Hydroxychloroquine/Chloroquine for the Treatment of Hospitalized Patients with COVID-19: An Individual Participant Data Meta-Analysis

Importance: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data (IPD), including unanalyzed data from trials terminated early, enables further investigation of the efficacy and safety of HCQ/CQ. Objective: To assess efficacy of HCQ/CQ in patients hospitalized with COVID-19, both overall and in prespecified subgroups. Data Sources: ClinicalTrials.gov was searched multiple times in May-June 2020. Principal investigators of US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients were invited to collaborate in this IPD meta-analysis. Study Selection: RCTs in which: (1) HCQ/CQ was a treatment arm; (2) patient informed consent and/or individual study IRB approval allowed for data sharing; (3) principal investigators/their institutions signed a data use agreement for the present study; and (4) the outcomes defined in this study were recorded or could be extrapolated. Data Extraction and Synthesis: Wherever possible, harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator, then shared via a secure online data sharing platform to create a pooled data set. When this was not possible, individual study data were harmonized and merged manually. Data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions. Main Outcome(s) and Measure(s): 7-point ordinal scale, measured between day 28 and 35 post-enrollment. Results: Eight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We found no evidence of a difference in ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively). Conclusions and Relevance: The findings of this IPD meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.

Identifying Potential Barriers and Solutions to Patient Partner Compensation (Payment) in Research

Research that engages patients on the research team is often supported by grant funding from different organizations and, in some cases, principal investigators (who control the grant funding) provide patient partners with compensation (or payment) for their contributions. However, we have noted a gap in resources that identify and address barriers to compensating patient partners. In this paper, we present thoughts and experiences related to barriers to compensating patient partners with the goal of helping individuals identify and find solutions to these obstacles.Based on our experiences as individuals who live with chronic conditions and are patient partners, and those who are researchers who engage patient partners, we have identified eight barriers to compensating patient partners. We discuss each of these barriers: lack of awareness about patient partnership, institutional inflexibility, policy guidance from funders, compensation not prioritized in research budgets, leadership hesitancy to create a new system, culture of research teams, preconceived beliefs about the skills and abilities of patient partners, and expectations placed on patient partners. We demonstrate these barriers with real life examples and we offer some solutions. To further demonstrate these barriers, we ask readers to reflect on some scenarios that present realistic parallel situations to those that patient partners face. The intention is to illustrate, through empathy or putting yourself in someone else’s shoes, how we might all do better with respect to institutional barriers related to patient partner compensation. Last, we issue a call to action to share resources and identify actions to overcome these barriers so we can create a resource hub.

Who funded the research behind the Oxford–AstraZeneca COVID-19 vaccine?

ObjectivesThe Oxford–AstraZeneca COVID-19 vaccine (ChAdOx1 nCoV-19, Vaxzevira or Covishield) builds on two decades of research and development (R&D) into chimpanzee adenovirus-vectored vaccine (ChAdOx) technology at the University of Oxford. This study aimed to approximate the funding for the R&D of ChAdOx and the Oxford–AstraZeneca vaccine and to assess the transparency of funding reporting mechanisms.MethodsWe conducted a scoping review and publication history analysis of the principal investigators to reconstruct R&D funding the ChAdOx technology. We matched award numbers with publicly accessible grant databases. We filed freedom of information (FOI) requests to the University of Oxford for the disclosure of all grants for ChAdOx R&D.ResultsWe identified 100 peer-reviewed articles relevant to ChAdOx technology published between January 2002 and October 2020, extracting 577 mentions of funding bodies from acknowledgements. Government funders from overseas (including the European Union) were mentioned 158 times (27.4%), the UK government 147 (25.5%) and charitable funders 138 (23.9%). Grant award numbers were identified for 215 (37.3%) mentions; amounts were publicly available for 121 (21.0%). Based on the FOIs, until December 2019, the biggest funders of ChAdOx R&D were the European Commission (34.0%), Wellcome Trust (20.4%) and Coalition for Epidemic Preparedness Innovations (17.5%). Since January 2020, the UK government contributed 95.5% of funding identified. The total identified R&D funding was £104 226 076 reported in the FOIs and £228 466 771 reconstructed from the literature search.ConclusionOur study approximates that public and charitable financing accounted for 97%–99% of identifiable funding for the ChAdOx vaccine technology research at the University of Oxford underlying the Oxford–AstraZeneca vaccine until autumn 2020. We encountered a lack of transparency in research funding reporting.

Diverse biological and engineering strategies towards organ regeneration

Organ regeneration is an important, fascinating, and old topic while much remains unknown in spite of extensive investigations for decades. From March 25th to 27th, 2021, the Third Chinese Symposium on Organ Regeneration took place in the beautiful ocean city of Zhoushan, Zhejiang, China. This biennial conference attracted ~ 300 academic attendees: students, postdoctoral fellows, and principal investigators, in addition to few industrial investigators. The mixed live and virtual talks covered the broad field of organ regeneration from different animal organisms to human organoids, and concluded with some impressive advances on inflammatory signaling, regenerative signaling mechanisms, new technologies, and applications for organ regeneration.

Gender Systematics in the NRAO Proposal Review System

Several recent investigations indicate the existence of gender-related systematic trends in the peer review of proposals for observations on astronomical facilities. This includes the National Radio Astronomy Observatory (NRAO) where there is evidence of a gender imbalance in the rank of proposals with male principal investigators (PIs) favored over female PIs. Since semester 2017A (17A), the NRAO has taken the following steps: (1) inform science review panels (SRPs) and the telescope time allocation committee (TAC) about the gender imbalance; and (2) increase the female representation on SRPs and the TAC to reflect the community demographics. Here we analyze SRP normalized rank-ordered scores, or linear ranks, by PI gender for NRAO observing proposals from semesters 12A–21A. We use bootstrap resampling to generate modeled distributions and the Anderson–Darling (AD) test to evaluate the probability that the linear rank distributions for male and female PIs are drawn from the same parent sample. We find that between semesters 12A–17A that male PIs are favored over female PIs (AD p-value 0.0084), whereas between semesters 17B–21A female PIs are favored over male PIs, but at a lower significance (AD p-value 0.11). Therefore the gender imbalance is currently being ameliorated, but this imbalance may have been reversed. Regardless, we plan to adopt a dual-anonymous approach to proposal review to reduce the possibility of bias to occur.

Assessing collaboration among team scientists within a triadic research center partnership

Few studies have utilized qualitative methods to assess the perceived effectiveness of collaboration among research center interdisciplinary team scientists. Stages of team development served as the theoretical framework to characterize minority serving institution (MSI) and predominantly White institutions (PWI) participants’ challenges and successes during a National Institutes of Health (NIH) sponsored cancer health disparities training and research program. We present the finding of an inductive analysis of four open-ended survey questions across two years. Fostering an awareness of the inherently taxing, yet centrality of group (team) development may advance an understanding of team dynamics and lead to increased team cohesion and productivity. In conclusion, we provide recommendations to assist multiple principal investigators who embark on team development.

Endovascular Treatment for Acute Stroke Patients With a Pre-stroke Disability: An International Survey

Background: It is unclear what factors clinicians consider when deciding about endovascular thrombectomy (EVT) in acute ischemic stroke patients with a pre-existing disability. We aimed to explore international practice patterns and preferences for EVT in patients with a pre-stroke disability, defined as a modified Rankin score (mRS) ≥ 2.Methods: Electronic survey link was sent to principal investigators of five major EVT trials and members of a professional interventional neurology society.Results: Of the 81 survey-responding clinicians, 57% were neuro-interventionalists and 33% were non-interventional stroke clinicians. Overall, 64.2% would never or almost never consider EVT for a patient with pre-stroke mRS of 4-5, and 49.3% would always or almost always offer EVT for a patient with pre-stroke mRS 2-3. Perceived benefit of EVT (89%) and severity of baseline disability (83.5%) were identified as the most important clinician-level and patient-level factors that influence EVT decisions in these patients.Conclusion: In this survey of 80 respondents, we found that EVT practice for patients with pre-stroke disability across the world is heterogenous and depends upon patient characteristics. Individual clinician opinions substantially alter EVT decisions in pre-stroke disabled patients.

The impact of the COVID-19 pandemic on perceived publication pressure among academic researchers in Canada

The phenomenon of “publish-or-perish” in academia, spurred on by limited funding and academic positions, has led to increased competition and pressure on academics to publish. Publication pressure has been linked with multiple negative outcomes, including increased academic misconduct and researcher burnout. COVID-19 has disrupted research worldwide, leading to lost research time and increased anxiety amongst researchers. The objective of this study was to examine how COVID-19 has impacted perceived publication pressure amongst academic researchers in Canada. We used the revised Publication Pressure Questionnaire, in addition to Likert-type questions to discern respondents’ beliefs and concerns about the impact of COVID-19 on academic publishing. We found that publication pressure increased across academic researchers in Canada following the pandemic, with respondents reporting increased stress, increased pessimism, and decreased access to support related to publishing. Doctoral students reported the highest levels of stress and pessimism, while principal investigators had the most access to publication support. There were no significant differences in publication pressure reported between different research disciplines. Women and non-binary or genderfluid respondents reported higher stress and pessimism than men. We also identified differences in perceived publication pressure based on respondents’ publication frequency and other demographic factors, including disability and citizenship status. Overall, we document a snapshot of perceived publication pressure in Canada across researchers of different academic career stages and disciplines. This information can be used to guide the creation of researcher supports, as well as identify groups of researchers who may benefit from targeted resources.

Principal Investigator’ Perceptions of Effective Academic Leadership in Chinese Research Institutions and Universities

Academic leadership is considered a key factor in university and research institute development. In a competitive environment, the role of academic leadership has become increasingly important. At present, China is committed to building world-class universities and advanced research institutes, while academic leadership is one of the key factors. Thus, what is the ideal academic leadership in China’s institutional environment? What professional qualities should principal investigators have? This study investigates these issues with in-depth interviews of six principal investigators. The finding shows that the definition of academic leadership by principal investigators refers to academic expertise, assigning the team member, setting a direction, academic social skills, managing team member relationships, boosting team morale, and teamwork skills. Furthermore, academic expertise is often supposed to be more important than other abilities. In terms of competence, the definitions of leadership by Chinese principal investigators and the literature on Western academic leadership are similar.