Responsible Conduct of Responsible Conduct of ResearchResearch

Professor A DhaiProfessor A DhaiHead – Bioethics Discipline Head – Bioethics Discipline

Wits Medical SchoolWits Medical School

Wits – GEMP Medical School DayWits – GEMP Medical School Day

IntroductionIntroduction 2 fundamental objectives of ethics:2 fundamental objectives of ethics:

● ● How we ought to act in a given How we ought to act in a given situationsituation

●● Provide us with strong reasons for Provide us with strong reasons for doing sodoing so involves a critical reflection of morality with its intent to safeguard human dignity and to promote justice, equality, truth, and trust.

Research EthicsResearch Ethics

About means of ensuring vulnerable people are About means of ensuring vulnerable people are protected from exploitation and other forms of harmsprotected from exploitation and other forms of harms

Evolving language : passive subject Evolving language : passive subject → active → active participantparticipant

Vulnerable: DOH / UNAIDS Vulnerable: DOH / UNAIDS GuidelinesGuidelines

• limited economic development• inadequate protection of human rights & discrimination on basis of health status• inadequate community / cultural experience with understanding of scientific research• limited availability of health care & treatment options• limited ability of individuals in community to provide informed consent

Ethical ConceptsEthical ConceptsPrinciple-based EthicsPrinciple-based Ethics

AutonomyAutonomy BeneficenceBeneficence Non-maleficenceNon-maleficence JusticeJustice

Prima faciePrima facie – not absolute; overridden by weightier – not absolute; overridden by weightier concernsconcerns - lack hierarchical order rendering ranking arbitrary - lack hierarchical order rendering ranking arbitrary

Ethics & LawEthics & Law

Distinct entitiesDistinct entities

Ethics constrained by lawEthics constrained by law

Law: minimal standardLaw: minimal standard

Quasi legal Quasi legal status of guidance documents status of guidance documents

Analysis ProcessAnalysis Process

Determine whether issue at hand is ethical oneDetermine whether issue at hand is ethical one Check facts of the caseCheck facts of the case Check for constraints on actionsCheck for constraints on actions Check which ethical values are involved Check which ethical values are involved Consult authoritative sourcesConsult authoritative sources Consider alternative solutions in light of values and Consider alternative solutions in light of values and

principles they uphold & their likely consequencesprinciples they uphold & their likely consequences Discuss proposed solutions with those whom it will effectDiscuss proposed solutions with those whom it will effect Make decision – act on it with sensitivity to others Make decision – act on it with sensitivity to others

affectedaffected Evaluate decision – be prepared to act differently in Evaluate decision – be prepared to act differently in

futurefuture

What are the boundaries between practice What are the boundaries between practice and research especially when the distinction and research especially when the distinction is blurred partly because both often occur is blurred partly because both often occur together? together?

PRACTICEPRACTICE

● ● Interventions designed solely to enhance Interventions designed solely to enhance wellbeing of patient and that have wellbeing of patient and that have reasonable expectation of successreasonable expectation of success

● ● Purpose – provide diagnosis, preventative Purpose – provide diagnosis, preventative treatments or therapytreatments or therapy

Research Research

● ● Activity designed to test an hypothesis, Activity designed to test an hypothesis, permit conclusions to be drawn, and thereby permit conclusions to be drawn, and thereby to develop or contribute to to generalizable to develop or contribute to to generalizable knowlege knowlege

DEFINITIONS - Health Research (NHA)

a) biological, clinical, psychological, social processes in human being;

b) improved methods for provision of health services; c) causes of disease, d) effects of environment on human body; e) development of new application of pharmaceuticals,

medicines and related substances f) development of new applications of health

technology

ETHICS IN RESEARCH

♦ Understanding the need for ethics in research

How can the rights of individual participants be reconciled with the demands of the scientific enterprise?

Natzi War Experiments – some Natzi War Experiments – some examplesexamples

High Altitude (low pressure) experimentHigh Altitude (low pressure) experiment Put into low pressure tanks to see how long they could survive with little oxygen. Put into low pressure tanks to see how long they could survive with little oxygen.

If did not die immediately, put under water – autopsies followedIf did not die immediately, put under water – autopsies followed Freezing Experiments Freezing Experiments

forced to remain outdoors without clothing in freezing weather for 9-14 hrs, or in forced to remain outdoors without clothing in freezing weather for 9-14 hrs, or in bath of freezing water for 3 hours. Then re-warmed if did not diebath of freezing water for 3 hours. Then re-warmed if did not die

Malaria experimentsMalaria experiments infected then given “antimalarial drugs”. Died from drugsinfected then given “antimalarial drugs”. Died from drugs

Sulphanilamide Sulphanilamide EExperiments Wounds inflicted then infected with bacterial or gangrene xperiments Wounds inflicted then infected with bacterial or gangrene

producing culture, wood shavings, glass shards. Followed by treatment and producing culture, wood shavings, glass shards. Followed by treatment and placebo group expertimentsplacebo group expertiments

Sterilization Sterilization chemical and Xray sterilization experimentschemical and Xray sterilization experiments

Transgressions Post NurembergTransgressions Post Nuremberg

Tuskegee Syphilis StudyTuskegee Syphilis Study Willowbrook Hepatitis StudyWillowbrook Hepatitis Study BezwodaBezwoda Virodene Virodene

ETHICS IN RESEARCH

Knowledge of: Guidance documents

Regulations

Past & current debate

Declarations and CodesDeclarations and Codes 19471947 Nuremberg CodeNuremberg Code

19641964 Declaration of HelsinkiDeclaration of Helsinki 19791979 Belmont ReportBelmont Report 19821982 CIOMSCIOMS 19911991 Common RuleCommon Rule

20002000 DOH SA Clinical Trials GuidelinesDOH SA Clinical Trials Guidelines

20042004 DOH Principles Structures & ProcessesDOH Principles Structures & Processes

Research Ethics ComponentsResearch Ethics Components

Procedural Procedural

Substantive Substantive

Role of REC ReviewRole of REC Review

Primary role – protection of rights & welfare of research participants

: Provide ethical advice to researchers to assist decision-making on adequacy of proposed research projects regarding participant protection

RECs also serve to protect investigators from unjust criticism

REC principles: competence, independence, pluralistic, transparent

Some BenchmarksSome Benchmarks Collaborative PartnershipsCollaborative Partnerships

ValueValue

ValidityValidity

+ Benefit / Risk ratio+ Benefit / Risk ratio

Respect for personsRespect for persons

Just & Fair processesJust & Fair processes

Avoiding Conflicts of InterestAvoiding Conflicts of Interest

NHA – CONSENT & RESEARCH

16(a) access to health records – authorization of user, head of health establishment & REC

76(1)(b) adult - written consent

76(2) minor – therapeutic research

76(3) minor – non therapeutic research

Privacy & ConfidentialityPrivacy & Confidentiality• Privacy – access to personal records (3rd part access)• Confidentiality – use of personal information once it has been disclosed• Privacy & confidentiality to be protected• Informed consent – inform participants of:

precautions to protect confidentiality limits to ensuring strict confidentiality foreseeable adverse social consequences of

breaches of confidentiality reporting of communicable diseases & child

abuse & neglect

Plans for dissemination of resultsPlans for dissemination of results

• Communities • Policy makers & health authorities • Publication • Conditions of publication to be spelt out clearly in protocol & REC to be satisfied that no interference with right to publish

Conflict of InterestConflict of Interest ““set of conditions in which professional judgement set of conditions in which professional judgement

concerning a primary interest tends to be unduly influenced concerning a primary interest tends to be unduly influenced by a secondary interest.” by a secondary interest.” ThompsonThompson

““set of circumstances in which a clinician’s or investigator’s set of circumstances in which a clinician’s or investigator’s own interests conflict with those with whom he/she has a own interests conflict with those with whom he/she has a fiduciary relationship” fiduciary relationship” SugarmanSugarman

““when a secondary interest compromises or appears to when a secondary interest compromises or appears to compromise or has a potential to compromise an compromise or has a potential to compromise an individual’s professional judgement towards the primary individual’s professional judgement towards the primary interest (people, institution, research).”interest (people, institution, research).” AAU AAU

Research – Types of Conflicts of Research – Types of Conflicts of InterestInterest

Financial Financial

Non-financial conflictsNon-financial conflicts

Scientific Misconduct

“Research misconduct is defined as fabrication, falsification, or plagiarism in proposing, performing, or reviewing research, or in reporting research results.”

Fabrication: making up data or results and recording or reporting them.

Falsification: manipulating research materials, equipment, or

processes, or changing or omitting data or results such that the research is not accurately represented in the research record.

Plagiarism: appropriation of another person's ideas, processes, results, or words without giving appropriate credit.

Research misconduct does not include honest error or honest difference of opinion.”

(http://www.ostp.gov/html/001207_3.htm)

Scientific Misconduct

Deviation from or failure to adhere to the proposed protocol without proper permission

Misrepresentation

Falsification of credentials

Deception in the research proposal

Deception in the carrying out of research

Piracy of materials

Failure of informed consent

Breaches of confidentiality

Anyone of all other deviations from accepted ethical standards.

Scientific MisconductRequirements :

Significant departure from accepted practices of relevant research community;

Misconduct committed intentionally, knowingly, recklessly;

Allegation proven by preponderance of evidence

Serious disciplinary offense!

Research MisconductResearch Misconduct

TuskegeeTuskegee

BezwodaBezwoda

HOMEWORKHOMEWORK

http//:www.ethics.medschool.co.za

dhaia@medicine.wits.ac.za

USEFUL WEBSITESUSEFUL WEBSITES٠Ethics in Health Research: Principles, Structures and Processes www.doh.gov.za ٠MRC Guidelines on Ethics for Medical Research: www.mrc.ac.za ٠Nuffield Council on Bioethics. The ethics of research related to healthcare in developing countries. www.nuffieldbioethics.org ٠Council for International Organizations of Medical Sciences (CIOMS) www.cioms.ch/guidelines_nov_2002_blurb.htm ٠Emanuel et al. What Makes Clinical Research in Developing Countries Ethical? The benchmarks of Ethical Research. www.journals.uchicago.edu/JID/journal/issues/v189n5/31380/31380.text.html