The modern patient-reported outcome (PRO) study does not unfold in a vacuum. Whether launched via the web, a telephone interactive voice response system (IVRS), or a dedicated handheld device, most PRO projects rely on an army of external consultants and suppliers.
Simple web- and IVRS-based PRO studies can handle only so much complexity, only so much branching logic, in which software automatically advances a patient to different parts of a questionnaire depending on previous answers. For embarrassing medical conditions or especially frequent reports from patients, the web and IVRS work well. But for graphics, interactivity and connections with physiological instruments like spirometers, a handheld device is obligatory.
At the moment, the ePRO device landscape is in flux. Many of the industry’s most sophisticated suppliers initially built their franchises around small lots of custom-manufactured gadgets or non-telephonic personal digital assistants from Palm. But Palm is facing significant market share losses, possibly even a protracted corporate death, because of competition from two ascendant smart phones: RIM’s Blackberry and Apple’s iPhone. So the pharmaceutical industry’s reliance on Palm for ePRO is ebbing, with few new trials still using its once market-leading devices.
At the same time, new comfort with the Windows mobile architecture has been building for a few years, with firms like Merge boasting a technology division that has extensive experience on the Microsoft platform.
The small screen environment on Windows, by most accounts, is not as intuitive for ordinary citizens as anything from Palm. But it offers superior foreign language support, lower development costs and multiple hardware suppliers for handsets and tablets. Microsoft, unlike Palm, never walked away from mobile solutions dedicated to business. Microsoft supports both a long list of telecommunications carriers and its own internal healthcare group for wireless devices.
Key ePRO Suppliers
By most estimates, the ePRO market might be in the vicinity of $100 million in annual sales, making it perhaps a tenth as large as the electronic data capture (EDC) market. The three apparent leaders—CRF, invivodata, PHT—have enough international project experience to be able to handle large trials for big pharma. But a host of firms also thrive in the sector and also have customers in big pharma. Those names include Almac, Arrowhead, Assistek, Certas, DSG, ERT, Exco, Icon, Medrio, MetriSense, Perceptive and Symfo.
All of them routinely combine ePRO with other trial technologies such as EDC, randomization or drug supplies. That may explain why Phase Forward this week plunged into ePRO with an $11 million purchase of Maaguzi. There’s a section of the ClinPage website dedicated to IVRS and diaries here, with links to additional stories at the bottom of that page.
At PHT, president and CEO Phil Lee concedes that a brutal economy has prompted a small number of customers to cancel or postpone projects. As with any industry in this economic climate, there is unrelenting pressure on prices. Which presents a dilemma for the ePRO suppliers. They confront complex logistical challenges and the knowledge that the sponsor community typically expands the scope of its projects over time.
Not A Frill
Lee says the centrality of ePRO has never been clearer for some customers. “If it wasn't central to the trial, they won't use ePRO," he says. "We are too expensive as a frill or nice-to-have. The quality of the data is paramount. We're in the business where the data we capture is the most important data in the study.”
Lee also reports more direct, private objections to paper diaries from regulatory agencies. In one respiratory trial requiring patients to use a spirometer, the sponsor elected to use paper diaries. Regulators balked. After all, they pointed out, the trial required the data to be recorded in 2-3 days. “The regulatory agency had advised them that for the data to be valid, ePRO was a superior technology,” Lee recalls. “That is very new. The regulatory body is actually pushing back on paper.”
Lee is careful to add that the FDA doesn’t explicitly require sponsors to stop using paper. There is no statutory basis for that. But data quality concerns around paper, chiefly related to whether patients fill them in exactly when directed, are apparently looming larger. Says Lee: “I don't think the FDA says, ‘You must.’ They say, ‘It makes more sense, and these are the reasons why.’ ”
Raising The Bar
PHT's chief quality and scientific officer, Steve Raymond, amiably allows that when he started the firm back in the 1990s, he and his investors were hoping to create what would become the electronic data capture (EDC) or electronic health record (EHR) industry. It didn't turn out that way. But the logic behind electronic data was obvious to early users of the systems. No transcription. Higher data quality. Done.
The centrality of the patient's perspective, he says, was something that came into view slowly. Technology solved a problem that the scientific and regulatory worlds didn't necessarily know they had with paper diaries. "It elevated the kind of information that had always been captured on paper but was always suspect," he says. "Who completed it? When was it completed? What happened when [the instrument] wasn't completed?"
Gradually, ePRO helped bring the patient's experience to the center of some protocols. "The quality of the data was so low that I think the paper diary element was relatively untrusted and secondary," says Raymond. "Moving the quality of the data up and providing more of it, and knowing for sure when it was completed, added to the credibility of the patient assessment. It really has transformed the face of clinical research."
It took a while for that message to sink in. In the interim, for better or worse, the clinical development community wrapped itself in a beloved security blanket—paper. Sponsors clung to pressed, dead trees partly out of a deep generalized timidity around any new technology, partly out of appropriate concern that regulators and sites were more comfortable with paper. So an early vision of paperless ePRO, i.e. ePRO via esource, was deferred. Paper was inserted back into a process that might have been born wholly electronic. "The paper CRF was in some ways a little like a treasure," says Raymond.
A former MIT professor, Raymond can recite chapter and verse from CFR Part 11. In presenting at conferences, he seems to delight in his command of both the verbatim text and the spirit of the federal regulations. But what energizes him most is the larger potential for the industry: "Our original vision was that an electronic methodology would so dramatically improve the quality of the data and the ease of conducting the trial that it would be essential for clinical trials to become eclinical trials."
With Washington's current focus on comparative effectiveness, Raymond thinks ePRO will be even better positioned as an indispensable element in the clinical toolbox. Patients themselves, he suggests, will be crucial participants when scientists sort out which of two interventions is best. Anticipating future regulatory reliance on comparative effectiveness data, some sponsors are considering ePRO for every trial. "They are adopting electronic information as a corporate level strategic objective," Raymond says.