Recruitment, retention and monitoring account for ~30% of trial costs, according to a study carried out by the Eastern Research Group. Leveraging digital tools can help to overcome challenges associated with traditional clinical trials and greatly enhance research. These range from devices for remotely monitoring biometric data, to platforms for collecting patient reported outcomes (PRO), and facilitating patient recruitment for trials. However, there are a number of challenges and key considerations when it comes to incorporating a digital element into a clinical trial, and we are yet to see this become standard practice in the industry. In this week’s blog, we deep dive into the potential of digital to augment and ease the running of clinical trials, and how to successfully execute one.
By now we are all aware that by remotely monitoring a patient, you eliminate the need for in-person visits, overcoming the physical barrier to participation that exists in standard clinical trials, enabling a more diverse patient representation, and expanding the reach of the study. Remotely monitoring a patient’s biometric data allows for objective, continuous monitoring, which provides more accurate, contextual data, eliminating retrospective bias that often exists in standard clinical trial PRO data collection. In many cases, the use of such tools also allow for the investigation of new digital biomarkers.
In Data We Trust
In a recent blog, we wrote about how regulation is catching up with digital health, exploring the steps that the FDA has taken in reaction to the burgeoning field of digital health. This activity not only applies to approval of SaMDs, but has recently been extended to the clinical trial space with the release of the FDA MyStudies App for open source data collection from patients in 'digital' trials, increasing the diversity of information available and enhancing clinical trials and other healthcare research.
“This digital platform enables developers to adapt our technology to advance new ways to access and use data collected directly from patients—with the necessary controls in place to ensure patient privacy. Our hope is that the collection of more real-world data directly from patients, using a secure app, will lead to more efficient product development and assist with safety monitoring.”
FDA Commissioner Scott Gottlieb, MD.
Having access to more data is particularly useful for diseases that have no cure, but in which medication is used to control symptoms, such as Parkinson’s Disease (PD). Being able to continuously monitor symptom data at a much higher frequency than in standard clinical trials can generate actionable, environmentally relevant insights on clinical endpoints that previously were unmeasurable or not collected, allowing symptom severity to be determined with greater sensitivity and objectivity than standard clinical rating scales.
In 2018, Roche and Prothena published a study that examined the feasibility, reliability, and validity of smartphone‐based digital biomarkers of PD in a clinical trial setting. The trial took place over 6 months and had 43 patients with PD enrolled, as well as 35 age/sex‐matched healthy controls. Participants were given a smartphone with an app on it, which included 6 active tests: Sustained phonation, rest tremor, postural tremor, finger-tapping, balance task, and gait task. Passive monitoring was also carried out via the smartphone, enabling assessment of time spent walking and sit‐to‐stand transitions. All active and passive features significantly differentiated PD from controls with P < 0.005, and all active test features (except sustained phonation) were significantly related to corresponding International Parkinson and Movement Disorder Society–Sponsored UPRDS clinical severity ratings, demonstrating the feasibility, reliability and validity of smartphone‐based digital biomarkers in PD.
Diversifying Patient Populations
Beyond just remote monitoring of patients, there are a number of solutions available that are enabling easier recruitment of patients for clinical trials, overcoming a longstanding challenge in this space, and broadening the potential patient population taking part in clinical trials.
According to research carried out by Tufts Medical Centre, around 50% of all trials fail to achieve planned patient enrollment targets. A number of companies have begun to take advantage of this and have developed solutions to identify patients to include/exclude in a trial, trying to find the most appropriate patient cohorts for a specific trial based on patients medical records.
Where we see a real benefit here is in greater diversity of patient populations, not just by race or genes, but also by age, disease states, urban/ rural, etc. According to Science37, most clinical research studies are made up predominantly of Caucasian participants - few studies reach even 10% minority enrollment. With their catchy tagline of ‘Thinking Outside the Box by Putting Clinical Research in a Box’, Science37 broke ground earlier this year when they completed the first fully site-less clinical trial. All of the initial screening and consent processes took place remotely from the platform and during a phone call, all of the study materials and drugs were sent directly to the patient, and they were also given access to a telemedicine app called NORA via which they could communicate with the trial creators. PROs were also collected, and virtual clinic visits conducted, via the NORA app.
Of the 8,000 remotely screened patients, 372 were enrolled in the study. The study boasts 41% of study participants to be non-Caucasian, noting that implicit physician bias for patient selection and physical barriers to access are the main reasons why there is so little diversity represented in standard clinical trials, and that the direct-to-patient outreach of Science37 helps to overcome these issues.
Retention of enrolled patients is another other important point - drop offs from prolonged studies is a major factor for protracted and failed trials. Incorporating smart devices and wearables into clinical trials may help to keep patients engaged throughout the trial, which can increase patient retention, particularly in trials which utilize the Bring Your Own Device (BYOD) model, and incorporate features such as gamification, daily reminders, and notifications to facilitate engagement from patients. We have yet to see any strong data on how using the above has impacted drop-off numbers.
Reduction in costs is also recognised as one of the benefits of incorporating digital tools into a clinical trial. According to Cutting Edge Information, the average trial rose in cost by 60% between 2008 and 2013, reaching an average of $48,500 per enrolled patient in Phase 3b trials. Tufts research puts the total cost of new prescription drug approval at roughly $2.6 million per drug.
Digitally-enabled clinical trials have real potential to reduce site-overheads by facilitating remote clinical trials. Continuous remote patient monitoring generates significantly larger volumes of data than in standard trials, increasing the number of data points generated from each patient, and in turn reducing the cost and time taken to conduct the trial. Although, at present, it appears that development and adoption costs of running digitally-enabled clinical trials are militating against the potential financial savings.
Although digital is very good for all reasons outlined and will ultimately reduce costs, in some cases it may actually cost more to run a digital trial, especially in the early days until the process is more streamlined. For example, running a trial with a sensor embedded capsule will surely cost way more than a pill without a sensor because of the more expensive manufacturing processes for a sensor embedded pill. However, the wealth of information received from a sensor embedded pill, particularly the objective adherence measure, may be worth the initial increased cost in the long term.
What a Robust Digitally Enabled Trial Looks Like
So, taking all of the above into consideration, what is the best way to actually execute a digital clinical trial?
- Patient Centric approach -> Whatever digital solution you decide to incorporate into a clinical trial must cause limited disruption to the patient’s day-to-day life. Passive data collection, if possible, is preferable for patients as it limits the burden of constantly reporting. Consider how well suited the solution is to the patient population, for example those who are less familiar with using digital solutions may need training and support. An important point to note regarding replacing in-person visits with remote consults or questionnaires is on the importance of the role of the physician and the human aspect they bring to the exchange? Some may say that this is a generational issue, and in order to overcome this, you may have to add an option to have numerous in-person visits, if desired. If you add an option to offer in-person visits, you must consider that this could lead to different clinical outcomes and be able to account for that accordingly.
- BYOD vs Recommended Medical Grade Device -> Ensure you have selected a device that is fit for purpose and will allow you to collect the desired data to add true value to the trial. This will be dependent on whether you intend to just passively monitor patient data, or if you are investigating digital biomarkers for clinical use. It is also important to consider how the metrics you are tracking compare to the standard clinical rating scales. Running feasibility studies prior to the clinical trial can help to gather information on the tolerability and fit of the device.
- Understand the Data ->Being able to process the data captured in order to maximise insights derived is crucial. Ensure that you can validate the data captured - is it as accurate as standard of care measurement? Is it reproducible at a large scale?
We are really excited at the the potential of digital health to improve clinical trials, and look forward to a time where we move beyond speculation and begin to see evidence from large-scale trials, driving the incorporation of digital solutions into standard clinical trial practice.
Are you a pharma company that is leveraging technology to enhance the clinical trial process? Or a company developing a digital health solution that could play a role in clinical trials? We’d love to hear from you!