Principle 1: Respect For Persons PDF

24-Dec-21 Principle 1: Respect for Persons The informed consent process Requirements for documentation of informed consent Waivers of informed consent Diminished autonomy and legally authorized representatives Participation of pregnant women in resear...

24-Dec-21 Principle 1: Respect for Persons The informed consent process Requirements for documentation of informed consent Waivers of informed consent Diminished autonomy and legally authorized representatives Participation of pregnant women in research Assent from children and permission from parents Obtaining informed consent from prisoners Community consent 1 The objectives are: To outline the requirements for informed consent To state when waivers of informed consent and legally authorized representatives are appropriate 2 1  24-Dec-21 Respect for Persons The principle of respect for persons can be broken down into two basic ideas: – Individuals should be treated as autonomous agents – Persons with diminished autonomy are entitled to additional protections 3 Informed Consent Principle of respect for persons is primarily applied by requiring that all human subjects research participants provide voluntary informed consent to participate in research. The three fundamental aspects of informed consent are: – Voluntariness – Comprehension – Disclosure 4 2  24-Dec-21 Voluntariness and Comprehension Voluntariness Individualsʼ decisions about participation in research should not be influenced by anyone involved in conducting the research: “...consent must be freely given or truly voluntary.” Comprehension Individuals must have the mental or decisional capacity to understand the information presented to them in order to make an informed decision about participation in research. 5 Disclosure Researchers must disclose: 1. The purpose of the study 2. Any reasonably foreseeable risks to the individual 3. Potential benefits to the individual or others 4. Alternatives to the research protocol 5. The extent of confidentiality protections for the individual 6. Compensation in case of injury due to the protocol 7. Contact information for questions regarding the study, par cipantsʼ rights, and in case of injury 8. The conditions of participation, including right to refuse or withdraw without penalty 6 3  24-Dec-21 Disclosure This disclosure must be made in such a way that it provides a reasonable person the information she or he would need in order to make an informed decision. Regulations require that investigators obtain legally effective informed consent from prospective participants in a way that allows them to consider whether or not to participate and that minimizes the possibility for coercion or undue influence. Potential participants must understand that enrolling in the research is voluntary and that they may withdraw from the study at any time without penalty or loss of benefits In order for participation in research to be voluntary, the potential for coercion and undue influence must be minimized. 7 Case Study: Sleeping Sickness Study on Campus An investigator, who is a professor at a large university, is developing a grant application for submission to the NIH to study sleeping sickness (trypanosomiasis). This study will investigate surface antigen expression in trypanosomes, the parasite that causes sleeping sickness, in order to develop a vaccine. These parasites grow in human blood and lymph. The study will require fresh human blood daily for several months, and thus will require research participants. A research assistant will maintain a schedule of research participants to ensure that the study performs one collection per day and that blood collections are in accordance with American Red Cross Blood Donation Eligibility Guidelines i.e., healthy, weigh at least 110 pounds, and have not donated a pint (570 ml.) of whole blood in the last 8 weeks (56 days). Participants will be compensated. 8 4  24-Dec-21 Case Study: Sleeping Sickness Study on Campus It is now time to make a decision about recruitment of the research participants. Based on the number of students and employees in her classes and lab, the researcher feels confident that she will have enough participants needed for the proposed research if she simply recruits among them. But she knows that some colleagues advertise their studies through postings on campus. The investigator is faced with two possible options for recruiting normal, healthy research participants: – Recruit the students in her upper level classes and the technicians from her lab, and give $5 compensation to participants per blood draw, or – Recruit from the general university population (students, faculty and staff) by posting fliers around campus, and give $5 compensation to participants per blood draw The investigator discusses the grant application and proposed research procedures with you. You think that the compensation plan is appropriate and that $5 would not be an undue influence for either population to participate. 9 From which population would you advise the researcher to recruit? 1. Recruit the students in her upper level classes and the technicians from her lab to participate in the study. 2. Post fliers around campus to recruit participants from the campus population (students, faculty, and staff). 10 5  24-Dec-21 Asking for study participants from a population over which a researcher has authority is not the best idea. It is generally agreed that students and employees are groups that can be vulnerable to coercion. Even though the researcher may feel confident that she would never let her studentsʼ and employeesʼ decisions about participation affect her opinions about them, her students and employees might feel pressured to participate simply because she is in a position of authority. Recruiting for the study participants from the students, faculty and staff of the university is the best choice. However, in this situation, the recruitment plans include the entire campus community. As long as she does not mention her proposed research in her classes and there is no indication that she will be in a position of authority over the individuals who choose to contact her, the proposed population is not vulnerable to coercion. The researcher should post fliers around campus to recruit participants from the campus population (students, faculty, and staff) - Answer 2 is correct. 11 Informed Consent Informed consent should be understood as an on-going process rather than a level of legal protection for an institution. It is not intended to be a one-time act of having a participant sign a form. Informed consent is designed to inform research subjects about the purpose, risks, potential benefits and alternatives to the research that allows people to make a decision about whether or not to participate based on their own goals and values. This exchange of such information should occur at enrollment and throughout the study. Investigators are responsible for providing information during the informed consent process in a manner that is understandable to the potential participants. Investigators should not enroll anyone in a study unless the investigator is confident that the individual comprehends all information disclosed and agrees to procedures described during the informed consent process. 12 6  24-Dec-21 Informed Consent Investigators can use methods in addition to a consent form to enhance individualsʼ comprehension. Some examples include: – Oral presentations that provide potential participants with the opportunity to discuss the information and ask questions – Providing additional educational materials, such as brochures, about research in general and/or the specific procedures that will be used in the study – Video presentations that familiarize potential participants with the procedures that will be used in the study The informed consent process must be delivered in “… language that is understandable to the subject …” This may mean adjusting the reading levels of documents provided or translating documents and presentations into the language with which participants are most comfortable. 13 Case Study: Sleeping Sickness Study on Campus Now that your colleague studying sleeping sickness has decided on the method of recruitment for the study participants, she must write an informed consent document for the participants to sign. The researcher has prepared two different draft consent documents and must select one to submit to her IRB for review. Read the two consent documents and then choose the document that best informs the potential participants about the study in which they will enroll 14 7  24-Dec-21 Consent Document 1 Dr. X You are invited to participate in this study by giving blood on a voluntary basis, but no more than five times in an eight week period. The research project is anticipated to continue for four years. All blood draws will be performed by qualified technicians at the Medical Center Blood Bank. 100 ml of blood will be withdrawn from a vein in your arm. Although you will not benefit directly from participating in this study, you will make a major contribution to the information known about trypanosomiasis, also known as sleeping sickness. In the future, others may benefit because scientists and doctors will learn about how parasites cause sleeping sickness, and will develop vaccines to prevent it. You will be paid $5 for the time and travel required to give blood. Your signature on this form means that you understand that participation is voluntary, and you may withdraw from the study at any time. _________________________________________ Signature of Participant Contact information for Dr. X: Email: [email protected] phone: 123-456-7890 15 Consent Document 2 Dr. X Dr. Xʼs laboratory studies the parasite which causes trypanosomiasis, also known as sleeping sickness. This study will look at the effects of different surface antigens (proteins) produced by the parasites in human blood. The goal is to identify how different surface antigens are expressed by the parasites. You are invited to participate in this study by giving blood on a voluntary basis, but no more than five times in an eight week period. The research project is anticipated to continue for four years. All blood draws will be performed by qualified technicians at the Medical Center Blood Bank. 100 ml of blood will be withdrawn from a vein in your arm. None of the procedures are experimental. During the collection of blood, you may experience discomfort and bruising at the site of collection. To minimize these risks, you will be asked to lie down while an experienced technician collects the blood sample. You may feel light-headed after having blood drawn. If you feel faint, you should not get up and should notify a nurse. Although you will not benefit directly from participating in this study, you will make a major contribution to the information known about sleeping sickness. In the future, others may benefit because scientists and doctors will learn about how parasites cause sleeping sickness and will develop vaccines to prevent it. A research assistant will keep a record of all blood draws in a secure database. Only the professional staff at the Medical Center will know the identity of study participants. You will be paid $5 for the time and travel required to give blood. If you feel that you have been injured as a direct result of participating in the study, please contact Dr. X at 123-456-7890. Your signature on this form means that you understand the information presented, and that you want to participate in the study. You understand that participation is voluntary, and you may withdraw from the study at any time. 16 8  24-Dec-21 Which of these two consent documents would you choose to use: Consent Document 1 or 2? Consent Document 1 does include information regarding potential benefits to others and compensation for participants, there is no information regarding the following: 1. Risks for the participant 2. Confidentiality protections 3. Contact information for questions regarding the study 4. The conditions of participation, including right to refuse or withdraw without penalty Consent Document 2 includes the following required elements of informed consent: 1. The purpose of the study 2. Foreseeable risks/discomforts to the individual 3. Potential benefits to the individual or others 4. Confidentiality protections for the individual 5. Compensation plan 6. Contact information for questions regarding the study, par cipantsʼ rights, and in case of injury 7. The conditions of participation, including right to refuse or withdraw without penalty 17 Therefore, Consent Document 1 does not include all of the required elements of informed consent and does not protect against the perception of coercion. Consent Document 2 contains all of the required elements of informed consent and protects against the perception of coercion by emphasizing the fact that participation is voluntary and explaining how someone can withdraw from the study if they wish. Consent Document 2 is the best choice. 18 9  24-Dec-21 Waivers of Informed Consent The HHS regulations allow institutional review boards (IRBs) to waive or alter some or all of the required elements of informed consent if all of the following conditions are met: – “The research or demonstration project is to be conducted by or subject to the approval of state or local government officials and is designed to study, evaluate, or otherwise examine: (i) public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; (iv) possible changes in methods or levels of payments for benefits or services under those programs, and – The research could not practicably be carried out without the waiver or alteration.” 19 Waivers of Informed Consent The HHS regulations also allow IRBs to waive or alter some or all of the required elements of informed consent if all of the following conditions are met: 1. “The research involves no more than minimal risk to the subjects 2. The waiver or alteration will not adversely affect the rights and welfare of the subjects 3. The research could not practicably be carried out without the waiver or alteration 4. Whenever appropriate, the subjects will be provided with additional pertinent information after participation” 20 10  24-Dec-21 Practicability and Waivers of Informed Consent Decisions about waivers of informed consent often concern the issue of practicability. Although practicability is not defined in the HHS regulations, it is not sufficient for an investigator to argue simply that seeking consent would be time consuming or incur additional cost. In some situations, a waiver of informed consent may be appropriate for a medical record review or for using existing data or specimens that can be linked to identifiable individuals. Specific decisions regarding practicability are made by the IRB. 21 Case Study: New Analyses of Existing Data An investigator has collected identifiable data from participants in a research study. He has completed the analyses that were originally proposed and described in the NIH grant application, the protocol approved by the IRB, and the informed consent document approved by the IRB. The informed consent document made no mention of using the data in additional research but gives permission for the investigator to re-contact the participants. Now, based on new hypotheses, the investigator plans to conduct new analyses to fulfill purposes different from those described in the informed consent document, the NIH grant application and the IRB-approved protocol. He knows that he needs to obtain approval for the new research from his IRB and his NIH Program Official. Does the investigator need to obtain new informed consent from the participants? 22 11  24-Dec-21 Either answer may be correct. The investigator needs to obtain informed consent unless: – The criteria for a waiver are met, and – The IRB has approved a waiver of informed consent. 23 Requirements for Documentation of Informed Consent Typical regulations require that informed consent be documented using a written form that either contains all of the required elements or a short form that states that all of the required elements have been presented orally. This form must be signed by either the participant or the par cipantʼs legally authorized Representative. 24 12  24-Dec-21 Requirements for Documentation of Informed Consent The HHS regulations allow IRBs to waive the requirement for documented informed consent if they find that either: – “The only record linking the participant to the research would be the (informed) consent document and the principal risk to the participants would be the potential harm resulting from a breach of confidentiality. Each subject will be asked whether the subject wants documentation linking the subject with the research, and the subjectʼs wishes will govern, or – The research presents no more than minimal risk to the participants and involves no procedures for which written consent is normally required outside of the research context.” 25 Diminished Autonomy An individualʼs autonomy can be affected by several factors including age, cognitive impairment, illness, and treatments. An individualʼs capacity to consent to a particular study should be assessed based on: 1. The individualʼs level of capacity, and 2. The complexity and risks of the study, i.e., the capacity needed for an individual to be able to understand the study well enough to consent to participate 26 13  24-Dec-21 Decisional Capacity and Legally Authorized Representatives The Belmont principle of respect for persons states that investigators need to make special provisions when including individuals in research who have diminished capacity for making decisions in their own best interests. The HHS regulations, therefore, require that legally authorized representatives provide voluntary informed consent for individuals with diminished capacity to participate in research. 27 Decisional Capacity and Legally Authorized Representatives While some typical regulations allow for legally authorized representatives to make substituted decisions for individuals who need assistance, investigators should obtain consent from the participants to the extent possible. Because some individuals may be only temporarily or intermittently incapacitated (e.g., due to injury or medications), investigators should attempt to approach these individuals at a time when they do have the capacity to consent to research. If a participant regains the capacity to consent to research after the research has begun, investigators should obtain the participantʼs informed consent before continuing his or her participation in the study. 28 14  24-Dec-21 Participation of Pregnant Women in Research Because research involving pregnant women may affect the woman, the fetus, or both the woman and the fetus, additional issues must be considered for studies of pregnant women. Typical regulations require: – Preclinical studies be completed prior to the involvement of pregnant women – A consideration of risks and potential benefits for the fetus and pregnant woman 29 Participation of Pregnant Women in Research Typical regulations prohibit: – Inducements of any kind to terminate a pregnancy – Investigators from taking part in decisions about terminating a pregnancy – Investigators from determining the viability of a neonate Investigators, IRBs, and funding agencies must comply with requirements described in Subpart B of the HHS regulations. 30 15  24-Dec-21 Children’s Participation in Research Children may not have full capacity to make decisions in their own best interests; and therefore: – Children are considered a vulnerable population, and – Children are unable to provide “legally effective informed consent” Because children cannot provide informed consent, children provide assent to participate in research, to the extent that they are able, and parents/guardians given permission for a child to participate in research. 31 Children’s Participation in Research The additional regulatory requirements of assent and permission for research involving children are intended to make sure that investigators respect the decisions of both children and their parents. Parental permission must be obtained for research involving children 32 16  24-Dec-21 Assent and Permission for Children’s Participation in Research The ages, maturity and psychological states of the children involved in the research should be taken into account when determining whether children have the capacity to assent. This determination is made by the IRB. The IRB may require that investigators conduct an individual assessment of each childʼs ability to assent or may make a general determination for all children involved in the study. The content and language of the assent process should be appropriate to the age and education/developmental stage of the children providing assent. It may be necessary to have multiple assent documents or assent processes if the children to be enrolled in the research are of different ages or at different stages of development. 33 Case Study: Lack of Assent from a Child A 7-year-old child has a rare genetic disorder. No treatment is currently available. You have designed a longitudinal study that will examine the progression of the disorder. The study will involve standard physical and psychological examinations, including drawing 10ml of blood 4 times per year. After enrollment, at which time the parents provided permission for the child to participate in the study and the child provided assent, he panics and screams that he doesnʼt want to participate and wants to go home when he sees the nurse holding a needle for the blood draw. The parents are present and want the child to participate. Do you need to withdraw this child from your study because he has withdrawn his assent? 34 17  24-Dec-21 A number of issues should be considered to assist with decision-making. First, investigators need to identify the institutional resources available to help decide the appropriate action, e.g. the IRB, the Ethics Committee, a research par cipantʼs advocate, the pa entʼs personal physician. Second, the investigators and others involved in the deliberations should consider issues such as: – Is the child old enough to provide assent? – Are there creative strategies the investigators could implement in order to gain the childʼs cooperation? – Does the study offer the prospect of direct benefit to the children enrolled? – How severe is the childʼs fear? How insistent is he that he not be stuck? – Is there a way to alleviate the childʼs fear so that he can participate without using coercion or undue influence? – Could the child wait for a year or two and enroll in the study later (once his fear may have decreased)? This is not an easy question because it does not have a clear “yes” or “no” answer. 35 Obtaining Informed Consent from Prisoners Research involving prisoners requires approval by an IRB whose membership is specifically constituted to address the concerns of this vulnerable population Additional protections for prisoners who are involved as participants in research are required because they may “be under constraints because of their incarceration which could affect their ability to make a truly voluntary and uncoerced decision whether or not to participate as subjects in research.” 36 18  24-Dec-21 Obtaining Informed Consent from Prisoners The requirements specific to informed consent for prisoners are: 1. “Any possible advantages accruing to the prisoner through his or her participation in the research, when compared to the general living conditions, medical care, quality of food, amenities and opportunity for earnings in the prison are not of such a magnitude that his or her ability to weigh the risks of the research against the value of such advantages in the limited choice environment of the prison is impaired” 2. “Adequate assurance exists that parole boards will not take into account a prisonerʼs participation in the research in making decisions regarding parole, and each prisoner is clearly informed in advance that participation in the research will have no effect on his or her parole” 37 Community Consultation In some cultures it is not appropriate to obtain informed consent solely from the individual participants, because the individualʼs interests may be considered to be intimately entwined with their communityʼs interests. The appropriate way to attain community consent may vary widely, but is often achieved through meetings with large groups of community representatives or community leaders. It is also appropriate to consult a community before conducting research when the research involves risk to discrete, identifiable populations. For example, members of a community may feel stigmatized if a number of members of that community participate in research that may reveal unpopular or dangerous traits. 38 19  24-Dec-21 Emergency Research One example of a situation in which community consent is required is emergency research in life-threatening situations where obtaining informed consent is not feasible. In order for investigators to obtain a waiver of informed consent for emergency research, investigators must obtain consent from the communities in which the research will be conducted in addition to a number of other requirements. These requirements are described in Informed Consent Requirements in Emergency Research Investigators should note that this emergency waiver of informed consent does not apply to research that deal with pregnant women, human fetuses and neonates or prisoners. 39 Respect for Persons: Summary During the informed consent process, the principle of respect for persons is applied by requiring that all human subjects provide voluntary informed consent to participate in the research. Practical application of this principle means that potential study participants must: – Give their consent freely and voluntarily – Have the decisional capacity to understand the information presented to them – Be provided complete information about the study in order to make an informed decision 40 20  24-Dec-21 Respect for Persons: Summary This module has examined: – Information that should be included during the informed consent process – The types of situations that can be considered for waiver of informed consent – The appropriate involvement of legally authorized representatives for consent – Obtaining consent from vulnerable populations, e.g. pregnant women, prisoners and children – The need to undertake community consultation when the individualʼs interests are intimately entwined with their communityʼs interests 41 Terminology on Respect Informed consent Disclosure Waiver of informed Informed decision consent Undue influence Diminished autonomy Coercion Legally authorized representative Minimal risk Assent and permission Practicability Community consent and Documentation of consultation informed consent Autonomous agent Identifiable population Voluntariness Emergency research Comprehension and emergency waiver 42 21