL PATIENT AND THE NORMAL VOLUNTEER (1976)).
185. 46 Fed. Reg. 8943 (1981) (quoting GEORGE J. ANNAS, THE LAW OF INFORMED CONSENT TO HUMAN EXPERIMENTATION: AN INTRODUCTION WITH SPECIFIC REFERENCE TO THE HOSPITAL PATIENT AND THE NORMAL VOLUNTEER (1976)).
186. Id.
187. KATZ, supra note 115, at 305-06; George J. Annas & Michael A. Grodin, Treating the Troops, 21 HASTINGS CTR. REP., at *9, available on LEXIS, NEWS library, ASAPII file; Bradley, supra note 4, at *6 (comment of Sen. John D. Rockefeller IV that DOD's mandatory treatment of troops violated Nuremberg Code).
188. KATZ, supra note 115, at 305-06; George J. Annas & Michael A. Grodin, Treating the Troops, 21 HASTINGS CTR. REP., at *9, available on LEXIS, NEWS library, ASAPII file; Bradley, supra note 4, at *6 (comment of Sen. John D. Rockefeller IV that DOD's mandatory treatment of troops violated Nuremberg Code).
189. David Brown & Bill McAllister, Two Studies Find No Gulf 'Mystery Illness'; Slight Health Differences Detected Between Deployed and Non-Deployed Veterans, WASH. POST, Nov. 14, 1996, at A3.
190. There is little scientific evidence, however, supporting the contention that troop commanders are potentially endangering the health of the troops' unborn children and families. David Brown & Dana Priest, Report Finds No Evidence of "Gulf War Syndrome," WASH. POST, Nov. 9, 1996, at A1.
191. PAUL FUSSELL, WARTIME (1989).
192. 21 C.F.R. § 50.23.
193. S. REP. NO. 97, supra note 1, at 7-8, 9-10; Schuchardt, supra note 138, at 284-85.
194. The Presidential Advisory Committee on Gulf War Veterans' Illnesses in us draft Final Report harshly criticized DOP for conducting a "superficial investigation of possible chemical warfare agent exposures, which is unlikely to provide credible answers to veterans' questions." Brown & Priest, supra note 178, at A1.
195. Dana Priest & Bill McAllister, Gulf War's Depot of Distrust; Pentagon Lagged in Noting Possible Chemical Exposure, WASH. POST. Nov. 10, 1996, at A1.
196. INTERIM REPORT, supra note 16, at 21.
197. Nightingale prepared statement, supra note 20, at 9.
198. This suggestion was developed by the author following a discussion with Georgetown University Law Center Professor Lawrence Gostin.
199. 55 Fed. Reg. at 52,817.
200. See id. at 52,815; Eugene G. LaForet, Limits of Loyalty and Obedience: Does the Military Physician Serve Two Masters, in ETHICS AND NATIONAL DEFENSE 101 (James C. Gaston et al. eds. 1993) (author argues that when physician's duty to military bureaucracy and its mission come in conflict with ethical duty and duty to patient that physician should resort to his or her informed conscience).
201. Interview with Jim Gottlieb, Minority Chief Counsel, Committee on Veterans' Affairs, U.S. Senate, Washington, D.C. (Oct. 23, 1996), See also LaForest supra note 189, at 104-10.
202. The minutes of DOD's IRB meetings relating to the three proposed drugs were not available to give a clearer idea of the rigor of these boards' analyses.
203. This suggestion also was proposed by R. Alta Charo. Charo prepared statement, supra note 106, at 13-14. Harold Edgar & David Jonathan Rothman, The Institutional Review Board and Beyond: Future Challenges to the Ethics of Human Experimentation , MILBANK Q. 489, Dec. 1, 1995, at *15, available in 1995 WL 12381760. The authors advocate for increased regulations governing IRBs and increased influence of outsiders on these boards. In the context of government-sponsored research, they argue that the need for external voices is even more important to ensure that such research remains within the bounds of ethical research, Id. While this would involve some complications, such as granting outsiders security clearances, the commitment to extra-institutional review could surmount these obstacles. Id. 193 45 C.F.R. § 46.107(a), (d) (1996).
204. Despite these pressures, FDA caught the problems with Multi-Shield and did not approve this application in the Persian Gulf War.
205. Public Citizen Petition, supra note 75, at 20, 21.
206. In its Final Report, the Presidential Advisory Committee on Gulf War Veterans' Illnesses also stressed the need to commit federal funds for scientific studies about the synergistic effects of PB and other chemicals and agents to which troops would be exposed. PRESIDENTIAL ADVISORY COMMITTEE ON GULF WAR VETERANS' ILLNESSES, FINAL REPORT 117 (1997) (on file with author).