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Breath Analyzer Monitors Drug Compliance

A new device could lead to better clinical trials.

For those with HIV, missing doses of medication can have a serious effect: it can make the deadly virus more drug resistant. Doctors have been trying to devise ways to monitor drug compliance among patients with a wide range of diseases. But each method has limitations. Patients who self-report aren’t always honest, and counting pills left in the bottle only indicates how many have been removed, not necessarily how many have been taken.

Breath check: Xhale’s Self-Monitoring and Reporting Therapeutics (SMART) device, illustrated above, analyzes a person’s breath to detect if medication has been ingested. The device, which is about the size of a shoebox, could help doctors track drug compliance.

Researchers at the University of Florida and Xhale are taking a different approach: they’re utilizing an off-the-shelf breath analyzer to confirm if a patient has taken her pills. The technique is straightforward. After a patient takes a pill, she breathes into a strawlike tube on the analyzer, which detects a compound in the medication. Instead of looking for the presence of complex and varying drugs, the researchers put an FDA-approved compound–an alcohol called 2-butanol–in the pills that they used during testing. Enzymes in the stomach convert the alcohol into a gas, which is what the device detects. The premise is that if the system proves useful, a wide range of drugs could be reformulated to include the alcohol.

The analyzer was originally developed for the military to test the surrounding air for agents of chemical warfare, says Richard Melker, a University of Florida professor and chief technology officer at Xhale. The team modified the device to add the straw and detect the alcohol. The screen on the front of the box provides instructions on which buttons to press and when to breathe into the straw. It also records the presence or absence of the telltale gas, as well as the time. The user can then upload this information from the device on a USB port and take it to a health-care provider.

Currently, the device is targeted toward pharmaceutical companies, which have no way to tell for sure if participants in clinical trials are taking the medicine as required. Ensuring drug compliance may make clinical trials more effective, says Melker, particularly because participants paid to take the medicine may not be honest if they skip doses. “We believe that having quality data will dramatically decrease the cost of trials, and that the drugs approved by the FDA would be safer,” says Melker.

A successful means of measuring drug compliance is needed, agrees Martin Hirsch, a professor of medicine at Harvard Medical School. “The number-one reason for failure of therapy in HIV infection is poor adherence,” he says.

Mallory Johnson, an associate professor of medicine at the University of California, San Francisco, who works on patient adherence at the Center for AIDS Prevention Studies, says that most doctors use self-reporting to monitor adherence, in addition to using compartmentalized pill organizers and pharmaceutical records. Researchers sometimes use pill bottles with sensors on the lid that indicate each time the bottle is opened. But this method doesn’t always work, says Johnson, because often patients don’t carry around the whole bottle. Attempts to remind people to take pills, such as text messages or phone calls, haven’t been shown to be extremely effective either. “Behavioral reminders are important, but not enough,” says Johnson. He adds that people tend to overestimate how much they comply with taking medicine. “I think we absolutely need innovative approaches for measuring adherence,” says Johnson, who was not involved in the Xhale project. “I imagine this [device] being particularly useful in controlled clinical trials, where it’s critical to know whether someone took doses of medicine.” But for individuals who have difficulty following medical regimens, he’s not sure it will help. He points out that “you still rely on someone being adherent on using this device.”

Drug adherence is not just important for combating infectious diseases. People with mental illness might skip pills because of unwanted side effects, like impotence. Those with chronic illness might stop treatment if they’re feeling better. Others, suffering from “drug fatigue,” simply get tired of taking medicine after many years and stop, says Hirsch. And of course, some people just forget.

Xhale intends for the monitoring device to be customizable, pairing it with, for example, an alert system that would beep, flash, or vibrate as a reminder when it’s time to take medication. Additionally, the company plans to shrink the device to make it portable, and bring down its cost from $1,000 to less than $200, according to Melker.

The team has tested the device on six healthy people and found that if the pill and test were taken after fasting, the device worked 100 percent of the time. When the test was performed after eating fatty foods, however, the accuracy of the device dropped markedly: it only worked 20 out of 30 times. But Melker says that the team has made the sensor 10 times more sensitive since those tests were performed. He adds that the company is planning to set up a double-blind trial within the next two to three months, and that it hopes to have a commercial product in 18 months. The company also plans to compare the device with programs in which caregivers watch the patients take their pills, which is widely accepted as the best method to get people to take medicine.

The Action Point Adherence Program at the Housing and Urban Health Clinic in San Francisco strives to help the people who have the most difficulty taking HIV medicine correctly: those who are homeless, severely mentally ill, or addicted to drugs. Patients meet with an adherence nurse every day or once a week, and the center occasionally reviews pharmaceutical records or counts pills to evaluate compliance. According to director Joseph Pace, the program has tried technologies such as watches and pagers to issue alerts when it is time for a patient to take medication, but it found that direct patient-doctor contact works best. “We’re not policing people,” he says, and adds that caregivers at the clinic have learned to live with a certain amount of ambiguity.

Pace is doubtful that a breath-analyzer device for compliance would be useful in this kind of program. Even if it were coupled with a reminder device, it might be hard for some patients to remember to both take the pill and breathe in the tube, says Pace. He points out that not all people would be willing to exhibit an obvious reminder of their condition in public. Moreover, asking patients to use the device implies that the medical staff believes that the patient won’t tell the truth, Pace notes, which could hurt the doctor-patient relationship. Building a strong relationship with patients, he says, is what will “engender the truth.”

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