Health Ethics Committee Research Articles

Building a practice-based research network for healthcare integration: a protocol paper for a mixed-method project

IntroductionPractice-based research networks (PBRNs) are sustained collaborations between healthcare professionals, researchers and members of the community that develop, conduct and report on research relevant to local needs. While PBRNs have...

Post–COVID-19 Lung Transplantation Italian Pivotal Protocol: Some Ethical Considerations

SARS‑CoV‑2 mostly affects the respiratory system with clinical patterns ranging from the common cold to fatal pneumonia. During the first wave of the COVID-19 pandemic, owing to the high number of patients who were infected with SARS‑CoV‑2 and subsequently recovered, it has been shown that some patients with post–COVID-19 terminal respiratory failure need lung transplantation for survival. There is increasing evidence coming from worldwide observations that this procedure can be performed successfully in post–COVID-19 patients. However, owing to the scarcity of organs, there is a need to define the safety and efficacy of lung transplant for post–COVID-19 patients as compared to patients waiting for a lung transplant for other pre-existing conditions, in order to ensure that sound ethical criteria are applied in organ allocation. The Milan's Policlinic Lung Transplant Surgery Unit, with the revision of the National Second Opinion for Infectious Diseases and the contribution of the Italian Lung Transplant Centres and the Italian National Transplant Centre, set up a pivotal observational protocol for the lung transplant of patients infected and successively turned negative for SARS‑CoV‑2, albeit with lung consequences such as acute respiratory distress syndrome or some chronic interstitial lung disease.The protocol was revised and approved by the Italian National Institute of Health Ethics Committee. Description of the protocol and some ethical considerations are reported in this article.

The challenges of keeping clinicians unaware of their participation in a national, cluster-randomised, implementation trial

BackgroundImplementation of recommendations from clinical practice guidelines is essential for evidence based clinical practice. However, the most effective methods of implementation are unclear. We conducted a national, cluster-randomised, blinded implementation trial to determine if midwife or doctor local implementation leaders are more effective in implementing a guideline for use of oral dextrose gel to treat hypoglycaemic babies on postnatal wards. To prevent any conscious or unconscious performance bias both the doctor and midwife local implementation leaders were kept unaware of the trial. This paper reports the ethical dilemmas and practical challenges of ensuring clinicians remained unaware of their involvement in an implementation trial.MethodsWe sought approval from the National Health and Disability Ethics committee to keep clinicians unaware of the trial by waiving the standard requirement for locality approval usually required for each district health board. The ethics committee did not approve a waiver of consent but advised that we approach the chief executive of each district health board to ask for provisional locality approval. Ultimately it was necessary to seek ethics approval for three separate study designs to keep clinicians unaware of the trial.ResultsThe median (IQR) time for chief executive approval was 16 (6–40) days and for locality approval was 57 (39–84) days. We completed 21 different locality approval forms for 27 hospitals.ConclusionsKeeping clinicians unaware of their involvement in a national implementation cluster-randomised trial is feasible. However, despite a national ethics committee, significant logistical challenges were time consuming and delayed trial completion. Co-ordination of the locality approval process would help facilitate multi-centre trials.

Implementation of a peer support intervention to promote the detection, reporting and management of adverse drug reactions in people living with HIV in Uganda: a protocol for a quasi-experimental study

IntroductionPatients have contributed <1% of spontaneous adverse drug reaction (ADR) reports in Uganda’s pharmacovigilance database. Peer support combined with mobile technologies could empower people living with HIV (PLHIV) to report...

Multisite sentinel surveillance of self-harm in New Zealand: protocol for an observational study

IntroductionNew Zealand (NZ) has a persistently high rate of suicide, particularly among young people. Hospital presentation for self-harm (SH) is one of the strongest predictors of death by suicide. Improving...

BIGDATA: A Protocol to Create and Extend a 25-Year Clinical Trial and Observational Data Asset to Address Key Knowledge Gaps in Otitis Media and Hearing Loss in Australian Aboriginal and Non-Aboriginal Children.

IntroductionOtitis media (OM) is a common childhood illness, often resolving without intervention and acute and long-term complications are rare. However, Australian Aboriginal and Torres Strait Islander infants and children experience a high burden of OM and are at high risk of complications (tympanic membrane perforation and chronic infections). Bacterial OM is commonly associated with Streptococcus pneumoniae, non-typeable Haemophilus influenzae, and Moraxella catarrhalis. BIGDATA is a data asset combining over 25 years of microbiology and OM surveillance research from the Ear Health Research Program at Menzies School of Health Research (Northern Territory, Australia), including 11 randomized controlled trials, four cohort studies, eight surveys in over 30 remote communities (including data from Western Australia), and five surveys of urban childcare centers including Aboriginal and Torres Strait Islander and non-Indigenous children. Outcome measures include clinical examinations (focusing on OM), antibiotic prescriptions, pneumococcal vaccination, modifiable risk factors such as smoking and household crowding, and nasopharyngeal and ear discharge microbiology including antimicrobial resistance testing.Methods and AnalysisThe initial series of projects are planned to address the following key knowledge gaps: (i) otitis media prevalence and severity over pre pneumococcal conjugate vaccines (PCVs) and three eras of increasing PCV valency; (ii) impact of increasing valency PCVs on nasopharyngeal carriage dynamics of pneumococcal serotypes, and antimicrobial resistance; (iii) impact of increasing valency PCVs on nasopharyngeal carriage dynamics and antimicrobial resistance of other otopathogens; and (iv) serotype specific differences between children with acute OM and OM with effusion or without OM. These data will be utilized to identify research gaps, providing evidence-based prioritization for ongoing research.Ethics and DisseminationData asset creation and priority analyses were approved by the Human Research Ethics Committee of Northern Territory Department of Health and Menzies School of Health Research (EC00153, 18-3281), the Child and Adolescent Health Service Human Research Ethics Committee and Western Australian Aboriginal Health Ethics Committee. Dissemination will be through peer review publication and conference presentations.

Assessment of serpin A5 levels and coagulation parameters of sickle cell anemia patients during bone pain vaso-occlusive crisis and steady state

Background Sickle cell anemia (SCA) is an inherited disorder linked to numerous complications including vaso-occlusive bone pain crisis. It is also associated with hypercoagulability and thromboembolic complications as a result of an imbalance between antithrombotic and prothrombotic substances, some of which are serpin A5 and D-dimer. This study aimed to assess these parameters during vaso-occlusive bone pain crisis and in steady state. Patients and methods This was a cross-sectional and prospective study involving SCA participants attending the Lagos State University Teaching Hospital, Ikeja following approval of the site's Health Research and Ethics Committee. Enzyme-linked immunosorbent assay was used to assay serpin A5 during vaso-occlusive bone pain crisis and in the same set of patients 3 months after, when they were in steady state. Similarly, D-dimers and prothrombin time were also performed in both crisis and steady states. Full blood count was done during vaso-occlusive crisis only. Data were analyzed with the Statistical Package for the Social Sciences (SPSS), version 23; P value was set at less than or equal to 0.05. Results A total of 44 participants were enrolled into the study with a mean age of 26.55 ± 7.31 years. The mean concentrations of serpin A5, D-dimer, and prothrombin time in crisis is and steady states were 0.57 ± 0.14 and 0.51 ± 0.11 mg/ml, 1613.12 ± 790.45 and 1209.95 ± 639.56 mg/ml, and 17.96 ± 1.55 and 17.04 ± 1.20 s, respectively. Paired t test in crisis and steady state for serpin A5 and prothrombin time were statistically significant. P values were 0.02 and 0.01, respectively, but not significant with D-dimer; the P value was 0.11. Conclusion The mean concentrations of serpin A5, D-dimer, and prothrombin time are higher in the SCA bone pain crisis compared with steady state.

Missing Piece Study protocol: prospective surveillance to determine the epidemiology of group A streptococcal pharyngitis and impetigo in remote Western Australia

IntroductionGroup A β-haemolytic Streptococcus (GAS), a Gram-positive bacterium, causes skin, mucosal and systemic infections. Repeated GAS infections can lead to autoimmune diseases acute rheumatic fever (ARF) and rheumatic heart disease...

Survivorship of Patients After Long Intensive Care Stay With Exploration and Experience in a New Zealand Cohort (SPLIT ENZ): Protocol for a Mixed Methods Study.

BackgroundPost Intensive Care Syndrome (PICS) was defined by the Society of Critical Care Medicine in 2012 with subsequent international research highlighting poor long-term outcomes; reduced quality of life; and impairments, for survivors of critical illness. To date, there has been no published research on the long-term outcomes of survivors of critical illness in New Zealand.ObjectiveThe aim of this study is to explore long-term outcomes after critical illness in New Zealand. The primary objectives are to describe and quantify symptoms and disability, explore possible risk factors, and to identify unmet needs in survivors of critical illness.MethodsThis will be a mixed methods study with 2 components. First, a prospective cohort study of approximately 100 participants with critical illness will be followed up at 1, 6, and 12 months after hospital discharge. The primary outcome will be disability assessed using the World Health Organization Disability Assessment Scale 2.0. Secondary outcomes will focus on mental health using the Hospital Anxiety and Depression Scale and the Impact of Events Scale-revised, cognitive function using the Montreal Cognitive Assessment (Montreal Cognitive Assessment–BLIND), and health-related quality of life using the European Quality of Life-Five Dimension-Five Level. The second element of the study will use qualitative grounded theory methods to explore participants experiences of recovery and highlight unmet needs.ResultsThis study was approved by the New Zealand Northern A Health and Disability Ethics Committee on August 16, 2021 (21/NTA/107), and has been registered with the Australian New Zealand Clinical Trials Registry on October 5, 2021. SPLIT ENZ is due to start recruitment in early 2022, aiming to enroll 125 patients over 2 years. Data collection is estimated to be completed by 2024-2025 and will be published once all data are available for reporting.ConclusionsAlthough international research has identified the prevalence of PICS and the extent of disability in survivors of critical illness, there is no published research in New Zealand. Research in this field is particularly pressing in the context of COVID-19, an illness that may include PICS in its sequelae.Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN1262100133588; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382566&showOriginal=true&isReview=trueInternational Registered Report Identifier (IRRID)PRR1-10.2196/35936

Protocol summary and statistical analysis plan for Intensive Nutrition Therapy comparEd to usual care iN criTically ill adults (INTENT): a phase II randomised controlled trial

IntroductionIt is plausible that a longer duration of nutrition intervention may have a greater impact on clinical and patient-centred outcomes. The Intensive Nutrition care Therapy comparEd to usual care iN...

Willingness to pay for an mHealth anti-retroviral therapy adherence and information tool: Transitioning to sustainability, Call for life randomised study experience in Uganda

IntroductionEvidence shows benefit of digital technology for people living with human immunodeficiency virus on antiretroviral therapy adherence and retention in care, however, scalability and sustainability have scarcely been evaluated. We assessed participants’ willingness to pay a fee for mHealth “Call for life Uganda” support, a mobile-phone based tool with the objective to assess sustainability and scalability.Methods“Call for Life study”, approved by Makerere University, School of Public Health research & ethics committee, at 2 sites in Uganda, evaluated a MoTech based software “CONNECT FOR LIFE™” mHealth tool termed “Call for life Uganda”. It provides short messages service or Interactive Voice Response functionalities, with a web-based interface, allows a computer to interact with humans through use of voice and tones input via keypad. Participants were randomized at 1:1 ratio to Standard of Care or standard of care plus Call for life Uganda. This sends pill reminders, visit reminders, voice messages and self-reported symptom support. At study visits 18 and 24 months, through mixed method approach we assessed mHealth sustainability and scalability. Participants were interviewed on desire to have or continue adherence support and willingness to pay a nominal fee for tool. We computed proportions willing to pay (± 95% confidence interval), stratified by study arm and predictors of willingness to continue and to pay using multivariate logistic regression model backed up by themes from qualitative interviews.Results95% of participants were willing to continue using C4LU with 77.8% willing to pay for the service. Persons receiving care at the peri-urban clinic (OR 3.12, 95% CI 1.43–9.11.86) and those with exposure to the C4LU intervention (OR 4.2, 95% CI 1.55–11.84) were more likely to continue and pay for the service. Qualitative interviews revealed mixed feelings regarding amounts to pay, those willing to pay, argued that since they have been paying for personal phone calls/messages, they should not fail to pay for Call for life.ConclusionsPayment for the service offers opportunities to scale up and sustain mHealth interventions which may not be priorities for government funding. A co-pay model could be acceptable to PLHIV to access mHealth services in low resource settings.Clinical Trial Number NCT 02953080.

An Observational Study to Assess the Effectiveness of 4CMenB against Meningococcal Disease and Carriage and Gonorrhea in Adolescents in the Northern Territory, Australia-Study Protocol.

Invasive meningococcal disease (IMD) causes significant morbidity and mortality worldwide with serogroup B being the predominant serogroup in Australia and other countries for the past few decades. The licensed 4CMenB vaccine is effective in preventing meningococcal B disease. Emerging evidence suggests that although 4CMenB impact on carriage is limited, it may be effective against gonorrhoea due to genetic similarities between Neisseria meningitidis and Neisseria gonorrhoeae. This study protocol describes an observational study that will assess the effect of the 4CMenB vaccine against meningococcal carriage, IMD and gonorrhoea among adolescents in the Northern Territory (NT). All 14–19-year-olds residing in the NT with no contraindication for 4CMenB vaccine will be eligible to participate in this cohort study. Following consent, two doses of 4CMenB vaccine will be administered two months apart. An oropharyngeal swab will be collected at baseline and 12 months to detect pharyngeal carriage of Neisseria meningitidis by PCR. The main methodological approaches to assess the effect of 4CMenB involve a nested case control analysis and screening method to assess vaccine effectiveness and an Interrupted Time Series regression analysis to assess vaccine impact. Research ethics approvals have been obtained from Menzies and Central Australian Human Research Ethics Committees and the Western Australian Aboriginal Health Ethics Committee. Results will be provided in culturally appropriate formats for NT remote and regional communities and published in international peer reviewed journals. ClinicalTrials.gov Identifier: NCT04398849.

Oral and intravenous tranexamic acid are equivalent at reducing blood loss following shoulder arthroplasty—A multicenter, double-blinded, randomized, placebo-controlled trial

BackgroundTranexamic acid (TXA) has been shown to reduce blood loss significantly in shoulder arthroplasty. Oral TXA is significantly cheaper than intravenous TXA, but there has been no published literature comparing oral and intravenous TXA in shoulder arthroplasty. The purpose of this study was to compare the efficacy and safety of oral versus intravenous TXA in shoulder arthroplasty. We hypothesized that oral and intravenous TXA are equivalent at reducing blood loss following shoulder arthroplasty. MethodsThis study was approved by the New Zealand Health and Disability Ethics Committee (HDEC) and registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR). Patients undergoing elective shoulder arthroplasties were prospectively randomized into one of two groups. In the oral TXA group, 2g of TXA was administered two hours prior to induction of anesthesia, and in the intravenous TXA group, 1.5g of TXA was administered as a bolus following induction of anesthesia. The primary outcome was a reduction in hemoglobin concentration. The secondary outcomes included drain output, number of blood units transfused, length of hospital stay, and complications. ResultsA total of 80 consecutive patients were randomized. The baseline demographics were comparable between the two groups. There was no difference in the primary outcome measure or any of the secondary outcome measures. With regards to the primary outcome measure, using a two one-sided test (TOST) for equivalence, with a P value of < 0.05 demonstrating equivalence, the mean reduction of hemoglobin was 23.30g/L (± 1.62) versus 22.45g/L (± 1.30) for the oral and the intravenous groups, respectively (P < .001). Postoperative drain output was 74.58mLs (± 11.27) versus 90.03mLs (± 14.53) for the oral and the intravenous groups, respectively (P = .41). Furthermore, there was no difference in the number of blood units transfused, length of hospital stay, and complications. DiscussionTo the best of our knowledge, this is the first study in the literature comparing oral and intravenous tranexamic in shoulder arthroplasty, and we found no difference in the efficacy of the two routes of administration. Surgeons should be encouraged to use the less expensive oral form of the medication as a means to minimize overall healthcare expenditure.

Vitamin K-dependent anticoagulant use and level of anticoagulation control in sub-Saharan Africa: protocol for a retrospective cohort study

BackgroundGiven that vitamin K-dependent anticoagulants (VKAs) will continue to be the primary anticoagulant in Africa for a long time, understanding the quality of anticoagulation services in the continent is vital...

Protocol for development and validation of instruments to measure women’s empowerment in urban sanitation across countries in South Asia and Sub-Saharan Africa: the Agency, Resources and Institutional Structures for Sanitation-related Empowerment (ARISE) scales

IntroductionDespite an increasing emphasis on gender and empowerment in water, sanitation and hygiene (WaSH) programmes, no rigorously validated survey instruments exist for measuring empowerment within the WaSH sector. Our objective...

Feasibility of implementing the advanced HIV disease care package as part of community-based HIV/TB activities: a mixed-methods study protocol

IntroductionAlthough the advanced HIV disease (AHD) care package reduces morbidity and mortality in people with AHD (defined in people living with HIV as WHO stage 3 or 4, CD4 count...

Assessment of the perception of the public on the impact of the lockdown due to the Coronavirus Disease 2019 (COVID-19)

Background: Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2 started in Wuhan, China in December 2019 and was declared pandemic by the World Health Organization (WHO) in March 2020. Globally, majority of nations worldwide with Nigeria inclusive were on lockdown. Variations exist in the way the public responded to the lockdown.Objective: The study is to determine the public perception on the impact of the lockdown due to COVID-19Methods: Pretested survey form prepared using the Google form app and distributed via social media - WhatsApp, Facebook, email and Instagram. Sample size was determined as 510. The data collected was exported to Microsoft Excel. Descriptive and inferential statistics were used. Inferential analysis was done using chi square, and fisher exact test at 95% confidence interval. Ethical approval was obtained from the University of Uyo Teaching Hospital Health Research and Ethics Committee, Uyo, Akwa Ibom State, Nigeria.Results: A total of 510 respondents participated in the study. The results revealed 52.2% female respondents. The data revealed 60% were employed with majority residing in the South Western part of Nigeria and are in a relationship. While self-employed participants comprised 25.9%. Respondents aged between 40-49 years were 28.6%, while 61.57% were postgraduate degree holders. The current data showed that 59.6% of the respondents think that the lockdown, irrespective of the dimension taken prevented the spread of the diseaseConclusion: A significant percentage of the public are of the opinion that the lockdown was effective.

Epidemiological and radiological patterns of paediatric fractures in an elite community in South West Nigeria

Background: Fracture remains a common cause of morbidity, mortality, and disability in childhood. The etiology of fractures varies between and within countries and depends on the socioeconomic and environmental conditions. Etiology of fractures from the elite and high socioeconomic class community has not been documented and this study aimed to document such, including the radiographic features. Methods: A prospective, descriptive, cross-sectional study conducted on 38 children below 17 years that presented with injured limb between July 1, 2018, and June 30, 2020, to a private facility located within a highbrow location in Lagos, Nigeria. Ethical approval was obtained from the Health Research and Ethics Committee, Lagos University Teaching Hospital, Idi-Araba. Data were collected with pro forma. Data analysis was done using the Microsoft excel and Statistical Package for the Social Sciences software (SPSS) for Windows version 21. Results: Thirty-eight children were recruited. The mean age was 8.78 ± 4.35 years. The male-to-female ratio was 3.2–1. Fall was the most common cause of the fracture. Injury occurred most within the school environment followed by the home environment. All the injured presented with pain and swelling of the affected parts. The upper limbs were more injured. Transverse fractures were the most common radiographic findings. Moderate-to-severe displacement of fracture edges was seen in 55.3%, with severe angulations of fracture edges in 23.4%. Majority of the fractures were managed conservatively. Conclusion: Majority of the fractures were due to falls. Most are complete and transverse fractures. A higher percentage was displaced. The management was mostly conservative.

Infigratinib in children with achondroplasia: the PROPEL and PROPEL 2 studies.

Background:Achondroplasia is the most common short-limbed skeletal dysplasia resulting from gain-of-function pathogenic variants in fibroblast growth factor receptor 3 (FGFR3) gene, a negative regulator of endochondral bone formation. Most treatment options are symptomatic, targeting medical complications. Infigratinib is an orally bioavailable, FGFR1–3 selective tyrosine kinase inhibitor being investigated as a direct therapeutic strategy to counteract FGFR3 overactivity in achondroplasia.Objectives:The main objective of PROPEL is to collect baseline data of children with achondroplasia being considered for future enrollment in interventional studies sponsored by QED Therapeutics. The objectives of PROPEL 2 are to obtain preliminary evidence of safety and efficacy of oral infigratinib in children with achondroplasia, to identify the infigratinib dose to be explored in future studies, and to characterize the pharmacokinetic (PK) profile of infigratinib and major metabolites.Design:PROPEL (NCT04035811) is a prospective, noninterventional clinical study designed to characterize the natural history and collect baseline data of children with achondroplasia over 6−24 months. PROPEL 2 (NCT04265651), a prospective, phase II, open-label study of infigratinib in children with achondroplasia, consists of a dose-escalation, dose-finding, and dose-expansion phase to confirm the selected dose, and a PK substudy.Methods and analysis:Children aged 3−11 years with achondroplasia who completed ⩾6 months in PROPEL are eligible for PROPEL 2. Primary endpoints include treatment-emergent adverse events and change from baseline in annualized height velocity. Four cohorts at ascending dose levels are planned for dose escalation. The selected dose will be confirmed in the dose-expansion phase.Ethics:PROPEL and PROPEL 2 are being conducted in accordance with the International Conference on Harmonization Good Clinical Practice guidelines, principles of the Declaration of Helsinki, and relevant human clinical research and data privacy regulations. Protocols have been approved by local health authorities, ethics committees, and institutions as applicable. Parents/legally authorized representatives are required to provide signed informed consent; signed informed assent by the child is also required, where applicable.Discussion:PROPEL and PROPEL 2 will provide preliminary evidence of the safety and efficacy of infigratinib as precision treatment of children with achondroplasia and will inform the design of future studies of FGFR-targeted agents in achondroplasia.Registration:ClinicalTrials.gov: NCT04035811; NCT04265651.

A Modern Flexitarian Dietary Intervention Incorporating Web-Based Nutrition Education in Healthy Young Adults: Protocol for a Randomized Controlled Trial.

BackgroundThe trend of flexitarian eating patterns is on the rise, with young adults among the biggest adopters claiming health and environmental reasons to reduce red meat intake. Nutrient-dense meat and animal products are often the lynchpin of these diets, even when consumed only occasionally and in moderate amounts. Red meat provides forms and concentrations of essential proteins, lipids, and micronutrients that are scarce in exclusively vegetarian regimens.ObjectiveThe aim of this study is to consider the effects of moderate consumption of lean red meat as part of an otherwise vegetarian balanced diet and its impact on biomarkers of sustained health and well-being.MethodsA cohort of healthy, young (20-34 years old, n=80) male and female participants will take part in a 2-arm, parallel randomized controlled trial (RCT) for a duration of 12 weeks, with a 3-month posttrial follow-up. The trial will commence with a 2-week assessment period followed by allocation to the intervention arms. The intervention will include the consumption of red meat or meat alternatives 3 times per week for 10 weeks. Blood samples of the participants will be collected to measure changes in erythrocyte fatty acid distribution, circulating amino acids, neurotransmitters, markers of mineral status, and inflammatory markers. Questionnaires to assess well-being and mental health will be undertaken every 2 weeks. Body composition, physical function, and blood parameters will be assessed at allocation (t0), week 5 into the intervention (t5), and post intervention (t10).ResultsThe protocol has been developed using the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) checklist and the outcomes will be reported in accordance with the CONSORT (Consolidated Standards of Reporting Trials) guidelines. The trial was approved by the New Zealand Ministry of Health’s Health and Disability Ethics Committees (protocol 20/STH/157). The results of this study will be communicated via publication.ConclusionsTo our knowledge, this is the first RCT investigating the overarching health consequences of consuming pasture-fed red meat or no meat as part of a healthy diet.Trial RegistrationClinicalTrials.gov NCT04869163; https://clinicaltrials.gov/ct2/show/NCT04869163International Registered Report Identifier (IRRID)PRR1-10.2196/30909