The drug industry loses tens of billions in global sales each year when patients don’t fill or refill prescriptions their doctors want them to take.

Big Pharma is going all out to change that.

Drug companies from Kendall Square to Tokyo are pouring money into campaigns to boost “medication adherence.’’ They’re investing in smart pills that can send alerts when patients forget to take them. They’re subsidizing gift cards to thank patients who refill. They’re even lobbying the federal government for permission to pay third parties, such as pharmacists, to remind patients to take their meds.

Drug companies say these investments are focused on improving 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,’’ Lamkin said. Doing all they can to urge patients to take their pills “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 lines.

Poor adherence 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: Some just don’t work well. Significant percentages of patients don’t respond to their medications or experience serious side effects.

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

GlaxoSmithKline is going further still. The London-based drug maker has enrolled 3,000 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 medications. Those individuals can get one-on-one health counseling with a pharmacist or a case manager, said Matt Rousculp, a senior director of health outcomes research for GSK.

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

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

Novartis, which runs its research and development in Cambridge, was an early investor in Proteus. 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.

The 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 leading industry group, Pharmaceutical Research and Manufacturers of America, are backing a lobbying campaign to get regulators to bless bold efforts by drug makers to push patients to take their medications. 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.

Biogen, based in Cambridge, last year relaunched a program geared to patients taking its drugs for multiple sclerosis. The program puts an emphasis on staying adherent.

Patients get e-mails 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 pills.

“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 helped build 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. 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.

Rebecca Robbins can be reached at rebecca.robbins@statnews.com. Follow her on Twitter @RebeccaDRobbins.