Can patients uphold the rigorous standards of clinical testing, outside of the clinic? Pfizer is betting that they can, at least for a drug that’s already spent a decade on the market.
Last week, Pfizer announced its new Research on Electronic Monitoring of OAB Treatment Experience (REMOTE) project—a clinical trial for already-approved overactive bladder medication Detrol LA that is to be conducted entirely remotely, using cell phones and Internet access to recruit and follow trial participants over the next year or so.
Why a clinical trial for a drug that’s been on the market for more than ten years? Pfizer decided that a safe, approved medication would be an ideal way to test the method of virtual clinical trials without too much worry about testing the drug itself—the remote trial will attempt to replicate past Detrol clinical trial results, thus helping determine the efficacy of the remote process, more so than the efficacy of the medication, explains Craig Lipset (pictured above), Pfizer’s head of clinical trial innovation (and one of this year’s Pharm Exec Emerging Pharma Leaders). “It’s new patients, but were using the same eligibility criteria and looking at the same endpoints in terms of measures of efficacy and safety,” he explains. “That will give us a good opportunity to understand if these patients are different in some way. First, demographically, when we’re finding patients entirely online versus through the more conventional brick and mortar site approach, and second, if the data we gather from these patients differs in some way in terms of the efficacy and safety they report.”
Patient recruitment is under way, and once patients have been selected, they will each receive a package in the mail containing the necessary medication and—of all things—a smartphone. “We are using a mobile app to enable patients to track what we call a bladder diary—a three-day diary to track their urinary frequency. For patients with overactive bladder, they use that diary a lot, so we didn’t want it to live on their computer where it may not always be accessible,” explains Lipset. “We’re looking at roadmaps for tomorrow where we could push an app to a patient’s own smartphone, but in the world of electronic patient-reported outcomes (EPRO), we’re still not there. We’re not fully comfortable and confident with the security. And if patients use their own smartphones for the trial and then download Angry Birds, what’s the impact going to be on the secure diary app? Is it somehow going to interfere?”
Though the process of conducting clinical trials remotely is unprecedented, Lipset insists that Pfizer didn’t come up with anything all that new—only leveraged existing technologies in new ways. “There really wasn’t a need to reinvent things—telemedicine and remote patient monitoring have already addressed many of the issues for us,” says Lipset. “Somebody chided me the other day, saying ‘Congrats, you’ve caught up with technology that’s 20 years old.’ We didn’t create the Internet, we didn’t create today’s e-patient system, and we didn’t create mobile apps or social media—these trends are happening all around us. It’s just important that we understand these trends and try to keep evolving.”
Be that as it may, when Pfizer brought the idea to FDA, it was still uncharted territory, with no existing paperwork or procedures in place. How was such a novel idea received by an organization that’s all about policies and regulations? “In our first meeting with the FDA, the room was packed—both with FDA and Pfizer bringing legions of people in. But it wasn’t really to debate—it was to collaborate and find solutions, and it was a great experience in demonstrating the FDA’s willingness to support innovation.” The only truly unheard of part of the new trial method that the FDA had to tackle, says Lipset, was drug distribution—Pfizer had to acquire a waiver in order to be able to ship drugs directly to patients’ homes. If remote clinical trials take off in a big way, Lipset predicts FDA will then have to institute further policies and standards, to avoid having to issue such a waiver every time.
So while the whole process seems relatively cut and dried—and shockingly simple—it does raise some questions, about safety, accuracy of reporting, and even cost. The biggest ethical concern and possible liability would come in the event of any serious adverse events (SAEs). While this may not be a huge concern with a medication for overactive bladder that’s already on the market, it’s something that’s got to be looked at down the line if remote trials will ever go mainstream. Lipset says that the process here is very much like the cautionary steps that are typically taken in any traditional, site-based trial—if serious side effects or problems occur, patients often report to their primary care physician (PCP) or local emergency room, not to the trial investigators.
“Imagine a trial for other types of drugs, such as a neuropsychiatric agent for a patient who is depressed. If you’re a patient in that trial who is suddenly suffering chest pain, you’re not going to go to your psychiatrist—you’re going to go to the ER or your cardiologist,” explain Lipset. “So even in those cases, where you’re going for acute care for an adverse event is not back to the investigator in your research study.” This is true regardless of whether the study is remote or site-based, he says.
“I think one of the interesting differences for this project is that patients are connected to the trial 24/7, and it gives us the opportunity to respond in real-time if there are safety issues. We feel that this level of continuous, real-time engagement actually exceeds the current standards and baseline for safety monitoring in conventional trials.”
Similarly, remote trials could potentially result in speedier, more accurate data as well, says Lipset. The key here is that patients can report outcomes, behaviors, side effects, and perceived results as they happen (such as checking in to a bladder diary throughout the day), rather than waiting six weeks or so to report back to a typical trial investigator on-site. “Think about the barriers in place for existing large-scale trials. With multiple sites to select and activate, we have to find patients and recruit them in proximity to those sites. This model has simplified many of those time-intensive tests,” explains Lipset. “And in terms of the quality of the data, we’re now more actively engaging the patient as a participant in the research. We believe that an engaged patient is more likely to persist in the study and more likely to self-report higher-quality data—their data is being reported to us as it happens.”
Finally, cost is something that may change down the line, as the remote trial process is perfected and mainstreamed. “For this first go as a pilot program, I think there’s a lot of buildup that’s needed and so we’re not going to see very significant savings. But our expectation is that this model will help mitigate rising costs of clinical trials, in that some of the most significant costs in clinical trials are starting up investigator sites,” says Lipset.
When pressed about whether these potential lower costs could contribute to lower drugs prices for consumers or generally lower healthcare costs down the line, Lipset responds carefully: “I think there are certainly many benefits to lower costs of clinical trials, both in terms of burden on the overall healthcare system but also the ability to—we in pharma have to constantly allocate a limited pool of resources to the development of new medicines. And so when we find better, smarter, faster ways to develop our medicines, it can also mean more resources available to move more of those other drugs through the pipeline.”
For now, Lipset makes no promises, but recognizes that what Pfizer is doing is a first attempt at a process that will require trial and error, as well as input from the rest of the industry. “Our underlying belief right now is that Pfizer doesn’t own this approach,” he says. “This is in the public domain, and the tools are readily available. And if we want to use this method more broadly at Pfizer, we need it to become a widely accepted method. If Pfizer is the only one doing this, it’s always going to come with challenges and questions and it won’t really become a robust method. So we have an interest in socializing this, and sharing what’s worked so far.”