By Deborah Borfitz
January 15, 2013 | Newly minted software facilitating the “crowdsourcing” of clinical trials has proven its worth in a recently-approved multiple sclerosis (MS) study that will make unusually high use of both telemonitoring and the measurement of patient mobility. The protocol, as originally proposed by Transparency Life Sciences (TLS), was significantly enriched after undergoing global scrutiny by researchers and MS patients, says Marc Foster, co-founder and chief operating officer of the open innovation drug development company. In December, it became the first crowdsourced protocol to be cleared by the U.S. Food and Drug Administration (FDA).
The most immediate goal of the new trial design approach is to break down the “wall of cost” that waylays promising drugs once they enter human testing, says Foster. A repurposed generic cardiovascular drug (lisinopril) whose safety profile is well known was a practical starting point for the phase II MS trial to keep the regulatory focus on study execution. A “very lively” MS online community also ensured a degree of patient engagement in the protocol-building process despite a modest marketing budget for the process.
Cost reduction is the “low-hanging fruit” of the study’s novel design and execution, but not the only benefit, says Tomasz Sablinski, TLS founder and chief executive officer. Remote monitoring of patients makes comprehensive, around-the-clock measurement of mobility a plausible endpoint and data collection more precise and objective. Notably, remote data collection is highly compatible with the multi-dimensional MS Functional Composite (MSFC) mobility assessment tool.
Using its Internet-based Protocol Builder software, TLS elicited input on the MS study from about 30 clinical researchers and 70 patients hailing largely from the U.S., says Sablinskli. Protocols more typically get composed by a handful of key opinion leaders who are costly to engage and invariably replicate the last FDA-approved drug in terms of endpoints and measurement methods. Patients, and their physicians, are “chronically under-represented,” he adds. “We aim to rectify that.”
Open, Transparent Process
The common theme among patient contributors was a preference for outcome measures “meaningful to them as people,” says Sablinski, formerly a transplant surgeon and vice president at Novartis. “They aren’t anti-science, but they… care more about getting up in the morning, moving around successfully, and not being wiped out by fatigue.” Capitalizing on ubiquitous, inexpensive, and FDA-sanctioned monitoring devices to make those sorts of measurements should result in a more successful repurposed drug on the back end because its label will be relevant to patients.
Feedback from the “crowd” has been discussed with MS researchers who have existing ties to TLS, says Foster. This includes Stanford University neurologist Jeffrey Dunn who is serving as the study’s principal investigator and was a strong proponent of incorporating movement measurements into the protocol, says Foster. All 150-180 study participants will be recruited from the Stanford catchment area.
Crowdsourcing will next be used to expand the MS study in terms of the statistical analysis plan and data collection devices to be used, says Sablinski. The possibilities include GPS-equipped smart phones. Clinical grade EKGs are also possible with a special iPhone case and an app (see, Heart Monitor for the iPhone). Telehealth specialist Advanced Monitored Caregiving is the only formal technology partner so far.
Feedback from patients and physicians will also be solicited regarding comfort level with a year of home monitoring and virtual visits, as well as their communication channels with clinical staff, Sablinski adds. The protocol calls for two in-person monitoring visits, at the start and end of the trial.
The number of protocol contributors will likely grow, as the TLS website has seen a three-fold increase in daily traffic since the FDA cleared the protocol, Sablinski says. The site has to date attracted 12,000 unique visitors, roughly half of whom reside in non-U.S. geographies.
Startup of the MS study is ambitiously projected to begin by the end of June, depending partly on the constituency of the institutional review board at Stanford University and its familiarity with telemonitoring, says Sablinski.
All real data from the study will be posted on the web and professional statisticians will be welcome to do their own analysis and find “hidden gems or red flags,” says Sablinski. “I’d rather know [there’s a problem] when we’re developing a drug than have it taken off the market [later].”
Trifecta of Benefits
Savings on the study execution side, primarily by reducing in-person monitoring visits, is expected to reduce overall clinical trial costs by at least 50%, says Sablinski. Study monitoring, which would otherwise run about $5,000 per visit per patient, costs between $500 and $600 to accomplish digitally.
TLC intends to build all its protocols via crowdsourcing, says Foster, and design time will quicken as fluency with Protocol Builder broadens. Ultimately, it is hoped that patients will be more interested in participating in a study they helped design, adds Sablinski. Retention rates should also improve by designing more meaningful studies, keeping the communication lines open with patients, and collecting data at home.
Additional phase II protocols for drugs targeting Parkinson’s and Crohn’s diseases will be built after TLS finishes upgrading its patented crowdsourcing technology and amassing “crowd recruitment” lists, says Foster. Assistance in this area is being provided by Karim Lakhani, a Harvard Business School associate professor and “rising star in crowdsourcing,” who is an advisor to TLS.
Successful molecules will be licensed to partners for phase III trials.