Presentation on theme: "Kusum Verma A.I.I.M.S. New Delhi"— Presentation transcript:
1Kusum Verma A.I.I.M.S. New Delhi ETHICAL ISSUESIN HEALTH RESEARCHKusum VermaA.I.I.M.S.New Delhi
2WHY - CONCERNResearch essential for advancement of scientific knowledge.Newer technologies & treatments.Require participation by human subjects.Essential that rights of research participants are protected as public willingness to participate depends on a trust that research is conducted according to strict ethical standards.
3Historical Perspectives Nuremberg trial (1946) – 23 Nazi physiciansCrimes against prisoners of warmutilating surgeries;infections with lethal pathogens;exposure to extremes of temp.Nuremberg Code (1947) – fundamental ethical codeVoluntary informed consentScientifically valid research design
4Misuse of Research Japanese war crimes Us radiation experiments Tuskegee syphilis studiesWillowbrook studies on hepatitis in Institutional children
5Historical Perspectives World Medical Association (1964) – Declaration of Helsinki : Recommendations guiding medical doctors in medical research involving human subjects.Revised – 1975, 1983, 1989, 1996, 2000
6Historical Perspectives Council for International organisations of Medical Sciences (CIOMS) and WHO (1982) – International ethical guidelines for biomedical research involving human subjectsRevised – 1993, 2002International conf. Harmonisation – Good clinical practice (ICH-GCP)-1996)International ethical and scientific quality standard for designing, conducting, recording and reporting trials involving human subjects.
7Landmark article on US abuses –Beecher (NEJM, 1966) Front line research in medical schools and major medical journalsDangerous researchNo or little benefit to patientNo informed consent
8Ethical Principles Belmont Report (1979) Principles Established three fundamental ethical principles relevant to all research involving human subjects.PrinciplesRespect for personsBeneficence & Non-male ficenceJustice & Equity
9Guidelines in IndiaICMR - `Policy statement on ethical considerations involved in Research on human subjects’ (1982)`Ethical guidelines for Biomedical research on Human subjects’ (2000)?LegislationDBT-guidelines for genetic research (2002)
10Concern of all guidelines is to protect and respect rights and welfare of human subjects as participants in research.OHRP – Office for Human Research Protections.
11Human beings have equal worth; their lives are equally valuable; and they deserve equal respect. We may not treat them as worthless, use them as mear means to our ends; misinform them; increase their risks of becoming ill or die; violate the integrity of their intimate relationships and treat with contempt what they deeply value.
12Respect for Person Self determination Individuals treated as autonomous agentsEnters into research VOLUNTARILY and with adequate information – INFORMED CONSENT.Persons with diminished autonomy are entitled to protection
13Diminished/Reduced Autonomy Impaired decision making capacityPrisonersStudentsSubordinate EmployeesServices personnelAdequate justification for their involvement as research subjects
14Informed Consent - Elements InformationPatient/subject information sheetComprehensionSimple and understandable languageLocal language translationsVoluntarinessConsent
15Patient/Subject Information State & DescribeNature & purpose of studyDuration of participationProcedures to be followedExperimental procedure, if any, to be identifiedDescribe – reasonably forseeable risks & discomfortsDescribe – benefits toSubjectCommunity/othersMedical professionalsContd…
16Patient/Subject Information Explain if project involves more than minimal riskPolicy on compensationAvailability of medical treatment for such injuriesDisclose – alternative procedures or treatmentsDescribe – steps for insuring confidentialityStateVoluntary participationNo loss of benefits on withdrawalExplain - whom to contact for questions on more information or in case of injuryContd…
17Patient/Subject Information Studies involving DNA Banking/Genetic materialRight to prevent use of his/her biological sample (DNA/cell line) at any time during conduct of research.
18Patient/Subject Information Disclosure to patient should be continuousNew knowledge must be informed as and when available.
19Patient/Subject Information Incomplete disclosure-justifiedTruly necessary to accomplish the goals of researchNo undisclosed risks to subjects that are more than minimalThere is adequate plan for debriefing subjects, when appropriate; and for dissemination of research results to them
20Patient/Subject Information Information about risks be never witheldTruthful answers be always given to direct questions
21Informed ConsentConsent valid only for research for which it is given by participant (Primary use).Information/samples to be used for other purposes or sharing with other investigators (secondary use)-clear mention made during process of obtaining informed consentNew consent needed for any use for which consent not obtained explicitlyConsent not needed-unidentified/unlinked samples.
22Informed Consent Community studies – Consent needed from Children Community – group consentIndividualsChildrenParent/guardianAssent of child to his/her capabilityMentally IllClose biological relativeLegally authorised personCertificate from psychiatristIlliterate personsWho explainsThumb impressionVideotape
23Informed Consent Genetic Studies Necessary & to be taken beforeScreening (except mandatory newborn screening).Diagnostic genetic testingTreatmentResearchWritten consent not necessary for procedures that form part of routine care.
25Genetic Databases Not to be collected for use DiscriminationPursuing eugenicsAppropriate ethical approval mechanism needed to oversee creation and maintenance of genetic databases
26Informed Consent DNA Banking Inform Donors/PatientsConditions under which samples will be provided to other researchersHow long samples will be preservedCost to individual researcher to obtain sample from repositoryCommercial benefits – donor, sample collector & repository director
27Informed Consent DNA Banking Donor to have right to order destruction of his/her sample from repository at any time.Fresh EC clearance for secondary use of material from DNA bank
28Informed Consent Transplantation Cadaveric DonorsBy person in lawful possession of the bodyLiving willLive DonorsBy donorInterest of donor to take priority over that of the recepientChildren, mentally incompetent persons, persons with restricted patient autonomy – not as donors
29Informed Consent Fetal & Embryonic Tissue Transplants Consent from mother sufficient, unless father objects in writingMother’s consent2 stagesFor abortionFor donation of fetal tissue
30Informed Consent Fetal Tissue Transplants Tissue from aborted fetuses can be cultured and banked for use in research.Fresh EC clearance for use of stored tissue in researchFetal tissue transplant in humansApproval local ECNational/Central EC
31Informed Consent-Waiver May be considered in conditions of emergency if study or use of drug has been earlier approved by EC.Patient/guardian be informed after he/she regains consciousness or is able to understand the study.
33Confidentiality EC-How ensured? Special value in genetic studies & research; and genetic databases.Indiscriminate disclosure of data may lead toPsychosocial harmStigmatisationDiscriminationFamily members not entitled to know each others diagnosis/test resultsConsent to be obtained specifically for revealing information to other family members.Codification of biological samples.
35Risk-Benefit RatioRisks of research be acceptable in relation to likely benefitsRisksPhysical harmPsychosocialDiscriminationStigmatisationBreach of confidentialityRisks can be reduced by screening potential participants and monitoring participants for adverse events.
36Risk-Benefit RatioEssentiality of research – should lead to advancement of knowledge for the benefit of all members of human speciesResearch design is soundResearch conducted by professionally competent persons.
37Research Related Injury Inbuilt mechanism for compensation/treatment of unforseeable risksTreatment – best possible treatment in the country.
38Compensation to Participants No inducements to participate in the studyInvestigator may provide forCost of travel to hospitalsVarious visitsMandays lost for above visitsInbuilt mechanism for all foreseeable and unforseeable risks due to research-provide for remedial action.Insurance cover/other mechanismAll payments, reimbursements to be approved by EC
39Justice & EquityRequires that benefits & burdens are distributed fairly.Subjects for research selected in a way that burdens and benefits of the research are distributed without arbitrariness, discrimination or caprice.Economically or socially disadvantaged subjects not to be used to benefit those who are better off than them.
40Justice Vulnerable populations With poor access to health careWith impaired decision making capacityResidents of old age/nursing homesPrisonersStudentsService personnelAdequate justification for involvement as subjectsShould not be targeted if other populations would also be suitable
41Special Groups- Research Subjects Pregnant/Nursing womenOnly if objective of research to obtain new knowledge about foetus, pregnancy and lactation; and research carries no more than minimal risk to the fetus or nursing infant.
42Special Groups- Research Subjects ChildrenNot to be involved in research that could be carried out equally well with adults.New drug trial – in children be carried out after Phase III clinical trials in adults.New drug trial can be carried out in children only if the drug has a therapeutic value in a primary disease of the chilrdren.
43Mandatory that all proposals on biomedical research involving human subjects are cleared by the institutional ethics committee.Rationale is “that an objective review of research activities involving human subjects by a group of diverse individuals is most likely to protect human subjects and promote ethically sound research”.
44Ethics Committee - Role Watch dogTo adequately protect rights & welfare of human subjects in clinical research.Committee is “patient’s advocate”.EC helps and guides but does not give ordersEducate faculty members on principles of biomedical ethics
45IRB/EC-Composition Multidisciplinary and multisectorial Independent CompetentNumbermax. recommendedQuorumChairperson – 0utside institutionMember-Secretary – Same institution
46IRB/EC-Composition Membership Medical & non-medicalScientific & non-scientificLegal expertSocial scientistPhilosopher/ethicistLay personAdequate representation of age, gender, community etc. to safeguard the interests and welfare of all sections of community/ society.
47Practice Vs. ResearchPractice – “interventions that are designed solely to enhance the well-being of an individual patient that has a reasonable expectation of success”Research – “activity designed to test an hypothesis’ permit conclusions to be drawn; and thereby develop or contribute to generalizable knowledge”.Distinction blurred as both often occur togetherLike when research is designed to evaluate safety and efficacy of a therapy.If any element of research in an activity – should undergo review.
48IRB Review-Exempt. Research Research on normal educational practices.Study of existing records, data, documents, pathological specimens or diagnostic specimensIf publicly availableIf information recorded in such a manner that subjects cannot be identified directly or through identifiers linked to subjects.
49IRB Review – Exempt Research Educational tests, survey procedures, interview procedures or observation of public behaviour unlessHuman subjects can be identified directly or indirectlyDisclosure of subjects responses could place them at risk for legal liability, damage financial standing, employability or reputation.
50? Exemption Collection and study of Samples from deceased individuals Samples collected for diagnostic purposes.Samples or data available from commercial or public repositories or registriesEstablished cell lines publicly available to qualified investigators.Self sustaining, cell free derivative preparations – viral isolates, cloned DNA or RNA.
51Ethical ReviewScientific review and ethical review cannot be separated.Scientifically unsound research is unethical that it may expose human subjects to risk or inconvenience to no purpose. Even if no risk of injury, wasting of participants time is loss of valuable resource.
52Flow Chart IRB Review Research Proposal Scientifically sound Risk Benefit RatioProcedures for obtaining informed consentProcedures for selections of subjects equitable
53IRB Initial review of project Progress report Amendments to protocol, informed consentSerious adverse eventsTermination of studies
54IRB-Expedited Review By a single reviewer rather than full committee. Research involves no more than minimal riskMinor changes in previously approved researchResearch study of minor nature such as examination of case recordsUrgent proposal of national interestDecisions taken to be brought to notice of main committee.
55PlaceboPlacebo may be used as a comparator, if there is no proven best treatment or procedure that can be used as a comparator
56Placebo Placebo controls may be justified Short term studies that do not offer serious risks to subjectsPotential subjects need to be informed of effective interventions available outside the research study.
57IRB Review – Multicenter studies To be approved by all IRB;s concerned.SituationStudy approved by IRB of one institution and not by IRB of another institutionResolvedDiscussions that clarity perceived problemsModifications
58Randomised Trials Ethical basis Treatment by both arms of the protocol are in equipoise – current evidence does not indicate superiority of one over another
59Clinical TrialsUnethical to continue a clinical trial after demonstration that one therapy is safer or more effective.Trial that will not answer the research question in an acceptable time frame – wrong to continue.
60Epidemiological studies Ethical Aspects Studies carry minimal risk to study subjectsInformed consent normally required except in very large cohort studies conducted exclusively by examining medical records.
61IRB-PowersIRB have no authority to impose sanctions on researchers who violate ethical standards.IRB can withdraw ethical approval of a research project if judged necessary
62Conflicts of Interest-Project support Funded projects – Pharmaceutical firms.Investigator hasLittle or no input into trial designLimited access to raw dataLimited participation in data interpretationResults of trial may not be published if unfavourable to sponsor
63Conflicts of InterestInvestment of investigator in a company or service on company advisory committee whose product is being tested.Such conflicts must be disclosed to IRBThese should be banned
64Conflicts of Interest Double blind study Investigator not aware of intervention being given to a patientIndependent monitoring boardInvestigator to haveUnrestricted access to primary dataFreedom to publishDisclose conflicting interests to potential participantsBan certain situations
65AuthorshipGhost AuthorHonorary AuthorsPlagiarismFabricated Data