Presentation on theme: "Ethical Legal/Issues in Human Subject Research II"— Presentation transcript:
1 Ethical Legal/Issues in Human Subject Research II ISD II – Infectious DiseasesBarbara BarrowmanAndrew LatusMarch 7, 2003
2 OutlineSecond of a two-part consideration of legal and ethical issues related to human subject research.In the first session (during the GI course), we considered the following issues:What is research?Rationale for research ethics reviewEthical/legal/regulatory framework for human subject research in Canada
3 Outline (cont.)We also identified a number of major ethical/legal issues in human subject research:1. Scope of acceptable research2. Conflicts of interest3. Consent - informed, voluntary4. Confidentiality, access to information5. Children, mentally incompetent individuals6. Justice in recruitment of subjectsCovered # 2 and 3 in the last session.Today, we will cover the other issues, with an emphasis on #1 and 4.
4 The Tuskegee Syphilis Experiment Clear example of ethically unacceptable research, at least by present standardsSome problems:Lack of informed consent due to deceptionStudy was presented as treatmentTreatments for syphilis were availableConflict of interest caused profound failure in duty to careInjustice in selection of subject populationUnacceptable form of researchClearly illustrates need for a focus on research ethics
5 Some History of Research Ethics Early codes of medical ethics tended to treat research as part of overall code of medical ethicsToday, treated as a distinct areaThomas Percivalfirst code of medical ethics to include requirements concerning research?The use of experimental techniques on patients should be “scrupulously and conscientiously governed by sound reason” and undertaken only after consulting with other physiciansNo mention of seeking the consent of the subjectQuotation is from (Beecher, 1970, 218)
6 Paternalistic Research Ethics “It is our duty and our right to perform an experiment on a man whenever it can save his life, cure him or gain him some personal benefit. … So, among the experiments that might be tried on man, those that can only harm are forbidden. Those that are innocent are permissible, and those that may do good are obligatory.”Claude Bernard, an influential French physiologist,First quotation is from (Grodin, 1992, 125-6)Second quotation is from
7 William Beaumont - Research Ethics Pioneer? Some credit Beaumont with the “oldest … code” specifically focussed on human experimentation (1833):“5. The voluntary consent of the subject is necessary…“6. The experiment is to be discontinued when it causes distress to the subject…7. The project must be abandoned when the subject becomes dissatisfied.”Some dispute about whether code actually existed.First quotation is from (Beecher, 1970)Dispute is explained in (Numbers, 1979)
8 Policy vs. PracticeIronically, some of the earliest and clearest pronouncements on the importance of consent in medical research are to be found in early 20th century GermanyVaccination trials without consent on poor and vulnerable people (abandoned children, prostitutes) led to research regulations in Prussia in 1900A 1931 directive from the German Reich Minister of the Interior forbids “innovative therapy” unless the “subject or his legal representative has unambiguously consented to the procedure in the light of relevant information provided in advance”Quotation is from (Grodin, 1992, 130)
9 The Nuremberg CodeThe modern era in research ethics begins with the Nuremberg Code (1947)Produced as part of the “Doctors’ Trial,” part of the post-W.W.II war crimes tribunalResponse to research atrocitiesDeliberate infection with malaria, smallpox, choleraSexual sterilization experimentsCold temperature experiments
10 From the Nuremberg Code “The voluntary consent of the human subject is absolutely essential.”“This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice … and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision. This latter element requires that before the acceptance of an affirmative decision by the experimental subject there should be known to him the nature, duration and purpose of the experiment; the methods and means by which it is to be conducted; all inconveniences and hazards reasonably to be expected; and the effects upon his health or person which may possibly come from his participation in the experiment.”
11 Not the End of Atrocities Unfortunately, as already noted policy is one thing and practice another. Some examples:Tuskegee Syphilis Experiment ( )Willowbrook hepatitis vaccination experiments ( )CIA funded LSD Experiments in Montreal (1950s & 1960s)Brooklyn Jewish Chronic Disease Hospital cancer study (1963)Note: all involved vulnerable participantsFrom 1963 to 1966, researchers deliberately infected newly admitted "mentally defective" children at the Willowbrook School, a State school in New York, with the hepatitis virus in order to study the natural history of the disease under controlled circumstances. In some cases, parents were not allowed to admit children to the institution unless they agreed to let them participate in the trials.In 1963, physician-investigators at the Jewish Chronic Disease Hospital in Brooklyn, New York, injected cancer cells grown in the lab into people hospitalized with various chronic diseases without informing the people or gaining their consent. In review proceedings, the Board of Regents of the State University of New York found that the trial had not been presented to the hospital's research committee; the researchers were found guilty of fraud, deceit, and unprofessional conduct.In 1970, came the revelation of the Tuskegee experiment. Starting in 1930 and continuing for four long decades, investigators began examining--but not treating--a group of 400 African-American men who had contracted syphilis. The researchers were interested in watching the natural course of the disease as it developed.
12 The Helsinki Declarations 1964 – World Medical Associations Declaration of Helsinki ‘replaces’ the Nuremberg CodeSince revised in 1975, 1983, 1989, 1996 and 20002000 version is contained in handoutLess stringent on consent, allows for proxy consentMost other national and international codes now share this approach
13 Some Major Ethical/Legal Issues in Medical Research Scope of acceptable researchConflicts of interestConsent - informed, voluntaryConfidentiality, access to informationChildren, mentally incompetent individualsJustice in recruitment of subjects
14 Scope of Acceptable Research Two issues:Is there some research which should never be done even if the other concerns on our list can be metXenotransplantation?Embryonic stem cell research?Cloning?
15 Scope of Acceptable Research 2. What do we do with the results of immoral research?“good science is incompatible with bad ethics”?“the Tuskegee study was and remains a key source of information about … syphilis.” (Caplan, 419)“The immorality of research methods should not blind us to the importance of noting and discussing them.” (Caplan, 423)
16 ConfidentialityGeneral obligation of confidentiality owed by physicians to patients extends to researchersEmbodied in research codes, guidelinesResearch Ethics Board’s (REB’s) typically require policies re. storage and destruction of data and samples, anonymization of dataShould also be addressed in consent forms
17 ConfidentialityTension between need to share data and privacy of subjectsBeware of over-promising confidentiality:Access to data for safety and ethics monitoringHealth Protection Branch, Health CanadaPeriodic review by REB’sGeneral legal/ethical obligations to break confidentialityE.g., child abuse revealed during interviewWill be discussed in more detail in subsequent session
18 Confidentiality in Genetic Research Genetics raises problems in that the information gathered through genetic research is not only information about an individual, but also about those to whom the individual is relatedIs there a duty to warn family members of being at risk?
19 Research Involving Children Application of ‘mature minor’ principle to research?Substitute consent by parents?Parents may consent to child’s participation in research that offers reasonable hope of benefiting childWhat about research that has no intended benefit for the child?Unclear
20 Research Involving Mentally Incompetent Individuals Significance - research into Alzheimer’s, stroke, emergency department research, etc.Substitute consent?Advance directives?e.g. NF Advance Health Care Directives Act
21 The TCPS ( )Research on incompetent subjects may be acceptable provided that:Consent is sought from the appropriate 3rd partyThe subject’s wishes are sought and the subject does not dissent from the researchUsing incompetent subjects is necessary in order for the research question to be addressedThe subjects are not exposed to more than minimal risks without the potential for benefits to the subjectU.S. will allow research which poses a greater than minor increase over minimal risk provided that:It presents a ‘reasonable’ opportunity to study a serious problem affecting the health and welfare of childrenThe study is approved by the secretary of the Department of Health and Human Services after consultation with experts.(Kopelman, 2000, )
22 Justice in the Recruitment of Research Subjects So why do research on children & incompetent subjects?Clinical research has potential to offer significant individual benefittreatment only available through trial, most up-to-date, financial coverage for new medications, etc.Also potential future benefit for class of patientsHistorically medications/interventions predominantly tested on narrow segment of population - young-middle aged white males (“the 70 kg man”)
23 Justice in Recruitment of Research Subjects Optimally, clinical trial sample population should mirror patient population in clinical practiceInclusion of women, the elderly, individuals of Aboriginal, Asian or African heritage, etcTri-Council Statement 1998Anti-discrimination provision, importance of research on children and elderly