Independent Ethical Review Research Articles

Fruquintinib plus oxaliplatin combined with S-1 (SOX) as neoadjuvant therapy for locally advanced gastric cancer (GC) or gastro-oesophageal junction adenocarcinoma (GEJ): a multicentre, phase II, single-arm, open-label clinical trial (FRUTINEOGA) protocol

IntroductionCuring locally advanced gastric cancer (GC) or gastro-oesophageal junction adenocarcinoma (GEJ) with surgery alone is challenging. Neoadjuvant chemotherapy (NCT) has become the standard treatment for patients with locally advanced GC/GEJ,...

Evidence from UK Research Ethics Committee members on what makes a good research ethics review, and what can be improved.

The rapid development of vaccines and other innovative medical technologies in response to the COVID-19 pandemic required streamlined and efficient ethics and governance processes. In the UK the Health Research Authority (HRA) oversees and coordinates a number of the relevant research governance processes including the independent ethics review of research projects. The HRA was instrumental in facilitating the rapid review and approval of COVID-19 projects, and following the end of the pandemic, have been keen to integrate new ways of working into the UK Health Departments' Research Ethics Service. In January 2022 the HRA commissioned a public consultation that identified strong public support for alternative ethics review processes. Here we report feedback from 151 current research ethics committee members conducted at three annual training events, where we asked members to critically reflect on their ethics review activities, and to share new ideas or ways of working. The results showed a high regard for good quality discussion among members with diverse experience. Good chairing, organisation, feedback and the opportunity for reflection on ways of working were considered key. Areas for improvement included the consistency of information provided to committees by researchers, and better structuring of discussions by allowing signposting of the key issues that ethics committee members might need to consider.

Reporting Ethics Approval in Articles on Criminality. An Audit of Adherence to Swedish Legislation.

According to the Swedish Ethics Review Act, research involving personal data on crimes should undergo independent ethics review. To explore the reporting of ethics approval, we extracted information from articles with Swedish personal data on crimes published in 2013-2021. Of the identified 298 articles, 92 (31%) failed to report ethics approval. Failures were particularly common in articles with a qualitative design, single or few authors and when there was a social science focus. Failures varied markedly between universities. We conclude that failures to report compulsory ethics approval are common in articles involving personal data on crime and that these failures vary markedly with the research setting. Several indicators of poor adherence to the Ethics Review Act have been identified.

The Problematic Path of Fundamental Rights in the European Union: Continuing the Journey on the Regulation on Clinical Trials

Abstract In this paper I have tried to identify and analyse some critical points that Regulation No. 526 of 2014 on clinical trials still presents. I have seen that in the face of a long gestation, the criticisms that have been made of the regulation have been various. If we think of the first criticism identified in the regulation, the so-called law shopping, we must affirm that the subject of experimentation is a very delicate matter since it has a direct and frontal impact on the guarantee of the right to health of European citizens and the use of law shopping does not provide adequate guarantees for the protection of the rights of those participating in a trial. Secondly, the marginalisation of the Ethics Committees whose role is decided at the level of the single national legal system does not ensure that components of independence and representation of the point of view of patients and their associations are guaranteed. This aspect is undoubtedly an important criticism of the regulation as the importance of the role played by the Ethics Committees in the assessment procedures for authorisation applications is not taken into fully consideration. Also, in this case, the economic need for simplification and speed of the evaluation procedure seem to prevail over the need to ensure a thorough and independent scientific and ethical review of authorisation applications. We believe that in the case of Regulation No. 536 of 2014, greater awareness of risks and opportunities will be achieved only by verifying in practice the possible distortions to which this legislation can lead. Only through serious monitoring and reporting of the effects of the regulation on the protection of patients’ rights will it be possible to identify and indicate targeted changes to the rules contained therein and, of course, to adopt the consequent measures to reduce possible damages. In this sense, also on the basis of a possible and foreseeable future phase of gestation of Regulation No. 534 of 2014, we believe that in the European area, in the field of clinical trials but not exclusively, that trend, developed above all in the French context, of the “experimentation of laws” should be further cultivated.

Reporting ethical approval in health and social science articles: an audit of adherence to GDPR and national legislation

BackgroundPrevious studies have indicated that failure to report ethical approval is common in health science articles. In social sciences, the occurrence is unknown. The Swedish Ethics Review Act requests that sensitive personal data, in accordance with the EU General Data Protection Regulation (GDPR), should undergo independent ethical review, irrespective of academic discipline. We have explored the adherence to this regulation.MethodsUsing the Web of Science databases, we reviewed 600 consecutive articles from three domains (health sciences with and without somatic focus and social sciences) based on identifiable personal data published in 2020.ResultsInformation on ethical review was lacking in 12 of 200 health science articles with somatic focus (6%), 21 of 200 health science articles with non-somatic focus (11%), and in 54 of 200 social science articles (27%; p < 0.001 vs. both groups of health science articles). Failure to report on ethical approval was more common in (a) observational than in interventional studies (p < 0.01), (b) articles with only 1–2 authors (p < 0.001) and (c) health science articles from universities without a medical school (p < 0.001). There was no significant association between journal impact factor and failure to report ethical approval.ConclusionsWe conclude that reporting of research ethics approval is reasonably good, but not strict, in health science articles. Failure to report ethical approval is about three times more frequent in social sciences compared to health sciences. Improved adherence seems needed particularly in observational studies, in articles with few authors and in social science research.

Understanding Constraints and Enablers of Turnaround Time for Ethics Review: The Case of Institutional Review Boards in Tanzania.

Background. Independent ethics review of research is required prior to the implementation of all health research involving human participants. However, ethics review processes are challenged by protracted turnaround times, which may negatively impact the implementation of socially valuable research. Previous research has documented delays in ethics review in developed and developing countries. This study aimed to determine the extent of variability in turnaround times for protocol review among different institutional review boards (IRBs) within Tanzania. Methods. This descriptive cross-sectional study employed a mixed-method approach, with qualitative and quantitative components. Seven IRBs were purposively sampled from the 15 accredited IRBs operational in Tanzania during the study period, April 2017-April 2018. Quantitative data were analysed using STATA software and qualitative data were analysed thematically. Results. The median time for review across all IRBs was 32 days, with a range of 1-396 days. Qualitative results identified five key themes related to turnaround time from interviews with participants. These included: (1) procedures for receiving and distribution of protocols, (2) number of reviewers assigned to protocols, (3) duration of reviewing protocols, (4) reasons for delayed feedback, and (5) training of research ethics committee members. Conclusion. The study showed that the median days for ethical approval in Tanzania was 32 days. We observed from this study that electronic submission systems facilitated faster turnaround times. Failure to adhere to the submission checklists and guidelines was a major obstacle to the turnaround time.

High-Flow Nasal Cannula Therapy for the Management of Hypoxaemic Respiratory Failure in Patients with SARS-CoV-2 Pneumonia: An Observational Cohort Study

Background: The utility of high-flow nasal cannula (HFNC) to reduce the need for invasive mechanical ventilation (IMV) in patients with hypoxaemic respiratory failure due to COVID-19 is poorly understood.Methods: We designed a prospective observational study of a large cohort of patients at the Temporary COVID-19 Hospital (TCH) in Mexico City who had COVID-19-related hypoxaemic respiratory failure. The primary outcome was the success rate of HFNC to prevent the progression to IMV. We also evaluated the risk factors associated with HFNC success or failure.Findings: This study included 378 patients who met the criteria for hypoxaemic respiratory failure and for HFNC use. This study showed that HFNC effectively prevented IMV in 71.4% of patients (n=270; 95% CI: 66·6–75·8). Factors that were significantly different between patients who were only treated with HFNC and those who progressed to IMV included age, the presence of hypertension, and the Charlson comorbidity index. Predictors of HFNC failure included the CALL score at admission (adjusted hazard ratio [HR]: 1·27; 95% CI, 1·09–1·47; pInterpretation: The present study showed that treating patients with HFNC at admission was effective and prevented the worsening of symptoms in some patients with COVID-19.Funding: Carlos Slim FoundationDeclaration of Interests: APC, ESL, MGN, RRVV, HHB, LMJ, MAA, LERG, LMC, RVB, RVAW, BSO, and MLRC are fulltime employees of the Temporary COVID-19 Hospital. HGR, JLG, LAMJ, and RTC are full-time employees of the Carlos Slim Foundation in Mexico. The authors declare no other conflicts of interest or outside funding from any other organizations.Ethics Approval Statement: The study protocol was approved by an independent Investigation Commission and Ethical Review Board. This study was submitted to the ethics committee of the National Autonomous University of Mexico (FM/DI/099/2020).

Integrating public health programs and research after the malaria vaccine implementation program (MVIP): Recommendations for next steps

BackgroundIn February 2020, international controversy arose about the ethical acceptability of the WHO Malaria Vaccine Implementation Program (MVIP). Whereas some have argued that this program must be seen as research that is not in line with international ethical standards, notably regarding informed consent and local ethical review, some WHO representatives consider the MVIP as a public health implementation program that need not adhere to these standards. MethodsWe performed a case analysis in light of the 2016 CIOMS International Ethical Guidelines for Health-related Research involving Humans. FindingsWe argue that the MVIP has a substantial research component, and that it is prudent to therefore apply ethical norms for research involving humans, such as the CIOMS guidelines. Accordingly, we agree that the ethical requirements of informed consent and independent ethical review have not been met. In addition, we are concerned that the study might not meet CIOMS’s social value requirement. RecommendationsWe urge WHO to release more details about the process that led to the MVIP program and make the MVIP protocol publicly available. The full protocol should be assessed by the relevant ethics committees, new and already enrolled parents should be informed about the uncertainties under investigation and given a real opportunity to consent or refuse (continued) participation, communities should be engaged, and aspects of MVIP that require alteration in light of ethical review should be altered, if possible. Furthermore, in order to improve good ethical practices, it is necessary to engage in international debate regarding the integration of research and public health programs. Procedurally, vaccine implementation programs that combine both prevention and research should involve the wider international ethics community and ensure participation of the target populations in setting the proper conditions for launching such programs.

Community engagement and ethical global health research

ABSTRACT Community engagement is increasingly recognized as a critical element of medical research, recommended by ethicists, required by research funders and advocated in ethics guidelines. The benefits of community engagement are often stressed in instrumental terms, particularly with regard to promoting recruitment and retention in studies. Less emphasis has been placed on the value of community engagement with regard to ethical good practice, with goals often implied rather than clearly articulated. This article outlines explicitly how community engagement can contribute to ethical global health research by complementing existing established requirements such as informed consent and independent ethics review. The overarching and interlinked areas are (1) respecting individuals, communities and stakeholders; (2) building trust and social relationships; (3) determining appropriate benefits; minimizing risks, burdens and exploitation; (4) supporting the consent process; (5) understanding vulnerabilities and researcher obligations; (6) gaining permissions, approvals and building legitimacy and (7) achieving recruitment and retention targets.

A Therapeutic Machine-Learned Triage Methodology for Moderate to Severe Asthmatics

Background: Current at-home asthma management protocols are crowded with paper guidelines and exploratory health apps that lack rigor and validation at the level of the individual patient. No clear medical consensus has emerged regarding the efficacy of such approaches. We developed a novel digital therapeutic application that uses machine learning predictions for real-time detection of exacerbations and on-demand decision support while obviating the need for burdensome daily symptom entry. Methods: Physician opinion on a statistically and clinically comprehensive set of simulated patient cases was used to train a set of prediction algorithms. The accuracy of the models was assessed by comparison to physician panel consensus in a representative, out-of-sample validation set of 100 vignettes. Algorithms were subsequently deployed in a mobile application and evaluated in a 6 month, pre-post, observational trial of 25 patients with persistent asthma. Outcome data was collected using scored assessments of asthma control (ACT), quality of life (EQ5D5L) and anxiety (AIR). Findings: Algorithm accuracy and safety indicators surpassed all individual pulmonologists in both identifying exacerbations and identifying the consensus triage. The algorithm was also the top performer in sensitivity, specificity, and PPV when predicting a patient's need for emergency care. The observational trial yielded statistically and clinically significant improvement in mean difference scores in asthma control, 4.8 [95\% CI 2.1 - 7.5] (p = 0.004); quality of life, 15.7 [8.0 - 23.3] (p = 0.001); and anxiety, -3.1 [(-5.2) - (-1)] (p = 0.001). Interpretation: A mobile application equipped with a highly accurate machine-learning triage algorithm presents a promising and viable support tool with strong early indications of therapeutic value to patients. A randomized control trial is required to prove causality. Funding: Revon Systems Inc, eThera Technologies, NSF Award No. (FAIN):1820049. Declaration of Interest: We would like to disclose that Anthony N. Gerber is a consultant for eThera Inc and holds stock options. This does not alter our adherence to the Lancet Respiratory Medicine policies on sharing data and materials. Ethical Approval: The study was approved by Quorum Review, an independent Ethics Review Board.

Overcoming a primary barrier to practice-based research: Access to an institutional review board (IRB) for independent ethics review.

Practice-based research is an important means of bridging the gap between the science and practice of psychotherapy. Unfortunately, numerous barriers exist for clinicians who want to conduct research in practice settings. One specific barrier that has received minimal attention in the literature-lack of access to institutional review board (IRB) oversight for independent ethics review-can impede the ability to carry out and disseminate research projects. This article identifies reasons that practice-based researchers may want to seek IRB review even when not required, reviews the pros and cons of a range of strategies that some practice-based researchers have used to try and address lack of access to an IRB, and describes a novel solution for this problem: the creation of the Behavioral Health Research Collective IRB, a nonprofit IRB whose mission is to provide ethical oversight to practice-based researchers. The authors describe their experiences of developing and running the Behavioral Health Research Collective IRB, with the intent of providing a model for other professionals to create similar mechanisms for supporting practice-based research. (PsycINFO Database Record

Impacts of smoke-free public places legislation on inequalities in youth smoking uptake: study protocol for a secondary analysis of UK survey data

IntroductionSmoke-free public places legislation has been introduced in many countries to protect the public from the harmful effects of secondhand smoking. While evaluations of smoke-free policies have demonstrated major public...

The development and improvement of ethical review of multi-center clinical trial

Objective Improve the ethical review models of multi-center clinical trial. Methods Analyze the ethical review models of multi-center clinical trial in China, and summarize advantages and disadvantages of the different methods. Then, clarify the development of ethical review methods of multi-center clinical trial in our hospital. Results Four methods were used to review the multi-center clinical trial in China, including independent ethical review, central institutional ethical review, central review made by committee cooperation, collaborative review. Each method has its advantages and disadvantages. Collaborative review about multi-center clinical trial is adopted now in our hospital. Conclusions Using collaborative review model of multi-center clinical trial, the ethical review could achieve timely and uniformly. Key words: Multi-center clinical trial; Ethical review committee; Subjects; Ethical review

Supplemental Material for Overcoming a Primary Barrier to Practice-Based Research: Access to an Institutional Review Board (IRB) for Independent Ethics Review

Supplemental Material for Overcoming a Primary Barrier to Practice-Based Research: Access to an Institutional Review Board (IRB) for Independent Ethics Review

P-145 - Understanding the hepatocellular carcinoma (HCC) patient landscape: Results of the first global survey of people living with HCC

Introduction: A global survey, the first of its kind, was undertaken to understand the experience of patients living with hepatocellular carcinoma (HCC), and their needs along the patient journey. Methods: A group of patient charities (7) and medical centres (>15) in 13 countries conducted the ‘HCC Patient Voices’ survey. The questionnaire was approved by scientific advisory boards and an independent ethics review board. It contains 32 closed- and open-ended questions on demographics, diagnosis, and treatments, including side effects, quality of life (QoL), treatment access and most-recent treatment, and was available at www.hcc-voices.com in 8 languages from November 2016 through April 2017. Results: We analysed preliminary results for 190 returned surveys (70% from male, 30% from female patients), with a median age of 62 (range, 23-88 years). Time since diagnosis was <1 year (32%), 1–3 years (35%), 4–6 years (15%) or > 6 years (18%). Hepatologists or Gastroenterologists diagnosed most (68%) patients. Just over a quarter of patients received a liver transplant (26%), and 65% were treated with surgery and/or ablation as primary therapy. Later lines of therapy included transarterial chemoembolisation (TACE, 40%), oral chemotherapy (sorafenib, 14%) and selective internal radiation therapy (SIRT, 11%). Two-fifths (41%) of respondents reported using supplementary health insurance during their treatment, but for more than three-quarters (76%) insurance did not cover all treatment options. Three-quarters (74%) said that their treatment was determined based on what was covered by their insurance plan. Only 32% of respondents felt that their information needs were fully met. Medical specialists and nurses were considered the most valuable source of HCC information, more than patient charities and websites. Medical websites also proved valuable for 47% of respondents, whilst 51% said friends and family were a ‘good’ or ‘excellent’ source of information. Initial analysis indicates patients who required additional treatments after surgery, transplant or ablation were more likely to experience side effects and diminished QoL. Although the percentages of those last treated with TACE (11%), SIRT (4%) or oral chemotherapy with sorafenib (6%) were relatively small, useful generalisations about the comparative effects of each can still be made. Those treated systemically with sorafenib were less likely to report improvement in their energy levels, ease of daily activities and QoL than those treated last with SIRT or TACE. Respondents said TACE and SIRT were associated with shorter-lasting, moderate-to-significant abdominal pain (30% and 38%, respectively), fatigue (40% and 38%) and appetite loss (25% and 0%). However, those treated with sorafenib reported experiencing side effects that were more frequent and more persistent, including fatigue (83%), abdominal pain (42%), appetite loss (58%), nausea (50%), diarrhoea (41%) and skin disorders (25%). Conclusion: The vast majority of patients with HCC feel inadequately informed about their disease. A greater proportion of patients who received palliative oral systemic chemotherapy report a negative impact on their QoL, and more frequent and long-lasting side effects than those treated with liver-directed SIRT or TACE. For patients with incurable HCC, better treatment strategies are needed to maintain QoL. This survey was made possible by educational grants from Sirtex.

A Role for Philosophers, Sociologists and Bioethicists in Revising the DSM: A Philosophical Case Conference

The recent publication of the latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was accompanied by heated debate. I argue that part of the reason for these recent controversies is that the process of DSM revision involves making certain value judgments, yet requires a better means for explicitly and expertly addressing these issues. It is important to do so because a) there are certain value-laden questions that science cannot answer but nevertheless need to be addressed in psychiatric classification, and b) the effects of psychiatric classification stretch far and wide. I suggest a means by which the value judgments involved in psychiatric classification can be more systematically and comprehensively examined—by including an independent ethics review panel in the revision process. An ethics review panel could include bioethicists, sociologists, and philosophers of psychiatry who would be in a better position to address these issues.

When clinical care is like research: the need for review and consent.

The prevailing "segregated model" for understanding clinical research sharply separates it from clinical care and subjects it to extensive regulations and guidelines. This approach is based on the fact that clinical research relies on procedures and methods-research biopsies, blinding, randomization, fixed treatment protocols, placebos-that pose risks and burdens to participants in order to collect data that might benefit all patients. Reliance on these methods raises the potential for exploitation and unfairness, and thus points to the need for independent ethical review and more extensive informed consent. In contrast, it is widely assumed that clinical care does not raise these ethical concerns because it is designed to promote the best interests of individual patients. The segregation of clinical research from clinical care has been largely effective at protecting research participants. At the same time, this approach ignores the fact that several aspects of standard clinical care, such as clinician training and scheduling, also pose some risks and burdens to present patients for the benefit of all patients. We argue that recently proposed learning health care systems offer a way to address this concern, and better protect patients, by developing integrated review and consent procedures. Specifically, current approaches base the need for independent ethical review and more extensive informed consent on whether an activity is categorized as clinical research or clinical care. An ethically sounder approach, which could be incorporated into learning health care systems, would be to base the need for independent ethical review and more extensive informed consent on the extent to which an activity poses risks to present patients for the benefit of all patients.

Knowledge and Practice of Research Ethics among Biomedical Researchers in Southern Nigerian Tertiary Institutions

Objective: The knowledge and application of ethical principles to the conduct of human subjects’ research is crucial to the integrity of the research industry. This study sought to assess the knowledge and practice of research ethics among biomedical researchers in research institutions in southern Nigeria. Methods: Four tertiary biomedical research institutions from the three geo-political zones situated in the southern part of Nigeria were selected using a stratified random sampling technique. Research participants were then selected by purposive sampling from these institutions. The knowledge and practice of research ethics among the study participants were assessed with a pre-tested structured questionnaire. Statistical analysis was done with Stata version 10SE. Results: A total of 102 biomedical researchers (66 males and 36 females) with a mean age of 39.8 (SD 7.0) years participated in the study. Forty-five percent knew that ethical review of research is for the protection of research participants from harm though sixty-four percent had attended at least one training seminar in research ethics. About fifteen percent knew of any international ethical guideline. Approximately eighty-five percent agreed that independent ethical review of protocol is important but only forty-eight percent received ethical approval for their research. Conclusion: The knowledge and practice of research ethics is inadequate among Nigerian biomedical researchers. Attendance at ethics seminar did not reflect knowledge and practice of research ethics. The knowledge and practice of research ethics need improvement. The independent review of research protocols must be obligatory.

Facebook study: a little bit unethical but worth it?

Human research involving the use social media raises many of the same issues as medical research. The publication of a paper in June 2014 investigating "emotional contagion" received extensive publicity recently because of the methods used. The approach involved manipulating the "News Feeds" of Facebook users, but the participants were not informed of their involvement in the research and had no opportunity to consent or opt out. Some commentators have argued that although it would have been preferable to obtain informed consent, it was not strictly required because the research was unlikely to cause significant harm and was important. This paper argues that the research was unethical because (i) it should have been overseen by an independent ethics committee or review board and (ii) informed consent could and should have been obtained. Regardless of the importance of any research and irrespective of its likelihood to cause harm, the ethical principles that have evolved since the 1940s should be followed in all instances when experimental research is being carried out on human participants.

Safety of Intravenous Application of Second-Generation Ultrasound Contrast Agent in Children: Prospective Analysis

The goal of the work described here was to assess the safety profile of intravenous second-generation ultrasound contrast agents (UCAs) containing sulfur hexafluoride in pediatric contrast-enhanced ultrasound. Between 2010 and 2013, a total of 167 examinations were performed in 137 children referred by the Oncology Department. Approval by an Independent Ethical Review Board on Scientific Research for the intravenous use of an UCA containing sulfur hexafluoride in children with oncologic diseases was obtained. Consent for UCA administration was acquired from the parents or legal guardians. Severe anaphylactic reaction was observed in 0.6% (n = 1). No other adverse events during or after intravenous administration of contrast were observed in the examined group (no changes in heart rate and rhythm, blood pressure, oxygen saturation or respiratory rate). There were no reports of subjective flushing, nausea, transient headaches or altered taste. Although second-generation ultrasound contrast agents are considered potentially safe, all investigators should be prepared for the development of adverse reactions and have provisions in place for all pediatric intravenous contrast-enhanced ultrasound examinations. More multicenter studies are essential to determination of an accurate UCA safety profile.