The Ethics of Innovation: Ethical Decision-Making and Review for Field Studies and Projects Targeting Dogs and Cats

To date, independent ethical oversight of many companion animal welfare initiatives has been limited and, in some instances, inadequate. Beyond a blurred line between “innovation” and “research,” the nature of the work conducted in animal welfare projects is often poorly aligned with established institutional ethical review structures, which are designed for research involving humans or research involving animals and are also focused on industry and academic institutions. This commentary details the struggle of one United States-based nonprofit organization to find ethical guidelines and support for conducting non-traditional field-based animal welfare studies, and subsequent experience establishing an Ethical Review Board to evaluate organizational initiatives. The commentary discusses member selection, materials and processes, and lessons and learnings from the creation and use of an Ethical Review Board. Sharing content of the ethical review process, as well as challenges and learnings from it, is intended to support other organizations and individuals seeking to ensure that innovation for animal welfare consistently meets high ethical standards.

Adapting the ethical review process for COVID-19 research: reviewers’ perspectives from Pakistan

Background: Research ethics committees (RECs) globally have adapted their responses to provide timely reviews of research proposals in the wake of the COVID-19 pandemic. The REC of the National Bioethics Committee (NBC) of Pakistan has followed suit. Aims: To explore perceptions of NBC-REC reviewers who reviewed COVID-19 research proposals while describing the newly instituted Rapid Turnaround Review (RTR) system. Methods: This cross-sectional study used 3 methods of data collection: a demographic questionnaire filled in by permanent members and co-opted reviewers; qualitative in-depth interviews conducted with both groups; and document review related to COVID-19 research proposals. Results: Eight permanent members and 3 co-opted members participated. Under the RTR system, the time for review was established as 72 hours after receipt of the proposal. The Committee reviewed 55 projects over 10 months. Participants described numerous strengths of the new system, including introduction of online discussions via Zoom as well as presence of co-opted members leading to learning opportunities, particularly for junior members. The RTR system also allowed NBC-REC to gain recognition it had not enjoyed previously. Challenges identified by respondents included initial difficulty in initiating the system and tighter deadlines that may have compromised review quality. Poor scientific quality of proposals, compounded by external pressures to provide rapid approval, added to reviewers’ frustrations. While fruitful, the RTR system was considered unsustainable beyond a public health emergency. Conclusion: Adaptation of ethical review processes is essential in emergencies, however, existing guidelines have to be modified to suit contextual needs.

What are the most common reasons for return of ethics submissions? An audit of an Australian health service ethics committee

One of the key criticisms of the ethical review process is the time taken to decision, and associated resource use. A key source of delay is that most submissions are required to respond to at least one request for further information or clarification from the Human Research Ethics Committee (HREC). This study audited the request letters of a single Australian public health HREC using content analysis. Twenty-four submissions were analysed, including 355 individual request elements. Most submissions received a single request letter. There was a mean number of 14.2 (SD = 5.5) elements per letter for the first request and a mean of 2.1 (SD = 1.2) for subsequent requests. Administrative errors were the most common source of request for further information, occurring in all submissions. The second most common theme was the content of the Participant Information and Consent Form, occurring in 79% of submissions. Other common themes, present in over 50% of submissions, concerned: data collection and study procedures; general ethical considerations; recruitment and consent; site, setting or patient pool; research design and methodology; and data management and security. In terms of the general purpose of the HREC comments, 44% were direct corrections or specific requests for changes, 42% were asking for more information or clarification of existing information, and 14% were the HREC expressing concerns about an element of the study, without directly suggesting a change. Overall, the study provides some evidence to show that the quality of the submission (ensuring correct attachments, up to date documents, clear information etc.) could account for a significant proportion of the burden and delay associated with ethical review.

Reviewing the Review: A Pilot Study of the Ethical Review Process of Animal Research in Sweden

The use of animals in research entails a range of societal and ethical issues, and there is widespread consensus that animals are to be kept safe from unnecessary suffering. Therefore, harm done to animals in the name of research has to be carefully regulated and undergo ethical review for approval. Since 2013, this has been enforced within the European Union through Directive 2010/63/EU on the protection of animals used for scientific purposes. However, critics argue that the directive and its implementation by member states do not properly consider all aspects of animal welfare, which risks causing unnecessary animal suffering and decreased public trust in the system. In this pilot study, the ethical review process in Sweden was investigated to determine whether or not the system is in fact flawed, and if so, what may be the underlying cause of this. Through in-depth analysis of 18 applications and decisions of ethical reviews, we found that there are recurring problems within the ethical review process in Sweden. Discrepancies between demands set by legislation and the structure of the application form lead to submitted information being incomplete by design. In turn, this prevents the Animal Ethics Committees from being able to fulfill their task of performing a harm–benefit analysis and ensuring Replacement, Reduction, and Refinement (the 3Rs). Results further showed that a significant number of applications failed to meet legal requirements regarding content. Similarly, no Animal Ethics Committee decision contained any account of evaluation of the 3Rs and a majority failed to include harm–benefit analysis as required by law. Hence, the welfare may be at risk, as well as the fulfilling of the legal requirement of only approving “necessary suffering”. We argue that the results show an unacceptably low level of compliance in the investigated applications with the legal requirement of performing both a harm–benefit analysis and applying the 3Rs within the decision-making process, and that by implication, public insight through transparency is not achieved in these cases. In order to improve the ethical review, the process needs to be restructured, and the legal demands put on both the applicants and the Animal Ethics Committees as such need to be made clear. We further propose a number of improvements, including a revision of the application form. We also encourage future research to further investigate and address issues unearthed by this pilot study.

The scientific basis of rational prescribing. A guide to precision clinical pharmacology based on the WHO 6-step method

Background and methods This opinion paper expanded on the WHO “six-step approach to optimal pharmacotherapy,” by detailed exploration of the underlying pharmacological and pathophysiological principles. This exercise led to the identification of a large number of domains of research that should be addressed to make clinical pharmacology progress toward “precision clinical pharmacology,” as a prerequisite for precision medicine. Result In order to improve clinical efficacy and safety in patient groups (to guide drug development) as well as in individuals (to guide therapeutic options and optimize clinical outcome), developments in clinical pharmacology should at least tackle the following: (1) molecular diagnostic assays to guide drug design and development and allow physicians to identify the optimal targets for therapy in the individual patient in a quick and precise manner (to guide selection of the right drug for the right patient); (2) the setting up and validation of biomarkers of target engagement and modification as predictors of clinical efficacy and safety; (3) integration of physiological PK/PD models and intermediate markers of pharmacological effects with the natural evolution of the disease to predict the drug dose that most effectively improves clinical outcome in patient groups and individuals, making use of advanced modeling technologies (building on deterministic models, machine-learning, and deep learning algorithms); (4) methodology to validate human or humanized in vitro, ex vivo, and in vivo models for their ability to predict clinical outcome with investigational therapies, including nucleic acids or recombinant genes together with vectors (including viruses or nanoparticles), cell therapy, or therapeutic vaccines; (5) methodological complements to the gold-standard, large Phase 3 randomized clinical trial to provide clinically relevant and reliable data on the efficacy and safety of all treatment options at the population level (pragmatic clinical trials), as well as in small groups of patients (as low as n = 1); (6) regulatory science, so as to optimize the ethical review process, documentation, and monitoring of clinical trials, improve efficiency, and reduce costs of clinical drug development; (7) interventions to effectively improve patient compliance and to rationalize polypharmacy for the reduction of adverse effects and the enhancement of therapeutic interactions; and (8) appraisal of the ecological and societal impact of drug use to safeguard against environmental hazards (following the “One Health” concept) and to reduce drug resistance. Discussion and conclusion As can be seen, precision clinical pharmacology aims at being highly translational, which will require very large panels of complementary skills. Interdisciplinary collaborations, including non-clinical pharmacologists, will be key to achieve such an ambitious program.

Ethical challenges in researching and telling the stories of recently deceased people

This paper explores ethical challenges encountered when conducting research about, and telling, the stories of individuals who had died before the research began. Cases were explored where individuals who lived alone had died alone at home and where their bodies had been undiscovered for an extended period. The ethical review process had not had anything significant to say about the deceased ‘participants’. As social researchers we considered whether it was ethical to involve deceased people in research when they had no opportunity to decline, and we were concerned about how to report such research. The idea that the dead can be harmed did not help our decision-making processes, but the notion of the dead having limited human rights conferred upon them was useful and aided us in clarifying how to conduct our research and disseminate our findings.

Conflicting interests: Critiquing the place of “institutional reputation” in research ethics reviews

Going through Research Ethics Boards (REB) and being held accountable to the highest ethical standards to conduct research with human subjects is commonplace. The goal of such a process helps ensure the selection and achievements not only of morally acceptable ends, but also of acceptable means to those ends when conducting research. Ultimately, REBs must pass judgment about the acceptability of harms and benefi ts to participants as they relate to research processes and outcomes. In this paper, we explore the implication of integrating “institutional reputation” as a category of analysis in the ethical review process. Informed by a recent Research Ethics Board (REB) review, we seek to engage with the readership in a constructive refl ection on the concept of institutional reputation as a source of confl icting interests in research ethics review process.

Challenges in obtaining research ethics and governance approvals for an Australian national intersector, multisite audit study

ObjectiveThe aim of this study was to describe timelines and challenges encountered in obtaining ethics and governance approvals for an Australian multicentre audit study involving 100 public (n=22) and private (n=78) sites from three health sectors and all eight Australian states and territories. MethodsWe determined and compared the processes, documentation and number of business days required to prepare applications and obtain research ethics and governance approvals. ResultsIn total, the full ethics and governance process (calculated from the date the first application was started to the date the final approval was granted) took 203 business days (79% of the study timeline). Standard risk ethics applications (n=4) took a median of 17 business days (range 3–35 days) to prepare and 32 business days (range 17–67 days) to be approved; expedited ethics applications (n=4) took a median of 5 business days (range 1–20 days) to prepare and 10 business days (range 1–44 days) to be approved. Governance approvals (n=23) took a median of 27 business days (range 4–63 days) to prepare and 20 business days (range 4–61 days) to be approved. Challenges included the lack of a nationwide single-site ethical review process, the extensive time required to duplicate content across applications, variability in application requirements and submission systems, and contract negotiations. ConclusionFurther improvements are needed to reduce duplication and increase the efficiency of Australian ethics and governance review processes. What is known about the topic?The process for obtaining ethics approval for multicentre research has been streamlined through the introduction of single-site ethics review. However, the process of gaining ethics and governance approvals for national multicentre research continues to be time-consuming, resource-intensive and duplicative. What does this paper add?This is the first study to examine the challenges of obtaining ethics and governance approvals for a non-interventional multicentre study involving three health sectors (hospital, aged care, general practice), both private and public services and all eight Australian jurisdictions. Previous examinations of Australian multicentre studies have considered only one health sector, focused on the public system and/or were not national in scope. What are the implications for practitioners?Researchers and funders need to be aware of the considerable time, resources and costs involved in gaining research ethics and governance approvals for multicentre studies and include this in budgets and study timelines. Policy makers and administrators of ethics and governance review processes must address barriers to conducting multicentre research in Australia.

Research Ethics Board/Institutional Review Board Variability and Other Ethical Challenges in Multi-Site Research Involving Participants on the Autism Spectrum

Doing research at multiple sites can create ethical challenges for researchers, especially those working with vulnerable populations. During the ethical review process, different research ethics boards can disagree on interpretations of research ethics concepts such as capacity to consent, vulnerability, and autonomy. In this chapter, experience in conducting a multi-year, multicentre study involving studying the communication skills of adults with autism is discussed, and the ethical challenges that arose are addressed, focusing on ethical challenges of recruiting participants from multiple sites and detailing interactions with the various research ethics boards involved. Advice and suggestions are provided for other researchers on how to address some of the challenges in doing multicentre research involving participants from vulnerable populations.

Researchers’ Perspectives on Informed Consent and Ethical Review of Biobank Research in South Africa: A Cross-Sectional Study

There is limited literature on the opinions and perspectives of researchers on the ethical issues in biobank research in South Africa. This study aimed to explore researchers’ perspectives on informed consent and ethical review of biobank research in South Africa. An online survey was conducted among researchers and scientists at Stellenbosch University and the University of Kwazulu-Natal. The majority of researchers opined that broad consent is appropriate for biobank research. However, there was no consensus on the necessity for re-consent. Researchers were also in agreement that issues concerning informed consent and future use of samples require thorough discussions during the ethical review process. Overall, the attitude of researchers on informed consent and ethical review of biobank research was positive and ethically informed.