The Declaration of Helsinki and Clinical Trials: A Focus on Placebo-Controlled Trials in Schizophrenia
American Journal of PsychiatryPublished 31 January 2003
William T. Carpenter, Paul S. Appelbaum, Robert J. Levine
Citations117
SJR quartileQ1
SJR score5.27
SNIP3.68
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The Helsinki Clarification constitutes an important advance in international approaches to placebo use, requiring protocol-by-protocol judgments on complex issues of clinical research ethics.
Abstract
The Helsinki Clarification constitutes an important advance in international approaches to placebo use, requiring protocol-by-protocol judgments on complex issues of clinical research ethics. When operationalized, it provides review boards with a useful methodology for reaching determinations on the appropriateness of placebo controls in particular studies.
Keywords
MedicineArts and HumanitiesNeuroscience
New England Journal of MedicineEquipoise and the Ethics of Clinical Research
2,305 Citations1987Benjamin Freedman
An alternative concept of equipoise is suggested, which would be based on present or imminent controversy in the clinical community over the preferred treatment, which is satisfied if there is genuine uncertainty within the expert medical community--not necessarily on the part of the individual investigator--about the preferredreatment.
New England Journal of MedicineA Controlled Trial of Arthroscopic Surgery for Osteoarthritis of the Knee
2,113 Citations2002J. Bruce Moseley, Kimberly J. OʼMalley +7 more
In this controlled trial involving patients with osteoarthritis of the knee, the outcomes after arthroscopic lavage or arthro scopic débridement were no better than those after a placebo procedure.
New England Journal of MedicineUnethical Trials of Interventions to Reduce Perinatal Transmission of the Human Immunodeficiency Virus in Developing Countries
885 Citations1997Peter Lurie, Sidney M. Wolfe
The authors oppose the use of placebo-controlled trials as unethical in the search for alternative antiretroviral drug regimens to prevent the perinatal transmission of HIV.
Annals of Internal MedicinePlacebo-Controlled Trials and Active-Control Trials in the Evaluation of New Treatments. Part 1: Ethical and Scientific Issues
881 Citations2000Robert Temple, Susan S. Ellenberg
It is concluded that placebo-controlled trials may be ethically conducted even when effective therapy exists, as long as patients will not be harmed by participation and are fully informed about their alternatives.
New England Journal of MedicineThe Ethics of Clinical Research in the Third World
862 Citations1997Marcia Angell
An essential ethical condition for a randomized clinical trial comparing two treatments for a disease is that there be no good reason for thinking one is better than the other.
New England Journal of MedicineThe Continuing Unethical Use of Placebo Controls
666 Citations1994Kenneth J. Rothman, Karin B. Michels
In these times of raised ethical consciousness, placebo treatments are still commonly used in medical research in circumstances in which their use is unethical.
Law and Human BehaviorThe MacArthur Treatment Competence Study. III: Abilities of patients to consent to psychiatric and medical treatments.
599 Citations1995Thomas Grisso, Paul S. Appelbaum
Three instruments assessing abilities related to legal standards for competence to consent to treatment were administered to patients recently hospitalized for schizophrenia, major depression, and ischemic heart disease, as well as three groups of non-ill persons in the community who were matched with the hospitalized patients on age, gender, race, and socioeconomic status.
New England Journal of MedicineSchizophrenia
516 Citations1994William T. Carpenter, Robert W. Buchanan
Archives of General PsychiatryDecisional Capacity for Informed Consent in Schizophrenia Research
507 Citations2000W. T. Carpenter
The decisional capacity for informed consent in schizophrenic research subjects is ascertained, to determine if reduced capacity relates to specific aspects of psychopathologic features and to test the hypothesis that reduced capacity can be remediated with an educational informed consent process.
Archives of General PsychiatryNeuroleptic Withdrawal in Schizophrenic Patients
439 Citations1995Patricia L. Gilbert
The risk-benefit ratio of neuroleptic maintenance vs withdrawal should be assessed carefully in individual patients, and a slow taper to the lowest effective dosage may be the preferred strategy in many patients.
Annals of Internal MedicinePlacebo-Controlled Trials and Active-Control Trials in the Evaluation of New Treatments. Part 2: Practical Issues and Specific Cases
340 Citations2000Susan S. Ellenberg, Robert Temple
It is concluded that placebo controls are ethical when delaying or omitting available treatment has no permanent adverse consequences for the patient and as long as patients are fully informed about their alternatives.
New England Journal of MedicineThe Ethical Problems with Sham Surgery in Clinical Research
336 Citations1999Ruth Macklin
The recent use of sham surgery in randomized, controlled trials raises three critical questions about research involving human subjects that points to ongoing uncertainties and disagreements in assessing the risks and benefits of research protocols.
New England Journal of MedicineThe Need to Revise the Declaration of Helsinki
262 Citations1999Robert J. Levine
The Declaration of Helsinki requires revision because it is defective in two important respects; it relies on a distinction between therapeutic and nontherapeutic research; all documents that rely on this spurious distinction contain errors not intended by their authors.
NeuropsychopharmacologyEnhancing Informed Consent for Research and Treatment
241 Citations2001Laura B. Dunn
Interventions designed to improve patient understanding of informed consent are reviewed, finding that effective interventions include corrected feedback, multiple learning trials, and more organized or simplified consent forms.
American Journal of PsychiatryInformed Consent: Assessment of Comprehension
205 Citations1998Donna A. Wirshing, William C. Wirshing +3 more
These findings demonstrate that when adequate informed consent procedures are established, schizophrenic research subjects are able to understand and retain critical components of informed consent information.
New England Journal of MedicineIs Placebo Surgery Unethical?
171 Citations2002Sam Horng, Franklin G. Miller
A placebo-controlled trial of arthroscopic surgery for osteoarthritis of the knee and a major difference between the use of placebo surgery 43 years ago and its use today is reported.
Statistical ScienceEthics and Statistics in Randomized Clinical Trials
131 Citations1991Richard M. Royall
It is concluded that statisticians should be more sensitive to the physician's responsibility to the individ- ual patient and should work to improve the planning, execution, and analysis of nonrandomized clinical studies.
The Journal of Law Medicine & EthicsPlacebo Orthodoxy in Clinical Research II: Ethical, Legal, and Regulatory Myths
131 Citations1996Benjamin Freedman, Kathleen Cranley Glass +1 more
In their attack on the prevailing use of placebo controls, Kenneth Rothman and Karin Michels emphasize that this practice stands in violation of the World Medical Association's guidelines on the ethics of human experimentation, most commonly known as the Helsinki Declaration.
American Journal of PsychiatrySymptom Reduction and Suicide Risk Among Patients Treated With Placebo in Antipsychotic Clinical Trials: An Analysis of the Food and Drug Administration Database
130 Citations2001Arif Khan, Shirin Khan +2 more
Assessment of symptoms and risks of suicide and suicide attempts in psychotic patients assigned to receive placebo in clinical trials of three new antipsychotics may help inform discussions about the use of placebo in antipsychotic clinical trials.
American Journal of PsychiatryPerspectives of Patients With Schizophrenia and Psychiatrists Regarding Ethically Important Aspects of Research Participation
127 Citations2000Laura Weiss Roberts, Teddy D. Warner +1 more
This study helps to characterize previously neglected attitudes of psychiatric patients and clinicians toward ethically important aspects of biomedical research participation.
New England Journal of MedicineProposed Revisions to the Declaration of Helsinki — Will They Weaken the Ethical Principles Underlying Human Research?
123 Citations1999T A Brennan
A proposed protocol involving an analysis of human immunodeficiency virus (HIV) infection in pregnant women and subsequent follow-up of their offspring in rural areas of a country in sub-Saharan Africa and some members of the committee thought that the proposed protocol was ethically suspect.
Archives of General PsychiatryThe Rationale and Ethics of Medication-Free Research in Schizophrenia
123 Citations1997William T. Carpenter
The purpose of medication-free protocols in new drug development and nontreatment research and methods for minimizing risk and increasing benefits are proposed as guidelines for the protection of individual subjects are discussed.
The Journal of Law Medicine & EthicsPlacebo Orthodoxy in Clinical Research I: Empirical and Methodological Myths
117 Citations1996Benjamin Freedman, Charles Weijer +1 more
BMJWhen placebo controlled trials are essential and equivalence trials are inadequate
112 Citations1998Martin R. Tramèr, D. John M. Reynolds +2 more
European PsychiatryThe scientific and ethical basis for placebo-controlled trials in depression and schizophrenia: an FDA perspective
93 Citations2001Thomas Laughren
The scientific principles supporting the need for placebo-controlled trials in depression and schizophrenia are reviewed, and preliminary data on failure rates of placebo- controlled trials for these disorders are provided, as illustrations of the application of these principles.
American Journal of PsychiatryEnhancing Comprehension of Consent for Research in Older Patients With Psychosis: A Randomized Study of a Novel Consent Procedure
77 Citations2001Laura B. Dunn, Laurie A. Lindamer +3 more
The enhanced consent method improved comprehension of information relevant for consent in older patients with psychosis, and significantly greater proportion of patients who received the enhanced consent procedure scored 100% on first and second trials of the posttest.
American Journal of PsychiatryPreliminary findings on psychiatric patients as research participants: a population at risk?
69 Citations1981Bárbara Stanley, Michael Stanley +3 more
Although Brief Psychiatric Rating Scale scores clearly differentiated between psychiatric and nonpsychiatric patients, psychopathology did not correlate with willingness to participate in any of the studies.
Schizophrenia ResearchPlacebo-controlled trials in schizophrenia:
68 Citations1999Charles Weijer
While the use of a placebo control may be acceptable in carefully defined circumstances, in most cases theUse of an active control in schizophrenia research is ethically and scientifically preferable.
IRB Ethics and Human ResearchDrug-Free Research in Schizophrenia: An Overview of the Controversy
53 Citations1996Paul S. Appelbaum
The roots of the controversy, the nature both of the disorder and of the research that lies at the core of the debate, and the ethical issues that have been raised are considered.
PubMedPlacebo-controlled clinical trials in multiple sclerosis: ethical considerations. National Multiple Sclerosis Society (USA) Task Force on Placebo-Controlled Clinical Trials in MS.
51 Citations2001Fred Lublin, Stephen C. Reingold
Controlled Clinical TrialsWhen are clinical trials of a given agent vs. placebo no longer appropriate or feasible?
50 Citations1997Robert J. Temple
This article discusses the reasons for such difficulty in placebo-controlled trials--principally, a belief that the effect of a therapy has already been established or the existence of another therapy already proved effective.
Annals of NeurologyPlacebo‐controlled clinical trials in multiple sclerosis: Ethical considerations
50 Citations2001Fred Lublin, Stephen C. Reingold
The Task Force concluded that placebo‐controlled clinical trials in forms of MS for which partially effective therapies exist were ethical, so long as study subjects were fully apprised of the availability of such therapies and were encouraged to pursue them outside of a clinical trial.
Biological PsychiatryThe use of placebo control groups in the assessment of psychiatric drugs: an historical context
44 Citations2000Paul Leber
This essay attempts to explain, within an historical context, not only why placebo is irreplaceable, but why it is often so difficult to communicate its advantages to those unfamiliar with the epistemological aims and methods of controlled clinical trials.
SciencePlacebo-Controls in Short-Term Clinical Trials of Hypertension
41 Citations2001Sana M. Al‐Khatib, Robert M. Califf +4 more
It was found that exposure to placebo-controls in short-term clinical trials of antihypertensives was not associated with an increased risk of serious adverse events, demonstrating the importance of using data to inform decisions about the appropriate selection of controls in clinical trials.
Archives of General PsychiatrySuicide Risk in Placebo vs Active Treatment in Placebo-Controlled Trials for Schizophrenia
39 Citations2003Jitschak G. Storosum, Barbara J. van Zwieten +4 more
Concern about increased risk of suicide or attempted suicide in the placebo group should not be an argument against the conduct of placebo-controlled trials in schizophrenia, provided that appropriate precautions are taken.
Biological PsychiatryThe long-term effects of placebo in patients with chronic schizophrenia
30 Citations1999Richard Jed Wyatt, Ioline D. Henter +1 more
The results indicate that given a sufficiently lengthy recovery period, patients with chronic schizophrenia who go through a placebo phase return to baseline, but that the speed with which they attain that recovery is highly variable.
Law Medicine and Health CareUncertainty in Clinical Research
30 Citations1988Robert J. Levine
It is a fact of life that human beings find it difficult to maintain a consistent, self-conscious appreciation of the extent to which uncertainty accompanies them on their daily rounds and to integrate that uncertainty with whatever certainties inform their conduct.
Annals of the New York Academy of SciencesSome Recent Developments in the International Guidelines on the Ethics of Research Involving Human Subjects<sup>a</sup>
26 Citations2000Robert J. Levine
A new standard is emerging for selecting therapies to be administered to participants in multinational clinical trials and for use as the control “treatment” in such trials, and it is called the “highest attainable and sustainable” therapeutic method.