Resilient Clinical Trial Infrastructure in Response to the COVID-19 Pandemic: Lessons Learned from the TOGETHER Randomized Platform Clinical Trial

In response to the COVID-19 pandemic, clinical research groups across the world developed trial protocols to evaluate the safety and efficacy of treatments for COVID-19. Despite this initial enthusiasm, only a small portion of these protocols were implemented. Of those implemented, a fraction successfully recruited their target sample size to analyze and disseminate findings. More than a year and a half into the COVID-19 pandemic, only a few clinical trials evaluating treatments for COVID-19 have generated new evidence. Productive randomized platform clinical trials evaluating COVID-19 treatments may attribute their success to intentional investments in developing resilient clinical trial infrastructures. Health system resiliency discourse provides a conceptual framework for characterizing attributes for withstanding shocks. This framework may also be useful for contextualizing the attributes of productive clinical trials evaluating COVID-19 therapies. We characterize the successful attributes and lessons learned in developing the TOGETHER Trial infrastructure using a health system resiliency framework. This framework may be considered by clinical trialists aiming to build resilient trial infrastructures capable of responding rapidly and efficiently to global health threats.

Target and actual sample sizes for studies from two trial registries from 1999 to 2020: an observational study

ObjectivesTo investigate differences between target and actual sample sizes, and what study characteristics were associated with sample sizes.DesignObservational study.SettingThe large trial registries of clinicaltrials.gov (starting in 1999) and ANZCTR (starting in 2005) through to 2021.ParticipantsOver 280 000 interventional studies excluding studies that were withheld, terminated for safety reasons or were expanded access.Main outcome measuresThe actual and target sample sizes, and the within-study ratio of the actual to target sample size.ResultsMost studies were small: the median actual sample sizes in the two databases were 60 and 52. There was a decrease over time in the target sample size of 9%–10% per 5 years, and a larger decrease of 18%–21% per 5 years for the actual sample size. The actual-to-target sample size ratio was 4.1% lower per 5 years, meaning more studies (on average) failed to hit their target sample size.ConclusionRegistered studies are more often under-recruited than over-recruited and worryingly both target and actual sample sizes appear to have decreased over time, as has the within-study gap between the target and actual sample size. Declining sample sizes and ongoing concerns about underpowered studies mean more research is needed into barriers and facilitators for improving recruitment and accessing data.

Persepsi Mahasiswa Akuntansi Terhadap Independensi Akuntan Publik: Studi Empirik pada Mahasiswa Akuntansi di Bandung

This study aims to determine the perceptions of accounting students towards the independence of public accountants in the city of Bandung. Positive perceptions indicate that the accounting profession, especially public accountants, has a proper place in accounting students. Through a questionnaire distributed with a sample of accounting students in the city of Bandung, with a target sample size of 60 students. From 137 respondents gathered, it can be seen based on the results of the analysis that students majoring in accounting in Bandung perceive that public accountants in Indonesia are not independent. In addition, the results of this study are expected to be inference for accounting students in Indonesia. The results of this study also show that there are differences in the perceptions of students majoring in accounting in Bandung who have never and who have taken auditing courses on the independence of public accountants in Indonesia. Keywords: Perception, Independence, Accounting Profession, and Public Accountant

85. Evaluation of Urinalysis and Urine Culture Use at a Community Health-system

Background The Infectious Diseases Society of America asymptomatic bacteriuria (ASB) guidelines recommend against screening for or treating ASB in most patients without symptoms of a urinary tract infection (UTI). The purpose of this study was to characterize current urine testing practices and their potential impact on identification and treatment of asymptomatic bacteriuria on hospitalized adults. Methods This retrospective, point prevalence study conducted at a 4 hospital community health-system that included all inpatients ≥ 18 years old present on November 13th, 2019. Patients were excluded if they were admitted or transferred to either a labor & delivery or mother-baby unit. A chart review was performed for a sub-group of patients with abnormal urine testing, with a target sample size of 200 (n=50 from each hospital). The primary outcome was the prevalence of patients with a urinalysis, urine culture, or both performed during their admission. Secondary outcomes included abnormal urine testing in the overall cohort and symptomatology and antibiotic use in the sub-group (Figure 1). Results 947 patients met inclusion criteria. Of those patients, 516 (54%) had urine testing performed during their admission. 322 (34%) patients had abnormal urine testing results (Table 1). In the sub-group, 192 patients with abnormal urine tests were included. Antibiotics with a documented indication of UTI were administered to 66 (34%) patients. Of those given antibiotics with a UTI indication, 49/66 (74%) did not have documented signs or symptoms of a UTI (Figure 2). Conclusion Urine testing was performed on the majority of admitted adult patients. Unnecessary testing likely contributes to guideline discordant screening and treatment of ASB. Future studies are needed to identify effective diagnostic stewardship interventions to decrease screening and treatment of ASB. Disclosures Ashley Wilde, PharmD, BCPS-AQ ID, Nothing to disclose

Prevalence of malaria in an area receiving seasonal malaria chemoprevention in Niger

Background Malaria transmission is highly seasonal in Niger. Despite the introduction of seasonal malaria chemoprevention (SMC) in the Magaria District, malaria incidence remains high, and the epidemiology of malaria in the community is not well-understood. Methods Four cross-sectional, household-based malaria prevalence surveys were performed in the Magaria District of Niger between October 2016 and February 2018. Two occurred during the peak malaria season and two during the low malaria season. Individuals in each of three age strata (3–59 months, 5–9 years, and 10 years and above) were sampled in randomly-selected households. Capillary blood was collected by fingerprick, thick and thin blood films were examined. Microscopy was performed at Epicentre, Maradi, Niger, with external quality control. The target sample size was 396 households during the high-season surveys and 266 households during the low-season surveys. Results Prevalence of parasitaemia was highest in children aged 5–9 years during all four surveys, ranging between 53.6% (95%CI 48.8–63.6) in February 2018 and 73.2% (66.2–79.2) in September 2017. Prevalence of parasitaemia among children aged 3–59 months ranged between 39.6% (33.2–46.4) in February 2018 and 51.9% (45.1–58.6) in October 2016. Parasite density was highest in children aged 3–59 months during all four surveys, and was higher in high season surveys than in low season surveys among all participants. The prevalence of gametocytaemia in children aged 3–59 months ranged between 9.9% (6.5–14.8) in February 2018 and 19.3% (14.6–25.2) in October 2016. The prevalence of gametocytaemia in children aged 5–9 years ranged between 6.3% (3.5–11.1) in February 2018 and 18.5% (12.7–26.1) in October 2016. Conclusions Asymptomatic malaria infection is highly prevalent in this area, even during the season with low incidence of clinical malaria. The high prevalence of parasitaemia in children aged 5–9 years warrants considering their inclusion in SMC programmes in this context.

Psychosocial impacts on the Christchurch Muslim community following the 15 March terrorist attacks: a mixed-methods study protocol

IntroductionOn 15 March 2019, a white supremacist gunman opened fire in two mosques in Christchurch, New Zealand, during Friday prayers, killing 51 people and injuring 40. The event was witnessed by at least 250 survivors and also live streamed on social media, leading to widespread and repeated exposure within the community. It is expected that survivors, families and community members will be at increased risk of developing mental disorders due to the scale and violence of these attacks.This protocol describes the first phase of a proposed longitudinal study to screen and assess the long-term impacts of the terrorist attack on members of the Christchurch Muslim community, to determine clinical need and facilitate access to appropriate interventions and to gain insights into working with such a traumatised, ethnically diverse population. It has been developed in close collaboration with members of that community.Methods and analysisA mixed-method design is described, combining self-report measures with a clinician-administered diagnostic interview. Participants include Christchurch Muslims aged 18 years and over, with a target sample size of n=200. Analyses will determine prevalence of major mental disorders, while regression analyses will model the relationship between pre-event features, trauma exposure and mental disorders. A small number of participants, stratified by exposure type, will also take part in a qualitative interview in English. All study information and self-report measures are provided in translations based on the ethnolinguistic composition of the group and are available in paper and online versions.Ethics and disseminationEthical approval was granted by the New Zealand Health and Disability Ethics Committee 19/NTA/147. All participants provide informed consent, either written or online via REDCap software. The study is registered with the Australian New Zealand Clinical Trials Registry. Findings will be disseminated initially to the impacted community, then by publication in scientific journals, presentations and to government agencies.Trial registration numberACTRN12620000909921.

1477The landscape of COVID-19 trials in Australia

Background The coronavirus disease 2019 (COVID-19) pandemic has seen a large number of clinical trials launched at unprecedented speed. We aimed to explore the landscape of COVID-19 trials in Australia, and to what extent Australian researchers have responded to global need for coordination and collaboration. Methods We systematically searched the Australian New Zealand Clinical Trials Registry (ANZCTR) and ClinicalTrials.gov from 1st January to 16th November 2020. We included all interventional studies addressing prevention, diagnosis or treatment of COVID-19, recruiting in Australia. We analysed the number and size of trials, additional recruitment countries, funding, trial purpose, study design, data sharing plans, and collection of COVID-19 core outcomes. Results We identified 56 COVID-19 trials, targeting 33,757 participants. They evaluated drugs (n = 34, 61%), vaccines (n = 10, 18%) or other interventions (n = 12, 21%), e.g. ventilators, digital health. Median target sample size was 150 (Q1-Q3=33-395). Only two trials utilised adaptive methods (Bayesian designs), and of the 34 COVID-19 treatment trials, only one included all core outcomes. Most (80%) indicated they were not planning to share data. Conclusions There has been impressive research scale-up and innovation in drug development and digital health, but fast-track procedures may have impacted scientific rigor and research prioritisation. Trials often lacked innovative study designs, were underpowered for clinical outcomes, collected limited core outcomes and did not intend to share data, precluding future evidence synthesis. Key messages The research response in Australia has been rapid, but better coordination is required. Infrastructure for innovation would support coordination of research efforts, and reduce research waste.

763Validity of algorithms for identifying five chronic conditions in MedicineInsight, Australian national primary care data

Background MedicineInsight is a database containing de-identified electronic health records (EHRs) from over 700 Australian general practices. To support the trust placed in analyses of MedicineInsight data, additional evidence regarding the accuracy of the data is needed. Methods This study measures the validity of algorithms available in MedicineInsight that identify patients with depression, anxiety, asthma, type 2 diabetes and osteoporosis. Fifty practices met eligibility criteria regarding patient load and location, five were randomly selected and four agreed to participate. Within each practice, 250 patients aged ≥ 40 years were randomly selected. This age restriction increased the prevalence of the evaluated conditions, thereby optimising statistical power. Trained staff review the full EHR for these patients, including progress notes and correspondence, which are not available in MedicineInsight because they may contain identifiable information. Results With data collection almost complete, the target sample size will not be attainable. Power calculations indicate the current sample of 479 should provide adequate precision. For each condition of interest, the sensitivity, specificity, positive predictive value and negative predictive value of the algorithm is calculated. The full EHR review is the gold standard against which the algorithms are benchmarked. Conclusions The findings will indicate whether these algorithms demonstrate adequate accuracy to be used for research and decision-making. Key messages This additional understanding regarding the accuracy of MedicineInsight data will facilitate the interpretation of analyses of MedicineInsight data and guide improvements to the algorithms.

The Impact of effective leadership on the performance of individuals in Saudi Airlines: تأثير القيادة الفعالة على أداء الأفراد في شركة الخطوط السعودية

The study aimed to get acquainted with the actual practices of effective leadership through the democratic style of the Saudi Airlines Company and to know the reality of the level of performance from their point of view of the Saudi Airlines Company, as well as to develop a proposed model to show the most important variables that affect raising the level of individuals ’performance according to effective leadership practices through the democratic pattern in Leadership at Saudi Airlines Company, the study relies on the descriptive and analytical approach to clarify its objectives, and to identify the extent of practicing effective leadership aspects by following the democratic management in the Saudi Arabian Airlines Company and its role in the performance of individuals. As this approach helps to study the reality, diagnose, express and describe the phenomenon under study accurately. The study population consists of all employees and employees working for the Saudi Airlines Company in the Jeddah branch (central) and their number reached 1497, and the target sample size was determined by 100 individuals, and the link to the questionnaire was distributed to them. The responses valid for statistical analysis reached 84 individuals, i.e. 84% of the target. According to the results, the study made several recommendations, the most important of which is raising the level of individuals' awareness of some democratic leadership practices and increasing human and social communication with subordinates as this contributes to raising performance efficiency.

Design of the RESILIENT Study: Rehabilitation at home using mobile health in older adults after hospitalization for ischemic heart disease (Preprint)

UNSTRUCTURED ABSTRACT Background: Participation in ambulatory cardiac rehabilitation (CR) remains low, especially among older adults. While mobile health CR (mHealth-CR) provides a novel opportunity to deliver care, age specific impairments may limit older adults’ uptake, and efficacy data are currently lacking. Methods/Design: The RESILIENT trial (NCT03978130) is a multicenter randomized clinical trial that is enrolling patients age ≥65 with ischemic heart disease in a 3:1 ratio to either intervention (mHealth-CR) or control (usual care), with a target sample size of 400 participants. mHealth-CR consists of a commercially available mHealth software platform coupled with weekly exercise therapist sessions to review progress and set new activity goals. The primary outcomes is change in functional mobility (6 minute walk distance) which is measured at baseline and 3 months. Secondary outcomes are health status, goal attainment, hospital readmission, and mortality. Among intervention participants, engagement with the mHealth-CR platform will be analyzed to understand characteristics that determine different patterns of utilization (e.g. persistent high engagement, declining engagement). Discussion: The RESILIENT trial will generate important evidence about the efficacy of mHealth-CR among older adults in multiple domains, as well as characteristics that determine sustained utilization of mHealth-CR. These findings will help in designing future precision medicine approaches to mHealth implementation in older adults. This knowledge is especially important in light of the COVID-19 pandemic which has shifted much of healthcare to the virtual setting.