Research Ethics Research Ethics & New & New

InvestigatorsInvestigatorsMelody Lin, Ph.D.Melody Lin, Ph.D.

Dec. 12, 2012Dec. 12, 2012

ObjectivesObjectives

Research Ethics & HSPResearch Ethics & HSP Pharmaceutical IncentivesPharmaceutical Incentives Conflict of InterestConflict of Interest Tissue IssuesTissue Issues

Research EthicsResearch Ethics

Definition Definition A set of guidelines to assist the A set of guidelines to assist the

researcher conduct ethical researchresearcher conduct ethical research

Research EthicsResearch Ethics

Ethical concerns Ethical concerns Relationship Between Society and Relationship Between Society and

Science Science Professional Issues Professional Issues Protection of Research SubjectsProtection of Research Subjects

Relationship Between Relationship Between Society Society

and Scienceand Science SocietySociety

Government funding researchGovernment funding research Congressional influence on which studies Congressional influence on which studies

are fundedare funded Corporate funding research Corporate funding research

CultureCulture ScientistScientist’’s own culturally based s own culturally based

interestsinterests

Professional IssuesProfessional Issues

Scientific MisconductScientific Misconduct Fabricating, Falsifying or Plagiarizing Fabricating, Falsifying or Plagiarizing

(FFP) (FFP) proposingproposing performingperforming reviewingreviewing reporting reporting

Protection of Research Protection of Research SubjectsSubjects

Right and welfare of the research Right and welfare of the research subjects ought not be disregarded in subjects ought not be disregarded in favor of sciencefavor of science

TrustTrust

Researchers maintains a relationship Researchers maintains a relationship of trust with the subjectsof trust with the subjects

CompromisedCompromised DeceptionDeception Confidentiality not maintainedConfidentiality not maintained

Monitoring ResearchMonitoring Research

Sponsor Sponsor Regulatory agencies Regulatory agencies IRBIRB DSMBDSMB Public interest groups Public interest groups

Sponsor ResponsibilitiesSponsor Responsibilities

Monitor the conduct of the Monitor the conduct of the researchresearch

MonitorsMonitors

Check the work of the EC or IRBCheck the work of the EC or IRB Make sure the protocol is followedMake sure the protocol is followed Verify dataVerify data Check safety issuesCheck safety issues

Regulatory AgenciesRegulatory Agencies

Government agencies have oversight Government agencies have oversight responsibilities responsibilities

FDA monitors clinical trialsFDA monitors clinical trials

Pharmaceutical Incentive Pharmaceutical Incentive $$$$$$

Recruit & retain subjects vs ss. Recruit & retain subjects vs ss. Vulnerability Vulnerability

May stretch inclusive/exclusive May stretch inclusive/exclusive criteriacriteria

Influence professional judgmentInfluence professional judgment Finder’s feeFinder’s fee

Physician InvestigatorsPhysician Investigators Prospects of PeerProspects of Peer

RecognitionRecognition PublicationPublication Financial gainFinancial gain

Economic incentives may create Economic incentives may create pressurespressures CompromiseCompromise Appearance of compromiseAppearance of compromise

IntegrityIntegrity ResearchResearch ResearcherResearcher

Issues need AddressIssues need Address

RespectRespect BeneficenceBeneficence JusticeJustice

Conflict of InterestConflict of Interest

Situation in which the integrity of academic activity, especially research, may be, or may be perceived to be, compromised by financial or other interests.

Conflicts of Interest

vs

Government Scientist Pleads Guilty

Senior Alzheimer’s Researcher Admits

Taking $285,000 In Fees, Expenses

A senior government scientist working in Alzheimer’s disease research pleaded guilty today to accepting $285,000 in consulting fees and travel expenses from the world’s largest drug manufacturer without proper approval from his bosses.

As part of his agreement with federal prosecutors, Pearson “Trey” Sunderland III, chief of the geriatric psychiatry branch of the National Institute of Mental Health, which is part of the National Institutes of Health, will be sentenced to two years of supervised probation and must forfeit $300,000.

Baltimore Sun December 8, 2006By Matthew Dolan

Sources of Potential Conflict

Consultant Speaker Stock or Other

Equity Management

Position Income from

Royalties or Licensing Fees

Board or Scientific Advisory Board Member

Gift Relationship with

Competitor Loans (To or From) Family Member has

Relationship

Does conflict of interestDoes conflict of interestpresent a legitimate concern?present a legitimate concern?

Financial interests steer the Research Financial interests steer the Research activity to the point where it is activity to the point where it is compromisedcompromised

Financial interest gives the appearance Financial interest gives the appearance that the research activity may be that the research activity may be compromisedcompromised

Maintaining full research integrity would Maintaining full research integrity would compromise the business plan and/or compromise the business plan and/or require excess resourcesrequire excess resources

What’s the worst that could What’s the worst that could happen?happen?

JesseGelsinger

Spectrum of Conflicts

Financial DisclosureFinancial Disclosure

Not meant to censor investigators Not meant to censor investigators from participationfrom participation

May reduce likelihood of May reduce likelihood of investigators biasing results of their investigators biasing results of their clinical studiesclinical studies

Financial DisclosureFinancial Disclosure

Questions of concern:Questions of concern: Does compensation to the Does compensation to the

investigator/study staff affect the investigator/study staff affect the value of the study outcome?value of the study outcome?

Is there proprietary interest by Is there proprietary interest by investigators/study staff in tested investigators/study staff in tested product?product?

Is there significant equity interest in Is there significant equity interest in sponsor of the study?sponsor of the study?

Financial DisclosureFinancial Disclosure

Is there significant payments by Is there significant payments by sponsor of other sortssponsor of other sorts Grant to fund ongoing researchGrant to fund ongoing research Compensation in the form of equipmentCompensation in the form of equipment Retainers for ongoing consultation or Retainers for ongoing consultation or

honorariahonoraria Disclosure statements also apply to Disclosure statements also apply to

investigator/study staff spouse and investigator/study staff spouse and dependent children.dependent children.

Tissue IssuesTissue Issues

Collection of new samples vs. use Collection of new samples vs. use of existing samplesof existing samples Plans for linking samples to medical Plans for linking samples to medical

records, identifiable informationrecords, identifiable information Use/disclosure of research resultsUse/disclosure of research results

Informed consentInformed consent Adequate disclosureAdequate disclosure

ProspectiveProspective Existing, stored samplesExisting, stored samples

Classification of samplesClassification of samples

Not identifiedNot identified No “human subject” if truly not No “human subject” if truly not

identifiedidentified How much clinical and demographic How much clinical and demographic

data can be retaineddata can be retained IdentifiedIdentified

Directly (name/ID)Directly (name/ID) Coded/linkableCoded/linkable

Risks of using identified Risks of using identified datadata

DisclosureDisclosure To third partiesTo third parties

Potential for breach of privacy and Potential for breach of privacy and confidentialityconfidentiality

To patients/subjectsTo patients/subjects Privacy intrusion from undesired Privacy intrusion from undesired

contactcontact Harm from disclosure of resultsHarm from disclosure of results

Research design Research design to reduce these risksto reduce these risks

Maximize confidentialityMaximize confidentiality The “least necessary” or “least identifiable” The “least necessary” or “least identifiable”

datasetdataset Use of intermediary to hold link between code Use of intermediary to hold link between code

and identifiersand identifiers Obtain maximal legal and practical protectionsObtain maximal legal and practical protections

e.g., data placed on computers not linked to the e.g., data placed on computers not linked to the InternetInternet

Develop approach for re-contacting Develop approach for re-contacting subjectssubjects Clinical relevance or valueClinical relevance or value Adequate counselingAdequate counseling

Informed consent for Informed consent for research on human research on human biological materialsbiological materials

If/when?If/when? For prospective collectionFor prospective collection Maybe for existing samples, depending on:Maybe for existing samples, depending on:

IdentifiabilityIdentifiability Adequacy of prior consentAdequacy of prior consent Setting in which collected (research vs. Setting in which collected (research vs.

clinical)clinical)

How?How? Extent of detail Extent of detail FrequencyFrequency

ResearchResearch

Conducted with Conducted with unidentifiedunidentified samples samples is not human subjects research and is not human subjects research and is not regulated by the Common is not regulated by the Common Rule.”Rule.”

““Using Using coded or identified samplescoded or identified samples requires the consent, unless the requires the consent, unless the criteria for a consent waiver have criteria for a consent waiver have been satisfied.”been satisfied.”

NBAC NBAC (1999)(1999)

Waiver of informed Waiver of informed consentconsent

for use of existing for use of existing samples samples

(see 45 CFR 46.116)(see 45 CFR 46.116) Protocol must pose minimal riskProtocol must pose minimal risk Determination of whether it might be Determination of whether it might be

desirable to communicate directly with desirable to communicate directly with patientspatients If yes, then > minimal risk, and consent should be If yes, then > minimal risk, and consent should be

obtainedobtained

Cannot adversely affect rights and Cannot adversely affect rights and welfarewelfare

Impracticability of obtaining consentImpracticability of obtaining consent From some or all participantsFrom some or all participants

New Physician New Physician InvestigatorsInvestigators

Ethical principlesEthical principles Right, safety & welfare as Right, safety & welfare as

paramountparamount Do no harmDo no harm