Data monitoring committees often are employed to review interim findings of randomised controlled trials. Interim findings are kept confidential until the data monitoring committee finds that they provide sufficiently compelling evidence regarding efficacy, typically because they have crossed the pre-defined statistical boundaries, or they raise serious concerns about safety. While this practice is vital to maintaining the scientific integrity of controlled trials and thereby ensuring their social value, it has been criticised as unethical. Commentators argue that withholding interim findings from (...) research participants is deceptive, inconsistent with valid informed consent, and a violation of respect for participants’ autonomy. The present article examines these arguments, focusing specifically on confidential data monitoring for efficacy. This practice need not be deceptive provided its use is disclosed to prospective research participants. In addition, confidential data monitoring does not make research participants worse off than they would be in the clinical setting and represents an acceptable limitation on the options available to prospective research participants. Taken together, these considerations suggest confidential data monitoring, subject to adequate safeguards, is ethically acceptable. (shrink)

Participants are often not informed by investigators who conduct randomised, placebo-controlled acupuncture trials that they may receive a sham acupuncture intervention. Instead, they are told that one or more forms of acupuncture are being compared in the study. This deceptive disclosure practice lacks a compelling methodological rationale and violates the ethical requirement to obtain informed consent. Participants in placebo-controlled acupuncture trials should be provided an accurate disclosure regarding the use of sham acupuncture, consistent with the practice of placebo-controlled drug trials.

Transplantation of vital organs has been premised ethically and legally on "the dead donor rule" (DDR)—the requirement that donors are determined to be dead before these organs are procured. Nevertheless, scholars have argued cogently that donors of vital organs, including those diagnosed as "brain dead" and those declared dead according to cardiopulmonary criteria, are not in fact dead at the time that vital organs are being procured. In this article, we challenge the normative rationale for the DDR by rejecting the (...) underlying premise that it is necessarily wrong for physicians to cause the death of patients and the claim that abandoning this rule would exploit vulnerable patients. We contend that it is ethical to procure vital organs from living patients sustained on life support prior to treatment withdrawal, provided that there is valid consent for both withdrawing treatment and organ donation. However, the conservatism of medical ethics and practical concerns make it doubtful that the DDR will be abandoned in the near future. This leaves the current practice of organ transplantation based on the "moral fiction" that donors are dead when vital organs are procured. (shrink)

Payment for research participation has raised ethical concerns, especially with respect to its potential for coercion. We argue that characterising payment for research participation as coercive is misguided, because offers of benefit cannot constitute coercion. In this article we analyse the concept of coercion, refute mistaken conceptions of coercion and explain why the offer of payment for research participation is never coercive but in some cases may produce undue inducement.

Risk–benefit assessment is a routine requirement for research ethics committees that review and oversee biomedical research with human subjects. Nevertheless, it remains unclear how to weigh and balance risks to research participants against the social benefits that flow from generating biomedical knowledge. In this article, we address the question of whether there are any reasonable criteria for defining the limit of permissible risks to individuals who provide informed consent for research participation. We argue against any a priori limit to permissible (...) research risks. However, attention to the uncertainty of potential social benefit that can be derived from any particular study warrants caution in exposing prospective research participants to a substantial likelihood of serious harm. (shrink)

Despite strong growth in scientific investigation of the placebo effect, understanding of this phenomenon remains deeply confused. We investigate critically seven common conceptual distinctions that impede clear understanding of the placebo effect: (1) verum/placebo, (2) active/inactive, (3) signal/noise, (4) specific/nonspecific, (5) objective/subjective, (6) disease/illness, and (7) intervention/context. We argue that some of these should be eliminated entirely, whereas others must be used with caution to avoid bias. Clearing away the conceptual underbrush is needed to lay down a path to understanding (...) and harnessing placebo effects in clinical medicine. (shrink)

Dual-track assessment directs research ethics committees to assess the risks of research interventions based on the unclear distinction between therapeutic and non-therapeutic interventions. The net risks test, in contrast, relies on the clinically familiar method of assessing the risks and benefits of interventions in comparison to the available alternatives and also focuses attention of the RECs on the central challenge of protecting research participants.Research guidelines around the world recognise that clinical research is ethical only when the risks to participants are (...) reasonable.1 Appropriate implementation of this requirement is vital to protecting research participants and allowing research to proceed when it poses acceptable risks. Unfortunately, as the US National Bioethics Advisory Commission notes: “current regulations do not further elaborate how risks and potential benefits are to be assessed, and little additional guidance is available to IRBs.”1The NBAC, as well as numerous commentators, recommend that research ethics committees , ethics review committees and institutional review boards should adopt what may be called dual-track risk assessment.2–5 Yet, dual-track assessment unnecessarily divides research interventions into two different categories before assessing their risks and relies on the unclear distinction between therapeutic and non-therapeutic interventions. As a result, dual-track assessment provides RECs with confusing guidance and has the potential to block valuable research that poses acceptable risks. This paper describes one alternative, the net risks test, and argues that this approach offers a better method for assessing research risks, one that puts RECs in a position to protect participants without blocking appropriate research studies.BACKGROUNDClinical research exposes participants to interventions and procedures to gather systematic data that may be used to improve overall health and well-being. To ensure that research is ethical, RECs must ensure that the risks and burdens to participants are not excessive and that …. (shrink)

Ethical guidelines for conducting clinical trials have historically been based on a perceived therapeutic obligation to treat and benefit the patient-participants. The origins of this ethical framework can be traced to the Hippocratic oath originally written to guide doctors in caring for their patients, where the overriding moral obligation of doctors is strictly to do what is best for the individual patient, irrespective of other social considerations. In contrast, although medicine focuses on the health of the person, public health is (...) concerned with the health of the entire population, and thus, public health ethics is founded on the societal responsibility to protect and promote the health of the population as a whole. From a public health perspective, research ethics should be guided by giving due consideration to the risks and benefits to society in addition to the individual research participants. On the basis of a duty to protect the population as a whole, a fiduciary obligation to realise the social value of the research and the moral responsibility to distribute the benefits and burdens of research fairly across society, how a public health perspective on research ethics results in fundamental re-assessments of the proper course of action for two salient topical issues in research ethics is shown: stopping trials early for reasons of efficacy and the conduct of research on less expensive yet less effective interventions. (shrink)

John McMillan's article raises numerous important points about the ethics of surgical castration of sex offenders.1 In this commentary, we focus solely on and argue against the claim that the offer of release from detention conditional upon surgical castration is a coercive offer that compromises the validity of the offender's consent. We take no view on the question as to whether castration for sex offenders is ethically permissible. But, we reject the claim that it is ethically permissible only if competing (...) ethical considerations outweigh worries about coercion. For in the situation described, the proposal is not coercive at all.McMillan states that if offenders agree to castration because they fear long-term detention, then ‘it seems, intuitively, as if agreeing to be castrated under these conditions makes the decision coerced in some way.’1 He adds that if castration is ‘the only way that they will be released back into the community, the status of this decision as a genuine expression of their autonomy is questionable.’1 In defence of his claim, he uses two analogies that he borrows from Joel Feinberg. First, if a governor offers to commute a death sentence if the prisoner agrees to participate in a medical experiment, then ‘it's clear that the governor is coercing the prisoner.’1 Second, if a millionaire offers to give a woman $1 000 000 …. (shrink)

Although established in the law and current practice, the determination of death according to neurological criteria continues to be controversial. Some scholars have advocated return to the traditional circulatory and respiratory criteria for determining death because individuals diagnosed as ‘brain dead’ display an extensive range of integrated biological functioning with the aid of mechanical ventilation. Others have attempted to refute this stance by appealing to the analogy between decapitation and brain death. Since a decapitated animal is obviously dead, and ‘brain (...) death’ represents physiological decapitation, brain dead individuals must be dead. In this article we refute this ‘decapitation gambit.’ We argue that decapitated animals are not necessarily dead, and that, moreover, the analogy between decapitation and the clinical syndrome of brain death is flawed. (shrink)

Male provisioning ability may have evolved as a “good dad” indicator through sexual selection, whereas male creativity may have evolved partly as a “good genes” indicator. If so, women near peak fertility (midcycle) should prefer creativity over wealth, especially in short-term mating. Forty-one normally cycling women read vignettes describing creative but poor men vs. uncreative but rich men. Women’s estimated fertility predicted their short-term (but not long-term) preference for creativity over wealth, in both their desirability ratings of individual men (r=.40, (...) p<.01) and their forced-choice decisions between men (r=.46, p<.01). These preliminary results are consistent with the view that creativity evolved at least partly as a good genes indicator through mate choice. (shrink)

Current guidelines on investigators' responsibilities to communicate research results to study participants may differ on whether investigators should proactively re-contact participants, the type of results to be offered, the need for clinical relevance before disclosure, and the stage of research at which results should be offered. Lack of consistency on these issues, however, does not undermine investigators' obligation to offer to disclose research results: an obligation rooted firmly in the principle of respect for research participants.

The practice of transplantation of vital organs from “brain-dead” donors is in a state of theoretical disarray. Although the law and prevailing medical ethics treat patients diagnosed as having irreversible total brain failure as dead, scholars have increasingly challenged the established rationale for regarding these patients as dead. To understand the ethical situation that we now face, it is helpful to revisit the writings of the philosopher Hans Jonas, who forcefully challenged the emerging effort to redefine death in the late (...) 1960s. (shrink)

Advances in life-saving technologies in the past few decades have challenged our traditional understandings of death. Traditionally, death was understood to occur when a person stops breathing, their heart stops beating and they are cold to the touch. Today, physicians determine death by relying on a diagnosis of ‘total brain failure’ or by waiting a short while after circulation stops. Evidence has emerged, however, that the conceptual bases for these approaches to determining death are fundamentally flawed and depart substantially from (...) the established biological conception of death. We argue that the current approach to determining death consists of two different types of unacknowledged legal fictions. These legal fictions were developed for practices that are largely ethically legitimate but need to be reconciled with the law. The considerable debate over the determination of death in the medical and scientific literature has not informed the public that vital organs are being procured from still-living donors and it seems unlikely that this information can remain hidden for long. Given the instability of the status quo and the difficulty of making the substantial legal changes required by complete transparency, we argue for a second-best policy solution: acknowledging the legal fictions involved in determining death to move in the direction of greater transparency. This may someday result in more substantial legal change to directly confront the challenges raised by life-sustaining and life-preserving technologies without the need for fictions. (shrink)

Using payment to recruit research subjects is a common practice, but it raises ethical concerns that coercion or undue inducement could potentially compromise participants’ informed consent. This is the first national study to explore the attitudes of IRB members and other human subjects protection professionals concerning whether payment of research participants constitutes coercion or undue influence, and if so, why. The majority of respondents expressed concern that payment of any amount might influence a participant’s decisions or behaviors regarding research participation. (...) Respondents expressed greater acceptance of payment as reimbursement or compensation than as an incentive to participate in research, and most agreed that subjects are coerced if the offer of payment makes them participate when they otherwise would not or when the offer of payment causes them to feel that they have no reasonable alternative but to participate . Views about undue influence were similar. We conclude that human subjects protection professionals hold expansive and inconsistent views about coercion and undue influence that may interfere with the recruitment of research participants and impede valuable research. (shrink)

The dominant unspoken philosophical basis of medical care in the United States is a form of Cartesian reductionism that views the body as a machine and medical professionals as technicians whose job is to repair that machine. The purpose of this paper is to advocate for an alternative philosophy of medicine based on the concept of healing relationships between clinicians and patients. This is accomplished first by exploring the ethical and philosophical work of Pellegrino and Thomasma and then by connecting (...) Martin Buber's philosophical work on the nature of relationships to an empirically derived model of the medical healing relationship. The Healing Relationship Model was developed by the authors through qualitative analysis of interviews of physicians and patients. Clinician-patient healing relationships are a special form of what Buber calls I-Thou relationships, characterized by dialog and mutuality, but a mutuality limited by the inherent asymmetry of the clinician-patient relationship. The Healing Relationship Model identifies three processes necessary for such relationships to develop and be sustained: Valuing, Appreciating Power and Abiding. We explore in detail how these processes, as well as other components of the model resonate with Buber's concepts of I-Thou and I-It relationships. The resulting combined conceptual model illuminates the wholeness underlying the dual roles of clinicians as healers and providers of technical biomedicine. On the basis of our analysis, we argue that health care should be focused on healing, with I-Thou relationships at its core. (shrink)

A letter to the editor from Howard Brody, David Buchanan, and Franklin G. Miller in response to the recent article by Erik Malmqvist Understanding Exploitation," March-April 2011).

This report describes the rationale, approaches, organization, and resource development leading to a large-scale deletion bin map of the hexaploid wheat genome. Accompanying reports in this issue detail results from chromosome bin-mapping of expressed sequence tags representing genes onto the seven homoeologous chromosome groups and a global analysis of the entire mapped wheat EST data set. Among the resources developed were the first extensive public wheat EST collection. Described are protocols for sequencing, sequence processing, EST nomenclature, and the assembly of (...) ESTs into contigs. These contigs plus singletons were used for selection of distinct sequence motif unigenes. Selected ESTs were rearrayed, validated by 5′ and 3′ sequencing, and amplified for probing a series of wheat aneuploid and deletion stocks. Images and data for all Southern hybridizations were deposited in databases and were used by the coordinators for each of the seven homoeologous chromosome groups to validate the mapping results. Results from this project have established the foundation for future developments in wheat genomics. (shrink)

First published in 2002. Routledge is an imprint of Taylor & Francis, an informa company.

Although informed consent is important in clinical research, questions persist regarding when it is necessary, what it requires, and how it should be obtained. The standard view in research ethics is that the function of informed consent is to respect individual autonomy. However, consent processes are multidimensional and serve other ethical functions as well. These functions deserve particular attention when barriers to consent exist. We argue that consent serves seven ethically important and conceptually distinct functions. The first four functions pertain (...) principally to individual participants: (1) providing transparency; (2) allowing control and authorization; (3) promoting concordance with participants' values; and (4) protecting and promoting welfare interests. Three other functions are systemic or policy focused: (5) promoting trust; (6) satisfying regulatory requirements; and (7) promoting integrity in research. Reframing consent around these functions can guide approaches to consent that are context sensitive and that maximize achievable goals. (shrink)

Despite the importance of extrapair copulation (EPC) in human evolution, almost nothing is known about the design features of EPC detection mechanisms. We tested for sex differences in EPC inference-making mechanisms in a sample of 203 young couples. Men made more accurate inferences (φmen = 0.66, φwomen = 0.46), and the ratio of positive errors to negative errors was higher for men than for women (1.22 vs. 0.18). Since some may have been reluctant to admit EPC behavior, we modeled how (...) underreporting could have influenced these results. These analyses indicated that it would take highly sex-differentiated levels of underreporting by subjects with trusting partners for there to be no real sex difference. Further analyses indicated that men may be less willing to harbor unresolved suspicions about their partners’ EPC behavior, which may explain the sex difference in accuracy. Finally, we estimated that women underreported their own EPC behavior (10%) more than men (0%). (shrink)

BackgroundIn the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies.MethodsBetween 2013 and 2019, 8252 participants (...) (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported.ResultsSevere structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy.ConclusionThe management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/nct02220582. (shrink)

Soil is fragile and nonrenewable but the most basic of natural resources. It has a capacity to tolerate continuous use but only with proper management. Improper soil management and indiscriminate use of chemicals have contributed to some severe global environmental issues, e.g., volatilization losses and contamination of natural waters by sediments and agricultural fertilizers and pesticides. The increasing substitution of energy for labor and other cultural inputs in agriculture is another issue. Fertilizers and chemicals account for about 25% of the (...) production energy investment in agriculture. An additional 60% is accounted for by machinery, gasoline, electricity, and power-related inputs. Fertilizer additions to cropland are not utilized fully and significant amounts, depending on conditions, are either lost in surface runoff or leached into the ground water. The annual discharge of dissolved solids from agricultural lands to the waterways in the USA is substantial. The increasing use of herbicides in agriculture is a threat to the quality of surface and ground water, although this threat is dependent upon both the chemistry of the compound and the ecosystem in which it is used. Especially within the Third World, development of an environmental ethic and environmental laws have not kept pace with the increase in pesticide use. Above all is the severe and global problem of soil degradation currently occurring at the rate of five to seven million hectares per year. The policy and moral aspects of these issues are discussed. (shrink)

We show that the Turing degrees are not sufficient to measure the complexity of continuous functions on [0, 1]. Computability of continuous real functions is a standard notion from computable analysis. However, no satisfactory theory of degrees of continuous functions exists. We introduce the continuous degrees and prove that they are a proper extension of the Turing degrees and a proper substructure of the enumeration degrees. Call continuous degrees which are not Turing degrees non-total. Several fundamental results are proved: a (...) continuous function with non-total degree has no least degree representation, settling a question asked by Pour-El and Lempp; every non-computable f $\epsilon \mathcal{C}[0, 1]$ computes a non-computable subset of $\mathbb{N}$ ; there is a non-total degree between Turing degrees $a _\eqslantless_{\tau}$ b iff b is a PA degree relative to a; $\mathcal{S} \subseteq 2^{\mathbb{N}}$ is a Scott set iff it is the collection of f-computable subsets of $\mathbb{N}$ for some f $\epsilon \mathcal{C}[O, 1]$ of non-total degree; and there are computably incomparable f, g $\epsilon \mathcal{C}[0, 1]$ which compute exactly the same subsets of $\mathbb{N}$ . Proofs draw from classical analysis and constructive analysis as well as from computability theory. (shrink)

Define z to be the smallest cardinality of a function f: X → Y with X. Y ⊆ 2ω such that there is no Borel function g ⊇ f. In this paper we prove that it is relatively consistent with ZFC to have b < z where b is, as usual, smallest cardinality of an unbounded family in ωω. This answers a question raised by Zapletal. We also show that it is relatively consistent with ZFC that there exists X ⊆ (...) 2ω such that the Borel order of X is bounded but there exists a relatively analytic subset of X which is not relatively coanalytic. This answers a question of Mauldin. (shrink)

Miller, D., G. Nadathur, F. Pfenning and A. Scedrov, Uniform proofs as a foundation for logic programming, Annals of Pure and Applied Logic 51 125–157. A proof-theoretic characterization of logical languages that form suitable bases for Prolog-like programming languages is provided. This characterization is based on the principle that the declarative meaning of a logic program, provided by provability in a logical system, should coincide with its operational meaning, provided by interpreting logical connectives as simple and fixed search instructions. (...) The operational semantics is formalized by the identification of a class of cut-free sequent proofs called uniform proofs. A uniform proof is one that can be found by a goal-directed search that respects the interpretation of the logical connectives as search instructions. The concept of a uniform proof is used to define the notion of an abstract logic programming language, and it is shown that first-order and higher-order Horn clauses with classical provability are examples of such a language. Horn clauses are then generalized to hereditary Harrop formulas and it is shown that first-order and higher-order versions of this new class of formulas are also abstract logic programming languages if the inference rules are those of either intuitionistic or minimal logic. The programming language significance of the various generalizations to first-order Horn clauses is briefly discussed. (shrink)