Metodologia cercet ă rii ş tiin ţ ifice Etica in cercetarea ştiinţifică

1. Metodologia cercetării ştiinţificeEtica in cercetarea ştiinţifică Corin Badiu, 2007

2. Etica Definitii academice si practice • Ramura a disciplinelor filozofice, considerata stiinta de normare intrucat se ocupa de normele conduitei umane. [academic] • Procesul prin care se aplica valorile morale la situatii actuale de viata.[practic]

3. Aspecte istorice si religioase • Etica: un corp de norme si standarde de conduita umana care guverneaza comportamentul indivizilor si grupurilor. [istoric] • Etica: disciplina de viata rezultata din aplicarea normelor si preceptelor religioase [Religie]

4. Individ si Grupuri • Etica: domeniu de studiu care ajuta individul pentru aplicarea propriilor valori si principii pentru a le conduce comportamentul. [individual] • Etica: un set de reguli pe care le studiem si aplicam pentru a duce la indeplinire misiunea unei organizatii / institutii. [group]

5. Etica institutionala • Institutie = grup: • Actioneaza colectiv pentru indeplinirea scopurilor institutionale • Institutie = individ: • Foloseste valori comune cu etica individuala pentru a lua decizii • Atat institutiile cat si indivizii: • Norme de etica

6. Protocolul de evaluare etica in cercetare Fond, Scopuri, Obiective Metodologia cercetarii Participanti Recrutare Riscuri si Beneficii Confidentialitate Compensare

7. Protocolul de evaluare etica in cercetare Conflict de Interese Elaborarea si aplicarea consimtamantului Informat Evaluarea prin comitete si institutii Contract Trialuri Clinice Anexe

8. Fond, Scopuri, Obiective • Care este subiectul cercetarii? • Ce scopuri se vor indeplini prin cercetare? • Care sunt principalele intrebari la care se doreste raspuns? • Descrie pe scurt fondul stiintific al studiului • ½ pagina

9. Metodologia cercetarii • Secventa logica de evenimente din cadrul studiului (protocol) • Cum se vor obtine datele? • Descriere detaliata pentru fiecare metoda. Pune urmatoarele intrebari: • Cat dureaza interviul/chestionarul/observatia experimentala? • Cand (in ce perioada) va avea loc? • Unde va avea loc? • Participantii vor avea posibilitatea sa intervina in chestionar/studiu? Daca da, ofera detalii. • Care sunt implicatiile /aplicatiile cercetarii?

10. Participanti • Cine sunt participantii? Organizatii? Indivizi? • De ce au fost alesi pentru studiu? (criterii de excludere / includere) • Cati sunt? • Argumenteaza dimensiunea esantionului

11. Recrutare • Cum veti obtine o lista a potentialilor participanti? • Sistem de contact • telefonic • Email • scrisoare ? • Grupuri de studiu: • control, • Test

12. Riscuri si Beneficii • Standarde de aplicare: • Nu exista risc minim anticipat. • Participantii vor fi informati despre natura studiului si modalitatii de participare, inclusiv asupra faptului ca se pot retrage oricand. • Participantii (si raspunsurile lor privind includerea in studiu) vor fi luate ca atare

13. Anexe • Text Telefonic/email • Exemple de scrisori de consimtamant • Ghiduri de observatie clinica • Chestionare • Interviu sau intrebari de grup

14. Principii ale eticii in cercetare • Onestitate • Obiectivitate • Integritate (cine esti, ce faci, ce spui) • Utilizarea eficienta a resurselor (timp, materiale, echipamente, personal) • Colegialitate (utilizare in comun) • Recunoasterea autoritatii (ca authorship si mentor) • Deschidere (dezvaluirea detaliilor)

15. Ethics of Clinical Research • Ethical requirements in clinical research aim to: • minimize the possibility of exploitation; • ensure that the rights and welfare of subjects are respected while they contribute to the generation of knowledge.

16. Codes and Guidelines • Nuremberg Code(1949) • Declaration Of Helsinki(1964- 2000) • The Belmont Report(1979) • CIOMS/WHO International Guidelines (1993, 2002) • ICH/GCP-International Conference on Harmonization- Good Clinical Practice(1996)

17. Emergence of Ethical Principles Nuremberg Code of 1947 • Judgment at Nuremberg trial included a set of standard known as the “Nuremberg Code” • “Ethical yardstick against which defendents were judged”

18. Nazi war crimes Human radiation experiments, etc. Tuskegee Syphilis study Nuremberg trial (1948) Declaration of Helsinki (1963) National Commission Belmont Report (1977) Sentinel events

19. Nuremberg, GermanyDecember 9, 1946 to August 20, 1947 • Required voluntary consent prior to participation • Investigator responsibility to obtain consent • Information gained by using human subjects would be unprocurable any other way

20. Declaration of Helsinki(World Medical Association) • Articulated ethical principles for use by physicians conducting human research • Affirmed the autonomy of the individual • Universally adopted to ensure the rights and welfare of human subjects of research

21. Declaration of Helsinki • World Medical Association, 1964. • Last amended 2000 • Ethical Principles for Medical Research Involving Human Subjects • Take home point: Research with human subjects is justified only when the degreee of risk to subjects does not exceed the humanitarian importance of the knowledge to be gained. The D of H is the basis for Good Clinical Practice used today.

22. Declaration of Helsinki Issues addressed: • Research with humans should be based on laboratory and animal experimentation • Experimental protocol should be reviewed by independent committee • Informed consent • Research conducted by medically/scientifically qualified individuals • Risks and benefits • Privacy of the subject • Publication of research results

23. Belmont Report • 3 basic principles that should govern all research involving human subjects • Respect for persons • Beneficence (maximize benefits, minimize risks, avoid harm) • Justice (benefits and burdens equally distributed)

24. The Belmont Report Ethical Principles and Guidelines for the Protection of Human Subjects of Research (April, 1979) • Established three basic principles which are the cornerstone of regulations involving human subjects protection • Autonomy/respect for persons • Beneficence • Justice

25. THE BELMONT REPORTNational Commission for the Protection of Human Subjects of Biomedical and Behavioral Research • Distinction between clinical research and clinical practice

26. THE BELMONT REPORT • Ethical principles underlying the conduct of research: • Respect for persons • Beneficence • Justice

27. Federal regulations (DHHS) • 1991 Federal Policy for Protection of Human Subjects (The Common Rule) • Adopted by all agencies which conduct, supervise, regulate, fund or sponsor human research • Two major requirements: • Informed Consent • IRB approval

28. Romanian regulations • National ethics committee • National Drug Agency • Nonclinical studies research guide • MHO 1224/2004 according to International Conference for Harmonisation – ICH, Committee for Proprietary Medicinal Products - CPMP guide 286/95 • Good clinical practice regulations - MHO 615/2004

29. Are we doing it right? • Voluntariness: • Freely coming to a decision • Free from coercion or undue influence • Assumes capacity • Capacity • Understand nature and ramifications • Who is not able to do this?

30. Vulnerable populations • Children ? • Prisoners? • Mentally retarded individuals • Dementia/Coma/Vegetative state • Mental illness • Pregnant women • Emergency patients? (pain, fear, etc.)

31. Vulnerable Populations: Children • If child can understand (> age 6-8) • We are obligated to obtain assent • Can parents overrule? • In studies with more than minimal risk and not without prospect of direct benefit

32. Other vulnerable populations • Research on individuals who lack capacity also requires prospect of benefit • Not promulgated in federal regulations • Family member can consent • If consistent with state law

33. How do we get informed consent? • Will vary according to study design and nature of participation • Verbal vs. Written • Investigator vs. proxy

34. Informed Consent Process • Cornerstone of human subjects research • Process and not just a form. Consent form is only the documentation that the consent process has taken place

35. Informed Consent Process Basic elements of the Informed consent process (ICP) • Oral and written info at the 7th grade level • Statement that study involves research, description of procedures, duration, identification of experimental procedures • Foreseeable risks and discomforts • Anticipated benefits to subject or others • Voluntary nature of participation • Ability to withdraw at any time

36. Informed Consent Process Basic elements of ICP (cont’d) • Disclosure of alternatives • Statement regarding confidentiality/anonymity • Statement regarding compensation/medical treatment • Statement regarding appropriate contact for inquiries related to subject rights, research concerns, and for research-related injury

37. Informed Consent Process Costs • The ICP must include a clear explanation of the costs for which the subject will be responsible

38. Managing Risks to Subjects Adverse Event Reporting • Unanticipated problems • Serious adverse events • New data May lead to: • Reassessment of risk • Changes to consent form or reconsent • More frequent oversight by the IRB • Early termination of the protocol

39. Healthy volunteers • Volunteers may not stand to benefit directly, but could ultimately contribute to development of a new therapy that the participant might then use. • Require particularly close monitoring, because they can pose a risk to a volunteer's health or life.

40. Why do people participate in biomedical research? • Altruism • Free medical care and medications • Trust • Self-interest • Attention • Do we want to constrain people if they are doing things for the wrong reasons?

41. Role of the IRB • Protect the institution • Can introduce complexity • Responsibility of PI to terminate if they sense the patient is not really involved in the process • No one knows how risk is really determined

42. Ethical framework: 7 principles • Valuable scientific question • Valid scientific methodology • Fair subject selection • Favorable risk-benefit evaluation • Independent review • Informed consent • Respect for enrolled subjects Emanuel E, Wendler D, Grady C. What makes clinical research ethical? Journal of the American Medical Association 2000; 283(20):2701-11

43. Essential Elements of Ethical Research Valuable Scientific Question Limited Resources and Avoidance of Exploitation A socially, clinically, or scientifically useful research question that will generate useful new knowledge about human health

44. Essential Elements of Ethical Research Valid Scientific Methodology Limited Resources and Avoidance of Exploitation Study design, methodology, statistical power, and feasible strategy that will yield valid, reliable, generalizable, and interpretable data.

45. Essential Elements of Ethical Research Fair Subject Selection Justice Selection of subjects for reasons of science, related to the purpose of the study, not because they are readily available, vulnerable, or otherwise easily exploited, or are favored.

46. Selection of subjects • Consistent with scientific goals: • Select subjects to minimize risks and maximize benefits • Do not exclude subjects without a good reason of science, vulnerability, or susceptibility to risk or burden. • Consider distribution of burdens and benefits of research

47. Research as burden or benefit? Research as ‘burden’ Subjects need protection Research as ‘benefit’ Subjects need access

48. Vulnerability • There is an order of preference in selecting subjects, for instance, adults before children (Belmont Report) • Exclude vulnerable subjects unless their participation is needed for scientific reasons (CIOMS)

49. Essential Elements of Ethical Research Balance of Risks and Benefits Non-maleficence and Beneficence • Minimize risks to subjects • Maximize benefits to individual subjects and to society • Benefits should be proportional to or outweigh risks.

50. Risks in research • Defining risks • Probability and magnitude • Types of risk • Uncertainty • Minimizing risks • Limiting risk