Traditionally, researchers seek to isolate their studies and the subjects from any variables and intrusions. However, removing research from the ‘real world’ completely can create a number of unexpected issues and prevent a study from yielding the best, most accurate results possible.
Francesca Rinaldo, senior vice president of clinical product and innovation with Sharecare, spoke with Outsourcing-Pharma about how removing all traces of the real world might not be the best idea, and how technology can be harnessed to bring back context and perspective.
OSP: Typically, a study occurs in a lab environment, isolated from the outside world and free from most variables. Could you please talk about why this is the case, and how it benefits researchers?
FR: Medicine is steeped in tradition, and the rituals of the ages extend to healthcare research as well. One of the foremost rituals in medicine in general--and certainly in healthcare research--is provider-centricity.
In other words, regardless of the nature of research, historically it was conducted in a manner that orbits the institution. Clinical assessments were done in the exam room, laboratory follow-up was completed and brought to the appointment or compiled through the medical record, referrals were conducted and faxed back, and patient-reported outcomes are documented in notebooks that were photographed or dictated to the institution.
Perhaps, at one point, this centripetal nature of research made sense; clinical technologies often lacked interoperability (for a long time, the Veterans Affairs system was one of the few with integrated electronic medical records), and consumer technologies often lacked sophistication and reliability. As such, provider-centricity was a matter of fidelity and veracity.
There are other practical reasons for institutions conducting trials isolated from the outside world. Higher levels of control, in terms of the variables influencing patient health, tend to increase effect sizes of interventions, while also augmenting the internal repeatability of specific findings. Increased effect sizes push up the statistical “power” of a study, which in turn reduces the required enrollment to prove a hypothesis. Reducing the required enrollment decreases overhead and variable costs associated with running the trial, and almost always also decreases the time needed to run the trial.
So, the net outputs of isolated clinical trials, from a theoretical and statistical standpoint, are studies that--taken at face value--appear to yield higher magnitude findings at a lower cost in less time.
OSP: How does such an isolated environment stand to impact a patient? What aspects (included, or omitted) might be impacting a patient and their study experience?
FR: From the patient standpoint, there are both advantages and disadvantages to provider-centric studies isolated from the real world. The advantages relate to simplicity: When the majority of the study takes place in a singular context, patients’ experience in the research can be somewhat streamlined. Everything they will do related to the trial either takes place at--or refers back to--a brick-and-mortar clinical setting they can plug into their GPS.
Typically, they will not be asked to do much in terms of data collection outside that setting. What data is collected is collated either in the brick-and-mortar setting itself or via phone calls where the onus is on the researchers.
However, there are numerous setbacks associated with research limited to institutional settings as well. The first is associated with differences in healthcare access. Individuals who are unable to routinely come to the institutional setting due to any number of reasons will be necessarily excluded from the study, even if they want to participate.
As another example, inadequate insurance coverage for research visits can impose a financial burden on patients that may dissuade their participation. Or, lack of transportation to and from the site (including gasoline and parking costs) can make attendance infeasible, unfavorable, or impossible. For patients participating in observational trials, these exclusions may be disappointing.
For those participating in interventional trials--such as for oncologic therapies, where the trial medicine may be the best available treatment for an end-stage condition, the exclusions can be devastating. Further, institutional settings give researchers a rich snapshot at best. Health is a far more continuous and rich variable than a single clinic visit can elucidate.
OSP: How can sites and sponsors evaluate the tech they use and determine what works best in terms of patient engagement, and what should be changed?
FR: The first metric for technology evaluation that sites and sponsors should assess is reliability. The technology of interest--be it legacy software, or a new cutting-edge sensor--must demonstrate accurate and repeatable (precise) measurement of the outcome of interest. These technologies must be calibrated to commonly accepted standards in the field of interest: for example, defining the appropriate planes and angles when using an accelerometer to assess the range of motion.
Second, sites and sponsors should analyze the dynamism of a technology. Ideally, new technologies collect data continuously or regularly. The intervals of data collection should be compared to the needs of the study; reliable data that is insufficiently granular or is collected in a discretized way may not serve the requirements of the research methods, even if the data itself is high-quality.
Third, sites and sponsors should evaluate the interoperability of a technology. New devices and modalities ought to be integrated readily and/or easily into standard research platforms. Without ease of integration, the routine use of new technologies becomes unrealistic, consuming undue time, labor, and expense.
OSP: Please share some examples of study technology that strikes a good balance between patient comfort/ease of use, and being able to get good results for the study team.
FR: Technologies harnessing the power of consumer smartphones offer enormous potential to combine usability and convenience for participants with rich, real-world data for researchers.
One such example is a pilot study in which researchers used the Smart Omix platform to predict the likelihood of seasonal allergy exacerbations. By integrating seamlessly with participant smartphones, researchers were able to extract geolocation data including humidity levels, pollen counts, and air quality indices while simultaneously collecting response data on the emergence of symptoms through an accessible survey tool.
This manner of data collection required little of participants beyond a short questionnaire, while also collecting continuous and comprehensive data about the environmental conditions to which they were exposed. Using a number of proprietary patient engagement and reward modules, the study was also able to retain 99% of the 2,000 recruited participants for 365 days.
Another example was a feasibility study that used a series of digital biomarkers to predict symptom flares of myasthenia gravis, a rare condition. In this study, investigators collected data on participant behaviors including physical activity levels, and linked them to self-reported emergence of symptoms. They also asked participants to complete custom electronic patient-reported outcome (ePRO) tasks like video and voice recordings. It provided another instance in which rich, continuous data was compiled—data that would not be accessible through traditional, institution-centric studies—and created empowering opportunities for participants to gain objective insight into their own management of the disease.
OSP: Could you please share some of the solutions Sharecare offers for clinical research/drug development clients?
FR: Simply put, we are taking the best of our existing tools – engagement, cross-platform integrations, and clinical validation – and directing them towards clinical research. Smart Omix, our flagship research solution is accelerating the world of decentralized real-world research.
Through a robust, scalable technology platform, Smart Omix is able to reimagine traditional methods and uses of real-world data collection. It does so through four powerful, yet intuitive steps that are embedded in the research platform: build, launch, manage, and analyze. Each of these steps contains numerous solutions within it, such as custom survey builder tools, cloud-based data collection warehouses, and sophisticated artificial intelligence tools capable of transforming raw data into impactful findings.
Accordingly, the innovative and multi-dimensional Smart Omix platform can better synthesize the broader influences on health and well-being than can institutional data alone. For example, as I mentioned previously, Smart Omix can extract data on patient behaviors such as activity levels and sleep time. It can also interpolate data related to the environment in which patients live such as pollen counts, humidity levels, or the presence of toxic chemicals (like asbestos or wildfire smoke).
All of these real-world data are critical for researchers and drug developers interested in understanding how their interventions will fare “out there.” Of course, this understanding is critical to both the impact of research studies (since those that cannot be replicated “out there” tend not to curry much long-term favor) and the profitability of prospective therapies (since those that do not exhibit the desired outcomes in real-world environments tend not to be reimbursed by cost-conscious payors).
OSP: Do you have anything to add?
FR: The COVID-19 pandemic has forced researchers to rethink their institution-based models out of necessity. Many institutes shut down or deferred projects temporarily, lacking the infrastructure, labor, technology, or training to operate remotely.
But, some embraced the opportunity to declare themselves at the cutting-edge, conducting research visits through telehealth and monitoring study outcomes through virtual means. Quickly, it became clear that these methods were feasible, tolerable, and even advantageous.
As such, conducting clinical trials in a decentralized manner will no longer be a “nice-to-have,” but a “need-to-have.” Researchers should view data not merely as “whatever is obtainable,” but rather, as an invaluable asset that can be drawn from a variety of rich sources—provided they have the right platform in hand. Thus, for researchers seeking to become early actors in the shifting paradigm—for those seeking to unlock the potential of decentralized real-world clinical research for their own practice—Smart Omix provides the keys.