It’s one of the least-appreciated aspects of medicine, but for a wide range of diseases, including AIDS, asthma, diabetes and hypertension, adherence to treatment recommendations can also be one of the most important factors. And not just in a patient’s health, but also in a drug’s success. Drugs with unpleasant side effects, high costs for patients or regimens that are difficult to comply with can face an uphill battle commercially. It’s one thing to convince doctors to prescribe them, but getting patients to take them regularly is a whole other matter.

Rates of non-adherence vary widely, and depend on the condition, costs and other issues. Sometimes patients just forget or simply can’t afford a medication, other times they don’t like the side effects. They may even have just Googled the drug and decided it’s not for them.

Whatever the cause, it’s estimated that between 20% to 50% of patients are non-compliant with drug therapy. The cost of all that medication skipping has been tallied at between $100 billion and $300 billion annually in the U.S. alone, according to one report.

A poster child for non-adherence

Take anti-hypertensives. Approximately one in three adults suffer from hypertension, but "up to 50% of patients have been labeled as non-adherent or poorly adherent to their hypertension medications," said P. Michael Ho, staff cardiologist at the VA Eastern Colorado Health Care System.

Not surprisingly, skipping one’s pills can lead to poorly controlled blood pressure. In some ways, hypertension is a poster child of non-adherence. Like many other conditions where compliance is a big issue, people don’t usually have symptoms (unless their blood pressure is very high), and they don't think they need medication if they feel ok. "Sometimes the medications cause more side-effects than the effects of the disease itself," Ho explained.

For hypertension, several types of interventions have been tried, including at-home blood pressure monitoring and pharmacist (or nurse)-led management and titration of medications. Each of these approaches has been shown to improve blood pressure, but the main issue, Ho said, "is engaging patients in their care, and having health providers, whether it is a nurse, pharmacist or whoever, who can then keep the patients engaged.”

In certain chronic viral infections, such as HIV, adherence is not just an issue of keeping a patient well, it can also impact whether the disease spreads.

"Antiretroviral treatment (ART) helps people with HIV infection live longer, healthier lives and dramatically reduces their risk of transmitting HIV to others," said Paul J. Weidle of the Centers for Disease Control (CDC)’s Division of HIV/AIDS Prevention. "ART reduces the amount of HIV in the blood and elsewhere in the body to very low levels — so low that HIV tests can’t detect it." That phenomenon is called viral suppression, and it is key to reducing HIV infection rates.

But people can only use ART effectively if they are first aware that they have HIV (i.e. have been tested), and then are receiving continuous care and encouragement to take their medications.

Once again, the key seems to be patient engagement.

"CDC supports efforts to link people to HIV care, retain them in care, help them adhere to treatment, and re-engage those who have disengaged from care," said Weidle. The number of reported HIV infections per year fell 18% between 2008 and 2014 in the U.S. — dropping to an estimated 37,600 infections from 45,700 previously. He attributes that decline in large part to efforts to both boost the number of people tested and increase the number of infected people who are "virally suppressed — meaning their HIV infection is under control through effective treatment."

Complications of aging

Older patients pose a particular challenge, since they may be suffering from multiple conditions and juggling many pill regimens at once.

"The elderly are different for biological, psychological and social reasons," said Kwan Yu Heng, of Duke-NUS Graduate Medical School, Singapore. Those with long term chronic diseases may even suffer from conditions such as "blurring of vision or poor hand dexterity, which make medication self-administration difficult," she added.

There are many different reasons for non-adherence in this group, so each older patient needs to be individually evaluated. Heng collaborated on a recent report that tried to put into perspective all the reasons older people might not take their meds, and suggested helpful interventions.

The study found about 80 reasons why elderly patients might be non-compliant. "It can be very complex," she noted, and popular solutions such as pillboxes, "may not be suitable for all elderly patients." De-prescribing, or reducing unnecessary medications, is another common approach, but the impact of that is still unclear.

Lower cost, higher adherence?

The range and types of steps to encourage adherence have increased. New uses of technology, such as cell phones, are especially popular. A variety of smart phone apps have been developed that remind patients with alarms to take their medications and even remind them when to renew their prescriptions. But the bottom line is that adherence rates can be improved, even with simple interventions.

A meta-analysis published in 2012 found that one of the most effective means of improving adherence was to reduce out-of-pocket costs. The high cost of drugs is not only getting backlash from the public and Congress, but it's pushing many people to conserve medications in an effort to save money. Some patients with chronic conditions like diabetes often skip doses of insulin or take lower doses than needed in order to stretch their medications further.

"We looked at an array of interventions, and several seemed to help with one condition or another," said Meera Viswanathan, director of the RTI International/University of North Carolina at Chapel Hill Evidence-based Practice Center, and an author on the paper.

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"Reducing patient costs seems to have a beneficial effect in many cases."

Meera Viswanathan

Director, RTI-UNC Evidence-based Practice Center

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"There is no cookbook method to get the perfect intervention that works across all indications," she said. "But reducing patient costs seems to have a beneficial effect in many cases." Viswanathan adds that the challenge is not just identifying helpful interventions, but making sure they have widespread uptake and then documenting whether they actually result in health benefits.

Ho expects a greater emphasis on compliance going forward. "There will be a bigger emphasis on ensuring adherence to medications for chronic condition as the healthcare system moves to value-based reimbursement, and health systems are being reimbursed on how well they treat patient populations," he said.

As value-based care catches on, metrics such as blood pressure, weight and HbA1c levels will increasingly help determine how well doctors are paid. That should create new incentives and possibly spur more effort and innovation in the area of adherence.