This document discusses various bioethical issues related to patient safety in clinical practice and research. It begins by defining bioethics and describing when an issue becomes an ethical one. It then discusses key principles like autonomy, beneficence and justice. Specific issues covered include informed consent and its components, disclosure, capacity, voluntariness and exceptions. Research ethics guidelines and principles are also summarized, including issues like clinical equipoise, dual role of doctors, informed consent in research, and managing conflicts of interest.

1. Bioethical Issues in Patients’ Safety Practice & Research Ghaiath M.A. Hussein MBBS, MHSc. (Bioethics) Patients’ Safety Proposal Development Workshop July 29, 08

2. Objectives To identify the ethical principles related to practice and research on human subjects To identify the ethical issues related to patient’s safety in clinical practice To identify the ethical issues related to research on patients’ safety To discuss how to resolve these issues (cases) Ghaiath Ethics of Pt. Safety, July 08.

3. What is Bioethics? Bioethics is about the study of ethical issues arising along health care or research, and the associated decision-making process to resolve them. Ghaiath Ethics of Pt. Safety, July 08.

4. When does an issue in practice/research be an ethical issue (i.e. S&S)? (modified from Barbara Secker and Frank Wagner) When there is conflict of moral values , beliefs, and objectives e.g. between the health care providers and the patients. When there is conflict of commitments and responsibilities : e.g. saving patients' lives vs. using the available resources "rationally" When there is the concern that our patients rights/values are not respected . When the issue in focus is related to justice in allocating the available resources Finally, when we, as care providers feel that we are not sure what we should do . Ghaiath Ethics of Pt. Safety, July 08.

5. Three Questions & Three Categories The three questions are: How to take an (and not the ) ethically acceptable decision to the issue in focus? Why did we take this decision? (i.e. why we chose this ethical option and not another?) How to implement the decision we have taken? Ghaiath Ethics of Pt. Safety, July 08.

6. Three Questions & Three Categories Clinical ethics: which is concerned with the ethical issues related to clinical practice in health care settings. Research Ethics is concerned with the protection of humans participating in research; & Organizational ethics, which is concerned more with fair allocation of health care resources. Ghaiath Ethics of Pt. Safety, July 08.

7. Ethical Principles in Clinical Practice and Research (Beauchamp & Childress) : Autonomy " self-rule " (Respect for persons): this refers to the person's right to make free decisions about his or her healthcare. Beneficence (Do Good) Non-malificence (Do No Harm) Justice Ghaiath Ethics of Pt. Safety, July 08.

8. Part I Ghaiath Ethics of Pt. Safety, July 08.

9. A. Free Informed Consent: "Without a consent, either written or oral, no surgery may be performed. This is not a mere formality; it is an important individual right to have control over one's own body, even where medical treatment is involved. It is the patient, not the doctor, who decides whether surgery will be performed, where it will be done, when it will be done and by whom it will be done." -- Allan v. New Mount Sinai Hospital (1980) 28 O.R. 356 Ghaiath Ethics of Pt. Safety, July 08.

10. Definition : "autonomous authorization of a medical intervention…by individual patients" (Beauchamp and Faden, 2004) It's the practical expression of patient's autonomy, and the respect for him/her personality Ghaiath Ethics of Pt. Safety, July 08.

11. Components of FIC : " Disclosure " refers to the provision of relevant information by the clinician and its comprehension by the patient. " Capacity " refers to the patient's ability to understand the relevant information and to appreciate those consequences of his or her decision that might reasonably be foreseen. " Voluntariness " refers to the patient's right to come to a decision freely, without force, coercion or manipulation. Ghaiath Ethics of Pt. Safety, July 08.

12. Exceptions to individually-given consent (from Hebert P. Doing Right) Waiver by patient (do what you think best!) Incompetence (consent given by SDM) Emergency “ therapeutic privilege” (if disclosure would do harm than good to the patient)- less acceptable Ghaiath Ethics of Pt. Safety, July 08.

13. FORMS OF CONSENT Normally, should be provided by participants themselves. • Deferred consent is where the subject is entered into a research study and consent is gained from surrogates after a specified period of time for continuation of the subject’s inclusion in the trial. • Prospective informed consent represents an attempt to canvass support in advance from a population considered at risk of developing a serious illness. • Surrogate consent (SDM): ideally a substituted judgment made by a person responsible for health care decision-making for a particular patient under the relevant legislation Ghaiath Ethics of Pt. Safety, July 08.

14. Practical challenges to a "Fully Informed Consent" Diagnostic uncertainty Complexity of medical information Linguistic and cultural differences Overworked health personnel Paternalistic approach in doctor-patient relationship in developing countries, including Sudan. Ghaiath Ethics of Pt. Safety, July 08.

15. B. Disclosure This refers to the process during which physicians provide information about a proposed medical investigation or treatment to the patient. Ghaiath Ethics of Pt. Safety, July 08.

16. Elements of disclosure (modified from Dickens, 1985): description of the patient's condition or illness; a description of treatment and its expected effects (e.g., duration of hospital stay, expected time to recovery, restrictions on daily activities, scars); information about relevant alternative reasonable treatment options and their expected benefits and relevant risks; side effects, both reversible and irreversible, and expected discomforts Ghaiath Ethics of Pt. Safety, July 08.

17. Elements of disclosure… cont. an explanation of the prognosis and consequences of declining or delaying treatment. the extent of uncertainty and/or limited medical knowledge surrounding the prognosis and recommended treatment options; information the patient specially asks about physician's opinion regarding which treatments should be undertaken The patient must be given an opportunity to ask questions, and the clinician must respond to questions or requests for further information. Ghaiath Ethics of Pt. Safety, July 08.

18. Principles for providing information to the patient: make it clear; avoid jargon use language appropriate to the patient's level of understanding in a language of their fluency pause and observe patients for their reactions invite questions from the patient and check for understanding invite the patient to share fears, concerns, hopes and expectations watch for patients' emotional response: verbal and non-verbal show empathy and compassion summarize the imparted information provide contact information (and other resources) Ghaiath Ethics of Pt. Safety, July 08.

19. C. Capacity : refers to the presence of a group/set of functional abilities a person needs to possess in order to make a specific decisions (Griso and Applebaum, 1998). These include: To UNDERSTAND the relevant information To APPRECIATE the relatively foreseeable consequences of the various available options available. Ghaiath Ethics of Pt. Safety, July 08.

20. D. Voluntariness : refers to a patient's right to make treatment decisions free of any undue influence. Influences include: Physical restraint or sedation Coercion involves the use of explicit or implicit threat to ensure that the treatment is accepted Manipulation involves the deliberate distortion or omission of information in an attempt to induce the patient to accept a treatment Ghaiath Ethics of Pt. Safety, July 08.

21. Part II Ghaiath Ethics of Pt. Safety, July 08.

22. Dr. B, a psychiatrist in private practice, is approached by a pharmaceutical company to assist with a clinical trial to test the efficiency of a new drug in the treatment of acute psychosis. The study will enroll acutely psychotic patients with no history psychosis (or of treatment with antipsychotic drugs) though physicians' clinics and emergency departments. Patients enrolled in the study will be randomly assigned to receive the new medication or a placebo and will remain in the hospital for eight weeks. During this time, they will not be permitted to receive antipsychotic medication other than the study drug. Informed consent will be obtained from each participant or proxy. Patients may be withdrawn from the study if their medical condition worsens substantially. Ghaiath Ethics of Pt. Safety, July 08.

23. Objectives of Part II To identify the main the international RE guidelines and their guiding principles To identify the main ethical issues in the conduct of research on humans To discuss how to resolve these issues using the guidelines Ghaiath Ethics of Pt. Safety, July 08.

24. Historical Background NUREMBERG CODE (1947) WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI (DoH) , 1964, amended in: Tokyo (1975), Venice (1983), Hong Kong (1989), South Africa (1996), Edinburgh (2000), Washington (2002), and Tokyo (2004) BELMONT REPORT (1979) Council of International Organization of Medical Sciences (CIOMS, 2002) Tri-Council Policy Statement (1994) Ghaiath Ethics of Pt. Safety, July 08.

25. Which Research needs ethical review? Medical research involving human subjects includes research on identifiable human material or identifiable data. (DoH) This includes: studies of physiological, biomedical or pathological process, or of the response to specific intervention; in health subjects or patients, controlled trials; and studies concerning human health-related behavior ( CIOMS ) Ghaiath Ethics of Pt. Safety, July 08.

26. Guiding Principles of Research Ethics "A physician shall act only in the patient's interest." (International Code of Medical Ethics) the well-being of the human subject should take precedence over the interests of science and society. Some research populations are vulnerable and need special protection (women, children, prisoners, minorities, etc.). Ghaiath Ethics of Pt. Safety, July 08.

27. Guiding principles Research Investigators should be aware of the ethical, legal and regulatory requirements for research It is the duty of the physician in medical research to protect the life, health, privacy, and dignity of the human subject. The design and performance of each experimental procedure involving human subjects should be clearly formulated in an experimental protocol. Ghaiath Ethics of Pt. Safety, July 08.

28. Guiding principles The research protocol should always contain a statement of the ethical considerations involved Medical research involving human subjects should be conducted only by scientifically qualified persons and under the supervision of a clinically competent medical person. Every medical research project should be preceded by careful assessment of predictable risks and burdens in comparison with foreseeable benefits. Ghaiath Ethics of Pt. Safety, July 08.

29. Guiding principles Physicians should abstain from engaging in research projects involving human subjects unless they are confident that the risks involved have been adequately assessed and can be satisfactorily managed For an incompetent research subject, the investigator must obtain informed consent from the legally authorized representative in accordance with applicable law Ghaiath Ethics of Pt. Safety, July 08.

30. Guiding principles The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. extreme care must be taken in making use of a placebo-controlled trial and that in general this methodology should only be used in the absence of existing proven therapy. identify post-trial access by study participants Ghaiath Ethics of Pt. Safety, July 08.

31. Participants should know about: aims, methods, sources of funding, any possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the study and the discomfort it may entail. the right to abstain from participation in the study or to withdraw consent to participate at any time without reprisal. Ghaiath Ethics of Pt. Safety, July 08.

32. Applications of the Principles Clinical Equipoise and Dual Role Obtain free informed consent Conflicts of interests Proper research design Ghaiath Ethics of Pt. Safety, July 08.

33. A. Clinical Equipoise and Dual Role Clinical Equipoise: “genuine uncertainty within the experts clinical community about the alternative merits of the alternatives being tested” (Freedman, 1997) Dual Role: Doctors involving their patients in research Ghaiath Ethics of Pt. Safety, July 08.

34. Key issues for Researching Clinicians Make a balance between risks and benefits for your patient Avoid exploiting your patients, promote justice in enrollment, & post-trial care Ensure that participation is voluntary and adequately informed Manage the dual role properly Ghaiath Ethics of Pt. Safety, July 08.

35. B. Consent for Research… what to disclose? what the research aims to achieve, an outline of the research method, and confirmation that a research ethics committee has approved the project; the reasons that the patient or volunteer has been asked to participate; In case of randomisation, explain the process and reasons for it, and the fact that in double-blind research trials neither the patient nor the treatment team will know whether the patient is receiving the treatment being tested or is in the control group; Ghaiath Ethics of Pt. Safety, July 08.

36. What to disclose?...cont. information about possible benefits and risks; an explanation of which parts of the treatment are experimental or not fully tested; advice that they can withdraw at any time and, where relevant, an assurance that this will not adversely affect their relationship with those providing care; Ghaiath Ethics of Pt. Safety, July 08.

37. What to disclose? an explanation of how personal information will be stored, transmitted and published; · what information will be available to the participant about the outcome of the research, and how that information will be presented; arrangements for responding to adverse events; details of compensation available, if applicable Ghaiath Ethics of Pt. Safety, July 08.

38. C. Confidentiality The duty to respect the patient’s/research participant confidence that the researcher/doctor will not disclose the information s/he received as part of research of health care. Ghaiath Ethics of Pt. Safety, July 08.

39. Measures to respect confidentiality Avoid identifiable data Encode the collected data Limit access to data Keep in password-protected PC Destroy the original copies after analysis, or publication To each of the previous conditions, there are ethically-acceptable exceptions Ghaiath Ethics of Pt. Safety, July 08.

40. D. Conflict of Interests (COIs) “ a set of conditions in which professional judgment concerning a primary interest tends to be unduely influenced by a secondary interest” (Thompson, 1993) Ghaiath Ethics of Pt. Safety, July 08.

41. Types of COIs (basically financial) Stock in the company producing/funding the tested intervention Consultant in its boards Paid for conferences’ talks Financial rewards (for recruitment; finder fees) Fund-raiser to the researcher’s institute Ghaiath Ethics of Pt. Safety, July 08.

42. Problems of the COIs Distorting the integrity of research : at levels of design, conduct, analysis, or presentation of results Distortion of research agenda : researchers’ priorities become that of the fund-raisers, not the people’s Creation of new categories of diseases No long-term studies on the products (Lemmens, 2004) Ghaiath Ethics of Pt. Safety, July 08.

43. How to minimize the ethical issues? Familiarization with, and adherence to the National Technical & Ethical Guidelines Familiarization with the ethical review processes (nationally & in the grant institute) Ghaiath Ethics of Pt. Safety, July 08.

44. Ethics Review Questions: Have the risks to subjects been minimized? Are the risks reasonable in relation to anticipated benefits? Is the selection of subjects equitable? Are adequate procedures in place to ensure privacy and confidentiality? Has informed consent been sought and appropriately documented? Are safeguards in place to protect vulnerable populations? If the research is federally funded, is the protocol consistent with the grant application? Ghaiath Ethics of Pt. Safety, July 08.

45. Before enrolling patients As part of the completed protocol, PI details safety monitoring plans and procedures including assessing, documenting, and reporting adverse events. PI sends to program officer or medical officer for approval. Program officer or medical officer review Does the PO or MO have concerns about patient safety? Yes, concerned PO or MO sends recommendations to the PI for collaborative revisions. No concerns  Approval PO or MO approves safety plan and adverse event reporting plan. Patients may be enrolled once the trial meets all approval requirements. Needs IRB approval of complete protocol as well as approval by other parties such as the DSMB, FDA, and division regulatory staff. After peer review NIAID commits funds. During a clinical trial PO monitors compliance with monitoring plan and adverse event reporting requirements. IRB, FDA, and NIAID address DSMB and SAE reports PO must email or fax PI within 10 days and send official letter within 30 days of receipt. NIAID can terminate award or take other action if PI does not comply with monitoring plan. Serious adverse events PI provides reports of serious adverse events following NIAID Clinical Terms of Award Guidance . For multi-site trials, PI also sends DSMB summary reports to all IRBs and program officer. Last reviewed June 27, 2007 (jlg) Relevant Extramural SOP: Adverse Events Reporting Requirements Example of Clinical Trial Safety Monitoring and Reporting Requirements

46. Back to our case Dr. B, a psychiatrist in private practice, is approached by a pharmaceutical company to assist with a clinical trial to test the efficiency of a new drug in the treatment of acute psychosis. The study will enroll acutely psychotic patients with no history of psychosis (or of treatment with antipsychotic drugs) through physicians' clinics and emergency departments. Patients enrolled in the study will be randomly assigned to receive the new medication or a placebo and will remain in the hospital for eight weeks. During this time, they will not be permitted to receive antipsychotic medication other than the study drug. Informed consent will be obtained from each participant or proxy. Patients may be withdrawn from the study if their medical condition worsens substantially. Ghaiath Ethics of Pt. Safety, July 08.

47. Ghaiath Ethics of Pt. Safety, July 08.