Today scientists are expected to be more accountable and transparent than at any time in history. Globally the pursuit of knowledge creation enjoys a place of distinction, and the public expects to reap considerable benefit from the innovative contributions made by researchers. It is therefore more important than ever that ethics, transparency and professionalism explicitly guide research integrity. Despite the clear importance of acquiring a fundamental understanding of clinical trials in the context of health research and innovation, medical (...) training generally fails to cover clinical trial integrity in its curriculum, including it neither at undergraduate nor at postgraduate levels. This new book provides a curriculum to address this gap, offering best practice guidelines to improve the quality, openness and trustworthiness of clinical trials and filling a current void in the market. Key Features: The first book on clinical trial integrity. Provides clear guidance on how to ensure probity in peer review, appraisal of trials and investigation of complaints concerning misconduct in clinical trials. Trains and supports researchers globally in how to undertake trials with integrity. Ensures the increasing demand for public documentation of all aspects throughout the lifecycle of a clinical trial can be met. The book is essential reading for master and doctoral students undertaking courses in clinical trials, epidemiology and medical statistics and an invaluable reference for medical journal editors and peer reviewers, clinicians who recruit patients into trials, pharmaceutical industry professionals, patient and public representatives who engage in clinical trials, systematic reviewers, guideline writers, funders and regulators of clinical trials. (shrink)

The maternal‐fetal HIV transmission trials, conducted in developing countries in the 1990s, undoubtedly generated one of the most intense, high profile controversies in international research ethics. They sparked off a prolonged acrimonious and public debate and deeply divided the scientific community. They also provided an impetus for the revision of the Declaration of Helsinki – the most widely known guideline for international research. In this paper, I provide a brief summary of the context, outline the arguments for and (...) against the controversial use of placebo controls, and focus on particular areas that I believe merit further discussion or clarification. On balance, I argue that the researchers failed in their duties to protect the best interests of their research subjects, and to promote distributive justice. I discuss the difficulties of obtaining valid consent in this research context, and argue that it is unethical to inform women of their HIV status without at least offering them prophylactic treatment for their unborn children. A global view of justice, which endorses international equity, cannot be squared with international research guidelines that allow ‘local conditions’ to define the scope of duty to the control group. Finally, I suggest that the heated debate reflects a tension, if not an outright war, between two conflicting meta‐ethical systems, or incommensurable paradigms, that underpin scientific research involving human subjects. (shrink)

This article focuses on maternal-fetal surgery (MFS) and on the concept of clinical equipoise that is a widely accepted requirement for conducting randomized controlled trials (RCT). There are at least three reasons why equipoise is unsuitable for MFS. First, the concept is based on a misconception about the nature of clinical research and the status of research subjects. Second, given that it is not clear who the research subject/s in MFS is/are, if clinical equipoise is to be (...) used as a criterion to test the ethical appropriateness of RCT, its meaning should be unambiguous. Third, because of the multidisciplinary character of MFS, it is not clear who should be in equipoise. As a result, we lack an adequate criterion for the ethical review of MFS protocols. In our account, which is based on Chervenak and McCullough's seminal work in the field of obstetric ethics, equipoise is abandoned. and RCT involving MFS can be ethically initiated when a multidisciplinary ethics review board (ERB), having an evidence-based assessment of the risks involved, is convinced that the value of answering the research hypothesis, for the sake of the health interests of future pregnant women carrying fetuses with certain congenital birth defects, justifies the actual risks research participants might suffer within a set limit of low/manageable. (shrink)

What kinds of evidence reliably support predictions of effectiveness for health and social care interventions? There is increasing reliance, not only for health care policy and practice but also for more general social and economic policy deliberation, on evidence that comes from studies whose basic logic is that of JS Mill's method of difference. These include randomized controlled trials, case–control studies, cohort studies, and some uses of causal Bayes nets and counterfactual-licensing models like ones commonly developed in (...) econometrics. The topic of this paper is the 'external validity' of causal conclusions from these kinds of studies. We shall argue two claims. Claim, negative: external validity is the wrong idea; claim, positive: 'capacities' are almost always the right idea, if there is a right idea to be had. If we are right about these claims, it makes big problems for policy decisions. Many advice guides for grading policy predictions give top grades to a proposed policy if it has two good Mill's-method-of difference studies that support it. But if capacities are to serve as the conduit for support from a method-of-difference study to an effectiveness prediction, much more evidence, and much different in kind, is required. We will illustrate the complexities involved with the case of multisystemic therapy, an internationally adopted intervention to try to diminish antisocial behaviour in young people. (shrink)

Background Pragmatic randomized controlled trials are designed to evaluate the effectiveness of interventions in real-world clinical conditions. However, these studies raise ethical issues for researchers and regulators. Our objective is to identify a list of key ethical issues in pragmatic RCTs and highlight gaps in the ethics literature. Methods We conducted a scoping review of articles addressing ethical aspects of pragmatic RCTs. After applying the search strategy and eligibility criteria, 36 articles were included and reviewed using (...) content analysis. Results Our review identified four major themes: 1) the research-practice distinction; 2) the need for consent; 3) elements that must be disclosed in the consent process; and 4) appropriate oversight by research ethics committees. 1) Most authors reject the need for a research-practice distinction in pragmatic RCTs. They argue that the distinction rests on the presumptions that research participation offers patients less benefit and greater risk than clinical practice, but neither is true in the case of pragmatic RCTs. 2) Most authors further conclude that pragmatic RCTs may proceed without informed consent or with simplified consent procedures when risks are low and consent is infeasible. 3) Authors who endorse the need for consent assert that information need only be disclosed when research participation poses incremental risks compared to clinical practice. Authors disagree as to whether randomization must be disclosed. 4) Finally, all authors view regulatory oversight as burdensome and a practical impediment to the conduct of pragmatic RCTs, and argue that oversight procedures ought to be streamlined when risks to participants are low. Conclusion The current ethical discussion is framed by the assumption that the function of research oversight is to protect participants from risk. As pragmatic RCTs commonly involve usual care interventions, the risks may be minimal. This leads many to reject the research-practice distinction and question the need for informed consent. But the function of oversight should be understood broadly as protecting the liberty and welfare interest of participants and promoting public trust in research. This understanding, we suggest, will focus discussion on questions about appropriate ethical review for pragmatic RCTs. (shrink)

Randomized controlled trial trial designs exist on an explanatory-pragmatic spectrum, depending on the degree to which a study aims to address a question of efficacy or effectiveness. As conceptualized by Schwartz and Lellouch in 1967, an explanatory approach to trial design emphasizes hypothesis testing about the mechanisms of action of treatments under ideal conditions, whereas a pragmatic approach emphasizes testing effectiveness of two or more available treatments in real-world conditions. Interest in, and the number of, pragmatic trials (...) has grown substantially in recent years, with increased recognition by funders and stakeholders worldwide of the need for credible evidence to inform clinical decision-making. This increase has been accompanied by the onset of learning healthcare systems, as well as an increasing focus on patient-oriented research. However, pragmatic trials have ethical challenges that have not yet been identified or adequately characterized. The present study aims to explore the views of key stakeholders with respect to ethical issues raised by the design and conduct of pragmatic trials. It is embedded within a large, four-year project that seeks to develop guidance for the ethical design and conduct of pragmatic trials. As a first step, this study will address important gaps in the current empirical literature with respect to identifying a comprehensive range of ethical issues arising from the design and conduct of pragmatic trials. By opening up a broad range of topics for consideration within our parallel ethical analysis, we will extend the current debate, which has largely emphasized issues of consent, to the range of ethical considerations that may flow from specific design choices. Semi-structured interviews with key stakeholders, across multiple jurisdictions, identified based on their known experience and/or expertise with pragmatic trials. We expect that the study outputs will be of interest to a wide range of knowledge users including trialists, ethicists, research ethics committees, journal editors, regulators, healthcare policymakers, research funders and patient groups. All publications will adhere to the Tri-Agency Open Access Policy on Publications. (shrink)

Background Ethical decision‑making and behavior of nurses are major factors that can affect the quality of nursing care. Moral development of nurses to making better ethical decision-making is an essential element for managing the care process. The main aim of this study was to examine and comparison the effect of training in ethical decision-making through lectures and group discussions on nurses’ moral reasoning, moral distress and moral sensitivity. Methods In this randomized clinical trial study with a pre- and post-test (...) design, 66 nurses with moral reasoning scores lower than the average of the community were randomly assigned into three equal groups (n = 22) including two experimental groups and one control group. Ethical decision-making training to experimental groups was provided through the lectures and group discussions. While, the control group did not receive any training. Data were collected using sociodemographic questionnaire, the nursing dilemma test (NDT), the moral distress scale (MDS) and the moral sensitivity questionnaire (MSQ). Unadjusted and adjusted binary logistic regression analysis was reported using the odds ratio (OR) and 95% confidence intervals. Results Adjusted regression analysis showed that the probability of increasing the nursing principle thinking (NPT) score through discussion training was significantly higher than lecture (OR: 13.078, 95% CI: 3.238–15.954, P = 0.008), as well as lecture (OR: 14.329, 95% CI: 16.171–2.005, P < 0.001) and discussion groups compared to the control group (OR: 18.01, 95% CI: 22.15–5.834, P < 0.001). The possibility of increasing moral sensitivity score through discussion training was significantly higher than lecture (OR: 10.874, 95%CI: 6.043–12.886, P = 0.005) and control group (OR: 13.077, 95%CI: 8.454–16.774, P = 0.002). Moreover, the moral distress score was significantly reduced only in the trained group compared to the control, and no significant difference was observed between the experimental groups; lecture group vs. control group (OR: 0.105, 95% CI: 0.015–0.717, P = 0.021) and discussion group vs. control group (OR: 0.089, 95% CI: 0.015–0.547, P = 0.009). Conclusions The results of this study indicate that ethical decision-making training is effective on empowerment of ethical reasoning. Whereas the group discussion was also effective on increasing the ethical sensitivity, it is recommended the training plan provided in this study to be held as workshop for all nurses in health and treatment centers and placed in curricular plan of nursing students. Registration This randomized clinical trial was registered in Iranian Registry of Clinical Trials under code (IRCT2015122116163N5) in 02/07/2016. (shrink)

This study explored drug users’ attitudes toward and understanding of randomized controlled trials testing addiction therapies. A video portraying a fictional consent conference for a randomized controlled trial with placebo arm was shown to poor male and female drug users of diverse ethnic status and sexual orientation. The video stimulated focus group discussion in which participants’ comments often reflected “experimental realism”—a realistic view of the trial—and adequate understanding of the uncertain efficacy of the treatment being (...) tested, as well as the concepts of randomization and placebo control. However, participants’ comprehension of the nature of placebos was compromised by the widespread view that placebos are a way of testing a subject’s willpower and personal control over his or her addiction. Comments also showed a mistrust of the video investigator’s integrity and competence and signs of therapeutic misconception and misestimation. The study’s findings underscore the importance of tailoring informed consent encounters to the personal and sociohistorical context of participants’ lived experiences. (shrink)

Background Ethically, informed consent regarding randomised controlled trials (RCTs) should be understandable to patients. The patients can then give free consent or decline to participate in a RCT. Little is known about what patients really understand in consultations about RCTs. Methods Cancer patients who were asked to participate in a randomised trial were surveyed using a semi-standardised interview developed by the authors. The interview addresses understanding, satisfaction and needs of the patients. The sample included eight patients who participated (...) in a trial and two who declined. The data were analysed on the basis of Mayring's qualitative analysis. Results Patients' understanding of informed consent was less developed than anticipated, especially concerning key elements such as randomisation, content and procedure of RCTs. Analysing the result about satisfaction of the patients, most of the patients described their consultations as hectic and without advance notice. Health limitations due to cancer played a decisive role. However, most of the patients perceived their physician to be sympathetic. Analysing the needs of patients, they ask for a clear informed consent consultation with enough time and adequate advance notice. Conclusion This study fills an important empirical research gap of what is ethically demanded in an RCT consultation and what is really understood by patients. The qualitative approach enabled us to obtain new results about cancer patients' understanding of informed consent, to clarify patients' needs and to develop new ideas to optimise the informed consent. (shrink)

Background: Explaining technical terms in consent forms prior to seeking informed consent to recruit into trials can be challenging in developing countries, and more so when the studies are randomized controlled trials. This study was carried out to examine the opinions of researchers on ways of dealing with these challenges in developing countries.Methods: Recorded in‐depth interviews with 12 lecturers and five doctoral students, who had carried out research in developing countries, at a leading school of public (...) health in the United Kingdom. A purposive, snowballing approach was used to identify interviewees.Results: Researchers were divided on the feasibility of explaining technical trials in illiterate populations; the majority of them held the view that local analogies could be used to explain these technical terms. Others were of the opinion that this could not be done since it was too difficult to explain technical trials, such as randomized controlled trials, even to people in developed countries.Conclusion: Researchers acknowledged the difficulty in explaining randomized controlled trials but it was also their perception that this was an important part of the ethics of the work of scientific research involving human subjects. These difficulties notwithstanding, efforts should be made to ensure that subjects have sufficient understanding to consent, taking into account the fact that peculiar situations in developing countries might compound this difficulty. (shrink)

Social anxiety disorders (SAD) are among the most prevalent mental disorders (lifetime prevalence: 7–12%), with high impact on the life of an affected social system and its individual social system members. We developed a manualized disorder-specific integrative systemic and family therapy (ISFT) for SAD, and evaluated its feasibility in a pilot randomized controlled trial (RCT). The ISFT is inspired by Helm Stierlin’s concept of related individuation developed during the early 1980s, which has since continued to be refined. It (...) integrates solution-focused language, social network diagnostics, and genogram work, as well as resource- and problem orientation for both case conceptualization and therapy planning. Post-Milan symptom prescription to fluidize the presented symptoms is one of the core interventions in the ISFT. Theoretically, the IFST is grounded in radical constructivism and “Cybern-Ethics,” multi-directional partiality, and a both/and attitude toward a disorder-specific vs. non-disorder-specific therapy approach. SAD is understood from the viewpoint of social systems theory, especially in adaptation to a socio-psycho-biological explanatory model of social anxiety. In a prospective multicenter, assessor-blind pilot RCT, we included 38 clients with SAD (ICD F40.1; Liebowitz Social Anxiety Scale, LSAS-SR > 30): 18 patients participated in the ISFT, and 20 patients in Cognitive Behavioral Therapy (CBT; age:M = 36 years,SD = 14). Within-group, simple-effect intention-to-treat analyses showed significant reduction in social anxiety (LSAS-SR; ISFT:d = 1.67; CBT:d = 1.04), while intention-to-treat mixed-design ANOVA demonstrated the advantage of ISFT (d = 0.81). Per-protocol analyses supported these results. The remission rate based on blind diagnosticians’ ratings was good to satisfactory (Structured Clinical Interview, SCID; 78% in ST, 45% in CBT,p = 0.083); this has yet to be verified in a subsequent confirmatory RCT. The article will present the ISFT rationale and manual, including a special focus on multi-person settings, and the central findings from our pilot RCT. (shrink)

BackgroundEarly in the COVID-19 pandemic, the urgent need to discover effective therapies for COVID-19 prompted questions about the ethical problem of randomization along with its widely accepted solution: equipoise. In this scoping review, uses of equipoise in discussions of randomized controlled trials of COVID-19 therapies are evaluated to answer three questions. First, how has equipoise been applied to COVID-19 research? Second, has equipoise been employed accurately? And third, do concerns about equipoise pose a barrier to the ethical (...) conduct of COVID-19 RCTs?MethodsGoogle Scholar and Pubmed were searched for articles containing substantial discussion about equipoise and COVID-19 RCTs. 347 article titles were screened, 91 full text articles were assessed, and 48 articles were included. Uses of equipoise were analyzed and abstracted into seven categories.Results and discussionApproximately two-thirds of articles used equipoise in a way that is consistent with the concept. They invoked equipoise to support RCTs of specific therapies, RCTs in general, and the early termination of RCTs after achieving the primary outcome. Approximately one-third of articles used equipoise in a manner that is inconsistent with the concept. These articles argued that physician preference, widespread use of unproven therapies, patient preference, or expectation of therapeutic benefit may undermine equipoise and render RCTs unethical. In each case, the purported ethical problem can be resolved by correcting the use of equipoise.ConclusionsOur findings highlight the continued relevance of equipoise as it supports the conduct of well-conceived RCTs and provides moral guidance to physicians and researchers as they search for effective therapies for COVID-19. (shrink)

BACKGROUND -/- The importance of ontologies in the biomedical domain is generally recognized. However, their quality is often too poor for large-scale use in critical applications, at least partially due to insufficient training of ontology developers. -/- OBJECTIVE -/- To show the efficacy of guideline-based ontology development training on the performance of ontology developers. The hypothesis was that students who received training on top-level ontologies and design patterns perform better than those who only received training in the basic principles of (...) formal ontology engineering. -/- METHODS -/- A curriculum was implemented based on a guideline for ontology design. A randomized controlled trial on the efficacy of this curriculum was performed with 24 students from bioinformatics and related fields. After joint training on the fundamentals of ontology development the students were randomly allocated to two groups. During the intervention, each group received training on different topics in ontology development. In the assessment phase, all students were asked to solve modeling problems on topics taught differentially in the intervention phase. Primary outcome was the similarity of the students’ ontology artefacts compared with gold standard ontologies developed by the authors before the experiment; secondary outcome was the intra-group similarity of group members’ ontologies. -/- RESULTS -/- The experiment showed no significant effect of the guideline-based training on the performance of ontology developers (a) the ontologies developed after specific training were only slightly but not significantly closer to the gold standard ontologies than the ontologies developed without prior specific training; (b) although significant differences for certain ontologies were detected, the intra-group similarity was not consistently influenced in one direction by the differential training. -/- CONCLUSION -/- Methodologically limited, this study cannot be interpreted as a general failure of a guideline-based approach to ontology development. Further research is needed to increase insight into whether specific development guidelines and practices in ontology design are effective. (shrink)

BackgroundThe participant recruitment process is a key ethical pivot point when conducting robust research. There is a need to continuously review and improve recruitment processes in research trials and to build fair and effective partnerships between researchers and participants as an important core element in ensuring the ethical delivery of high-quality research. When participants make a fair, informed, and voluntary decision to enroll in a study, they agree to fulfill their roles. However, supporting study participants to fulfill study requirements (...) is an important ethical obligation for researchers, yet evidenced as challenging to achieve. This paper reports on participants’ motivations to volunteer and remain part of a dietary study conducted in Kasungu District, Malawi.MethodsWe conducted twenty in-depth interviews (with chiefs, religious leaders, trial participants, and health surveillance assistants), five systematic ethnographic observations, and fourteen focus group discussions with trial participants and their partners. Interviews were audio-recorded and transcribed verbatim. We used a grounded theory methodology to analyse data that included coding, detailed memo writing, and data interpretation.FindingsThe findings reveal that many participants had concerns during the trial. Thematically, experiences included anxieties, mistrust of researchers, rumours, fears of exploitation, and misconceptions. Anonymous concerns collected from the participants were reported to the trial team which enabled the researchers to appropriately support participants. Despite initial concerns, participants described being supported and expressed motivation to take up their role.ConclusionThese findings highlight a diverse map of multiple notions of what is ethically relevant and what can impact participation and retention within a study. The study has revealed how embedding a responsive approach to address participants’ concerns and ethical issues can support trust relationships. We argue for the need to employ embedded ethics strategies that enhance informed consent, focus on participants’ needs and positive experiences, and support researchers to fulfill their roles. This work highlights the need for research ethics committees to focus on the risks of undue influence and prevent exploitation especially in settings with a high asymmetry in resources and power between researcher and participant groups.Trial Registration: The Addressing Hidden Hunger with Agronomy (Malawi) trial was registered on 5th March 2019 (ISCRTN85899451). (shrink)

The COVID-19 pandemic touched off an unprecedented search for vaccines and treatments. Without question, the development of vaccines to prevent COVID-19 was an enormous scientific accomplishment. Further, the RECOVERY and Solidarity trials identified effective treatments for COVID-19. But all was not success. The urgent need for COVID-19 prevention and treatment fueled an embrace of risks—to research participants and to the reliability of the science itself—as allegedly necessary costs to speed scientific progress. Scientists and (even) ethicists supported overturning longstanding norms (...) protecting healthy volunteers in human challenge trials to speed vaccine development, but these trials led to no vaccines. Physicians, with the approval of research ethics committees, designed hundreds of unblinded, single-center clinical trials at high risk of bias to speed the identification of new treatments. But these clinical trials led to no treatments. The lesson for future pandemics is that the acceptance of greater risks to participants or science does not reliably lead to progress. We are better served by science that upholds the highest ethical and methodological standards. (shrink)

This new edition of Charles Fried's Medical Experimentation includes a general introduction by Franklin Miller and the late Alan Wertheimer, a reprint of the 1974 text, an in-depth analysis by Harvard Law School scholars I. Glenn Cohen and D. James Greiner, and a new essay by Fried reflecting on the original text and how it applies to the contemporary landscape of medicine and medical experimentation.

The current controversy as to the proper role of the placebo control in the evaluation of new treatments for schizophrenia requires an analysis that is sensitive to both ethical and scientific issues. Clinical equipoise, widely regarded as the moral foundation of the randomized controlled trial (RCT), requires the use of best available treatment as the control in RCT. Scientific criticisms of the use of an active control are examined and none present an insuperable barrier to the use of (...) an active control. Indeed, scrutiny of the most recent argument for the use of placebo controls, 'assay sensitivity', suggests that the use of placebo may be the cause of the problem pointed to. Scientific, regulatory, ethical and legal advantages of the use of an active control are described. While the use of a placebo control may be acceptable in carefully defined circumstances, in most cases the use of an active control in schizophrenia research is ethically and scientifically preferable. (shrink)

Background: Family members are often required to act as substitute decision-makers when health care or research participation decisions must be made for an incapacitated relative. Yet most families are unable to accurately predict older adult preferences regarding future health care and willingness to engage in research studies. Discussion and documentation of preferences could improve proxies' abilities to decide for their loved ones. This trial assesses the efficacy of an advance planning intervention in improving the accuracy of substitute decision-making and increasing (...) the frequency of documented preferences for health care and research. It also investigates the financial impact on the healthcare system of improving substitute decision-making. Methods/DesignDyads (n = 240) comprising an older adult and his/her self-selected proxy are randomly allocated to the experimental or control group, after stratification for type of designated proxy and self-report of prior documentation of healthcare preferences. At baseline, clinical and research vignettes are used to elicit older adult preferences and assess the ability of their proxy to predict those preferences. Responses are elicited under four health states, ranging from the subject's current health state to severe dementia. For each state, we estimated the public costs of the healthcare services that would typically be provided to a patient under these scenarios. Experimental dyads are visited at home, twice, by a specially trained facilitator who communicates the dyad-specific results of the concordance assessment, helps older adults convey their wishes to their proxies, and offers assistance in completing a guide entitled My Preferences that we designed specifically for that purpose. In between these meetings, experimental dyads attend a group information session about My Preferences. Control dyads attend three monthly workshops aimed at promoting healthy behaviors. Concordance assessments are repeated at the end of the intervention and 6 months later to assess improvement in predictive accuracy and cost savings, if any. Copies of completed guides are made at the time of these assessments. DiscussionThis study will determine whether the tested intervention guides proxies in making decisions that concur with those of older adults, motivates the latter to record their wishes in writing, and yields savings for the healthcare system. Trial RegistrationISRCTN89993391. (shrink)

OBJECTIVES: To study whether linguistic analysis and changes in information leaflets can improve readability and understanding. DESIGN: Randomised, controlled study. Two information leaflets concerned with trials of drugs for conditions/diseases which are commonly known were modified, and the original was tested against the revised version. SETTING: Denmark. PARTICIPANTS: 235 persons in the relevant age groups. MAIN MEASURES: Readability and understanding of contents. RESULTS: Both readability and understanding of contents was improved: readability with regard to both information leaflets and (...) understanding with regard to one of the leaflets. CONCLUSION: The results show that both readability and understanding can be improved by increased attention to the linguistic features of the information. (shrink)

Telemedicine is a complex field including various applications and target groups. Especially telehealthcare is seen by many as a means to revolutionize medicine. It gives patients the opportunity to take charge of their own health by using self-tracking devices and allows health professionals to treat patients from a distance. To some, this means an empowerment of patient autonomy as well as an improvement in the quality of care. Others state the dangers of depersonalization of medicine and the pathologization of daily (...) life. This paper examines the ethical implications of telehealthcare, focusing on patient autonomy and quality of care by analyzing metareviews, randomized controlled trials and narrative ethical analyses on the topic. As a result, we conclude that the technically enhanced encounter between patients and health professionals may mean an empowerment of patient autonomy when it goes along with a personal relationship based on trust, assistance and support. When it comes to the quality of care, telehealthcare may lead to an improvement as long it is adopted to the patient’s individual needs. (shrink)

During the recent Ebola epidemic, some commentators and stakeholders argued that it would be unethical to carry out a study that withheld a potential treatment from affected individuals with such a serious, untreatable disease. As a result, the initial trials of experimental treatments did not have control arms, despite important scientific reasons for their inclusion. In this paper, we consider whether the duty to rescue entails that it would be unethical to withhold an experimental treatment from patient-participants with serious (...) diseases for which there are no effective treatments, even when doing so is scientifically necessary to test the effectiveness of the treatment. We argue that the duty to rescue will rarely apply. The context of medical research also throws new light on the content of the duty to rescue, since the interests of future patients—who stand to benefit from the fruits of medical research—are relevant to whether the duty applies. (shrink)

The principle of clinical equipoise has been variously characterized by ethicists and clinicians as fundamentally flawed, a myth, and even a moral balm. Yet, the principle continues to be treated as the de facto gold standard for conducting randomized control trials in an ethical manner. Why do we hold on to clinical equipoise, despite its shortcomings being widely known and well-advertised? This paper reviews the most important arguments criticizing clinical equipoise as well as what the most prominent proposed (...) alternatives are. In the process, it evaluates the justification for continuing to use clinical equipoise as the gold standard for randomized control trials. (shrink)

Positive Psychology Interventions as an Opportunity in Arab Countries to Promoting Well-being AbstractIn this perspective paper, we emphasize the importance of further research on culturally-sensitive positive psychology interventions in the Arab region. We argue that these interventions are needed in the region because they not only reduce mental health problems but also promote well-being and flourishing. To achieve this, we shed light on the cultural elements of the Arab region and how the concept of well-being differs from that of Western (...) culture. We review the research conducted in Arabia, briefly evaluate the quality of this research and list some adapted measurements. We furthermore propose guidelines and recommendations for future evidence-based positive psychology interventions research to align with the national culture in various sectors and community samples that contribute to the development of well-being in the Arab world.Introduction Extensive research on Positive Psychology Interventions (PPIs) - defined as activities focus on promoting positive feelings, thoughts, or behaviour (Sin & Lyubomirsky, 2009) - has shown their effectiveness in well-being and mental illness (e.g., Chakhssi et al., 2018; Hendriks et al., 2020). A recent review of 347 studies showed that PPIs have a significant effect on promoting quality of life and well-being and reducing anxiety and depression (Carr et al., 2020). However, the issue is that most of these studies (82%) remain narrow in focus only on Western Educated Industrialised Rich Democratic (WEIRD) countries (Hendriks et al., 2019). Therefore, they may not be effective for other countries such as the Arab countries where there are various cultural differences. This highlights the key role that culture can play in enhancing PPIs engagement, acceptability, and eventually, effectiveness (Hendriks & Graafsma, 2019). Recently, the field of PP in the Arab region has begun to grow (Basurrah et al., 2021; Rao et al., 2015). However, studies conducted in these countries are scant and of poor methodological quality. We have found humble quantity and quality of empirical studies. Yet, Arab countries, home to 5% of the world’s population, have a burden of mental health problems above global levels (GBD 2015 Eastern Mediterranean Region Mental Health Collaborators, 2018). Prevalent stigma, war and conflict were some of the contributors (Maalouf et al., 2019). Thus, to properly address this cultural stigma against mental health problems, PPIs could provide an additional role alongside traditional psychology approaches (e.g., Cognitive Behavioural therapy - CBT). Further, in light of the political conditions that some Arab countries are going through and the negative effects that they cause, it has become necessary to use the method of prevention that is the focus of PP and not only of treatment as a strategy for applications and practice. It has been noted that the mental health care system in the Arab region focuses highly on illnesses treatment and neglects the significant role that PP plays in enhancing human potential and well-being. We - here in Arabia –are becoming more influenced by many global issues particularly the COVID-19 pandemic and their impact on mental health and well-being (e. g. prevalence of stress, anxiety, depression among the general population during the pandemic (Salari et al., 2020). In response, Waters et al. (2021) have recently presented how positive psychological factors can play a significant role in buffering mental illness, enhancing mental health throughout the pandemic, and building positive processes and capacities that can help to promote future mental health.Here in this perspective paper, we highlight the cultural aspects of Arab countries. Specifically, we present previous PPIs research conducted in Arabia and briefly evaluate the quality of this research. Importantly, we discuss the need of developing an indigenous and culturally sensitive PP among the Arab region (Lambert et al., 2015).Arab Culture “Arab World,” which comprises 5% of the world’s population, refers to the Arab countries in the Middle East and North Africa. Despite the increasing pace and progress of different businesses in many Arab countries, individual communities are still limited in certain prominent economic places. Arab people rather gather in collective communities. They generally share the same Arabic Islamic culture, speak the same language, and descend from the same Arab families when going back in history no matter what nationality they have nowadays. Yet, very many changes came to communities before borders were drawn between countries and after. For instance, geography, topography, demography, and socio-economic status affect peoples’ nature of jobs and lifestyles. For example, Arabs in the east, west, or the middle have similar tongues; however, almost every Arab country has its accent. Therefore, people need to go back to the formal Arabic language ‘Fus-ha’ or learn more about different Arabic dialects when communicating cross-countries. According to Hofstede’s model (2011) based on the individualism-collectivism dimension, the Arab countries (Eastern society) have been classified as a collectivist culture, where their identity and decisions are influenced by social systems. In contrast, the United States (Western society) has been classified as an individualist culture focusing on individual decisions. Although there are degrees of individualism among Arabs in certain countries, they still share collective common characteristics. Here, we explore the meaning of collectivistic conceptions of the self, emotions, values, and religion in Arab countries and how they differ from those in individual Western cultures. The Self Since the field of PP focuses on the development of self, it is vital to recognize that self-concept varies across cultures. Individualism generally emphasises the self-directed and autonomous individual (Realo et al., 2002). People in individualist countries focus primarily on their personal characteristics (e.g., motives, abilities) to build their self-concept. On the other hand, collectivism refers to several social structures that highly value the groups to which people belong, such as family and tribe (Realo, 2003). People in collectivist countries such as the Arab countries focus primarily on their relationships with others to build their self-concept (Markus & Kitayama, 1991). Hence, research from Arab countries should focus on the core elements of collectivism when implementing PPIs to make a significant, meaningful impact. For example, people from a collective culture may experience a greater enhancement in well-being when practising interventions that are more prosocial and group-oriented such as compassion, performing acts of kindness, writing a gratitude letter, and using character strengths in everyday context including social context, compared with self-oriented interventions such as identifying character strengths. Emotions, value, and Religion Research shows that Western culture emphasises the goal of maximizing positive emotions, while Eastern culture emphasises embracing and balancing positive and negative emotions (Leu et al., 2011). To illustrate, culture plays an important role in influencing perceptions of happiness. People in individualist countries value happiness highly. In contrast, people from the collective countries value low arousal positive emotions (Leu et al., 2011) and exhibit a fear of happiness (Joshanloo & Weijers, 2014; Joshanloo, 2013). Hence, the influence of positive emotions plays a limited role in the mental health of Eastern society. Speaking of Value, for an Arab, the family is the centre of honour and the most important social unit. This loyalty has an impact on every part of an Arab’s life. Arabs honour their families and highly value their friendships. Therefore, future research could shed more light on group-oriented interventions (e.g., kindness) that focus more on the relationship with family, friends, and community. When it comes to religion, Arab society has a rich culture in values and believes that place a high emphasis on spirituality. Religion is the most important and distinctive aspect of Arab culture. Arab countries vary in terms of religion, with Islam being the predominant religion in most of them. Well-being (Hedonic and Eudaimonic) It is necessary here to clarify what is meant by hedonic and eudaimonic definitions of well-being. While the term ‘Hedonic’ is based on the pursuit of maximum levels of pleasure (feeling good), the term ‘Eudaimonic’, on the other hand, is based on meaning and the development of virtues (functioning well; Keyes & Annas, 2009). Research indicates that cultures are not equally supportive of hedonic and eudaimonic aspects (Joshanloo & Jarden, 2016). In comparison to collectivism, hedonism appears to be more congruent with individualism (Joshanloo, 2014). Pleasure and positive emotions are considered a way to pursue happiness in Western culture, while this method is not highly favoured in Eastern cultures (Lee et al., 2013); Because they consider suffering and negative emotions as contributing factors to spiritual development. Therefore, the eastern perspective is more in line with a eudaimonistic view which emphasises virtues, meaning, and feeling of belongingness. However, although we believe that both approaches can be found to a certain level in both cultures, the differences suggest that there are different routes to happiness. Positive Psychology in the Arab region Positive psychology - "the scientific study of what makes life most worth living" (Seligman & Csikszentmihalyi, 2000) - is one of the newest branches of psychology. It focuses on three main pillars: (1) positive subjective experiences (such as happiness and love); (2) positive individual characters (such as gratitude and compassion); and (3) positive institutions (for the application of positive principles within institutions and organizations; Seligman & Csikszentmiha lyi, 2000). Some of the main topics of interest in positive psychology include character strengths, gratitude, hope, happiness, mindfulness, optimism, positive thinking, and resilience. Within the applications of this science, various domains of well-being (such as happiness, engagement, positive emotions, and meaning) can be enhanced by practising positive psychology interventions (Sin & Lyubomirsky, 2009). Interestingly, these interventions have also produced benefits beyond well-being, such as reduced mental health issues (Chakhssi et al., 2018; Hendriks et al., 2020).Nowadays, PP is increasingly noticed in the Arab world (Lambert & Pasha-Zaidi, 2019; Rao et al., 2015). In recent years, there has been a great effort to explore the PP field across Arab countries. Several initiatives have emerged aimed at promoting well-being and flourishing. For example, the Middle East Journal of Positive Psychology published its first volume in 2015. On the International Day of Happiness in 2017, United Arab Emirates University launched its Emirates Center for Happiness Research. Meanwhile, Effat University in Saudi Arabia started the first Positive Psychology and Well-being Research Lab, the first symposium, and the first PP course. In 2019, Louise Lambert and Nausheen Pasha-Zaidi published the first regional text entitled “Positive Psychology in the Middle East/North Africa.” There are other efforts spent in the region as well; such as the work conducted in Egypt. Ibrahim Younus established the Arab Association for Positive Psychology https://www.psycholearn.com/en/associative.php which provides several courses on PP and also published a book entitled “The Power of Positive Psychology” (Younus, 2017). Despite this development, nothing can compare to the quantity and even quality of research in other countries. In light of our observations, the few PP studies may be attributed to the lack of awareness of the constructive approach and prevention compared to problem-solving. An Arab dentist once said: “people do not come to me until they are badly in pain.” In any case, many studies have taken place in Arab countries in the last decade, more of which are descriptive and less of which experimental. For example, Abdel-Khalek (2010) found positive correlations between quality of life, subjective well-being, and religiosity among students in Kuwait. Abdel-Khalek (2016) developed “the Arabic Scale of Religiosity,” which significantly correlated with PP variables among students in Algeria, Kuwait, and Egypt. Recently, empirical studies on PPIs have arisen in Arab-Islamic countries. More attention has been focused on promoting well-being and alleviating the high burden of mental health problems in the region (GBD 2015 Eastern Mediterranean Region Mental Health Collaborators, 2018). For instance, several studies examined the effectiveness of mindfulness among university students (e.g., Al-Ghalib & Slim, 2018; Awad, 2019; Thomas et al., 2016), parents of children with autism (Rayan & Ahmed, 2016) and addicted adults (Al-Rashidi, 2018). Such an intervention has positive effects. Participants who practised mindfulness reported reduction in stress and depression as well as improvement in well-being and resilience. Moreover, the results of a recent pilot study found positive impacts on enhancing emotional regulations and reducing stress among Arab teachers (Berkovich-Ohana et al., 2020). Some studies have also begun to examine various interventions targeting character strengths (Basurrah et al., 2020; Chérif et al., 2020), self-compassion (Elaiwah, 2017), positive thinking (Mohammed et al., 2014; Hadad, 2014), and hope (Zaki, 2016). Interestingly, a new finding considering the fear of happiness among people from collective countries has been examined. Lambert et al. (2019) provided evidence that a 14-week PPIs programme has an impact on reducing the fear and fragility of happiness beliefs among university students in the United Arab Emirates.Since Arab countries place great emphasis on spirituality, several authors have considered the aspect of religion when implementing PPIs. For instance, an empirical study by Al-Seheel and Noor (2016) found that expressing gratitude towards God “Allah” increases the happiness of the Muslim more than the usual gratitude intervention. Additionally, Al-Ghalib and Salim (2018) examined a religiously sensitive mindfulness-training programme with university students and found a positive effect on life satisfaction and a slight reduction in stress, depression, and anxiety. Hence, the role of religion is vital to make the interventions more relevant to Arab culture where people can connect Islamic philosophy with PP theories and practices. These studies reviewed here provide further support for the need for culturally sensitive interventions among the Arab population. More recently, the first systematic review of PPIs in Arab countries was conducted by Basurrah et al. (2021; the protocol has been published in BMJ Open and the final manuscript has been submitted for publication). Reviewing a total of 39 studies, the most commonly studied interventions were mindfulness, positive thinking, and resilience. Only a handful of studies examined gratitude, character strengths, forgiveness, self-compassion, savouring, or finding flow. Further analysis revealed that most studies from Arab countries have several methodological limitations. This included a lack of protocol guidelines, few well-designed randomized controlled trials (RCTs), blinding issues, small sample sizes, lack of active control groups, and lack of research into certain populations (e.g., teachers, employees, and people in distress in refugee camps). Discussion PP was founded on an individualistic framework (Christopher & Hickinbottom, 2008). To ensure that PPIs are culturally meaningful, this paper includes some cultural elements of the Arab region that should be considered to serve the needs of the Arab population. In the Arab world, some people may believe that PP is solely about happiness and being positive. If so, it is important to educate the public about the findings of rigorous studies evaluating PPIs such as gratitude, hope or flow on health, well-being and performance. To explain the value and effectiveness of these evidence-based approaches, examples might include studies linking gratitude with benefits for people with heart disease (Cousin et al., 2021), or how PPIs can promote quality of life in cancer patients (Casellas-Grau et al., 2014). There is some evidence about PPIs being effective in improving well-being in the Arab region, but research in this region is still in its infancy and little information is available regarding PPIs and the experience of Arabs participating in such interventions. Hence, there is still much more to investigate in this regard. Future research should empirically examine the effectiveness of various unstudied interventions such as savouring, gratitude, self-compassion, character strengths or finding flow. A combination of quantitative and qualitative approaches is required to provide an in-depth understanding of Arabs’ experience and impressions of PPIs and how and why they work. This may provide useful information to inform the appropriate design of PPIs to suit Arab culture and needs. Furthermore, while some research on PPIs has been carried out in the region, most of these studies have been of poor quality that suffered from small sample sizes, confounding factors, and a high degree of bias. To overcome these issues, future research should improve research quality, including protocol guidelines and well-designed RCTs. In particular, research should include randomization, allocation, blinding, power analysis to determine adequate sample size, active control groups to reduce bias, and follow-up periods of at least 12 months.Among the most popular resources that future PP practitioners may refer to are the International Positive Psychology Association (IPPA) and the International Positive Education Network (IPEN). Also, we recommend the Middle East Journal of Positive Psychology and the first regional book (Lambert & Pasha-Zaidi, 2019). To develop and/or adapt a multi-component PPIs, we would recommend referring to Character Strengths (Peterson & Seligman, 2004), the theory of well-being (PERMA Model: Positive Emotion, Engagement, Relationships, Meaning, and Accomplishment; Seligman, 2011), and the Five Ways to Well-being: Connect, Be Active, Take Notice, Keep Learning, and Give (Aked et al., 2008). Finally, single-component PPIs are based on theories like Broaden-And-Build (Fredrickson, 2004), Hope (Snyder et al., 2002), and Self-Determination (Deci & Ryan, 2012) can be also considered. Two other concepts that would be usefully applied are ‘Savouring’ (Bryant & Veroff, 2007) and Phillip Zimbardo’s Time Perspective (Stolarski et al., 2015). For instance, savouring has a positive temporal orientation to reminiscing the good memories from the past, enjoying the hedonic present moments, and willing proactively to make a better future. Now, what is even maybe more interesting for Muslims is “Transcendent Future” where all intentions, words and actions are devoted to that life after death. In addition, there is a model already prepared for the clinical purpose called Positive Psychotherapy (PPT). Tayyab Rashid and Martin Seligman published a PPT manual for clinicians in 2018. And for cross-cultural applications, including Muslim Arab culture, Rashid and Al-Haj Baddar (2019) have written a paper presenting PPT and its efficacy. PPT overview in detail shows sessions, themes, skills, practice, and cultural considerations where a mixture of PPIs based on PERMA, Strengths, and other PP concepts can be found. Regarding PP measurements, it is highly recommended to generate indigenous tools based on cultural backgrounds reviewed here in the article. An example of this is a tool for measuring Muslim well-being by including domains beyond what is found in Western literature. So far, in the Arab region, several attempts have been made to adapt PP tools. For example, Marei Salama-Younes (2018) validated the Arabic versions of different measures of well-being (e.g., satisfaction with life scale, the subjective vitality scale). Other validated scales as well include the self-compassion scale (Alabdulaziz et al., 2020), and the passion scale (Salama-Younes & Hashim, 2018). Conclusion This paper has discussed the cultural aspects of Arab countries and the need of developing culturally sensitive PPIs. The past decade has seen an increase in mental health problems in the Arab region. Stigma and lack of awareness have been always there. Among the issues are also wars, conflicts, and displacement in many Arab countries such as Iraq, Lebanon, and Palestine (Hassan et al., 2016). These indicate an urgent need to prevent mental illness and promote well-being. Indeed, we highlighted the importance of integrating culture with PPIs, following the guidelines for the cultural adaptation of PPIs (Hendriks & Graafsma, 2019) and the ethical guidelines for PP practice (Jarden et al., 2020). Another significant contribution of this paper is to highlight the importance of improving the quality of research conducted in Arab countries. In brief, this paper has several practical implications. It is an open invitation for researchers, policymakers, and practitioners alike to be more exposed to PP; as well as to better conceptualising and adapting interventions and measurement tools to the local culture in different sectors to maximize their effectiveness. And as we consider it as an invitation for us too, here we are starting a PPIs practice guide in Arabic language and for Arab practitioners. The insights gained from this paper may be useful for placing well-being on top of priorities for achieving individual, organizational, and optimal national functioning in different sectors. There is also a need to change the stigma or negative beliefs about seeking health for psychological support, which is an issue for countries in the Middle East (Baess, 2018). (shrink)

This paper describes the unique values of, challenges within, and opportunities presented by embedded ELSI ethnography. Drawing from our six‐year embedded ELSI study of the WISDOM (Women Informed to Screen Depending on Measures of Risk) trial, we present three examples of the variable ways we engaged with the WISDOM trial's scientific team. WISDOM is a preference‐sensitive, pragmatic, randomized controlled trial of risk‐based breast cancer screening informed by genomics. Our embedded ELSI approach included multiple modes of engagement: (a) Trial (...) investigators sought bioethics expertise; for example, we were asked to consult on traditional bioethics topics such as consent as well as more complex questions about whether to implement a specific risk‐assessment approach on only one race‐defined group of trial participants. (b) As the ELSI investigators, we identified ethical concerns in issues that surfaced via ethnography and considered them in the Bioethics Working Group; for example, there were concerns about the implementation processes that the WISDOM team viewed as logistical challenges. (c) Our presence in WISDOM working group conversations and our expertise on classic social science topics, including race and gender, offered opportunities to engage on the spot with topics such as how to include transgender participants in a trial initially focused on “women's health”; through such engagement, the value of social science became clear to the trial investigators. The paper elaborates on the dynamic relationship between our ethnographic observations, the Bioethics Working Group discussions, and the contributions of each to our real‐time ELSI interventions in these examples. The methods and experiences we describe here suggest modes of engagement that, in combination, have the potential to expand the role of ELSI to offer real‐time intervention on issues related to equity, inclusion, and justice in genetic and genomic research. (shrink)

Many in the international development community have embraced the randomized controlled field experiment, akin to a biomedical clinical trial for social interventions, as the new “gold evidential standard” in program impact evaluation. In response, critics have called upon the method’s advocates to consider the moral dimensions of randomization, leading to a debate about the method’s ethics. My research intervenes in this debate by empirically investigating how researchers manage the perception of randomization in the field. Without the possibility (...) of a placebo, researchers rhetorically and materially frame the experiment differently for the control and treatment groups. Three technologies allow for this differential framing: geographic separation, temporal delay, and public randomization ceremonies. Geographic separation is a “technology of opacity” designed to obscure unequal resource distribution by disentangling the intervention and research components of the experiment for the control group. The latter two are technologies of transparency designed to expose the element of randomization but downplay conditions that may affect participant buy in. All three technologies work to preclude collective definitions of fair resource allocation, yet they are not fully successful in preventing modes of confrontation and resistance that lie outside of the experiment’s framing. (shrink)

Background: COVID-19 has taken many lives worldwide and due to this, millions of persons are in grief. When the grief process lasts longer than 6 months, the person is in risk of developing Complicated Grief Disorder. The CGD is related to serious health consequences. To reduce the probability of developing CGD a preventive intervention could be applied. In developing countries like Mexico, the psychological services are scarce, self-applied interventions could provide support to solve this problem and reduce the health impact (...) even after the pandemic has already finished.Aims: To design and implement a self-applied intervention composed of 12 modules focused on the decrease of the risk of developing CGD, and increasing the life quality, and as a secondary objective to reduce the symptomatology of anxiety, depression, and increase of sleep quality. The Intervention Duelo COVID follows the principles of User Experience and is designed according to the needs and desires of a sample of the objective participants, to increase the adherence to the self-applied intervention, considered one of the main weaknesses of online interventions.Methods: A Randomized Controlled Trial will be conducted from the 22nd of December of 2020 to the first of June 2021. The participants will be assigned to an intervention with elements of Cognitive Behavioral Therapy, Acceptance and Commitment Therapy, Mindfulness and Positive Psychology. The control group will be a wait-list condition, that will receive the intervention 1.5–2 months after the pre-measurement were taken. The Power Size Calculation conducted through G*Power indicated the need for a total of 42 participants, which will be divided by 21 participants in each group. The platform will be delivered through responsive design assuring with this that the intervention will adapt to the screen size of cellphones, tablets, and computers.Ethics and Dissemination: The study counts with the approval of the Research Ethics Committee of the Autonomous University of Ciudad Juárez, México, and it is registered in Clinical Trials. The article is sent and registered in clinical trials before the recruitment started. The results will be reported in future conferences, scientific publications, and media. (shrink)

The use of placebo as a control condition in clinical trials of major depressive disorder and anxiety disorders continues to be an area of ethical concern. Typically, opponents of placebo controls argue that they violate the beneficent-based, “best proven diagnostic and therapeutic method” that the original Helsinki Declaration of 1964 famously asserted participants are owed. A more consequentialist, oppositional argument is that participants receiving placebo might suffer enormously by being deprived of their usual medication(s). Nevertheless, recent findings of potential (...) for suicidality in young people treated with antidepressants, along with meta-analyses suggesting that antidepressants add no significant clinical benefit over placebos, warrant a re-evaluation of the arguments against placebo. Furthermore, the nature of placebo treatment in short-term clinical trials is often not well understood, and lack of understanding can foster opposition to it. This paper will show how scientific justifications for placebo use are morally relevant. The fundamental ethical importance of placebo controls is discussed in relation to several aspects of clinical trials, including detection of adverse events, accurate assessment of clinical benefit, advancing understanding of the heterogeneity of depression and anxiety disorders and respecting informed consent requirements. Prohibiting the use of placebo controls is morally concerning in that such prohibitions allow for the possibility of serious adverse public health consequences. Moral worries that research participants receiving placebo are being unduly jeopardised will be shown to be exaggerated, especially in relation to the net benefits for end-users to be gained from the quality of data resulting from using placebo controls. (shrink)

ABSTRACT I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments. INTRODUCTION In contrast to the classic model of randomized-control trials, often with a (...) large number of subjects enrolled, precision medicine attempts to optimize therapeutic outcomes by focusing on the individual.[i] A recent publication highlights the strengths and weakness of both traditional evidence-based medicine and precision medicine.[ii] Plus, it outlines a tension in the shift from evidence-based medicine’s inductive reasoning style (the collection of data to postulate general theories) to precision medicine’s abductive reasoning style (the generation of an idea from the limited data available).[iii] The paper’s main example is the application of precision medicine for the treatment of cancer.[iv] I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. As the name suggests, brain-computer interfaces are a significant advancement in neurotechnology that directly connects someone’s brain to external or implanted devices.[v] Among the various kinds of brain-computer interfaces, adaptive deep brain stimulation devices require numerous personalized adjustments to their settings during the implantation and computation stages in order to provide adequate relief to patients with treatment-resistant disorders. What makes these devices unique is how adaptive deep brain stimulation integrates a sensory component to initiate the stimulation. While not commonly at the level of sophistication as self-supervising or generative large language models,[vi] they currently allow for a semi-autonomous form of neuromodulation. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments.[vii] ANALYSIS I. The State of Precision Medicine in Oncology and the Epistemological Shift While a thorough overview of precision medicine for the treatment of cancer is beyond the scope of this article, its practice can be roughly summarized as identifying clinically significant characteristics a patient possesses (e.g., genetic traits) to land on a specialized treatment option that, theoretically, should benefit the patient the most.[viii] However, in such a practice of stratification patients fall into smaller and smaller populations and the quality of evidence that can be applied to anyone outside these decreases in turn.[ix] As inductive logic helps to articulate, the greater the number of patients that respond to a particular therapy the higher the probability of its efficacy. By straying from this logical framework, precision medicine opens the treatment of cancer to more uncertainty about the validity of these approaches to the resulting disease subcategories.[x] Thus, while contemporary medical practices explicitly describe some treatments as “personalized”, they ought not be viewed as inherently better founded than other therapies.[xi] A relevant contemporary case of precision medicine out of Norway focuses on the care of a patient with cancer between the ventricles of the heart and esophagus, which had failed to respond to the standard regimen of therapies over four years.[xii] In a last-ditch effort, the patient elected to pay out-of-pocket for an experimental immunotherapy (nivolumab) at a private hospital. He experienced marked improvements and a reduction in the size of the tumor. Understandably, the patient tried to pursue further rounds of nivolumab at a public hospital. However, the hospital initially declined to pay for it given the “lack of evidence from randomised clinical trials for this drug relating to this [patient’s] condition.”[xiii] In rebuttal to this claim, the patient countered that he was actually similar to a subpopulation of patients who responded in “open‐label, single arm, phase 2 studies on another immune therapy drug” (pembrolizumab).[xiv] Given this interpretation of the prior studies and the patient’s response, further rounds of nivolumab were approved. Had the patient not had improvements in the tumor’s size following a round of nivolumab, then pembrolizumab’s prior empirical evidence in isolation would have been insufficient, inductively speaking, to justify his continued use of nivolumab.[xv] The case demonstrates a shift in reasoning from the traditional induction to abduction. The phenomenon of ‘cancer improvement’ is considered causally linked to nivolumab and its underlying physiological mechanisms.[xvi] However, “the weakness of abductions is that there may always be some other better, unknown explanation for an effect. The patient may for example belong to a special subgroup that spontaneously improves, or the change may be a placebo effect. This does not mean, however, that abductive inferences cannot be strong or reasonable, in the sense that they can make a conclusion probable.”[xvii] To demonstrate the limitations of relying on the abductive standard in isolation, commentators have pointed out that side effects in precision medicine are hard to rule out as being related to the initial intervention itself unless trends from a group of patients are taken into consideration.[xviii] As artificial intelligence (AI) assists the development of precision medicine for oncology, this uncertainty ought to be taken into consideration. The implementation of AI has been crucial to the development of precision medicine by providing a way to combine large patient datasets or a single patient with a large number of unique variables with machine learning to recommend matches based on statistics and probability of success upon which practitioners can base medical recommendations.[xix] The AI is usually not establishing a causal relationship[xx] – it is predicting. So, as AI bleeds into medical devices, like brain-computer interfaces, the same cautions about using abductive reasoning alone should be carried over. II. Responsive Neurostimulation, AI, and Personalized Medicine Like precision medicine in cancer treatment, computer-brain interface technology similarly focuses on the individual patient through personalized settings. In order to properly expose the intersection of AI, precision medicine, abductive reasoning, and implantable neurotechnologies, the descriptions of adaptive deep brain stimulation systems need to deepen.[xxi] As a broad summary of adaptive deep brain stimulation, to provide a patient with the therapeutic stimulation, a neural signal, typically referred to as a local field potential,[xxii] must first be detected and then interpreted by the device. The main adaptive deep brain stimulation device with premarket approval, the NeuroPace Responsive Neurostimulation system, is used to treat epilepsy by detecting and storing “programmer-defined phenomena.”[xxiii] Providers can optimize the detection settings of the device to align with the patient’s unique electrographic seizures as well as personalize the reacting stimulation’s parameters.[xxiv] The provider adjusts the technology based on trial and error. One day machine learning algorithms will be able to regularly aid this process in myriad ways, such as by identifying the specific stimulation settings a patient may respond to ahead of time based on their electrophysiological signatures.[xxv] Either way, with AI or programmers, adaptive neurostimulation technologies are individualized and therefore operate in line with precision medicine rather than standard treatments based on large clinical trials. Contemporary neurostimulation devices are not usually sophisticated enough to be prominent in AI discussions where the topics of neural networks, deep learning, generative models, and self-attention dominate the conversation. However, implantable high-density electrocorticography arrays (a much more sensitive version than adaptive deep brain stimulation systems use) have been used in combination with neural networks to help patients with neurologic deficits from a prior stroke “speak” through a virtual avatar.[xxvi] In some experimental situations, algorithms are optimizing stimulation parameters with increasing levels of independence.[xxvii] An example of neurostimulation that is analogous to the use of nivolumab in Norway surrounds a patient in the United States who was experiencing both treatment-resistant OCD and temporal lobe epilepsy.[xxviii]Given the refractory nature of her epilepsy, implantation of an adaptive deep brain stimulation system was indicated. As a form of experimental therapy, her treatment-resistant OCD was also indicated for the off-label use of an adaptive deep brain stimulation set-up. Another deep brain stimulation lead, other than the one implanted for epilepsy, was placed in the patient’s right nucleus accumbens and ventral pallidum region given the correlation these nuclei had with OCD symptoms in prior research. Following this, the patient underwent “1) ambulatory, patient-initiated magnet-swipe storage of data during moments of obsessive thoughts; (2) lab-based, naturalistic provocation of OCD-related distress (naturalistic provocation task); and (3) lab-based, VR [virtual reality] provocation of OCD-related distress (VR provocation task).”[xxix] Such signals were used to identify when to deliver the therapeutic stimulation in order to counter the OCD symptoms. Thankfully, following the procedure and calibration the patient exhibited marked improvements in their OCD symptoms and recently shared her results publicly.[xxx] In both cases, there is a similar level of abductive justification for the efficacy of the delivered therapy. In the case study in which the patient was treated with adaptive deep brain stimulation, they at least had their neural activity tested in various settings to determine the optimum parameters for treatment to avoid them being based on guesswork. Additionally, the adaptive deep brain stimulation lead was already placed before the calibration trials were conducted, meaning that the patient had already taken on the bulk of the procedural risk before the efficacy could be determined. Such an efficacy test could have been replicated in the first patient’s cancer treatment, had it been biopsied and tested against the remaining immunotherapies in vitro. Yet, in the case of cancer with few options, one previous dose of a drug that appeared to work on the patient may justify further doses. However, as the Norwegian case presents, corroboration with known responses to a similar drug (from a clinical trial) could be helpful to validate the treatment strategy. (It should be noted that both patients were resigned to these last resort options regardless of the efficacy of treatment.) There are some elements of inductive logic seen with adaptive deep brain stimulation research in general. For example, abductively the focus could be that patient X’s stimulation parameters are different from patient Y’s and patient Z’s. In contrast, when grouped as subjects who obtained personalized stimulation, patients X, Y, and Z demonstrate an inductive aspect to this approach’s safety and/or efficacy. The OCD case holds plenty of abductive characteristics in line with precision medicine’s approach to treating cancer and as more individuals try the method, there will be additional data. With the gradual integration of AI into brain-computer interfaces in the name of efficacy, this reliance on abduction will continue, if not grow, over time. Moving forward, if a responsive deep brain stimulation treatment is novel and individualized (like the dose of nivolumab) and there is some other suggestion of efficacy (like clinical similarities to other patients in the literature), then it may justify insurance coverage for the investigative intervention, absent other unrelated reasons to deny it. III. Ethical Implications and Next Steps While AI’s use in oncology and neurology is not yet as prominent as its use in other fields (e.g., radiology), it appears to be on the horizon for both.[xxxi] AI can be found in both the functioning of the neurotechnologies as well as the implementation of precision medicine. The increasing use of AI may serve to further individualize both oncologic and neurological therapies. Given these implications and the handful of publications cited in this article, it is important to have a nuanced evaluation of how these treatments, which heavily rely on abductive justification, ought to be managed. The just use an abductive approach may be difficult as AI infused precision medicine is further pursued. At baseline, such technology relies on a level of advanced technology literacy among the general public and could exclude populations who lack access to basic technological infrastructure or know-how from participation.[xxxii] Even among nations with adequate infrastructure, as more patients seek out implantable neurotechnologies, which require robust healthcare resources, the market will favor patient populations that can afford this complex care.[xxxiii] If patients already have the means to pay for an initial dose/use of a precision medicine product out of pocket, should insurance providers be required to cover subsequent treatments?[xxxiv] That is, if a first dose of a cancer drug or a deep brain stimulator over its initial battery life is successful, patients may feel justified in having the costs of further treatments covered. The Norwegian patient’s experience implies there is a precedent for the idea that some public insurance companies ought to cover successful cancer therapies, however, insurance companies may not all see themselves as obligated to cover neurotechnologies that rely on personalized settings or that are based on precision/abductive research more than on clinical trials. CONCLUSION The fact that the cases outlined above rely on abductive style of reasoning implies that there may not be as strong a justification for coverage by insurance, as they are both experimental and individualized, when compared to the more traditional large clinical trials in which groups have the same or a standardized protocol (settings/doses). If a study is examining the efficacy of a treatment with a large cohort of patients or with different experimental groups/phases, insurance companies may conclude that the resulting symptom improvements are more likely to be coming from the devices themselves. A preference for inductive justification may take priority when ruling in favor of funding someone’s continued use of an implantable neurostimulator. There are further nuances to this discussion surrounding the classifications of these interventions as research versus clinical care that warrant future exploration, since such a distinction is more of a scale[xxxv] than binary and could have significant impacts on the “right-to-try” approach to experimental therapies in the United States.[xxxvi] Namely, given the inherent limitations of conducting large cohort trials for deep brain stimulation interventions on patients with neuropsychiatric disorders, surgically innovative frameworks that blend abductive and inductive methodologies, like with sham stimulation phases, have traditionally been used.[xxxvii] Similarly, for adaptive brain-computer interface systems, if there are no large clinical trials and instead only publications that demonstrate that something similar worked for someone else, then, in addition to the evidence that the first treatment/dose worked for the patient in question, the balance of reasoning would be valid and arguably justify insurance coverage. As precision approaches to neurotechnology become more common, frameworks for evaluating efficacy will be crucial both for insurance coverage and for clinical decision making. ACKNOWLEDGEMENT This article was originally written as an assignment for Dr. Francis Shen’s “Bioethics & AI” course at Harvard’s Center for Bioethics. I would like to thank Dr. Shen for his comments as well as my colleagues in the Lázaro-Muñoz Lab for their feedback. - [i] Jonathan Kimmelman and Ian Tannock, “The Paradox of Precision Medicine,” Nature Reviews. Clinical Oncology 15, no. 6 (June 2018): 341–42, https://doi.org/10.1038/s41571-018-0016-0. [ii] Henrik Vogt and Bjørn Hofmann, “How Precision Medicine Changes Medical Epistemology: A Formative Case from Norway,” Journal of Evaluation in Clinical Practice 28, no. 6 (December 2022): 1205–12, https://doi.org/10.1111/jep.13649. [iii] David Barrett and Ahtisham Younas, “Induction, Deduction and Abduction,” Evidence-Based Nursing 27, no. 1 (January 1, 2024): 6–7, https://doi.org/10.1136/ebnurs-2023-103873. [iv] Vogt and Hofmann, “How Precision Medicine Changes Medical Epistemology,” 1208. [v] Wireko Andrew Awuah et al., “Bridging Minds and Machines: The Recent Advances of Brain-Computer Interfaces in Neurological and Neurosurgical Applications,” World Neurosurgery, May 22, 2024, S1878-8750(24)00867-2, https://doi.org/10.1016/j.wneu.2024.05.104. [vi] Mark Riedl, “A Very Gentle Introduction to Large Language Models without the Hype,” Medium (blog), May 25, 2023, https://mark-riedl.medium.com/a-very-gentle-introduction-to-large-language-models-without-the-hype-5 f67941fa59e. [vii] David E. Burdette and Barbara E. Swartz, “Chapter 4 - Responsive Neurostimulation,” in Neurostimulation for Epilepsy, ed. Vikram R. Rao (Academic Press, 2023), 97–132, https://doi.org/10.1016/B978-0-323-91702-5.00002-5. [viii] Kimmelman and Tannock, 2018. [ix] Kimmelman and Tannock, 2018. [x] Simon Lohse, “Mapping Uncertainty in Precision Medicine: A Systematic Scoping Review,” Journal of Evaluation in Clinical Practice 29, no. 3 (April 2023): 554–64, https://doi.org/10.1111/jep.13789. [xi] Kimmelman and Tannock, “The Paradox of Precision Medicine.” [xii] Vogt and Hofmann, 1206. [xiii] Vogt and Hofmann, 1206. [xiv] Vogt and Hofmann, 1206. [xv] Vogt and Hofmann, 1207. [xvi] Vogt and Hofmann, 1207. [xvii] Vogt and Hofmann, 1207. [xviii] Vogt and Hofmann, 1210. [xix] Mehar Sahu et al., “Chapter Three - Artificial Intelligence and Machine Learning in Precision Medicine: A Paradigm Shift in Big Data Analysis,” in Progress in Molecular Biology and Translational Science, ed. David B. Teplow, vol. 190, 1 vols., Precision Medicine (Academic Press, 2022), 57–100, https://doi.org/10.1016/bs.pmbts.2022.03.002. [xx] Stefan Feuerriegel et al., “Causal Machine Learning for Predicting Treatment Outcomes,” Nature Medicine 30, no. 4 (April 2024): 958–68, https://doi.org/10.1038/s41591-024-02902-1. [xxi] Sunderland Baker et al., “Ethical Considerations in Closed Loop Deep Brain Stimulation,” Deep Brain Stimulation 3 (October 1, 2023): 8–15, https://doi.org/10.1016/j.jdbs.2023.11.001. [xxii] David Haslacher et al., “AI for Brain-Computer Interfaces,” 2024, 7, https://doi.org/10.1016/bs.dnb.2024.02.003. [xxiii] Burdette and Swartz, “Chapter 4 - Responsive Neurostimulation,” 103–4; “Premarket Approval (PMA),” https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P100026. [xxiv] Burdette and Swartz, “Chapter 4 - Responsive Neurostimulation,” 104. [xxv] Burdette and Swartz, 126. [xxvi] Sean L. Metzger et al., “A High-Performance Neuroprosthesis for Speech Decoding and Avatar Control,” Nature 620, no. 7976 (August 2023): 1037–46, https://doi.org/10.1038/s41586-023-06443-4. [xxvii] Hao Fang and Yuxiao Yang, “Predictive Neuromodulation of Cingulo-Frontal Neural Dynamics in Major Depressive Disorder Using a Brain-Computer Interface System: A Simulation Study,” Frontiers in Computational Neuroscience 17 (March 6, 2023), https://doi.org/10.3389/fncom.2023.1119685; Mahsa Malekmohammadi et al., “Kinematic Adaptive Deep Brain Stimulation for Resting Tremor in Parkinson’s Disease,” Movement Disorders 31, no. 3 (2016): 426–28, https://doi.org/10.1002/mds.26482. [xxviii] Young-Hoon Nho et al., “Responsive Deep Brain Stimulation Guided by Ventral Striatal Electrophysiology of Obsession Durably Ameliorates Compulsion,” Neuron 0, no. 0 (October 20, 2023), https://doi.org/10.1016/j.neuron.2023.09.034. [xxix] Nho et al. [xxx] Nho et al.; Erik Robinson, “Brain Implant at OHSU Successfully Controls Both Seizures and OCD,” OHSU News, accessed March 3, 2024, https://news.ohsu.edu/2023/10/25/brain-implant-at-ohsu-successfully-controls-both-seizures-and-ocd. [xxxi] Awuah et al., “Bridging Minds and Machines”; Haslacher et al., “AI for Brain-Computer Interfaces.” [xxxii] Awuah et al., “Bridging Minds and Machines.” [xxxiii] Sara Green, Barbara Prainsack, and Maya Sabatello, “The Roots of (in)Equity in Precision Medicine: Gaps in the Discourse,” Personalized Medicine 21, no. 1 (January 2024): 5–9, https://doi.org/10.2217/pme-2023-0097. [xxxiv] Green, Prainsack, and Sabatello, 7. [xxxv] Robyn Bluhm and Kirstin Borgerson, “An Epistemic Argument for Research-Practice Integration in Medicine,” The Journal of Medicine and Philosophy: A Forum for Bioethics and Philosophy of Medicine 43, no. 4 (July 9, 2018): 469–84, https://doi.org/10.1093/jmp/jhy009. [xxxvi] Vijay Mahant, “‘Right-to-Try’ Experimental Drugs: An Overview,” Journal of Translational Medicine 18 (June 23, 2020): 253, https://doi.org/10.1186/s12967-020-02427-4. [xxxvii] Michael S. Okun et al., “Deep Brain Stimulation in the Internal Capsule and Nucleus Accumbens Region: Responses Observed during Active and Sham Programming,” Journal of Neurology, Neurosurgery & Psychiatry 78, no. 3 (March 1, 2007): 310–14, https://doi.org/10.1136/jnnp.2006.095315. (shrink)

_The_ _Routledge Companion to Philosophy of Medicine _is a comprehensive guide to topics in the fields of epistemology and metaphysics of medicine. It examines traditional topics such as the concept of disease, causality in medicine, the epistemology of the randomized controlled trial, the biopsychosocial model, explanation, clinical judgment and phenomenology of medicine and emerging topics, such as philosophy of epidemiology, measuring harms, the concept of disability, nursing perspectives, race and gender, the metaphysics of Chinese medicine, and narrative medicine. (...) Each of the 48 chapters is written especially for this volume and with a student audience in mind. For pedagogy and clarity, each chapter contains an extended example illustrating the ideas discussed. This text is intended for use as a reference for students in courses in philosophy of medicine and philosophy of science, and pairs well with _The_ _Routledge Companion to Bioethics_ for use in medical humanities and social science courses. (shrink)

Various publications claim that medical AI systems perform as well, or better, than clinical experts. However, there have been very few controlled trials and the quality of existing studies has been called into question. There is growing concern that existing studies overestimate the clinical benefits of AI systems. This has led to calls for more, and higher-quality, randomized controlled trials of medical AI systems. While this a welcome development, AI RCTs raise novel methodological challenges that (...) have seen little discussion. We discuss some of the challenges arising in the context of AI RCTs and make some suggestions for how to meet them. (shrink)

Robert Truog describes the controversial randomized controlled trials (RCTs) of extracorporeal membrane oxygenation (ECMO) therapy in newborns. Because early results with ECMO indicated that it might be a great advance, saving many lives, Truog argues that ECMO should not have been tested using RCTs, but that a long-term, large-scale observational study of actual clinical practice should have been conducted instead. Central to Truog’s argument, however, is the idea that ECMO is an unusual case. Thus, it is an (...) open question whether Truog’s conclusions can be extended to other areas of medical research. In this paper, I look at epistemological and ethical issues arising in the care of patients with chronic diseases, using ECMO as a starting point. Both the similarities and the dissimilarities of these two cases highlight important issues in biomedical research and support a conclusion similar to Truog’s. Observational studies of clinical practice provide the best evidence to inform the treatment of patients with chronic disease. (shrink)

Objective: Ethical guidelines are designed to ensure benefits, protection and respect of participants in clinical research. Clinical trials must now be registered on open-access databases and provide details on ethical considerations. This systematic survey aimed to determine the extent to which recently registered clinical trials report the use of standard of care and post-trial obligations in trial registries, and whether trial characteristics vary according to setting. Methods: We selected global randomized trials registered on http://www.clinicaltrials.gov and http://www. (...) class='Hi'>controlled-trials.com. We searched for intervention trials of HIV/AIDS, malaria, and tuberculosis from 9 October 2004, the date of the most recent version of the Helsinki Declaration, to 10 April 2007. Results: We collected data from 312 trials. Fifty-eight percent (58%, 95% CI = 53 to 64) of trial protocols report informed consent. Fifty-eight percent (58%, 95% CI = 53 to 64) of trials report active controls. Almost no trials (1%, 95% CI = 0.5 to 3) mention post-trial provisions. Most trials measure surrogate outcomes. Twenty percent (20%, 95% CI = 16 to 25) of trials measure patient-important outcomes, such as death; and the odds that these outcomes are in a low income country are five times greater than for a developed country (odds ratio (OR) 5.03, 95% CI = 2.70 to 9.35, p = < 0.001). Pharmaceutical companies are involved in 28% (CI = 23 to 33) of trials and measure surrogate outcomes more often than nonpharmaceutical companies (OR 2.45, 95% CI = 1.18 to 5.09, p = 0.31). Conclusion: We found a large discrepancy in the quality of reporting and approaches used in trials in developing settings compared to wealthier settings. (shrink)

Background Informed consent is a universally accepted precondition for scientific researches involving human participants. However, various factors influence the process of obtaining authentic informed consent, and researchers particularly working in resource-poor countries often face considerable difficulties in implementing the universally recommended procedures for obtaining informed consent. We have conducted this Rapid Ethical Assessment to accommodate the local cultural norms and to understand the relevant ethical issues in the Silti community before the conduct of a cluster-randomized controlled trial. Methods (...) This REA was conducted in two purposively selected Woredas/Districts and Worabe Town administration of Silti Zone. Data were collected using in-depth interviews and focus group discussions. Purposive and convenient sampling techniques were used to select respondents. Five in-depth interviews and 15 Focus Group Discussions were conducted in the Amharic language. The collected data was transcribed, translated, and analyzed using a thematic approach. Result Most of the community members never heard about research and therapeutic misconception was common. In the area, the permission of people working in the formal and informal community administration is essential before approaching individuals. The male head of the household should also be involved in the decision before individual household members participate in research. Furthermore, sensitizing the community using public and religious gatherings was suggested before individual recruitment. In the consent process, delivering selected information particularly the purpose and benefits of the research was emphasized and the tendency of preferring verbal consent was documented despite the willingness of the individuals to sign on the consent form. Local health workers were identified as appropriate personnel to communicate information and the procedures of the research were found to be acceptable. However, the value of small incentives was suggested to motivate potential participants. Finally, involving all concerned stakeholders and respecting the cultural norm of the community was emphasized. Conclusion Through REA, we understand the research awareness of the community, their expectation, and the cultural norms relevant to the ethical conduct of research. It enabled us to devise culturally sensitive and scientifically sound strategies to secure authentic informed consent. The process of conducting REA was found to be feasible, quick, and efficient. (shrink)

The random]ized clinical trial is widely accepted as the optimal approach to evaluating the safety and efficacy of medical treatments. Resistance to randomized treatment assignment arises regularly, most commonly in situations where the disease is life-threatening and treatments are either unavailable or unsatisfactory. Historical control designs, in which all participants receive the experimental treatment with results compared to a prior cohort, are advocated by some as more ethical in such circumstances; however, such studies are often highly biased in favor (...) of the new treatment and frequently yield misleading results. Alternative controlled designs motivated by the desire to maximize the number of patients with the treatment ultimately determined to be superior have been proposed, but have been challenged on both methodological and ethical grounds. Debates about appropriate and ethical study designs recurred during the recent Ebola Virus Disease epidemic in West Africa. Despite its devastating nature, the EVD epidemic showed the ongoing necessity of conducting randomized trials to obtain convincing evidence of the safety and efficacy of therapeutic interventions. (shrink)

The complexity of biobank research raises concerns about individuals’ understanding of the information conveyed in the consent process for such research.. We report the results of a qualitative, cognitive interview study with an ethnically, linguistically, and educationally diverse sample of 43 respondents to assess the clarity and utility of a multimedia tool developed for a biobank. Using weighted randomization, respondents were assigned to either view the multimedia tool or read a written consent document . The study illustrates the utility of (...) cognitive interviews for gaining insights from prospective research participants about the clarity of informed consent tools. Findings suggest that a multimedia tool is useful for communicating key messages but should be combined with a written consent document and personal interaction with the study staff. We recommend that the potential value of multimedia tools should be more rigorously tested in a randomized controlled trial. (shrink)

ABSTRACT“Evidence-based” methods, which most prominently include randomized controlled trials, have gained increasing purchase as the “gold standard” for assessing the effect of public policies. But the enthusiasm for evidence-based research overlooks questions about the reliability and applicability of experimental findings to diverse real-world settings. Perhaps surprisingly, a qualitative study of British educators suggests that they are aware of these limitations and therefore take evidence-based findings with a much larger grain of salt than do policy makers. Their experience (...) suggests that the real world is more heterogeneous than the world imagined by evidence-based policy enthusiasts. (shrink)

Randomized controlled trials (RCTs) are a major success story, promising to improve science and policy. Despite some controversy, RCTs have spread toward Northern and Southern countries since the early 2000s. How so? Synthesizing previous research on this question, this article argues that favorable institutional conditions turned RCTs into “hinges” between the fields of science, politics, and business. Shifts toward behavioral economics, New Public Management, and evidence-based philanthropic giving led to a cross-fertilization among efforts in rich and poor (...) countries, involving states, international organizations, NGOs, researchers, and philanthropic foundations. This confluence of favorable institutional conditions and savvy social actors established a “global interstitial field” inside which support for RCTs has developed an unprecedented scope, influence, operational capacity, and professional payoff. However, the article further argues that the hinges holding together this global interstitial field are “squeaky” at best. Because actors inherit the illusio of their respective fields of origin—their central incentives and stakes—the interstitial field produces constant goal conflicts. Cooperation between academics and practitioners turns out to be plagued by tensions and contradictions. Based on this analysis, the article concludes that the global field of RCT support will probably differentiate into its constituent parts. As a result, RCTs may lose the special status they have gained among social science and policy evaluation methods, turning into one good technique among others. (shrink)

Research over the past few decades has shown the positive influence that cognitive, social, and physical activities have on older adults’ cognitive and affective health. Especially interventions in health-related behaviors, such as cognitive activation, physical activity, social activity, nutrition, mindfulness, and creativity, have shown to be particularly beneficial. Whereas most intervention studies apply unimodal interventions, such as cognitive training, this study investigates the potential to foster cognitive and affective health factors of older adults by means of an autonomy-supportive multimodal intervention. (...) The intervention integrates everyday life recommendations for six evidence-based areas combined with psychoeducational information. This randomized controlled trial study compares the effects of a MMI and CT on those of a waiting control group on cognitive and affective factors, everyday life memory performance, and activity in everyday life. Three groups, including a total of 119 adults aged 65–86 years, attended a 5- or 10-week intervention. Specifically, one group completed a 10-week MMI, the second group completed 5-week of computer-based CT followed by a 5-week MMI, whereas the third group paused before completing the MMI for the last 5 weeks. All participants completed online surveys and cognitive tests at three test points. The findings showed an increase in the number and variability of activities in the everyday lives of all participants. Post hoc analysis on cognitive performance of MMI to CT indicate similar or better effects. Furthermore, results on far transfer variables showed interesting trends in favor of the MMI, such as increased well-being and attitude toward the aging brain. Also, the MMI group showed the biggest perceived improvements out of all groups for all self-reported personal variables. The results implicate a positive trend toward MMI on cognitive and affective factors of older adults. These tendencies show the potential of a multimodal approach compared to training a specific cognitive function. Moreover, the findings suggest that information about MMI motivates participants to increase activity variability and frequency in everyday life. Finally, the results could also have implications for the primary prevention of neurocognitive deficits and degenerative diseases. (shrink)

This article brings a historical perspective to explain the recent dissemination of randomized controlled trials (RCTs) as the new “gold standard” method to assess international development projects. Although the buzz around RCT evaluations dates from the 2000s, we show that what we are witnessing now is a second wave of RCTs, while a first wave began in the 1960s and ended by the early 1980s. Drawing on content analysis of 123 RCTs, participant observation, and secondary sources, we (...) compare the two waves in terms of the participants in the network of expertise required to carry out field experiments and the characteristics of the projects evaluated. The comparison demonstrates that researchers in the second wave were better positioned to navigate the political difficulties caused by randomization. We explain the differences in the expertise network and in the type of projects as the result of concurrent transformations in the fields of development aid and the economics profession. We draw on Andrew Abbott’s concept of “hinges,” as well as on Bourdieu’s concept of “homology” between fields, to argue that the similar positions and parallel struggles conducted by two groups of actors in the two fields served as the basis for a cross-field alliance, in which RCTs could function as a “hinge” linking together the two fields. (shrink)

The Flash Technique of Eye Movement Desensitization and Reprocessing is widely recognized for its effectiveness in reducing the effects of emotional responses associated with traumatic memories. Using a randomized-controlled trial methodology, this study attempts to establish the efficacy of the EMDR Flash Technique. This study’s sample includes volunteers who were involved in traffic accidents and were given the randomized EMDR Flash Technique and Improving Mental Health Training for Primary Care Residents Stress management module. The participants were given (...) a socio-demographic data form, the Depression-Anxiety-Stress 21 scale, the Impact of Event Scale-Revised, and the WHOQOL Quality of Life scale. Participants were evaluated using measurements taken before and after the application, as well as a one-month follow-up. The mean age of the participants was 36.20 years and 82.1% were female. The DASS-21 Anxiety, IES-R Intrusion, Avoidance, Total, and WHOQOL-BREF Psychological score improvements of the EMDR Flash Technique group were shown to be statistically significant when compared to the mhGAP group. However, no statistically significant difference in the DASS-21 Depression, Stress, Impact of Event Scale-Revised Hyperarousal WHOQOL-BREF General Health, Physical, Social Relationships, and Environment component scores was reported between the two groups. The present study’s findings clearly demonstrate that the EMDR Flash technique, when applied to persons involved in traffic accidents, is successful in improving anxiety, intrusion, avoidance, total traumatic stress, and mental quality of life symptoms for at least 1 month. We believe that these findings will improve the reliability and applicability of the EMDR Flash Technique, which was tested for the first time in a clinical randomized-controlled trial. (shrink)

Pragmatic comparative effectiveness randomized controlled trials evaluate the effectiveness of one interventions under real-world clinical conditions. The results of ceRCTs are often directly generalizable to everyday clinical practice, providing information critical to decision-making by patients, clinicians, and healthcare policymakers. The PRECIS-2 framework identifies nine domains that serve to score a trial on a continuum between very explanatory to very pragmatic. According to the framework, pragmatic trials may have one or more of the following features: there are (...) fewer eligibility criteria for participants, in an... (shrink)

In 2003 and 2018 researchers discussed the perils of blind reliance on randomized controlled trials that have been substituted for medical experience and clinical acumen. Although these past articles do well to shed light on this issue, they neglect to discuss the topic of all-cause mortality in controlled trials. The current essay seeks to fill this void and expand the thought put into the appropriateness of all-cause mortality, especially when trials extend excessively far (...) into the future. To do this effectively the current essay leans on trial data from statin research and evidence from cancer screening—where researchers have explicitly called for all-cause mortality to be used in lieu of cancer or cardiovascular specific mortality. The issue with such an endpoint is that it obfuscates the issue at hand, namely that a specific intervention is intended to have a specific effect, not that a specific intervention is supposed to have any kind of effect. The effect(s) of medical interventions ought to be relevant to their intended mechanism of action and not simply any positive effect that can be pulled from trial data. (shrink)

Governments are increasingly using randomized controlled trials (RCTs) to evaluate policy interventions. RCTs are often understood to provide the highest quality evidence regarding the causal efficacy of an intervention. While randomization plays an essential epistemic role in the context of policy RCTs however, it also plays an important distributive role. By randomly assigning participants to either the intervention or control arm of an RCT, people are subject to different policies and so, often, to different types and levels (...) of benefits. In this paper, I identify one necessary condition as well as a set of sufficient conditions for the permissible use of random assignment by government agencies. I argue first that random assignment is permissible only if it is consistent with governments’ duty to realize morally important outcomes. I argue second that random assignment is permissible in cases where investigators are in a state of genuine equipoise regarding all arms of the experiment and the policy to which people have a claim of justice. Finally, I defend a set of conditions under which random assignment is permissible in cases where one or more arms of a policy RCT are reasonably expected to be either superior or inferior to this policy. (shrink)

Background Randomized controlled trials are central to generating knowledge about effectiveness of interventions as well as risk, protective and prognostic factors related to diseases in emergency newborn care. Whether prospective participants understand the purpose of research, and what they perceive as the influence of the context on their understanding of the informed consent process for RCTs in emergency obstetric and newborn care are not well documented. Methods Conceptual review. Discussion Research is necessary to identify how the illnesses (...) may be prevented, to explore the causes, and to investigate what medications could be used to manage such illness. Voluntary informed consent requires that prospective participants understand the disclose information about the research, and use this to make autonomous informed decision about participation, in line with their preferences and values. Yet the emergency context affects how information may be disclosed to prospective research participants, how much participants may comprehend, and how participants may express their voluntary decision to participate, all of which pose a threat to the validity of the informed consent. I challenge the claim that the ‘understanding’ of research is always necessary for ethical informed consent for research during emergency care. I argue for reconceptualization of the value of understanding, through recognition of other values that may be equally important. I then present a reflective perspective that frames moral reflection about autonomy, beneficence and justice in research in emergency research. Conclusion While participant ‘understanding’ of research is important, it is neither necessary nor sufficient for a valid informed consent, and may compete with other values with which it needs to be considered. (shrink)

Biomedical research and study design have recently been examined in detail by philosophers of science, who, like biomedical researchers, are concerned with the ability to accurately represent causal relationships through scientific study and apply these relationships to improve the health of individuals and populations. Epistemology—defined by the OED as "the theory of knowledge, especially with regard to its methods, validity, and scope, and the distinction between justified belief and opinion"—is fundamental to these concerns. In particular, philosophers of science and biomedical (...) researchers have discussed the epistemological value of randomized-controlled trials in regards to their individual components.... (shrink)