The ethical anatomy of payment for research participants.

In contrast to most publications on the ethics of paying research subjects, which start by identifying and analyzing major ethical concerns raised by the practice (in particular, risks of undue inducement and exploitation) and end with a set of-more or less well-justified-ethical recommendations for using payment schemes immune to these problems, this paper offers a systematic, principle-based ethical analysis of the practice. It argues that researchers have a prima facie moral obligation to offer payment to research subjects, which stems from the principle of social beneficence. This principle constitutes an ethical "spine" of the practice. Other ethical principles of research ethics (respect for autonomy, individual beneficence, and justice/fairness) make up an ethical "skeleton" of morally sound payment schemes by providing additional moral reasons for offering participants (1) recompense for reasonable expenses; and (2a) remuneration conceptualized as a reward for their valuable contribution, provided (i) it meets standards of equality, adequacy and non-exploitation, and (ii) it is not overly attractive (i.e., it does not constitute undue inducement for participation or retention, and does not encourage deceptive behaviors); or (2b) remuneration conceptualized as a market-driven price, provided (i) it is necessary and designed to help the study achieve its social and scientific goals, (ii) it does not reinforce wider social injustices and inequalities; (iii) it meets the requirement of non-exploitation; and (iv) it is not overly attractive. The principle of justice provides a strong ethical reason for not offering recompenses for lost wages (or loss of other reasonably expected profits).

Tough Clinical Decisions: Experiences of Polish Physicians.

The paper reports results of the very first survey-based study on the prevalence, frequency and nature of ethical or other non-medical difficulties faced by Polish physicians in their everyday clinical practice. The study involved 521 physicians of various medical specialties, practicing mainly in inpatient healthcare. The study showed that the majority of Polish physicians encounter ethical and other non-medical difficulties in making clinical decisions. However, they confront such difficulties less frequently than their foreign peers. Moreover, Polish doctors indicate different circumstances as a source of the experienced problems. The difficulties most often reported relate to (i) patients (or their proxies) requests for medically non-indicated interventions; (ii) problems with communication with patients (or their proxies) due to the patients' negative attitude, unwillingness to cooperate, or aggression; and (iii) various difficulties with obtaining informed consent. Polish physicians report difficulties associated with disagreements among care givers or scarcity of resources less frequently than doctors from other countries. The study's findings provide support for the thesis that a significant portion of Polish physicians still follow a traditional, paternalistic, and hierarchical model of healthcare practice. Instead of promoting patient's empowerment, engagement, and rights, they often consider these ideas as a threat to physicians' professional authority and autonomy. The study leads to the conclusion that due to insufficient training in medical ethics, communication skills, and medical law, many Polish physicians lack the knowledge and competence necessary to adequately respond to challenges posed by modern healthcare practice.

Taking the principle of the primacy of the human being seriously.

This paper targets an orphan topic in research ethics, namely the so called principle of the primacy of the human being, which states that the interests of the human subject should always take precedence over the interests of science and society. Although the principle occupies the central position in the majority of international ethical and legal standards for biomedical research, it has been commented in the literature mainly in passing. With a few notable exceptions, there is little in-depth discussion about the meaning and role of the principle. Several authors note that the principle is vogue, ambiguous and apparently conflicting with the accepted practice of conducting non-beneficial research on individuals unable to give consent. There are opinions that it is just "a vacuous figure of speech" and should be abandoned. This paper argues that the primacy principle is far from being "a vacuous figure of speech", rather it should be seen as a threefold concept: a fundamental interpretative rule, a procedural rule, and a substantive rule aimed at protecting research subjects from instrumental treatment and unacceptable risks. This interpretation tracks back to the principle regulatory and normative origins in the Declaration of Helsinki of 1975, but also acknowledges changes in research ethics and practice, which took place at the turn on the twentieth and twenty-first centuries. Thus, the proposed reading of the principle is not only original, but also historically grounded and normatively fruitful. It provides a fresh and ethically rich perspective on extensively debated, but still controversial problem of an upper limit of permissible risks in non-beneficial studies.

What makes clinical labour different? The case of human guinea pigging.

Each year thousands of individuals enrol in clinical trials as healthy volunteers to earn money. Some of them pursue research participation as a full-time or at least a part-time job. They call themselves professional or semiprofessional guinea pigs. The practice of paying healthy volunteers raises numerous ethical concerns. Different payment models have been discussed in literature. Dickert and Grady argue for a wage-payment model. This model gives research subjects a standardised hourly wage, and it is based on an assumption that research participation is morally indistinguishable from other forms of unskilled labour. In this paper, I will challenge this assumption. I will argue that human guinea pigging has particular characteristics which taken together make it significantly different from other forms of labour. (1) Participation in research is skill-independent. Healthy volunteers are valuable not because they are skilful persons, but because they are human bodies. (2) The role of research volunteers is mainly passive. They are not asked to produce goods or deliver services. They are paid for enduring unpleasant, painful and risky interventions performed by investigators. (3) Research volunteering involves inherent risks and uncertainties, and subjects have little or no control over their minimisation and materialisation. I conclude that participation in clinical research is a specific kind of activity. It is more like renting out one's body to strangers, than working. Thus, research participation should not be treated on par with other forms of employment.

Fair, just and compassionate: A pilot for making allocation decisions for patients requesting experimental drugs outside of clinical trials.

Patients have received experimental pharmaceuticals outside of clinical trials for decades. There are no industry-wide best practices, and many companies that have granted compassionate use, or 'preapproval', access to their investigational products have done so without fanfare and without divulging the process or grounds on which decisions were made. The number of compassionate use requests has increased over time. Driving the demand are new treatments for serious unmet medical needs; patient advocacy groups pressing for access to emerging treatments; internet platforms enabling broad awareness of compelling cases or novel drugs and a lack of trust among some that the pharmaceutical industry and/or the FDA have patients' best interests in mind. High-profile cases in the media have highlighted the gap between patient expectations for compassionate use and company utilisation of fair processes to adjudicate requests. With many pharmaceutical manufacturers, patient groups, healthcare providers and policy analysts unhappy with the inequities of the status quo, fairer and more ethical management of compassionate use requests was needed. This paper reports on a novel collaboration between a pharmaceutical company and an academic medical ethics department that led to the formation of the Compassionate Use Advisory Committee (CompAC). Comprising medical experts, bioethicists and patient representatives, CompAC established an ethical framework for the allocation of a scarce investigational oncology agent to single patients requesting non-trial access. This is the first account of how the committee was formed and how it built an ethical framework and put it into practice.

Child's objection to non-beneficial research: capacity and distress based models.

A child's objection, refusal and dissent regarding participation in non-beneficial biomedical research must be respected, even when the parents or legal representatives have given their permission. There is, however, no consensus on the definition and criteria of a meaningful and valid child's objection. The aim of this article is to clarify this issue. In the first part we describe the problems of a child's assent in research. In the second part we distinguish and analyze two models of a child's objection to research: the capacity-based model and the distress-based model. In the last part we present arguments for a broader and unified understanding of a child's objection within regulations and practices. This will strengthen children's rights and facilitate the entire process of assessment of research protocols.

On the Alleged Right to Participate in High-Risk Research.

Reigning regulatory frameworks for biomedical research impose on researchers and research ethics committees an obligation to protect research participants from risks that are unnecessary, disproportionate to potential research benefits, and non-minimized. Where the research has no potential to produce results of direct benefit to the subjects and the subjects are unable to give consent, these requirements are strengthened by an additional condition, that risks should not exceed a certain minimal threshold. In this article, I address the question of whether there should be limits of permissible risks in non-therapeutic research involving competent and healthy subjects. Some commentators argue that competent and informed individuals should have a right to participate even in extremely risky research and that research ethics committees should never reject studies because they are too dangerous. To use David Shaw's expression, competent volunteers should have 'a right to participate in high-risk research'. I argue that this idea is ill-founded, as it does not take into account the social mission and complex collaborative nature of research practice as well as the inequity of power between researchers and subjects. Imposition of limits on permissible risks for healthy volunteers is justified by the need to protect research enterprise and the need to protect the weaker party, namely the subjects. Also, I suggest that the best way to set boundaries on research risks is to leave the judgment of risk acceptability to research ethics committees.

The Principle of the Primacy of the Human Subject and Minimal Risk in Non-Beneficial Paediatric Research.

Non-beneficial paediatric research is vital to improving paediatric healthcare. Nevertheless, it is also ethically controversial. By definition, subjects of such studies are unable to give consent and they are exposed to risks only for the benefit of others, without obtaining any clinical benefits which could compensate those risks. This raises ethical concern that children participating in non-beneficial research are treated instrumentally; that they are reduced to mere instruments for the benefit of science and society. But this would make the research incompatible with the widely endorsed principle of the primacy of the human subject (henceforth PP), which stipulates that the interests of the participating individual should prevail over the interests of science and society. This paper deals with this conflict. It analyses solutions to this problem developed in the literature, and shows that they are unsuccessful. Finally, it offers a new idea of how to reconcile the conduct of non-beneficial paediatric research with the PP. The paper argues for a new formula of the PP, and shows that it implies a specific non-comparative definition of the minimal risk threshold.

Clinical Ethics Consultations in the Opinion of Polish Physicians.

Clinical Ethics Consultations (CEC) are an important tool for physicians in solving difficult cases. They are extremely common in North America and to a lesser extent also present in Europe. However, there is little data on this practice in Poland. We present results of a survey of 521 physicians practising in Poland concerning their opinion on CECs and related practices. We analysed the data looking at such issues as CECs' perceived availability, use of CECs, and perceived usefulness of such support. Physicians in our study generally encounter hard ethics cases, even-surprisingly-those who do not work in hospitals. Most physicians have no CEC access, and those that do still do not employ CECs. However, physicians perceive this form of support as useful-even more so among actual users of CECs. We compared these findings with similar studies from other European countries and the North America. We point out peculiarities of our results as compared to those in other countries, with some possible explanations. We hope the results may encourage regulatory debate on the need to formally introduce CECs into the Polish healthcare system.

Emergency research without consent under Polish law.

Although Directive 2001/20/EC of the European Parliament and of Council of 4 April 2001 on the approximation of the laws regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use does not contain an exception for emergency situations, and requires the informed consent of a legal representative in all cases where research is conducted on legally competent individuals who are unable to give informed consent, in Poland, emergency research can be conducted without consent. Polish regulations on emergency research can hardly be treated as a result of intentional legislative policy. Our provisions arise from multiple and sophisticated interpretations of different regulations that govern medical experiments on human subjects and clinical trials. These interpretations can be summarized as follows: (1) There are two categories of medical experiments: therapeutic and non-therapeutic experiments. Emergency research without consent may be conducted in the category of therapeutic experiment only (therapeutic experiment consists of the introduction by the physician of new or only partially proven diagnostic, therapeutic or preventive methods in order to achieve direct benefit to the health of the patients, and it can be carried out when hitherto applied methods were ineffective or their effectiveness was insufficient). (2). Emergency research may be conducted without consent if there is a situation of great urgency in which the research subject's life is in danger and there is no possibility of obtaining immediate consent from the research subject him or herself, or from his or her legal representative or guardianship court, and the research subject has not refused to give consent for the participation in an emergency therapeutic experiment. The legal representative or guardianship court shall be provided with all the relevant information concerning subject's participation in an experiment as soon as possible. All projects of emergency research with intent to be done without the research subject's consent must be approved by an independent bioethics committee. Because these five requirements seem to provide insufficient protection for a subject's autonomy and rights it is necessary to add to them two other conditions: (1) the emergency research could not be conducted using other research participants capable of giving informed consent; and (2) informed consent for continued participation in the emergency research shall be obtained from either the participant him or herself or the legally authorized representative as soon as possible (requirement of obtaining deferred consent). A consolidated single Act that will govern all aspects of medical experiments on human subjects, including emergency research, should be prepared and enacted as soon as possible.

Regulation of healthcare ethics committees in Europe.

In this article, the question is discussed if and how Healthcare Ethics Committees (HECs) should be regulated. The paper consists of two parts. First, authors from eight EC member countries describe the status quo in their respective countries, and give reasons as to the form of regulation they consider most adequate. In the second part, the country reports are analysed. It is suggested that regulation of HECs should be central and weak. Central regulation is argued to be apt to improve HECs' accountability, relevance and comparability. To facilitate biomedical citizenship and ethical reflection, regulation should at the same time be weak rather than strict. Independence of HECs to deliberate about ethical questions, and to give solicited and unsolicited advice, should be supported and only interfered with by way of exception. One exception is when circumstances become temporary adversarial to ethical deliberation in healthcare institutions. In view of European unification, steps should be taken to develop consistent policies for both Eastern and Western European countries.