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Resistance persists, but inventors undismayed
Medication monitors — gadgets intended to help patients remember to take their medication, as well as to record when and how often they go astray — traditionally have garnered little respect in the TB world. Part of the opposition to the idea of using the monitors seems to be philosophical, while part probably stems from assorted kinks and drawbacks associated with various candidate monitors’ designs.
That hasn’t deterred the small universe of determined inventors from continuing to tinker with their beloved gizmos. As technical advances in the prototype products continue to pile up, it seems likely that sooner or later, a compliance monitor will hit the market that’s simply too user-friendly and inexpensive to ignore.
Consider two recent developments: Sequella Inc., a Rockville, MD-based company that nurtures promising research into marketable products, is conducting animal studies on a monitor that will, if all goes well, begin trials in humans in a little over a year. The Sequella prototype is notable for the way it vaults over what some critics say is the concept’s biggest shortcoming — namely, that the devices can’t tell whether patients have simply removed their pills from the container, or if they’ve actually swallowed them.
Shining a light on the subject
Sequella’s solution — originally the brainchild of University of Alabama researcher Candace McCombs, PhD, and chief of experimental medicine at the University of South Alabama in Mobile — has been to add a fluorescing molecule, or fluorophore, to the TB drug; and then shine a tiny laser (concealed in an otherwise ordinary-looking wristwatch) onto the veins that run close to the skin’s surface on the inside of the wrist. Once the drug has been ingested, the fluorophore reflects light; and a recording is made of the event to provide a record of when the pill was taken.
Sequella scientists think the monitor will prove useful in a variety of settings where compliance is problematic —including treatment for TB, HIV/AIDS, and alcoholism. A grant that will take the device at least partway through initial development, and which will pay for animal studies, comes, in fact, from the National Council on Alcoholism and Alcohol Abuse.
Meanwhile, Tom Moulding, MD, a professor of clinical medicine at Harbor-UCLA whose name is virtually synonymous with the concept of TB medication monitors, has been in discussion with George Bergeron, director of technical laboratory development at SAIC, an engineering firm in Washington, DC; and with Edward Aten, MD, a physician with a longstanding experience in developing compliance monitors for research applications. With Moulding’s knowledge of the TB field and passion for the concept, Aten’s prototype device, and Bergeron’s engineering know-how, the trio hopes to find the money needed to produce a batch of devices.
In this instance, the monitor would likely be a variation of a monitor Aten has already produced. It consists of a blister pack covered with paper imbedded with strips of electrically conductive material. By passing a current through the paper periodically, the device detects and records when the package is opened and the circuit interrupted. To be useful in a TB arena, Aten’s monitor still would need some tweaking, since it now dispenses only one pill at a time.
Features that are user-friendly
Along with being simple to make, Aten’s device, or a variation thereof, would be easy to read, its inventor says. An outreach worker or clinic nurse could "hook it up to a Palm Pilot or a similar system," Aten says. Then, using the software Aten has developed, users would simply hit a key to generate a report. Up would pop a graph or other representation showing, perhaps by means of color-coding, whether a patient had been compliant. "It’s not entirely clear to me that there’s a place in TB for such a device," Aten adds. "But it certainly seems logical that there could be."
Unlike the Sequella monitor, Moulding’s contender can’t tell for sure whether a pill’s been ingested. But Aten cites research that shows that once patients have gone to the trouble to take their medicine out of the blister pack, experience shows it’s likely they’ll go ahead and swallow it.
Critics of medication monitors counter that regardless of how clever the device, some patients will somehow manage to defeat its purpose. "They’ll lose them or throw them away," protests John Sbarbaro, MD, professor of medicine at the University of Colorado Health Sciences Center in Denver. "They’ll forget to bring them into the clinic." Alternately, the readouts may be too puzzling for outreach workers to decode properly.
But will patients cooperate?
During an experiment conducted years ago at National Jewish Hospital in Denver, patients once volunteered to use a new atropine inhaler outfitted with a compliance-monitoring device, Sbarbaro recalls. Of 32 volunteers, "only one person used the inhaler correctly," he chuckles. "Ten volunteers actuated the inhaler up to 100 times right before they came in." Others did the same, and in addition falsified accounts in their medication diaries to make it look as if they’d been model patients.
To Moulding and other compliance monitor aficionados, that’s not the point. After all, they explain patiently, the whole idea of compliance monitors is not just to help patients remember to take their meds faithfully, but also to identify those who fail to do so — and then give them extra attention to make sure they do better.
But the prospect of using monitors to screen for those at risk for noncompliance doesn’t necessarily sit well with critics either. "Now look what happens," says Sbarbaro. "If the monitor shows you didn’t take your medication, then we’re going to punish’ you, by singling you out for DOT [directly observed therapy]. Suddenly, we can no longer represent DOT as a caring service we provide to all patients; instead, it’s become a punishment we inflict on bad’ patients." (For patients with job conflicts or family duties, or who have to travel long distances to get to a clinic, DOT may not seem quite so caring, says Moulding.)
At about $5 apiece or even less, the Moulding device would certainly be cheaper than Sequella’s contender, which the company estimates would cost about $50 each. Another difference between the two is that the Sequella prototype faces a hurdle at the Food and Drug Administration, which will need to be convinced of that long-term use of Sequella’s fluorophore, called indocyanide green, or ICG, will be safe.
Katherine Sacksteder, PhD, the Sequella researcher who’s overseeing the monitor’s development, notes that ICG already is approved for short-term use in the field of retinal angiography. In fact, Sequella has an agreement with an ophthalmologist to test a laser-equipped wristwatch on patients undergoing the procedure. Plus, if ICG runs into toxicity trouble, there are plenty of other fluorophores out there that could work, she adds.
The more important question, probably, is whether the Sequella monitor or Moulding’s device will manage to persuade skeptics that monitors have a place in a TB treatment program.
Aten, who’s tried for years to convince the pharmaceutical industry to use his monitor to check compliance in clinical trials, frames the problem more pragmatically. "Historically, Big Pharma is very conservative, and they’re reluctant to change the way they do clinical trials," he says. But eventually, some drug maker poring over a batch of trial data will decide to publicize the way better compliance boosts a product’s efficacy, Aten says. And as soon as the first package insert mentions compliance data, other pharmaceutical companies will race to do the same thing, he believes. From the package insert, it’s a relatively short hop into the program arena. The rest, as Moulding might say, could very well be history.