Research ethics

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Research ethics, Dr. Mujtaba Guadri, Research Summer School

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Research ethics

  1. 1. ReseaRch ethics and PLaGiaRisMReseaRch ethics and PLaGiaRisMProf. K. H. Mujtaba QuadriProf. K. H. Mujtaba QuadriChairman, Department of Medicine and Hospital Ethics CommitteeChairman, Department of Medicine and Hospital Ethics CommitteeProfessor of Medicine/NephrologyProfessor of Medicine/NephrologyKing Saud Bin Abdulaziz University of Health Sciences,King Saud Bin Abdulaziz University of Health Sciences,National Guard Health Affairs, KAMC, JeddahNational Guard Health Affairs, KAMC, JeddahDiplomate American Boards of Internal Medicine (1990-2020 ) and Nephrology (1992-2022)Diplomate American Boards of Internal Medicine (1990-2020 ) and Nephrology (1992-2022)Certification in Principles and Practice of Clinical Research (Harvard)Certification in Principles and Practice of Clinical Research (Harvard)
  2. 2. ObjectivesObjectives To establish awareness about Research ethics andTo establish awareness about Research ethics andanswer “why research ethics”?answer “why research ethics”? To examine some principles of Islamic ResearchTo examine some principles of Islamic ResearchEthicsEthics To encourage reflection on illustrative casesTo encourage reflection on illustrative cases To introduce the concepts of plagiarism and otherTo introduce the concepts of plagiarism and otherforms of ‘scientific misconduct’forms of ‘scientific misconduct’
  3. 3. Case: 1Case: 1 ProfessorProfessor ‘Greedy‘Greedy’ is about to land his “biggest grant” yet. The’ is about to land his “biggest grant” yet. Theindustry ‘sponsorindustry ‘sponsor’ would like him to be a’ would like him to be a Principle InvestigatorPrinciple Investigatorand first author for a study on a new ace-inhibitor. He has aand first author for a study on a new ace-inhibitor. He has abrilliant PhD, Doctorbrilliant PhD, Doctor ‘Sincere‘Sincere’, who has joined the project’, who has joined the projectwhich translates his basic science work into clinicalwhich translates his basic science work into clinicalapplication. The idea of Dr. Sincere’s preliminary work wasapplication. The idea of Dr. Sincere’s preliminary work waspicked up by Professor Greedy and discussed with thepicked up by Professor Greedy and discussed with theindustry, who are keen to cash in on Professor Greedy’sindustry, who are keen to cash in on Professor Greedy’sname. Halfway into the project, the two have an intensename. Halfway into the project, the two have an intenseargument onargument on first authorshipfirst authorship and Prof Greedy indicates thatand Prof Greedy indicates thathe has alternate PhD candidates that “he is currentlyhe has alternate PhD candidates that “he is currentlyinterviewing” to complete the study . Dr. Sincere reflects oninterviewing” to complete the study . Dr. Sincere reflects onwhat to do next?…what to do next?…
  4. 4.  DoctorDoctor ‘Ambitious’‘Ambitious’ is completing the 2is completing the 2ndndand crucial periodand crucial periodof his phase 3 clinical trial, comparing in anof his phase 3 clinical trial, comparing in an RCTRCT , a novel, a novelanti-coagulant NAC with oral warfarin. He has beenanti-coagulant NAC with oral warfarin. He has beenprovided the results of anprovided the results of an interim analysisinterim analysis that the datathat the datasafety monitoring board requires. On eyeballing thesafety monitoring board requires. On eyeballing thefigures, he notices that omission of just one patient forfigures, he notices that omission of just one patient foran “additional” previouslyan “additional” previously unspecifiedunspecified exclusionexclusion criterion,criterion,may make his data highly significant in favour of NAC .may make his data highly significant in favour of NAC .He daydreams of how people will read his paper in theHe daydreams of how people will read his paper in theLancet !…Lancet !…Case: 2Case: 2
  5. 5.  DoctorDoctor ‘Conscience‘Conscience’ has been approached with a 800,000’ has been approached with a 800,000Riyal grant by an International funding agency to conductRiyal grant by an International funding agency to conductan RCT in Jeddah, comparing an established sedative-an RCT in Jeddah, comparing an established sedative-hypnotic (“hypnotic (“sweetdreamsweetdream”) with a new drug (“”) with a new drug (“nightmarenightmare”)”)watching for the effects of sleep-deprivation of greater thanwatching for the effects of sleep-deprivation of greater than48hrs on cognitive skills of patients with chronic insomnia.48hrs on cognitive skills of patients with chronic insomnia.‘Nightmare’ was tolerated successfully in phase 1 trials for‘Nightmare’ was tolerated successfully in phase 1 trials forsafety but insafety but in phase11phase11 trials for efficacy and safety it wastrials for efficacy and safety it wasmarginally superior to placebomarginally superior to placebo in its sedative hypnoticin its sedative hypnoticeffects when tested in European population.effects when tested in European population. The study is part of aThe study is part of a proposed Phase 111 multicenter trialproposed Phase 111 multicenter trialbeing done in the Middle East to see its effects in thebeing done in the Middle East to see its effects in theMiddle EasternMiddle Eastern population: Doctor ‘Conscience’ now losespopulation: Doctor ‘Conscience’ now losessleep!sleep!Case: 3Case: 3
  6. 6.  Thiazolidinedione Intervention with Vitamin D EvaluationThiazolidinedione Intervention with Vitamin D Evaluation (TIDE) trial(TIDE) trialcompared thecompared the cardiovascular outcomescardiovascular outcomes of long-term treatment withof long-term treatment withrosiglitazone with those of pioglitazone (Actos, Takeda) in patients with typerosiglitazone with those of pioglitazone (Actos, Takeda) in patients with type2 diabetes as a Phase 1V RCT .2 diabetes as a Phase 1V RCT . TheThe FDA haltedFDA halted the trial and at their request an Institute of Medicinethe trial and at their request an Institute of Medicine(IOM) committee was convened to independantly examine the ethics and(IOM) committee was convened to independantly examine the ethics andscience of FDA required post-marketing researchscience of FDA required post-marketing researchAnyAny volunteersvolunteers as to what were the ethical concerns?as to what were the ethical concerns?Ethical Considerations in Studying Drug SafetyEthical Considerations in Studying Drug Safety——The Institute of Medicine ReportThe Institute of Medicine ReportMichelle M. Mello, J.D., Ph.D., Steven N. Goodman, M.D., M.H.S., Ph.DMichelle M. Mello, J.D., Ph.D., Steven N. Goodman, M.D., M.H.S., Ph.D.,.,and Ruth R. Faden, Ph.D., M.P.H.NEJM SEP 6, 2012and Ruth R. Faden, Ph.D., M.P.H.NEJM SEP 6, 2012Case: 4Case: 4
  7. 7. Table 1.Table 1. Major Deficiencies in the Informed-Consent Form forMajor Deficiencies in the Informed-Consent Form forthe TIDE Trialthe TIDE Trial InadequateInadequate explanationexplanation of the purpose of researchof the purpose of research Did not clearly explain that the purpose of the study was to definitively establish thatDid not clearly explain that the purpose of the study was to definitively establish thatrosiglitazone involved a significantly higher risk ofrosiglitazone involved a significantly higher risk of serious harmsserious harms than pioglitazone.than pioglitazone. Title included minor intervention (vitamin D) whose effects were not a subject of FDA concernTitle included minor intervention (vitamin D) whose effects were not a subject of FDA concern Inadequate explanation of theInadequate explanation of the risks of research participation.risks of research participation. Did not convey that the FDA was concerned primarily about theDid not convey that the FDA was concerned primarily about the safetysafety of rosiglitazone and wasof rosiglitazone and wasrequiring the sponsor to conduct the TIDE trial to investigate safety signals.requiring the sponsor to conduct the TIDE trial to investigate safety signals. SubmergedSubmerged cardiovascular risks associated with rosiglitazone in a list of outcomes related tocardiovascular risks associated with rosiglitazone in a list of outcomes related topotential effects of vitamin D on cancer and bone fractures.potential effects of vitamin D on cancer and bone fractures.
  8. 8. Table 1.Table 1. Major Deficiencies in the Informed-Major Deficiencies in the Informed-Consent Form for the TIDE TrialConsent Form for the TIDE Trial Characterized previous studies as having providedCharacterized previous studies as having provided conflicting findingsconflicting findingsconcerning the cardiovascular safety of rosiglitazone, when the weight of theconcerning the cardiovascular safety of rosiglitazone, when the weight of theevidence was against rosiglitazone.evidence was against rosiglitazone. Inadequate explanation of alternativesInadequate explanation of alternatives to research participation.to research participation. DidDid not disclosenot disclose that the current clinical standard of care had moved awaythat the current clinical standard of care had moved awayfrom the use of rosiglitazone.from the use of rosiglitazone. Did not mention that the American Diabetes Association had recommendedDid not mention that the American Diabetes Association had recommendedrosiglitazone not be used.rosiglitazone not be used.
  9. 9. ““What is the fuss aboutWhat is the fuss aboutethics and regulatoryethics and regulatoryrequirements in research?”requirements in research?”Adapted from: Steve Freedman, PPCRAdapted from: Steve Freedman, PPCRcourse, Harvard Med School 2011course, Harvard Med School 2011Research Ethics: Why?Research Ethics: Why?
  10. 10. TragedyTragedy In 1937, the manufacturer of sulfanilamide tablets, aIn 1937, the manufacturer of sulfanilamide tablets, apopular cold remedy, produced a more ‘palatable’popular cold remedy, produced a more ‘palatable’liquid version, with a ‘sweet raspberry’ taste.liquid version, with a ‘sweet raspberry’ taste. AMA received numerous reports of patients with:AMA received numerous reports of patients with:abdominal pain, nausea / vomiting, renal failure andabdominal pain, nausea / vomiting, renal failure anddeath.death. 105 people in 15 states died, including 34 children105 people in 15 states died, including 34 children The compound used to dissolve the tablets intoThe compound used to dissolve the tablets intosolution was diethylene glycol!solution was diethylene glycol! The manufacturer had done nothing legally wrong!The manufacturer had done nothing legally wrong!
  11. 11. Adverse EffectsAdverse Effects1959: West German physicians began to1959: West German physicians began toprescribe thalidomide to relieve morningprescribe thalidomide to relieve morningsickness and insomniasickness and insomnia40 U.S. physicians were authorized to use40 U.S. physicians were authorized to usethalidomide in clinical trials.thalidomide in clinical trials.After the link was made between thalidomideAfter the link was made between thalidomideand fetal malformations, the approval wasand fetal malformations, the approval waswithdrawn.withdrawn.
  12. 12. Adverse EffectsAdverse Effects FDA discovered that 2.5 million tablets ofFDA discovered that 2.5 million tablets ofthalidomide were distributed to 1,270 U.S.thalidomide were distributed to 1,270 U.S.physicians as samplesphysicians as samples 200,000 American patients received200,000 American patients receivedthalidomidethalidomide Mid-1960s: 10,000 birth defects worldwideMid-1960s: 10,000 birth defects worldwide
  13. 13. Regulations:Regulations:Kefauver-Harris Drug act 1962Kefauver-Harris Drug act 1962 Safety requirements tightened.Safety requirements tightened. Drugs to be proven effective as well as safe prior toDrugs to be proven effective as well as safe prior tomarketing.marketing. Drug companies to register with the FDA, and gaveDrug companies to register with the FDA, and gaveFDA explicit authority to require compliance with goodFDA explicit authority to require compliance with goodmanufacturing practices.manufacturing practices. Drug1966: the FDA released the Guidelines forDrug1966: the FDA released the Guidelines forReproduction Studies specifying that a new drug mustReproduction Studies specifying that a new drug musthave reproduction studies in at least two species ofhave reproduction studies in at least two species ofanimals, using two dosage levels of the drug.animals, using two dosage levels of the drug.
  14. 14. Pre World War 11: EthicsPre World War 11: Ethics No regulations concerning the practice of clinicalNo regulations concerning the practice of clinicalresearch.research. Investigators guided by “conscience” and the “ethicsInvestigators guided by “conscience” and the “ethicsof immediate peers and Mentors”of immediate peers and Mentors” 1932: the Tuskegee Study was funded by the Public1932: the Tuskegee Study was funded by the PublicHealth Service which had black men with latentHealth Service which had black men with latentsyphilis remain untreated ,with 28 deaths fromsyphilis remain untreated ,with 28 deaths fromsyphilis, 100 from related complications, 40 wivessyphilis, 100 from related complications, 40 wiveseffected, 19 children born with congenital syphilis!effected, 19 children born with congenital syphilis!
  15. 15. Criminal StudiesCriminal Studies Nazi physicians conducted cruel and lethalNazi physicians conducted cruel and lethalexperimentation on concentration camp inmates andexperimentation on concentration camp inmates andprisoners of war during WWIIprisoners of war during WWII December 9, 1946, the military trial (Nazi DoctorsDecember 9, 1946, the military trial (Nazi DoctorsTrial) began in Nuremberg, Germany; guilty verdictsTrial) began in Nuremberg, Germany; guilty verdictswere returned for 15 of 23 defendants; sevenwere returned for 15 of 23 defendants; sevenreceived death sentences.received death sentences. Final judgment: human experimentation wasFinal judgment: human experimentation wasnecessary for the advancement of medicalnecessary for the advancement of medicalknowledge, but ONLY if done consistent with theknowledge, but ONLY if done consistent with theprinciples of what has come to be known as theprinciples of what has come to be known as theNuremberg CodeNuremberg Code
  16. 16. Code of Ethics:Code of Ethics:The Nuremberg CodeThe Nuremberg Code Nuremberg Code describes 10 basic principles of ethical conduct ofNuremberg Code describes 10 basic principles of ethical conduct ofhuman experimentationhuman experimentation Pivotal principles:Pivotal principles:–– Voluntary consent of the subject must be obtainedVoluntary consent of the subject must be obtained–– Prior animal experimentation to determine risk must bePrior animal experimentation to determine risk must beperformedperformed Investigators must be qualified medical personnelInvestigators must be qualified medical personnel Adopted by the United Nations in 1948Adopted by the United Nations in 1948 Recognized as international ‘common law’ guiding medical researchRecognized as international ‘common law’ guiding medical research
  17. 17. Any impact of Nuremberg Code?Any impact of Nuremberg Code? The Tuskegee Syphilis Study proceeded through theThe Tuskegee Syphilis Study proceeded through the1950s and 1960s despite data suggesting arsenic and1950s and 1960s despite data suggesting arsenic andbismuth were effective and even when penicillin becamebismuth were effective and even when penicillin becameestablished as standard therapy.established as standard therapy. Enrolled subjects were told they were receiving therapy forEnrolled subjects were told they were receiving therapy fortheir disease, when in fact they never received any study-their disease, when in fact they never received any study-related treatment!related treatment! In 1963, institutionalized mentally retarded children wereIn 1963, institutionalized mentally retarded children wereintentionally exposed to Hepatitis A virus and their clinicalintentionally exposed to Hepatitis A virus and their clinicalcourse followed!course followed!
  18. 18. Helsinki Declaration: 1964Helsinki Declaration: 1964 Responding to the thalidomide disaster, the 18Responding to the thalidomide disaster, the 18ththWorldWorldMedical Assembly, held in Helsinki, adopted a resolutionMedical Assembly, held in Helsinki, adopted a resolutionon human experimentation.on human experimentation. Outlines basic principles of human experimentationOutlines basic principles of human experimentation Requires informed consent of study subjectsRequires informed consent of study subjects Describes ethical approval and review of researchDescribes ethical approval and review of research
  19. 19. National Research Act: 1974National Research Act: 1974 1972: US Congress passed the National Research Act.1972: US Congress passed the National Research Act. Required the review of all clinical research by an IRB.Required the review of all clinical research by an IRB. Set up commission to define ethical standards for clinicalSet up commission to define ethical standards for clinicalresearch in the U.S.research in the U.S. The recommendations, known as the Belmont Report,The recommendations, known as the Belmont Report,published in the Federal Register in April, 1979, whichpublished in the Federal Register in April, 1979, whichled to new regulations issued by the FDA and the DHHSled to new regulations issued by the FDA and the DHHSin 1981.in 1981.
  20. 20. Belmont report and Principles ofBelmont report and Principles ofResearch :Research : AutonomyAutonomy Autonomy; The ability to make thought outAutonomy; The ability to make thought outdecisions for oneself without any coercion,decisions for oneself without any coercion,with full mental capacitywith full mental capacity
  21. 21. BeneficenceBeneficence Refers to the concept of always doing good, orRefers to the concept of always doing good, orto do no harm.to do no harm. To accomplish beneficence, risks must beTo accomplish beneficence, risks must bebalanced against benefits.balanced against benefits.
  22. 22. JusticeJustice Groups defined by socioeconomic status, intelligence,Groups defined by socioeconomic status, intelligence,race, etc should not be singled out for participation in arace, etc should not be singled out for participation in atrial.trial. Prevents subgroups of patients, especially vulnerablePrevents subgroups of patients, especially vulnerablepopulations, from being unfairly targeted and bearingpopulations, from being unfairly targeted and bearingthe burden of research that will benefit others.the burden of research that will benefit others. Demands an equal and fair selection of subjectsDemands an equal and fair selection of subjects
  23. 23. Modern significant reported eventsModern significant reported events:: Death of an 18-year-old research subject in a geneDeath of an 18-year-old research subject in a genereplacement study at U Penn in 1999 (Jesse Gelsinger)replacement study at U Penn in 1999 (Jesse Gelsinger) Raised concerns about financial relationships andRaised concerns about financial relationships andinterests on the part of biomedical researchers thatinterests on the part of biomedical researchers thatcould compromise the safety of research subjects.could compromise the safety of research subjects. Kennedy-Krieger Institute case: Raised concerns aboutKennedy-Krieger Institute case: Raised concerns aboutthe distinction between doctor-patient relationship andthe distinction between doctor-patient relationship andinvestigator-subject relationshipinvestigator-subject relationship Federal shutdowns of academic clinical researchFederal shutdowns of academic clinical researchprograms for a variety of reasons (Duke, Johnsprograms for a variety of reasons (Duke, JohnsHopkins).Hopkins).
  24. 24. Steps of Drug Development: FDASteps of Drug Development: FDAPhase IPhase I Normal VolunteersNormal Volunteers SafetySafety Dose-KineticsDose-Kinetics ActionActionPhase IIPhase II PatientsPatients Evidence of ActivityEvidence of Activity DoseDosePhase IIIPhase III Pivotal StudiesPivotal StudiesPhase IVPhase IV Post NDAPost NDA Expanded IndicationsExpanded Indications Safety StudiesSafety StudiesWhat is the process forWhat is the process for drug developmentdrug development??
  25. 25. Clinical Drug trialsClinical Drug trialsPhase IPhase I 12 - 18 months, 200 volunteers12 - 18 months, 200 volunteersPhase IIPhase II 1.5 – 2.5 years, 300 - 5001.5 – 2.5 years, 300 - 500patientspatients Phase IIIPhase III and beyond 3 – 4 years, 2000and beyond 3 – 4 years, 2000–– 3000 patients3000 patients
  26. 26. Saudi Council For Health SpecialtiesSaudi Council For Health Specialties..Guidelines 2003: Human researchGuidelines 2003: Human research Objectives and Methods in conformity with ShariahObjectives and Methods in conformity with Shariah Should significantly contribute to enriching medicalShould significantly contribute to enriching medicalknowledgeknowledge In conformity with scientific and morally-approvedIn conformity with scientific and morally-approvedprinciples e.g Helsinki Principleprinciples e.g Helsinki Principle Desired benefits should outweigh potential harmsDesired benefits should outweigh potential harms The researcher must be qualified.The researcher must be qualified.
  27. 27. SCHS GuidelinesSCHS Guidelines Must respect patient rights and treat them humanelyMust respect patient rights and treat them humanely Research on humans should be with full informedResearch on humans should be with full informedconsentconsent Physician must explain all the details and potentialPhysician must explain all the details and potentialharmsharms The consenting subject must be adult and mentallyThe consenting subject must be adult and mentallysound (for minors, guardian’s consent necessary)sound (for minors, guardian’s consent necessary)
  28. 28. SCHS GuidelinesSCHS Guidelines Written consentWritten consent Consent should not involve any pressure, coercion orConsent should not involve any pressure, coercion orexploitationexploitation The researcher must comply with laws of the land (forThe researcher must comply with laws of the land (forNational Guard, KAIMRC- ICH-GCP)National Guard, KAIMRC- ICH-GCP) Researcher must obtain permission from InstitutionalResearcher must obtain permission from InstitutionalReview Board and Ethics Committee and the relevantReview Board and Ethics Committee and the relevantdepartmentdepartment
  29. 29. ConductingConducting Research On AnimalsResearch On Animals Prophet Muhammad (SAW) enjoined kindness andProphet Muhammad (SAW) enjoined kindness andmercy towards animals, so the sacrificial animal must bemercy towards animals, so the sacrificial animal must besubject to principles of slaughter in Islam.subject to principles of slaughter in Islam. Animal must not be tortured.Animal must not be tortured. The aim of the experiment should not be frivolous.The aim of the experiment should not be frivolous. Permission must be obtained from the relevant sector forPermission must be obtained from the relevant sector forsacrificing animals.sacrificing animals.
  30. 30. SCHS: Controls For AcceptingSCHS: Controls For Accepting GrantsGrants Researcher may accept grants subject to abiding by theResearcher may accept grants subject to abiding by theguiding principles of Shariah and scientific integrity.guiding principles of Shariah and scientific integrity. Research must be conducted in a proper, scientificResearch must be conducted in a proper, scientificmethod.method. Grant body awarding financial support should notGrant body awarding financial support should notinterfere in the research findings or the conduct of theinterfere in the research findings or the conduct of theresearchresearch
  31. 31. SCHS: Research InvolvingSCHS: Research Involving UnprecedentedUnprecedentedInterventionalInterventional OperationsOperations Must be confident of his/her and the work team’sMust be confident of his/her and the work team’sabilities in performing the operation complying withabilities in performing the operation complying withtechnical considerations.technical considerations. Such interventions should have been performed onSuch interventions should have been performed onexperimental animals first, except in very specialexperimental animals first, except in very specialcases conducted by experts after approval ofcases conducted by experts after approval ofMedical Research Ethics Committee.Medical Research Ethics Committee. These procedures must be performed in recognizedThese procedures must be performed in recognizedhospitals with appropriate specializationhospitals with appropriate specialization
  32. 32. Ethical & Scientific Implications ofEthical & Scientific Implications ofGlobalizationGlobalization of Clinical Researchof Clinical Research Globalization of clinical research fairly recentGlobalization of clinical research fairly recentphenomenon. Possible reasons include cost-saving byphenomenon. Possible reasons include cost-saving byconducting trials in developing countries for Phase 2 andconducting trials in developing countries for Phase 2 andPhase 3, e.g. South Asia and South American countries.Phase 3, e.g. South Asia and South American countries. Advantages : shortening time to approval of the drug.Advantages : shortening time to approval of the drug. A major concern is ethical oversight due to disparities inA major concern is ethical oversight due to disparities ineducation, economic and social standing, and healthcareeducation, economic and social standing, and healthcaresystems.systems. Another concern is the transparency of research inAnother concern is the transparency of research indeveloping countries. NEJM 360; 8 Feb 2009 (Glickmandeveloping countries. NEJM 360; 8 Feb 2009 (Glickmanet al)et al)
  33. 33. International Conference for Harmonization ofInternational Conference for Harmonization ofResearch: Good Clinical PracticesResearch: Good Clinical PracticesThe ICH-GCP guidelines are currentlyThe ICH-GCP guidelines are currentlyaccepted as global standards governingaccepted as global standards governingclinical research:clinical research:-Technical standards-Technical standards-Ethical oversight-Ethical oversight-Appropriate monitoring of trials-Appropriate monitoring of trials
  34. 34. Ethical Issues Of Clinical Trials InEthical Issues Of Clinical Trials InChildrenChildren: A European Perspective: A European Perspective Children should not be harmed by their participation in clinicalChildren should not be harmed by their participation in clinicaltrials.trials. Children are not young adults and trials of adults cannot beChildren are not young adults and trials of adults cannot beextrapolated to children.extrapolated to children. Consent and assent is a dynamic and continuous processConsent and assent is a dynamic and continuous processwhen a child is involved in a trial, involving on-goingwhen a child is involved in a trial, involving on-goingdialogue between children, their parents and thedialogue between children, their parents and theinvestigators.investigators. Study design should allow for smallest number of patients toStudy design should allow for smallest number of patients tobe recruited to give statistically and clinically significantbe recruited to give statistically and clinically significantresult.result. Study design needs to limit invasiveness.Study design needs to limit invasiveness. Risks and benefits should be carefully weighed.Risks and benefits should be carefully weighed. Safety monitoring should be conducted at appropriateSafety monitoring should be conducted at appropriateintervals.intervals. H Salmons Arch.Dis.Child 2009; 94 Pg 474-477H Salmons Arch.Dis.Child 2009; 94 Pg 474-477
  35. 35. Ethics ofEthics of Informed ConsentInformed Consent :Key Elements ::Key Elements : Purpose of the research projectPurpose of the research project ProceduresProcedures Risks and DiscomfortRisks and Discomfort BenefitsBenefits Alternatives to participationAlternatives to participation ConfidentialityConfidentiality Request for more informationRequest for more information Right for Refusal or withdrawalRight for Refusal or withdrawal Injury StatementInjury Statement Consent StatementConsent Statement SignaturesSignaturesFoundations of Clinical Research :Portney Watkins: 2009 P 47-59Foundations of Clinical Research :Portney Watkins: 2009 P 47-59
  36. 36. ICMJE: ResearchICMJE: Research AuthorshipAuthorship EthicsEthics:: Comply with international committee of medicalComply with international committee of medicaljournal editors – Significant contribution in researchjournal editors – Significant contribution in researchidea, methodology ,collection of data, analysis of dataidea, methodology ,collection of data, analysis of data++ Write distinct portion of article +Write distinct portion of article + Review/rewrite the final draft of the articleReview/rewrite the final draft of the article
  37. 37. Research MisconductResearch Misconduct•FalsificationFalsification: The manipulation of research: The manipulation of researchmaterials, equipment,processes, or changing ormaterials, equipment,processes, or changing oromitting data or results thus affecting accuracyomitting data or results thus affecting accuracyof reportingof reporting..Fabrication:Fabrication: Making up results and recording orMaking up results and recording orreporting themreporting them..Plagiarism:Plagiarism: the appropriation of other person’sthe appropriation of other person’sideas, processes, results, or words withoutideas, processes, results, or words withoutgiving appropraite credit and includesgiving appropraite credit and includescitation plagiarismcitation plagiarismUS National Science FoundationUS National Science Foundation
  38. 38. Research MisconductResearch MisconductPlagiarism-fabrication :Plagiarism-fabrication : taking an unrelated figuretaking an unrelated figurefrom an unrelated publication andfrom an unrelated publication andreproducing it exactly in a new publicationreproducing it exactly in a new publicationSelf-plagiarism:Self-plagiarism: multiple publication of samemultiple publication of samecontent with different titles and /or in differentcontent with different titles and /or in differentjournalsjournalsUS National Science FoundationUS National Science Foundation
  39. 39. Research MisconductResearch MisconductGhost-writing:Ghost-writing: Where someone other than theWhere someone other than thenamed author makes a major contributionnamed author makes a major contributionGuest/Gift authorship:Guest/Gift authorship: Where there is statedWhere there is statedauthorship in the absence of involvementauthorship in the absence of involvementUS National Science FoundationUS National Science Foundation
  40. 40. Research MisconductResearch MisconductCoercion authorshipCoercion authorship: the practice of being: the practice of beingpressured to give authorship to individualspressured to give authorship to individualsbecause of their positionsbecause of their positionsMutual support/admiration authorship:Mutual support/admiration authorship: TheThepractice of authors placing each other’spractice of authors placing each other’snames on papers even though they madenames on papers even though they madelittle or no direct contributionslittle or no direct contributionsUnapproved authorshipUnapproved authorship: listing someone as: listing someone asauthor who has not agreed to be an author orauthor who has not agreed to be an author ornot consulted about authorshipnot consulted about authorshipUS National Science FoundationUS National Science Foundation
  41. 41. Case: 1Case: 1 Professor ‘Greedy’ is about to land his “biggest grant” yet. TheProfessor ‘Greedy’ is about to land his “biggest grant” yet. Theindustry ‘sponsor’ would like him to be a Principle Investigatorindustry ‘sponsor’ would like him to be a Principle Investigatorand first author for a study on a new ace-inhibitor. He has aand first author for a study on a new ace-inhibitor. He has abrilliant PhD, Doctor ‘Sincere’, who has joined the projectbrilliant PhD, Doctor ‘Sincere’, who has joined the projectwhich translates his basic science work into clinicalwhich translates his basic science work into clinicalapplication. The idea of Dr. Sincere’s preliminary work wasapplication. The idea of Dr. Sincere’s preliminary work waspicked up by Professor Greedy and discussed with thepicked up by Professor Greedy and discussed with theindustry, who are keen to cash in on Professor Greedy’sindustry, who are keen to cash in on Professor Greedy’sname. Halfway into the project, the two have an intensename. Halfway into the project, the two have an intenseargument on first authorship and Prof Greedy indicates thatargument on first authorship and Prof Greedy indicates thathe has alternate PhD candidates that “he is currentlyhe has alternate PhD candidates that “he is currentlyinterviewing” to complete the study . Dr. Sincere reflects oninterviewing” to complete the study . Dr. Sincere reflects onwhat to do next?…what to do next?…
  42. 42. Case: 2Case: 2 Doctor ‘Ambitious’ is completing the 2Doctor ‘Ambitious’ is completing the 2ndndand crucial periodand crucial periodof his phase 3 clinical trial, comparing in an RCT , a novelof his phase 3 clinical trial, comparing in an RCT , a novelanti-coagulant ( NAC) with oral warfarin. He has beenanti-coagulant ( NAC) with oral warfarin. He has beenprovided the results of an interim analysis that the dataprovided the results of an interim analysis that the datasafety monitoring board requires. On eyeballing thesafety monitoring board requires. On eyeballing thefigures, he notices that omission of just one patient forfigures, he notices that omission of just one patient foran “additional” previously unspecified exclusion criterion,an “additional” previously unspecified exclusion criterion,may make his data highly significant in favour of NAC . Hemay make his data highly significant in favour of NAC . Hedaydreams of how people will read his paper in thedaydreams of how people will read his paper in theLancet !…Lancet !…Case: 2Case: 2
  43. 43.  Doctor ‘Conscience’ has been approached with a 800,000Doctor ‘Conscience’ has been approached with a 800,000Riyal grant by an International funding agency to conductRiyal grant by an International funding agency to conductan RCT in Jeddah, comparing an established sedative-an RCT in Jeddah, comparing an established sedative-hypnotic (“sweetdream”) with a new drug (“nightmare”)hypnotic (“sweetdream”) with a new drug (“nightmare”)watching for the effects of sleep-deprivation of greater thanwatching for the effects of sleep-deprivation of greater than48hrs on cognitive skills of patients with chronic insomnia.48hrs on cognitive skills of patients with chronic insomnia.‘Nightmare’ was tolerated successfully in phase 1 trials for‘Nightmare’ was tolerated successfully in phase 1 trials forsafety but in phase11 trials for efficacy and safety it wassafety but in phase11 trials for efficacy and safety it wasmarginally superior to placebo in its sedative hypnoticmarginally superior to placebo in its sedative hypnoticeffects when tested in European population.effects when tested in European population. The study is part of a proposed Phase 111 multicenter trialThe study is part of a proposed Phase 111 multicenter trialbeing done in the Middle East to see its effects in thebeing done in the Middle East to see its effects in theMiddle Eastern population: Doctor ‘Conscience’ now losesMiddle Eastern population: Doctor ‘Conscience’ now losessleep!sleep!Case: 3Case: 3
  44. 44. Some ‘Q-Tips’ to avoid scientificSome ‘Q-Tips’ to avoid scientificmisconductmisconductSearch intoyour soulbeforeresearchDo No harm Think ofadvancingscienceprimarily andyourselfsecondarilyDo notdisclosepreliminarydata to pressor mediaAvoidfabrication ofdata andfalsificationof resultsAvoidvoluntary andinvoluntaryplagiarismAvoidselectiveomission ofdataAvoid hidingadversereactionsAvoid ghostand giftauthorshipExercisehumility inresearch andlearn to reflectandreevaluate
  45. 45. Email your Reflections!Email your Reflections!quadrimu@ngha.med.saquadrimu@ngha.med.saAcknowledgement: Ms M Khalil Res Asst.Acknowledgement: Ms M Khalil Res Asst.THANK YOU!THANK YOU!and enjoy the fruits of ethical research!and enjoy the fruits of ethical research!

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