Biotech 4BS3 2024 Bioethics Pt3 PDF

BIOTECH 4BS3: Biotechnology Regulations BIOETHICS pt3 1 Overview Navigating the Ethics of Human Research in Canada History Tri-Council Policy Statement - Principles Research and Research Ethics Boards Risks and Benefits Consent Fairness and Equity...

BIOTECH 4BS3: Biotechnology Regulations BIOETHICS pt3 1 Overview Navigating the Ethics of Human Research in Canada History Tri-Council Policy Statement - Principles Research and Research Ethics Boards Risks and Benefits Consent Fairness and Equity Privacy and Confidentiality Conflict of Interest 2 Navigating the ethics of human research – History In 2001, Canada's three federal research agencies: CIHR – Canadian Institute of Health Research NSERC – Natural Sciences and Engineering Research Council of Canada SSHRC – Social Sciences and Humanities Research Council of Canada The Panel develops, interprets and implements the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS). 2010 – TCPS was updated in a second edition: TCPS 2 2014, 2018, and then 2022 TCPS 2 was updated These are the most current guidelines used for research on humans and human tissue All government and private research groups/agencies use the TCPS 2 as a guide for research program development http://pre.ethics.gc.ca/eng/home.html 3  Bioethics TCPS 2– Defining Research TCPS defines Research as: "an undertaking intended to extend knowledge through a disciplined inquiry or systematic investigation.“ What is research involving humans? According to TCPS 2, research involving humans is research that: involves living human participants involves human biological materials The three core principles of this Policy – Respect for Persons, Concern for Welfare, and Justice – help to shape the relationship between researchers and participants 4 Bioethics TCPS 2– Core Principles The guidelines in this Policy are based on the following three core principles: 1) Respect for Persons… Includes: Respect autonomy Respect - treatment of persons involved directly, or Respect of persons involved indirectly - their data or human biological materials 5 Bioethics TCPS 2– Core Principles 2) Concern for Welfare Welfare consists of the impact of the proposed research on individuals; such as their: Physical, mental and spiritual health, as well as their economic and social circumstances Doing your utmost to ensure participants are not exposed to unnecessary risks: Knowing a drug will fail Knowing that a drug is superior 6 Bioethics TCPS 2– Core Principles 3) Justice Refers to the obligation to treat people fairly and equitably Fairness does not mean treat “everyone the same” Equity, in this context, means to distribute benefits and burdens of research participation. No one group should be unfairly burdened with potential harm People or groups whose circumstances cause them to be vulnerable or marginalized may need to be afforded special attention in order to be treated justly in research Threat to justice is the imbalance of power that may exist in the relationship between researcher and participant These principles are complementary and interdependent. How they apply and the weight accorded to each will depend on the nature and context of the research being undertaken 7 Bioethics TCPS 2– Research Ethics Board The Research Ethics Board (REB) is responsible, on behalf of the institution, for ensuring that all research involving human subjects at an institution meets current ethical standards Ethics review starts with an assessment of the magnitude and probability of harm REB should use a proportionate approach to research ethics review Scrutiny of the research is proportional to the level of risk Minimal risk: delegated review Above minimal risk: board review Minimal risk: the probability and magnitude of possible harm are no greater than those encountered by participants in their everyday life Committee that reviews research proposals, provides feedback and requires that all human research studies be approved by the REB prior to pursuit 8 Bioethics TCPS 2– Research Ethics Board The REB Mandate Research Ethics Boards (REBs) are mandated by their institution to assess whether the research proposals they review are ethically acceptable according to TCPS 2. Any institution that is eligible to receive federal research funding is obligated to provide support (funding, space, personnel) to: At least one REB or To make arrangements to have their research proposals reviewed by another TCPS 2 compliant REB The goal of an REB is to represent the interests of participants by: Assessing the foreseeable risks Ensure that participants are not exposed to unnecessary or avoidable risks Ethical implications Potential benefits See that, on the whole, the potential benefits outweigh the foreseeable risks Help research proceed in accordance with the core principles of TCPS2 Researchers can consult with REB staff at the design phase of their project, while they are preparing their application for REB review, and during the review process 9 Bioethics TCPS 2 – Research and Research Ethics Boards As a general rule, all research involving humans requires REB review and approval, with some exceptions: Publicly available information (with no expectation of privacy) Observation in public places (no interaction, no expectation of privacy, no ID) Secondary use of anonymous data or biological materials (no ID) Not every activity involving inquiry and/or human participation is considered to be research involving humans that requires REB review Quality assurance, testing and performance review Creative practice Whenever there is doubt about whether a particular research project should undergo research ethics review, the REB should be contacted. 10  Bioethics TCPS 2 – Risks and Benefits Depending on the nature of the study (e.g. sociological, psychological, observational, biomedical), different types of risk & benefits may be assessed: Research involving humans may produce benefits that positively affect: Direct (e.g. exercise and pregnancy study; or knowing that participation can help others brings satisfaction) Indirect (development of better treatments or policies that can be of benefit in the future) Advancement of knowledge Research is a step into the unknown, which means risk Risk is a function of the magnitude of a harm, and the probability that it will occur Magnitude Spectrum: minimal (inconvenient) to substantial (major physical injury, or trauma) Probability Assessments of this can be based on: Researchers’ past experiences Review of existing publications with similar issues Empirical evidence The harm could be: Social Psychological Physical Economic 11  Bioethics TCPS 2 – Consent Consent - fundamental to the principle of Respect for Persons Prospective participants, who have the capacity to consent on their own behalf, expect to be: treated as autonomous individuals able to make decisions about the risks they consider acceptable and the information they choose to share with researchers It is the responsibility of researchers to be aware of any additional consent guidance or regulations that apply to their research The consent process begins with the recruitment and screening of participants and continues throughout their involvement in the research 12 Bioethics TCPS 2 – Consent The Consent Process Recruitment Information Documenting Consent Debriefing (when required) The general principles of consent are that it must be: Free Informed Ongoing Keep everyone informed at each point 13 Bioethics TCPS 2 – Consent TCSP-2 definition of consent: free (voluntary), informed, and ongoing consent Consent shall be voluntary No undue influence (from a position of power) No coercion (more extreme than the above; threatening in nature) Incentives should be not too large to encourage disregard of risks Onus is on the researcher to justify the incentives Consent can be withdrawn at any time Payment is given if it is in the form of a lump-sum If a participant withdraws, then they can request the withdrawal of their data or biological samples If it’s impossible to withdraw data (it has been anonymized), then this has to be included in the consent form The principal investigator (PI) is responsible for making sure that the consent process is followed 14 Bioethics TCPS 2 – Consent TCSP-2 definition of consent: free (voluntary), informed, and ongoing consent Consent shall be informed: Information that the individual is being invited to participate in a research project Statement of the research purpose in plain language Identity of the researcher(s), funder or sponsor Duration of the study Research procedures Explanation of the responsibilities of the participant throughout the duration Description of the foreseeable risks and potential benefits Assurance that the participants: Are under no obligation to participate and free to withdraw Will be kept informed on anything related to their decision to participate or withdraw Will be given information on their right to request the withdrawal of data or biological samples Will be informed about potential commercialization and potential conflicts of interest Will be informed about how the information will be disseminated Will be given a statement that by participating the participants have not waived any rights to legal recourse 15  When a person lacks the ability to consent; this is the hierarchy Bioethics 1. Partner 2. Adult children 3. Parents TCPS 2 – Consent 4. Adult siblings 5. Grandparents 6. Adult grandchildren 7. Uncle and Aunts Capacity to Consent 8. Nieces and Nephews Ability to understand the risks and benefits of participating If not capable → Consent of an authorized third party Capacity to consent can change (not static) depending upon: the complexity of the choice being made the circumstances surrounding the decision any change in the participant's condition If a participant regains capacity at any point in time after an authorized party has provided consent, the researcher must seek consent directly from the participant before they can continue in the study 16 Bioethics TCPS 2 – Consent Individuals that “lack capacity” are those that can’t make informed decisions on their own. They are unable to understand the information that could affect their decision They are unable to retain that information They are unable to communicate the decision Examples: babies, young children, patients with dementia, unconscious patients…etc. Assent & Dissent Even when an individual’s authorized third party gives consent → must involve the individual to the greatest extent possible - who may: agree (assent) or not agree (dissent) When individuals know that their capacity is likely to diminish, they may make their wishes known in the form of a research directive like a will 17  Bioethics TCPS 2 – Consent Acceptable Alterations of Consent The consent process may be altered (or waived / delayed) with REB approval if all the following conditions apply: research involves no more than minimal risk (Affecting the daily life) waiver or alteration is unlikely to have a negative effect on participants’ welfare it is impossible to carry out the research, given the research design, if prior consent of the participant is required whenever possible, participants will be (debriefed) provided with all information pertinent to their consent at the earliest possible opportunity, and will be given the option to withdraw their consent waived or altered consent does not involve a therapeutic, clinical, or diagnostic intervention 18  Bioethics TCPS 2 – Consent REBs may allow research to be carried out without consent in a medical emergency if all of the following apply: the individual needs immediate treatment and is unconscious or lacks the capacity to consent there is no existing treatment or, the treatment offered by the researcher is likely to be of more benefit to the participant than the existing treatment the risk of the research treatment is < risk of the existing treatment, or, the likely direct benefit of the research treatment > its foreseeable risks Efforts to reach an authorized third party have failed A research directive by this individual is not known to exist As soon as the individual regains consciousness or capacity, or an authorized third party is found, consent is sought promptly for continuation in the project, and for any follow-up examinations or tests related to the research 19  Bioethics TCPS 2 – Fairness and Equity (Justice) In the evolution of research ethics policies, there has been a progression: A lack of adequate safeguards protecting participant safety and autonomy, to An emphasis on protecting those deemed to be vulnerable, to A more balanced approach to the overall application of fairness and equity to all research participants. 20  Bioethics TCPS 2 – Fairness and Equity (Justice) Applying the principle of Justice to research design Researchers and REB members should understand vulnerable circumstances from the perspective of the participant Individuals or groups whose circumstances may make them vulnerable in the context of research should not be inappropriately included or automatically excluded Creating Vulnerable Circumstances Vulnerable - Diminished ability to protect ones self, and rights Watch your Language / Avoid Misunderstandings….Be Careful of Context 21  Bioethics TCPS 2 – Fairness and Equity (Justice) Varying Vulnerable Circumstances Research ethics policy previously reflected a concern for who were considered "vulnerable populations”: Children, the elderly, the mentally ill, the institutionalized, and impoverished people All considered to be vulnerable populations in need of special protection in the context of research. TCPS 2 takes the view that categorizing people in this manner fails to consider the nature and stability of each participant’s circumstances in the context of specific research. Anyone may be in vulnerable situations at some point in time! 22 Bioethics TCPS 2 – Fairness and Equity (Justice) Examples: Minors TCPS 2 does not specify a minimum age of consent for participation in research. It considers participants' capacity to consent, which can be affected by factors other than age Brain Injury Survivors Those whose injuries heal sufficiently to permit independent decision-making are no longer considered to be in vulnerable circumstances due to their brain injury Students The relationship between the student and the researcher creates a vulnerable circumstance TCPS 2 requires that individuals not be excluded from the opportunity to participate in research on the basis of attributes such as culture, language, religion, race, disability, sexual orientation, ethnicity, linguistic proficiency, gender or age - unless there is a valid reason for the exclusion 23 Do you think pregnant women should be included in clinical trials? YES If yes, how do we protect the fetus? 1. Avoid things that affect the immunity 2. Check on maternal health both physically and mentally 3. Monitor the health of the fetus 4. Time it when all the organs are developed and its not early on 24  Bioethics TCPS 2 – Fairness and Equity (Justice) Inappropriate Exclusion TCPS 2 recognizes… There are ways to safely conduct research with pregnant and nursing women Also recognizes the fairness and equity of the appropriate inclusion of people who lack cognitive capacity and provides specific guidance to researchers and REBs. Sometimes, researchers exclude participants who represent the very population they are trying to help 25 Bioethics TCPS 2 – Privacy and Confidentiality Many areas of research, such as epidemiology, history, genetics and psychology, depend on access to personal information Privacy Prior to the collection of data Individuals have privacy interests in relation to their bodies, personal information, expressed thoughts and opinions, personal communication with others, and the spaces they occupy Confidentiality After the collection of data Researchers have an ethical obligation to keep anything participants reveal to them in confidence Essential to the trust relationship between researcher and participant, and to the integrity of the research project. 26  Bioethics TCPS 2 – Privacy and Confidentiality Expectations of Confidentiality Participants may reasonably expect that any personal information given in a research study that could be used to identify them will: not be linked to other information about them (e.g. health, employment, or educational records) without their consent not be made available to anyone except those involved in collecting, analyzing, or monitoring the data for that research project be stored securely until no longer needed and then be destroyed not be released to anyone outside the study, unless permission to do so has been explicitly granted 27  Bioethics TCPS 2 – Conflicts of Interest There is a need for conflict of interest policies because some COI are: Easy to avoid Foreseeable but not avoidable Others can arise unexpectedly as circumstances change Policies are required to help researchers, REBs and administrators identify, eliminate, minimize, or manage any real, perceived, or potential COI that may affect the ethical conduct of research These policies need to deal specifically with each of the following types of COI: Institutional COI REB member COI Researcher COI 28  Bioethics TCPS 2 – Conflicts of Interest - Example In late 1995 and early 1996, after 6 years of clinical trials at Hospital for Sick Children (HSC), Dr. Nancy Olivieri (HSC scientist and UofT Professor) began to have concerns about Deferiprone — an Apotex drug she was testing for the treatment of thalassemia major. Dr. Olivieri's data suggested that deferiprone leads to progressive hepatic fibrosis Dr Olivieri told Apotex that the Research Ethics Board (REB) at the Hospital for Sick Children would have to be advised of her findings regarding loss of efficacy, and that the existing protocols and consent forms would have to be modified 29  Bioethics TCPS 2 – Conflicts of Interest Apotex disputed her claims about unexpected risk to patients and contested the need for her to inform patients of the ‘‘risk’’ When Apotex received the revised information and consent forms, it terminated the trial and informed Dr. Olivieri that all information about the trial was to remain confidential, or there would be legal consequences Olivieri accused her home institutions — the HSC and the UofT— of failing to support her …………………………………………………………………………………….. Do drug companies silence researchers in order to keep secrets? Have academic institutions put their interest in wealthy donors above all others? And are research subjects adequately protected from potential risks? CMAJ. 1998 Oct 20; 159(8): 955–957. ; CMAJ 1999;160(3):386-8. 30  Bioethics TCPS – Conflict of Interest – Institutional Conflict of Interest: Activities or situations that create a real, perceived or potential conflict between personal, professional or institutional interest(s) (including, without limitation, financial interests) i.e Money includes a situation where financial, personal, professional, or institutional considerations may compromise judgement in the conduct or reporting of research. Institutional COI: Occurs when there is undue influence on human research from institutional financial investments/holdings or personal financial interests/holdings of key institutional representatives 31  Bioethics TCPS – Conflict of Interest – Institutional When should institutional COI be disclosed to the REB? When should the REB disclose institutional COI to researchers and require that it be disclosed to participants during the consent process? How can the institution ensure its researchers are able to conduct independent research without interference from institution funders? How can institutions ensure their researchers will be supported by their administration in the event of a conflict with a research sponsor who is also a funder of the institution? 32 Bioethics TCPS – Conflict of Interest – REB Member Examples of REB Member COI Their own research projects are under review by their REB They are a co-investigator on a proposal under review They are in a supervisory or mentoring relationship with a graduate student applicant They have interpersonal or financial relationships with the researchers named in a proposal They have personal or financial interests in the sponsor of the research project They may be personally or professionally affected by the research 33  Bioethics TCPS – Conflict of Interest - Researcher Researcher COI Pressures to delay or withhold results or to use questionable recruitment strategies are some possible outcomes of COI. The most common types of researcher COI: Interpersonal Family, colleagues, or community relationships – stand to benefit from the outcome of the study Dual Roles Researcher has dual roles in academic and other professional settings – Identify and avoid COI Financial Disclose and document all kinds and amounts of financial incentives 34  Scenario: An REB member receives a research proposal from a professor who, in addition to government funding, is receiving external funding from a biotechnology company called Zenon Technologies. The REB member currently sits on the board of directors for Zenon. In this role he receives a salary from the company. What is the conflict of interest? How could it be resolved? They have personal or financial interests in the sponsor of the research project, allow people who have no relationship with the company review the proposal 35  Bioethics TCPS – Conflict of Interest Once a conflict of interest is identified and determined to be a real, perceived or potential threat to the ethical conduct of interest, the next step is to choose one of the following strategies: Eliminate Recusal from decision making Divestment Minimize Due to COI, a professor is not involved in REB but can still give information about the discipline to other members of the REB Reduce financial stakes Manage For example disclose financial COI to participants in the consent process 36  Bioethics TCPS – Regulations and Guidelines – Stem Cells All human embryonic stem cell lines generated using CIHR funds or derived by an institution receiving funds from any of the research councils, must be listed in the National Embryonic Stem Cell Registry According to the Guidelines, types of research that are NOT eligible for CIHR funding: Creating embryos to use in the derivation of stem cells, Research involving somatic cell nuclear transfer into human oocytes for the purposes of developing human embryonic stem cell lines or to the cell lines of a pluripotent nature (e.g., cloning), Research involving the directed donation of stem cell lines or, other human cells or cell lines of a pluripotent nature to particular individuals, unless the research involves autologous donation, means to oneself Research in which human or non-human embryonic stem (ES) cells, embryonic germ (EG) cells or other cells of a pluripotent nature are combined with a human embryo, Research in which human or non-human ES cells, EG cells or other cells of a pluripotent nature are grafted to a human fetus, Research in which human or non-human ES cells, EG cells or other cells of a pluripotent nature are combined with a non-human embryo, and Research in which human or non-human ES cells, EG cells or other cells of a 37 pluripotent nature are grafted to a non-human fetus Bioethics TCPS – Regulations and Guidelines – Stem Cells Research Involving Human Embryos: OK if… Article 12.7 (TCPS 2) Research on in vitro embryos already created and intended for implantation to achieve pregnancy is acceptable if: a) the research is intended to benefit the embryo; b) research interventions will not compromise the care of the woman, or the subsequent fetus; c) researchers closely monitor the safety and comfort of the woman and the safety of the embryo; and d) consent was provided by the gamete donors. 38 Bioethics TCPS – Regulations and Guidelines – Stem Cells Article 12.7 (TCPS 2) Research potentially altering the embryo by chemical or physical manipulation shall be distinguished from research directed at ensuring normal fetal development Research potentially altering the embryo by chemical or physical cannot be transplanted For example, the evaluation of potential teratogens and their effects on certain cell lineages may use early embryos, but those embryos must not be implanted for an ongoing pregnancy The Assisted Human Reproduction Act prohibits the creation of a human embryo specifically for research purposes, with the limited exception of creating an embryo for the purpose of improving, or providing instruction in, assisted reproduction procedures 39 Bioethics TCPS – Regulations and Guidelines – Stem Cells Research Involving Human Embryos: Article 12.8 (TCPS 2) Research involving embryos that have been created for reproductive or other purposes permitted under the Assisted Human Reproduction Act, but are no longer required for these purposes, may be ethically acceptable if: a) the ova and sperm from which they are formed were obtained in accordance with Article 12.7; b) consent was provided by the gamete donors; c) embryos exposed to manipulations not directed specifically to their ongoing normal development will not be transferred for continuing pregnancy; and d) research involving embryos will take place only during the first 14 days after their formation by combination of the gametes, excluding any time during which embryonic development has been suspended (e.g. cryogenically frozen) Article 12.6 (TCPS 2) Materials related to human reproduction for research use shall not be obtained through commercial transaction, including exchange for services 40