Lindsay McNair and Josh Rose explore the status quo for virtual clinical trials
Evidence shows that when patients are engaged and empowered in the clinical trials process, trial efficiency improves. In the last few years, as patients became more involved in the design and conduct of research programmes, there has been a notable increase in the idea of decentralised or ‘virtual’ clinical trials. While the term can be used in different ways, ‘virtual clinical trials’ are fundamentally a movement of clinical studies away from medical institutions. In the virtual trial model, clinical studies are focused on bringing the clinical study directly to the participant and allowing data collection to be completed in participants’ homes or communities.
Virtual clinical trials encompass different organisational models. At one end of the spectrum is a pure virtual delivery model in which all study activities are conducted remotely, with no travel requirement for participants. Even the informed consent process is conducted electronically online or through a tablet or smartphone application. These studies also take advantage of mobile phone apps like the Apple ResearchKit, fitness trackers and online patient-reported outcome assessments to collect data either passively (eg fitness trackers recording sleep patterns and automatically transmitting data to the study database) or actively (eg participants completing quality of life or other outcome surveys online).
The first virtual trial was the REMOTE study of overactive bladder disease sponsored by Pfizer in 2011, which was entirely home-based for participants. Informed consent was obtained online and documented by electronic signature, the study drug was delivered directly to participants’ homes, and adverse event reports and efficacy outcomes were recorded using mobile devices and web-based measurement tools. Sage Bionetworks conducted a completely virtual clinical study in 2015 to assess the natural history of the symptomatic progression of Parkinson’s disease in 9,500 participants. In this observational study (which did not include administering an investigational product), the entire study – including documenting informed consent and recording all measurements – was conducted through the mPower app on participants’ iPhones.
Another delivery modality is a hybrid virtual trial, which mixes remote data collection with clinical site visits. For example, initial study screening or complex procedures required mid-study are conducted at the clinical site, while activities like intermittent check-in visits and routine blood draws can be completed via tele-visits or deployment of home health nurses.
Gathering a more diverse patient population
Advocates of virtual clinical trials see many potential benefits. First, they can make involvement in research more feasible for more patients. Reorganising trials around participants’ schedules may eliminate the need to travel repeatedly to a medical centre, wait in line at the lab, or juggle time constraints of work and family obligations. This, in turn, leads to easier enrolment and higher rates of retaining participants through study completion. Virtual trials should certainly put an end to the common finding that, on average, 20% of clinical sites opened for trials never enrol any participants.
The virtual research model also means that study participation should be available to a broader geographic and demographic distribution of patients. There is hope that virtual trials can expand the racial, ethnic and age diversity of study populations, allowing a more complete understanding of how investigational products work in more diverse, real-world settings. Since this research model is fairly new, we will have to wait for concrete data across a broad spectrum of studies to show impact.
Navigating regulatory oversight
Regulatory leadership is broadly committed to modernising clinical trials, increasing clinical trials access and strengthening diversity. While specific guidance on virtual trials could be years away, the FDA, for one, has participated in related discussions at CTTI, and with sponsors and providers alike. Its primary concerns revolve around the same priorities as in traditional trials: for example, ensuring data integrity and patient safety, such as establishing a clear path for dealing with adverse events.
One common question from sponsors considering or planning decentralised (virtual) clinical trials is about FDA Form 1572, the form submitted to the FDA to identify the principal investigator (PI), clinical site staff and facilities to be used for each clinical ‘site’. When there are no actual physical clinical sites, sponsors struggle with whom to list as the PI. In some cases, they may decide to submit one Form 1572, identifying one person as the PI for the entire study. This may best reflect the decentralised study model, but the PI should be aware that he or she is assuming training and oversight responsibility for all members of the study team. Other suggested models include identifying one PI for each state in which participants will be enrolled.
While the European Medicines Agency (EMA) has not issued specific guidance for virtual clinical trials, it has published its draft Regulatory Science to 2025 strategy plan to drive collaborative evidence generation that improves the scientific quality of evaluations. Core recommendations include developing a regulatory framework for emerging clinical data collection, which will involve revising regulatory oversight to enable decentralised clinical trial models with direct data accrual, and creating methodology around wearables and training for healthcare professionals and patients to participate in virtual trials.
With this vision in mind, it is anticipated that the EMA will be working closely with stakeholders to develop guidance on virtual clinical trials. To date, the EMA has published a draft qualification opinion concerning the use of eSource Direct Data Capture (DDC) in the conduct of clinical trials in the EU (EMA/282576/2018). Draft guidance on electronic source data is anticipated to be released in 2019.
Overcoming potential roadblocks
It is essential to remember that digital devices, mobile applications and online communication methods are useful tools but are not complete solutions. The launch of Apple’s ResearchKit facilitated the enrolment of thousands of participants into research programmes on a wide variety of chronic diseases but, several weeks later, about 90% of initial enrollees had dropped out of the projects. The Pfizer REMOTE study was stopped after failing to recruit sufficient participants. It did, however, provide important information to that study team and the research community about the need for greater support and resourcing to handle participant questions and concerns about sharing personal medical details online. For these reasons, it is important for companies that are initiating decentralised clinical trial projects to work with partners who have experience in the actual conduct of virtual studies and can offer an end-to-end solution, rather than relying on grouping random technological tools to make the study flow easily.
Some patient populations may be uncomfortable with technical aspects of decentralised clinical trials. On the other hand, some patient populations may be ideal for this type of communication. For example, UCB and Science 37 are collaborating on a study of restless leg syndrome expected to enrol 138 participants age 13-17. UCB had originally delayed the trial due to expected challenges for clinical sites to find eligible patients in this age category. But with a decentralised model targeting a group extremely comfortable with online communication, they project an enrolment time of 18 months.
Virtual clinical trials offer potential advantages in moving toward a more patient-centric research model and a more diverse patient community in clinical trials and thereby bringing trial data closer to real-world experience. Decreasing the burden on research participants may improve study enrolment rates, allowing for faster trials and the ability of biopharma and other study sponsors to reach decision points sooner, and in turn optimise research investments and pipelines. While there are an increasing number of internet-based and electronic tools available for these studies, they do not provide complete solutions. As more researchers move toward the virtual trial model they must be mindful to seek out partners with experience in the unique design, conduct and ethical challenges of this research approach.
Lindsay McNair is chief medical officer of WCG, Josh Rose is VP of clinical development strategy and innovation and global head of virtual trial operations at IQVIA