30 March 2020
COVID-19 and Virtual Trials: What does the FDA’s guidance mean for drug development?
The FDA have released guidance urging clinical trials to go virtual where possible in response to the COVID-19 pandemic – so what are the best methods for ensuring patient safety and trial integrity during this transition? In this article, we will discuss some of the important aspects to consider when taking a therapeutic trial from the clinic to the patient’s home.
The full FDA Guidance on Conduct of Clinical Trials of Medical Products During the COVID-19 Pandemic is available here.
Amid rising concerns around COVID-19, everyone is being encouraged to limit the physical contact they have with others - particularly those who are most vulnerable to infection i.e. older adults and those with co-morbid conditions. This poses a significant consideration for sponsors who are either actively planning, or currently undertaking, drug development programs with the very people who are at most risk of the virus.
So when is continuing or discontinuing with a trial in the best interests of the patient? In efforts to support drug developers in navigating this sensitive decision-making process, the FDA have released new guidance on how to assure the safety of trial participants and minimize risks to the integrity of the trial during the COVID-19 pandemic. One of the central tenants of this guidance is, wherever possible, to supplant in-clinic interactions with virtual measures such as phone interviews, self-administration and remote monitoring.
In this article, we will discuss the operational and scientific considerations of enacting this guidance in ongoing and future drug development programs.
What are the operational considerations for teams conducting virtual trials?
Central to the guidance is the FDA’s clear statement: “ensuring the safety of trial participants is paramount”. For sponsors this will involve weighing whether their participants’ safety, welfare and rights are best protected by continuing or discontinuing with the trial in the current climate. A key factor in this decision-making process will be establishing whether virtual visits are feasible and sufficient for assuring participant safety. Here we will cover the operational considerations for those trials that can safely continue, or begin, by deploying virtual visits and remote monitoring.
A key consideration for any trial is ensuring that study site staff are fully comfortable. Whether in-person, or as a virtual presence, these study co-ordinators are the first point of contact for the patient and are pivotal to successful implementation. Providing clear instructions that carefully reflect the practicalities for the protocol administration really help with this. As does openly communicating the benefits, and potential challenges, of delivering virtual assessments.
For example, high-frequency data collection offers a rich picture of the patient status over the course of the study. However, with an increase in measurement time-points also comes an increased burden in data monitoring. In order to mitigate concerns, drug developers should engage in an open discussion with site staff to ensure they share the benefits of virtual data collection and understand the different challenges and expectations from the outset.
In further efforts to gain a comprehensive picture of patient functioning and safety, a trial may choose to use multiple, third-party devices. With the deployment of multiple devices comes the challenge of ensuring they work in synchrony: integrating together to ensure a seamless and hassle free experience for the participant. Although rigorous testing is the primary course of action for mitigating this issue, when rolling out to participants, something as simple as QR codes could help to streamline the on-boarding process.
Although some questionnaires are technically simple to transition from in-person to online, there are ethical considerations in doing so. For example, the Columbia-Suicide Severity Rating Scale [C-SSRS] which asks participants about suicidal ideation. To ensure patient safety in a virtual environment, there must be a reliable alerting system in response to questions concerning patient-wellbeing and adverse events related to drug administration. For a worked example, take a look at this remote-alerting case study with PagerDuty.
What are the scientific considerations of conducting virtual trials?
By deploying a trial on patients’ own devices, studies no longer have to be designed to simulate situations as a proxy for lived-experience. Instead, clinical assessments can be interwoven into patients’ day-to-day lives. Although this holistic form of data collection presents new operational considerations, it can also offer several scientific opportunities. Read on to find out the key areas our science team have highlighted, and take a look at this blog-post series for a full discussion.
Inclusive, representative studies
Remote delivery enables patients to engage with research from the comfort and safety of their own homes. Without the burden of having to travel to study sites, participating in studies becomes a realistic option for those patients who may otherwise struggle to attend a centralised location. The end-result is a more inclusive and representative study cohort. Furthermore, by leveraging the scalability of technology, the diversity of participants can better reflect the eventual end-users of the product post-approval, increasing the relevance and applicability of the clinical data collected.
The contemporary framework for designing clinical trials is to build a comprehensive cognitive profile of the patient population from thorough but infrequent assessments. However, this framework struggles to capture the daily fluctuations in mood and cognition that many individuals with psychiatric disorders experience. At-home testing makes high-frequency data collection a credible option: the benefits of which include a more comprehensive picture of an individual’s fluctuations in wellbeing. High-frequency data collection offers particularly poignant insights for those studying neurological or psychiatric conditions, which have a high-rate of within- and between-subject variability. For a worked example, take a look at this wearable technology case study in major depressive disorder.
At-home testing allows clinical trials to capture data related to side effects, new diagnoses/ illnesses and adverse events in real time: generating an accurate picture of drug safety in the real world. This is critical information to know in order to help create sustainable and meaningful improvements for the patient. Furthermore, tracking the benefits and side-effects of an intervention in patients’ everyday lives pulls the focus towards what really matters most to patients: the ability to undertake their day-to-day activities.
The FDA Guidance on Conduct of Clinical Trials of Medical Products During the COVID-19 Pandemic hinges on ensuring patient safety and trial integrity: endorsing virtual trials as a possible means of enacting this guidance at a time when face-to-face contact is limited by necessity. In this article, we have outlined some of the scientific and operational considerations in making this shift. Of course, for some trials going virtual will not be a credible alternative and even those considering this protocol deviation will need to consult with their review division. Nevertheless, whether drug developers are considering starting or halting a trial during the COVID-19 pandemic, remote monitoring could provide valuable support for those who need to continue tracking patient safety.
Sally Jennings, PhD