A few months back, we noted that AstraZeneca and PHT announced that e-diaries had supplied data for the July 2006 approval of Symbicort, a combination therapy for asthma.

Recently we caught up with PHT to discuss the announcement. Its diaries were used in two pivotal trials that supplied the primary endpoint data for the approval. The studies involved 1,076 patients at 45 sites in the U.S. The patients were adolescents ages 12 and older who used the PHT hand-held device, called the LogPad, to complete daytime and nighttime entries.

To quote the news release: “Patients recorded information on their Peak Expiratory Flow (PEF) scores, nighttime awakenings, sputum, coughing and breathlessness in order to provide scientific researchers with insights into treatment improvements in asthma symptoms and health-related quality of life.”

Steve Raymond is the co-founder and chief scientific officer at PHT. He notes the the project in question began some years ago. Even so, the effort was interesting for the importance that AstraZeneca and the FDA attached to accurate, direct input from patients.

“The stuff is out there and working,” he says of the diaries. “The thing that is unusual is the trust that seems to be placed in the voice of the patient. The increase in data quality is altering the scientific terrain.”

Higher Profile

There is some murkiness around how many approvals have been based on PHT’s technology. Customers don’t necessarily volunteer that PHT’s Palm devices were used in an important trial. Most likely, four other products have been approved using PHT devices, but the company doesn’t identify them.

“Approvals are useful,” says Raymond. “We often get asked about them. We don’t always know when a drug is approved based on our material.” By the same token, the absence of approvals in a therapeutic area hardly means regulators are uncomfortable with electronic patient-reported outcomes (ePRO).

Quoting an ex-FDA official, Raymond says it’s likely that the prominence of patient-based data will continue to grow: “The patient has an intrinsic right to undersand what is likely to happen to them. Will I function better? Will I feel better? They do have a right to the information. We see that as the future, even though it isn’t being harvested in any meaningful way now. The vision is more palpable and more likely.”

Teenager Trial

The age threshold of young patients who are able to use patient diaries, Raymond relates, has little to do with the software or hardware. (The devices themselves are manageable by even very young children.)
Rather, it has to do with pediatric patients’ inherent psychological immaturity. “The reliability and capacity of a child to do a self-assessment is getting a little fuzzy below 10 years old,” says Raymond.

In some cases, of course, parents were helping children use the devices. And in such cases the diaries, as it turns out, can help sponsors finesse a thorny regulatory tangle: overlappping rules about privacy that pertain not only to patients but also caregivers—and to others who record information on behalf of patients.

The FDA wants sponsors to know who gathered the data and who the data pertains to. Perhaps the father always thought a child was ill, and the mother never did. Recording which parent made the record is one issue.

Recording the anonymity of the person making the record is another. “If you have it on paper, you cannot perform that miracle,” says Raymond. “It would have been impossible to capture that same information on paper and honor the privacy constraints that have grown up with HIPAA.”

Real Data

And of course one issue with respiratory studies (some 30 percent of the projects at PHT) is that just as patients invent future and past paper diary entries, they also fabricate PEF meter readings rather than actually breathe into a device. Says Raymond: “We’ve endeavored to have a product which a patient uses that automatically sends the data to the LogPad. The only way to get the data into the LogPad is to blow into the PEF meter.”

The PHT devices also assisted with the management of the trial, with the devices calculating eligibility criteria and alerting study participants to contact study personnel when PEF scores decreased 20 percent or more from the baseline over three days within an interval of seven consecutive days. The devices don’t make medical decisions, but they can facilitate communication between patients and sites.

e-Diary-Safety Link

Raymond suggests that diaries may be one tool to address heightened industry and FDA concerns about drug safety, both during and after Phase III trials, “The programing of alerts is coming up more often. You have even more ready access to the data than you do with standard electronic data capture,” he says. “The kind of information you’re getting about how a subject is doing lends itself to monitoring or surveillance.”

In many ways, although the data is not required by regulators, e-diaries in clinical trials could be leveraged to collect data about quality of life and pharmacoeconomic benefits of various therapies. Raymond says the company is interested in that niche, and has already developed physical activity monitors that record when patients are moving throughout the day.

In some cases, such movements (or lack therof) could be both scientifically significant and set in motion the remote intervention of other health care professionals. But this correspondent’s impression is that funding and enthusiasm for such projects seems confined to the world of health-care conferences, not actual research projects.

PHT has a newly redesigned website. It includes a demo of their technology. You can find that here.

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