When we think about clinical research innovation, we usually focus on the science. What is our inspired hypothesis, and how are we going to prove or disprove it?
But there’s another, more pragmatic layer to research: What are the operational issues that influence our practical ability to accomplish cost-effective studies that yield actionable, reliable results — fast? And what are the most efficient ways of maximizing our chances for success?
The COVID-19 pandemic has turned research business-as-usual upside down. At the same time, it has exponentially raised the stakes in our search for answers. The obvious solution to the logistics problem of running a trial without spreading the infection you are trying to extinguish is the virtual trial.
Somewhat novel, “virtual” or “decentralized” trials have been in use for only a few years, and their increased adoption has gathered momentum and strength as industry-wide experience has accrued. Clinical Ink is the leader in virtual trial conduct. From a pioneering Ebola vaccine study of 6,000 patients in sub-Saharan Africa to our track record of successful BYOD studies involving 15,000 patients across Phase I–IV+ clinical trials, we have spent years developing the solutions in our Lumenis™ toolbox along with the know-how to implement and run virtual studies.
What does “virtual trial” even mean?
Our industry tends to use shortcut definitions that become confusing as various vendors and companies latch on to the latest buzzwords. Generally, a virtual trial means any study design that supplants or replaces the need for onsite patient visits. Clinical Ink further separates these types of studies into four buckets:
- Hybrid Virtual Visit: These types of studies allow for sites to interact with patients remotely, typically via a variety of online video platforms: Zoom, GoToMeeting, WebEx, and even FaceTime. Although there hasn’t been a lot of formal regulatory guidance, both the FDA and EMA have recently stated that phone/video interactions could be considered acceptable alternatives in lieu of on-site visits. Critically, this option is for existing patients that have already been screened, consented, and enrolled in a study. In this model, sites continue to record patient observations and capture study data as they would during an on-site visit.
- Site-to-Patient Direct Data Capture (DDC): Another option is to conduct home visits; essentially, bring the site to the patient. In this model, the home study coordinator should be able to capture data electronically at the point of care. This DDC model has been successfully used in many therapeutic settings to reduce patient burden while still maintaining control over the protocol execution and data capture.
- BYOD ePRO: We consider BYOD ePRO to be part of the available options for those considering virtual studies. In BYOD ePRO, patients use their own devices rather than provisioned devices. Particularly in a situation like the COVID-19 pandemic, the logistics and supply chain issues of getting devices to sites (and ultimately to patients) can become impossible in some settings. Additionally, reusing devices among patients also increases concerns about infection risks.
- Fully Virtual: These types of study designs are theoretical and visionary. They typically are touted in conferences as “the future,” and depending on the setting, can be said to include eConsent, screening, virtual visits, sensor-based data collection, EMR integration, and any number of additional technology approaches. These types of study designs are not currently executed at scale anywhere in the industry, and from a practical standpoint, these potential future innovations do not offer sponsors with a real-world path toward getting things done today.
What are key considerations in arranging and conducting a virtual trial?
Since many in the industry have questions about what virtual trials entail, here are a few virtual trial considerations and options, with particular attention to the systematic application of eSource DDC tools that make these trials so efficient.
- DDC vs. electronic data capture (EDC): The difference and why it matters
DDC and EDC sound as if they might be the same, but they are fundamentally different. In most trials, data from various sources are transcribed into the EDC tool — a time-consuming, error-prone process. With DDC and other eSource data capture methods, the original source data is entered directly into the electronic research record, saving time, reducing errors, and eliminating the need for later verification. The success of virtual trials hinges on this new, clean operational approach.
- The FDA and EMA both encourage eSource DDC
Both the FDA and EMA recently released guidelines for running studies in a COVID-19-impacted world. In those guidelines, the agencies indicated support for a variety of technology-enabled approaches to reduce onsite visits, ensure patient safety through remote monitoring, and encouraged sponsors to focus on protocol compliance. A landmark EMA opinion on a Novartis study that utilized Clinical Ink technologies found DDC methods to not only be acceptable, but advantageous. The FDA had already accepted use of these technologies in an earlier case
- A complete eSource platform integrates a range of useful eSource data capture methods
An integrated, streamlined eSource solution such as Lumenis provides a clear view of cleaner data quickly and efficiently when compared with standard trials. This real-time view of ongoing trial results enables confident decision-making. It also lowers costs and facilitates regulatory submissions. Optional methods for virtual trials include:
- BYOD ePRO: BYOD-enabled ePRO is a key tool in virtual trials. It takes advantage of the devices already in people’s pockets to gather data, send information and instructions, and maintain patient engagement for better retention. Logistically, it’s easier and less costly to implement than provisioning devices. And it can be supplemented with provisioned devices as needed.
- eCOA + Telemedicine: eCOA can be combined with telemedicine and other tools (for example, a home blood pressure cuff) to gather data remotely and enter it directly into the electronic research record.
- eConsent + Telemedicine: Explanations, ID verification, and signing can all be done remotely.
- Other DDC Methods: Physician notes or other, miscellaneous kinds of data can also be entered into the electronic research record to be preserved for later reference or compliance purposes.
- Logistics of ensuring all necessary technologies are in place
By nature, virtual and BYOD studies lessen the logistics burden. A system that works seamlessly and a team with experience applying it in a variety of environments, including high-risk countries, can lessen the burden further.
What are virtual trials’ specific advantages for the study of infectious disease?
In an emerging situation, such as the current COVID-19 pandemic, operational issues are more acute, monitoring is more complicated, and risk is higher because of the potential spread of disease. In this time of major stress to the healthcare system, virtual trials can help.
- Ease physician office and patient burden with:
- No transcription — enter data once
- Recruitment and retention of patients via virtual trial tools
- Data validated at time of capture; no later validation needed
- All eCOA data captured in the same tool as other clinical trial data
- Data entry screens based on familiar documents
- Easy patient communications
- Remote monitoring — few site visits
- Accelerate the entire process to reach data lock ASAP through:
- Easier recruitment and retention
- No time lag between patient visit and monitoring data — monitors and sponsors see effects in real time and make well-informed, optimal decisions
- Reduced monitoring fees
- Closer communication with sites
- Streamlined site analytics and reporting
- Reduced cycle time for database lock, typically 24 hours
A past-due industry advance asserts itself
The full spectrum of DDC, including BYOD ePRO — all the timely advancements to study implementation that are so useful for virtual trials — are widely applicable. The benefits of cleaner data, reduced cost, improved patient engagement, and accelerated results are impossible to deny.
Even at times when contagion is not an overriding concern, we live in a world where 70% of patients live more than two hours from any research site. As time goes on, these innovations will be more relevant than ever.
— Ed Seguine