ABSTRACT
OBJECTIVES: To review the pragmatism of published randomized trials of remdesivir and favipiravir based on the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS-2) framework. STUDY DESIGN AND SETTING: Ten eligible trials were identified from an existing comprehensive living review and were evaluated across the nine PRECIS-2 domains by two independent reviewers. RESULTS: All 10 trials had mostly pragmatic design characteristics. Four of the domains (i.e., recruitment, setting, organization, and primary analysis) were found to be pragmatic with most trials scoring four or five across the two interventions. In comparison scores for four other design domains (i.e., eligibility, follow-up, flexibility of delivery, and primary outcome) varied across the trials with some design choices being more explanatory. CONCLUSION: In our descriptive review of randomized controlled trails for two drugs for patients infected with COVID-19 early in the pandemic, we found that most trials had more pragmatic than explanatory characteristics. Some design choices for some of the trials, however, were not consistent with the urgent goal of informing clinical decision making in an epidemic. PRECIS-2 should be used as a guide by trialists, to help them match their trial design choices to the intended purpose of their trial.
ABSTRACT
Despite important advances in the linkage of residents' Medicare claims and Minimum Data Set (MDS) information, the data infrastructure for long-term care remains inadequate for public health surveillance and clinical research. It is widely known that the evidence base supporting treatment decisions for older nursing home residents is scant as residents are systematically excluded from clinical trials. Electronic health records (EHRs) hold the promise to improve this population's representation in clinical research, especially with the more timely and detailed clinical information available in EHRs that are lacking in claims and MDS. The COVID-19 pandemic shined a spotlight on the data gap in nursing homes. To address this need, the National Institute on Aging funded the Long-Term Care (LTC) Data Cooperative, a collaboration among providers and stakeholders in academia, government, and the private sector. The LTC Data Cooperative assembles residents' EHRs from major specialty vendors and facilitates linkage of these data with Medicare claims to create a comprehensive, longitudinal patient record. These data serve 4 key purposes: (1) health care operations and population health analytics; (2) public health surveillance; (3) observational, comparative effectiveness research; and (4) clinical research studies, including provider and patient recruitment into Phase 3 and Phase 4 randomized trials. Federally funded researchers wanting to conduct pragmatic trials can now enroll their partnering sites in this Cooperative to more easily access the clinical data needed to close the evidence gaps in LTC. Linkage to Medicare data facilitates tracking patients' long-term outcomes after being discharged back to the community. As of August 2022, nearly 1000 nursing homes have joined, feedback reports to facilities are being piloted, algorithms for identifying infections are being tested, and proposals for use of the data have been reviewed and approved. This emerging EHR system is a substantial innovation in the richness and timeliness of the data infrastructure of the nursing home population.
ABSTRACT
Background: At the initiation of the COVID-19 pandemic, restrictions forced researchers to decide whether to continue their ongoing clinical trials. The PREPARE (Pragmatic Randomized Trial Evaluating Pre-Operative Alcohol Skin Solutions in Fractured Extremities) trial is a pragmatic cluster-randomized crossover trial in patients with open and closed fractures. PREPARE was enrolling over 200 participants per month at the initiation of the pandemic. We aim to describe how the COVID-19 research restrictions affected participant enrollment. Methods: The PREPARE protocol permitted telephone consent, however, sites were obtaining consent in-person. To continue enrollment after the initiation of the restrictions participating sites obtained ethics approval for telephone consent scripts and the waiver of a signature on the consent form. We recorded the number of sites that switched to telephone consent, paused enrollment, and the length of the pause. We used t-tests to compare the differences in monthly enrollment between July 2019 and November 2020. Results: All 19 sites quickly implement telephone consent. Fourteen out of nineteen (73.6%) sites paused enrollment due to COVID-19 restrictions. The median length of enrollment pause was 46.5 days (range, 7-121 days; interquartile range, 61 days). The months immediately following the implementation of restrictions had significantly lower enrollment. Conclusion: A pragmatic design allowed sites to quickly adapt their procedures for obtaining informed consent via telephone and allowed for minimal interruptions to enrollment during the pandemic.
ABSTRACT
Starting from historic reflections, the current SARS-CoV-2 induced COVID-19 pandemic is examined from various perspectives, in terms of what it implies for the implementation of non-pharmaceutical interventions, the modeling and monitoring of the epidemic, the development of early-warning systems, the study of mortality, prevalence estimation, diagnostic and serological testing, vaccine development, and ultimately clinical trials. Emphasis is placed on how the pandemic had led to unprecedented speed in methodological and clinical development, the pitfalls thereof, but also the opportunities that it engenders for national and international collaboration, and how it has simplified and sped up procedures. We also study the impact of the pandemic on clinical trials in other indications. We note that it has placed biostatistics, epidemiology, virology, infectiology, and vaccinology, and related fields in the spotlight in an unprecedented way, implying great opportunities, but also the need to communicate effectively, often amidst controversy.