Medication adherence has emerged as a hot-button issue in health care.

Most retail pharmacy operators have placed new emphasis on helping ensure that patients take prescription drugs as directed, the topic is high on the agenda at industry forums and the National Consumers League is in the midst of a campaign to promote the proper use of medicines.

The benefits of improved adherence are widely recognized: People will live healthier lives; pharmaceutical manufacturers and pharmacies will sell more products; and payers, despite potentially higher expenditures for medications and pharmacy care, will save money. One widely quoted study by the New England Healthcare Institute puts the annual cost of medication nonadherence at $290 billion, or some 13% of the country’s total health care bill.

With so much at stake, it’s not surprising that a variety of health care providers are tackling the problem. Among the organizations that have risen to the challenge is the top-tier research-based pharmaceutical maker Merck & Co. The supplier is not new to the fight, having had a program focused on enhancing medication adherence in place for more than two decades. It has in recent years, however, stepped up its efforts to the point where the issue now rates as one of Merck’s strategic priorities.

Asked why adherence has received more attention of late, Newell McElwee, Merck’s executive director of outcomes research in the United States, says, “The external environment is more ripe for medication adherence. We’re gaining a lot of traction with other health care stakeholders, including physicians, pharmacists, health plans and PBMs.

“The other thing that’s different is the internal landscape within Merck. Historically pharmaceutical companies have focused more on the first prescription and less on what happens after that, which meant that many patients didn’t get the full benefit of our products. Now we’re putting as much effort as possible into keeping patients on the medicines.”

Merck’s research, which has resulted in a steady stream of published papers on various aspects of adherence, is carried out within a conceptual framework called a proximal-distal continuum. “Those words are used in other situations,” explains McElwee, “but one of the investigators here put this together for medication adherence and identified something like 250 variables that affect it.”

Factors that can have an impact on the behavior of an individual patient are surprisingly diverse. They range from age and personality traits to attitudes about health and concerns about medication safety and side effects.

“We placed the variables within the framework to identify the ones that were most strongly predictive for nonadherence,” says McElwee. “Subsequent focus groups, cross-sectional research and a longitudinal predictive validity study demonstrated that the framework was very useful, that the things closest to the patient are stronger predictors than the things that are farther away. All of that work really helps us do segmentation of patients who are at high risk.”

One important product of the research is Merck’s Adherence Estimator. Unveiled last year in Current Medical Research and Opinion, the tool equips pharmacists and other health care professionals to pose questions to patients about attitudes in three areas related to nonadherence — their belief in the need to take a prescription drug, concerns about the medication and the perceived financial burden of treatment. The adherence estimator has been shown by Merck studies to be 86% accurate in pinpointing patients likely to deviate from their medication regimen.

“A lot of things that popped up in the research were related to health beliefs, and these are consistent with many of the theoretical constructs about patient behavior and what factors change it,” McElwee notes. “Aside from the identification of patients at risk, we’ve also started looking at the question, ‘Once you find these patients, then what do you do?’ ”

That aspect of Merck’s work centers on modes of communication, and which of them are most effective for a given patient ­population.

“For a little over two years we’ve been engaged in messaging research,” says McElwee, “testing different ways to frame messages to find the ones that have the greatest impact. For instance, we compared messages that are gain-framed or loss-framed — meaning you talk about either the benefits of the medicine or all of the bad things that can happen downstream if you don’t take it — to see which type worked better. What we’ve found is that it really doesn’t matter; both are equally effective. We’re continuing to look at other elements that affect communication about medication usage.”

With the tools it is developing, Merck intends to enable health care providers and payers to identify patients likely to become nonadherent and intervene to address the problem.

About 100 entities, including retail pharmacies, PBMs and physician groups, are currently using the adherence estimator, according to McElwee, who adds that others may be drawing on the company’s research, since it has all been published and is in the public domain.

In several instances Merck researchers are working with companies (including two large drug chains that, for contractual reasons, cannot be identified)­ on adherence, particularly as it relates to prevalent disease states. Projects now under way address diabetes, asthma, hypertension and cardiovascular disease. As in the past, all of the results of the research on adherence that Merck is involved in will be published.

The pharmaceutical company’s efforts in the field are geared toward filling what McElwee characterizes as evidence gaps. That means bypassing research about the economic impact of improving medication adherence, an area where many studies already exist, to zero in on the patient.

“One key component of what we’re trying to do is really focus on patient outcomes,” he says. “We’re also doing a couple things to improve the operating characteristics of the adherence estimator.

“The estimator was based on six chronic diseases. When we look at the performance in each of those six areas, some of them clump together and some don’t. Most of the adherence research that has been published generally takes on the therapeutic category in isolation. So one of the things that we’re looking at right now is which of the disease states cohere.

“For example, we may be able to clump together chronic diseases that are asymptomatic, like hypertension and high lipids, as opposed to diseases that are symptomatic but episodic, like arthritis and asthma. It may be that we need to use a slightly different approach in the segmentation, depending on how the disease states match up.”

Other projects address how new technologies, such as smartphones, can be brought to bear on the problem of medication compliance. “We’re just putting together our research agenda for the next few years and it includes areas like the use of social networking and how patients interact with caregivers,” says McElwee.

One of Merck’s biggest contributions is to call attention to the complexity of the problem and the extent of the effort that will be required to ameliorate it.

“We have been humbled by just how difficult this is,” McElwee notes. “One of the major learnings that we’ve had is just how complicated it really is. When you think about it, what we’re really trying to do is change patient behavior, and that’s very difficult. In the process, there may also be a need to change the behavior of physicians and pharmacists and how they interact with patients.”

The challenge is daunting but not insurmountable. The success that Merck and other researchers have had in understanding and addressing medication nonadherence should inspire health care providers that haven’t already done so to get involved.