The researchers acknowledge the federal grants awarded in their published report (Scc, Pine, et al, 1997; and Halperin, et al, 1997): MH-16432; MH-43878; MH-01391; MH-01039; 1 RO1 MH-46448; 5MO1 RR0071. Factors contributing to unethical experimental exploitation -- especially of vulnerable persons, including children, who are unable to refuse: (1) Federal regulations are silent about what is not permissible in human experimentation particularly in cxperiments involving those whose condition renders them “decisionally impaired," persons incapable, therefore, of protecting themselves from unwanted experimentation. (2) Federal regulations leave the entire human research enterprise in the hands of researchers and their colleagues on Institutional Review Boards (IRBs). This includes evaluation of the merit of the proposed research, the design of the protocol, the procedures, risks, selection of subjects and capacity assessment, determining what is disclosed in informed consent documents and the procedures for obtaining consent -- monitoring the subjects' well-being and reporting "adverse incidents" are also left to their discretion. This absolute power in the hands of researchers over helpless and disenfranchised persons gave rise to major conflicts of interest. Indeed, three federal agencies, the General Accounting Office, the Office of Protection from Research Risks, and the Office of the Inspector General each concluded after their separate investigations, that IRBs often do not, in fact, examine even the high risk human studies they approve. IRB are almost exclusively composed of colleagues of the researchers whose own and the institution's interest in obtaining lucrative research contracts can easily override their sense of moral responsibility toward vulnerable human subjects. (3) the absence of accountability for causing human subjects undue pain and torment (4) a powerful consortium of “confluent” interests has set the practice standards for psychiatric research and given themselves permission to use uncomprchcnding, “decisionally impaired” patients as mcans to their end: the American College of Neuropsychopharmacologists (ACNP) and NIMH who are actively lobbying against regulatory reforms such as independent oversight. Page 2 of 12 NIMH bears the major responsibility for current ethical violations in psychiatric research: As the authorized federal agency approving federal mental health grant proposals involving mentally disabled human subjects and children, NIMH is also entrusted to ensure that "the rights and safety of participants of clinical rcscarch" are protected. However, NIMH is contradicting public policy by supporting, conducting and funding experiments in which human rights are violated, and the welfare of disabled subjects endangered. The agency's failure to protect "the rights and safety" of disabled research subjects, as is its public responsibility, arises from a fundamental, though undisclosed conflict of interest: NIMH's leading researchers and administrators are members of ACNP, some actually serving on its governing Council, formulating lobbying strategies against federal regulatory safeguards. This conflict of interest is reflected in NIMH's January 30, 1998 response to our requests, under the Freedom of Information Act (FOIA), for Informed Consent documents involving symptom-provoking experiments conducted at, or funded by NIMH: "NIMH is not a repository for informed consent documents; grantee institutions are not routinely required to submit copies of these records in clinical research studies." Who then, ensures that ethical and legal safeguards are followed and that Informed Consent forms fully disclose the risks involved to comprehending subjects? NIMH's failure to review Informed Consent documents demonstrates the agency's disregard for the rights and welfare of human subject and an absence of monitoring and accountability -- thereby validating the need for oversight by independent auditors. Citizens for Responsible Care in Psychiatry & Research consequently call for a thorough, independent examination of the nature and conduct of neuropsychiatric experiments so that meaningful protections are enacted. As the attached list of over 100 published symptom-provocation experiments shows, such experiments are funded by the federal government and conducted at premier academic medical research centers, Veterans Affairs hospitals and the National Institute of Mental Health. Who is accountable for the conduct of biomedical research on vulnerable persons such as Breier A, Su TP, Saunders R, Carson RE, Kolachana BS, de Bartolomeis A, Weinberger DR, Weisenfeld N, Malhotra AK, EckelmanWC, and Pickar D: "Schizophrenia is associated with elevated amphetamineinduced synaptic dopamine concentrations: evidence from a novel positron emission tomography method," Proceedings National Academy of Science, 1997, 94:2569-74 Breier A, Malhotra AK, Pinals DA, Weisenfeld NI, Pickar D: “Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers,” American Journal of Psychiatry, 1997, 154: 805-811 Daniel DG; Weinberger DR; Jones DW; Zigun JR; Coppola R; Handel S; Bigelow LB; Goldberg TE; Berman KF; Kleinman JE: "The cffect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia," Journal of Neurosciencc, 1991, 11: 1907-1917 Goldberg TE; Bigelow LB; Weinberger DR; Daniel DG, Kleinman JE: "Cognitive and behavioral cffects of the coadministration of dextroamphetamine and haloperidol in schizophrenia," American Journal of Psychiatry 1991 Jan; 148 (1): 78-84 Goodwin, FK, "Psychiatric Side Effects of Levodopa in Man," Journal of the American Medical Association, Dec. 27, 1971, 218:1915-1920 Goodwin FK, Sack RL: "Affective disorders: the catecholamine hypothesis revisited," Frontiers in Catecholamine Research, 1973, Pergamon Press, pp. 1157-1164 Lucas PB, Gardner DL, Wolkowitz OM Cowdry RW: "Dysphoria associated with methylphenidate infusion in borderline personality disorder,” American Journal of Psychiatry, 1987, 144:1577-1579 Malhotra, AK, Pinals DA, Adler CM, Elman I, Clifton A, Pickar D, Breier, A: "Ketaminc-Induced Exacerbation of Psychotic Symptoms and Cognitive Impairment in Neuroleptic-Free Schizophrenics," Malhotra, A.K, Adler, C. M., Kennison, S.D., Elman, L, Pickar, D, Brcicr, A: “Clozapine blunts N-Methyl-dAspartate antagonist-induced psychosis: a study with Ketamine, “ Biological Psychiatry, 1997b, 42: 664-668 Prien RF, Cole JO, Belkin NF: "Relapse in chronic schizophrenics following abrupt withdrawal of tranquilizing medication,” British Journal of Psychiatry, 1969, 115: 679-686 Schulz SC; Cornelius J; Schulz PM; Soloff PH: "The amphetamine challenge test in patients with borderline disorder," American Journal Psychiatry, 1988 Jul; 145 (7): 809-14 Page 4 of 12 Department of Psychiatry, University of Illinois at Chicago: Sharma RP; Janicak PG; Bissette G; Nemeroff CB: TITL: CSF neurotensin concentrations and antipsychotic treatment in schizophrenia and schizoaffective disorder, American Journal of Psychiatry 1997, 154: 1019-21 NIH-GRANT-NUMBER: MH-48888MHNIMH;. MH-39415MHNIMH. Sharma RP; Shapiro LE; Kamath SK; Soll EA; Watanabe MD; Davis JM: "Acute dietary tryptophan depletion: effects on schizophrenic positive and negative symptoms," Neuropsychobiology 1997, 35: 5-10 NIH-GRANT-NUMBER: MH48888MHNIMH. Sharma RP; Dowd SM; Davis JM; Janicak PG: "Age of illness onset and schizophrenic symptomatology during an inpatient washout period," Schizophrenia Research, 1996, 20: 295-300 NIH-GRANT-NUMBER: MH 48888MHNIMH. Sharma RP; Bissette G; Janicak PG; Davis JM; Nemeroff CB: "Elevation of CSF somatostatin concentrations in mania." American Journal of Psychiatry 1995, 152: 1807-9 NIH-GRANT-NUMBER: MH-48888MHNIMH. MH-42088MHNIMH. MH-39415MHNIMH. Sharma RP; Faull K; Javaid JI; Davis JM: "Cerebrospinal fluid levels of phenylacetic acid in mental illness: behavioral associations and response to neuroleptic treatment." Acta Psychiatry Scandinavia 1995, 91: 293-8 NIH-GRANT-NUMBER: MH-48888MHNIMH. MH-30854MHNIMH. Sharma RP; Javaid JI; Faull K; Davis JM; Janicak PG: “ CSF and plasma MHPG, and CSF MHPG index: pretreatment levels in diagnostic groups and response to somatic treatments." Psychiatry Research, 1994, 51: 51-60 Pandey GN; Pandey SC; Dwivedi Y; Sharma RP; Janicak PG; Davis JM: "Platelet serotonin-2A receptors: a potential biological marker for suicidal behavior." Am J Psychiatry 1995 Jun; 152 (6): 850-5 NIH-GRANT-NUMBER: MH-36169MI INIMH. Pandey SC; Sharma RP; Janicak PG; Marks RC; Davis JM; Pandey GN: "Platelet serotonin-2 rcceptors in schizophrenia: effects of illness and neuroleptic treatment” Psychiatry Research, 1993 48: 57-68 NIH-GRANT-NUMBER: RO1-MH36169MHNIMH. Pandey GN; Sharma RP; Janicak PG; Davis JM: “Monoamine oxidase and cortisol response in depression and schizophrenia." Psychiatry Research 1992 Oct; 44 (1): 1-8 Sharma, RP, Javaid, JI, Pandey, GN, Jainacak, PG, Davis, JM, “Behavioral and biochemical effects of methylphenidate in schizophrenic and nonschizophrenic patients," Biological Psychiatry, 1991, 30:459-66 Sharma RP, Javaid JI, Pandey GN, Easton M, Davis JM: "Pharmacological effects of methyl-phenidate on plasma homovanillic acid and growth hormone," Psychiatry Research, 1990, 32: 9-17 University of Cincinnati College of Medicine: Strakowski SM, Sax KW, Setters MJ, Stanton SP, Keck Jr. PE: “Lack of enhanced response to repeated d-amphetamine challenge in first-episode psychosis: implications for a sensitization model of psychosis in humans,” Biological Psychiatry, 1997, 42: 749-755 NIH Public Service GRANT: MOIRR08084 Duke University Medical Center Mathew RJ, Wilson WH: "Changes in cerebral blood flow and mental state after amphetamine challenge in schizophrenic patients," Neuropsychobiology, 1989, 21:117-123 NIH-GRANT-NUMBER: MH42114MHNIMH. Mathew RJ, Wilson WH: “Cerebral blood flow responses to inhaled carbon dioxide in schizophrenia,” Acta Psychiatry Scandinavia, 1990, 81: 497-506 Hillside Hospital, Long Island Jewish Medical Center: Jody, D, Lieberman, JA, Geisler, S, Szymanski, S, Alvir, JM, “Behavioral response to methylphenidate and treatment outcome in first episode schizophrenia," Psychopharmacol Bull, 1990, 26:224-30 Koreen, AR, Lieberman, JA, Alvir, J, Chakos, M, “The behavioral cffcct of m-chlorophenylpiperazine (mCPP) and methylphenidate in first episode schizophrenia and normal controls," Neuropsychopharmacology, 1997, 16:61-8 NIH-GRANT-NUMBER: MH-41646MHNIMH. MH-41960MHNIMH. MH-00537MHNIMH. Levy, DL, Smith, M, Robinson, D, Jody, D, Lerner, G, Alvir, J, Geisler, SH, Szymanski, SR, Gonzalez, A, Mayerhoff, DI, et al. "Methylphenidate increases thought disorder in recent onset schizophrenics, but not in normal controls," Biological Psychiatry, 1993, 34:507-14 Lieberman JA, Kane JM, Gadalcta D, et al: "Methylphenidate challenge as predictor of relapse in schizophrenia," American Journal of Psychiatry. 1984, 141: 633-638 Lieberman JA; Kane JM; Sarantakos S; Gadaleta D; Woerner M; Alvir J; Ramos-Lorenzi J "Prediction of relapse in schizophrenia.” Archives of General Psychiatry, 1987, 44: 597-603 Lieberman JA, Kane JM, Alvir J: "Provocative tests with psychostimulant drugs in schizophrenia," Lieberman JA; Alvir JM; Woerner M; Degreef G; Bilder RM; Ashtari M; Bogerts B; Mayerhoff DI; Geisler SH; Loebel A; et al: "Prospective study of psychobiology in first-episode schizophrenia at Hillside Hospital," Schizophrenia Bulletin, 1992, 18: 351-7 NIH-GRANT-NUMBER: MH-41646MHNIMH, MH-00537MHNIMH. MH-41960MHNIMH. Lieberman, JA: "Prediction of outcome in first-episode schizophrenia," Journal of Clinical Psychiatry, 1993, 54 Suppl: 13-17 NIH-GRANT-NUMBER: MH-3880MHNIMH. MH-00537MHNIMH. Lieberman JA; Jody D; Alvir JM; Ashtari M; Levy DL; Bogerts B; Degreef G; Mayerhoff DI; Cooper T Page 6 of 12 |