Research Ethics Committee Review Research Articles

The Ottawa Statement implementation guidance document for cluster randomized trials in the hemodialysis setting

Research teams are increasingly interested in using cluster randomized trial (CRT) designs to generate practice-guiding evidence for in-center maintenance hemodialysis. However, CRTs raise complex ethical issues. The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials, published in 2012, provides 15 recommendations to address ethical issues arising within 7 domains: justifying the CRT design, research ethics committee review, identifying research participants, obtaining informed consent, gatekeepers, assessing benefits and harms, and protecting vulnerable participants. But applying the Ottawa Statement recommendations to CRTs in the hemodialysis setting is complicated by the unique features of the setting and population. Here, with the help of content experts and patient partners, we co-developed this implementation guidance document to provide research teams, research ethics committees, and other stakeholders with detailed guidance on how to apply the Ottawa Statement recommendations to CRTs in the hemodialysis setting, the result of a 4-year research project. Thus, our work demonstrates how the voices of patients, caregivers, and all stakeholders may be included in the development of research ethics guidance.

Effects of a therapeutic lifestyle modification intervention on cardiometabolic health, sexual functioning and health-related quality of life in perimenopausal Chinese women: protocol for a randomised controlled trial

IntroductionPerimenopause is a critical transitional period in reproductive ageing. A set of physiological and psychological changes can affect perimenopausal women’s quality of life and further threaten their older adult health...

Challenges to the delivery and utilisation of child healthcare services: a qualitative study of the experiences of nurses and caregivers in a rural district in Ghana

BackgroundSub-Saharan Africa has one of the poorest child health outcomes in the world. Children born in this region face significant health challenges that jeopardise their proper growth and development. Even though the utilisation of child healthcare services safeguards the health of children, the challenges encountered by nurses in the delivery of services, and caregivers in the utilisation of these services, especially in rural areas, have contributed to poor child health outcomes in this region.AimThis study explored the experiences of nurses and caregivers in respect of the nursing human resource challenges to the delivery and utilisation of child healthcare services in a rural district in Ghana.MethodsIndividual qualitative interviews were conducted with ten nurses, who rendered child healthcare services; nine caregivers, who regularly utilised the available child healthcare services; and seven caregivers, who were not regular users of these services. These participants were purposively selected for the study. Data were collected using individual semi-structured interview guides and analysed qualitatively using content analysis. Themes and sub-themes were generated during the data analysis. The Ghana Health Service Research Ethics Review Committee and the Nelson Mandela University’s Research Ethics Committee approved the study protocol prior to data collection.ResultsThree main themes emerged from the data analysis. Theme One focused on the shortage of nurses, which affected the quality and availability of child healthcare services. Theme Two focused on inexperienced nurses, who struggled to cope with the demands related to the delivery of child healthcare services. Theme Three focused on the undesirable attitude displayed by nurses, which discouraged caregivers from utilising child healthcare services.ConclusionNurses contribute significantly to the delivery of child healthcare services; hence, the inadequacies amongst nurses, in terms of staff numbers and nursing expertise, affect the quality and availability of child healthcare services. Also, caregivers’ perceptions of the quality of child healthcare services are based on the treatment they receive at the hands of nurses and other healthcare workers. In this respect, the bad attitude of nurses may disincentivise caregivers in terms of their utilisation of these services, as and when needed. There is an urgent need to comprehensively address these challenges to improve child healthcare outcomes in rural areas in Ghana. Relevant authorities should decentralise training workshops for nurses in rural areas to update their skills. Additionally, health facilities should institute proper orientation and mentoring systems to assist newly recruited nurses to acquire the requisite competences for the delivery of quality family-centred care child healthcare services.

A socially interdependent choice framework for social influences in healthcare decision-making: a study protocol

ObjectivesCurrent choice models in healthcare (and beyond) can provide suboptimal predictions of healthcare users’ decisions. One reason for such inaccuracy is that standard microeconomic theory assumes that decisions of healthcare...

Experiences with smoking habits and the need for cessation among habitual smokers in Japan: a qualitative study based on semi-structured interviews

BackgroundAlthough more than half of the habitual smokers recognize that they want to quit smoking cigarettes, approximately half have failed to quit and experienced distress relapse; therefore, there is an urgent need to focus on these populations. When chronic behavior occurs, it is necessary to view the behavior in the context of the entire life of the person involved, considering the history of the person. In this study, we aimed to describe experiences with smoking from the onset to the present and the need for smoking cessation among habitual smokers in Japan and to explore efforts to address them.MethodsSemi-structured interviews that lasted for 55–90 min were conducted with the cooperation of 16 habitual smokers who smoked cigarettes daily. The content of the interviews included demographic characteristics, experiences with smoking from the onset to the present, whether they have attempted to quit and related experiences, and their thoughts on smoking. Interviews were transcribed verbatim and analyzed qualitatively. The Medical Research Ethics Review Committee of Jikei University approved this study (approval number: 33–384(11008)).ResultsThe participants were aged 26–59 years (mean ± SD: 40.8 ± 8.9 years) and included 10 men and 6 women. The participants started smoking between age 13 and 24 years. The highest number of cigarettes smoked in the participants’ lives ranged from 10 to 80 daily, and 12 participants had attempted to quit smoking so far without success. Regarding experiences with smoking from the onset to the present, four themes of “expand one’s world,” “unconscious attachment,” “attempts and failures,” and “losing oneself” were extracted. Regarding the need for smoking cessation, four themes of “empowerment from experts,” “peer interaction,” “social commitment,” and “recovery of confidence” were extracted.ConclusionTo support smoking cessation from the perspective of habitual smokers, in addition to improvements through the existing approaches, it is important to recover their confidence using ongoing activities in peer groups according to the target background and support from experts incorporating visual assessments of lung function, along with multiple short-term goals. It is also necessary to raise awareness in communities through activities.

Multicountry research on comprehensive abortion policy implementation in Latin America: a mixed-methods study protocol

IntroductionAccess to comprehensive abortion care could prevent the death of between 13 865 and 38 940 women and the associated morbidity of 5 million women worldwide. There have been some...

The associations of hair cortisol and DHEA with posttraumatic stress disorder symptoms in refugees

BackgroundExposure to traumatic events, ongoing adversity, and posttraumatic stress disorder (PTSD) are associated with altered activity of the hypothalamic-pituitary-adrenal (HPA) axis, but findings are mixed. This may be explained in part by heterogeneity in PTSD symptom profiles. AimThe aim of this study was to investigate the complex relationships between the number of traumatic events and post-displacement stressors, individual symptoms of PTSD, and HPA-axis hormones cortisol and dehydroepiandrosterone (DHEA) in refugees. MethodsAdult (18+ years) Syrian refugees with increased levels of distress participating in a randomized controlled trial completed baseline measures to assess traumatic events (trauma checklist), post-displacement stressors (Post-Migration Living Difficulties checklist), symptoms of PTSD (PTSD Checklist for DSM-5; PCL-5), and provided a hair sample for additional stress hormone analyses. We used R-packages qgraph and bootnet to perform network analysis on the number of traumatic events and post-displacement stressors, individual symptoms of PTSD, and HPA-axis hormones cortisol and DHEA. The final network model was corrected for depression severity. Results115 (53% male, M age = 36.9, SD = 12.7) of 206 participants provided a hair sample. A higher number of traumatic events was directly associated with three symptoms of the PTSD cluster arousal and reactivity, i.e., sleep disturbance, hypervigilance and physiological reactivity, and with three other PTSD symptoms, namely flashbacks, avoidance of reminders, and self-destructive behavior. A higher number of post-displacement stressors was associated with four symptoms of the PTSD cluster cognition and mood, i.e., trauma-related amnesia, negative beliefs, blaming of self/others, and detachment, as well as with intrusive thoughts, sleep disturbance, hypervigilance, and exaggerated startle response. The number of traumatic events and post-displacement stressors were not associated with cortisol or DHEA. Cortisol was positively associated with two symptoms of the PTSD cluster cognition and mood, i.e., negative beliefs and negative trauma-related emotions, and negatively associated with avoidance of reminders. DHEA was positively associated with restricted affect and with three symptoms of the PTSD symptom cluster arousal and reactivity, i.e., irritability/anger, sleep disturbance, and self-destructive behavior, and negatively associated with avoidance of thoughts. ConclusionsThis study demonstrated that exposure to traumatic events and post-displacement stressors is not related to cortisol and DHEA, but that cortisol and DHEA are differentially related to individual symptoms of PTSD. While lower levels of both cortisol and DHEA were associated with increased avoidance, higher levels of cortisol were mostly associated with symptoms of the PTSD cluster cognition and mood and higher levels of DHEA were mostly associated with symptoms of the PTSD cluster arousal and reactivity. These findings contribute to explaining the variability of findings in the literature on HPA-axis activity in PTSD. EthicsThe study was approved by the Research Ethics Review Committee at VU Medical Center, the Netherlands (Protocol ID: NL61361.029.17, 7 September 2017) and prospectively registered online (https://www.trialregister.nl/trial/6665).

Reliability of the respiratory rate and oxygenation index for successful high-flow nasal cannula support in coronavirus disease pneumonia: a retrospective cohort study

BackgroundHigh-flow nasal cannula (HFNC) therapy is an important non-invasive respiratory support in acute respiratory failure, including coronavirus disease (COVID-19) pneumonia. Although the respiratory rate and oxygenation (ROX) index is a simple and useful predictor for HFNC failure and mortality, there is limited evidence for its use in patients with COVID-19 pneumonia. We aimed to evaluate the ROX index as a predictor for HFNC failure in patients with COVID-19 pneumonia. We also evaluated the ROX index as a predictor for 28-day mortality.MethodsIn this single-center, retrospective, cohort study, 248 patients older than 18 years of age with COVID-19 pneumonia received HFNC therapy for acute respiratory failure. The ROX index was evaluated within 4 h from the start of HFNC therapy. Past medical history, laboratory data, and the ROX index were evaluated as predictors for HFNC failure and 28-day mortality.ResultsThe ROX index < 4.88 showed a significantly high risk ratio for HFNC failure (2.13 [95% confidence interval [CI]: 1.47 – 3.08], p < 0.001). The ROX index < 4.88 was significantly associated with 28-day mortality (p = 0.049) in patients with COVID-19 pneumonia receiving HFNC therapy. Age, chronic hypertension, high lactate dehydrogenase level, and low ROX index showed significantly high risk ratio for HFNC failure. C-reactive protein level and low ROX index were predictors of 28-day morality.ConclusionThe ROX index is a useful predictor for HFNC success and 28-day mortality in patients with COVID-19 pneumonia receiving HFNC therapy.Trial registrationAn independent ethics committee approved the study (Research Ethics Review Committee of Kobe City Medical Center General Hospital [number: zn220303; date: February 21, 2022]), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice.

WHO O2CoV2: oxygen requirements and respiratory support in patients with COVID-19 in low-and-middle income countries—protocol for a multicountry, prospective, observational cohort study

IntroductionSARS-CoV-2 has been identified as the cause of the disease officially named COVID-19, primarily a respiratory illness. COVID-19 was characterised as a pandemic on 11 March 2020. It has been...

Effectiveness of a participatory approach to develop school health interventions in four low resource cities: study protocol of the ‘empowering adolescents to lead change using health data’ cluster randomised controlled trial

IntroductionComprehensive local data on adolescent health are often lacking, particularly in lower resource settings. Furthermore, there are knowledge gaps around which interventions are effective to support healthy behaviours. This study...

Randomised controlled trial of cultural-adapted and programme-adopted cognitive behavioural therapy for children and adolescents’ anxiety in Japan: protocol for a Multi-, Inter-, and Cross-cultural Clinical Child Study (MIXCS)

IntroductionThe primary objective of the Multi-, Inter-, and Cross-cultural Clinical Child Study (MIXCS) is to evaluate the hypothesis that the effects of cultural-adapted cognitive behavioural therapy (CA-CBT) and programme-adopted cognitive...

Protocol for improving the costs and outcomes of assistive reproductive technology fertility care pathways: a study using cost measurement and process mining

IntroductionValue-based healthcare suggests that care outcomes should be evaluated in relation to the costs of delivering that care from the perspective of the provider. However, few providers achieve this because...

Barriers and facilitators of nutrition service utilization among adolescent girls in Southern Ethiopia

Health and nutrition service for adolescents, will serve as a future investment for breaking the cycle of intergenerational poor health. Thus, understanding barriers and facilitators for nutrition service utilization is critical to timely address malnutrition problem in this age group. This study was conducted in Wolaita and Hadiya zones, Ethiopia. A qualitative study was conducted from April 30/2019 to May 30/2019. Purposively selected health extension workers, school leaders, gender focal persons, health center experts, and youth center leaders from each village were involved in this study as key informants. In addition to this, a total of 6 FGDs were conducted. Eight adolescent girls were included in each focus group discussion. The process of analysis was conducted with open coding, identifying concepts, categories and properties/subcategories. The study was approved by Addis Ababa University (AAU), College of Natural Sciences Research Ethics Review Committee. Official letter of cooperation was written to Wolaita and Hadiya zones, and districts of health offices. The nature of the study was fully explained to the study participants. Informed verbal and written consent was obtained from each participant. The collected data has been kept confidential. Barriers for nutrition service utilization among adolescent girls were lack of awareness for study participants and their families, shortage of iron-folate and deworming tablets, lack of trained experts who were responsible for the nutrition service implementation, low economic status of the family, lack of coordination among different sectors for nutrition service, low educational status of the adolescent girls’ family. Facilitators for nutrition service utilization among adolescent girls in the study area were supplementation of iron-folate and deworming tablets was without payment. In addition, the utilization of social and community networks motivates the utilization of nutrition services among adolescent girls. Recommendation: Awareness creation training should be given for adolescent girls and their families, and male adolescent before the implementation of nutrition service provision.

Effectiveness of digital adherence technologies in improving tuberculosis treatment outcomes in four countries: a pragmatic cluster randomised trial protocol

IntroductionSuccessful treatment of tuberculosis depends to a large extent on good adherence to treatment regimens, which relies on directly observed treatment (DOT). This in turn requires frequent visits to health...

Preventing cardiotoxicity in patients with breast cancer and lymphoma: protocol for a multicentre randomised controlled trial (PROACT)

IntroductionAnthracyclines are included in chemotherapy regimens to treat several different types of cancer and are extremely effective. However, it is recognised that a significant side effect is cardiotoxicity; anthracyclines can...

Effectiveness of a community-integrated intermediary care (CIIC) service model to enhance family-based long-term care for Thai older adults in Chiang Mai, Thailand: a cluster-randomized controlled trial TCTR20190412004

BackgroundPopulations around the world are ageing faster, with the majority living in low- and middle-income countries where health and social care are yet to be universal and inclusive for the ageing population. This community-integrated intermediary care (CIIC) model is a novel prevention-based, long-term care model enhancing the family-based care system traditionally practised in Thailand and neighbouring Asian countries, and many low-and middle-income countries globally. This study assessed the effectiveness of the CIIC model in Chiang Mai, Thailand.MethodsThe two-arm parallel intervention study was designed as a cluster-randomized controlled trial. The study population at randomization and analysis was 2788 participants: 1509 in six intervention clusters and 1279 in six control clusters. The research protocol was approved by the WHO Research Ethics Review Committee (WHO/ERC ID; ERC.0003064).The CIIC service intervention model is a combination of formal care and informal care in a subdistrict setting consisting of three components: (1) care prevention delivered as community group exercise and home exercise; (2) care capacity-building of the family caregiver; and (3) community respite service. The primary outcome was family caregivers’ burden at 6-month follow-up, and secondary outcome was activities of daily living. Analysis applied the intention-to-treat approach using cluster-level analysis via STATA 16 SE.ResultsBaseline characteristics did not differ between the two arms. Loss of follow up was 3.7%. Mean age of the participants was 69.53 years. Women constituted 60%. The COVID-19 pandemic caused delayed implementation. The proportion of families with reduced caregiver burden at 6-month follow-up was higher among the intervention clusters (mean 39.4%) than control clusters (mean 28.62%). The intervention clusters experienced less functional decline and fewer people with depression.ConclusionsWhen communities are integrated for preventing care, and families are empowered for giving care, it is possible to secure universal access to health and social care for the older persons, with basic resources mobilized from communities. This study had shown the CIIC model as an effective and potential step to the realization of universal health and long-term care coverage being inclusive of ageing populations in Thailand and globally.Trial registration: This trial was registered at the Thailand Clinical Trial Registry—Trial registration number TCTR20190412004, https://www.thaiclinicaltrials.org/#

Chimeric antigen receptor T-cell therapy targeting a MAGE A4 peptide and HLA-A*02:01 complex for unresectable advanced or recurrent solid cancer: protocol for a multi-institutional phase 1 clinical trial

IntroductionAdoptive cell transfer of genetically engineered T cells is a promising treatment for malignancies; however, there are few ideal cancer antigens expressed on the cell surface, and the development of...

Unravelling the reservoirs for colonisation of infants with Campylobacter spp. in rural Ethiopia: protocol for a longitudinal study during a global pandemic and political tensions

IntroductionUndernutrition is an underlying cause of mortality in children under five (CU5) years of age. Animal-source foods have been shown to decrease malnutrition in CU5. Livestock are important reservoirs for...

Efficacy of a smartphone-based care support programme in improving post-traumatic stress in families with childhood cancer: protocol of a randomised controlled trial

IntroductionDiagnosis and treatment represent distressing experiences for the families of children with cancer. Psychosocial challenges are faced by these families in China because of limited health services and resources for...

The role of public involvement in the design of the first SARS-CoV-2 human challenge study during an evolving pandemic

High quality health care research must involve patients and the public. This ensures research is important, relevant and acceptable to those it is designed to benefit. The world’s first human challenge study with SARS-CoV-2 undertook detailed public involvement to inform study design despite the urgency to review and establish the study. The work was integral to the UK Research Ethics Committee review and approval of the study. Discussion with individuals from ethnic minorities within the UK population supported decision-making around the study exclusion criteria. Public review of study materials for consent processes led to the addition of new information, comparisons and visual aids to help volunteers consider the practicalities and risks involved in participating. A discussion exploring the acceptability of a human challenge study with SARS-CoV-2 taking place in the UK, given the current context of the pandemic, identified overall support for the study. Public concern for the wellbeing of trial participants, as a consequence of isolation, was identified. We outline our approach to public involvement and its impact on study design.