Asia is the most diverse continent in the world in terms of culture, religion, population size, finance, education, health care, academic research, general population skills, and governmental drug regulations. Each Asian country has its own unique qualities when it comes to attracting industry sponsored clinical trials. Factors that influence selecting location of a study site for a sponsored trial are mainly population size, infrastructure, education levels, and quality of health care, cost and drug regulatory platform. Conducting research (...) in traditional countries like Pakistan adds another dimension to the problems in assuring that research conducted in an ethical manner. The indigenous layer of the cultural values makes it even more difficult task, but this is the task that we are morally and ethically bound to shoulder. (shrink)

Despite ample evidence of the efficacy and effectiveness of evidence-based parenting programmes (EBPPs) within research-led environments, there is very little evidence of maintenance of effectiveness when programmes are delivered as part of regular service provision. The present study examined the effectiveness of EBPPs provided during a period of sustained service-led implementation in comparison to research-led effectiveness evaluation. Data from 3706 parents who received EBPPs during sustained implementation by services were compared to data from 1390 parents who had participated (...) in an earlier researcher-led effectiveness trial of a national roll-out of EBPPs in England. In both phases, parents completed measures of child behaviour problems, parenting style and parental mental well-being prior to starting parenting programmes (pre-test), at the end of the programmes (post) and at 12-months follow up. Results from Generalised Estimating Equations controlling for potential covariates indicated significant improvements in child behaviour problems during sustained implementation, similar to the effectiveness phase; significant improvements in parenting style which were larger than the effectiveness phase at 12-month follow up; and significant improvements in parental mental well- being. Our findings demonstrate effective maintenance of gains when EBPPs are provided as part of regular provision across a large sample of English parents. Successful long-term implementation should consider effectiveness of EBPPs across the population, given the large contextual changes that take place between researcher-led evaluations and service take-up. Our findings support the integration of EBPPs in public health approaches to addressing child behaviour problems and parent well-being. (shrink)

Research ethics committees (RECs) evaluate whether the risk-benefit ratio of a study is acceptable. Decentralized clinical trials (DCTs) are a novel approach for conducting clinical trials that potentially bring important benefits for research, including several collateral benefits. The position of collateral benefits in risk-benefit assessments is currently unclear. DCTs raise therefore questions about how these benefits should be assessed. This paper aims to reconsider the different types of research benefits, and their position in risk-benefit assessments. We first (...) propose a categorization of research benefits, based on the types of benefits that can be distinguished from the literature and ethical guidelines. Secondly, we will reconsider the position of collateral benefits. We argue that these benefits are not fundamentally different from other benefits of research and can therefore be included in risk-benefit assessments of DCTs. (shrink)

We examined the efficacy of including a research intermediary (RI) during the consent process in reducing participants' perceptions of coercion to enroll in a research study. Eighty-four drug court clients being recruited into an ongoing study were randomized to receive a standard informed consent process alone (standard condition) or with an RI (intermediary condition). Before obtaining consent, RIs met with clients individually to discuss remaining concerns. Findings provided preliminary evidence that RIs reduced client perceptions that their participation might (...) influence how clinical and judicial staff view them. This suggests that using RIs may improve participant autonomy in clinical studies. (shrink)

Background This article describes the issues encountered when designing a study to evaluate recruitment of minority ethnic groups into clinical cancer research in order to monitor adherence to the principles for good practice set out in the Department of Health, Research Governance Framework, England. Methods (i) A review of routine data sources to determine whether their usefulness as a source of data on prevalence of cancer in the population by ethnic category. (ii) A local case study at one (...) hospital trust to ascertain whether the ethnicity of cancer trial participants was representative of admitted cancer patients. Results (i) The lack of a comparator population makes it problematic to assess recruitment levels by ethnic group in clinical research. (ii) The odds of being in a trial were 30% lower for a member of a minority ethnic group compared to a white cancer patient after adjusting for disease, age and gender, OR 0.70 (0.53 to 0.94). These results differed for each ethnic group; Asian patients did not appear under-represented while Black and Chinese did so. However, there are important caveats to the findings based on the limited recording of ethnicity. Conclusions The lack of available data on the ethnicity of participants in clinical research and the prevalence of cancer in the population according to ethnicity makes it difficult to design a study to monitor representation of minority ethnic groups. This information is necessary to assess adherence to the Research Governance Framework principle that research evidence reflects the diversity of the population. (shrink)

There is an alleged tension between undue inducement and exploitation in research trials. This paper considers claims that increasing the benefits to research subjects enrolled in international, externally-sponsored clinical trials should be avoided on the grounds that it may result in the undue inducement of research subjects. This article contributes to the debate about exploitation versus undue inducement by introducing an analysis of the available empirical research into research participants' motivations and the influence of payments (...) on research subjects' behaviour and risk assessment. Admittedly, the available research in this field is limited, but the research that has been conducted suggests that financial rewards do not distort research subjects' behaviour or blind them to the risks involved with research. Therefore, I conclude that research sponsors should prioritise the prevention of exploitation in international research by providing greater benefits to research participants. (edited). (shrink)

Current clinical research lacks diversity in those that participate. This lack of diversity is concerning given its importance for successful drug development. The frequency and severity of many diseases, along with the pharmacological properties of therapies, can display significant differences based on patient diversity. A clinical trial population that is more reflective of these differences will help researchers better understand the therapeutic profile of the treatment and provide generalizable knowledge to the medical community. The advent of decentralized clinical (...) trial designs is meant to help address this lack of diversity by using portable digital health technologies and virtual interactions to enhance clinical trial access and broaden participation. By leveraging these technologies, trial conduct can occur at locations other than traditional research sites. This shift in trial location may help address some of the logistical, educational, engagement, and trust barriers that have historically prevented enrollment of diverse populations. However, these types of trials still have limitations. Ethical concerns around justice, equity, and diversity will still exist with decentralized clinical trials, which could be mediated using clinical research vehicles. When utilized, this modality may enhance the scientific design and conduct of clinical trials and better follow these ethical principles. These enhancements and improved ethical direction could be accomplished through increasing community involvement, improving health literacy, supporting more diverse trial sites, creating community‐based research footholds, fostering connections with researchers, limiting technical challenges, and preventing data security issues. (shrink)

De Bie et al. (2023) propose an organizing framework for different stages of human gestational development from conception to the viable premature. They also identify ethical considerations and con...

Biomedical research involving human participants is highly regulated and subject to stringent ethical requirements. Clinical research ethics, regulation and policy have tended to focus almost exclusively on the protection of participants' interests against harms that might result from taking part in research. Less consideration, however, has been given to the interests that patients may themselves have in research participation, even in trials that may be beyond the bounds of current clinical research practice. In this paper, (...) we consider the case of a suggested extension to clinical trial protocols to explore the ethics of participation in ‘risky’ research. We argue that patients may have a strong interest in taking part in research, and that even when greater-than-usual risks may be present, such research can be both ethically and scientifically justified. Finally, we suggest that there might be scope in some cases to assert a right to participate in research, and that the possibility of such a right merits further consideration. (shrink)

“Responsible research” and “good science” are concepts with various meanings depending on one’s perspective and assumptions. Fellow researchers, research participants, policy makers and the general public also have differing expectations of the benefits of research ranging from accurate and reliable data that extend the body of knowledge, to solutions to societal concerns. Unless these differing constituencies articulate their differing views they may fail to communicate and undermine the value of research to society.

Aims and background: Little is known about how participants perceive prevention trials, particularly trials designed to prevent mental illness. This study examined participants’ motives for participating in a trial and their views of randomisation and the ability to withdraw from a randomised controlled trial for prevention of depression. Methods: Participants were older adults reporting elevated depression symptoms living in urban and regional locations in Australia who had consented to participate in an RCT of interventions to prevent depression. Participants (...) rated their agreement with various statements describing motivations for enrolment in the trial and opinions regarding randomisation and withdrawal. Results: The majority of participants expressed a triad of altruistic motivation for participation, relative lack of concern about randomisation and commitment to the trial. Certain subgroups of participants, such as women and those with higher depression scores, reported higher levels of concern about specific issues. Conclusions: The findings suggest that participants enrolled in prevention trials for mental illness are likely to hold positive attitudes towards research trials. The identification of relationships between key person factors and trial-related attitudes enabled profiling of participant groups, which can inform recruitment strategies and interactions of participants and research projects in future prevention trials. (shrink)

Recent controversy surrounding the Surfactant Positive Airway Pressure and Pulse Oximetry Trial and the Office for Human Resource Protection’s judgment that its informed consent procedures were inadequate has unmasked considerable confusion about OHRP’s definition of research risks. The controversy concerns application of that definition to trials comparing multiple treatments within the existing standard of care. Some have argued that it is impossible for such trials to pose research risks on the grounds that all risks associated with a (...) standard-of-care treatment should instead be considered risks of treatment. However, analysis of OHRP’s definition demonstrates that some risks in such trials can be research risks. (shrink)

In this paper, we discuss challenges associated with implementing a policy for Ancillary Care (AC) for related and unrelated (serious) adverse events during an Ebola vaccine trial conducted in a remote area of the Democratic Republic of the Congo. Conducting clinical trials in resourceconstrained settings can raise context-related challenges that have implications for study participants’ health and wellbeing. During the Ebola vaccine study, three participants were injured in road traffic accidents, but there were unexpected difficulties when trying to apply (...) the AC policy. First, because of the nature of the adverse events, the insurer refused to cover the costs. Second, the AC policy did not address treatments by traditional medicine, even though traditional medicines are frequently used and highly trusted in the study community. This highlighted a contrast between the researchers’ well-intentioned AC approach and the participants’ legitimate preferences. The way in which researchers should address their responsibility to provide AC is not straightforward; it requires contextualization. Our experience highlights the importance of involving community representatives and the local ethics committee to ensure development of an AC policy that is culturally and ethically appropriate. Additionally, the insurance contract should clearly stipulate which adverse events are linked to the trial participation, and thus eligible for coverage, to avoid controversies when claims are made. (shrink)

Informed by interviews conducted with members of a local research ethics committee (REC), this article reflects upon how RECs can act to improve the quality of patient consent to clinical trials. Two emergent narratives which trial participants have drawn upon to account for their experiences are explored: the narrative of the clinical trial itself and a narrative of individualized treatment. Informed consent requires participants to recognize that only the first of these narratives is relevant to the design, (...) and their experience, of randomized controlled trials. Improving the clarity of patient information is argued to be a relevant, but insufficient, strategy for increasing patient familiarity with the methodology of clinical trials. In the concluding sections of the article, other approaches, and the role of RECs, are considered. (shrink)

BackgroundWhile ethicists have for many years called for human subject trial participants and, in some cases, local community members to benefit from participation in pharmaceutical and other intervention-based therapies, little is known about how these discussions are impacting the practice of research ethics boards that grant ethical approval to many of these studies.MethodsTelephone interviews were conducted with 23 REB members from across Canada, a major funder country for human subject research internationally. All interviews were digitally recorded and (...) transcribed verbatim. After coding, the data was analyzed to identify central themes and topics. Themes were identified, application of the themes was confirmed, and these themes were then used to populate the findings of this manuscript.ResultsOur analysis of the interviews identified two primary themes when considering what benefits are owed to research participants and their communities. 1) Most study participants felt that given that these studies are led by persons in the role of researcher rather than health care provider, they had a limited obligation to provide benefits to study participants. 2) These REB members were all working in Canada, a high income country where most residents enjoy high levels of access to health care. As a result of this context, the study participants tended to focus on ethical concerns including obtaining informed consent and avoiding undue inducement to participate in research rather than ensuring that study participants directly benefit from successful trials.ConclusionsResearch on REB members’ attitudes toward what benefits are owed to study participants and community members is needed in other countries in order to determine how context affects these attitudes. (shrink)

This article seeks to advance ethical dialogue on choosing standards of prevention in clinical trials testing improved biomedical prevention methods for HIV. The stakes in this area of research are high, given the continued high rates of infection in many countries and the budget limitations that have constrained efforts to expand treatment for all who are currently HIV-infected. New prevention methods are still needed; at the same time, some existing prevention and treatment interventions have been proven effective but are (...) not yet widely available in the countries where they most urgently needed. The ethical tensions in this field of clinical research are well known and have been the subject of extensive debate. There is no single clinical trial design that can optimize all the ethically important goals and commitments involved in research. Several recent articles have described the current ethical difficulties in designing HIV prevention trials, especially in resource limited settings; however, there is no consensus on how to handle clinical trial design decisions, and existing international ethical guidelines offer conflicting advice. This article acknowledges these deep ethical dilemmas and moves beyond a simple descriptive approach to advance an organized method for considering what clinical trial designs will be ethically acceptable for HIV prevention trials, balancing the relevant criteria and providing justification for specific design decisions. (shrink)

Despite their clearly demonstrated safety and effectiveness, approved vaccines against COVID-19 are commonly mistrusted. Nations should find and implement effective ways to boost vaccine confidence. But the implications for ethical vaccine development are less straightforward than some have assumed. Opponents of COVID-19 vaccine challenge trials, in particular, made speculative or empirically implausible warnings on this matter, some of which, if applied consistently, would have ruled out most COVID-19 vaccine trials and many non-pharmaceutical responses.

Objectives: To review the performance of research ethics committees in Spain in assessing multicentre clinical trial drug protocols, and to evaluate if they would comply with the requirements of the new EU Directive to be implemented by May 2004.Design and setting: Prospective study of applications of MCT submitted to RECs.Main measurements: Protocol related features and evaluation process dynamics.Results: 187 applications to be performed in 114 centres, were reviewed by 62 RECs. RECs had a median number of 14 members, (...) of which three were lay members. All applications were approved except four which were however approved by the other RECs involved. The median times from submission to approval and from submission to reception at the sponsor’s offices were 48 and 62 days, respectively. In 55% of all applications approved, 41 RECs raised 307 queries, 40% of these were protocol related issues, and 38% related to the patients’ information sheets. RECs charging an evaluation fee in advance and applications with no queries raised were statistically significantly associated with shorter evaluation times. However, there is a gap of at least 1.5 weeks between the date of the meeting and the reception of the approval letter in the sponsor’s office.Conclusions: Evaluating MCT protocols by RECs is a time consuming process. Needing 1.5 weeks for communicating the decision taken by RECs to the sponsor suggests serious administrative shortcomings within most RECs. By significantly reducing the time for communication of their decisions, the majority of RECs would comply with the Directive requirement of a maximum 60 day period for the assessment of MCT. (shrink)

Mood disorders, including major depressive disorder and bipolar disorder, are highly prevalent, frequently disabling, and sometimes deadly. Additional research and more effective medications are desperately needed, but clinical trials research in mood disorders is fraught with ethical issues. Although many authors have discussed these issues, most do so from a theoretical viewpoint. This manuscript uses available empirical data to inform a discussion of the primary ethical issues raised in mood disorders research. These include issues of consent and (...) decision-making capacity, including patients’ motivations for participating in research. We also address drug withdrawals, placebo controls, and the overall safety of research. Finally, we examine the extant literature for studies discussing potential indirect benefits of clinical trials research to participants. Taken together, the evidence suggests that clinical trials research incorporating drug withdrawals and placebo controls can be conducted safely and ethically, even in patients with severe or treatment-resistant mood disorders. In fact, given the dearth of effective treatment options for this population, it is our opinion that a moral imperative exists to extend the offer of research participation to severely ill or treatment-resistant groups. (shrink)

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)

The protection of human research subjects in clinical studies is regulated by international guidelines and national laws. Research Ethics Committees play an important role here, as they review the documentation for clinical studies under consideration of ethical aspects. This documentation includes an exclusion or wash-out period which designates when study subjects may not have participated in another study or be allowed to take part in a future one within a specified time period. However not all research subjects (...) comply with their applicable exclusion period. This prohibited multi-participation in clinical studies is known as ‘research subject tourism,’ ‘clinical study overlapping’, or ‘guinea-pigging’. This practice brings with it additional risks for the research subject and the integrity of the research being conducted. No comprehensive data are available to demonstrate exactly how many research subjects participate in overlapping multiple studies. However, the number of them who ‘travel’ from one study to another seems to be significant. Preventing this practice is a matter of concern for ethics committees, but the responsibility for protecting research subjects in this respect apart from approving the ethics of a wash-out period and recruiting from a specific pool or database of patients is solely that of the investigating physician. But how can the investigating physician be certain that a research subject complies with their exclusion period? An international data bank for research subjects who have participated, or are participating, in clinical studies, is a measure that would serve to prevent prohibited multi-participation in clinical studies and thereby protect the research subject, the investigating physician and their institution. VIP Check, International, which was founded by the author in 1990, is an example of such a data bank. This article examines the existence of prohibited multi-participation in clinical studies, the additional risk this practice of itself poses to the research subjects and the integrity of clinical studies, and how this practice might best be reduce or even eliminated through use of an international data bank of research subjects such as that of VIP Check. (shrink)

The ethical controversies raised by an industry-sponsored placebo-controlled trial of Risperidone for mania, conducted across eight sites in India, provide opportunities for dialogue, reflection and interdisciplinary consensus building on the processes and validity of the methods of evaluating the efficacy of interventions in health care. This commentary contextualises the debate in considerations of the evolution of morality and double standards. It is suggested that a productive interpretation of this unfolding drama should appreciate the folly of dissociating ethical standards in (...) routine health care from those used in health research, the culturally and economically grounded preferences in research priority setting, and the choice of ethical principles underlying participation in, and conduct of, clinical research. A broader discussion of ethical problems in clinical trials which includes questions about the evidence that informs ethical opinion is required to prevent harm to participants and subsequent recipients of health care and to restore confidence in the methods and the results of research in health care. (shrink)

We simulate trial data to test speculative claims about research methods, such as the impact of publication bias.

Over the past decade, the management of clinical trials of pharmaceuticals has become a veritable industry, as evidenced by the emergence and proliferation of contract research organizations (CROs) that co‐ordinate and monitor trials. This article focuses on work performed by one CRO involved in the introduction of new software, modelled on industrial production processes, into clinical trial practices. It investigates how this new management technique relates to the work performed in the clinic to ensure that trial participants (...) comply with the protocol. Using an analytical distinction between ‘classical’ management work and invisible work, the article contextualizes the meaning of compliance in the clinic and suggests that the work involved in producing compliance should be taken into consideration by those concerned with validity of trials, as clinical trials are put under private industrial management. The article builds on participant observation at a Swedish university hospital and interviews the nurses, dieticians, doctors and a software engineer, all part of a team involved in pharmaceutical drug trials on a potential obesity drug. (shrink)

This paper focuses on invasive therapeutic procedures, defined as procedures requiring the introduction of hands, instruments, or devices into the body via incisions or punctures of the skin or mucous membranes performed with the intent of changing the natural history of a human disease or condition for the better. Ethical and methodological concerns have been expressed about studies designed to evaluate the effects of invasive therapeutic procedures. Can such studies meet the same standards demanded of those, for example, evaluating pharmaceutical (...) agents? This paper describes a research project aimed at examining the interplay and sometimes apparent conflict between ethical standards for human research and standards for methodological rigor in trials of invasive procedures. The paper discusses how the authors plan to develop a set of consensus standards that, if met, would result in substantial and much-needed improvements in the methodological and ethical quality of such trials. (shrink)

As the_number of clinical trials continues to grow, there is an increasing need for education and training in the field. The clinical research climate is less forgiving of errors and oversights and therefore requires more knowledge of regulations and requirements. This brand new edition details new laws and regulations in protecting children participating in clinical trials and how a new focus on privacy of individual health information in the United States has changed how medical records are handled. Includes a (...) manual for investigators, research nurses and study coordinators with minimal experience or who are new to clinical research An easy-to-read and open text design using ‘sidebars’ of examples and information boxes related to the main text Includes a list of Frequently Asked Questions and Glossary Duke Clinical Research Institute is the world’s largest academic clinical research organisation and is well known and respected within the clinical research community. (shrink)

Intervention studies with developmental samples are difficult to implement, in particular when targeting demographically diverse communities. Online studies have the potential to examine the efficacy of highly scalable interventions aimed at enhancing development, and to address some of the barriers faced by underrepresented communities for participating in developmental research. During the COVID-19 pandemic, we executed a fully remote randomized controlled trial language intervention with third and fourth grade students from diverse backgrounds across the United States. Using this as (...) a case study, we discuss both challenges and solutions to conducting an intensive online intervention through the various phases of the study, including recruitment, data collection, and fidelity of intervention implementation. We provide comprehensive suggestions and takeaways, and conclude by summarizing some important tradeoffs for researchers interested in carrying out such studies. (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)

Controversy persists over the ethics of compensating research participants and providing posttrial benefits to communities in developing countries. Little is known about residents' views on these subjects. In this study, interviews about compensation and posttrial benefits from a hypothetical HIV vaccine trial were conducted in Uganda’s Rakai District. Most respondents said researchers owed the community posttrial benefits and research compensation, but opinions differed as to what these should be. Debates about posttrial benefits and compensation rarely include residents' (...) views like these, but future ones should. (shrink)

There is a gap in evidence regarding how research trial closure processes are managed to ensure continuity of HIV care for HIV positive participants following trial closure within low income settin...

Regulators rely on clinical trials for drug approval and labeling decisions. Health systems and clinicians rely on the evidence from trials to determine treatment, and patients rely on it to decide which courses of care to undertake. Many of these stakeholders presume that the careful review of individual studies is enough to address the ethical and scientific questions that arise in clinical trials. In what follows, however, we demonstrate that explicit consideration of trial portfolios—series of trials that are interrelated (...) by a common set of objectives—is crucial. the ethical acceptability and evidentiary probity of individual trials can change depending on the characteristics of the portfolios in which they are embedded. Second, how trial portfolios are composed, how well they are coordinated, and how efficiently they use information determines the balance of risks and benefits they present as well as their different prospects for generating socially valuable information; these three factors also raise distinct questions of justice. (shrink)

To reduce the global burden of the COVID-19 pandemic, there is an urgent need to develop a safe vaccine. Vaccine development usually takes many years as it goes through several different phases. To hasten COVID-19 vaccine development, it has been suggested that the final stage could be replaced with a human challenge trial (HCT). Volunteers would be intentionally infected with SARS-CoV-2 to see how the vaccine candidate works. To intentionally infect a healthy human being with a potentially deadly virus (...) is contrary to the highest ethical standards in medical research. This article highlights the benefits and risks of COVID-19 HCTs and summarises what research ethics committees (RECs) need to consider during the ethical assessment of such trials including risk reduction, strict containment measures, specific informed consent measures and avoiding high monetary inducements. (shrink)

The West African Ebola epidemic has set in motion a collective endeavour to conduct accelerated clinical trials, testing unproven but potentially lifesaving interventions in the course of a major public health crisis. This unprecedented effort was supported by the recommendations of an ad hoc ethics panel convened in August 2014 by the WHO. By considering why and on what conditions the exceptional circumstances of the Ebola epidemic justified the use of unproven interventions, the panel's recommendations have challenged conventional thinking about (...) therapeutic development and clinical research ethics. At the same time, unanswered ethical questions have emerged, in particular: the specification of exceptional circumstances, the specification of unproven interventions, the goals of interventional research in terms of individual versus collective interests, the place of adaptive trial designs and the exact meaning of compassionate use with unapproved interventions. Examination of these questions, in parallel with empirical data from research sites, will help build pragmatic foundations for disaster research ethics. Furthermore, the Ebola clinical trials signal an evolution in the current paradigms of therapeutic research, beyond the case of epidemic emergencies. (shrink)

Though antiretroviral therapy is the standard of care for people living with HIV, its treatment limitations, burdens, stigma and costs lead to continued interest in HIV cure research. Early-phase cure trials, particularly those that include analytic treatment interruption, involve uncertain and potentially high risk, with minimal chance of clinical benefit. Some question whether such trials should be offered, given the risk/benefit imbalance, and whether those who choose to participate are acting rationally. We address these questions through a longitudinal decision-making (...) study nested in a Thai acute HIV research cohort. In-depth interviews revealed central themes about decisions to join. Participants felt they possessed an important identity as members of the acute cohort, viewing their bodies as uniquely suited to both testing and potentially benefiting from HIV cure approaches. While acknowledging risks of ATI, most perceived they were given an opportunity to interrupt treatment, to test their own bodies and increase normalcy in a safe, highly monitored circumstance. They were motivated by potential benefits to themselves, the investigators and larger acute cohort, and others with HIV. They believed their own trial experiences and being able to give back to the community were sufficient to offset participation risks. These decisions were driven by the specific circumstances experienced by our participants. Judging risk/benefit ratios without appreciating these lived experiences can lead to false determinations of irrational decision- making. While this does not minimise vital oversight considerations about risk reduction and protection from harm, it argues for inclusion of a more participant-centered approach. (shrink)

While an ethical obligation to report findings of clinical research to trial participants is increasingly recognised, the academic debate is often vague about what kinds of data should be fed back and how such a process should be organised. In this article, we present a classification of different actors, processes and data involved in the feedback of research results pertaining to an individual. In a second step, we reflect on circumstances requiring further ethical consideration. In regard to (...) a concrete research setting—the one of clinico-genomic research—we discuss what kinds of difficulties have to be faced when returning individual research results to trial participants. In a last step, we elaborate on a stepwise model to trigger the individual feedback process. Hence, this paper gives guidance on how to feedback individual research results in a specific research setting and responds at the same time to new challenges in the debate on the duty to return individual research findings. (shrink)

In 2004, the first ever multi‐sited clinical trials studied the prospect of HIV biomedical prevention (referred to as pre‐exposure prophylaxis—‘PrEP’). The trials were implemented at several international sites, but many officially closed down before they completed. At most sites, both scientists and community AIDS advocates raised concerns over the ethics and scientific rationales of the trial. Focusing on the Nigerian trial site, we detail the controversy that emerged among mostly Nigerian research scientists who scrutinized the research (...) design and protocol. While some of the disputes, especially those pertaining to community engagement mechanisms, were ultimately resolved in international fora and implemented in later PrEP trials, concerns over science rationales and assumptions were never addressed. We argue that scientific rationales should be treated as ethical concerns and suggest that such concerns should be deliberated at host sites before the trial protocol is finalized. (shrink)

The ethical value—and to some scholars, necessity—of providing trial patients with post-trial access (PTA) to an investigational drug has been subject to significant attention in the field of research ethics. Although no consensus has emerged, it seems clear that, in some trial contexts, various factors make PTA particularly appropriate. We outline the atypical aspects of psychedelic clinical trials that support the case for introducing the provision of PTA within research in this field, including the broader (...) legal status of psychedelics, the nature of the researcher-therapist/participant relationship, and the extended time-frame of the full therapeutic process. As is increasingly understood, the efficacy of psychedelic-assisted psychotherapy is driven as much by extrapharmacological elements and the cultural therapeutic container as by the drug itself. As such, we also advocate for a refocusing of attention from post-trial access to a broader concept encompassing other elements of post-trial care. We provide an overview of some of the potential post-trial care provisions that may be appropriate in psychedelic clinical trials. Although the World Medical Association’s Declaration of Helsinki calls on researchers, sponsors, and governments to make provisions for post-trial access, such provision may feel impracticable or out-of-reach within psychedelic trials that are already constrained by a high resource demand and significant bureaucratic burden. We show how conceiving of post-trial provision as an integral site of the research process, and an appropriate destination for research funding, will serve to develop the infrastructure necessary for the post-legalisation psychedelic medicine ecosystem. (shrink)

Visual cortical prostheses (VCPs) have the potential to provide artificial vision for visually impaired persons. However, the nature and utility of this form of vision is not yet fully understood. Participants in the early feasibility trial for the Orion VCP were interviewed to gain insight into their experiences using artificial vision, their motivations for participation, as well as their expectations and assessments of risks and benefits. Analyzed using principles of grounded theory and an interpretive description approach, these interviews yielded (...) six themes, including: the irreducibility of benefit to device functionality, mixed expectations for short-term device functionality and long-term technological advancement of visual prostheses, and a broad range of risks, concerns, and fears related to trial participation. We argue that these narratives motivate a nuanced set of ethical considerations related to the complex relationship between functionality and benefit, the intersection of user experience with disability justice, and the import of expectations and indirect risks on consent. (shrink)

Over recent years, considerable attention has been paid to the National Health Service research governance and ethics approvals process in the UK. New regulations mean that approval from the Medicines and Healthcare Products Regulatory Agency is now also needed for conducting all clinical trials. Practical experience of gaining MHRA and sponsorship approval has yet to be described and critically explored in the literature. Our experience, from start to finish, of applying for these four approvals for a multicentre randomised controlled (...) trial of two licensed drugs for opiate detoxification in the prison setting is described here. In addition, the implications of the approvals process for research projects, particularly clinical trials, in terms of time and funding, and also indirect implications for NHS patients are discussed. Inconsistencies are discussed and suggestions that could improve and streamline the overall process are made. The current approvals process could now be hindering non-commercial clinical trials, leading to a loss of important evidence-based medical information. (shrink)

Between 1993 and 2002, 39 clinical trial staff were investigated for scientific misconduct by the Office of Research Integrity (ORI). Analysis of ORI case records reveals practices regarding workload, training and supervision that enable misconduct. Considering the potential effects on human subjects protection, quality and reliability of data, and the trustworthiness of the clinical research enterprise, regulations or guidance on use of clinical trial staff ought to be available. Current ORI regulations do not hold investigators or (...) institutions responsible for supervision and training of clinical trial staff. Given the important issues at stake, the definition of research misconduct should encompass the intentional or negligent mismanagement of scientific projects. Individual institutions and professional associations not only can but should adopt stricter standards of conduct than those reflected in federal regulations. (shrink)