UNLOCKING THE POTENTIAL OF REMOTE (“VIRTUAL”) CLINICAL TRIALS
By Dr. Roberta Vezza Alexander
San Diego, May 4, 2017
On May 3, the San Diego Clinical Research Network (SDCRN) organized a very interesting event focused on how mobile technologies could be used in clinical research. The event was at the beautiful Genesee Point facility at Campus Point Court and was sponsored by TriNetX.
The event was very well attended, and there was plenty of time to network before and after the presentations. The social aspect of the night was very enjoyable, thanks also to fabulous pizza, snacks, cookies and a variety of wines and craft beers.
Mark Rice of TriNetX described how his company could facilitate enrollment of patients in clinical studies. TriNetX mines electronic medical records to empower members of the TriNetX network to analyze patient populations with specific characteristics. Thus, sponsors can target healthcare organizations where these patients are located. Or they can revise their inclusions and exclusion criteria to reach a broader patient population and increase their chances of enrolling the necessary number of patients.
Teresa Gallagher of SDCRN spoke about the organization that she so passionately leads. She encouraged the attendees to sign-up (registration is free!) to the weekly electronic newsletter Clinical Research Currents (clinicalresearchcurrents.com/newsletter/) to stay abreast of what is new in clinical research nationally and in San Diego. The website clinicalresearchcurrents.com is a great resource for local happenings, and members can submit their events to Clinical Research Currents as a way to promote them.
The main part of the event was moderated by Jennifer Reichuber of Altani Associates . Panelists included: Jeff Frazier, CEO and Founder of THREAD Research ,David Turner, President and Founder of Parallel 6, and Penny Randall, M.D., VP and Global Therapeutic Head of CNS at QuintilesIMS. They discussed how mobile technologies can facilitate enrollment, engagement, and retention of patients in clinical studies, ultimately leading to accelerated approval of new medicines, saving time and money.
WHAT IS A VIRTUAL TRIAL?
Virtual trial, remote trial, remote research, or similar terms can be used to indicate the broad use of technologies to get patients’ data between doctor visits or in place of doctor’s office visits. Traditionally, data is collected only when the patient goes to the study site. Virtual trials allow the collection of data at home, which can be more feasible and cost-effective than collecting data at physician office visits. Obviously, the data collected need to be encrypted, secure, and compliant with privacy laws. Among the different available technologies, wearable devices can theoretically collect data continuously and cheaply from a large number of patients. These devices can also track patient location. The research team can see if patients leave the house or go to work, and this can suggest whether the participation in the study affects normal daily activities.
Certain therapeutic areas may be better suited to virtual trials than others. As the panelists described, rare diseases, diabetes, and Alzheimer’s disease are amenable to remote trials. Other therapeutic areas may be more difficult to translate into virtual research. For example, trials that involve controlled substances may need to be conducted in person because of the possibility for fraud or diversion.
“CRAWL, WALK, AND RUN”
The implementation of virtual trials does not need to be all or nothing. Jeff Frazier from THREAD Research used the analogy of “crawl, walk, run” to describe how companies can use technology in their studies.
One can begin by “crawling” — for example, using traditional study sites and traditional office visits while having patients fill out patient reported outcome measures (PROM) at home between visits. While PROM are a good example of remote research, mobile devices can also be used– for balance tests, spatial memory tests, tests to measure tremor, and to collect a myriad of data in real time.
The “Walk” stage would be substituting some office visits with virtual visits, for example using videos. Video consults with physicians are becoming more and more popular in clinical practice and in trials.
One enters the “Run” stage when very few of the study visits are in a doctor’s office, and there are no clinical research sites. This approach can be harder to implement, but not impossible. For example, a diabetes trial can be done remotely with the help of home nurses. Patients enroll in the study from home, sign the informed consent document via a mobile device, and provide study data via the device as well. Home nurses visit the patients periodically to do blood draws and other tests., but the bulk of the study is done remotely.
REMOTE INFORMED CONSENT
Although one thinks at the informed consent form as a document that requires a wet signature, this is not necessarily the case, and mobile technologies can be used to administer informed consent. Different countries have different regulations, but in general, an electronic signature on a tablet is sufficient. In some cases, security features in the device can be unlocked, or a video can be added to verify that the person signing the form is the patient. Importantly, the patient has the opportunity to ask questions during the virtual informed consent process, as is the case in traditional enrollment at the study site.
Technologies designed to collect more data, more often, from more people, need to be user friendly. Patients are no different, from this point of view, from the consumers that use Parallel 6’s technology to bet on horses at the Del Mar racetrack. Apps or other electronic tools do not appeal to anyone, study participants included, if they drain the cell phone battery, load slowly, or their use is non-intuitive. If you want to keep patients engaged, which is the point of virtual trials, the app has to be good. and secure, and patients need to have the same experience on any device – that is running Android, iOS, or whatever else will be developed in the future. Surprisingly, gamification is a patient engagement tool that works. People like to get congratulatory messages and badges for completing tasks, or for having finished X number of visits.
APPLICATION TO INTERNATIONAL TRIALS
Mobile technologies and apps in multiple languages are proving very effective in trials done around the globe. Industrialized countries are not the only ones where remote trials can take place. In fact, people in third world countries are usually well equipped with mobile devices and tend to have very sophisticated smart phones that lend themselves well to remote trials. The ability to reach people around the word can facilitate enrollment for rare diseases studies. For example, David Turner from Parallel 6 described a rare disease trial where the principal investigator, who is in Italy, sees patients from all over the world remotely, using Parallel 6’s technology. As this trial will last 20 years, it is paramount that the technology can evolve and be adapted to whatever devices may be used in the future.
CASE STUDY: ALZHEIMER’S DISEASE
The last presentation of the evening was a case study presented by Dr. Penny Randall from QuintilesIMS, which illustrated how a remote approach can facilitate the development of drugs for Alzheimer’s disease (AD).
AD begins as asymptomatic. With time, some memory loss symptoms start to appear, and eventually the patient develops dementia and loses independent function. Pharmaceutical companies have been focusing so far on developing therapies for late stage AD, which have shown little success in the clinic. As early AD may be easier to treat than late stage AD, pharmaceutical companies are beginning to focus on this stage. The presence of specific biomarkers or suboptimal performance in cognitive testing suggests the presence of AD, even in the absence of symptoms.
To enroll a large number of asymptomatic AD patients in their study, QuintilesIMS used a telemedicine partner and primary care physicians (PCP). In fact, primary care providers are the ones who see these early stage AD patients, not for AD, but for all types of medical issues. QuintilesIMS used a central clinical site with experience in AD, and recruited for the study PCPs in Arizona who see a total of 450,000 patients. One can estimate that, of these, 10,000 or 15,000 have early stage AD. The patients were screened for Alzheimer’s, either face-to-face or remotely, using cognitive testing. To minimize bias, the study was a cross over design, so that each patient served as his own control, and the order in which the test was administered – in person or virtual – was randomized. Using the virtual model, enrollment was 3 times faster than one would have expected using traditional methods. More importantly, the study data were robust, and there was a high correlation between the test scores in the telemedicine and in-person group.
The event was very informative, and provided a broad perspective on how the virtual trial model can utilize patient-reported outcome measures (PROs) done by patients at home using mobile devices, and clinician-administered measures done remotely. Compared to traditional clinic-based clinical trials, virtual trials can enroll more patients faster and keep them engaged for a longer followup period, while reducing the time and cost associated with the development of new therapies or devices.