Fully remote clinical trials – The dawn of a new era

We implemented a fully randomized controlled trial of patients with COVID-19 with cardiac monitoring using a mobile six-lead electrocardiogram. Our study represents the first successful implementation of digital technologies to conduct a fully remote clinical trial with QT interval monitoring.
Fully remote clinical trials – The dawn of a new era
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Clinical trials have traditionally been conducted at research institutions that require travel for treatment and safety monitoring. The execution of a proper clinical trial requires selecting an appropriate study population and can be limited by volunteer bias due to geographic distance from study site, education, and socioeconomic status limiting enrollment[1]. Safety monitoring during clinical trials is the primary focus of the US Food and Drug Administration during drug development,[2] a key component of which is surveillance for cardiovascular toxicity[3].

COVID-19, which remains a critical public health issue,[4] has spurred unprecedented advances in vaccine developments and digital health[5]. As with the shift towards remote schooling and remote work, many aspects of life have undergone dramatic digitization. When we set out to design this study, we were faced with the need to minimize contact between participants and the wider world, including the research team. To overcome this hurdle, we designed a fully remote randomized controlled clinical trial. Given the concern for potential cardiovascular toxicity related to hydroxychloroquine and azithromycin, this study was specifically designed to evaluate QT prolongation [6, 7].

 In this trial, we randomized patients age 18-80 at who tested positive for SARS-CoV-2 virus, as previously described[8]. The entire trial was conducted remotely and each participant was delivered a self-monitoring kit, which included a 6-lead ECG monitor (KardiaMobile 6L, AliveCor Inc.). In our paper, Implementation of a fully remote randomized clinical trial with cardiac monitoring, we describe the steps we took to implement internet-based recruitment, patient enrollment, data storage, rapid machine-assisted data analysis, and interfacility collaboration. Although we now know that these agents are not effective for the treatment of COVID-19, our trial is a proof-of-concept demonstrating that QT-related cardiac toxicity monitoring in clinical trials can be executed remotely.

 Given the traditional barriers to clinical trial enrollment, this may improve access for patients and improve diversity and equity in research – our study population was more diverse population than average US demographics. Of the participants who met our inclusion criteria, we had a lower percentage of patients who self-identified as white, compared to the general population[9]. Additionally, our participants had great adherence to our ECG testing protocol, indicating reproducibility with future trials. While there is concern that technological advancements and remote testing may contribute to future disparities in care, we did not find a digital divide with our cohort of patients. While there was varying skill level in the technological skill of our patients, after proper guidance there was no trouble with participating in or completing our trial.

 While there have been several studies showing that remote cardiac monitoring can be useful in arrhythmia detection, our work demonstrates that these tools can also be utilized to safely and remotely monitor cardiac toxicity in clinical trials[10]. With the rise of digital health, ECG monitoring devices are an important tool we can leverage to further assess the cardiac safety profiles for drugs in clinical trials. We showed a proof of concept by being able to study the efficacy and safety of a medication using a low-cost device. As medical innovation continues to advance, we hope to see a rise of cardiac monitoring devices, including low-cost ECG monitors and ultrasounds, that can be used to study research questions across different populations.

 The future of clinical trials is inclusive,  cost-effective and unbound by geography

 Although developing countries represent the majority of the global population, they remain underrepresented in research and in clinical trials [11]. Access to research materials through low-cost devices, research infrastructure through a core-central laboratory, and remote research training and monitoring may remove some of the traditional barriers to clinical trials in developing countries. We hope that the advances in medical technology and the growing digitalization of research will contribute to a new future where we can ethnically test the safety and efficacy of medications across a wide range of populations to truly have diversity in clinical trials.

 

Read the article published in Nature Communications Medicine at https://www.nature.com/articles/s43856-021-00052-w

 References

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  3. Seltzer, J.H., et al., Assessing cardiac safety in oncology drug development. Am Heart J, 2019. 214: p. 125-133.
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