I. EXECUTIVE SUMMARY The MRCT Center Post-trial Responsibilities: Continued Access to an Investigational Medicine Framework outlines a case-based, principled, stakeholder approach to evaluate and guide ethical responsibilities to provide continued access to an investigational medicine at the conclusion of a patient’s participation in a clinical trial. The Post-trial Responsibilities (PTR) Framework includes this Guidance Document as well as the accompanying Toolkit. A 41-member international multi-stakeholder Workgroup convened by the Multi-Regional Clinical Trials Center of Brigham and (...) Women’s Hospital and Harvard University (MRCT Center) developed this Guidance and Toolkit. Project Motivation A number of international organizations have discussed the responsibilities stakeholders have to provide continued access to investigational medicines. The World Medical Association, for example, addressed post-trial access to medicines in Paragraph 34 of the Declaration of Helsinki (WMA, 2013): “In advance of a clinical trial, sponsors, researchers and host country governments should make provisions for post-trial access for all participants who still need an intervention identified as beneficial in the trial. This information must also be disclosed to participants during the informed consent process.” This paragraph and other international guidance documents converge on several consensus points: • Post-trial access (hereafter referred to as “continued access” in this Framework [for terminology clarification – see definitions]) is the responsibility of sponsors, researchers, and host country governments; • The plan for continued access should be determined before the trial begins, and before any individual gives their informed consent; • The protocol should delineate continued access plans; and • The plan should be transparent to potential participants and explained during the informed consent process. -/- However, there is no guidance on how to fulfill these responsibilities (i.e., linking specific responsibilities with specific stakeholders, conditions, and duration). To fill this gap, the MRCT Center convened a working group in September of 2014 to develop a framework to guide stakeholders with identified responsibilities. This resultant Framework sets forth applicable principles, approaches, recommendations and ethical rationales for PTR regarding continued access to investigational medicines for research participants. (shrink)

We argue that in implanted neurotechnology research, participants and researchers experience what Henry Richardson has called “moral entanglement.” Participants partially entrust researchers with access to their brains and thus to information that would otherwise be private, leading to created intimacies and special obligations of beneficence for researchers and research funding agencies. One of these obligations, we argue, is about continued access to beneficial technology once a trial ends. We make the case for moral entanglement in this context through exploration (...) of participants’ vulnerability, uncompensated risks and burdens, depth of relationship with the research team, and dependence on researchers in implanted neurotechnology trials. (shrink)

The need for continuing provision of beneficial experimental interventions after research is concluded remains a controversial topic in bioethics for research. Based on the principle of beneficence, justice as reciprocity, concerns about exploitation and fair benefits, participants should be able to have continuing access to benefits beyond the research period. However, there is no consensus about whether or not post-trial provision of beneficial interventions should be mandatory for participants from developing countries. This paper summarises recommendations from international and (...) national guidelines. Ethical principles and practical issues relating to post-trial provision are also discussed. In conclusion, post-trial provision is not necessary in all situations and a set of criteria are proposed to identify the situations that beneficial interventions should be provided beyond the research period. However, mandatory post-trial supply of beneficial experimental interventions should be assured for those who still need and are able to benefit from them but have no alternative access. Mandatory provision is based on universal bioethical principles such as beneficence and justice. Furthermore, difficulties associated with implementation of post-trial provision are not unmanageable. Careful advanced planning and a comprehensive partnership among relevant parties would be very helpful in solving these difficulties in practice, which therefore should not be taken as an excuse to escape post-trial responsibility. (shrink)

The general aim of this article is to give a critical interpretation of post-trial obligations towards individual research participants in the Declaration of Helsinki 2013. Transitioning research participants to the appropriate health care when a research study ends is a global problem. The publication of a new version of the Declaration of Helsinki is a great opportunity to discuss it. In my view, the Declaration of Helsinki 2013 identifies at least two clearly different types of post-trial (...) obligations, specifically, access to care after research and access to information after research. The agents entitled to receive post-trial access are the individual participants in research studies. The Declaration identifies the sponsors, researchers and host country governments as the main agents responsible for complying with the post-trial obligations mentioned above. To justify this interpretation of post-trial obligations, I first introduce a classification of post-trial obligations and illustrate its application with examples from post-trial ethics literature. I then make a brief reconstruction of the formulations of post-trial obligations of the Declaration of Helsinki from 2000 to 2008 to correlate the changes with some of the most salient ethical arguments. Finally I advance a critical interpretation of the latest formulation of post-trial obligations. I defend the view that paragraph 34 of ‘Post-trial provisions’ is an improved formulation by comparison with earlier versions, especially for identifying responsible agents and abandoning ambiguous ‘fair benefit’ language. However, I criticize the disappearance of ‘access to other appropriate care’ present in the Declaration since 2004 and the narrow scope given to obligations of access to information after research. (shrink)

There is a growing recognition that the ongoing use of investigational neural implants requires continued access to clinical expertise and specialized healthcare (e.g., Hendriks et al., 2019). Howe...

Objectives To analyse the perspective of clinical research stakeholders concerning post-trial access to study medication. Methods Questionnaires and informed consents were sent through e-mail to 599 ethics committee (EC) members, 290 clinical investigators (HIV/AIDS and Diabetes) and 53 sponsors in Brazil. Investigators were also asked to submit the questionnaire to their research patients. Two reminders were sent to participants. Results The response rate was 21%, 20% and 45% in EC, investigators and sponsors’ groups, respectively. 54 patients answered the (...) questionnaire through their doctors. The least informative item in the consent form was how to obtain the study medication after trial. If a benefit were demonstrated in the study, 60% of research participants and 35% of EC answered that all patients should continue receiving study medication after trial; 43% of investigators believed the medication should be given to participants, and 40% to subjects who participated and benefited from treatment. For 50% of the sponsors, study medication should be assured to participants who had benefited from treatment. The majority of responders answered that medication should be provided free by sponsors; investigators and sponsors believed the medication should be kept until available in the public health sector; EC members said that the patient should keep the benefit; patients answered that benefits should be assured for life. Conclusions Due to the study limitations, the results cannot be generalised; however, the data can contribute to discussion of this complex topic through analysing the views of stakeholders in clinical research in Brazil. (shrink)

Purpose We examine the levels of post-trial responsibility ascribed to different stakeholders, following a community-based clinical trial and how the ‘responsibility’ is understood. Methods We employed photovoice, unstructured observations and key informant interviews to gain insights into contexts of access to care following transition to the public health system post trial. We used an inductive narrative analysis to explore experiences and understandings of post-trial access. Results In their photovoice stories, many participants (...) expressed a sense of abandonment after the trial. This was viewed as a contributing factor to failing to re-engage with care available in the public health system. This led to the experiences of loss as some trial participants defaulted and died. Research investigators, department of health participants and sponsor agreed that PTA was especially important for communities in resource-limited settings. The government has an obligation towards its citizens while researchers have a responsibility to ensure a smooth transition of patients to public clinics. Sponsors have a responsibility to ensure that the trial is conducted in accordance with the protocol and post-trial agreements are in place and adhered to. Research partnerships among stakeholders were affected by power imbalances making it difficult to negotiate and plan for post-trial care responsibilities. Conclusions The research community still struggles with understanding the scope of PTA responsibilities. Power dynamics between public health actors and research sponsors need to be managed to ensure that government involvement is not tokenistic. The responsibility of trial participants and ethics committees needs to be investigated further. Data are available upon request. (shrink)

This paper discusses so-called post-trial access to drugs for patients who participated in clinical trials in Brazil. Brazil is currently a relevant country for the pharmaceutical industry due to the dimensions of its actual and potential market. As a consequence, the number of pharmaceutical trials has been rising. It is the largest market for pharmaceutical companies in Latin America, the 8th biggest in the world and second only to China among the so-called BRICS’s emerging countries. The demand for (...) pharmaceutical products in the country has been increasing by double digits over the last few years, reaching 20% in 2008. Not surprisingly, we are also witnessing a steady increase in the number of applications by national and international pharmaceutical companies before ethical research authorities for authorization to perform clinical trials of drugs. (shrink)

This book begins the discourse on post-trial access to drugs in developing countries. Underlying ethical issues in global health inequalities and global health research serve as the context of the debate. Due to rampant allegations of violations of rights of research participants, especially in developing countries, it discusses the regulatory infrastructure and ethical oversight of international clinical research, thus emphasizing the priority of safeguarding the rights of research participants and host populations as desiderata in conducting clinical trials in (...) developing countries. This is the first book that analyzes the major obstacles of affordable access to drugs in developing countries - patent and non-patent factors and how they can be overcome through a middle ground approach and a new paradigm to establish global health justice which includes national and global health responsibilities. The book also deals extensively with all complex aspects of the discourse on affordable access to drugs in developing countries, including intellectual property law, international regulations, political and cultural systems, international trade agreements. Furthermore it contains a robust ethical debate and in-depth analysis. The book crafts a paradigm of global health justice involving a sliding scale of national and global responsibilities for the realization of the right to health in general and access to drugs in particular. (shrink)

The principle of providing post-trial access for research participants to successful products of that research is widely accepted and has been enshrined in various declarations and guidelines. While recent ethical guidelines recognise that the responsibility to provide post-trial access extends to sponsors, regulators and government bodies as well as to researchers, it is the researchers who have the direct duty of care to participants. Researchers may thus need to act as advocates for trial participants, (...) especially where government bodies, sponsors, and regulatory bodies have complex interests vested in decisions about whether or not new interventions are made available, how, and to whom. This paper provides an empirical account of post-trial access in the context of HIV prevention research. It describes both access to the successful products of research and the provision antiretroviral drugs for trial participants who acquire HIV. First, we provide evidence that, in the current system, there is considerable variation in the duration and timeliness of access. We then argue that by analysing the difficulties faced by researchers to this point, and their efforts to meet this obligation, much can be learned about how to secure post-trial access in HIV biomedical preventions trials. While researchers alone have a limited obligation, their advocacy on behalf of trial participants may be necessary to call the other parties to account. (shrink)

Background In the EU, clinical assessors, rapporteurs and the Committee for Medicinal Products for Human Use are obliged to assess the ethical aspects of a clinical development program and include major ethical flaws in the marketing authorization deliberation processes. To this date, we know very little about the manner that these regulators put this obligation into action. In this paper, we intend to look into the manner and the extent that ethical issues discovered during inspection have reached the deliberation processes. (...) Methods To gather data, we used the Dutch Medicines Evaluation Board database and first searched for the inspections, and their accompanying site inspection reports and integrated inspection reports, related to central marketing authorization applications of drugs submitted to the European Medicines Agency from 2011 to 2015. We then extracted inspection findings that were purely of ethical nature, i.e., those that did not affect the benefit/risk balance of the study. Only findings graded at least major by the inspectorate were included. Lastly, to identify how many of the ethically relevant findings reach the application deliberation processes, we extracted the relevant joint response assessment reports and reviewed the sections that discussed inspection findings. Results From 2011 to 2015, there were 390 processed applications, of which 65 had inspection reports and integrated inspection reports accessible via the database of the Dutch Medicines Evaluation Board. Of the 65, we found ERFs in 37. The majority of the ERFs were graded as major and half of the time it was informed-consent related. A third of these findings were related to research ethics committee processes and requirements. Of the 37 inspections with ERFs, 30 were endorsed in the integrated inspection reports as generally GCP compliant. Day 150 joint response assessment reports and Day 180 list of outstanding issues were reviewed for all 37 inspections, and none of the ERFs were carried over in any of the assessment reports or list of outstanding issues. Conclusion None of the ethically relevant findings, all of which were graded as major or critical in integrated inspection reports, were explicitly carried over to the joint assessment reports. This calls for more transparency in EMA application deliberations on how ERFs are considered, if at all, in the decision-making processes. (shrink)

While the HVTN 505 trial showed no overall efficacy of the tested vaccine to prevent HIV infection over placebo, markers measuring immune response to vaccination were strongly correlated with infection. This finding generated the hypothesis that some marker-defined vaccinated subgroups were partially protected whereas others had their risk increased. This hypothesis can be assessed using the principal stratification framework (Frangakis and Rubin, 2002) for studying treatment effect modification by an intermediate response variable, using methods in the sub-field of principal (...) surrogate (PS) analysis that studies multiple principal strata. Unfortunately, available methods for PS analysis require an augmented study design not available in HVTN 505, and make untestable structural risk assumptions, motivating a need for more robust PS methods. Fortunately, another sub-field of principal stratification, survivor average causal effect (SACE) analysis (Rubin, 2006) – which studies effects in a single principal stratum – provides many methods not requiring an augmented design and making fewer assumptions. We show how, for a binary intermediate response variable, methods developed for SACE analysis can be adapted to PS analysis, providing new and more robust PS methods. Application to HVTN 505 supports that the vaccine partially protected individuals with vaccine-induced T-cells expressing certain combinations of functions. (shrink)

This is the second paper in a two-part series describing subject and family perspectives from the CENTURY-S (CENtral Thalamic Deep Brain Stimulation for the Treatment of Traumatic Brain InjURY-Safety) first-in-human invasive neurological device trial to achieve cognitive restoration in moderate to severe traumatic brain injury (msTBI). To participate, subjects were independently assessed to formally establish decision-making capacity to provide voluntary informed consent. Here, we report on post-operative interviews conducted after a successful trial of thalamic stimulation. All five (...) msTBI subjects met a pre-selected primary endpoint of at least a 10% improvement in completion time on Trail-Making-Test Part B, a marker of executive function. We describe narrative responses of subjects and family members, refracted against that success. Interviews following surgery and the stimulation trial revealed the challenge of adaptation to improvements in cognitive function and emotional regulation as well as altered (and restored) relationships and family dynamics. These improvements exposed barriers to social reintegration made relevant by recoveries once thought inconceivable. The study’s success sparked concerns about post-trial access to implanted devices, financing of device maintenance, battery replacement, and on-going care. Most subjects and families identified the need for supportive counseling to adapt to the new trajectory of their lives. (shrink)

ObjectiveCo-morbid insomnia and sleep apnea is a common and debilitating condition that is more difficult to treat compared to insomnia or sleep apnea-alone. Emerging evidence suggests that cognitive behavioral therapy for insomnia is effective in patients with COMISA, however, those with more severe sleep apnea and evidence of greater objective sleep disturbance may be less responsive to CBTi. Polysomnographic sleep study data has been used to predict treatment response to CBTi in patients with insomnia-alone, but not in patients with COMISA. (...) We used randomized controlled trial data to investigate polysomnographic predictors of insomnia improvement following CBTi, versus control in participants with COMISA.MethodsOne hundred and forty five participants with insomnia and sleep apnea [apnea-hypopnea index ≥ 15] were randomized to CBTi or no-treatment control. Mixed models were used to investigate the effect of pre-treatment AHI, sleep duration, and other traditional, and novel [quantitative electroencephalography ] polysomnographic predictors of between-group changes in Insomnia Severity Index scores from pre-treatment to post-treatment.ResultsCompared to control, CBTi was associated with greater ISI improvement among participants with; higher AHI, less wake after sleep onset, and less N3 sleep. No quantitative electroencephalographic, or other traditional polysomnographic variables predicted between-group ISI change.DiscussionAmong participants with COMISA, higher OSA severity predicted a greater treatment-response to CBTi, versus control. People with COMISA should be treated with CBTi, which is effective even in the presence of severe OSA and objective sleep disturbance. (shrink)

What are the moral obligations of participants and bystanders during—and in the wake of –a conflict? How have theoretical understandings of justice, peace and responsibility changed in the face of contemporary realities of war? Drawing on the work of leading scholars in the fields of philosophy, political theory, international law, religious studies and peace studies, the collection significantly advances current literature on war, justice and post-conflict reconciliation. Contributors address some of the most pressing issues of international and civil (...) conflict, including the tension between attributing individual and collective responsibility for the wrongs of war, the trade-offs made between the search for truth and demands for justice, and the conceptual intricacies of coming to understand just what is meant by ‘peace’ and ‘conflict.’ Individual essays also address concrete topics including the international criminal court, reparations, truces, political apologies, truth commissions and criminal trials, with an eye to contemporary examples from conflicts in the Middle East, Africa and North and South America.​. (shrink)

There is a gap of knowledge about the extent to which gratitude is indeed the working mechanism of change in gratitude interventions aiming to promote mental well-being. This study explores the mediational role of gratitude as mood in the context of a recently conducted randomized controlled trial on the effects of a 6-week gratitude intervention on mental well-being in comparison with a waitlist control group. Gratitude as mood was measured at 2, 4, and 6 weeks. Both simple and multiple (...) mediation models were conducted as well as various sensitivity analyses. Results showed a gradual increase of gratitude as mood during the intervention. The effects of the 6-week gratitude intervention on mental well-being were mediated by increases of gratitude as mood at 4 weeks but not at 2 weeks. These findings suggest a dose-response relationship for gratitude interventions, but more research is warranted. (shrink)

In the transition from a repressive to a democratic society, the successor government faces the problem of how to deal with grave human rights violations such as killings and torture committed under its predecessor. This paper analyzes the dilemma a new government may encounter when it attempts to prosecute and punish those found responsible. On one hand, trials of chargeable officers may be able to prevent human rights abuses in the future and to facilitate instituting or restoring democracy. On the (...) other, in the case that there were no legal rules definitively prohibiting the abuses committed by these officers, the trials require ex post facto laws, which breach the principle of nulla poena sine lege, and more generally violate the rule of law. These retroactive laws not only break legal predictability but treat individuals unfairly. After identifying both the need for, and the legal and political losses incurred by such criminal trials, the author examines the claims that international law resolves the dilemma of retroactive justice or that prosecution is justified as a fulfillment of international obligation. Then the author refers to this dilemma as “dirty hands” to characterize a circumstance in which one cannot avoid using the wrong means to obtain the best ends. Such characterization has normative implications for three aspects of trials: the process of enacting retroactive laws and the process of conducting the trials; the choice of other possible legal remedies; and the principles related to reactions in the international community. (shrink)

As clinical trials end, little is understood about how participants exiting from clinical trials approach decisions related to the removal or post-trial use of investigational brain implants, such as deep brain stimulation (DBS) devices. This empirical bioethics study examines how research participants experience the process of exit from research at the end of clinical trials of implanted neural devices. Using a modified grounded theory study design, we conducted semi-structured, in-depth interviews with 16 former research participants from clinical trials (...) of DBS and responsive neurostimulation (RNS). Open-ended questions elicited motivations for joining the trial, understanding of study procedures at the time of initial informed consent, the process of exiting from research, and decisions about device removal or post-trial device use. Thematic analysis identified categories related to: limited preparedness for the end of research participation, straightforwardness of decisions to explant or keep the device, reconciling with the end of research participation, reconciling post-trial expectations, and achieving a sense of closure after exit from research. A preliminary theoretical model describes contextual factors influencing the process and experience of exit from research. Experiences of clinical trial participants should guide research practices to enhance the ethical design and conduct of clinical trials in DBS and other brain devices. (shrink)

We report the results of a randomized trial to assess the impact of an innovative ethics curriculum on the knowledge and confidence of 85 medical house officers in a university hospital programme, as well as their responses to a simulated clinical case. Twenty-five per cent of the house officers received a lecture series, 25 per cent received lectures and case conferences, with an ethicist in attendance, and 50 per cent served as controls. A post-intervention questionnaire was administered. Knowledge (...) scores did not differ among the groups. Confidence regarding ethical issues was significantly greater in the aggregate intervention group compared to the control group. Confidence regarding procedural issues related to ethics was significantly higher for the EI group than for the controls. Responses to a simulated case showed that significantly fewer house officers in the EI group would intubate a patient for whom such therapy would be futile. We conclude that ethics education can have an impact on house officers' confidence and their responses to a simulated case, and that the EI was more effective than the LI. Such results have implications regarding the implementation of ethics education during residency. (shrink)

Background To allow patients to reflect about a decision to participate in a clinical trial, guidelines suggest a 24-h delay from when they are informed about the trial to when they give consent. In certain clinical settings, this is likely to hamper recruitment. Method After oral and written information about the trial has been given in person, the patient signs the declaration of consent knowing that they will be asked again after 24 h whether they confirm or (...) regret the decision. This procedure can be done by SMS. The investigators must document the response. The procedure was tried in a study in which the doctors were randomly assigned to receive a clinical communication skills course, and encounters with patients were videotaped before and after the course. Results 553 patients were approached, 530 (95.8%) gave initial consent, eight of these later regretted their consent. Discussion The low level of regrets suggests this is an acceptable procedure for patients. Trial registration The RCT was registered before initiation – registration # ISRCTN22153332. (shrink)

To investigate the effects of two different modes of physical activity on body composition, physical fitness, cardiometabolic risk, and psychological responses in female adolescents participating in a multi-disciplinary program. The 12-week randomized intervention included 25-adolescents with overweight divided into two groups: sports practice-SPG and functional training-FTG. The SPG intervention was divided into three sports: basketball, handball, and futsal. SPG participants performed one sport 3-times/week, over the course of 1 month. The FTG performed concurrent exercises 3-times/week. This study was registered in (...) Clinical Trials Registry Platform under number: RBR-45ywtg and registered in Local Ethics Committee number: 2,505.200/2018. The intensity of physical exercises-PE was matched between groups by the rating of perceived exertion. The primary outcome was body composition, and secondary outcomes were physical fitness, cardiometabolic risk, and psychological responses. There was a significant time-effect for body mass, body mass index, and low-density lipoprotein, all being reduced. There were increases over time for musculoskeletal mass, aerobic fitness, and high-density lipoprotein. There was a group time interaction with body fat percentage being lower post-intervention in the SPG. No significant differences were observed for the other variables. Both physical activity models were effective in improving a subset of obesity-related health parameters. The findings should be extended by further investigation using more sophisticated measures of energy expenditure.Clinical Trial Registration:https://ensaiosclinicos.gov.br/, identifier: RBR-45ywtg. (shrink)

Objective: Inhibitory control training has shown promise for improving health behaviours, however, less is known about its mediators of effectiveness. The current paper reports whether ICT reduces smoking-related outcomes such as craving and nicotine dependence, increases motivation to quit and whether reductions in smoking or craving are mediated by response inhibition or a devaluation of smoking stimuli.Method: Adult smokers were randomly allocated to receive 14 days of smoking-specific ICT or active control training. Participants were followed up to 3-months post-intervention. (...) This trial was preregistered.Results: There were no significant differences between ICT and active control training groups. Specifically, participants in both groups showed significant reductions in craving, nicotine dependence, motivation and a devaluation of smoking-stimuli up to 3-months follow-up compared to baseline. Inhibition and devaluation of smoking stimuli did not act as mediators. Devaluation of smoking stimuli was an independent predictor of smoking and craving at follow-up.Conclusion: Inhibitory control training was no more effective at reducing smoking-related outcomes compared to the active control group, however, significant improvements in craving, dependence indicators and evaluation of smoking stimuli were observed across both groups. A return to basic experimental research may be required to understand the most effective ICT approach to support smoking cessation. (shrink)

In research involving patients with implantable brain–computer interfaces (BCIs), there is a regulatory gap concerning post-trial responsibilities and duties of sponsors and investigators towards implanted patients. In this article, we analyse the case of patient R, who underwent non-voluntary explantation of an implanted BCI, causing a discontinuation in her sense of agency and self. To clarify the post-trial duties and responsibilities involved in this case, we first define the ontological status of the BCI using both externalist (...) (EXT) and internalist (INT) theories of cognition. We then give particular focus to the theories of extended and embedded cognition, hence considering the BCI either as a constitutive component of the patient’s mind or as a causal supporter of her brain-based cognitive capacities. We argue that patient R can legitimately be considered both as an embedded and extended cognitive agent. Then, we analyse whether the non-voluntary explantation violated patient R’s (neuro)rights to cognitive liberty, mental integrity, psychological continuity and mental privacy. We analyse whether and how different mental ontologies may imply morally relevant differences in interpreting these prima facie neurorights violations and the correlational duties of sponsors and investigators. We conclude that both mental ontologies support the identification of emerging neurorights of the patient and give rise to post-trial obligations of sponsors and investigators to provide for continuous technical maintenance of implanted BCIs that play a significant role in patients’ agency and sense of self. However, we suggest that externalist mental ontologies better capture patient R’s self-conception and support the identification of a more granular form of mental harm and associated neurorights violation, thus eliciting stricter post-trial obligations. (shrink)

BackgroundIn many Western countries like Germany, the social integration of children with an immigrant background has become an urgent social tasks. The probability of them living in high-risk environments and being disadvantaged regarding health and education-related variables is still relatively higher. Yet, promoting language acquisition is not the only relevant factor for their social integration, but also the support of earlier developmental processes associated with adequate early parenting in their first months of life. The Emotional Availability Scales measure the quality (...) of caregiver-child-interactions as an indicator of the quality of their relationship and thus of such early parenting, focusing on mutual and emotional aspects of their interaction.MethodThis pilot study examined in a randomized controlled trial the effects of the prevention project First Steps regarding the hypothesis that the Emotional Availability improved to a greater extent in “difficult-to-reach” immigrant mother-child dyads in a psychoanalytically oriented early intervention compared to a usual care intervention offered by paraprofessionals with an immigrant background. A sample of N = 118 immigrant women in Germany from 37 different countries and their children was compared with regard to the parental EA-dimensions sensitivity, structuring, non-intrusiveness and non-hostility and the child dimensions responsiveness to and involvement of the caregiver in the pre-post RCT design.Results and ConclusionDifferent from what was expected, repeated ANOVAs revealed no significant pre-post group differences for the parental dimensions. For the child dimensions the effect of time of measurement was highly significant, which can be interpreted as mostly natural developmental effects. Still, on the level of simple main effects for each intervention, only in the FIRST STEPS groups child responsiveness significantly improved. When controlled for confounding variables, a significant interaction effect for maternal sensitivity in favor of the FIRST STEPS intervention was found. The systematic group differences indicate that the more extensive and professional intervention, focusing on the individual needs of the participants, is more suitable to support the quality of the mother-child-relationship amongst immigrant mother-child dyads than usual care. The results are discussed taking into account the context of the maternal migration process and potential maternal traumatization.Clinical Trial Registration[https://clinicaltrials.gov], identifier [DRKS00004632]. (shrink)

El objetivo del presente trabajo es analizar la nueva formulación del principio de acceso posinvestigación en la más reciente (2008) revisión de la Declaración de Helsinki. Se identifican los artículos relevantes de la Declaración y se presentan dos interpretaciones posibles del principio de acceso posinvestigación: una interpretación robusta y otra permisiva, inspiradas cada una por modelos de justicia distintos. Luego, se hace una evaluación crítica de dichas interpretaciones y se intenta avanzar argumentos en contra de la interpretación permisiva. [The objective (...) of this study is to critically analyze the new formulation of the principle of post-trial access in the most recent (2008) revision of the Helsinki Declaration. The relevant articles of the declaration are identified and two possible interpretations of the principle of post-trial access are set out; one robust and one permissive, inspired by different models of distributive justice. A critical evaluation of both interpretations is presented and arguments against the permissive one advanced.]. (shrink)

El problema de la transición de los participantes desde una investigación hacia la atención de la salud apropiada es un problema global. La publicación de una nueva versión de la Declaración de Helsinki es una excelente oportunidad para repensar este problema. Según mi interpretación, la Declaración de Helsinki 2013 introduce dos tipos diferentes de obligaciones posinvestigación, a saber, (1) obligaciones de acceso a atención de la salud y (2) obligaciones de acceso a información. Los beneficiarios pretendidos de estas obligaciones son (...) los participantes individuales de estudios de investigación. Y la Declaración identifica a los patrocinadores, investigadores y gobiernos de los países anfitriones como los principales agentes responsables de cumplir con las obligaciones posinvestigación. Para justificar esta interpretación de los tipos, agentes y beneficiarios de las obligaciones posinvestigación, presento primero una clasificación tentativa de las obligaciones posinvestigación. Luego hago una breve reconstrucción conceptual de las formulaciones de las obligaciones posinvestigación en las versiones anteriores de la Declaración y reviso las principales críticas. Finalmente presento un análisis crítico de la nueva formulación de las obligaciones posinvestigación basándome en la discusión de las secciones anteriores. [ABSTRACT] The problem of transitioning research participants when the study is concluded to the appropriate health care is a global problem. The publication of a new version of the Declaration of Helsinki and its public discussion is a great opportunity to rethink this problem. According to my interpretation, the Declaration of Helsinki 2013 identifies two different types of post-trial obligations, namely, (1) obligations of access to health care and (2) the obligations of access to information. The intended beneficiaries of these obligations are individual participants of research studies. And the Declaration identifies the sponsors, researchers and host country governments as the main agents responsible for complying with the post-trial obligations mentioned above. To justify this interpretation of the types, agents and beneficiaries of post-trial obligations, I first introduce a tentative classification of post-trial obligations. Then I make a brief conceptual reconstruction of formulations of post-trial obligations in earlier versions of the Declaration and revise the main critiques. Finally I advance a critical analysis of the new formulation of post-trial obligations based on the discussion in the previous sections. (shrink)

The article discusses the criteria for authentic humanity within the moral paradigm of Russian philosophy. In Russian philosophy, the disciplines of ethics and anthropology are intertwined, as the question of human nature is primarily addressed from a moral perspective. The article primarily focuses on the interplay between faith and conscience, a topic that is approached and resolved differently within the context of Russian philosophy compared to Western European philosophy. For instance, the concept of “elimination of the ethical,” a fundamental aspect (...) of S. Kierkegaard’s existential philosophy, is discussed. The transcendence of ethical rationalism through a leap of faith, exemplified by Abraham’s act, forms the essence of authentic Christian ethics. It explores how faith is challenged by ethics, which requires not blind faith, but rational behavior in accordance with the widely accepted norms of social morality. The article highlights the conflict between existential faith and social ethics as the primary contradiction identified by S. Kierkegaard. The author revisits the ideas of F.M. Dostoevsky, N.A. Berdyaev, and others to illustrate that within the context of Russian philosophy, the critical situation is less about the anticipation of death and more about the moral anguish of conscience arising from the evil and falsehood prevalent in the world, a sentiment shared by diverse individuals like V.S. Solovyov and V.M. Shukshin. This perspective significantly redefines the concept of the existential in Russian philosophy, equating it with profound moral reflection. In discussing philosophical and anthropological issues under the “post-human threat,” the author introduces the concept of “conscientious faith.” This concept, serving as a fundamental anthropological unit, posits that it is the conscience, with its appeal to personal moral responsibility, that reveals the moral essence of an individual, thereby establishing human uniqueness. (shrink)

Arendt’s reflections on the reverberations of the bureaucratic way of governing give rise to two distinct and, above all, complementary argumentative trajectories: 1) its investigation as a form of domination originating from imperialism and later used as a model of totalitarian; 2) the role of bureaucrats. Both help to understand why the bureaucracy not only survived the fall of totalitarian regimes, but also remained the organizational model of nations. At the intersection of these readings, the essay “Auschwitz on Trial” (...) presents two types of participants in the Nazi bureaucratic apparatus: bureaucratic assassins (desk murderes) and subordinate men. In common among them was a lack of responsibility for the crimes perpetrated by the regime and thoughtlessness; however, their degree of participation in the hierarchy and their punishability in post-war trials differed greatly. In these terms, this article aims to analyze the similarities and differences between subordinate men and bureaucratic murderers. To do so, it is assumed that understanding them helps to understand bureaucracy as a form of government that makes public freedom and the free exercise of spiritual activities unfeasible. (shrink)

We typically think of prosecutorial ethics as encompassing a special set of obligations for prosecutors during the pretrial and trial stages of a criminal case. In the literature and in rules of professional responsibility much attention is paid to the charging function, contact with unrepresented persons, plea negotiations, discovery, and courtroom decorum. Our concern with prosecutorial ethics at these stages is rooted primarily in due process and fairness to the accused. [W]hile he may strike hard blows, the Supreme (...) Court wrote in Berger v. United States, [a prosecutor] is not at liberty to strike foul ones. Whether it is a recognition that the prosecutor acts as a representative of the sovereign or that he or she possesses extraordinary power over people's lives, we speak about the prosecutor's ethical duties as special or additional to those of ordinary lawyers. By preventing a prosecutor from litigating unfairly, the aim is to protect a criminal defendant from an unjust or unwarranted conviction. What, then, are the ethical duties of prosecutors after the defendant has had his fair shot at trial, but lost? The literature and standards are surprisingly silent, with rare exception, on the post-conviction ethics of prosecutors. Constraints on the prosecutorial function seem to reach their apex at trial. Why? Are the reasons for special or additional ethics for prosecutors non-existent on appeal? Is the vast discretion, present at the pretrial and trial stages and thought by some to justify special ethical duties, absent on appeal? As a recent case from Texas illustrates, ethical issues still abound even after a jury returns a verdict of guilty. Nevertheless, the traditional discourse on pre-conviction duties can help us determine how prosecutorial discretion should be exercised after a conviction has been obtained. (shrink)

The paper suggests that Samuel Taylor Coleridge’s arguments against sympathy after the French Revolution, Walter Benjamin’s claims against empathy following the traumatic shock of Modernity and the First World War, and Hannah Arendt’s critical take on compassion. after the Holocaust are similar responses to singular historical crises. Reconsidering Arendt’s On Revolution (1963) and its evocation of Hermann Melville’s novella Billy Budd (1891), I show first that the novella bears the traces of an essay by Samuel Taylor Coleridge, “The Appeal to (...) Law” (1809). Then, drawing on Walter Benjamin’s writings on trauma in Illuminations (1968, edited by Arendt), I discuss the political importance Arendt attaches to the proper way of telling a story, at a time when “the communicability of experience is decreasing” (Benjamin, Illuminations, 86). Through the analysis of Benjamin’s “The Storyteller” and Arendt’s “heartless” report on the Eichmann trial (1963), I equally show that, according to Arendt, testimonies must be narrated, or rather performed, in a dispassionate, dry, and compact manner so that they can be historically and politically relevant. (shrink)

Importance: Given the importance of apathy for stroke, we felt it was time to scrutinize the psychometric properties of the commonly used Starkstein Apathy Scale for this purpose.Objectives: The objectives were to: estimate the extent to which the SAS items fit a hierarchical continuum of the Rasch Model; and estimate the strength of the relationships between the Rasch analyzed SAS and converging constructs related to stroke outcomes.Methods: Data was from a clinical trial of a community-based intervention targeting participation. A (...) total of 857 SAS questionnaires were completed by 238 people with stroke from up to 5 time points. SAS has 14 items, rated on a 4-point scale with higher values indicating more apathy. Psychometric properties were tested using Rasch partial-credit model, correlation, and regression. Items were rescored so higher scores are interpreted as lower apathy levels.Results: Rasch analysis indicated that the response options were disordered for 8/14 items, pointing to unreliability in the interpretation of the response options; they were consequently reduced from 4 to 3. Only 9/14 items fit the Rasch model and therefore suitable for creating a total score. The new rSAS was deemed unidimensional. Apathy was correlated weakly with anxiety/depression and uncorrelated with physical capacity. Regression showed that the effect of apathy on participation and health perception was similar for rSAS/SAS versions: R2 participation measures ranged from 0.11 to 0.29; R2 for health perception was ∼0.25. When placed on the same scale, rSAS value was 6.5 units lower than SAS value with minimal floor/ceiling effects. Estimated change over time was identical which was not substantial but greater than expected assuming no change.Conclusion: The retained items of the rSAS targeted domains of behaviors more than beliefs and results support the rSAS as a robust measure of apathy in people with chronic stroke. (shrink)

In recent years, science and technology have made great progress towards a better understanding of fundamental biological mechanisms of the diseases. Physicians, relying just on their own clinical experience, have long recognized that each patient is different from every other patient in many aspects. It is a matter of simple facts that many patients die without responding to any treatment, while others with the same disease survive. In oncology, the variability of treatment response has been a long-standing problem. Nowadays, thanks (...) to genomics and post-genomics advancements, we have identified an indication for that individual variability: tumor heterogeneity. Each tumor has a different genomic basis... (shrink)

Beginning with a brief presentation of the historical data and conceptual issues that have led to the emergence of the doctrine of the notion of Transitional Justice, I will describe the orientation adopted in two paradigmatic historical contexts, the Nuremberg trial at the end of the Second World War and the post-apartheid reconciliation process in South Africa. Supported by documents from International Human Rights Law and other international legal sources (Rome Statute) I will then offer a provisional definition (...) of what I call a Critical Transitional Justice. The conclusion highlights how the relationship between retrospective and prospective responsibility today is not exclusionary: as central principles of Critical Transitional Justice, they contribute in conferring normative legitimacy to transformative processes of adapting the international system to compliance to general principles of human rights. (shrink)

In its essence, post-trial obligations describe a duty by research sponsors to provide a successfully tested drug to research participants who took part in the relevant clinical trials after the trial has been concluded. In some instances,this duty is extended beyond the research participants. This article is divided into three main parts. The first part outlines the legal basis for post-trial obligations by looking at international guidelines, including those issued by the World Medical Association. National (...) legislation is exemplified through resolutions and guidelines issued by Brazil and South Africa respectively. The second part analyses the ethical foundation for post-trial obligations, in particular the attempt to minimize exploitation of research subjects. The third part raises obstacles and challenges for the implementation of post-trial obligations. The jury is still out on whether post-trial obligations in the form of access to drugs for clinical trial participants is the best, or even a good way, to avoid exploitation in medical research. (shrink)

The commercialization of transgenic crops has engendered significant resistance from environmental groups and defensive responses from industry. A part of this struggle entails the politicization of science as groups gather evidence from the scholarly literature to defend a supportive or opposing position to transgenic crop commercialization. The authors argue that novel technology development and associated scientific uncertainty have led to two competing approaches to risk management: precaution and ex post trial and error. In this paper we use the (...) controversies over currently commercialized transgenic crops to analyze the debate over these competing approaches. We also suggest a hybrid approach that incorporates a precautionary selection process, but also relies on ex post trial and error after commercialization. This approach is labeled precaution through experience since the development of a technology’s characteristics would ideally take into account previous experience with similar technologies, or rather technologies with similar applications. The authors argue that substantial public participation and dialogue is needed to identify socially desirable crop traits to guide research and development. Policy tools are also recommended that provide incentives to private-sector firms to engineer the identified traits into crops. (shrink)

Journalism educators who appear as expert witnesses and consultants in media law cases such as libel and invasion of privacy are often unfamiliar with the practical aspects of serving as an eflective, efficient, and ethical expert. These practical dimensions include federal and state rules of evidence and civil procedure, the process of deciding whether or not to accept a case, negotiations over fees and employment conditions, ethical conflicts associated with representation, the litigation process, and post-trial issues. It is (...) unusual, especially in media law cases, for an expert's testimony to make or break a case, but a client has a right to expect aggressive and rigorous representation and ready accessibilityfrom the expert. The challenge facing the journalism educator who serves as an expert witness is balancing those demands with the responsibilities of being a professor while avoiding conflicts of interest. (shrink)

Introduction Perhaps more than any other member of the Frankfurt School, Herbert Marcuse articulated a hope for a radically transfigured world. He imagined a world characterized by receptive, generous relationships rather than domination and violence. Yet Marcuse's philosophy of liberation has been placed on trial within various critical circles. Michel Foucault's rejection of the “repressive hypothesis” and his concomitant analysis of power as generative is typically interpreted as an indirect response to Marcuse's tendency to treat the social order as (...) a primarily repressive force vis-à-vis our instincts and desires.1 Martin Jay has expressed concerns about the…. (shrink)

Background HIV prevention research has been fraught with ethical concerns since its inception. These concerns were highlighted during HIV vaccine research and have been elaborated in microbicide research. A host of unique ethical concerns pervade the microbicide research process from trial design to post-trial microbicide availability. Given the urgency of research and development in the face of the devastating HIV pandemic, these ethical concerns represent an enormous challenge for investigators, sponsors and Research Ethics Committees (RECs) both locally (...) and internationally. Discussion Ethical concerns relating to safety in microbicide research are a major international concern. However, in the urgency to develop a medically efficacious microbicide, some of these concerns may not have been anticipated. In the risk-benefit assessment of research protocols, both medical and psycho-social risk must be considered. In this paper four main areas that have a potential for medical and/or psycho-social harm are examined. Male partner involvement is controversial in the setting of covert use of microbicides. However, given the long-term exposure of men to experimental products, this may be methodologically, ethically and legally important. Covert use of microbicides may impact negatively on relationship dynamics leading to psychosocial harm to varying extents. The unexpectedly high rates of pregnancy during clinical trials raise important methodological and ethical concerns. Enrollment of adolescents without parental consent generates ethical and legal concerns that must be carefully considered by RECs and trial sites. Finally, paradoxical outcomes in recent trials internationally have advanced the debate on the nature of informed consent and responsibility of researchers to participants who become HIV positive during or after trials. Summary Phase 3 microbicide trials are an undisputed research and ethical priority in developing countries. However, such trials must be conducted with attention to both methodological and ethical detail. It is imperative that guidelines are formulated to ensure that high ethical standards are maintained despite the scientific urgency of microbicide development. Given the controversy raised by emergent ethical issues during the course of microbicide development, it is important that international consensus is reached amongst the various ethics and regulatory agencies in developing and developed countries alike. (shrink)

ABSTRACT Many recent articles argue that participants who seroconvert during HIV prevention trials deserve treatment when they develop AIDS, and there is a general consensus that the participants in HIV/aids treatment trials should have continuing post‐trial access. As a result, the primary concern of many ethicists and activists has shifted from justifying an obligation to treat trial participants, to working out mechanisms through which treatment could be provided. In this paper I argue that this shift frequently conceals (...) an important assumption: that if there is an obligation to supply treatment, then any party who could provide it may be prevailed upon to discharge the obligation. This assumption is false. The reasons why trial participants should get ART affect who has the duty to provide it. We should not burden governments with the obligations of sponsors, nor researchers with the obligations of the international community. And we should not deprive a group of treatment because their need is less salient than that of research participants. Insisting otherwise may lead to people being wrongfully deprived of access to antiretrovirals. (shrink)

We address some concerns related to the use of post-trial attribution judgments, originally developed for artificial grammar learning , during the version of the serial reaction time task used by Fu, Dienes, and Fu . In particular, intuition attributions, which are central to Fu et al.’s arguments, seem problematic: This attribution is likely to be made when stimuli contain several competing sources of information to which subjective feelings could be attributed. The interpretation of intuition attributions in Fu et (...) al.’s SRT generation task is problematic because the procedure involved a 2-element sequence where items varied only in position. In our view, responses categorised as intuitions might have been a variety of guess response where neither judgement knowledge nor structural knowledge were conscious. The results would then be compatible with previous findings showing that people can control the use of unconscious structural knowledge even when judgement knowledge is unconscious. (shrink)

Bioethicists have long debated the content of sponsors and researchers' obligations of justice in international clinical research. However, there has been little empirical investigation as to whether and how obligations of responsiveness, ancillary care, post-trial benefits and research capacity strengthening are upheld in low- and middle-income country settings. In this paper, the authors argue that research ethics guidelines need to be more informed by international research practice. Practical guidance on how to fulfil these obligations is needed if research (...) groups and other actors are to successfully translate them into practice because doing so is often a complicated, context-specific process. Case study research methods offer one avenue for collecting data to develop this guidance. The authors describe how such methods have been used in relation to the Shoklo Malaria Research Unit's vivax malaria treatment (VHX) trial (NCT01074905). Relying on the VHX trial example, the paper shows how information can be gathered from not only international clinical researchers but also trial participants, community advisory board members and research funder representatives in order to: (1) measure evidence of responsiveness, provision of ancillary care, access to post-trial benefits and research capacity strengthening in international clinical research; and (2) identify the contextual factors and roles and responsibilities that were instrumental in the fulfilment of these ethical obligations. Such empirical work is necessary to inform the articulation of obligations of justice in international research and to develop guidance on how to fulfil them in order to facilitate better adherence to guidelines' requirements. (shrink)

Background The post-trial period is the time period after the end of study drug administration. It is unclear whether post-trial arrangements for patient surveillance are routinely included in study protocols and consents, and whether research ethics boards (REB) consider the post-trial period. Objectives The objective was to determine whether trial protocols and consent forms reviewed by the REB describe procedures for post-trial period surveillance. Methods An observational study of protocols of randomised (...) trials of chronic therapies for cardiac conditions, approved by the REB of two academic institutions affiliated with the University of Toronto in Canada (University Health Network and Mount Sinai Hospital) from 1995 to 2007. Plans for patient surveillance in the post-trial period described in the protocol or in the consent form before and after REB approval were recorded. Results 42 studies were identified including 18 heart failure and 15 coronary artery disease trials. Only four studies planned a clinical visit after trial termination, and an additional three planned a telephone contact after trial completion. Five trials submitted consent forms to the REB with a discussion of the post-trial period. Conclusions The majority of protocols and consent forms did not discuss plans for post-trial period surveillance. The post-trial period and the REB approval process could be improved by systematic follow-up being described in the protocol and consent form. The small number of trial protocols evaluated in the study may impair the degree to which the results can be generalised. (shrink)

Increasing ethical attention and debate is focusing on whether individuals who take part in clinical trials should be given access to post-trial care. However, the main focus of this debate has been upon drug trials undertaken in low-income settings. To broaden this debate, we report findings from interviews with individuals (n = 24) who participated in a clinical trial of a closed-loop system, which is a medical device under development for people with type 1 diabetes that automatically (...) adjusts blood glucose to help keep it within clinically recommended ranges. Individuals were recruited from UK sites and interviewed following trial close-out, at which point the closed-loop had been withdrawn. While individuals were stoical and accepting of the requirement to return the closed-loop, they also conveyed varying degrees of distress. Many described having relaxed diabetes management practices while using the closed-loop and having become deskilled as a consequence, which made reverting back to pre-trial regimens challenging. Participants also described unanticipated consequences arising from using a closed-loop. As well as deskilling, these included experiencing psychological and emotional benefits that could not be sustained after the closed-loop had been withdrawn and participants reevaluating their pre- and post-trial life in light of having used a closed-loop and now perceiving this life much more negatively. Participants also voiced frustrations about experiencing better blood glucose control using a closed-loop and then having to revert to using what they now saw as antiquated and imprecise self-management tools. We use these findings to argue that ethical debates about post-trial provisioning need to be broadened to consider potential psychological and emotional harms, and not just clinical harms, that may result from withdrawal of investigated treatments. We also suggest that individuals may benefit from information about potential nonclinical harms to help make informed decisions about trial participation. (shrink)

Todos los días se prueban nuevos psicofármacos, tratamientos para el VIH/SIDA o el cáncer, entre otras enfermedades. Algunos de esos tratamientos son lo suficientemente exitosos como para cronificar enfermedades antes consideradas mortales, como los antirretrovirales para el VIH/SIDA o el imatinib para la leucemia mieloide a principios del 2000. No obstante, antes de que puedan ser comercializados o estar disponibles en los sistemas de salud pública, deben pasar por una serie de rigurosas pruebas de calidad, seguridad y eficacia. Estas pruebas (...) implican el testeo de las drogas en animales y su estudio en seres humanos, sanos o enfermos. Estrictas normas de buenas prácticas científicas y éticas regulan todo el proceso de las investigaciones biomédicas. El problema de mi tesis se centra en el momento de la finalización de los estudios en seres humanos. Alguien podría preguntarse qué pasa con las personas si se benefician clínicamente del tratamiento experimental durante el estudio cuando este finaliza. La interrupción abrupta de un tratamiento beneficioso podría poner en peligro la salud de los sujetos. Y en el caso de sujetos de investigación afectados por enfermedades crónicas, es probable que deban continuar con el tratamiento beneficioso u otra atención adecuada por el resto de sus vidas. Un sujeto de investigación estadounidense sin seguro de salud que participó en un estudio de largo plazo de diabetes resume estas preocupaciones: "de repente cortan la cuerda, y uno está solo por su cuenta ... O conseguís trescientos o cuatrocientos dólares por mes para seguir con esto o simplemente seguís adelante y morís". Este tipo de casos me llevaron a preguntar si existe alguna obligación moral de proveer el tratamiento beneficioso a un sujeto de investigación que no puede pagárselo. Muchas personas podrían pensar que interrumpir el tratamiento beneficioso al sujeto de investigación que padece de diabetes y no tiene seguro para cubrir un tratamiento es incorrecto, porque nadie debería morir de una enfermedad o dedicar todos los recursos disponibles para sobrevivir, especialmente cuando se contribuyó a encontrar una cura o a obtener la evidencia científica necesaria para desarrollar un mejor tratamiento que el existente. Otras personas podrían pensar que lo correcto es ofrecer el tratamiento a un "precio justo", y si la persona no puede pagar por la continuidad de tratamiento es su responsabilidad. Mi intuición es que una sociedad democrática justa tiene una obligación moral de establecer un sistema de continuidad de tratamiento beneficioso para los sujetos de investigación. En esta tesis intento justificar filosóficamente esta última intuición básica utilizando el marco teórico de la teoría de la justicia de Rawls. Elijo utilizar la teoría rawlsiana, porque esta teoría me permite ubicar los problemas morales con respecto a la continuidad de tratamiento beneficioso en su contexto social adecuado y en el contexto de la búsqueda general de una sociedad más justa. En particular, la encuentro especialmente adecuada para explicar fenómenos complejos de responsabilidad social como los que creo que subyacen en el problema de la obligación de continuidad de tratamiento beneficioso hacia los sujetos de investigación. Como mostraré más adelante, es imposible tener en cuenta los aspectos morales de la continuidad de tratamiento beneficioso aislada de la sociedad en la que se realizan los estudios con seres humanos. En el capítulo 1 presento una introducción general al tema de la ética de la investigación y al problema de la continuidad de tratamiento beneficioso. En el capítulo 2 intento determinar el campo de estudio de la obligación de continuidad de tratamiento beneficioso hacia los sujetos de investigación. Para eso, mi estrategia es la siguiente. Primero, busco identificar los casos de estudios clínicos donde se daría la obligación de continuidad beneficiosa hacia los sujetos de investigación. Segundo, presento el problema de la justificación moral de la obligación de continuidad y la necesidad de discutir las justificaciones basadas en la idea de justicia como reciprocidad. Para esto, en la sección 2, identifico la obligación de continuidad de tratamiento a través de una selección de sus casos paradigmáticos en la literatura. Comienzo con el caso de los estudios clínicos con antirretrovirales llevados a cabo en Sudáfrica en personas con VIH/SIDA. Luego, introduzco el concepto teórico de sistema de continuidad de tratamiento beneficioso. Este concepto me permite evaluar y comparar teóricamente cómo diferentes sociedades hacen frente al problema de proveer la continuidad de tratamiento beneficioso a los sujetos de investigación. Por último, rastreo los casos ejemplares de obligación de continuidad de tratamiento beneficioso hacia los sujetos en países desarrollados, con énfasis especial en los Estados Unidos. En la sección 3, analizo algunos problemas de confusión o ambigüedad más importantes en torno a la obligación. Primero, analizo el nombre de la obligación. Luego, trato de distinguir la obligación de continuidad de tratamiento hacia los sujetos de investigación de la obligación de disponibilidad razonable, una confusión muy común en la literatura de la ética de la investigación. Finalmente, me detengo a analizar una posible ambigüedad en el concepto de "tratamiento beneficioso" y utilizo algunos de los casos paradigmáticos identificados para argumentar a favor de mi interpretación. Atacado el primer problema, en la sección 4 y 5 me vuelco a relevar el problema de la justificación moral de la obligación de continuidad. En la sección 4, reconstruyo lo que llamo la "versión simple" del concepto de obligación a partir de la discusión sobre las fuentes de la obligación de continuidad de tratamiento beneficioso. Luego, planteo la necesidad de investigar las justificaciones basadas en la idea de justicia como reciprocidad debido a las ambigüedades y la falta de un marco teórico claro dentro del campo de la ética de la investigación en seres humanos. Finalmente, en la sección 5, introduzco algunas distinciones clásicas con el fin de complejizar el marco teórico de las obligaciones, el cual será utilizado en la discusión de los próximos dos capítulos. En el capítulo 3 discuto la justificación de la obligación de continuidad de tratamiento que da el modelo económico de Alan Wertheimer. En la sección 1 del capítulo, debido a lo específico del tema y lo poco conocido del autor, introduzco a la persona y el contexto institucional de su obra. En la sección 2 del capítulo, distingo tres interpretaciones del concepto de justicia como reciprocidad e intento mostrar que Wertheimer utiliza una interpretación caracterizada por el uso mutuo y el intercambio de beneficios, a la cual llamo "reciprocidad de mercado". En la sección 3, presento el marco teórico del modelo económico. La pregunta fundamental de Wertheimer es la siguiente: ¿tienen los investigadores o patrocinadores una obligación supercontractual de proporcionar la continuidad de tratamiento u otros beneficios a los sujetos de investigación? Según el autor, el consenso en ética de la investigación responde de manera afirmativa a esta pregunta y como fundamento de esta obligación se encontraría lo que Wertheimer llama "el principio de interacción". Analizo este principio y presento las críticas que hace Wertheimer al mismo. En la sección 4, presento la respuesta a la pregunta fundamental que da Wertheimer mediante su "argumento estratégico". En la sección 5 analizo la solución dada por Wertheimer e intento explicar algunos de los supuestos principales del modelo, a saber, (i) la lógica del argumento estratégico, (ii) la fuerza moral de los conceptos de Pareto y (iii) el compromiso del modelo económico con la restricción de la información. Por último, en la sección 6 presento mis críticas al modelo económico. En el capítulo 4 presento el modelo de reciprocidad democrática, inspirado en la teoría de la justicia de Rawls. Este modelo se presenta como un marco teórico y una interpretación de la justicia como reciprocidad alternativos al modelo económico presentado en el capítulo anterior. En la sección 2 del presente capítulo, explicito los problemas del marco teórico relacionados con el concepto de justicia como reciprocidad que subyacen a la discusión sobre la obligación de continuidad de tratamiento beneficioso hacia los sujetos de investigación. Para esto, me centro en tres puntos: (i) la relación del principio de justicia como reciprocidad y el concepto de obligación; (ii) el problema del alcance del principio de reciprocidad, y (iii) la relación entre el principio de reciprocidad y el concepto de equidad, o lo que llamo "el problema de la medida de la reciprocidad". En la sección 3, defino con mayor claridad el enfoque rawlsiano de la justicia distributiva y expongo una crítica a los argumentos antirrawlsianos esgrimidos por los defensores del modelo económico que afirman que los principios de justicia política de Rawls no se aplican a los individuos. Si mi respuesta a los defensores del modelo económico es correcta, los principios de justicia política se aplican a los individuos de manera indirecta, mediante la asignación de obligaciones posicionales por parte de la estructura básica de instituciones de una sociedad democrática, y permiten garantizar igual justicia a todos los miembros de la sociedad. En la sección 4, presento mi propuesta original de cómo entender la obligación de continuidad de tratamiento beneficioso hacia los sujetos de investigación. Esta sería una obligación posicional perfecta correlativa con el derecho a la salud en sociedades democráticas justas o moderadamente injustas. En la sección 5, muestro de manera detallada el mecanismo apropiado para extender los principios de justicia política al caso de la obligación de continuidad de tratamiento beneficioso hacia los sujetos de investigación. Con este objetivo, introduzco la idea de secuencia en cuatro etapas, que permite evaluar y diseñar nuevos esquemas institucionales para dar contenido a la obligación de continuidad de tratamiento. Y presento los principios de obligaciones y deberes individuales, que cierran el sistema rawlsiano brindando razones morales a los individuos para extender los esquemas institucionales justos a nuevas situaciones, reformar los existentes y cumplir con las obligaciones posicionales asignadas por estos nuevos esquemas. Por último, en la sección 6, discuto las objeciones más importantes al modelo de justificación de reciprocidad democrática. Por último, en la conclusión general, hago un intento de aplicación del marco teórico del modelo de reciprocidad democrática al análisis de los sistemas de continuidad de tratamiento para países como Argentina o Brasil y presento las líneas más importantes para la investigación futura. (shrink)

Ethics guidance increasingly recognises that researchers and sponsors have obligations to consider provisions for post-trial access to interventions that are found to be beneficial in research. Yet, there is little information regarding whether and how such plans can actually be implemented. Understanding practical experiences of developing and implementing these plans is critical to both optimising their implementation and informing conceptual work related to PTA. This viewpoint is informed by experiences with developing and implementing PTA plans for six large-scale (...) multicentre HIV prevention trials supported by the HIV Prevention Trials Network. These experiences suggest that planning and implementing PTA often involve challenges of planning under uncertainty and confronting practical barriers to accessing healthcare systems. Even in relatively favourable circumstances where a tested intervention medication is approved and available in the local healthcare system, system-level barriers can threaten the viability of PTA plans. The aggregate experience across these HIV prevention trials suggests that simply referring participants to local healthcare systems for PTA will not necessarily result in continued access to beneficial interventions for trial participants. Serious commitments to PTA will require additional efforts to learn from future approaches, measuring the success of PTA plans with dedicated follow-up and further developing normative guidance to help research stakeholders navigate the complex practical challenges of realising PTA. (shrink)

Exercise may influence components of executive functioning, specifically cognitive control and action monitoring. We aimed to determine whether high level exercise improves the efficacy of cognitive control in response to differing levels of conflict. Fitter individuals were expected to demonstrate enhanced action monitoring and optimal levels of cognitive control in response to changing task demands. Participants were divided into the highly active or low-active group based on self-reported activity using the International Physical Activity Questionnaire. A modified flanker task was then (...) performed, in which the level of conflict was modulated by distance of distractors from the target and congruency of arrows. Electroencephalography was collected during 800 trials; trials were 80% congruent, 20% incongruent, 50% close, and 50% far. The error-related negativity and error positivity were extracted from the difference wave of correct and incorrect response locked epochs, the N2 from the difference wave of congruent and incongruent stimulus locked epochs and the P3 from stimulus locked epochs. The HA group showed a larger Pe amplitude compared to the low-active group. Close trials elicited a larger N2 amplitude than far trials in the HA group, but not the low-active group, the HA group also made fewer errors on far trials than on close trials. Finally, the P3 was smaller in the lowest conflict condition in the HA, but not the low-active group. These findings suggest that habitual, high levels of exercise may influence the endogenous processing involved in pre-response conflict detection and the post-error response. (shrink)

In what ways is the conduct of prosecutors constrained by the presumption of innocence? To address this question, I first develop an account of the presumption in the trial context, according to which it is a vital element in a moral assurance procedure for the justified infliction of legal punishment. Jurors must presume the factual innocence of defendants at the outset of trials and then be convinced beyond a reasonable doubt by the government’s evidence before they convict defendants. Prosecutors’ (...) responsibilities to promote the integrity of this moral assurance procedure are then divided into pre-trial, during-trial, and post-trial phases. Since most charge adjudication is effected through plea bargaining, the ways in which plea procedures must be modified to conform to this moral assurance procedure, and thus honor the presumption of innocence, are also discussed. (shrink)

Background : researchers and sponsors increasingly confront the issue of whether participants in a clinical trial should have post-trial access (PTA) to the trial drug. Legislation and guidelines are inconsistent, ambiguous or silent about many aspects of PTA. Recent research highlights the potential importance of systematic reviews (SRs) of reason-based literatures in informing decision-making in medicine, medical research and health policy. Purpose: to systematically review reasons why drug trial participants should, or need not be ensured (...) PTA to the trial drug and the uses of such reasons. Data sources: databases in science/medicine, law and ethics, thesis databases, bibliographies, research ethics books and included publications’ notes/bibliographies. Publication selection: a publication was included if it included a reason as above. See article for detailed inclusion conditions. Data extraction and analysis: two reviewers extracted and analyzed data on publications and reasons. Results: of 2060 publications identified, 75 were included. These mentioned reasons based on morality, legality, interests/incentives, or practicality, comprising 36 broad (235 narrow) types of reason. None of the included publications, which included informal reviews and reports by official bodies, mentioned more than 22 broad (59 narrow) types. For many reasons, publications differed about the reason’s interpretation, implications and/or persuasiveness. Publications differed also regarding costs, feasibility and legality of PTA. Limitations: reason types could be applied differently. The quality of reasons was not measured. Conclusion: this review captured a greater variety of reasons and of their uses than any included publication. Decisions based on informal reviews or sub-sets of literature are likely to be biased. Research is needed on PTA ethics, costs, feasibility and legality and on assessing the quality of reason-based literature. (shrink)

Care after research is for participants after they have finished the study. Often it is NHS-provided healthcare for the medical condition that the study addresses. Sometimes it includes the study intervention, whether funded and supplied by the study sponsor, NHS or other party. The NHS has the primary responsibility for care after research. However, researchers are responsible at least for explaining and justifying what will happen to participants once they have finished. RECs are responsible for considering the arrangements. There (...) are ethical and practical issues, in particular when participants may wish to continue on the study intervention after the study. There are also various guidelines and legislation. This document presents a framework of questions to help NHS RECs and their applicants. Information on this document’s development is here. (shrink)

Clinical trials are essential to establish the safety and efficacy of investigational products, contributing to risk/benefit assessments that ultimately determine whether these products meet the criteria for market authorisation. Clinical trials are also an important source of revenue and expertise generation for countries in which they are conducted. In developing countries, they represent substantial foreign direct investment. In spite of the substantial capital input that clinical trials require, the issue of funding post-trial access to beneficial therapies remains contentious, (...) especially in resource-limited settings. In this article, we explore this situation and propose mechanisms to establish ‘win-win’ situations where both patients and clinical trial sponsors derive benefit from post-trial access programmes in low- and middle-income countries. (shrink)