Drug companies around the globe are spending big to push patients to take their pills.

The pharma industry loses tens of billions in worldwide sales each year when patients don’t fill, or refill, their prescriptions.

So drug makers from London to Tokyo to Cambridge, Mass., are pouring money into programs aimed at cajoling — or nagging — patients to take every last pill their doctors prescribe. The companies are investing in smart pills that will send alerts when they haven’t been swallowed at the prescribed time. They’re subsidizing gift cards to thank patients who remember to refill. They’re paying patients to go on talk circuits to tout the virtues of taking medication properly.

They’re even lobbying the federal government for permission to pay third parties, such as pharmacists, to encourage patients to take their pills.

Drug companies say these investments are focused on improving patients’ health. “We’re not pushing pills here, we’re pushing adherence,” said Joel White, president of the Council for Affordable Health Coverage, an advocacy group that works with the industry.

But Matt Lamkin, an assistant professor at the University of Tulsa College of Law who’s studied the issue, sees another motive.

Pharma companies have the sense “that they are leaving billions on the table” when medicine isn’t taken and prescriptions aren’t filled, Lamkin said. The push to improve adherence, he said, “reframes the goal of boosting sales as a goal of public service.”

Of course, when patients fail to take their meds, they’re not just hurting drug makers’ bottom line. Poor adherence to prescription medications has been estimated to drive up medical spending in the United States by nearly $300 billion each year. Patients sometimes end up sicker when they skip too many pills both for acute conditions and for chronic diseases like diabetes and multiple sclerosis.

It’s a complicated problem. Patients may decide not to fill prescriptions because they don’t have the money or can’t get to a pharmacy.

Another big reason pills get skipped: They just don’t work very well. Significant percentages of patients don’t respond to the medications they’re prescribed or experience serious side effects.

Pharma companies traditionally have tried to address the financial concerns with rebates and the health concerns by staffing hotlines that patients can call with questions.

Now, however, they’re going further.

In the past, drug companies “weren’t as likely to have a view on what should be done in clinical practice or systemically,” said Tom Hubbard, vice president of policy research at the Network for Excellence in Health Innovation, which counts pharma companies among its members. “These days, interest is considerably greater.”

Take GlaxoSmithKline. The London-based drug maker has enrolled 3,000 of its employees, retirees, and their family members in North Carolina in a pilot program to better coordinate their health care. Among other things, it uses sophisticated analytics to determine who’s not sticking with their medication. Those individuals can get one-on-one health counseling with a pharmacist or case manager, according to Matt Rousculp, a senior director of health outcomes research for GSK.

Rewards and reminders

The industry is also pushing solutions more directly focused on making sure patients remember their pills.

Japanese giant Otsuka Pharmaceutical is collaborating with Silicon Valley startup Proteus Digital Health on the first “smart pill,” embedded with an ingestible sensor that could send a patient or a doctor alerts when it’s swallowed — or when a dose is missed. They’re seeking approval for the technology from the US Food and Drug Administration.

The big drug maker Novartis, which runs its research and development in Cambridge, Mass., was an early investor in Proteus. And Novartis is also working with the mobile chip giant Qualcomm to develop an inhaler that would record the date and time of every use, to improve adherence in patients with chronic obstructive pulmonary disease.

Danish drug maker Novo Nordisk is taking another tack: It’s working with a company called HealthPrize to promote adherence to diabetes medication, according to HealthPrize’s chief medical officer, Katrina Firlik. HealthPrize encourages patients to document their prescription refills by rewarding them with gift cards or charitable donations.

Big Pharma’s growing interest in medication adherence is even making ripples in Washington.

Industry giants like Merck, Pfizer, and Sanofi, as well as the big industry group, the Pharmaceutical Research and Manufacturers of America, are backing a lobbying campaign to, among other things, get regulators to bless bold efforts by drug makers to push patients to take medication. For instance, they want to be able to pay pharmacists to call patients directly.

As federal law now stands, some executives fear such payments could be prosecuted because they’d resemble kickbacks to boost sales. The lobbying campaign is run by the Council for Affordable Health Coverage.

A personal approach

Biogen last year relaunched a program geared at patients taking its drugs for multiple sclerosis.

The Cambridge, Mass.-based drug maker’s program puts an emphasis on staying adherent. Patients get emails about why it’s necessary to take their pills. They can read online advice about “dealing with medication fatigue.” And they can download a smartphone app that features an alarm clock that can be set to go off when it’s time to take their pills. (Patients taking Biogen’s MS drugs get special information, but anyone can access the app or the program’s online content.)

“It’s all in the service of educating the patient … so that as they become more informed, they’re able to recognize this is why [they] need to stay on therapy, regardless of what that therapy might be,” said Mat Hesser, director of Biogen’s Patient Center of Excellence, who was involved in building the program.

Biogen also pays patients such as Jessica Thomas, a therapist from North Carolina, to talk about their experiences managing their disease through the company’s medications. Thomas takes Biogen’s MS drug Tecfidera twice a day — one pill with breakfast and another with dinner.

Over the years, Thomas has managed to be remarkably adherent to her regimen. One piece of advice she doles out to other women: Keep a pillbox in your purse, rather than stuffing a pill in your pocket.

But once every few months, even she forgets to take a pill on hectic mornings when she rushes out of the house without eating breakfast.

“When that happens, I usually feel really bad,” Thomas said. “It doesn’t happen often at all, but I know how important it is to take it two times a day.”

That’s a message that Biogen is eager for other patients to hear.