As oral chemotherapy becomes more widely used, adherence issues increase.
As more patients with cancer embrace the convenience and control offered by oral anticancer therapies, they also face the daunting task of policing themselves when it comes to taking their medicine. Many aren’t doing a good job, which can lead to potentially harmful consequences.
“There’s been a seismic shift in the way we treat cancer over the last several years,” says Ellen Stovall, senior health policy advisor for the National Coalition for Cancer Survivorship. “And adherence has become a serious issue.”
There is no consensus in the healthcare industry on exactly how adherence to medication is defined. The term “compliance” has given way in recent years to “adherence,” a less judgmental term that refers to how consistently a patient takes a medication exactly as prescribed. In a 2003 report, the World Health Organization defined adherence to longterm therapy as “the extent to which a person’s behavior—taking medication, following a diet,and/or executing lifestyle changes, corresponds with agreed recommendations from a healthcare provider.”
Before the rise in oral anticancer therapy—any cancer medication in liquid, tablet or capsule form that is taken by mouth—cancer treatment was typically administered on-site at hospitals and clinics, where patients were closely monitored by doctors and nurses who could actually see patients receive their treatment, such as through intravenous (I.V.) infusion, and adherence was assured. Today, though, many cancer patients take their oral anticancer therapy at home, shifting the burden of adherence to patients and their families.
‘‘The thought was that cancer patients in general adhere better to their medication because of the implications of not doing so, but that’s not actually the case.’’
And, as it turns out, many patients are not doing that. Studies show that adherence rates for oral anticancer therapies are as low as 16 percent and as high as 100 percent, indicating we really don’t have a clear picture of the adherence issue. Cancer patients are like many other patients taking oral medications, especially for chronic conditions that often require long-term treatment, such as diabetes and high blood pressure, where nonadherence rates average about 50 percent. The challenge of nonadherence is expected to increase in coming years with the rise in chronic health conditions, increased long-term maintenance therapy for cancer and the growth in oral anticancer therapies—about 25 percent of cancer medications in development are oral formulations, with more than a dozen already on the market. Also, with more supportive medications for symptoms, bone health and other chronic conditions, the sheer number of pills a patient requires creates more chance of missing doses.
“The thought was that cancer patients in general adhere better to their medication because of the implications of not doing so, but that’s not actually the case,” says Robin Sommers, a nurse practitioner in the Center for Gastrointestinal Oncology at the Dana-Farber Cancer Institute in Boston. “Even when faced with lifethreatening disease, a patient’s adherence can fall short.”
The consequences of not adhering to medication exactly as prescribed are numerous and potentially harmful. It’s estimated that nonadherence across all health conditions causes 125,000 deaths annually in the U. S. and generates as much as $300 billion in healthcare costs. In cancer patients, poor adherence may be associated with disease progression and resistance to the medication. It also can lead to medical complications, more frequent doctor visits and more frequent and longer hospitalizations. Even some participants in clinical trials are nonadherent, which can lead to inaccurate information about medication safety and efficacy.
Nonadherence is typically traced to any of five interrelated factors: the healthcare system, socio-economic factors, patient behavior, treatment-related factors and disease-related factors. Some patients, for example, can’t afford their medication, so they don’t get refills. Others have trouble understanding the directions or have difficulty in swallowing pills.
Nonadherence doesn’t simply mean forgetting a dose; it occurs in many ways. Some patients may forget to take several doses because they’re traveling or they feel well and cancer is no longer at the forefront of every thought. Nonadherence also occurs when a patient doesn’t take the medication at the right time of day or with the appropriate foods. And, because serious side effects, such as frequent diarrhea, can affect how much of a medication the body absorbs, patients are considered nonadherent when they fail to report these side effects to their healthcare team. At the other end of the spectrum, some patients are nonadherent because they arbitrarily double up on doses, believing it will give them a cancerfighting advantage or because they worry that an oral formulation isn’t as effective.
Leibel Harelik of Austin, Texas, found out about the dangers of nonadherence. Harelik, 63, received a diagnosis of advanced prostate cancer in July 2002 and tried numerous treatments. He had been taking Zytiga (abiraterone acetate) for only a few months when he began experimenting with the dosing of the drug and his other medications in an attempt to reduce the side effects. “I was having such a hard time trying to adapt to the medication,” Harelik says. “So I’d drop a pill, and, instead of taking four a day, I’d take three. And I’d either not take my prednisone, or I’d take half a prednisone. I was trying to manipulate it.” Although he admits to experimenting with the drugs on his own, he says he told his doctors what he was doing.
The results were disastrous. Harelik wound up hospitalized with life-threatening health problems and later needed rehabilitation to regain strength. “It was a newer medication, and no one knew much about it,” he says. Harelik doesn’t blame his doctors for what happened. “They were doing their best to appease me and help me. I don’t think I would manipulate my medications any more. I learned my lesson the hard way.”
In some cases though, it’s doctors who aren’t following recommended prescribing guidelines. This so-called off-label prescribing practice leads to inadvertent nonadherence. This is a problem in treating chronic myeloid leukemia (CML), says Greg Stephens, executive director of the National CML Society in Birmingham, Ala.
“We hear about patients, even today, who are on unsupported dosing regimens, having been told to take their therapy drug every other day or to skip a day periodically,” he says. As a result, he continues, “They’re perhaps getting a suboptimal dose, and over time that has proven to be detrimental.”
Numerous methods to improve adherence have been tried. Alarm clocks, talking pill bottles, reminder phone calls and emails, diaries, online patient portals, even web chats—all have been tried with varying levels of success. And yes, there’s even an app for that.
Adherence problems so troubled healthcare workers at Rex Hematology Oncology Associates in Raleigh, N.C., that they developed an oral chemotherapy nurse position to specifically care for patients taking oral anticancer therapies. The program was prompted, in part, because patients were going to their cancer appointments so ill from unreported side effects and other adherence issues that they were sent directly to the hospital, says Mendy Moody, an oncology nurse who initially ran the program and now is manager of Rex Cancer Center of Wakefield in North Carolina. “The goal of the oral chemotherapy program is to help our patients remain safe while taking oral anticancer therapies, and at the same time intervening before the patient becomes so sick that an inpatient hospital admission is needed,” Moody says.
As part of the Rex program, all new patients starting an oral anticancer regimen are given an individual one-hour education session with an oral chemotherapy educator, during which they address potential barriers to adherence and find solutions to increase adherence, such as follow-up phone calls and mandatory appointments before prescription refills. “I think for the most part our patients feel a certain amount of security by doing this,” says Christy Rhodes, an oncology nurse and one of two oral chemotherapy educators at Rex. “We try to make it a good working relationship. I don’t want them hiding side effects from us. And I don’t think anyone has voiced an opinion that they feel overwatched.”
None of the methods to improve adherence have been fail-safe, though, and overall adherence rates to all types of oral medications have changed little in the past few decades. And some experts fear that the problem will only get worse with the growth in oral anticancer therapy and increase in chronic conditions.
“We don’t know what the solutions are,” Stovall says. “Everyone’s talking about the problems right now. But they don’t have a lot of ideas about how to solve the problem. There is no gold standard.”
The National Coalition for Cancer Survivorship is pushing for reforms that it says would improve medication adherence, including working with pharmaceutical companies to develop less toxic medications and oral drug parity in healthcare insurance that would cover costs for healthcare professionals to provide patient education.
I was having such a hard time trying to adapt to the medication. So I’d drop a pill, and, instead of taking four a day, I’d take three.
“We know we need payment reform, delivery reform and regulatory reform, but we don’t have the details on how all these would work,” Stovall says. “Our focus is to identify the policy issues by doing what we do best—bringing stakeholders together to identify causes of nonadherence, to consider policy solutions, and to have coalitions of advocates who are dedicated to implementing the policy issues. It’s irresponsible to put these oral medications out there and not educate patients about adherence.”