Challenges and Lessons Learned From COVID-19 Trials: Should We Be Doing Clinical Trials Differently?
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ABSTRACT:
SUBMITTER: Janiaud P
PROVIDER: S-EPMC8164884 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The current health-care environment is demanding evidence-based medicine that relies on clinical trials as the basis for decisions. Clinician investigators are more often finding that they are personally responsible for coordinating large, multisite trials. We present strategies for successful implementation and management of multisite clinical trials and knowledge gained through an international, multisite randomized clinical trial. Topics include team composition, regulatory requirements, study organization and governance, communication strategies, recruitment and retention efforts, budget, technology transfer, and publication.
| S-EPMC3935288 | biostudies-literature
Project description:BackgroundThere is increasing recognition among trialists of the challenges in understanding how particular 'real-life' contexts influence the delivery and receipt of complex health interventions. Evaluations of interventions to change health worker and/or patient behaviours in health service settings exemplify these challenges. When interpreting evaluation data, deviation from intended intervention implementation is accounted for through process evaluations of fidelity, reach, and intensity. However, no such systematic approach has been proposed to account for the way evaluation activities may deviate in practice from assumptions made when data are interpreted.MethodsA collective case study was conducted to explore experiences of undertaking evaluation activities in the real-life contexts of nine complex intervention trials seeking to improve appropriate diagnosis and treatment of malaria in varied health service settings. Multiple sources of data were used, including in-depth interviews with investigators, participant-observation of studies, and rounds of discussion and reflection.Results and discussionFrom our experiences of the realities of conducting these evaluations, we identified six key 'lessons learned' about ways to become aware of and manage aspects of the fabric of trials involving the interface of researchers, fieldworkers, participants and data collection tools that may affect the intended production of data and interpretation of findings. These lessons included: foster a shared understanding across the study team of how individual practices contribute to the study goals; promote and facilitate within-team communications for ongoing reflection on the progress of the evaluation; establish processes for ongoing collaboration and dialogue between sub-study teams; the importance of a field research coordinator bridging everyday project management with scientific oversight; collect and review reflective field notes on the progress of the evaluation to aid interpretation of outcomes; and these approaches should help the identification of and reflection on possible overlaps between the evaluation and intervention.ConclusionThe lessons we have drawn point to the principle of reflexivity that, we argue, needs to become part of standard practice in the conduct of evaluations of complex interventions to promote more meaningful interpretations of the effects of an intervention and to better inform future implementation and decision-making.
| S-EPMC4079170 | biostudies-literature
Project description:The recipients of NIH's Clinical and Translational Science Awards (CTSA) have worked for over a decade to build informatics infrastructure in support of clinical and translational research. This infrastructure has proved invaluable for supporting responses to the current COVID-19 pandemic through direct patient care, clinical decision support, training researchers and practitioners, as well as public health surveillance and clinical research to levels that could not have been accomplished without the years of ground-laying work by the CTSAs. In this paper, we provide a perspective on our COVID-19 work and present relevant results of a survey of CTSA sites to broaden our understanding of the key features of their informatics programs, the informatics-related challenges they have experienced under COVID-19, and some of the innovations and solutions they developed in response to the pandemic. Responses demonstrated increased reliance by healthcare providers and researchers on access to electronic health record (EHR) data, both for local needs and for sharing with other institutions and national consortia. The initial work of the CTSAs on data capture, standards, interchange, and sharing policies all contributed to solutions, best illustrated by the creation, in record time, of a national clinical data repository in the National COVID-19 Cohort Collaborative (N3C). The survey data support seven recommendations for areas of informatics and public health investment and further study to support clinical and translational research in the post-COVID-19 era.
| S-EPMC8209435 | biostudies-literature
Project description:Global health education programs should strive continually to improve the quality of education, increase access, create communities that foster excellence in global health practices, and ensure sustainability. The COVID-19 pandemic forced the University of Minnesota's extensive global health education programs, which includes a decade of hybrid online and in-person programing, to move completely online. We share our experience, a working framework for evaluating global health educational programming, and lessons learned. Over the decades we have moved from a predominantly passive, lecture-based, in-person course to a hybrid online (passive) course with an intensive hands-on 2-week requirement. The pandemic forced us to explore new active online learning models. We retained our on-demand, online passive didactics, which used experts' time efficiently and was widely accessible and well received. In addition, we developed a highly effective synchronous online component that we felt replaced some of the hands-on activities effectively and led us to develop new and innovative "hands-on" experiences. This new, fully online model combining quality asynchronous and synchronous learning provided many unanticipated advantages, such as increasing access while decreasing our carbon footprint dramatically. By sharing our experience, lessons learned, and resources, we hope to inspire other programs likewise to innovate to improve quality, access, community, and sustainability in global health, especially if these innovations can help decrease negative aspects of global health education such as its environmental impact.
| S-EPMC8641357 | biostudies-literature
Project description:SARS-CoV-2 has spread across the globe in no time. In the beginning, people suffered due to the absence of efficacious drugs required to treat severely ill patients. Nevertheless, still, there are no established therapeutic molecules against the SARS-CoV-2. Therefore, repurposing of the drugs started against SARS-CoV-2, due to which several drugs were approved for the treatment of COVID-19 patients. This paper reviewed the treatment regime for COVID-19 through drug repurposing from December 8, 2019 (the day when WHO recognized COVID-19 as a pandemic) until today. We have reviewed all the clinical trials from RECOVERY trials, ACTT-1 and ACTT-2 study group, and other major clinical trial platforms published in highly reputed journals such as NEJM, Lancet, etc. In addition to single-molecule therapy, several combination therapies were also evaluated to understand the treatment of COVID-19 from these significant clinical trials. To date, several lessons have been learned on the therapeutic outcomes for COVID-19. The paper also outlines the experiences gained during the repurposing of therapeutic molecules (hydroxychloroquine, ritonavir/ lopinavir, favipiravir, remdesivir, ivermectin, dexamethasone, camostatmesylate, and heparin), immunotherapeutic molecules (tocilizumab, mavrilimumab, baricitinib, and interferons), combination therapy, and convalescent plasma therapy to treat COVID-19 patients. We summarized that anti-viral therapeutic (remdesivir) and immunotherapeutic (tocilizumab, dexamethasone, and baricitinib) therapy showed some beneficial outcomes. Until March 2021, 4952 clinical trials have been registered in ClinicalTrials.gov toward the drug and vaccine development for COVID-19. More than 100 countries have participated in contributing to these clinical trials. Other than the registered clinical trials (medium to large-size), several small-size clinical trials have also been conducted from time to time to evaluate the treatment of COVID-19. Four molecules showed beneficial therapeutic to treat COVID-19 patients. The short-term repurposing of the existing drug may provide a successful outcome for COVID-19 patients. Therefore, more clinical trials can be initiated using potential anti-viral molecules by evaluating in different phases of clinical trials.
| S-EPMC8636940 | biostudies-literature
Project description:The past few years have witnessed many promising advances in HIV prevention strategies involving preexposure prophylaxis approaches. Some may now wonder whether an HIV vaccine is still needed, and whether developing one is even possible. The partial efficacy reported in the RV144 trial and the encouraging results of the accompanying immune correlates analysis suggest that an effective HIV vaccine is achievable. These successes have provided a large impetus and guidance for conducting more HIV vaccine trials. A key lesson learned from RV144 is that assessment of HIV acquisition is now a feasible and valuable primary objective for HIV preventive vaccine trials. In this article we review how RV144 and other HIV vaccine efficacy trials have instructed the field and highlight some of the HIV vaccine concepts in clinical development. After a long and significant investment, HIV vaccine clinical research is paying off in the form of valuable lessons that, if applied effectively, will accelerate the path toward a safe and effective vaccine. Together with other HIV prevention approaches, preventive and therapeutic HIV vaccines will be invaluable tools in bringing the epidemic to an end.
| S-EPMC4000156 | biostudies-literature
Project description:Background/aimsHigh follow-up is critical in randomized clinical trials. We developed novel approaches to modify in-person visits and complete follow-up during COVID-19. Since these strategies are broadly applicable to circumstances wherein follow-up is difficult, they may help in contingency planning. The objective of this article is to develop and evaluate new approaches to replace detailed, in-person study visits for two trials focused on preventing diabetic foot complications.MethodsA quasi-experimental pre-post design compared approaches for follow-up during COVID-19 to approaches pre-COVID-19. Study subjects were outpatients at two Veterans Affairs Medical Centers. Following a research "hold," research resumed in February 2021 for Self-monitoring, Thermometry and Educating Patients for Ulcer Prevention (STEP UP) (n = 241), which focused on preventing recurrent foot ulcers, and in April 2021 for Preventing Amputation by Tailored Risk-based Intervention to Optimize Therapy (PATRIOT) (n = 406), which focused on preventing pre-ulcerative and ulcerative lesions. To complete data collection, we shortened visits, focused on primary and secondary outcomes, and conducted virtual visits when appropriate. For STEP UP, we created a 20-min assessment process that could be administered by phone. Since PATRIOT required plantar photographs to assess foot lesions, we conducted short face-to-face visits. We explored differences and assessed proportion completing visit, visit completion/100 person-months and compared COVID-19 to pre- COVID-19 using unadjusted risk ratios, incidence rate ratios, all with associated 95% confidence intervals (CIs). Finally, we report time-to-visit curves.ResultsIn both studies, participants whose follow-up concluded pre- COVID-19 seemed older than those whose follow-up concluded during COVID-19 (PATRIOT: 68.0 (67.2, 68.9) versus 65.2 years (61.9, 68.5); STEP UP: 67.5 (66.2, 68.9) versus 65.3 (63.3, 67.3)). For STEP UP, we completed 91 visits pre- COVID-19 (37.8% (31.6%, 44.2%)) and 63 visits during COVID-19 (78.8% (68.2%, 87.1%)). This was over 1309 person-months pre-COVID-19, and over 208.8 person-months during COVID-19; the visit completion rate/100 person-months were: pre-COVID-19 7.0 (5.6, 8.5), COVID-19 30.2 (23.2, 38.6); risk ratio: 2.1 (1.7, 2.5); and incidence rate ratio 4.3 (3.1, 5.9). Similarly, for PATRIOT, we completed 316 visits pre-COVID-19 (77.8% (73.5%, 81.8%)) and 27 assessments during COVID-19 (84.4% (67.2%, 94.7%)). This was over 1192.7 person-months pre-COVID-19 and 39.3 person-months during COVID-19. The visit completion rate/100 person-months in PATRIOT were: pre-COVID-19 2.7 (2.4, 3.0), COVID-19 6.9 (4.5, 10); risk ratio 1.1 (0.9, 1.3); incidence rate ratio 2.6 (1.8, 3.8). For both studies, the follow-up curves began separating at < 2 months.ConclusionsWe achieved higher completion rates during COVID-19 compared to pre-COVID-19 by modifying visits and focusing on primary and secondary outcomes. These strategies prevent excessive missing data, support more valid conclusions, and improve efficiency. They may provide important alternative strategies to achieving higher follow-up in randomized clinical trials.
| S-EPMC9790858 | biostudies-literature
Project description:Two COVID-19 outbreaks occurred in residential buildings with overcrowded housing conditions in the city of Göttingen in Germany during May and June 2020, when COVID-19 infection incidences were low across the rest of the country, with a national incidence of 2.6/100,000 population. The outbreaks increased the local incidence in the city of Göttingen to 123.5/100,000 in June 2020. Many of the affected residents were living in precarious conditions and experienced language barriers. The outbreaks were characterized by high case numbers and attack rates among the residents, many asymptomatic cases, a comparatively young population, and substantial outbreak control measures implemented by local authorities. We analyzed national and local surveillance data, calculated age-, and gender-specific attack rates and performed whole genome sequencing analysis to describe the outbreak and characteristics of the infected population. The authorities' infection control measures included voluntary and compulsory testing of all residents and mass quarantine. Public health measures, such as the general closure of schools and a public space as well as the prohibition of team sports at local level, were also implemented in the district to limit the outbreaks locally. The outbreaks were under control by the end of June 2020. We describe the measures to contain the outbreaks, the challenges experienced and lessons learned. We discuss how public health measures can be planned and implemented through consideration of the needs and vulnerabilities of affected populations. In order to avoid coercive measures, barrier-free communication, with language translation when needed, and consideration of socio-economic circumstances of affected populations are crucial for controlling infectious disease transmission in an outbreak effectively and in a timely way.
| S-EPMC8490676 | biostudies-literature
Project description:While COVID-19 is still ongoing and associated with more than 5 million deaths, the scope and speed of advances over the past year in terms of scientific discovery, data dissemination, and technology have been staggering. It is not a matter of "if" but "when" we will face the next pandemic, and how we leverage technology and data management effectively to create flexible ecosystems that facilitate collaboration, equitable care, and innovation will determine its severity and scale. The aim of this review is to address emerging challenges that came to light during the pandemic in health care and innovations that enabled us to adapt and continue to care for patients. The pandemic highlighted the need for seismic shifts in care paradigms and technology with considerations related to the digital divide and health literacy for digital health interventions to reach full potential and improve health outcomes. We discuss advances in telemedicine, remote patient monitoring, and emerging wearable technologies. Despite the promise of digital health, we emphasise the importance of addressing its limitations, including interpretation challenges, accuracy of findings, and artificial intelligence-driven algorithms. We summarise the most recent recommendation of the Virtual Care Task Force to scaling virtual medical services in Canada. Finally, we propose a model for optimal implementation of health digital innovations with 5 tenets including data management, data security, digital biomarkers, useful artificial intelligence, and clinical integration.
| S-EPMC8632798 | biostudies-literature
Project description:BackgroundThe COVID-19 pandemic has considerably disrupted nearly all aspects of daily life, including healthcare delivery and clinical research. Because pragmatic clinical trials are often embedded within healthcare delivery systems, they may be at high risk of disruption due to the dual impacts on the conduct of both care and research.MethodsWe collected qualitative data using multiple methods to characterize the impact of COVID-19 on the research activities of 14 active pragmatic clinical trials in the National Institutes of Health (NIH) Health Care Systems Research Collaboratory. A COVID-19 impact questionnaire was administered electronically to principal investigators in June 2020. Text responses were analyzed thematically, and qualitative summaries were subsequently reviewed by five independent reviewers, who made iterative revisions. Additional COVID-19-related impacts were identified during virtual meetings with trial teams during April-July 2020 and combined with questionnaire responses for analysis.ResultsImpacts of the pandemic were broadly classified into two main types: healthcare operations and social distancing. In some instances, trial delays created statistical challenges, particularly with trials using stepped-wedge designs, and necessitated changing data collection strategies or modifying interventions. The majority of projects used existing stakeholder-driven approaches to adapt interventions. Several benefits of these adaptions were identified, including expanded outreach capabilities and ability to study virtual intervention delivery. All trial teams were able to adapt to pandemic-related modifications.ConclusionIn a group of 14 ongoing pragmatic clinical trials, there was significant impact of COVID-19 on trial activities. Engaging appropriate stakeholders was critical to designing and implementing trial modifications and making continued safe progress toward meeting research objectives.
| S-EPMC9123729 | biostudies-literature