Principle 3: Justice PDF

24-Dec-21 Principle 3: Justice The definition of justice has two parts: Fair procedures and outcomes are used to select research participants, and There is a fair distribution of benefits and burdens to populations who partic...

24-Dec-21 Principle 3: Justice The definition of justice has two parts: Fair procedures and outcomes are used to select research participants, and There is a fair distribution of benefits and burdens to populations who participate in research 1 Individual Justice and Social Justice The Belmont Report distinguishes social justice and individual justice in the selection of subjects: Individual justice requires that investigators “should not offer potentially beneficial research only to some patients who are in their favor or select only ʻundesirableʼ persons for risky research.” Social justice “requires that distinction be drawn between classes of subjects that ought, and ought not, to participate in any particular kind of research, based on the ability of members of that class to bear burdens and on the appropriateness of placing further burdens on already burdened persons.” 2 1  24-Dec-21 More on Social Justice “The choice of participants in research needs to be considered carefully to ensure that groups (e.g., welfare patients, particular racial and ethnic minorities, or persons confined to institutions) are not selected for inclusion mainly because of easy availability, compromised position, or manipulability.” These advancements are provided to those who can benefit from them, and The research should involve persons from groups who are likely to benefit from subsequent applications of the research 3 Equity vs. Equality in Human Subjects Research The meanings of “equity” and “equality” are similar, but not the same. The difference between equity and equality has important implications for justice in research. To treat “equitably” means to treat fairly; To treat “equally” means to treat in exactly the same way. Research should strive for equitable distribution of the risks and potential benefits of the research. This means that investigators are treating the groups involved in the research fairly and justly. It does not necessarily mean that all groups are equally represented, but that their representation is fair and just based on the risks and potential benefits associated with the research. 4 2  24-Dec-21 Equitable Distribution In order to achieve an equitable distribution of the risks and potential benefits of the research, investigators must determine the distribution of different groups (men and women, racial or ethnic groups, adults and children, age, etc.) in the populations that: 1. May be affected by the disease or condition under study, and 2. That are anticipated to benefit from the knowledge gained through the research 5 Challenges to Achieving an Equitable Distribution of Benefits and Burdens Investigators must ensure that the participants recruited for the research will not be unduly burdened and that recruitment reflects the diversity of the population that may benefit from the knowledge generated from the study. Individuals with the advantages of wealth and education may have an unfair advantage in terms of reaping the benefits of research because they may be able to afford new and costly treatments more easily than individuals in resource-poor settings. 6 3  24-Dec-21 Inclusion Policies: Women and Minorities One way the justice principle is applied is through the inclusion of women and minorities as participants in human subjects research. Because knowledge gained from clinical research may define health policy and shape standards of care for all patients, it is important to consider whether the intervention or therapy under scrutiny “affects women or men or members of minority groups and their subpopulations differently.” 7 Case Study: Migraine Intervention Trial A researcher seeks to improve treatment for severe migraines that are partially responsive to oral medication. He proposes to test whether acupuncture, in addition to a suffererʼs oral medication, is more effective treatment than oral medication alone. Because women are three times more likely to experience migraines than men, he proposes to enroll three times as many women as men. They will be recruited from racially and ethnically diverse communities. Does this study design fulfill the principle of justice? 8 4  24-Dec-21 Case Study: Migraine Intervention Trial The research includes women and men in proportion to the rates of severe migraines experienced by each sex, and is designed to have racial and ethnic diversity. The study provides both sexes and racial/ethnic communities with the opportunity for benefits from the clinical trials, and does not unfairly burden any single group with the risks of research. Its design is fair. This study design does fulfill the principle of justice. 9 Case Study: Esophageal Cancer A group of investigators proposes to investigate genetic factors that may increase risks for esophageal cancer. Genetic factors in esophageal cancer are not well understood and esophageal cancer occurs in many racial and ethnic populations. The investigators propose to collect DNA from cheek swabs and administer a risk factor questionnaire. Both cancer patients and age-matched controls will be included. The investigators have access to a predominantly Caucasian sample, and have no plans to recruit participants outside of their available pool. Is this an acceptable strategy? 10 5  24-Dec-21 Case Study: Esophageal Cancer Policies require that inclusion be generalizable to the population of the country. Acceptable inclusion of women and/or minorities depends both upon the scientific question addressed by the study and the prevalence of the disease, disorder, or condition in these populations. In this case, it is scientifically appropriate to include a broad population. Failure to include groups that would be affected by this condition could result in gaps in scientific knowledge. This is not an acceptable strategy. 11 Inclusion of Children in Research Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects. The policy emerged from the observation that children have often received treatments that have only been tested in adults, and that there is insufficient data on safe and effective uses for many treatments provided to children. Although the past practice of excluding children may have stemmed from good motives, “protecting” children in this way has resulted in: Denying children the benefits of participation in research, and Preventing the collection of sufficient data about the effects of agents in children 12 6  24-Dec-21 Question: If disease X affects children twice more than adults and affects male three times more than female, then what would be an equitable distribution of research participants: male-adult : female-adult : male-child : female-child The answer is: 3:1:6:2 13 Excluding Children from Research Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects states that children must be included in all supported human subjects research unless “… there are scientific and ethical reasons not to include them.” If an investigator proposes to conduct clinical research that does not include children, the exclusion of children must be fully justified using one or more of the exceptions described in the Policy. 14 7  24-Dec-21 Policy Exceptions 1. The research topic to be studied is irrelevant to children … 2. There are laws or regulations barring the inclusion of children in the research … 3. The knowledge is already available for children or will be obtained from another on-going study, and an additional study will be redundant … 4. A separate, age-specific study in children is warranted and preferable … 5. Insufficient data are available in adults to judge potential risk in children … in some instances, the nature and seriousness of the illness may warrant (childrenʼs) participation based on careful risk and benefit analysis... 6. The study design is aimed at collecting additional data on pre-enrolled adult study participants … 7. Other special cases justified by the investigator and found acceptable to the review group and Institute Director 15 Definition of Children Children are: “Persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted.” The need for protections for “children” is defined by the location in which the study will take place and the research procedures. Research that involves children must follow the requirements for parental permission and child assent. 16 8  24-Dec-21 Inclusion Policy The Policy and Guidelines on the Inclusion of Children as Participants in Research defines children as: “Individuals under the age of 21.” Research conducted or supported must follow both the requirements for protections and the requirements for the inclusion of children. 17 Case Study: Selecting Populations to Include in Clinical Research Below are a series of three different proposed clinical research studies and the appropriate population that should be used for each. Match the appropriate population with the proposed clinical research below: 18 9  24-Dec-21 Case Study: Selecting Populations to Include in Clinical Research Match the appropriate population with the proposed clinical research below: Research on early diagnosis of senile dementia The appropriate population for this clinical research is adults only. Senile dementias most commonly affect adults and it would not be appropriate to include children in research for which there is no clinical relevance. 19 Clinical trial comparing approved treatments for leukemia The appropriate population for this clinical research is children and adults. Since leukemia is a disease that can affect both children and adults, it is appropriate to include both populations in a clinical trial of approved treatments. 20 10  24-Dec-21 Experimental behavioral intervention to reduce bullying in elementary school classrooms The appropriate population for this clinical research is children only. An elementary school-based intervention would include whole schools or whole grades of children who, with parental permission, would participate in the research. 21 Justice and the Use of Placebos The use of placebos in clinical research is relevant to justice, respect for persons, and beneficence: researcherʼs duty not to exploit or deceive research participants and to treat them fairly. Risks associated with the use of placebos in research are: Deception Misleading research participants about the research purpose or procedures. Therapeutic misconception The tendency for research participants to: “downplay or ignore the risks posed to their own well-being by participation... [due to] the participants’ deeply held and nearly unshakeable conviction that every aspect of their participation in research has been designed for their own individual benefit.” 22 11  24-Dec-21 Justice and the Use of Placebos The principle of Justice requires that when placebos are used, prospective research participants must be treated fairly. Unless justifications for a waiver are approved, the informed consent process must disclose sufficient information to ensure that potential research participants: Understand what placebos are Understand the likelihood that they will receive a placebo Are able to provide their fully informed consent that they are willing to receive a placebo 23 Justifying the Use of Placebos Examples of justifications for the use of placebos include: 1. When there are no approved, effective treatments for the condition, or 2. If there is disagreement about whether standard treatment is better than placebo, or 3. When the additional risk posed by the use of placebo is minor and withholding the current standard therapy would not lead to serious or permanent harm, or 4. If the study is anticipated to result in widespread or major benefits and the receipt of placebo by individuals poses minimal risk 24 12  24-Dec-21 Incomplete Disclosure and Deception Incomplete disclosure and deception may be useful for some research goals, but researchers may use them only after thorough consideration of: Whether the scientific goals of the research can be achieved by methods that do not involve incomplete disclosure or deception Whether participants would consider the information withheld during the informed consent process important to their decision to participate in the study Whether it is possible to inform participants that they will only learn about all the goals of the research after the research study is over 25 Waiver of Informed Consent Incomplete disclosure and deception present challenges to justice because prospective par cipants ʼ “informed consent” will not be fully informed. Regulations allow informed consent to be waived only if: Participation in the research involves no more than minimal risk The waiver must not adversely affect the rights and welfare of research participants Incomplete disclosure or deception must be essential to the ability to carry out the research Whenever appropriate, research participants will be given additional pertinent information after they have participated in such a study (debriefing) 26 13  24-Dec-21 To Debrief or Not to Debrief Debriefing of research participants after the study involves an explanation of the deception or incomplete disclosure of research goals to participants as well as a complete disclosure of the true goals of the research. Debriefing is generally considered to be appropriate, but must depend on whether the disclosure will result in harm. Debriefing is appropriate when it will benefit the research par cipantʼs welfare by: “… correct(ing) misperceptions, or reduc(ing) pain, stress, or anxiety concerning the (research participant's) self- perception or performance …“ 27 Fairness in International Research When supported research takes place outside of the country questions about fair treatment and fair standards may arise. This may be especially true of research conducted in countries where: Resources may be scarce and/or Other vulnerabilities may be pronounced 28 14  24-Dec-21 A few of the many issues that demand careful consideration with respect to justice, as well as beneficence and respect for persons, include: How can research conducted in resource-poor setting avoid exploiting participants? What is owed to participants in clinical research and to the population of the host country after studies are complete? In addition to following the regulations, what standards and assurances to protect research participants should investigators and foreign institutions use when conducting research abroad? How can regional or cultural differences be negotiated? For settings where cultural values impact informed consent, how should processes be altered? 29 Sustaining Benefits Locally Investigators should think about how benefits to individual research participants and the local population may be sustained after the study is complete. When planning a study, researchers and sponsors may: “… make reasonable, good faith efforts before the initiation of a trial to secure, at its conclusion, continued access for all participants to needed experimental interventions that have proven effective for the participants …” Consider how any effective treatment emerging from the research could be provided to the rest of the population. 30 15  24-Dec-21 IRB Review for Research in International Settings Institutions have a profound responsibility to ensure that all IRBs designated under Federalwide Assurance possess sufficient knowledge of the local research context to satisfy the requirements for human subjects protections regardless of the IRBʼs geographic location relative to the institution and the research. Knowledge of the local context may be provided by: Specialists with personal, direct knowledge of the local research context who participate in IRB discussions and provide insight on achieving protections for research participants An IRB situated within the local research context 31 Local Cultural Norms and Informed Consent In unfamiliar settings, investigators should: Become familiar with local cultural norms and Seek guidance from community advisors and the IRB Investigators should incorporate cultural norms into the research process whenever possible and appropriate. Examples of cultural norms include community consent and informed consent from family representatives: If community consent is the cultural norm, it may be appropriate to obtain community consent in advance of obtaining informed consent from individuals. Community consent cannot replace the informed consent from individuals. If cultural norms require permission from a family member before an individual may enroll in research, it may be appropriate to obtain permission from the family member in addition to informed consent from the prospective research participant. 32 16  24-Dec-21 Justice: Summary Justice requires: Fair procedures and outcomes in the selection of research participants, and Distribution of benefits and burdens among the populations participating in research. Individual justice requires that: Benefits of participation in research are offered to a diverse eligible population, and Risks of participation in research are shared by a diverse population Social justice requires that consideration is given to classes of subjects that ought, and ought not, to participate in research. Considerations are based on: The ability of members of that class to bear burdens and The appropriateness of placing further burdens on already burdened persons. 33 The Justice section also examines: Inclusion of women, minorities and children Placebos Incomplete disclosure and deception Debriefing participants after the study International research Research in resource-poor countries Justice section also discusses the NIH guidelines regarding continued treatment for research participants in HIV/AIDS antiretroviral studies. 34 17  24-Dec-21 Terminology on Justice Benefits and burdens Therapeutic misconception Inclusion Waiver of informed consent Social justice Fair treatment / fair standard Individual justice Debriefing Fair and just treatment Undue burden IRB Equitable distribution Local cultural norms Permission and assent Community consent Deception / incomplete disclosure 35 18