Patients With CLL Willing to Trade Treatment Efficacy for Reduced Costs and Adverse Events

Some patients living with chronic lymphocytic leukemia (CLL) are willing to accept drugs that are less effective in exchange for reduced adverse events (AEs) when making treatment decisions, according to results from a discrete-choice experiment published in Blood Advances. Findings from the study, which surveyed patients about treatment preferences, also suggest that out-of-pocket costs can override both safety and efficacy.

Although participants placed the greatest importance on longer progression-free survival (PFS), “any increase in AEs or the risk of AEs would require a potentially large improvement in efficacy to offset the disutility to respondents associated with the AEs,” noted Carol Mansfield, PhD, of RTI Health Solutions in Research Triangle Park, North Carolina, and co-authors.

The researchers, along with representatives from The Leukemia & Lymphoma Society (LLS), Lymphoma Research Foundation, and Genentech, designed a patient-preference survey that presented participants with a choice between pairs of hypothetical CLL treatments. Each hypothetical treatment was defined by five attributes: PFS, mode of administration, typical severity of diarrhea, chance of serious infection, and chance of organ damage. Patients were asked to rank the importance of each attribute in their treatment choice.

Respondents were recruited between March and April 2016 from the LLS database of 4,420 adult patients with a self-reported physician diagnosis of CLL. They were offered a $20 incentive for survey completion.

A total of 384 patients (median age = 64.6 years; range = 30-89 years) completed the study; 53 percent were women and 94 percent were white. Most patients (69%) had a form of public insurance (including Medicare, Medicaid, and/or Veterans Health Insurance), and 48 percent were retired.

Respondents ranked change in PFS (from 10 to 60 months) as the most important attribute in their treatment decisions, followed by (in order of importance):

  • a decreased risk of infection (preferring a medication with no risk of infection over one with a 30% risk)
  • a lower chance of organ damage (preferring a medication with no risk over one with an 8%risk)
  • a lower grade of diarrhea (preferring one with no risk over one with a severe risk)
  • mode of administration (preferring oral over intravenous routes)

Although the risk of AEs was important, results from the minimum acceptable benefit calculation showed that, on average, patients would choose a treatment that carried a 30 percent risk of serious infection if it extended PFS by 36 months.

Prior exposure to treatment did not appear to influence decisions, according to a subgroup analysis in which the researchers compared patients who were receiving firstline therapy (n=23), had relapsed/refractory disease (n=39), or were treatment naïve (n=20) at the time they completed the survey. “There were no statistically significant differences between the preferences of any subgroup and the full sample,” the authors wrote. “This suggests that patient preferences may be stable over the stages of the disease; however, it is possible that sample size was not large enough to estimate the difference in preferences across groups.”

More than half (53%) of the entire group reported receiving financial aid from patient-support programs and 40 percent reported difficulty paying out-of-pocket costs, indicating that cost played a major role in treatment decisions.

When participants were allowed to choose between a medication with a shorter PFS (Medicine A) or a longer PFS (Medicine B) without knowing the cost, 91 percent chose Medicine B; however, when they were presented with scenarios in which the monthly out-of-pocket costs for Medicine B were $75 higher than Medicine A, 50 percent of patients chose the lower-cost option. As price increased, so did the number of patients choosing lower cost over improved efficacy (FIGURE). “Cost is clearly something that has an impact,” said Dr. Mansfield. “When patients [are] prescribed something they can’t afford, they have to make very difficult choices.”

Given the value of testing minimal residual disease (MRD) to guide treatment decisions for CLL, the authors also asked respondents about MRD monitoring. Approximately 82 percent were interested in the testing, of which 58 percent were very interested. Interest in MRD testing decreased with age, was lower in women, and was higher in those with public insurance.

“We hope that our findings can help doctors to have frank discussions with their patients about the differences between treatments and how these might affect their lives,” Dr. Mansfield concluded.

The study is limited by its use of a patient advocacy organization for recruitment, which may not be representative of the overall CLL population. In addition, discrete-choice experiments rely on hypothetical scenarios and only a limited number of treatment attributes can be included. “The answers do not carry the weight of real choices,” the authors explained. Disease stage and prior treatment regimens were not defined, which could have further limited the implications of the study’s findings.

Genentech, Inc., provided funding for the study.

The authors report receiving funding from Genentech, Inc.


Mansfield C, Masaquel A, Sutphin J, et al. Patients’ priorities in selecting chronic lymphocytic leukemia treatments. Blood Advances. 2017 November 14.