Strengths and weaknesses of guideline approaches to safeguard voluntary informed consent of patients within a dependent relationship

BACKGROUND: It is thought that a dependent relationship between patients and physicians who enroll their own patients in research compromises voluntary informed consent. Therefore, several ethical guidelines for human subject research provide approaches to mitigate these compromises. Currently, these approaches have not been critically evaluated. In this article, we analyze the approaches of ethical guidelines to manage the influence of a dependent relationship between patients and physicians on voluntary informed consent and discuss the strengths and weaknesses of these approaches. METHODS: We performed a review of international ethical guidance documents on human subject research, listed in the Oxford Textbook of Clinical Research Ethics and found through cross referencing. We also searched Global Ethics Observatory (GEObs) and the World Health Organization (WHO) website. Guidelines from all years were eligible for inclusion. The date last searched was December 2013. DISCUSSION: We identified two basic guideline approaches: 1. a process approach, which focuses on the person who obtains informed consent, that is, an independent individual, such as a research nurse or counselor; and 2. a content approach, emphasizing the voluntary nature of participation. Both approaches are valuable, either because the influence of the physician may diminish or because it empowers patients to make voluntary decisions. However, the approaches also face challenges. First, research nurses are not always independent. Second, physician-investigators will be informed about decisions of their patients. Third, involvement of a counselor is sometimes unfeasible. Fourth, the right to withdraw may be difficult to act upon in a dependent relationship. CONCLUSIONS: Current guideline approaches to protect voluntary informed consent within a dependent relationship are suboptimal. To prevent compromises to voluntary informed consent, consent should not only be obtained by an independent individual, but this person should also emphasize the voluntary nature of participation. At the same time, dependency as such does not imply undue influence. Sometimes the physician may be best qualified to provide information, for example, for a very specialized study. Still, the research nurse should obtain informed consent. In addition, patients should be able to consult a counselor, who attends the informed consent discussions and is concerned with their interests. Finally, both physicians and research nurses should disclose research interests

The unique status of first-in-human studies: strengthening the social value requirement

For clinical research to be ethical, risks need to be balanced by anticipated benefits. This is challenging for first-in-human (FIH) studies as participants are not expected to benefit directly, and risks are potentially high. We argue that this differentiates FIH studies from other clinical trials to the extent that they should be given unique status in international research ethics guidelines. As there is a general positive attitude regarding the benefits of science, it is important to establish a more systematic method to assess anticipated social value to safeguard participants not only from enrolling in risky, but also in futile trials. Here, we provide some of necessary steps needed to assess the anticipated social value of the intervention

Some Unresolved Ethical Challenges in Healthcare Decision-Making : Navigating Family Involvement

Peer reviewedPublisher PD

How Should the Precautionary Principle Apply to Pregnant Women in Clinical Research?

The precautionary principle is often invoked in relation to pregnant women and may be one of the underlying reasons for their continuous underrepresentation in clinical research. The principle is appealing, because potential fetal harm as a result of research participation is considered to be serious and irreversible. In our paper, we explore through conceptual analysis whether and if so how the precautionary principle should apply to pregnant women. We argue that the principle is a decision-making strategy underlying risk-benefit decisions in clinical research, which can be applied to pregnant women. However, the current application is a strong one, leading to the promotion of absolute exclusion or, less often, absolute inclusion of pregnant women. In order to change this paralyzing situation, a shift toward weak precautionary thinking is necessary. Instead of automatic extreme precaution, a balance will be found between harms and potential benefits of including pregnant women in clinical research

What do international ethics guidelines say in terms of the scope of medical research ethics?

BACKGROUND: In research ethics, the most basic question would always be, "which is an ethical issue, which is not?" Interestingly, depending on which ethics guideline we consult, we may have various answers to this question. Though we already have several international ethics guidelines for biomedical research involving human participants, ironically, we do not have a harmonized document which tells us what these various guidelines say and shows us the areas of consensus (or lack thereof). In this manuscript, we attempted to do just that. METHODS: We extracted the imperatives from five internationally-known ethics guidelines and took note where the imperatives came from. In doing so, we gathered data on how many guidelines support a specific imperative. RESULTS: We found that there is no consensus on the majority of the imperatives and that in only 8.2% of the imperatives were there at least moderate consensus (i.e., consensus of at least 3 of the 5 ethics guidelines). Of the 12 clusters (Basic Principles; Research Collaboration; Social Value; Scientific Validity; Participant Selection; Favorable Benefit/Risk Ratio; Independent Review; Informed Consent; Respect for Participants; Publication and Registration; Regulatory Sanctions; and Justified Research on the Vulnerable Population), Informed Consent has the highest level of consensus and Research Collaboration and Regulatory Sanctions have the least. CONCLUSION: There was a lack of consensus in the majority of imperatives from the five internationally-known ethics guidelines. This may be partly explained by the differences among the guidelines in terms of their levels of specification as well as conceptual/ideological differences

Нарушение репродуктивной функции при простатите/синдроме хронической тазовой боли

Показано, что нелеченное хроническое воспаление предстательной железы приводит к нарушению показателей спермограммы и в ряде случаев к бесплодию при нормальном развитии половых желез и достаточном гормональном обеспечении организма. Бактерии, вирусы, лейкоциты, свободные радикалы, цитокины, иммунологические изменения и обструкция семявыводящих путей при простате являются кофакторами в развитии бесплодия.It is shown that untreated chronic inflammation of the prostate gland causes disturbances of spermogram count and strility in a number of cases at normal development of sex glands and sufficient hormone supply of the organism. Bacteria, viruses, leukocytes, free radicals, cytokines, immunological changes and obstruction of the deferent ducts in prostatitis are co−factors of sterility development

Continuous deep sedation at the end of life:a qualitative interview-study among health care providers on an evolving practice

Background:Continuous deep sedation (CDS) can be used for patients at the end of life who suffer intolerably from severe symptoms that cannot be relieved otherwise. In the Netherlands, the use of CDS is guided by an national guideline since 2005. The percentage of patients for whom CDS is used increased from 8% of all patients who died in 2005 to 18% in 2015. The aim of this study is to explore potential causes of the rise in the use of CDS in the Netherlands according to health care providers who have been participating in this practice. Methods: Semi-structured interviews were conducted and thematically analysed. Participants were Dutch health care providers (HCPs), working at patients’ homes, hospices, elderly care facilities and in hospitals and experienced in providing CDS, who were recruited via purposeful sampling. Results: 41 Health care providers participated in an interview. For these HCPs the reason to start CDS is often a combination of symptoms resulting in a refractory state. HCPs indicated that symptoms of non-physical origin are increasingly important in the decision to start CDS. Most HCPs felt that suffering at the end of life is less tolerated by patients, their relatives, and sometimes by HCPs; they report more requests to relieve suffering by using CDS. Some HCPs in our study have experienced increasing pressure to perform CDS. Some HCPs stated that they more often used intermittent sedation, sometimes resulting in CDS. Conclusions: This study provides insight into how participating HCPs perceive that their practice of CDS changed over time. The combination of a broader interpretation of refractory suffering by HCPs and a decreased tolerance of suffering at the end of life by patients, their relatives and HCPs, may have led to a lower threshold to start CDS. Trial registration: The Research Ethics Committee of University Medical Center Utrecht assessed that the study was exempt from ethical review according to Dutch law (Protocol number 19–435/C).</p

End-of-Life Decision-Making in Canada: The Report by the Royal Society of Canada Expert Panel on End-of-Life Decision-Making

This report on end-of-life decision-making in Canada was produced by an international expert panel and commissioned by the Royal Society of Canada. It consists of five chapters

Визначення вальпроєвої кислоти у крові методом реакційної високоефективної рідинної хроматографії

Здійснена взаємодія вальпроєвої кислоти з 3-(2'-бромацетил)-7-метоксикумарином і розроблено її визначення у крові методом реакційної високоефективної рідинної хроматографії. Вивчений вплив різних методів депротоїнізації на вивільнення вальпроєвої кислоти та оптимізовані умови пробопідготовки.Осуществлено взаимодействие вальпроевой кислоты с 3-(2'-бромацетил)-7-метоксикумарином и разработано ее определение в крови методом реакционной высокоэффективной жидкостной хроматографии. Изучено влияние различных методов депротеинизации на выходы вальпроевой кислоты и оптимизированы условия пробоподготовки.The interaction of the valproic acid with 3-(2'-bromoacetyl)-7-methoxicoumarin has been carried out and its determination in blood by the reaction high performance liquid chromatography method has been developed. The influence of various methods of deproteinization on the yields of the valproic acid has been studied and the conditions of the sample preparing has been optimized

Experiences and perceptions of continuous deep sedation:An interview study among Dutch patients and relatives

Background: The incidence of continuous deep sedation (CDS) has more than doubled over the last decade in The Netherlands, while reasons for this increase are not fully understood. Patients and relatives have an essential role in deciding on CDS. We hypothesize that the increase in CDS practice is related to the changing role of patients and relatives in deciding on CDS. Objective: To describe perceptions and experiences of patients and relatives with regard to CDS. This insight may help professionals and policymakers to better understand and respond to the evolving practice of CDS. Methods: Qualitative interviews were held with patients and relatives who had either personal experience with CDS as a relative or had contemplated CDS for themselves. Results: The vast majority of respondents appreciated CDS as a palliative care option, and none of the respondents reported (moral) objections to CDS. The majority of respondents prioritized avoiding suffering at the end of life. The patients and families generally considered CDS a palliative care option for which they can choose. Likewise, according to our respondents, the decision to start CDS was made by them, instead of the physician. Negative experiences with CDS care were mostly related to loss of sense of agency, due to insufficient communication or information provision by healthcare professionals. Lack of continuity of care was also a source of distress. We observed a variety in the respondents' understanding of the distinction between CDS and other end-of-life care decisions, including euthanasia. Some perceived CDS as hastening death. Conclusion: The traditional view of CDS as a last resort option for a physician to relieve a patient's suffering at the end of life is not explicit among patients and relatives. Instead, our results show that they perceive CDS as a regular palliative care option. Along with this normalization of CDS, patients and relatives claim a substantial say in the decision-making and are mainly motivated by a wish to avoid suffering and exercise control at the end of life. These distinct views on CDS of patients, their relatives and healthcare providers should be reconciled in guidelines and protocols for CDS. Patient or Public Contribution: One of the authors in our team (G. H.) has experience with CDS as a relative and ensured that the patient/relative viewpoint was adequately reflected in the design and conduct of our study. In the preliminary phase of our study, G. H. adjusted the topic list so it was better adapted to the current practice of CDS. During the data analysis, G. H. read several interviews and took part in the open and critical discussion on central themes and core concepts as an important member of the author team, thereby guaranteeing the central position of the patient/relative perspective in our final research outcome.</p