Abstract
Terminating an investigational drug in a clinical trial carries with it certain risks for subjects that are too often disregarded in the research protocol despite clinical indications that this critical posttrial period be anticipated prior to initiating the study. The potential for adverse consequences, as well as ethical considerations underlying all human experimentation, make it essential to consider special areas of concern relevant to the postadministration phase of the clinical trial. There are specific ethical and moral rights of subjects which may be jeopardized at trial conclusion, and there are direct harmful effects that may occur only in the posttrial period. These two concepts may be further divided into the following separate topics that warrant individual discussion:
-
1
The failure to include the posttrial period in the requirements of informed consent.
-
2
The failure to recognize that psychological and physical difficulties may result from the emotional consequences of loss of the trial agent.
-
3
The failure to consider potentially negative and harmful physical effects subsequent to agent withdrawal.
-
4
The failure to take account of long-term effects of an agent’s administration that are neither predictable nor foreseeable from short-term trials.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Alderman, E. L., 1974, Coronary artery syndromes after sudden propranolol withdrawal, Ann. Intern. Med. 81:625–627.
Beecher, H. K., 1955, The powerful placebo, JAMA 5(159):1602–1606.
Benson, H., and McCallie, D. T., 1979, Agina pectoris and the placebo effect, N. Eng. J. Med. 300:1424–1429.
Brody, H., 1980, Placebos and the Philosophy of Medicine: Clinical, Conceptual, and Ethical Issues, University of Chicago Press, Chicago.
Burden, A. C., and Alexander, C. P. T., 1976, Rebound hypertension after acute methydopa withdrawal, Br. Med. J. 1:1056–1057.
Cousins, N., 1981, Anatomy of an Illness as Perceived by the Patient, p. 176, Bantam, New York.
Editorial, 1976 The heterogeneity of “psychosomatic” disease, Psychosom. Med. 38:371-372.
Finkel, M. J., 1974, Investigational drug studies: Recent FDA efforts, in: Principles and Techniques of Human Research and Therapeutics (G. F. McMahon, ed.), pp. 45–49, Futura, New York.
Finkel, M. J., 1980, The FDA’s classification system for new drugs: An evaluation of therapeutic gain, N. Engl. J. Med. 302(3):181–183.
FDA Drug Bulletin, 1980, February 10, Number 1, pp. 3-4. Goldberg, H. L., and Finnerty, R. J., 1979, Comparative efficacy of torfisopan and placebo, Am. J. Psychiatry 136:196–199.
Healy, M. J. R., 1978, New methodology in clinical trials, Biometrics 34:709–710.
Hill, A. B., 1963, Medical ethics and controlled trials, Br. Med. J. 1:1043–1049.
Hodges, R. M., 1974, Ethical considerations in clinical research, in: Principles and Techniques of Human Research and Therapeutics (G. F. McMahon, ed.), pp. 31-38, Futura.
Lasagna, L., 1975, Clinical trials of drugs from viewpoint of the academic investigator (a satire), Clin. Pharmacol. Ther. 18:629–633.
Lasagna, L., and Wardell, W. M., 1975, Commentary: The FDA, politics, and the public, JAMA 232:141–142.
Lebacqz, K., and Levine, R. J., 1977, Respect for persons and informed consent to participate in research, Clin. Res. 25:101–107.
Letters to the editor, 1979, N. Engl. J. Med. 301:1179–1181.
Levine, J. D., Gordon, N. C., and Fields, H. L., 1978, The mechanism of placebo analgesia, Lancet 2:654–657.
Lorber, M., 1975a, When is double-blind evaluation improper? J. Clin. Pharmacol. 15:84.
Lorber, M., 1975b, Delaying double-blind drug evaluation in usually fatal diseases (Pelter), N. Engl. J. Med. 293:508–509.
Mundy, G. R., 1974, Current medical practice and the Food and Drug Administration: Some evidence for the existing gap, JAMA 229:1744–1748.
McNair, D. M., Gardos, G., Haskell, D. S., and Fischer, S., 1979, Placebo response, placebo effect, and two attributes, Phycopharmacology, 63:245–250.
Peck, A. W., 1975, Letter and ethics of randomized trials, N. Engl. J. Med. 293:1270.
Sadusk, J. F., Jr., 1974, The effect of drug regulation on the development of new drugs, in: Principles and Techniques of Human Research and Therapeutics (G. F. McMahon, ed.), pp. 58–68, Futura, Mt. Kisco, N.Y.
Schiffrin, M. J., 1977, The regulation of clinical research, J. Clin. Pharmacol. 17:686–690.
Shand, D. G., and Wood, A. J. J., 1978, Propranolol withdrawal syndrome—Why? (editorial), Circulation 58(2):202–203.
Shapiro, A. K., 1964, Etiological factors in placebo effect, JAMA 187:712–714.
Shapiro, A. K., 1968, Study of the placebo effect with a placebo test, Comp. Psychiat. 9:118–137.
Strauss, F. G., 1977, Withdrawal of antihypertensive therapy. Hypertensive crisis in renovascular hypertension, JAMA 238:1734–1736.
Trout, M. E., 1976, Ethics of clinical research, Conn. Med. 40(4):201–204.
United States Department of Health, Education, and Welfare, 1977, Guidelines for the clinical evaluation of anti-anginal drugs, HEW(FDA) 78-3047.
Wardell, W. M., 1974, Drug development, regulation and the practice of medicine, JAMA 229:1457–1461.
Webster, J., 1974, Withdrawal of antihypertensive therapy, Lancet 2:1381–1382.
Wolf, S., 1959, Placebos, Res. Pub. Assoc. Res. Nerv. Ment. Dis. 37:147–161.
Zelen, M., 1979, New design for randomized clinical trials, N. Eng. J. Med. 300:1242–1245.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1982 Plenum Press, New York
About this chapter
Cite this chapter
Roginsky, M. (1982). Clinical Trials of New Drugs Special Problems. In: Greenwald, R.A., Ryan, M.K., Mulvihill, J.E. (eds) Human Subjects Research. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4157-4_14
Download citation
DOI: https://doi.org/10.1007/978-1-4684-4157-4_14
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-4159-8
Online ISBN: 978-1-4684-4157-4
eBook Packages: Springer Book Archive