ANOTHER LOOK AT THE PRESUMED-VERSUS-INFORMED CONSENT DICHOTOMY IN POSTMORTEM ORGAN PROCUREMENT

In this paper I problematise quite a simple assertion: that the two major frameworks used in assessing consent to post‐mortem organ donation, presumed consent and informed consent, are procedurally similar in that both are ‘default rules.’ Because of their procedural common characteristic, both rules do exclude marginalized groups from consent schemes. Yet this connection is often overlooked. Contract theory on default rules, better than bioethical arguments, can assist in choosing between these two rules. Applying contract theory to the question of post‐mortem organ donation suggests that the default rule should be one that goes against the wishes of the stronger party in consent decisions.     

The student and the ovum: The lack of autonomy and informed consent in trading genes for tuition

Rising tuition costs have forced university students to become creative in finding ways to fund their education. Some female university students have decided that ova donation may be an acceptable alternative in which to pay for their tuition. This alternative presents itself because of the insufficient number of ova available for assisted reproduction and emerging stem cell technologies. Young female university students are encouraged by Internet sources and respectable electronic and print media to donate their ova in the cause of assisted reproduction for monetary compensation. While university students generally exhibit autonomy, the constraining influence of their financial predicament compromises the elements of informed consent (voluntariness, competence, capacity, understanding, and disclosure) as to their making an autonomous decision in regard to egg donation. Thus, any moral possibility of giving informed consent is negated. Informed consent can only occur through autonomy. A female university student in need of financial resources to pay for her education cannot make an autonomous choice to trade her genes for tuition. Donated ova are not only needed for assisted reproduction, but for stem cell technologies. While the long-term health of women who donate their ova is of concern (a potential risk of cancer after long term use of ovulation induction), of equal concern is the possibility of a growth in the trade of ova targeting third world and Eastern European women where the precedence for autonomy and informed consent is not well established.     

‘Science is really needed—that’s all I know': informed consent and the non-verbal practices of collecting blood for genetic research in northern Sweden

In Va¨sterbotten County in northern Sweden a start-up biotech company has recently gained all commercial rights to one of the worlds largest population based research biobanks. The biobank and the company have publicly emphasized that all donors have given their informed consent to participate, but within the academy it has become debated whether people have been adequately informed. Based on anthropological fieldwork it is shown that many people do not read the information provided. The data do not, however, suggest that donors themselves perceive a lack of information. This article endeavours to make meaningful the apparent lack of interest among donors in the information they are offered. It is argued that the donation of blood should be analysed in its social and historical context rather than as a response to rational assessment of information of research purposes. It implies a conceptualisation of agency more aware of the intersubjective nature of moral negotiation than usually implied in studies of informed consent.     

The Consequences of Vagueness in Consent to Organ Donation

In this article I argue that vagueness concerning consent to post‐mortem organ donation causes considerable harm in several ways. First, the information provided to most people registering as organ donors is very vague in terms of what is actually involved in donation. Second, the vagueness regarding consent to donation increases the distress of families of patients who are potential organ donors, both during and following the discussion about donation. Third, vagueness also increases the chances that the patient's intention to donate will not be fulfilled due to the family's distress. Fourth, the consequent reduction in the number of donated organs leads to avoidable deaths and increased suffering among potential recipients, and distresses them and their families. There are three strategies which could be used to reduce the harmful effects of this vagueness. First, recategorizing the reasons (commonly referred to as ‘overrules’ under the current system) given by families who refuse donation from registered donors would bring greater clarity to donation discussions. Second, people who wish to donate their organs should be encouraged to discuss their wishes in detail with their families, and to consider recording their wishes in other ways. Finally, the consent system for organ donation could be made more detailed, ensuring both that more information is provided to potential donors and that they have more flexibility in how their intentions are indicated; this last strategy, however, could have the disadvantage of discouraging some potential donors from registering.     

'Science is really needed--that's all I know': informed consent and the non-verbal practices of collecting blood for genetic research in northern Sweden

In Vasterbotten County in northern Sweden a start-up biotech company has recently gained all commercial rights to one of the worlds largest population based research biobanks. The biobank and the company have publicly emphasized that all donors have given their informed consent to participate, but within the academy it has become debated whether people have been adequately informed. Based on anthropological fieldwork it is shown that many people do not read the information provided. The data do not, however, suggest that donors themselves perceive a lack of information. This article endeavours to make meaningful the apparent lack of interest among donors in the information they are offered. It is argued that the donation of blood should be analysed in its social and historical context rather than as a response to rational assessment of information of research purposes. It implies a conceptualisation of agency more aware of the intersubjective nature of moral negotiation than usually implied in studies of informed consent.     

Consenting to donation: an examination of current practices in informed consent for tissue donation in the US

Informed consent is the primary moral principle guiding the donation of human tissue for transplant purposes. When patients’ donation wishes are not known, family members making the decision about tissue donation should be provided with requisite information needed to make informed donation decisions. Using a unique dataset of 1,016 audiotaped requests for tissue obtained from 15 US tissue banking organizations, we examined whether the information provided to families considering tissue donation met current standards for informed consent. The results indicated that many elements of informed consent were missing from the donation discussions, including the timeframe for procurement, autopsy issues, the involvement of both for-profit and nonprofit organizations, and the processing, storage and distribution of donated tissue. A multiple linear regression analysis also revealed that nonwhites and family members of increased age received less information regarding tissue donation than did younger, white decision makers. Recommendations for improving the practice of obtaining consent to tissue donation are provided.     

Who Should Control the Use of Human Embryonic Stem Cell Lines: A Defence of the Donors' Ability to Control

In this paper I analyse who should be able to control the use of human embryonic stem cell lines. I distinguish between different kinds of control and analyse a set of arguments that purport to show that the donors of gametes and embryos should not be able to control the use of stem cell lines derived from their embryos. I show these arguments to be either deficient or of so general a scope that they apply not only to donors but also to those who derived the stem cell lines. Since we normally think that stem cell derivers have the right to control the use of the cell lines they derived, we have no justification for denying donors similar rights of control. In the final section I briefly discuss why informed consent is not an appropriate vehicle for transferring or alienating control rights.     

Factors associated with consent for organ donation: a retrospective population-based study

Background:Optimizing the approach to and consent of potential organ donors maximizes patient autonomy and the availability of organs for transplants. We set out to identify modifiable factors associated with donation consent.Methods:We conducted a retrospective cohort study of consecutive adults (≥ 18 yr) referred for organ donation in Ontario between April 2013 and June 2019. We analyzed patient clinical data and demographics, data on substitute decision-makers and characteristics of the donation consent approach. Study outcomes were consent for organ donation and approach rate. We evaluated independent associations between consent and approach-and system-level factors.Results:We identified 34 837 referrals for organ donation, of which 6548 (18.8%) substitute decision-makers were approached for consent. Of these, 3927 (60.0% of approaches) consented for organ donation and 1883 (48.0% of consents) patients proceeded to be organ donors. The most common reason substitute decision-makers were not approached for consent in a case with donation potential was a late referral by the health care team (45.2%). Modifiable factors independently associated with consent included a telephone approach for consent (adjusted odds ratio [OR] 0.46, 95% confidence interval [CI] 0.35–0.58) and a collaborative approach by a physician and donation coordinator (adjusted OR 1.26, 95% CI 1.01–1.59).Interpretation:Consent for organ donation was associated with several modifiable factors. Organizations should target interventions to ensure timely referrals to organ donation organizations, increase in-person consent approaches and increase physician participation in the approach process.

Many people die on transplant waiting lists because the demand for organs outstrips supply. Almost 4500 people are on organ transplant waiting lists in Canada. Despite public support for organ donation across Canada,¹ donation rates vary between 8.8 and 21.2 donors per million population, ² and a substantial pool of potential donors is not being realized. ^2,3 The identification, referral and approach of potential donors can be facilitated by policy, legislation and best practices, ^3,4 although the efficacy of interventions is variable across jurisdictions.^5,6 Some comprehensive interventions to increase donor numbers have not changed consent rates,⁷ suggesting that the consent approach process may be a target for improvement.Substitute decision-makers play an important role in the organ donation process, even in jurisdictions with donation consent registries or opt-out consent systems. Substitute decision-makers are almost always asked permission for organ donation, even when there is a registered donation consent,⁸ and their consent rates vary widely.⁹ Substitute decision-makers faced with consent decisions often do so in emotionally charged circumstances, and many do not know the explicit wishes of the patient.¹⁰ Given this context, the process of obtaining consent and the supports provided may have a substantial impact on the decision. Practices have been identified that improve consent rates from substitute decision-makers,¹¹ and these are routinely performed by large, high-performing organ donation organizations. Several epidemiological studies have identified nonmodifiable factors associated with donation consent (e.g., race, age, socioeconomic status and education).^12–15 The persistent variability in consent rates suggests that other modifiable factors may influence a substitute decision-maker’s decision to consent.We aimed to identify modifiable approach-and system-level factors that were associated with positive consent for organ donation in Ontario, Canada.     

Donation of embryos for human development and stem cell research

Using donated human embryos for scientific research raises ethical questions about the donation process. We describe a two-stage consent process designed to help couples make informed decisions about embryo disposition. This consent methodology minimizes conflict of interest, respects patient choice, and provides a much-needed resource to patients and the research community.     

Charitable State-Controlled Foundation Human Tissue and Cell Research: Ethic and Legal Aspects in the Supply of Surgically Removed Human Tissue For Research in the Academic and Commercial Sector in Germany

Tissue engineering using human cells and tissue has one of the greatest scientific and economical potential in the coming years. There are public concerns during the ongoing discussion about future trends in life sciences and if ethic boundaries might be respected sufficiently in the course of striving for industrial profit and scientific knowledge. Until now, the legal situation of using human tissue material for research is not clear. Accordingly, transparency of action and patients' information are a central component when handling patient material inside and outside of the patient-specific treatment. Whereas in the field of therapeutic use of tissue (e.g. transplantation) there is an emergency situation by the shortage of organs with the risk of the premature death of the potential recipient, this cannot be claimed for tissue donation for research. The basis of every surgical operation is the treatment contract, which places the doctor under obligation to the careful exercise of medical treatment containing the patient's informed consent. This contract only covers the treatment that is intended to cure the patient and the medical measures that are necessary therefor. The further scientific use of body-substances, which are discarded after an operation, are not included. Therefore a personal and independent written enlightenment of the patient and a declaration of informed consent is necessary. Examples of guidelines for tissue supply, Patients information and consent were worked out by theologists, lawyers, scientists and physicians reflecting their practical experience in transplant surgery and liver cell research. As a consequence to cover the ethical and legal aspect of tissue donation in Germany a charitable state-controlled foundation Human Tissue and Cell Research (HTCR) was introduced and established.     

A Confucian View of Personhood and Bioethics

This paper focuses on Confucian formulations of personhood and the implications they may have for bioethics and medical practice. We discuss how an appreciation of the Confucian concept of personhood can provide insights into the practice of informed consent and, in particular, the role of family members and physicians in medical decision-making in societies influenced by Confucian culture. We suggest that Western notions of informed consent appear ethically misguided when viewed from a Confucian perspective.     

TRUSTED CONSENT AND RESEARCH BIOBANKS: TOWARDS A ‘NEW ALLIANCE’ BETWEEN RESEARCHERS AND DONORS

We argue that, in the case of research biobanks, there is a need to replace the currently used informed consent with trusted consent. Accordingly, we introduce a proposal for the structure of the latter. Further, we discuss some of the issues that can be addressed effectively through our proposal. In particular, we illustrate: i) which research should be authorized by donors; ii) how to regulate access to information; iii) the fundamental role played by a Third Party Authority in assuring compliance with the reciprocal expectations and obligations of donors and scientists. Finally, we briefly analyse two issues that might represent important elements of a ‘new alliance’ between researchers and donors to which the trusted consent could pave the way: i) the correlations between needs and rights of the two parties, and ii) possible economic transactions.     

Registry of unrelated bone marrow donors.

Reports of successful transplantation of bone marrow obtained from unrelated donors who were histocompatibility leukocyte antigen (HLA) identical prompted the Canadian Red Cross Blood Transfusion Service in Ottawa to assess the possibility of developing a bone marrow donor registry in Canada. We sent a pamphlet that explained the program to 1568 people who had undergone apheresis and asked them to reply, stating their interest. At the same time the pamphlets and a poster were placed in the blood donor clinic. We received 1232 replies (78.6%) from the apheresis donors, 838 (68.0%) of which indicated a willingness to attend information sessions. Of the 7158 people who gave blood during the 3-month study period, 225 (3.1%) were interested. At the time this paper was written 47 information sessions had been held, and 721 people had attended, 624 (86.5%) of whom had signed a consent form. This indicates a clear interest in a bone marrow donation program. We believe that the ethical issues are overcome by requesting the donation before identification of any patient. From our experience a national registry of unrelated donors seems feasible, and steps are being taken to implement such a program.     

An Australian Based Study on the Readability of HIV/AIDS and Type 2 Diabetes Clinical Trial Informed Consent Documents

The aims of this study were to measure the readability of Australian based informed consent documents and determine whether informed consent readability guidelines have been established by Australian human research ethics committees (HRECs). A total of 20 informed consent documents, 10 HIV/AIDS and 10 type 2 diabetes, were measured for readability using the Simple Measure of Gobbledygook (SMOG) and Gunning Fog Index (Fog). Published guidelines and policy statements of the two local HREC who approved the 20 clinical trials under study where examined to identify whether they had any formal policies/guidelines on the readability of informed consent documents. The two HRECs were contacted via e-mail to also determine whether they utilised any informal readability standards or “rules of thumb” that may not have been mentioned in the published documents. The HIV/AIDS and type 2 diabetes informed consent documents were, on average, written at a grade 13 reading level. Formal readability standards had not been established by the two local HRECs, however, they did verify the use of informal rules for assessing readability of informed consent documents. Based on Australian literacy data, the majority of informed consent documents were written well beyond the reading ability of many Australians. Unreadable informed consent documents may result in patients rejecting trial participation altogether or conversely may result in their participating in a trial with inadequate consent. Therefore, a step toward reducing the complexity of informed consent documents may be to implement objective readability assessments into the human research ethics application and review process.     

The ethics of biobanking: Assessing the right to control problem for broad consent

The biobank consent debate is one with deeply held convictions on both the ‘broad’ and ‘specific’ side with little sign of resolution. Recently, Thomas Ploug and Soren Holm have developed an alternative to both specific and broad consent: a meta‐consent framework. The aim here is to consider whether meta‐consent provides a ‘solution’ to the biobank consent debate. We clarify what ‘meta‐consent’ actually is (arguing that the label is a misnomer and ‘consent à la carte’ is more accurate). We identify problems with Ploug and Holm's arguments, and some challenges for meta‐consent. We focus on whether there is any ethical obligation to provide consent à la carte. There may seem to be so, especially if we draw upon an unclear appeal to the ethical significance of ‘respect for autonomy’. Similarly, there might seem to be an intuitive inference from the fact that ethically legitimate research requires informed consent to the conclusion that it thereby requires consent à la carte. It is shown that this line of inference is mistaken.     

Manufacturing of gene-modified cytotoxic T lymphocytes for autologous cellular therapy for lymphoma

BACKGROUND: The production of therapeutic T-cell populations for adoptive immunotherapy of cancer requires extensive ex vivo cell processing, including the isolation or creation of Ag-specific T cells and their subsequent propagation to clinically relevant numbers. These procedures must be performed according to the principles of current good manufacturing practices (cGMP) for phase I clinical trials to ensure the identity, purity potency and safety of the cellular product. In this report we describe our approach to manufacturing and characterizing bulk populations of gene-modified autologous T cells for use in treating follicular lymphoma. METHODS: PBMC from healthy donors, obtained after informed consent, were stimulated in vitro with Ab to CD3epsilon (OKT3) and recombinant human IL-2 and then electroporated with plasmid DNA containing a human CD19-specific chimeric Ag receptor (CAR) gene and HSV-1 thymidine kinase (TK) gene. Stably transfected cells were selected in cytocidal concentrations of hygromycin B over multiple 14-day stimulation culture cycles and then cryopreserved. Vials of cryopreserved/selected T cells were used to initiate T-cell expansion cultures to produce cell products for clinical infusion. These cultures were characterized for phenotype, function and suitability for use in adoptive immunotherapy studies. RESULTS: Our results demonstrate that bulk populations of gene-modified T cells derived from peripheral blood of healthy donors express CD19+ chimeric Ag receptor at low levels and can specifically lyse CD19+ target cells in vitro. These cells display a differentiated T-effector phenotype, are sensitive to ganciclovir-mediated killing and display a non-transformed phenotype. TCR Vbeta usage indicated that all populations tested were polyclonal. Ex vivo cell expansion from cryopreserved cell banks is sufficient to produce doses of between 5 x 10(9) and 1 x 10(10) cells/run. One of three transductions resulted in a population of cells that was not suitable for infusion but was identified during release testing. No populations displayed any evidence of bacterial, fungal or mycoplasma contamination. DISCUSSION: We have established a manufacturing strategy that is being used to produce T cells for a phase I clinical trial for follicular lymphoma. Genetically modified T cells have been characterized by cell-surface marker phenotype, functional activity against CD19+ targets and requisite safety testing. These pre-clinical data confirm the feasibility of this approach to manufacturing T-cell products.     

Anonymity and informed consent in artificial procreation: a report from Denmark

The practice of informed consent in biomedicine is so widely spread that it must be considered the most important principle within bioethics, and the most universally appealed to within recent legislation. There seems to be a consensus as to its value in research on autonomous persons, but also a problem concerning its application when dealing with people having a serious mental, social or even physical disability.
Within the field of artificial procreation there are even more problems. Informed written consent is often demanded from anonymous donors of gametes in order to ensure their consent to the legal and moral consequences of their anonymity. The child resulting from the artificial procreation, on the contrary, cannot consent to, nor be informed before being conceived, of the secrecy laid on the identity of its genetic parents. Some countries resolve this problem by allowing the children, when they reach their majority, to obtain some information pertaining to the health or the identity of their genetic parents.
This presents ethical problems. It can be argued that the anonymity of the parents chiefly affects the children, so that an agreement on this point among parents, doctors and others must be regarded as invalid. The paper will argue that a law ensuring the complete anonymity of the parents is disregarding the informed consent and the interests of the children resulting from artificial procreation, and is thus doing more damage to society than good.     

Anonymity and Informed Consent in Artificial Procreation

The practice of informed consent in biomedicine is so widely spread that it must be considered the most important principle within bioethics, and the most universally appealed to within recent legislation. There seems to be a consensus as to its value in research on autonomous persons, but also a problem concerning its application when dealing with people having a serious mental, social or even physical disability.
Within the field of artificial procreation there are even more problems. Informed written consent is often demanded from anonymous donors of gametes in order to ensure their consent to the legal and moral consequences of their anonymity. The child resulting from the artificial procreation, on the contrary, cannot consent to, nor be informed before being conceived, of the secrecy laid on the identity of its genetic parents. Some countries resolve this problem by allowing the children, when they reach their majority, to obtain some information pertaining to the health or the identity of their genetic parents.
This presents ethical problems. It can be argued that the anonymity of the parents chiefly affects the children, so that an agreement on this point among parents, doctors and others must be regarded as invalid. The paper will argue that a law ensuring the complete anonymity of the parents is disregarding the informed consent and the interests of the children resulting from artificial procreation, and is thus doing more damage to society than good.     

Trouble in the Gap: A Bioethical and Sociological Analysis of Informed Consent for High-Risk Medical Procedures

Concerns are frequently raised about the extent to which formal consent procedures actually lead to “informed” consent. As part of a study of consent to high-risk medical procedures, we analyzed in-depth interviews with 16 health care professionals working in bone-marrow transplantation in Sydney, Australia. We find that these professionals recognize and act on their responsibility to inform and educate patients and that they expect patients to reciprocate these efforts by demonstrably engaging in the education process. This expectation is largely implicit, however, and when it is not met, this can give rise to trouble that can have adverse consequences for patients, physicians, and relationships within the clinic. We revisit the concept of the sick role to formalize this new role expectation, and we argue that “informed” consent is a process that is usually incomplete, despite trappings and assumptions that help to create the illusion of completeness.     

Influencing relatives to respect donor autonomy: Should we nudge families to consent to organ donation?

Refusing consent to organ donation remains unacceptably high, and improving consent rates from family or next‐of‐kin is an important step to procuring more organs for solid organ transplantation in countries where this approval is sought. We have thus far failed to translate fully our limited understanding of why families refuse permission into successful strategies targeting consent in the setting of deceased organ donation, primarily because our interventions fail to target underlying cognitive obstacles. Novel interventions to overcome these hurdles, incorporating an understanding of cognitive psychology and behavioral change therapy, may be beneficial. One potential intervention is to use the concept of nudge theory, where decision‐making is influenced by encouraging positive reinforcement and indirect suggestion. Purposefully nudging families to given consent for organ donation by understanding, and then overcoming, their inherent cognitive biases is novel but also controversial. This article explores the roles of relatives in decisions about organ donation, how nudge theory translates to organ donation and discusses the arguments for and against its application.