Sought consent Sought consent for blood for blood sampling, made sampling, made no reference to no reference to studystudy

Acquired patients' Acquired patients' medical records / medical records / data without their data without their consent & used consent & used them for them for recruitmentrecruitment

Make no reference to studyMake no reference to study

Told Parkinson’s Told Parkinson’s patients to delay, patients to delay, omit or vary L-Dopa omit or vary L-Dopa dosage without dosage without getting approval getting approval from their doctors from their doctors or checking or checking patients’ suitabilitypatients’ suitability

HA Policy & Strategy

on Research Ethics

- Investigator’s Perspective

Clinical Effectiveness Unit PS & MD Division

2005

Outline of Discussion

Ethical concerns of clinical research

Ethical foundations of clinical research

Enforcing research ethics in HA

Managing research-related liabilities

Clinical Research has Ethical ConcernsClinical Research has Ethical Concerns

Place some people Place some people at risk for the good of othersat risk for the good of othersInvolved parties have Involved parties have conflicting interests & valuesconflicting interests & values Clinical judgment about a patient’s well-being (primary Clinical judgment about a patient’s well-being (primary

interest) is subject to influence by… research agenda, interest) is subject to influence by… research agenda, sponsorship, personal ambition & conveniencessponsorship, personal ambition & conveniences

Academia competes for research output & resourcesAcademia competes for research output & resources

Multibillion dollar business with huge potential profitsMultibillion dollar business with huge potential profitsInvolved parties have Involved parties have unequal powersunequal powers

Improper decision is a real risk

Research EthicsResearch EthicsClinical research Clinical research is uis ultimately ltimately premised on TRUSTpremised on TRUST, , embodied in the willing cooperation of people serving embodied in the willing cooperation of people serving as subjects, thus creates aas subjects, thus creates a legitimate expectation for legitimate expectation for a system of protection that is TRUSTWORTHYa system of protection that is TRUSTWORTHY

Research ethics, however, was notResearch ethics, however, was not addressed addressed systematically until the late 1940s, systematically until the late 1940s, following following revelations of human experimentation in WWIIrevelations of human experimentation in WWII

Social Conventions → Professional Codes → Law(Shared norms, values & practices rooted in ‘respect for

persons’, ‘nonmaleficence’, ‘beneficence’ & ‘justice’)

Research Ethics DevelopmentResearch Ethics DevelopmentResearch ethics often evolves in response to Research ethics often evolves in response to disgraceful events. The price of inadequate ethical disgraceful events. The price of inadequate ethical scrutiny could be serious…scrutiny could be serious…– Human suffering, injury, deathHuman suffering, injury, death– Bad science, e.g. fabrication & plagiarism of dataBad science, e.g. fabrication & plagiarism of data– Loss of credibility, regulatory enforcement, legal Loss of credibility, regulatory enforcement, legal

liabilities (Tort, Malpractice Law)liabilities (Tort, Malpractice Law)

Mistreatment of human in research is not exclusive to wartime or less developed countries. In the Tuskegee study, doctors of US PHS denied syphilis Rx to 399

African-Americans from 1932-72

Is Protection Adequate?Is Protection Adequate?

ShortfallsShortfalls– Systems are largely “self-regulating” & Systems are largely “self-regulating” &

work in work in favor of research communitiesfavor of research communities– Scientific community & industry Scientific community & industry

dominatedominate– Professional paternalism undermines Professional paternalism undermines

ethical concernethical concern– Lack reliable enforcement mechanismLack reliable enforcement mechanism

Ethics is often disturbing as we do not like being told what to do

Until recently,Until recently, systems of research subject protectionsystems of research subject protection rely rely heavily on EC / IRBheavily on EC / IRB

2001

Ethical Foundations of Clinical Research (& Policy Implications)

Ethical principles

Respect for persons

Nonmaleficence (Do No Harm)

Beneficence (Do Good)

Justice

Putting ethics into practice

Ethical PrincipleEthical Principle Policy & RequirementsPolicy & RequirementsDo unto others as you Do unto others as you would have them do would have them do unto youunto you

Respect privacyRespect privacy

HonestyHonesty

Do not exploit research Do not exploit research subjectssubjects

Ensure data confidentialityEnsure data confidentiality

Adhere to consent grantedAdhere to consent granted

Respect for Persons:Respect for Persons: Human DignityHuman Dignity

己所不欲己所不欲 ,, 勿施於人勿施於人

Ethical Ethical ConsiderationConsideration

Policy & RequirementsPolicy & Requirements

Basic human rightBasic human right

The decision The decision making capacity, making capacity, rather than the rather than the outcome, is outcome, is important … even important … even if decision is if decision is seemingly not in seemingly not in favor of one’s own favor of one’s own interestinterest

Voluntary participation, Voluntary participation, with great with great emphasis on emphasis on informed consentinformed consent

Free from misrepresentation, duress Free from misrepresentation, duress & undue influence& undue influence

Right to withdraw at any time without Right to withdraw at any time without reprisalreprisal

No No exculpatory clauseexculpatory clause Consent form & subsequent Consent form & subsequent

changes changes must be approved by RECmust be approved by REC ICH GCP has detailed requirementsICH GCP has detailed requirements

Respect for Persons:Respect for Persons: Self-determinationSelf-determination

Must use an approved consent form unless waived by RECUse language & wordings suitable for subjects’ understandingPurpose of study, which aspects arewhich aspects are experimentalexperimentalStudy details (nature of intervention, ?invasiveness, ?use of placebo, method of assignment & probability to different arms, duration of involvement, sample size, likelihood of premature termination, etc.)Foreseeable risks & discomfortsForeseeable risks & discomforts to subject (± embryo, fetus, nursing infant)Expected benefits (must specify if none is expectedmust specify if none is expected)

Consent for Clinical ResearchREC will scrutinize the consent form for evidence of:

Participants being given inadequate or misleading information is the most frequent cause of concern to REC, & a common cause of GCP inspection failure in US & UK

Update of new informationUpdate of new information relevant to willingness to continue study (consent is a continuous process)Protection of privacy (subject to potential audit needs)Right to refuse, withdraw at any timeRight to refuse, withdraw at any time without reprisalAlternatives if refuse studyPossible reasons to terminate subject’s participationAnticipated expenses by or payment to subjectCommitments of sponsor(s), study institute(s) & investigatorsCompensation & Rx available for study-related injuryResearch institution & investigatorsContacts Contacts for queries & adverse event reporting

Besides observing these requirements, they must be adequately explained to subject !

Ethical ConsiderationEthical Consideration Policy & RequirementsPolicy & RequirementsUtilitarianismUtilitarianism

Beware that Beware that unchecked unchecked utilitarianism could utilitarianism could infringe human right infringe human right & contradict other & contradict other principles of ethicsprinciples of ethics

Study has aStudy has a reasonable reasonable expectation expectation in improving health, in improving health, healthcare or furthering knowledge healthcare or furthering knowledge

Considerations related to the Considerations related to the well-well-being of trial subjects should take being of trial subjects should take precedenceprecedence over the interests of over the interests of science & societyscience & society

((Declaration of Helsinki)Declaration of Helsinki)

BeneficenceBeneficence::

UtilitarianismUtilitarianism

Ethical ConsiderationEthical Consideration Policy & RequirementsPolicy & RequirementsWithout validity, a Without validity, a research cannot research cannot generate benefit to generate benefit to justify its riskjustify its risk

Equipoise exists between therapies to be compared

Methodology is scientifically valid & Methodology is scientifically valid & practically feasiblepractically feasible

Hypothesis is testableHypothesis is testable Objectives & research questions are

clear Design reduces bias & confounders Statistically sound, with sufficient

power to test research objectives

BeneficenceBeneficence::

Scientific ValidityScientific Validity

Ethical ConsiderationEthical Consideration Policy & RequirementsPolicy & RequirementsSubjects are entitled to Subjects are entitled to receive appropriate receive appropriate medical care after medical care after completion of studycompletion of study

A study article that benefits the A study article that benefits the subjects should continue to be subjects should continue to be available after study until it is available after study until it is commercially availablecommercially available

If it is foreseeable that anIf it is foreseeable that an effective effective (but (but expensiveexpensive)) Rx Rx may may notnot be be financed by the PHSfinanced by the PHS, the possible , the possible consequence must be explained & consequence must be explained & documented in the consentdocumented in the consent

Beneficence:Beneficence: Availability of Study Article after StudyAvailability of Study Article after Study

Ethical ConsiderationEthical Consideration Policy & RequirementsPolicy & RequirementsAnticipated benefitsAnticipated benefits should outweigh should outweigh risksrisks

Design must minimize risk to Design must minimize risk to participants & other individualsparticipants & other individuals

Not only must the risk be reasonable Not only must the risk be reasonable in relation to the potential benefits in relation to the potential benefits but but even reasonable risks must be even reasonable risks must be minimized to the extent possibleminimized to the extent possible

Do not include vulnerable subjects Do not include vulnerable subjects unless research is necessary to unless research is necessary to promote the health of the population promote the health of the population represented & it cannot be otherwise represented & it cannot be otherwise performedperformed

Nonmaleficence:Nonmaleficence: Favorable Risk-benefit RatioFavorable Risk-benefit Ratio

What are the risks linked to research as distinct from those associated with standard care?

– Not limited to the study articles, e.g. additional invasive IxAre foreseeable risks minimized to the extent possible?Are there adequate provisions for early detection of risks?Is there necessary expertise to carry out the research? Do anticipated benefits (excluding extraneous ones, e.g. excluding extraneous ones, e.g. more attentionmore attention) outweigh risks (all risks & burdensall risks & burdens)?Will subjects be adequately informed & updated of risks, burdens & anticipated benefits?Are there sufficient additional safeguards for vulnerable subjects?

Risk & Benefit Considerations

Ethical ConsiderationEthical Consideration Policy & RequirementsPolicy & RequirementsStudy is performed Study is performed with necessary with necessary competence competence

Investigators are qualified in Investigators are qualified in scienscientific tific & ethical capacities& ethical capacitiesStudy sites are adequately equippedStudy sites are adequately equippedInvestigators are obliged toInvestigators are obliged to monitor participants’ well-being monitor participants’ well-being

throughout studythroughout study manage record & data manage record & data to preserve to preserve

accuracy of accuracy of reporting, interpretation reporting, interpretation & verification of research data& verification of research data

safe custody of study articles, esp. safe custody of study articles, esp. unlicensed drugsunlicensed drugs

Nonmaleficence:Nonmaleficence: CompetenceCompetence

Ethical ConsiderationEthical Consideration Policy & RequirementsPolicy & RequirementsThis concerns people who This concerns people who discharge duty as a result of discharge duty as a result of holding an office or act in an holding an office or act in an official / professional capacity, official / professional capacity, so that those relying on him so that those relying on him have legitimate expectationhave legitimate expectation

It is irrelevant whether the It is irrelevant whether the decision was actually biased. decision was actually biased. As long as the personal interest As long as the personal interest aappppears sufficient to influence ears sufficient to influence the objective exercise of his/ the objective exercise of his/ her official duty, conflict of her official duty, conflict of interest existsinterest exists

Both Both investigators & investigators & reviewersreviewers need to address need to address conflict of interestconflict of interest

Declare interest & refrain Declare interest & refrain from activity if conflict is from activity if conflict is considered seriousconsidered serious

‘‘Trust testTrust test': “Would relevant ': “Would relevant others (employer, clients, others (employer, clients, peers or the general public) peers or the general public) trust my judgment if they trust my judgment if they knew I was in this situation”knew I was in this situation”

Justice:Justice: Avoid Avoid Conflict of InterestConflict of Interest

Ethical ConsiderationEthical Consideration Policy & RequirementsPolicy & RequirementsFair subject selectionFair subject selection

Fair use of resourcesFair use of resources

Neither privilege nor vulnerability, but suitability & equity, should drive the recruitment & allocation process

Study must be endorsed by heads of all departments providing support to study

Prompt & appropriate dissemination of results

Justice:Justice: Distributive justiceDistributive justice

Ethical ConsiderationEthical Consideration Policy & RequirementsPolicy & RequirementsIndependent review & Independent review & study oversight are study oversight are cornerstones in research cornerstones in research subject protectionsubject protectionGate keepingGate keepingReview panel must Review panel must involve lay & non-involve lay & non-affiliated reviewersaffiliated reviewers

Research organization has Research organization has obligation to enforce research obligation to enforce research ethicsethics

Mandatory ethical review & Mandatory ethical review & study oversight by RECstudy oversight by REC

REC performance subjects to REC performance subjects to independent monitoringindependent monitoring

Putting Ethics into PracticePutting Ethics into Practice

Healthcare professionals & bio-medical scientists are not lay members

Enforcing Research Ethics in HA(Outline of Discussion) Sharing ethical responsibilities Enforcing research ethics

Jurisdiction & power of Cluster REC Activities requiring review The review process Necessary approvals for clinical research Compliance oversight

Obligations of investigator & study site

CUHK, HKUMedical Faculty

Hospital Authority

Study Site Administration

Teaching hospitalsNon-teachinghospitals

Sharing Ethical ResponsibilitiesSharing Ethical ResponsibilitiesSponsors

Cluster REC

Investigators

Research subjects

• Policy & Standards• Compliance oversight• Training• Appeal (REC decision)

Dept of Health Medical Council Global references

University facilities

Research OrganizationsResearch Organizations

HApatients

Non-HApatients

Research subjects

Investigators

HA REC

• Investigator privilege• Study site facilities• Clinical trial

agreement• Indemnity agreement• Risk Mx, insurance• Handle complaints &

malpractice

Policy & requirements on researchStudy Site

Administration

CU / HKU REC

• Gate keeping• Ethical review• Study oversight• AE oversight• Progress reports

HA’sHA’s jurisdictionjurisdiction

• IDMC• Site audit

HA’s Role in Research EthicsHA’s Role in Research Ethics

HK has no Statute specifically on clinical researchHK has no Statute specifically on clinical research

Ethical oversight in HK relies onEthical oversight in HK relies on– Professional self-disciplineProfessional self-discipline– Administrative control (HC providers, academia)Administrative control (HC providers, academia)

HA is obliged to develop research ethicsHA is obliged to develop research ethics– Practically the sole provider of study sitesPractically the sole provider of study sites– Research subjects are invariably HA patientsResearch subjects are invariably HA patients– Bear direct & vicarious liabilitiesBear direct & vicarious liabilities

Research Ethics DevelopmentResearch Ethics Development in HAin HAPolicyPolicy Protect HA patientsProtect HA patients

Uphold standard of research conduct among Uphold standard of research conduct among employees & affiliated investigatorsemployees & affiliated investigatorsManage research-related liabilitiesManage research-related liabilitiesEnsure service priorityEnsure service priority

StrategyStrategy Assure outcome by a Quality System approach Assure outcome by a Quality System approach emphasizing emphasizing explicit standards & proceduresexplicit standards & proceduresHarmonize standard & practice with medical schoolsHarmonize standard & practice with medical schoolsSegregate standard setting function (Segregate standard setting function (HA RECHA REC) from ) from execution (execution (Cluster RECCluster REC))Compliance oversightCompliance oversight

Goal: Develop a sound ethical framework for clinical research

by adopting a Quality System approachby adopting a Quality System approach

HA delivers research ethics throughHA delivers research ethics through

Research Research SubjectSubjectProtectionProtection

InvestigatorsInvestigators

HospitalHospital(Study Sites(Study Sites))

AdministrationAdministration

HA RECHA RECCluster RECsCluster RECs

3 guiding documents3 guiding documents

& forms& forms

lay out explicit lay out explicit standardsstandards

Establishing REC Operating Requirements Establishing REC Operating Requirements

HA Guide forCluster REC

Established by HA REC:Established by HA REC:• HA-wide StandardsHA-wide Standards• Guiding document for Cluster Guiding document for Cluster

RECREC• Enables auditEnables audit• Basis for harmonizing with CU Basis for harmonizing with CU

& HKU& HKU

ICH GCP (E6)Other references,e.g. FDA IRB Guide

InternationalInternationalrequirementsrequirements& practices& practices

Applicable regulationsProfessional Code & Conduct

HA policy

Cluster REC Standard OperatingProcedure & Forms

Established by Cluster REC:Established by Cluster REC:• Guides operationGuides operation• Enables auditEnables audit

Local standards & practicesLocal standards & practices

Declaration of Helsinki

Local requirementsLocal requirements

Jurisdiction & Power of Cluster-RECJurisdiction & Power of Cluster-REC

Cluster REC is institutional (HA) based & charged Cluster REC is institutional (HA) based & charged with a mandate to protect research subjectswith a mandate to protect research subjects

Jurisdiction applies to theJurisdiction applies to the respective cluster respective cluster – Sole ethical review right Sole ethical review right (decision from another (decision from another

REC has reference value only) REC has reference value only) – Validity of approval links to Validity of approval links to study oversightstudy oversight

(reports of AE & study progress)(reports of AE & study progress)– Authority to examine all aspects of study & Authority to examine all aspects of study &

intervene, even terminating a studyintervene, even terminating a study

Activities Requiring Ethical ReviewActivities Requiring Ethical Review

Clinical research on human including body tissue, Clinical research on human including body tissue, fluid, records & data. This also applies tofluid, records & data. This also applies to– prior collected data in a format linking to individual prior collected data in a format linking to individual identifiersidentifiers

– ‘‘waste’ or ‘extra’ tissue / fluidwaste’ or ‘extra’ tissue / fluid– collection & storage of ‘extra’ material for future collection & storage of ‘extra’ material for future studystudy

QA activity involving QA activity involving additional risk, burdens, additional risk, burdens, intrusion of privacy & possibly overlap with researchintrusion of privacy & possibly overlap with research

Consistent, impartial & transparent procedure is the Consistent, impartial & transparent procedure is the best guarantee for fair outcomes & to gain trustbest guarantee for fair outcomes & to gain trust

Justice must be seen to be doneJustice must be seen to be done

Standard of documentation Standard of documentation must allow evaluation of must allow evaluation of the conduct of review & the quality of the decision the conduct of review & the quality of the decision reachedreached– In audit, In audit, not documented ≡ not donenot documented ≡ not done– In dispute, intention is judged (inferred) objectivelyIn dispute, intention is judged (inferred) objectively

Procedural Justice Procedural Justice 必須有目共睹必須有目共睹

Ethical ReviewEthical Review

Application DossierApplication DossierDuly cDuly completed ‘Application Form’ompleted ‘Application Form’ MandatoryMandatoryResearch ProtocolResearch Protocol** MandatoryMandatoryPI’s short CVPI’s short CV MandatoryMandatorySubject Consent FormSubject Consent Form** MandatoryMandatoryInvestigator’s BrochureInvestigator’s Brochure** If availableWritten information to be given to subject, e.g. Written information to be given to subject, e.g. recruitment advertisement, information sheet recruitment advertisement, information sheet

If available

Conflict of Interest Declaration by investigatorsConflict of Interest Declaration by investigators Study article / purpose of Study article / purpose of study has commercial intereststudy has commercial interest

Indemnity Indemnity aagreementgreement ( (standard form by Legal standard form by Legal ServicesServices) ) I Insurance policy certificatensurance policy certificate

Pre-licensing trial or study oPre-licensing trial or study off unlicensed useunlicensed use

Other documents Other documents aas required by RECs required by REC e.g. Endorsement from other e.g. Endorsement from other departments supporting departments supporting

study, clinical trial agreementstudy, clinical trial agreement* Indicate version / revision number & date* Indicate version / revision number & date

A structured approach to obtain A structured approach to obtain information necessary for information necessary for ethical reviewethical reviewInvestigators’ responsibility to submit information Investigators’ responsibility to submit information ((impractical for REC secretaries to extract informationimpractical for REC secretaries to extract information from research protocols)from research protocols)Download file of updated Application Form & Download file of updated Application Form & complete all complete all sections (nilsections (nil entry is required) entry is required)– ““As per protocol” is not acceptedAs per protocol” is not accepted– Information is genuine, accurate & layman friendlyInformation is genuine, accurate & layman friendly– The declaration section must be signed by all The declaration section must be signed by all

investigators & endorsed by COS / Head of Departmentinvestigators & endorsed by COS / Head of DepartmentEndorsement from other involved departmentsEndorsement from other involved departmentsIndemnity agreement & clinical trial agreement, where Indemnity agreement & clinical trial agreement, where applicable, must be signed by appropriate authoritiesapplicable, must be signed by appropriate authorities

Application, studyoversight report

No additional invasive interventionNo vulnerable subjectNo sensitive privacy concern(Section 5.3 HA Guide)

HOW?

What is suitable?

WHO to decide?

Cluster REC Office

Expedited Review

Report to Committee

Uncertain orunfavorable

opinion

CREC Chairman

CREC Chairmanassign reviewers

Full Panel or Expedited Review?Full Panel or Expedited Review?

Approve

All fulfilledAll fulfilled

Not fulfilledNot fulfilled

Full Panel Review

REC ConsiderationsREC Considerations

Value of studyScientific validity Scientific validity of study design & methodologyRisks & benefitsRisks & benefitsEquity: subject selection, treatment allocation, special special considerations for vulnerable subjectsconsiderations for vulnerable subjectsInformed consentInformed consent: freedom of choice, absence of undue influence, right to withdraw (consent formconsent form)Risk of inducement arising from paymentResearch plan has adequate provision for monitoring the data collected to ensure safety of subjects Foreseeable problem after study (removal of an effective Rx)Indemnity agreementIndemnity agreement / insurance coverSubject’s privacy & data confidentialityDisclosure of funding source & potential conflicts of interestpotential conflicts of interest

General Considerations

Nature of Ethical ApprovalNature of Ethical Approval

Ethical Ethical approval is conditionedapproval is conditioned on on– Compliance Compliance with ethical principles, institution policy & with ethical principles, institution policy &

applicable regulationsapplicable regulations– Adherence to approved protocol & documents, which Adherence to approved protocol & documents, which

can only be changed upon approval from the REC can only be changed upon approval from the REC (unless required urgently to eliminate immediate hazard)(unless required urgently to eliminate immediate hazard)

– Prompt reporting of SAEPrompt reporting of SAE– Submit progress report at least annually & as requested Submit progress report at least annually & as requested

by RECby REC– Abide by other REC decisionsAbide by other REC decisions

Failure to comply invalidates an ethical approval

Necessary Approvals for Clinical TrialNecessary Approvals for Clinical Trial

Initial & Initial & continualcontinual ethical approval ethical approval– Ignoring REC requirement may invalidate approvalIgnoring REC requirement may invalidate approval

Administrative endorsement fromAdministrative endorsement from– Heads of Heads of allall departments involving in trial departments involving in trial– Hospital administration to sign contract (Clinical Hospital administration to sign contract (Clinical

Trial Agreement) with external sponsorTrial Agreement) with external sponsor– Authorities of non-affiliated study sitesAuthorities of non-affiliated study sites– Education institute if study is part of a student’s Education institute if study is part of a student’s

course work course work

Regulatory requirement, e.g. clinical trial certificateRegulatory requirement, e.g. clinical trial certificate

Compliance OversightCompliance Oversight

REC is institutional based & its performance is REC is institutional based & its performance is subject to monitoring by the institutionsubject to monitoring by the institutionAnnual inspection by Annual inspection by HA RECHA REC– Review CREC operating procedures against HA Review CREC operating procedures against HA

standardsstandards– Random checking of records for compliance to HA Random checking of records for compliance to HA

standards & CREC operating proceduresstandards & CREC operating procedures– Interview staff on practicesInterview staff on practices

Report to respective CREC, CCE & HA RECReport to respective CREC, CCE & HA RECContinuous improvement: corrective actions, revising Continuous improvement: corrective actions, revising standards, refresher trainingstandards, refresher training

Study Site’s ObligationsStudy Site’s Obligations “Clinical Research Study Site Guide” “Clinical Research Study Site Guide”

Institutes engaging in clinical research are obliged to: Institutes engaging in clinical research are obliged to: – Support RECSupport REC– Control research privilege: investigator qualification, Control research privilege: investigator qualification, policy in gpolicy in granting access right to non-employeesranting access right to non-employees

– Verify adequate facility & resource support for study & Verify adequate facility & resource support for study & no undue influence on serviceno undue influence on service

– Undertake formal dealings with sponsor: indemnity Undertake formal dealings with sponsor: indemnity agreement, clinical trial agreementagreement, clinical trial agreement

– Manage risk: insurance, policy on collaboration with Manage risk: insurance, policy on collaboration with non-affiliated study sitesnon-affiliated study sites

– HandleHandle complaint complaint & misconduct& misconduct

Investigator’s ObligationsInvestigator’s Obligations“Investigator’s Code of Practice in Undertaking Clinical Research”“Investigator’s Code of Practice in Undertaking Clinical Research”

Has prime responsibility in protecting research subjects & Has prime responsibility in protecting research subjects & be answerable to the institution. Investigator should:be answerable to the institution. Investigator should:– qualify scientifically, i.e. proficient in the area of studyqualify scientifically, i.e. proficient in the area of study– understand & willing to comply with regulatory, understand & willing to comply with regulatory,

professional & institutional requirements on researchprofessional & institutional requirements on research– declare conflict of interest declare conflict of interest – abide by REC decisionsabide by REC decisions

PI has overall responsibilityPI has overall responsibility in in technical, administrativetechnical, administrative & & fiscal management of fiscal management of study. Need to address financial study. Need to address financial liabilities &liabilities & avoid unfair contract terms with sponsor avoid unfair contract terms with sponsor

Research-related Liabilities

Research-related liability

Vicarious liability

Investigator is not an Employee

Performing Study in an Non-affiliated Site

Control Risk & LiabilityControl Risk & LiabilityControl Risk & LiabilityControl Risk & Liability

Liability can not be waived Liability can not be waived but risk can be controlledbut risk can be controlled

Indemnity & insurance are last resort for transferring / financing risk - one should aim at prevention

Investigators, study site administration & REC have Investigators, study site administration & REC have sshared responsibilities in chared responsibilities in controlling riskontrolling risk

Basic considerationBasic consideration– What is the risk?What is the risk?– Is it worthy to take the risk?Is it worthy to take the risk?– Can myself, the organization bear the risk?Can myself, the organization bear the risk?

Liability can not be waived Liability can not be waived but risk can be controlledbut risk can be controlled

Indemnity & insurance are last resort for transferring / financing risk - one should aim at prevention

Investigators, study site administration & REC have Investigators, study site administration & REC have sshared responsibilities in chared responsibilities in controlling riskontrolling risk

Basic considerationBasic consideration– What is the risk?What is the risk?– Is it worthy to take the risk?Is it worthy to take the risk?– Can myself, the organization bear the risk?Can myself, the organization bear the risk?

Research-related LiabilityResearch-related LiabilityMalpracticeMalpractice No MalpracticeNo Malpractice

SponsorSponsor usu. not liable (indemnity usu. not liable (indemnity is often conditional)is often conditional)

Finance compensation according Finance compensation according to indemnity agreementto indemnity agreement

Research Research organization organization (RO)(RO)

Vicarious liability (Vicarious liability ( direct liability if allowed direct liability if allowed unqualified persons to unqualified persons to conduct research)conduct research)Insurance for Insurance for malpracticemalpracticeDamage to credibilityDamage to credibilityRegulatory enforcementRegulatory enforcement

When there is no external When there is no external sponsor, the RO is deem to be sponsor, the RO is deem to be the sponsorthe sponsorIf the financial risk is not If the financial risk is not transferred to a third-party transferred to a third-party through an indemnity or through an indemnity or insurance arrangement (minsurance arrangement (may not ay not be covered by malpractice be covered by malpractice insuranceinsurance), the ), the research instituteresearch institute

InvestigatorInvestigator Disciplinary & legal Disciplinary & legal proceedingsproceedings

& investigators are liable to bear & investigators are liable to bear the financial consequencethe financial consequence

Vicarious LiabilityVicarious LiabilityAn employer is vicariously liable for negligent acts or An employer is vicariously liable for negligent acts or omissions by her employee in the course of omissions by her employee in the course of employment. Vicarious liability does not apply if:employment. Vicarious liability does not apply if:– employee was not negligentemployee was not negligent– employee is acting in his/her own right rather than employee is acting in his/her own right rather than

on the employer's businesson the employer's business– investigator is not an employeeinvestigator is not an employee

Is a trial without ethical approval part of RO’s business?Is research part of the terms of appointment of an honorary staff?Case: a Govt driver used a Govt vehicle for his own purpose & the Court ruled that Govt (employer) was not liable

Special ConsiderationsSpecial ConsiderationsInvestigator is not an employeeInvestigator is not an employee

– Vicarious liability does not apply, insurance does not coverVicarious liability does not apply, insurance does not cover– RO may be charged direct liability for granting patient RO may be charged direct liability for granting patient

access / research rights to an unsuitable personaccess / research rights to an unsuitable person– RO bears OS&H liability to investigatorRO bears OS&H liability to investigator

Study site is not affiliated to ROStudy site is not affiliated to RO– REC has REC has no jurisdictionno jurisdiction over non-affiliated sites over non-affiliated sites– RO has RO has no controlno control over non-affiliated sites over non-affiliated sites– Investigator has duty of care to research subjects & RO by Investigator has duty of care to research subjects & RO by

endorsing the research may be vicariously liable for endorsing the research may be vicariously liable for negligent acts or omissions by her employeenegligent acts or omissions by her employee

More stringent standards for approval

Pietro Perrugino1497

Prudence & JusticePrudence & Justice

Research ethics has evolved into a complex Research ethics has evolved into a complex system of system of social conventions, professional social conventions, professional

codes, institutional procedures & lawcodes, institutional procedures & law

HA web-page on HA web-page on Research Ethics: Research Ethics: a comprehensive a comprehensive

source of source of informationinformation