Published Online: June 01, 2007
Hae Mi Choe, PharmD; James G. Stevenson, PharmD; Daniel S. Streetman, PharmD; Michele Heisler, MD, MPA; Connie J. Standiford, MD; and John D. Piette, PhD
Objectives: To examine willingness to participate in a pill-splitting program and the impact of pill splitting on patients’ adherence and lipid control.
Study Design: Nested randomized trial.
Methods: A total of 200 patients who used statins and were candidates for a pill-splitting regimen were identified from a large university-based health plan. Sixty-three percent of study participants were female, 41% were nonwhite, and 94% had at least some college education. Patients were surveyed regarding their willingness to split pills, and 111 consented to participate in a 6-month trial in which half were randomized to receive a financial incentive to split pills: a 50% reduction in their per-refill copayment. Data on patients’ statin refills and lipid control were obtained from billing and medical records.
Results: Compared with patients unwilling to participate in the program, those agreeing to split pills were more likely to be female and white. After 6 months, most patients in the trial (89%) were willing to continue pill splitting for a 50% copayment reduction. Patients reported few problems with pill splitting and had no noticeable change in their adherence. The financial-incentive group and the control group did not differ significantly with respect to their low-density lipoprotein cholesterol levels after pill splitting: -2.0 mg/dL and -1.2 mg/dL, respectively.
Conclusions: Most patients indicated that at least a 50% copayment reduction would be required to enroll in a pill-splitting program after the study ended. However, in this relatively educated population, financial incentives did not influence patients’ adherence, satisfaction, or health outcomes.
(Am J Manag Care. 2007;13(part 1):298-304)
A 50% reduction in patients’ per-refill copayment was used to promote adherence to a pill-splitting statin regimen in a randomized trial involving a relatively educated population.
Pill splitting did not adversely affect cholesterol levels, nor did it hinder compliance with medication therapies.
During the 6-month trial, the financial incentive did not influence patients’ adherence, satisfaction, or health outcomes.
After the trial, 89% of patients were willing to continue pill splitting for
a 50% copayment reduction.
As medication costs continue to escalate, many institutions and managed care organizations are seeking to maximize the cost-effectiveness of individual pharmacotherapy. Pill-splitting programs have been implemented in various settings in an attempt to decrease medication costs.1-8 However, concerns have been raised that splitting could compromise patient safety due to uneven drug distribution in the split pills and loss of medication potency due to fragmentation.4 Although these concerns are legitimate for a fraction of the drugs available, for most medications, especially those with a long half-life, small variations due to fragmentation are not clinically important. In a randomized cross-over study, Rindone evaluated the impact of splitting lisinopril pills in 29 patients with hypertension; patients received a full pill for 2 weeks and a split pill for 2 weeks with no significant differences in systolic and diastolic blood pressures.5 Duncan et al evaluated the effects of pill splitting on low-density lipoprotein (LDL) and total cholesterol levels in a retrospective chart review of 125 patients receiving atorvastatin or simvastatin therapy who were switched to pill splitting. The results of that study demonstrated no statistically significant changes in LDL and total cholesterol levels.3 Another study conducted by Gee et al found that pill splitting of statins had no negative effects on patients' cholesterol profile.6
Concerns also have been raised about patient satisfaction and adherence with pill splitting.4 The few studies that examined these outcomes have reported variable results. McDevitt et al surveyed 94 patients with hypertension after 10 days of splitting their hydrochlorothiazide pills. Most of the subjects stated a preference for the commercially available lower-strength pills, and 77% reported a willingness to pay more for them.4 In contrast, Carr-Lopez et al reported that splitting lovastatin pills was easy to do and did not hinder medication adherence in the majority of patients.1 A study of fosinopril pill splitting reported no significant difference in medication adherence between patients who split pills and those who did not. In fact, the patients splitting fosinopril pills reported positive experiences.2 In the study by Gee et al, the majority of patients who split statin pills were satisfied and adherent to the new regimen.6
Although these prior studies provide some insight, the majority of studies to date were retrospective, were based on very small samples, or evaluated effects after brief periods of splitting pills. Finally, it is unclear whether patients who split pills will be more satisfied and adherent to their regimens if they share in the financial benefit associated with this change.
The objectives of this study were (1) to evaluate the impact of pill splitting on clinical measures, patient satisfaction, and acceptance and (2) to determine whether a financial incentive would affect patients' decision to split pills.
In the current study, we addressed the previously mentioned issues by using a large survey sample with a nested randomized trial of financial incentives to promote adherence to a pill-splitting statin regimen. First, we recruited patients with hyperlipidemia who were candidates for pill splitting, and we assessed their perceptions about pill splitting. Second, survey respondents were invited to participate in a randomized trial in which they would receive a free pill cutter, would be encouraged to split their lipid-lowering medication, and would have a 50% chance of being randomized to a group who received a reduction in copayment for the split-pill regimen. We compared the characteristics of patients who did and did not consent to participate in the pill-splitting trial. Trial participants were randomized to either pill splitting only or pill splitting plus a 50% reduction in their per-refill copayment. Randomization was done using a blocked randomization and random-number generator with random block sizes of 2, 4, or 6.
After 6 months, we compared patients with and without the copayment reduction in terms of their satisfaction with pill splitting and willingness to continue splitting pills. Finally, we examined pre-post changes in the adherence and lipid levels of patients in the trial to determine whether patients who split pills had any evidence of altered lipid control.
The study was conducted among patients using cholesterol-lowering medications (statins) in a university-based healthcare system. Statin use provides an ideal context in which to evaluate the outcomes of an incentive-based splitting program because these treatments are common, and many patients use brand-name drugs that are expensive to third-party payers. Moreover, hyperlipidemia has a clear, regularly measured physiologic outcome that can be used to quantify any potential negative effects of splitting on patients' health status.
Patient Identification and Recruitment
This study was approved by the University of Michigan Human Subjects Committee. Potential participants were identified through prescription claims data. Using these data, we identified all patients with 1 or more prescriptions written by a health center physician for atorvastatin, simvastatin, or pravastatin over a 6-month period. Lovastatin was excluded because at the time of the study drug costs varied according to the strength of the tablets. Crestor® was not included because it was not a preferred agent on the formulary. We excluded patients who changed health centers or prescription benefit plans, no longer took 1 of the study drugs, or were deceased. Approval from patients' primary care providers was obtained before patients were contacted regarding the study.
Eligible patients were sent a letter on health system letterhead and signed by the principal investigator. The letter explained the goals of the study and included consent forms, a brief baseline survey, a postage-paid reply envelope, and $5.00 as an incentive for returning the baseline survey. Patients did not have to agree to pill splitting to participate in the baseline survey.
Randomization and Interventions
Patients who returned the signed consent form and baseline survey by mail indicated whether they would be willing to participate in a randomized trial of copayment reduction associated with pill splitting. All patients agreeing to participate in the trial received a patient education sheet on pill splitting and free pill cutters through the mail. Based on feedback from some of the patients, all patients received 2 different types of pill cutter in the mail to assess which type patients preferred. Their primary care physicians were contacted for a written prescription of the pill-splitting regimen or a verbal order enabling the study investigators to call in the prescription to the patient's pharmacy. The study investigators also called all participants to ensure that the pill cutter was being used properly and to answer questions within 1 month of enrollment in the trial.
Patients randomized to the copayment reduction group received a 50% discount on their copayment for refills of their statin medication, regardless of whether they filled those prescriptions at a university-based or a community-based pharmacy. Because participants differed in their initial copayments, the absolute dollar value of the decrease varied across copayment reduction patients. However, the majority of patients in this group had $7 or $5 savings a month depending on whether their prescription was filled at a retail pharmacy or by mail order, respectively. Patients randomized to the comparison group received no discount copayments for pill splitting. Patients were informed of their random assignment within 7 days of enrollment via mail or telephone.
The baseline survey was used to better understand how patients perceive pill splitting and the characteristics that determine adoption of pill splitting. We also sought to determine whether some patients might not want to participate in research on splitting pills but would be willing to split pills if pill splitting were offered as an established program. The key survey items included demographics, number of medications and cost, health status, adherence, willingness to split pills to save money for the patient or prescription benefit plan, and copayment savings necessary to split pills.
At 6 months postenrollment in the active pill-splitting portion of the study, patients in the trial were mailed an endpoint survey to determine their satisfaction and willingness to continue with the pill splitting after the study was over. Key survey items included willingness to continue pill splitting after the study was completed, copayment savings necessary to continue with pill splitting, perceived effort required to split pills, ease of using the pill cutter, and medication nonadherence due to pill splitting. These survey items were developed specifically for this study. Eight patients who ended the study early (due to discontinuation of study drugs, moving, or refusal to continue) completed the endpoint survey at the time they dropped out. Patients' LDL cholesterol test results were obtained from the lab and compared before and after implementation of pill splitting to determine longitudinal changes in patients' lipid control.
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