IT’S A SAD FACT OF MODERN MEDICINE that many diseases—cancer, Alzheimer’s, Parkinson’s—remain difficult to treat. But for many of the most prevalent disorders, chronic diseases that affect large swaths of the population, there’s little mystery about what it takes to get better. Nutrition and lifestyle improvements can go a long way in keeping such diseases at bay. Still, those changes are hard, and a tough sell for doctors to make to patients. But we also have simpler and still highly effective ways to treat these diseases—shelves full of medications to reduce high blood pressure, lower cholesterol and decrease high blood sugar levels.

Yet there’s one big problem with that solution. C. Everett Koop, the former U.S. surgeon general, once noted that “drugs don’t work in patients who don’t take them,” and remarkably often, that’s exactly what happens. Over half of all prescriptions in the United States are not taken as directed, and 20% of new prescriptions are not filled. Many people don’t take any of their pills, while others omit doses, cut pills in half or take them less often than prescribed to save money. Or they take doses at the wrong time of day, with food instead of on an empty stomach, or with other medications that may undercut their effectiveness. Patients may discontinue therapies too early or fail to refill prescriptions.

In other words, they are nonadherent—and that’s exacting an underappreciated toll on patient care and the medical system. Adherence to a medication regimen means taking the prescribed dose on the right schedule and for the right length of time. “Incomplete adherence is the most common reason for the failure of medicine to achieve its intended goal,” says David Bangsberg, director of the Center for Global Health at Massachusetts General Hospital.

The nonadherence malady afflicts all demographic groups, although it is worse among the poor, the less educated, minorities, and those without health insurance or ongoing relationships with providers. Chronic diseases pose the biggest challenge. Patients who have an acute disease are likely to take their medicine. They can feel their symptoms subside, and they get to stop taking their antibiotics or other pills after a short course of treatment. Those with chronic diseases, in contrast, often don’t feel sick, and prescribed therapies may have side effects that make them feel worse. There’s also no end to their drug regimens, and elderly patients in particular may need to take several kinds of pills, for different conditions, with a complicated choreography of what to take when.

Patients are not the only ones at fault. Many doctors, pressed for time, scribble prescriptions with no explanation and then fail to follow up to see whether a patient is tolerating the drug. Improving both sides of the ledger—with physicians helping patients become more adherent—will require a range of remedies. The system will need to revamp the way doctors are compensated so that they’re rewarded for keeping patients with chronic diseases healthy, experts say. Pharmacists, nurses and office staff will need to get involved, and patients can be helped by various technological approaches. The payoff could be very large. “Improving adherence is easy pickings to improve health outcomes, rather than having to discover new ways to treat a disease—or reduce the cost of medicine,” says Janet Wright, a cardiologist and executive director of the national public-private Million Hearts initiative.

Concerns about nonadherence have been rising as many chronic diseases become more common. Almost half of the U.S. adult population now has at least one chronic condition, and treating those diseases accounts for three-fourths of all health expenditures. Seven out of 10 deaths result from chronic diseases, a reality that exacts a huge toll in disability and in loss of productivity and earning power.

Yet even looming death doesn’t seem to scare patients into adherence. Heart attack survivors, for example, may leave the hospital with instructions to take aspirin, a statin and a beta-blocker. A week later, almost a quarter of patients won’t have filled the prescriptions, and within a month, one-third will have stopped taking at least one medication, according to a 2009 study published in the journalCirculation. Only 40% will have remained on statins after two years. This nonadherence leads to more severe complications and more frequent emergency room visits, hospital admissions and readmissions. Nonadherence is thought to cause 125,000 deaths each year and a quarter of all nursing home admissions.

It also comes with a high price tag. Diabetes, hypertension and high cholesterol nonadherence cost the United States $106 billion a year, according to a 2012 analysis. In contrast, a 2011 study by national insurer CVS Caremark found that when patients take their medicine as prescribed, annual medical spending is reduced by almost $9,000 per patient with congestive heart failure, more than $4,000 per patient with hypertension or diabetes, and about $2,000 per patient with high cholesterol.

In many cases, patients may intend to take their medicine but forget or get confused, says Pascal Imperato, dean of the School of Health at SUNY Downstate in Brooklyn. Unintentional slipups are especially likely for elderly patients, those with cognitive decline or psychiatric disorders, and those who have to deal with multiple chronic conditions and may be taking several medications prescribed by different doctors. Affordability is another major hurdle. Study after study finds that the high cost of drugs and steep insurance co-payments prevent many patients from filling prescriptions and taking full dosages.

In some cases, though, patients just don‘t want to take what has been prescribed for them. They may not believe they are sick or that they need a drug, or they simply don’t care about their health. When asked about their adherence, they often lie. In a recent case study at Columbia University Medical Center in New York City, for example, one elderly patient who’d had a heart attack was discharged with several medications. A month later, he reported taking them every day. But an electronic pillbox and pharmacy records revealed he’d taken three of the drugs only a few times and never filled the fourth prescription.

Often, a lack of health literacy holds patients back, particularly when they’ve been prescribed pills for a condition without obvious symptoms. “You need to believe in a disease that’s silent,” says Edward Boyer, a physician affiliated with Boston Children’s Hospital and University of Massachusetts Medical School.


IF THERE IS A POSTER CHILD FOR NONADHERANCE, it’s probably hypertension. It affects 68 million Americans and causes an estimated 1,000 deaths a day. But hypertension is an asymptomatic condition, and getting blood pressure down requires improvements in diet and exercise as well as a long-term regimen of medications that have side effects. About half of such patients become nonadherent within a year, and 36 million of those with the condition have yet to get it under control.

Hypertension is a primary target of Million Hearts, a national initiative launched by the U.S. Department of Health and Human Services in late 2011 that has set its sights on preventing 1 million heart attacks and strokes by 2017, according to Wright. And as part of its efforts, Million Hearts recognized in September 2012 two very different medical organizations for their efforts to combat nonadherence and control their patients’ hypertension. At the tiny end of the scale is Ellsworth Medical Clinic, a practice in western Wisconsin that has two doctors and a physician assistant to treat some 5,000 patients. “We are the cheese curd capital of the world, so we see lots of chronic disease,” says primary care physician Christopher Tashjian.

About five years ago, Ellsworth began a concerted effort to help its patients manage their chronic conditions. It decided that disease management had to be a “team sport” involving everyone in the office. That meant, for example, having medical assistants do a pre-visit chart review and put a red magnet on the exam door if a patient’s blood pressure was elevated. In 2010 the practice switched to an electronic health records system that further enhanced its ability to track patients’ conditions and to make sure that at every point of contact, patients heard a consistent message about the importance of lowering blood pressure. Patients can drop in at any time to have their blood pressure checked, and after an exam, patients receive a visit summary noting current blood pressure and showing when they need to come in again.

None of these measures required adding to the clinic’s small staff. Yet the results were dramatic, with the number of patients whose hypertension was under control more than doubling—to 90% by August 2012. “It was transformational,” says Tashjian. “We went from being a system of illness to a system of health.”

The other Million Hearts award went to the large health maintenance organization Kaiser Permanente Colorado, which serves 500,000 patients in the Denver area. The group collaborated with the Denver Health and Hospital and the Veterans Affairs Eastern Colorado Health Care System on a six-month randomized controlled study involving a series of interventions to help patients control their blood pressure. There were 145 patients in the control group, while 138 participants got home blood pressure monitors and used an interactive voice response system to report weekly readings. The automated telephone system provided immediate feedback to patients about their readings and contacted patients who did not report. Pharmacists from each of the institutions reviewed these reports and called patients to make adjustments to medications if indicated.

“We intended for patients to become more engaged, and those who were engaged had better results,” says Michael Ho, a cardiologist at VA Eastern Colorado Health Care System who helped conduct the study. Patients who received the interventions lowered their systolic blood pressure by an average of 13.1 mm Hg (6 mm Hg more than the control group)—enough to reduce the risk for death from heart disease or stroke by 25%, according to the CDC. The program’s costs were minimal, with pharmacists and nurses at Kaiser, the VA, and Denver Health and Hospital providing services as part of their regular duties and a onetime outlay of $25,000 for the voice response system. Overall, since 2008, the proportion of Kaiser patients who had their blood pressure under control rose from 61% to 83%.

OTHER LOW-TECH APPROACHES ALSO INVOLVE pharmacists in improving adherence. For example, they’re a crucial part of “medication therapy management” programs, or MTMs, which were recognized by a 2003 law that requires Medicare Part D plans that offer prescription drug coverage to establish MTM programs. A study by CVS Caremark found that every $1 invested in MTMs saved $5 overall. Pharmacists can help patients by explaining how to take medications and discussing strategies for remembering doses. They may also be able to provide combination pills to simplify a regimen, and can synchronize refills of multiple drugs, send reminder messages and suggest cheaper generic alternatives.

Medication management measures can be especially crucial in drug therapy for HIV/AIDS patients. The so-called AIDS cocktail requires 95% adherence to a complex regimen to keep the virus at bay (compared with 80% for hypertension patients). That high bar for effective treatment inflamed a heated debate during the late 1990s, recalls Bangsberg of MGH, with some people arguing that it was irresponsible to give the drugs to homeless people and drug users—because they couldn’t be expected to remember to take the then-required 15 pills a day.

There were similar questions about using HIV drugs in Africa, where many patients are uneducated. But there was no data supporting these assumptions, says Bangsberg, who set out to study adherence, first among the homeless and drug users in San Francisco and now in rural areas of Africa. His work demonstrates that such groups, with appropriate support, can indeed adhere to the AIDS cocktail (which now requires taking only one pill a day). In a pilot program in Uganda, Bangsberg’s group is dispensing medications in a sleeve that patients insert into an interactive “wise” pillbox. The box detects when patients open it to remove a pill, and if a dose is skipped, an Internet or cellular signal is sent to a provider who checks to see what’s wrong. The key is monitoring adherence in real time, says Bangsberg, who notes that even in rural Uganda, most people use mobile phones, and HIV patients like receiving lab results via text message.

BACK IN THE UNITED STATES, many researchers expect that mobile devices will soon be at the heart of efforts to improve adherence. Smartphone apps are already replacing phone, e-mail and text messages for informing patients about appointments and prescriptions and letting them report pulse rates and blood pressure or glucose measurements.

Some physicians have embraced such high-tech tools. Others, however, are less confident about technology or worry that it depersonalizes the doctor-patient relationship. And while mobile devices are supposed to encourage patients to become more engaged in their health, Stephen Wilkins, a former hospital executive and consumer health behavior researcher in San Jose, believes the problem is that physicians must be more engaging to patients. As he wrote on his blog, Mind the Gap: “Doctors need to know who the patient is, what their fears, concerns and expectations are, and what the patient is able and willing to do…. As far as I know, we do not have an app for that.”

The barriers to providing that kind of engagement drove physician John Moore to quit the practice of medicine and co-found the MIT Media Lab’s New Media Medicine group. In one ongoing project, Moore addresses what he sees as an ignored barrier to adherence—discomfort with the math that usually couches health care messages. Using HIV/AIDS as an example, he designed an interactive graphic that depicts concentrations of drugs and the virus in the blood. Patients see cartoons of viruses receding as the drug concentration increases, or surrounding the white blood cells as drug concentrations fall. In a 2009 pilot program involving four HIV patients with low numeracy skills, all of the participants demonstrated an understanding of the basic features of HIV infection and the implications of adhering to the combination medicines. Participants who initially were least adherent showed the greatest gains using the app.

“Yes, apps can help remind patients to take medications,” Moore says, “but I believe it’s the deep collaboration between physicians and patients, supported by technology, that will make the difference.”