COVID-19 Clinical Trials Research Articles

Using ethnographic approaches to document, evaluate, and facilitate virtual community-engaged implementation research

BackgroundCommunity Advisory Boards (CABs) have been frequently used to engage diverse partners to inform research projects. Yet, evaluating the quality of engagement has not been routine. We describe a multi-method ethnographic approach documenting and assessing partner engagement in two “virtual” CABs, for which we conducted all meetings remotely.MethodsTwo research projects for increasing equitable COVID-19 testing, vaccination, and clinical trial participation for underserved communities involved remote CAB meetings. Thirty-three partners representing 17 community groups participated in 15 sessions across the two CABs facilitated by a social change organization. We developed ethnographic documentation forms to assess multiple aspects of CAB member engagement (e.g., time spent speaking, modality used, types of interactions). Documenters were trained to observe CAB sub-groups via virtual sessions. Debriefing with the documentation team after CAB meetings supported quality assurance and process refinement. CAB members completed a brief validated survey after each meeting to assess the quality and frequency of engagement. Content and rapid thematic analysis were used to analyze documentation data. Quantitative data were summarized as frequencies and means. Qualitative and quantitative findings were triangulated.ResultsA total of 4,540 interactions were identified across 15 meetings. The most frequent interaction was providing information (44%), followed by responding (37–38%). The quality and frequency of stakeholder engagement were rated favorably (average 4.7 of 5). Most CAB members (96%) reported good/excellent engagement. Specific comments included appreciation for the diversity of perspectives represented by the CAB members and suggestions for improved live interpretation. Debriefing sessions led to several methodological refinements for the documentation process and forms.ConclusionWe highlight key strategies for documenting and assessing community engagement. Our methods allowed for rich ethnographic data collection that refined our work with community partners. We recommend ongoing trainings, including debriefing sessions and routinely reviewed assessment of data to strengthen meaningful community engagement.

Characteristics and result reporting of registered COVID-19 clinical trials of Chinese and Indian traditional medicine: A comparative analysis.

To assess the main characteristics and result reporting of registered COVID-19 interventional trials of traditional Chinese medicine and traditional Indian medicine. We assessed design quality and result reporting of COVID-19 trials of traditional Chinese medicine (TCM) and traditional Indian medicine (TIM) registered before 10 February 2021, respectively, on Chinese Clinical Trial Registry (ChiCTR) and Clinical Trial Registry-India (CTRI). Comparison groups included registered COVID-19 trials of conventional medicine conducted in China (WMC), India (WMI), and in other countries (WMO). Cox regression analysis was used to assess the association between time from trial onset to result reporting and trial characteristics. The proportion of COVID-19 trials investigating traditional medicine was 33.7% (130/386) among trials registered on ChiCTR, and 58.6% (266/454) on CTRI. Planned sample sizes were mostly small in all COVID-19 trials (median 100, IQR: 50-200). The proportion of trials that were randomized was 75.4 and 64.8%, respectively, for the TCM and TIM trials. Blinding measures were used in 6.2% of the TCM trials, and 23.6% of the TIM trials. Cox regression analysis revealed that planned COVID-19 clinical trials of traditional medicine were less likely to have results reported than trials of conventional medicine (hazard ratio 0.713, 95% confidence interval: 0.541-0.939; p = 0.0162). There were considerable between-country and within-country differences in design quality, target sample size, trial participants, and reporting of trial results. Registered COVID-19 clinical trials of traditional medicine were less likely to report results than trials of conventional medicine.

Jordanian Undergraduate Students' Views of Participation in Clinical Trials: The COVID-19 Example.

The emergence of the COVID-19 pandemic has necessitated broad public participation in clinical trials. Knowledge of the attitudes of the relatively young would provide a perspective on future representative public enrollment in clinical trials. This study investigated the attitudes of undergraduate university students toward participation in COVID-19 clinical trials and determined the predictors of their attitudes. Using a validated, web-based questionnaire, 61.2% of the 425 respondents had heard about clinical trials before. Web-based media were the main sources of this knowledge. Less than 20% expressed willingness to participate in COVID-19 clinical trials or support the participation of a family member. The predictors were personal and family protection from the disease. On the contrary, being a female, possible political exploitation of the vaccine or drug, and their potential inefficacy were predictors of unwillingness to participate. This study may inform different stakeholders in developing effective study recruitment strategies to combat current and emerging pathogens.

The need for COVID-19 clinical trials in LMICs.

The need for COVID-19 clinical trials in LMICs.

An in silico drug repurposing pipeline to identify drugs with the potential to inhibit SARS-CoV-2 replication

BackgroundDrug repurposing provides an opportunity to redeploy drugs, which are already tested for safety or approved for use in humans, for the treatment of diseases distinct from their primary indication. For example, the repurposing of dexamethasone and baricitinib has played a crucial role in saving patient lives during the SARS-CoV-2 pandemic. There remains a need to expand therapeutic approaches to prevent life-threatening complications in vulnerable patients with COVID-19. MethodUsing an in silico approach based on structural similarity to drugs already in clinical trials for COVID-19, potential drugs were predicted for repurposing. For a subset of identified drugs with different targets to their corresponding COVID-19 clinical trial drug, a mechanism of action analysis based on affected pathways in the context of the first 24 h of infection was applied to establish whether they might have a role in inhibiting the replication of SARS-CoV-2. ResultsTwenty-nine structurally similar drugs with potential for repurposing against COVID-19 were predicted. Two of these with the potential to inhibit SARS-CoV-2 replication were identified using mechanism of action analysis. Triamcinolone is a corticosteroid that is structurally similar to dexamethasone; gallopamil is a calcium channel blocker that is structurally similar to verapamil. ConclusionThe identification of these drugs as potentially useful for patients with COVID-19 who are at a higher risk of developing severe disease supports the use of in silico approaches to facilitate quick and cost-effective identification of drugs for repurposing. Such drugs could expand the number of treatments available to the subset of patients who are not fully protected by vaccination.

Clinical trials of COVID-19 vaccine development: a global overview.

This study aims to report analyses regarding the global distribution of institutions involved in clinical trials of COVID-19 vaccines throughout February 2022. We retrieved global data from the World Health Organization report on vaccine development. These data allowed us to identify project institutions and plot their geographic coordinates. We produced a georeferenced map using an R programming environment and, based on the geographical location of vaccine developers, we analyzed the subcontinental distribution of clinical trials and the nature of the vaccines. Regionally, South-Southeast Asian countries carried out more clinical trials than any other region, proportionally, although this happened solely for mature technologies. Few trials were under implementation in Latin America and Africa. Our findings confirm previous studies on the regional concentration in the development of technology. However, our contribution lies in showing these phenomena for COVID-19 vaccines in specific subcontinents and technologies, at a country level. Our data underscores which subcontinents perform very few clinical trials for COVID-19 and seem to be ill-prepared for future disease outbreaks, and if these become epidemics or even pandemics and require domestic vaccine development or production. We also consider the case of Brazil, which did not finish the complete cycle of COVID-19 vaccine development in the indicated period; but, with favorable policies, it has potential to engage further in COVID-19 vaccine technology.

Hydroxyurea and pyridostigmine repurposed for treating Covid-19 multi-systems dysfunctions

<abstract> <p>Early in the COVID-19 pandemic, medical care providers at an acute illness hospital received increasing numbers of post-acute advanced COVID-19 patients from referring hospitals where they were showing no signs of improvement after receiving treatments from standard Emergency Use Authorization (EUA)-type protocols. The care providers turned to repurposing medications to treat these patients and added hydroxyurea, a medication commonly used for treating sickle cell anemia, to the hospital's COVID-19 treatment protocol and began to see notable clinical improvements. As the pandemic continued and new concerns arose concerning COVID-19 complications, those same care providers again turned to repurposing drugs. Focusing on the neuromuscular effects seen in COVID-19 patients, care providers turned to medications used to treat chronic neuromuscular conditions. Post-acute advanced Covid-19 patients initially received an abbreviated course of hydroxyurea followed by titrated doses of pyridostigmine. Positive responses were noted with cognition, diminished oxygen demands, progressive decrease in ventilator support, improved swallowing, and mobility. The authors suggest repurposed drugs could have great utility for treating COVID-19. It is recommended larger, COVID-19 clinical trials be completed to include hydroxyurea and pyridostigmine for validating the outcomes and clinical observations seen in these presented cases.</p> </abstract>

1065. Patient-Reported Reasons for Non-Participation in Inpatient COVID-19 Clinical Research: Results from a Multi-Center VA Embedded Randomized Trial

Abstract Background Early in the COVID-19 pandemic, no evidence-proven therapeutics were approved, and thus participation in a clinical trial was often the only way to access experimental medications. However, in the US, participation in medical research is low. Patient-stated factors impacting enrollment decisions are poorly characterized. Thus, the aim of this study was to identify patient-reported reasons for declining enrollment in a COVID-19 clinical trial. Methods As part of an open-label, pragmatic randomized trial across five VAs from 4/10/20 – 2/3/21, SARS-COV-2 positive inpatients with moderate to severe disease were screened for eligibility. Potentially eligible patients received an informed consent packet with a letter explaining the study and were then contacted remotely to assess willingness to participate. If eligible patients declined to participate, if willing, they were asked an open-ended question about the reasons behind their decision. If they were not able to provide a specific answer, then general categories were offered. Qualitative responses were analyzed using a directed content analysis approach; responses were categorized using previously defined factors that have contributed to decisions not to enroll in other clinical therapeutics trials, primarily conducted in oncology. Results Among 417 patients screened, 162 met eligibility criteria. Of these, 53 consented (32.7%), 102 declined to participate (62.9%), and 7 were unable to give consent. Themes and examples of reasons for declining participation are presented in Table 1. Among the patients who declined to participate, the four most cited factors were limited perceived benefit, competing priorities, physician or family influence and presence of comorbidities. Several patients reported that their decision was influenced by physician or family recommendation to decline, which was reported as physician lack of support for participation due to the presence of comorbidities or physician perceived lack of benefit given clinical improvement prior to study enrollment. Conclusion Understanding reasons and attitudes driving enrollment may help investigators address them during the recruitment process and increase participation in clinical trials in the US. Disclosures Karen Visnaw, RN, Hologic Inc: Stocks/Bonds|Liquidia Corporation: Stocks/Bonds Paul Monach, MD, PhD, Celgene / Bristol-Myers Squibb: Advisor/Consultant|ChemoCentryx: Advisor/Consultant|Gilead: Grant/Research Support|Kiniksa: Advisor/Consultant Westyn Branch-Elliman, MD, MMSc, DLA Piper,LLC/Medtronic: Advisor/Consultant|Gilead Pharmaceuticals: Grant/Research Support.

Preparing for compounding crises: Staff shortages and cyber-attack vulnerability in the era of COVID-19

In 2020, while the USA was experiencing successive waves of COVID-19, Universal Health Services experienced a major cyber attack that crippled electronic systems in over 200 hospitals, including a major academic medical centre that was playing a key regional role in COVID-19 care and clinical trials. This paper discusses the impact of the attack on clinical operations, informatics, research and teaching, contextualising the case study within more wide-scale trends driving the rise in cyber attacks on healthcare systems. The compounding relationships between COVID-19, healthcare workforce depletion and cyber-security vulnerabilities form the framework of the discussion and action plan. Commitments to institutional best practices, large-scale investments in infrastructure, and above all increasing support for the critical human actors carrying out the work, are urgently needed to secure the healthcare system against these destabilising threats. Within this context, this paper argues that information security in the healthcare sector must be reimagined and integrated with greater support for the needs of frontline healthcare workers.

Sex, Racial, and Ethnic Representation in COVID-19 Clinical Trials

Since the onset of the COVID-19 pandemic, there have been calls for COVID-19 clinical trials to be fully representative of all demographic groups. However, limited evidence is available about the sex, racial, and ethnic representation among COVID-19 prevention and treatment trials. To investigate whether female participants and racial and ethnic minority individuals are adequately represented in COVID-19 prevention and treatment trials in the US. Identified studies were registered on ClinicalTrials.gov or published in the PubMed database from October 2019 to February 2022. Included studies must have provided the number of enrolled participants by sex, race, or ethnicity. Only interventional studies conducted in the US for the primary purpose of the diagnosis, prevention, or treatment of (or supportive care for) COVID-19 conditions were included. Data on counts of enrollments by demographic variables (sex, race, and ethnicity) and location (country and state) were abstracted. Studies were broadly categorized by primary purpose as prevention (including vaccine and diagnosis studies) vs treatment (including supportive care studies). A random effects model for single proportions was used. Trial estimates were compared with corresponding estimates of representation in the US population with COVID-19. Sex, racial, and ethnic representation in COVID-19 clinical trials compared with their representation in the US population with COVID-19. Overall, 122 US-based COVID-19 clinical trials comprising 176 654 participants were analyzed. Studies were predominantly randomized trials (n = 95) for treatment of COVID-19 (n = 103). Sex, race, and ethnicity were reported in 109 (89.3%), 95 (77.9%), and 87 (71.3%) trials, respectively. Estimated representation in prevention and treatment trials vs the US population with COVID-19 was 48.9% and 44.6% vs 52.4% for female participants; 23.0% and 36.6% vs 17.7% for Hispanic or Latino participants; 7.2% and 16.5% vs 14.1% for Black participants; 3.8% and 4.6% vs 3.7% for Asian participants; 0.2% and 0.9% vs 0.2% for Native Hawaiian or Other Pacific Islander participants; and 1.3% and 1.4% vs 1.1% for American Indian or Alaska Native participants. Compared with expected rates in the COVID-19 reference population, female participants were underrepresented in treatment trials (85.1% of expected; P < .001), Black participants (53.7% of expected; P = .003) and Asian participants (64.4% of expected; P = .003) were underrepresented in prevention trials, and Hispanic or Latino participants were overrepresented in treatment trials (206.8% of expected; P < .001). In this systematic review and meta-analysis, aggregate differences in representation for several demographic groups in COVID-19 prevention and treatment trials in the US were found. Strategies to better ensure diverse representation in COVID-19 studies are needed, especially for prevention trials.

Fireside Chat on the Asian American, Native Hawaiian, and Pacific Islander Special Edition of the Health Equity Journal Featuring Authors.

Fireside Chat on the Asian American, Native Hawaiian, and Pacific Islander Special Edition of the Health Equity Journal Featuring Authors.

Urologic research in the COVID-19 Era: Challenges and Opportunities

The Coronavirus (COVID-19) pandemic, typified as such in March 2020 by the World Health Organization (WHO), has exceeded the capacity of health systems to aid victims, and triggered a radical change in medical research, and in the monitoring of the enrollment for clinical trials in urologic fields around the world. Last year, almost 90% of clinical sites closed patient enrollment, while at the same time, researchers around the world initiated almost 1000 COVID-19 clinical trials. This catastrophic pandemic has allowed us to expand our medical knowledge exponentially. The global urological community has created and published an infinity of scientific articles: establishing guideline reactions for diagnosis, treatment, and follow-up of the different urologic conditions across all areas of the field, reporting the experiences at urology services, and putting forward new strategies. The Confederación Americana de Urología (CAU) has promoted international collaborative projects that have led to gaining insight into how the Latin American Urology Services faced the pandemic, including the challenges, strengths, and the areas of opportunity for urologic care. It also allowed us to increase the number and quality of publications. Also, we have created new virtual platforms and international networks to exchange our knowledge. We have as well transformed this social, economic and health crisis brought upon us by COVID-19, into a source of opportunities for the growth and promotion of research in Latin America. Urologic patients, require researchers to work on favoring their goals. A collaborative network, the established and coordinated protocols, the safety of patients and researchers, assertive and constant communication, and effective technology use, are the essential tools to resume institutional investigation under these critical conditions.

BC-11 is a covalent TMPRSS2 fragment inhibitor that impedes SARS-CoV-2 host cell entry.

Host cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is facilitated via priming of its spike glycoprotein by the human transmembrane protease serine 2 (TMPRSS2). Although camostat and nafamostat are two highly potent covalent TMPRSS2 inhibitors, they nevertheless did not hold promise in COVID-19clinical trials, presumably due to their short plasma half-lives. Herein, we report an integrative chemogenomics approach based on computational modeling and in vitro enzymatic assays, for repurposing serine-targeted covalent inhibitors. This led to the identification of BC-11 as a covalent TMPRSS2 inhibitor displaying a unique selectivity profile for serine proteases, ascribable to its boronic acid warhead. BC-11 showed modest inhibition of SARS-CoV-2 (omicron variant) spike pseudotyped particles in a cell-based entry assay, and a combination of BC-11 and AHN 1-055 (a spike glycoprotein inhibitor) demonstrated better viral entry inhibition than either compound alone. Given its low molecular weight and good activity against TMPRSS2, BC-11 qualifies as a good starting point for further structural optimizations.

Therapeutic advances in COVID-19.

Over 2 years have passed since the start of the COVID-19 pandemic, which has claimed millions of lives. Unlike the early days of the pandemic, when management decisions were based on extrapolations from in vitro data, case reports and case series, clinicians are now equipped with an armamentarium of therapies based on high-quality evidence. These treatments are spread across seven main therapeutic categories: anti-inflammatory agents, antivirals, antithrombotics, therapies for acute hypoxaemic respiratory failure, anti-SARS-CoV-2 (neutralizing) antibody therapies, modulators of the renin–angiotensin–aldosterone system and vitamins. For each of these treatments, the patient population characteristics and clinical settings in which they were studied are important considerations. Although few direct comparisons have been performed, the evidence base and magnitude of benefit for anti-inflammatory and antiviral agents clearly outweigh those of other therapeutic approaches such as vitamins. The emergence of novel variants has further complicated the interpretation of much of the available evidence, particularly for antibody therapies. Importantly, patients with acute and chronic kidney disease were under-represented in many of the COVID-19 clinical trials, and outcomes in this population might differ from those reported in the general population. Here, we examine the clinical evidence for these therapies through a kidney medicine lens.

Clinical trial research agenda on COVID-19 – the first two years in Germany and beyond

BackgroundWe have followed the COVID-19 clinical trial research agenda from the beginning using the COVID-evidence.org platform. Now, two years after the COVID-19 pandemic started, our aim was to re-examine this research agenda with the latest data to provide a global perspective on the research landscape with a focus on Germany. MethodsWe reviewed and updated previously published data on the COVID-19 clinical research agenda as of 28February 2022 focusing on randomized trials. We used the COVID-evidence.org platform including registry entries from ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform as well as publications from the Living OVerview of Evidence platform for COVID-19 (L·OVE). ResultsTwo years on from the pandemic outbreak, there were 4,673 registered trials. The majority of these trials have remained small with a median of 120 planned participants (IQR 60-320). In the first hundred days of the pandemic most of them (50%) had been registered in China. More than two years later, the five countries with the most registered trials (alone or within a framework of international collaborations) were the USA (825 trials; 18%), Iran (619 trials; 13%), India (566 trials; 12%), China (353 trials; 8%), and Spain (309 trials; 7%). Only 119 trials were reported to have a study site in Germany (2.5% of the registered trials). Of the 4,673 trials registered, 15% (694 trials) had published their results by February 2022. The clinical research agenda has been marked by both successes, such as the large RECOVERY trial providing evidence on 10 treatments for COVID-19 including over 45,000 patients as of February 2022, and failures: worldwide only 57 randomized trials have been registered over two years that aimed to assess non-pharmaceutical interventions (e.g., face mask policies and lockdown measures) to prevent COVID-19, and only 11 of them had published results informing decisions that have an impact on the life of billions of people worldwide. ConclusionsThe COVID-19 clinical research agenda has highlighted the substantial effort of the research community but also the challenges of the clinical research ecosystem. Most importantly, it has shed light on the ability to circumvent traditional barriers and to make trials more useful even under extraordinary conditions. The time to learn our lessons and apply them is now, and the time to demonstrate how we have improved the system is before the next pandemic.

Therapeutic Approaches in COVID-19 Patients: The Role of the Renin-Angiotensin System.

Two and a half years after COVID-19 was first reported in China, thousands of people are still dying from the disease every day around the world. The condition is forcing physicians to adopt new treatment strategies while emphasizing continuation of vaccination programs. The renin-angiotensin system plays an important role in the development and progression of COVID-19 patients. Nonetheless, administration of recombinant angiotensin-converting enzyme 2 has been proposed for the treatment of the disease. The catalytic activity of cellular ACE2 (cACE2) and soluble ACE2 (sACE2) prevents angiotensin II and Des-Arg-bradykinin from accumulating in the body. On the other hand, SARS-CoV-2 mainly enters cells via cACE2. Thus, inhibition of ACE2 can prevent viral entry and reduce viral replication in host cells. The benefits of bradykinin inhibitors (BKs) have been reported in some COVID-19 clinical trials. Furthermore, the effects of cyclooxygenase (COX) inhibitors on ACE2 cleavage and prevention of viral entry into host cells have been reported in COVID-19 patients. However, the administration of COX inhibitors can reduce innate immune responses and have the opposite effect. A few studies suggest benefits of low-dose radiation therapy (LDR) in treating acute respiratory distress syndrome in COVID-19 patients. Nonetheless, radiation therapy can stimulate inflammatory pathways, resulting in adverse effects on lung injury in these patients. Overall, progress is being made in treating COVID-19 patients, but questions remain about which drugs will work and when. This review summarizes studies on the effects of a recombinant ACE2, BK and COX inhibitor, and LDR in patients with COVID-19.

Transparency and reporting characteristics of COVID-19 randomized controlled trials

BackgroundIn the context of the COVID-19 pandemic, randomized controlled trials (RCTs) are essential to support clinical decision-making. We aimed (1) to assess and compare the reporting characteristics of RCTs between preprints and peer-reviewed publications and (2) to assess whether reporting improves after the peer review process for all preprints subsequently published in peer-reviewed journals.MethodsWe searched the Cochrane COVID-19 Study Register and L·OVE COVID-19 platform to identify all reports of RCTs assessing pharmacological treatments of COVID-19, up to May 2021. We extracted indicators of transparency (e.g., trial registration, data sharing intentions) and assessed the completeness of reporting (i.e., some important CONSORT items, conflict of interest, ethical approval) using a standardized data extraction form. We also identified paired reports published in preprint and peer-reviewed publications.ResultsWe identified 251 trial reports: 121 (48%) were first published in peer-reviewed journals, and 130 (52%) were first published as preprints. Transparency was poor. About half of trials were prospectively registered (n = 140, 56%); 38% (n = 95) made their full protocols available, and 29% (n = 72) provided access to their statistical analysis plan report. A data sharing statement was reported in 68% (n = 170) of the reports of which 91% stated their willingness to share. Completeness of reporting was low: only 32% (n = 81) of trials completely defined the pre-specified primary outcome measures; 57% (n = 143) reported the process of allocation concealment. Overall, 51% (n = 127) adequately reported the results for the primary outcomes while only 14% (n = 36) of trials adequately described harms. Primary outcome(s) reported in trial registries and published reports were inconsistent in 49% (n = 104) of trials; of them, only 15% (n = 16) disclosed outcome switching in the report. There were no major differences between preprints and peer-reviewed publications. Of the 130 RCTs published as preprints, 78 were subsequently published in a peer-reviewed journal. There was no major improvement after the journal peer review process for most items.ConclusionsTransparency, completeness, and consistency of reporting of COVID-19 clinical trials were insufficient both in preprints and peer-reviewed publications. A comparison of paired reports published in preprint and peer-reviewed publication did not indicate major improvement.

The association between non-English primary language and COVID-19 clinical trial eligibility and enrollment: A retrospective cohort study

BackgroundEstablishing equitable access to COVID-19 clinical trials is an important step in mitigating outcomes disparities. Historically, language has served as a barrier to equitable clinical trial participation. MethodsA centralized research infrastructure was established at our institution to screen potential trial participants and to promote efficient and equitable access to COVID-19 clinical trials. Rates of eligibility and enrollment in COVID-19 clinical trials by primary language between April 9 and July 31, 2020 (during the first regional COVID-19 surge) were evaluated using logistic regression. Estimates were adjusted for potential confounders including age, sex, and time. ResultsA total of 1245 patients were admitted to the hospital with COVID-19 during the study period and screened for clinical trial eligibility. Among all screened patients, 487 (39%) had a non-English primary language. After adjustment, patients with a non-English primary language had 1.98 times higher odds (CI 1.51 to 2.59) of being eligible for 1 or more COVID-19 clinical trials. Among eligible patients, those with a non-English primary language had 1.83 times higher odds (CI 1.36 to 2.47) of enrolling in COVID-19 clinical trials than patients with English as the primary language. ConculsionThese findings suggest that there are modifiable barriers that can be addressed to lessen the impact of language discordance on access to clinical trials and provide an opportunity to further investigate factors associated with clinical trial participation for patients whose primary language is not English.

Changes in lactate dehydrogenase on admission throughout the COVID-19 pandemic and possible impacts on prognostic capability.

Introduction: The enzyme lactate dehydrogenase (LDH) is a good marker of general hyperinflammation correlated with mortality for COVID-19, and is therefore used in prognosis tools. In a current COVID-19 clinical randomized trial (CRT), the blood level of LDH was selected as an inclusion criterion. However, LDH decreased during the pandemic; hence, the impact of this decrease on the prognostic value of LDH for mortality was evaluated. Methods: Data on LDH levels in 843 patients were obtained and analyzed. Relative risk, standard error and receiver operating characteristic curves were calculated for two cutoff values. Results: Relative risk lost validity and the area under the curve narrowed by trimester during the pandemic. Conclusion: The progressive decrease in LDH impacted the capacity to predict mortality in COVID-19. More studies are needed to validate this finding and its implications.

Advancing multi-regional research in Canada through collaboration.

ObjectivesCOVID-19 accentuated the importance of breaking down data siloes and aligning incentives for data access, collection, and use. Health Data Research Network Canada (HDRN Canada) is responding to this challenge, bringing together people and organizations to transform health data use in Canada. ApproachHDRN Canada’s foundation is its partnership of 20 pan-Canadian, provincial and territorial data organizations that together are enabling multi-regional research. This is being enriched with HDRN Canada’s development of the Canada Health Data Research Alliance (HDR Alliance). The HDR Alliance coordinates expansion of sources and types of data available while retaining organizational independence. A project-based pilot approach is underway with two large pan-Canadian, longitudinal, consented cohort studies being linked at HDRN Canada sites. In addition, a collaboration with a pan-Canadian COVID19 clinical trials network is ensuring that clinical data are collected in ways that enables linkage with population-based administrative data. ResultsHDRN Canada has created a single data access portal for researchers with information on over 500 datasets and supported 72 research projects to date. Work on the HDR Alliance adds data from the Canadian Partnership for Tomorrow’s Health and the Canadian Longitudinal Survey on Aging. The former includes 350,000 individuals, and survey data (including related to COVID-19), physical measures and genomics. The latter includes 50,000 individuals with survey data and physical measures. Four multi-region clinical trials are being planned with the support of HDRN Canada. Even with aligned incentives, challenges navigating data governance and access processes remain. Collaborations are necessary to address these complexities and enable access to richer data in an efficient and timely matter. ConclusionStrong partnerships are critical to unlocking the potential of Canada’s data assets and expertise. The HDR Alliance provides a collaboration mechanism to increase the “findability”, accessibility and utility of data assets, while addressing complex issues in the data landscape. This increases research opportunities and the impact of population-based, linkable data.