1. ETHICAL ISSUES AND INFORMED CONSENT Juan M. Lozano, MD, MSc Department of Paediatrics and Clinical Epidemiology Unit School of Medicine, Javeriana University Bogota, Colombia

2. OBJECTIVES Describing the three major ethical principles in health research involving human beings Describing the major ethical issues in RCTs: Informed consent Therapeutical equipoise and randomisation Therapy for control group: placebo, standard therapy

3. BASIC ETHICAL PRINCIPLES 1.Respect for people: self-determination Each person is autonomous and has the capacity to deliberate about his/her personal objectives, acting under the results of such deliberation The rights, safety and well-being of participants are the most important consideration and should prevail over interest of science and society Practical points: Informed consent Protection to subjects with reduded autonomy

4. BASIC ETHICAL PRINCIPLES 2. Beneficence / non-maleficence: the moral principles of doing good and not bad Ethical duty of, as possible, increasing the benefits and reducing the risks associated with research (primum non nocere) Expected risk must be reasonable given the expected benefits Practical points: Appropriate research design Competent researchers

5. BASIC ETHICAL PRINCIPLES 3. Justice: resources and tasks must be fairly allocated amongst individuals The risks and the benefits of health research should be equally distributed

6. INFORMED CONSENT Consent given by the individual according to which: The subject has received all information about the study that is required for deciding participation The subject has understood the information After considering the information the subject has decided to participate without undue pressure

7. INFORMED CONSENT (1) Components: Invitation to participate as research subject Objectives of the study Main procedures that are to be used Risks, burdens and uncomfortable procedures associated with the study Expected duration of participation Benefits expected for the subject and for others

8. INFORMED CONSENT (2) Components: Alternative procedures or treatments that could be advantageous for the subject Right to receive answers for any question Right to not participate or to withdraw without penalty All information collected will be confidential Compromise to give updated information about the study progress Right to medical treatment in case of harm suffered as part of the research

9. STUDIES WITHOUT INFORMED CONSENT Studies without risk: Data collected previously (secondary analysis of databases) There are no interventions or modifications of biological, physiological, psychological o social variables Interviews or questionnaires in which that do not include sensible issues about the subjects´ behaviour

10. STUDIES WITHOUT WRITTEN INFORMED CONSENT Studies with risks equal to those associated with routine clinical procedures Conventional clinical exam Collection of urine or stool Collection of blood by venous tap in adults

11. RESTRICTION OF INFORMATION To preserve internal validity the researcher does not disclose part of the information to be obtained during the study Some study procedures (tests for measuring compliance with medications) Partial information (the researcher acts as a patient to assess the provider´s attitudes and practice)

12. SUBJECTS WITH REDUCED AUTONOMY Children Mental illness Employees, students, members of the army In-mates

13. REASONS FOR INCLUDING SUBJECTS WITH REDUCED AUTONOMY Only if: It is not possible to get relevant information in a population without limitations to consent The study will provide knowledge that is relevant for the subjects studied It is possible to obtain consent from a legal representative of the person- involved

14. CLINICIAN – RESEARCHER CONFLICT IN RCTs In a trial the decision about the treatment given to each subject is decided by mechanisms different to clinical decision This could jeopardise the clinician´s duty to always act in the patient´s best interest Therapeutical equipoise: there is genuine uncertainty within the medical community (not necessarily on the part of the individual investigator) about the preferred treatment

15. USE OF PLACEBOS IN RCTs Ethically is justified only if there is not a “proven” therapeutic method. If such a therapy exists it should be offered to the subjects in the control group. Helsinki Declaration (2000): “.. A new method method should be tested against those of best current prophylactic, diagnostic and therapeutic method Placebos should be used just it is appropriate for the study design (masked studies)

16. RESEARCH IN LESS DEVELOPED AREAS Agreement: Researchers from a developed community / country willing to conduct research in a less developed place must adhere to: –The ethical principles in her/his own country –The cultural characteristics of the society where the research is to be carried out The information collected must be useful for the needs of the less developed place

17. RESEARCH IN LESS DEVELOPED AREAS Controversial points: Research on interventions that are not to be available in the host country The treatment used in the control group does not include interventions considered as standard of practice in more developed areas due to economical limitations in the host country