by Sonia Shah
APACHE II (Acute Physiology and Chronic Health Evaluation), 124–25, 127
Applied Clinical Trials (journal), 149
Argentina, 12, 127
arthritis, 58
Asia: and globalization of clinical trials, 7, 9, 10–11, 12; HIV/AIDS in, 82, 92, 167; and risk-benefit analysis, 167. See also specific nation
Association for Consumers’ Action on Safety and Health, 113
asthma, 14
AstraZeneca, 9, 55, 56, 60, 137
Atomic Energy Commission, 67–68
atorvastatin (Lipitor), 53
Australia, 22, 40, 68–69
Avorn, Jerry, 31
Ayers, Marc, 20, 21
AZT (Retrovir). See zidovudine
bacterial infections, 38
Bahlman, Bill, 22
Bal, Arun, 113
Bangladesh, 148
Baraff, Larry, 152–53, 162
Bayer, 37, 55, 56
Bayh-Dole Act, 43
Baycol. See cerivastatin
Beckerman, Karen, 140
Beecher, Henry K., 73
Belgian Congo, 72
Belmont Report, 75, 76, 154
Benatar, Solomon, 153, 166, 173–74, 175–76
Berkley, Seth, 171
Bernard, Claude, 62–63
Bernard, Gordon, 123, 126
“best proven” methods, 77, 97–98, 133, 138, 141, 153, 168
Biggar, Robert, 101
biotech revolution, 42
birth defects, 41–42. See also thalidomide (Contergan)
Black, Robert, 34
blockbuster drugs, 45, 46–47, 51–53, 61. See also specific drug
blood pressure, 47, 59
Bodenheimer, Thomas, 6, 158
Boehringer Ingelheim, 15, 86, 108, 109, 156–57
Botswana, 111, 167
Boyd, Mark, 64
Boyer, Herbert, 42–43
Brazil, 9, 11, 15, 127, 148
breast cancer, 1, 161
Bristol-Myers Squibb, 47, 53, 152, 154
British Medical Journal, 114, 128, 138
Bulgaria, 9
buprenorphine (Subutex), 141
Buxton, Peter J., 74
calcium channel blockers, 59
Cambodia, 166–67, 168
Cameroon, 167, 168, 169
Canada, 130
cancer: failure in research about, 5; and globalization of clinical trials, 5, 8; and humans as test subjects, 73; and informed consent, 160, 161; reluctance of Americans to participate in trials for, 4, 5; and risk-benefit analysis, 165; “war” on, 165. See also type of cancer
cardiovascular disease, 1, 8, 14, 41, 44, 45, 165
ceftriaxone (Rocephin), 146, 152
Center for AIDS Prevention Studies, 89, 95
Centers for Disease Control (CDC): and HIV/AIDS, 78, 81, 88, 89, 90–91, 94, 95, 97, 111; and humans as test subjects, 73–74; and risk-benefit analysis, 167, 168, 170
Centers for Medicare and Medicaid, 126
CenterWatch, 3, 8, 118, 149
Centocor, 121–22
Centoxin, 121–22
cerebrovascular diseases, 165
cerivastatin (Baycol), 53, 55
cervical cancer, 1
cetirizine (Zyrtec) 50
Chemie Grunenthal, 39, 40
children: and ethics, 134; and HIV/AIDS, 26–29, 32–33, 34, 85, 93–94, 101; as test subjects, 67–68, 72, 73, 77; in India, 116; and informed consent, 146, 152, 157, 163; lung-impaired, 134; and meningitis, 144–46, 152, 163; in Nigeria, 144–46, 152, 163; and nitazoxanide-placebo study, 26–29, 32–33, 34; sulfa deaths of, 38; in Zambia, 26–29, 32–33, 34. See also pregnant women
Chile, 9, 127
China, 14, 69, 117, 140–43, 149, 152
Chiron, 116
chloramphenicol, 146
cholera, 12, 69, 145
cholesterol, 45, 47, 53, 55
Chotchatmala, Wivat, 149
Chowpatty Medical Centre (CMC) (India), 118–19
cimetidine (Tagamet), 45
Cipla, 15
Clarinex. See desloratadine
Claritin. See loratadine
Clark, Taliaferro, 64
Clinical Solutions, 159
clinical trials: breadth of data about, 75; conflicts of interest in, 83–85; cost of, 4, 5, 8, 9, 47, 96; decline in U.S.–based, 7; duration of, 4, 47; emergence of controlled, 6; exclusion of pregnant women from, 41–42; globalization of, 1–17, 76, 133, 135–36; guidelines for conducting in India, 113; Indian incentives for industry-sponsored, 116–17; legal codification of, 6; public mistrust of, 4, 154; purpose of, 36–37, 174–78; reluctance of Americans to participate in, 3–5, 9; size and scope of, 41, 161; as time-consuming, 46. See also specific topic
clinics: incentives/money for, 158–59, 172–73; and risk-benefit analysis, 172–73
Clinton (Bill) administration, 102
Coca-Cola, 13, 15
Cohen, Jon, 84, 85
concentration camps, 69–71, 77
conflict of interest, 18–19, 137, 158–61
Contergan. See thalidomide
continuing medical education, 55, 56
contraceptives, 112, 148
contract research organizations (CROs): emergence of, 6–7; and globalization of clinical trials, 7, 8, 9, 127; and HIV/AIDS, 104; and informed consent, 149, 158–59, 162; and outsourcing to India, 117; pool of potential subjects used by, 7; reputation of, 36; and risk-benefit analysis, 170, 171
Coovadia, Hoosen, 82
Coovadia, Jerry, 94
Côte d’Ivoire, 88
Council for International Organization of Medical Sciences, 139
Covance, 6, 9
Crestor. See rosuvastatin
Critical Care Medicine (journal), 128
Croatia, 9, 127
CROs. See contract research organizations
cryptosporidiosis. See nitazoxanide
CT scans, 9
Cymbalta. See duloxetine
Daily International Pharma Alert, 116
Darder, Marta, 16–17
Declaration of Helsinki (1975), 75–76, 77, 92, 132–34, 135, 136–39, 140, 146, 168
Deeb, Mirryena, 102
DeMets, David L., 46–47
dengue fever, 12
DeRosia, Dennis, 4
desloratadine (Clarinex), 60
diabetes, 8, 14, 33, 118
Diamond, Aaron, 96
diarrhea, 116
Dickert, Neal, 157
DiGiorgio, Mark, 50
doctors. See physicians
Dole, Bob, 51
dosage, drug, 55–56
double-blind studies, 30
double standard, 132–43
DPT immunizations, 12
drotrecogin alfa (Xigris) 120–31
drug industry: accountability in, 176–78; growth of, 36–61; and independence of academic researchers, 57–60; in India, 114–15; multinational, 3, 14–15, 115, 116, 118; physicians as checks on, 50–51; pressure on physicians by, 55–57; problems faced by, 3; profits of, 39, 79, 120, 176; public confidence in, 178; regulation of, 36–38, 39, 40–41, 42, 48, 75, 76; reputation of, 37, 38, 39–41, 42; as special interest, 178. See also specific corporation or topic
Drug Information Association, 136–37
drugs: access to, 137, 138, 170–71, 176; adverse reactions to, 61; cost of, 74, 122–23, 127, 131, 169; essential, 60, 141; fake/substandard, 115; illicit marketing of, 115; pricing of, 38–39; side effects of, 47, 48–50, 115; withdrawal of approved, 42, 48. See also specific drug
duloxetine (Cymbalta), 155–56
DuPont, Herbert, 27–28
Eastern Europe, 1–2, 7. See also specific nation
effectiveness, drug, 41, 46, 50, 56
Egypt, 28, 33, 127
Eichacker, Peter Q., 126
Eli Lilly: blockbuster drugs from, 45; and duloxetine (Cymbalta), 155–56; incentives/money paid by, 155–56; and informed consent, 155–56; and outsourcing to India, 116, 118, 120–21, 126–31; prisoner studi
es of, 154; problems faced by, 3; and fluoxetine (Prozac), 45, 53, 121; reputation of, 37; and drotrecogin alfa (Xigris), 120–31
emtricitabine (Emtriva) 107–8
Emtriva. See emtricitabine
encainide, 47
Enkaid. See encainide
Epivir. See lamivudine
erectile dysfunction (ED), 51–53, 60–61, 118
esomeprazole (Nexium), 60
Estonia, 9, 147–48
ethics: and accountability in drug industry, 178; calibrating codes of, 132–43; and double standard for poor subjects, 132–43; and globalization of clinical trials, 133, 135–36; and HIV/AIDS, 91, 93, 95, 96; and informed consent, 71, 137, 142, 143, 152, 153, 156–58; as limitation on clinical studies, 175; and main purpose of medical research, 177; and outsourcing to India, 112, 113, 114, 117–18, 120; and placebo studies, 18–19, 133, 134, 137, 139, 141; and principles governing clinical trials, 70–76; and risk-benefit analysis, 173–74; and substandard care, 132, 140–41. See also “Declaration of Helsinki” (1975); Nuremberg Code
European Group on Ethics in Science and New Technologies, 139
experimentation: in ancient times, 5–6; depersonalization of, 178; therapy differentiated from, 158–59, 161. See also clinical trials
Eyetech, 5
Faden, Ruth, 132, 165
fast food, 13
Fauci, Anthony, 84
Femara. See letrozole
Fernald School (Massachusetts): children as test subjects in, 67–68
fertility, 113
fexofenadine (Allegra) 49–50
flecainide (Tambocor), 47
Fleming, Thomas R., 46–47
fluconazole, 58
fluoxetine (Prozac), 45, 53, 121, 155
Food and Drug Administration (FDA), U.S.: and accountability in drug industry, 177–78; and advertising, 48–50; approval of foreign investigators by, 7; compassionate use program of, 21; criticisms of, 46; and Declaration of Helsinki, 133–34, 135; and ethics, 132, 133–34, 135, 137; flexibility for approval by, 46–47; and globalization of clinical trials, 3, 7; and HIV/AIDS, 78, 81, 106, 109–10; increase in applications to, 43; and informed consent, 156–57, 162–63; and legislation of 1962, 41; and main purpose of clinical trials, 176; and “me-too” drugs, 53, 55, 60; and outsourcing to India, 113, 119; placebo-controlled studies as preferred by, 32; and risk-benefit analysis, 171; safety and effectiveness proof for approval by, 41; standards/guidelines of, 3, 58, 133–34, 135, 176, 177–78; streamlining of review process by, 44, 47–48; and weakening of regulations, 46; withdrawal of drugs approved by, 42, 48. See also specific person or drug
Food and Drug Act (1906), 37
Food and Drug Act (1962), 40–41, 42, 154
Food, Drug and Cosmetic Act (1938), 38
foreign investigators: FDA approval of, 7
Fost, Norman, 94
Framingham Heart Study, 45
France, 130
Francis, Don, 85, 96
Fromell, Greg, 6
Furberg, Curt, 59
Gallo, Robert, 82, 101
Garrett, Laurie, 12, 78
Gates (Bill and Melinda) Foundation, 165–66, 167
Gay Men’s Health Crisis, 142
Gazi, Costa, 102
Gelles, Jonathan, 79
Gelsinger, Jesse, 160
Genentech, 4, 43, 83–84, 105, 161
generic drugs, 44, 102, 111, 116, 123
genetics revolution, 42, 57
Germany, 69–71, 73, 77, 130
Ghana, 12, 167
Gilead Sciences, 107–8, 167–70
Gish, Oscar, 11
GlaxoSmithKline, 8, 9, 115, 116, 118, 137, 154. See also AZT
Global Campaign for Microbicides, 169
globalization: of clinical trials, 1–17, 76, 133, 135–36
gonorrhea, 67
Gore, Al, 98
government experiments: and humans as test subjects, 67–72. See also specific government
gp120 vaccine, 83–84, 85, 96
Grady, Christine, 157
Groote Schur Hospital (Cape Town, South Africa), 17, 101
Guerrini, Anita, 70
Guess, Harry, 138
Guidelines for the Conduct of Research Involving Human Subjects (NIH), 61
Guinea Pig Zero (journal), 157
guinea pigs. See test subjects
Gulati, Rajiv, 131
Gulhati, Chandra, 34, 115
Haiti, 101, 135, 148
Halsey, Neal, 93, 94
Harrington, Mark, 169
Harvard Medical School, 161
Hashwani, S., 151
Health and Human Services, U.S. Department of, 7, 157, 159
health care: cost of, 60, 74, 82
heart attacks, 47, 55, 59
heart disease. See cardiovascular disease
Heart Disease Weekly, 56
Heller, Jean, 74
hepatitis, 73, 116
Herceptin, 4, 161
Hilts, Philip, 18, 38, 78
Hinduja Hospital (Mumbai, India), 120–21
Hirsch, Laurence, 138
HIV/AIDS: access to drugs for, 81–83, 94; conferences/meetings about, 89–90, 94, 95, 111; and conflicts of interest in clinical trials, 83–85; cost of drugs for, 79, 80, 81, 82–83, 89, 95, 99, 102, 105, 108, 110–11; denialism of, 100–111; emergence of, 100; and ethics, 133, 139–43; and globalization of clinical trials, 8, 13, 14, 15, 16; increase in research about, 76; and informed consent, 107, 109–10, 148, 149; isolation of cause of, 78; lack of subjects for trials for, 80; and megamarkets for drugs, 44; and outsourcing to India, 116; and placebo studies, 19–29, 31–35, 80, 87–91, 93–95, 97–98, 106, 107, 110, 111; and risk-benefit analysis, 166–70, 171; second rate treatments, 111; side effects of drugs for, 47; and substandard care, 77–99. See also nevirapine; nitazoxanide; VaxGen
HIVNET 012 trial, 97–98, 108, 109–10, 139
Ho, David, 92–93, 96
Hoescht Marion Roussel, 48–50
Hollinger, Mannfred, 100
Hollis-Eden, 105, 106
Hollis, Richard, 105, 106, 111
homeless, 154–55
Hopkins, Scott, 145–46
Horrobin, David, 5
Horton, Richard, 142
hospitals: in India, 116. See also specific hospital
Human, Delon, 133, 136–138
human rights, 76, 91, 103, 110, 164, 168, 175
Human Rights Watch, 168
Hungary, 1
hypertension, 8, 14, 44
Ijsselmuiden, Carel, 10
Immunitin (HE2000), 105–6, 107
Imperial College (London, England), 154
impotence: See also sildenafil (Viagra)
incentives/money: for Indian clinical trials, 116–17; and informed consent, 149, 154–57, 158–61; for physicians, 158–60, 161, 173; and risk-benefit analysis, 171–74
India: as British colony, 11; drug industry in, 114–15; ethics in, 112, 113, 114, 117–18, 120; generic manufacturers in, 111; and globalization of clinical trials, 7, 8, 9, 12, 14, 15, 119, 120–21, 126–30; HIV/AIDS in, 116; humans as test subjects in, 112–13; incentives/money in, 172–73; informed consent in, 151; licensing in, 114; medical schools in, 113–14; medical services in, 115–16; and nitazoxanide-placebo study, 34; outsourcing to, 112–31; and risk-benefit analysis, 171, 172–73
Indian Council of Medical Research, 113
Indian Medical Association, 114, 120
Indiana Bible College, 155–56
infant mortality, 12, 74
infectious diseases, 72–73. See also specific disease
informed consent, 144–63; barriers to, 150–52; and children, 146, 152, 158; and conflict of interest, 158–61; and deliberate misleading of subjects, 152, 158–62; and “don’t ask, don’t tell” atmosphere, 147; and ethics, 71, 137, 142, 143, 152, 153, 156–57; and HIV/AIDS, 107, 109–10, 148, 149; and humans as test subjects, 64, 71, 72, 75–76; as impossible standard, 162–63; and incentives/money, 149, 154–57, 158–60, 161; legis
lation about, 41; and main purpose of medical research, 176, 177; and methods for bridging gulf between investigators and patients, 150–51; as not voluntary, 148; and outsourcing to India, 113, 119–20; and oversight committees, 75; and physicians, 151–52; and placebo studies, 154, 156, 160–61; and therapy versus experimentation, 158–59, 161; in U.S., 153–57, 158, 159–60
institutional review boards (IRBs), 75–76, 85, 117
insulin: Boyer’s work on, 42–43
International Military Tribunal (Nuremberg, Germany), 69–71
International Monetary Fund (IMF), 12, 13, 25
International Nursing Review, 151
intravenous drug users, 140–42, 143, 167, 168
invasive procedures, 8–9
iron supplements, 148
irregular heartbeats, 47
Ivory Coast. See Côte d’Ivoire, 88
Ivy, Andrew, 70–71, 72
Jackson, Jay Brooks, 85–88, 97–99, 108, 109–10, 111, 139, 140–42, 171
Japan, 69, 149
Jesani, Amar, 117–18
Jews, 68–69
Johns Hopkins University, 88, 93, 96, 171
Johnson, Traci, 155–56
Journal of Infectious Diseases, 107
Journal of Medical Ethics, 139
Journal of the American Medical Association (JAMA), 57, 72
Journal of the Medical Association of Thailand, 148
Journal of the Royal Society of Medicine, 151
journals: drug advertising in, 48. See also specific journal
justice, 75, 76
Kaninda, Anne-Valerie, 150
Kano Infectious Disease Hospital (Nigeria), 146, 150, 172
Kapadia, Farhad, 119, 120–21, 127, 131, 162
Katz, Jay, 71
Kelder, Indrek, 147–48
Kelly, Paul S., 28, 29, 31, 32–33
Kennedy, Donald, 165
Kennedy, John F., 40
Kenya, 12, 101–2, 149
Koop, C. Everett, 159
Koprowski, Hilary, 72
Kramer, Larry, 78
Krugman, Saul, 73
Kumar, Vijai, 9
Kusel, Elaine, 152
kwashiorkor, 101
labels: listing of ingredients on, 37
Lallemant, Marc, 91, 93, 98, 111
lamivudine (Epivir), 107
Lancet (journal), 5, 94, 142
Lasagna, Louis, 32
Latin America, 7, 9, 12, 14, 134, 151–52. See also specific nation
Latinos: as test subjects, 72
Latvia, 9
Lebanon, 127
Lee, John C.M., 152
Leff, Ben, 155, 156
leprosy, 112
letrozole (Femara), 113
Levine, Robert, 132–33, 136
Levy, Jean-Paul, 84
