John D. Piette, PhD

: To examine willingness to participate in a pill-splitting program and the impact of pill splitting on patientsâ€™ adherence and lipid control. 

: 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 patientsâ€™ statin refills and lipid control were obtained from billing and medical records.

: 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. 

: 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 patientsâ€™ adherence, satisfaction, or health outcomes.

(Am J Manag Care. 2007;13(part 1):298-304) 

A 50% reduction in patientsâ€™ 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 patientsâ€™ adherence, satisfaction, or health outcomes.

After the trial, 89% of patients were willing to continue pill splitting for

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.

 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.

 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.

 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.

Another study conducted by Gee et al found that pill splitting of statins had no negative effects on patients' cholesterol profile.

Concerns also have been raised about patient satisfaction and adherence with pill splitting.

 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.

 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.

 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.

 In the study by Gee et al, the majority of patients who split statin pills were satisfied and adherent to the new regimen.

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.

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.

All statistical calculations were performed using SAS for Windows 9.1 (SAS Institute Inc, Cary, NC). Using LDL data from the study by Duncan et al,

 we determined that a sample size of 96 subjects would be required to detect a between-group difference of 9 mg/dL in LDL concentrations with 90% power at 

 = .05 (2-sided test). We used χ2 tests and  cross-tabulations to identify variation across demographic groups in the survey sample's perceptions about pill splitting. We used similar statistics to compare the subsets of initial survey respondents who did and did not consent to participate in the financial-incentive trial and outcomes between the groups that did and did not receive the financial incentive. Pre-post comparisons of patients' adherence and lipid levels were based on either paired Wilcoxon signed rank tests for continuous data or McNemar's test for dichotomous variables. All analyses were conducted on an intent-to-treat basis.

Recruitment and Characteristics of the Study Sample

The majority of the 200 patients returning the baseline surveys were age 50 years or older, Caucasian, and had at least some college education. Nearly 80% of respondents rated their own health as very good or good, compared with only 12% who rated their health as excellent and only 8% who rated their health as fair or poor. Most respondents spent $50 or less per month on their prescriptions, but 5% reported spending more than $100 per month. Although only 11% reported missing 1 or more medication doses due to cost concerns, 86% of respondents reported being extremely or moderately concerned about the cost of their medications.

Most patients had a positive attitude about splitting pills, with 88% indicating a willingness to split pills in exchange for a reduced medication copayment and 84% willing to split pills to save money for their plan provider. When asked to identify how much money they would need to save per prescription for them to be willing to split pills, only 12% of respondents stated that pill splitting would not be worth any amount of monetary savings, and 59% stated that only a $5 to $10 savings per prescription would be needed for them to be willing to split pills. The remaining 57 respondents (29%) indicated that a $15 to $20 savings per prescription would be needed. 

Baseline characteristics of patients who agreed to participate in the pill-splitting trial were compared with those of respondents who declined trial participation. Patients who participated in the trial were more likely to be more than 50 years old, female, and taking more than 4 medications per month. Level of education did not correlate with patients' willingness to participate in the randomized phase of the study. There was no significant difference in health perceptions, amount of money spent on medications, compliance, or concerns about medication costs between trial participants and patients who only completed the baseline survey. However, there was a significant difference between the groups regarding their willingness to split pills to save money.

Overall, 89% of all trial participants expressed a willingness to continue splitting pills for a 50% copayment reduction until the degree of copayment reduction was determined for a future pill-splitting program, with a nonsignificantly larger proportion of those in the copayment reduction group expressing a willingness to continue pill splitting after the study (92.7% vs 85.2%) (

). Responses in the 2 trial groups were generally similar with respect to the perceived effort of splitting pills, and when asked whether they agreed with the statement that the “effort to split pills is no big deal,â€ approximately 80% of trial participants either “strongly agreedâ€ or “agreed.â€ Patients were asked to select how much of a copayment reduction would be necessary for them to participate in a pill-splitting program after the end of the study. Of the 3 possible response categories, 73% reported that they would require a 50% reduction in copayment, 26 (24%) stated that they would need their copayment waived, and 3 (3%) reported that splitting would not be worth the effort regardless of savings. Overall, there were few differences in the required copayment for splitting pills between the group who received a copayment reduction and group who did not.

Patients in the 2 groups had few significant differences in their willingness to continue pill splitting after the trial. Also, individuals willing to continue splitting pills tended to take more medications per month (27% took 7 or more medications per month vs only 8% of those who were not willing to continue splitting pills). Patients willing to split pills also spent more per month out of pocket on their medications, although these differences did not reach statistical significance.

Impacts of Pill Splitting on Medication Adherence Participants in the trial strongly indicated that splitting pills did not negatively affect their adherence. More than 90% either agreed or strongly agreed with the statement that “pill splitting has not affected my willingness to take my medication,â€ and fewer than 5% disagreed or strongly disagreed. Similarly, 90% disagreed or strongly disagreed with the statement that they had “missed more medication doses because of pill splitting.â€ Only 5% reported having 3 or more occasions on which they had to discard pills due to splitting-related problems, compared with 92 (84%) who reported zero such occasions and 12 (11%) who reported only 1-2 such occasions. Self-reported adherence rates were similar for patients with and without the copayment reduction. 

A total of 94 trial participants had at least 2 prescription fills identified during the follow-up period, allowing us to calculate MPRs. The mean Â± SD MPR in the 6 months prior to tablet splitting was 94% Â± 17%. The mean Â± SD MPR during the pill-splitting period was virtually unchanged at 94% Â± 14%.

Overall, lipid profiles did not change significantly over the course of the pill-splitting period in either patients randomized to receive the copayment reduction or those with no copayment reduction (

This study is the first prospective randomized trial evaluating the impact of pill-splitting financial incentives on patients' adherence, satisfaction, and health outcomes. It is also unique because the population includes more women and because pretrial and posttrial surveys were used in conjunction with lipid data. With respect to the impact of pill splitting on patients' adherence and health status, our results were very similar to those of other pill-splitting studies. Overall patient satisfaction was high, patients' medication adherence did not change once splitting was initiated, and lipid levels were not negatively affected.

This study provides insight into voluntary pill splitting accompanied by sharing of insurance plan cost savings with patients. The copayment incentive did not influence patient satisfaction, adherence, or cholesterol profiles during the study. Although many participants in the trial reported that they would require a financial incentive to continue splitting pills, the impact of the incentive in the randomized study suggests that in fact such incentives may not influence their willingness to adhere to a split-pill regimen.

Rather than financial incentives, this study identified specific characteristics of a split-pill regimen that can affect patients' acceptance. One of the main reported reasons for dissatisfaction with splitting was difficulty in using the pill cutter for some patients (eg, failure to yield evenly split pills, crushing the tablet). Recognizing the importance of using the proper pill cutter, we provided 2 different types of pill cutters: a small blue splitter without rubber padding and a clear splitter with both rubber padding and a wider cutting area to fit larger pills. Most of the patients preferred the clear splitter, especially those patients taking larger-sized pills. Another reported reason for dissatisfaction with splitting was difficulty in swallowing split pills due to rough edges and bitter taste (reported by 3 patients).

One of the limitations of our study is that it was conducted at a single university-based health center. It remains to be seen whether pill splitting will be well received and accepted across our whole healthcare system or within health systems treating a more socioeconomically and racially diverse patient population. Compared with some previous pill-splitting trials, our study population was younger and highly educated. Although income data were not collected, such patients may have had relatively high incomes and they may have been less sensitive to the small cost savings associated with pill splitting. Also, we did not distinguish between patients receiving statins for primary versus secondary prevention in our data collection. We found that patients less likely to be interested in pill splitting included those who had more formal education, spent less on medications, and took fewer medications. In conjunction with other studies, this result suggests that patients receiving Medicaid or other financially pressed pharmacy insurance programs may be more willing to split pills if the program effectively addresses patients' concerns about using the splitter. Another limitation of this study was its short duration. Our prescription plan allowed for a 3-month supply per refill, providing only 2 opportunities to observe compliance. This may have biased the MPR estimates to reflect overall optimistic adherence levels compared with what would have been observed given a longer follow-up period.

The financial benefits of moving to a split-pill regimen can be enormous. Since this study was completed, we have implemented a pill-splitting program for all university employees through the university pharmacy benefit plan. All patients will be offered a 50% copayment reduction for splitting atorvastatin, pravastatin, and simvastatin, with a free pill cutter provided once a year. Without much marketing effort, 5.3% of statin users were splitting pills within less than 3 months of implementation of the pill-splitting program, yielding $33 000 savings. Extrapolated annual cost savings of this program would be $1.3 million if 45% of current statin users started to split pills.

When pill-splitting plans are implemented, only the prescription plan benefits financially unless there is some sharing of cost savings with patients. Although in our study sharing cost savings with patients did not significantly impact their willingness to participate, most patients said that they would expect some financial incentive in order to continue splitting pills. Because there are a variety of patient and product factors involved, voluntary pill-splitting programs seem to be more optimal when some of the financial benefits are shared with patients. This strategy should increase patient participation in a nonmandatory pill-splitting program. In any program, pill splitting should be implemented with consideration of which pills can be split without compromising clinical outcomes, as well as recognizing that this practice is safe only in patients who are able to cognitively and physically split pills. 

The current study found that many patients using lipid-lowering therapies, particularly those using a larger number of drugs, were willing to participate in a pill-splitting program. Although patients reported that financial incentives would increase their willingness to split pills, our randomized trial did not indicate that such incentives had influenced patients' adherence, satisfaction with splitting, or lipid levels.

John Piette, PhD, is a VA Research Career Scientist. Michele Heisler, MD, MPA, is a VA Career Development Awardee. Jennifer Kim, PharmD, and Diane Domas, PharmD, were University of Michigan research assistants for this study. We wish to thank Dawn M. Parsons, RPH, MBA, for assisting in the system set up of PBM. 

: From the College of Pharmacy (HMC, JGS, DSS) and the Department of Internal Medicine (MH, CJS, JDP), University of Michigan, and the University of Michigan Hospitals and Health Centers (HMC, JGS, CJS), Ann Arbor, Mich; the Center for Practice Management and Outcomes Research, VA Ann Arbor Health Care System (MH, JDP); and the Michigan Diabetes Research and Training Center, Ann Arbor (JDP).

 The University of Michigan Employee Benefits Office provided funding for this study. The principal investigator had full access to all of the data in the study

and takes responsibility for the integrity of the data and the accuracy of the data analysis. 

: Hae Mi Choe, PharmD, East Ann Arbor Health Center Pharmacy, 4260 Plymouth Rd, Ann Arbor, MI 48109-2704. E-mail: 

: The authors (HMC, JGS, DSS, MH, CJS, JDP) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter discussed in this manuscript. 

: Concept and design (HMC, JGS, DSS, MH, CJS, JDP); acquisition of data (HMC, JDP); analysis and interpretation of data (HMC, JGS, DSS, MH, JDP); drafting of the manuscript (HMC, JGS, DSS, MH, CJS, JDP); critical revision of the manuscript for important intellectual content (HMC, JGS, MH, CJS, JDP); statistical analysis (JGS, DSS, JDP); provision of study materials or patients (HMC); obtaining funding (HMC, CJS); administrative, technical, or logistic support (HMC, JGS); and supervision (HMC).

. Relationship between pill splitting and compliance, drug acquisition cost, and patient acceptance. 

. Effects of a tablet-splitting program in patients taking HMG-CoA reductase inhibitors: analysis of clinical effects, patient satisfaction, compliance, and cost avoidance. 

. The practice of splitting tabletsâ€” cost and therapeutic aspects. 

Articles

Impact of Patient Financial Incentives on Participation and Outcomes in a Statin Pill-splitting Program

Our understanding of diabetes and its managementis evolving rapidly based on informationfrom researchers and the world of healthcaredelivery about "what works" to improve outcomes.This theme issue of the 

includes studies thatcan inform efforts to improve diabetes care on manylevels, including more effective clinical decision-making,improvements in health systems that promotetreatment quality, and health policies that encouragethe best disease management practices.

Despite years of research on diabetes managementand quality improvement, these new studies are worthwhilebecause, unfortunately, diabetes treatmentprocesses and outcomes remain disappointing in manyhealthcare systems. The study by Godley and colleagues

highlights the gap between guideline recommendationsand the care many patients with diabetesreceive. Through a review of claims data and charts,the authors found that less than 20% of patients withdiabetes achieved blood pressure goals, and many hadadditional cardiovascular risk factors. Perhaps mostdisturbing, 42% of patients with poor blood pressurecontrol were on only 1 antihypertensive agent or noblood pressure treatment at all, suggesting significantroom for improvement via appropriate medicationintensification. The problem of "clinical inertia" in thecontext of poor physiologic outcomes has been documentedin glucose management as well,

and mayrequire system-level changes to ensure that patientsare prescribed drug regimens that can reduce the riskof costly complications.

Fortunately, the quality of diabetes care in manyhealthcare systems is improving, and this is shownclearly in the study by McBean and colleagues.

Theseresearchers demonstrate that most Medicare beneficiarieswith diabetes now receive guideline-recommendedservices such as testing for regular hemoglobin(HbA

) and low-density lipoprotein (LDL) tests.However, rates of other recommended care processesremain unacceptably low. The investigators also foundthat treatment processes vary across racial groups andhealth plan types. This variation provides importantclues about how to foster further quality improvements,and suggests opportunities for healthcare managersto learn from one another about how best toachieve goals set by the National Committee for QualityAssurance and other organizations.

Lessons about developing more effective models ofdiabetes care sometimes are best learned by examininghealthcare systems that seem to have gotten it right.The US Department of Veterans Affairs (VA) healthcaresystem provides better diabetes care than many privatemanaged care organizations,

through a structure thatpromotes and rewards quality via information systemsand management incentives. Jackson and colleagues

linked organizational-level data from 177 VA clinics topatient outcomes and identified a number of organizationalcharacteristics associated with improved diabetescontrol. Their study reinforces prior findings about theimportance of system changes, such as electronicreminders, and identifies other provocative correlates ofglycemic control, such as managerial autonomy and theextent to which physicians as well as nurses participatein quality improvement efforts. These results shouldfoster discussion within non-VA health systems (aswell as in poorly performing VA facilities) about howthey can adopt managerial practices that promotemore effective diabetes management.

Much of the focus in chronic disease care has beenon disease management programs, and Knight et al

provide a systematic review of programs for patientswith diabetes. These researchers report that overall,diabetes disease management can lead to modestimprovements in patients' glycemic control, as well asimprovements in related care such as retinal examinations.The authors also rightly caution readers againstadopting programs without critically appraising theircharacteristics and goals. Publication bias may welllead to an overly optimistic picture of these programs'benefits, and even in the published literature, rigorousstudies have not been uniformly positive.

As theauthors point out, many innovations in disease managementare occurring without public evaluation ofprogram effects.

Nevertheless, the generally positiveeffects demonstrated by this review are encouraging.Health plans should continue to innovate in this area,taking what has been shown to be feasible and effectivein other settings and adapting it to their own practicesand patients.

Pharmaceutical researchers have developed a fullmenu of medications that can improve glycemic control,blood pressure, and lipid levels in patients withdiabetes. Medication management is central to mostpatients' care, and pharmacists may play an importantrole in achieving physiologic targets. Choe and colleagues

conducted a randomized trial of diabetes diseasemanagement delivered by a clinical pharmacist.After more than a year of follow-up, patients whoreceived the service had greater improvements in bloodglucose levels than those receiving usual care.Intervention patients also had more frequent LDL testing,retinal examinations, and monofilament footscreening, suggesting that the pharmacist fosteredimproved treatment quality that extended beyond medicationuse. This study illustrates 1 specific strategy forachieving improvements in diabetes care, even withoutmore global changes in the way health systems areorganized.

also supportsthe need for greater attention to patients' medicationmanagement, demonstrating that many patients withdiabetes need insulin plus insulin-sensitizing agents toachieve target blood glucose levels. The study was conductedwithin the Kaiser Permanente (KP) healthcaresystem, which (like the VA) has become a model ofhow to evaluate and improve chronic illness care.Nevertheless, many patients with diabetes and poorglycemic control who were treated in the KP systemreceived monotherapy with sulfonylureas (in agreementwith current practice guidelines), which appearsto be less effective in achieving glucose level targets.Karter and other KP researchers provide a valuableservice to that system's patients, and their studiesoften provide the evidence base for quality improvementinitiatives both within and outside of the KPsystem. Other health systems should consider encouraginghealth services research that leverages the enormouspotential of their own data systems for improvingthe knowledge base available to their clinicians andmanagers.

Finally, the article by Herman and colleagues

addsto the growing body of evidence that appropriate medicationuse may not only improve the health status ofpatients with diabetes, but may also reduce their use ofcostly health services. The investigators compared outcomesfor patients with type 2 diabetes who were randomizedto either monotherapy with sulfonylureas orcombination therapy with rosiglitazone. After 2 years offollow-up, patients in the combination therapy groupexperienced fewer emergency department visits andhospitalizations and lower per-patient treatment costs.In addition to the study's important clinical implications,findings such as these provide an important contextfor payer decisions about out-of-pocket drug costsand the influence they may have on the behavior ofpatients taking multiple medications. Too often, thesecosts inhibit appropriate adherence and foster poorerhealth outcomes.

Collectively, these studies provide an exciting pictureof where we have come in diabetes clinical andhealth services research. They also highlight the workthat remains to be done in order to ensure that as manypatients with diabetes as possible can lead healthy andproductive lives. We must continue to develop newstrategies for designing health systems that foster qualitydiabetes care. Given the demonstrated benefit ofmedication intensification for diabetes as well as othercommon chronic illnesses, future work should identifythe barriers to appropriate prescribing, regimen adjustments,and patient adherence. Redesigning prescriptiondrug benefits so that patients' out-of-pocket costs reflecttheir expected benefit from pharmacotherapy is an ideathat has been championed by Fendrick and others foryears.

Studies such as those in this special issue add tothe growing evidence supporting this innovativeapproach. The "business case" for effective diseasemanagement is growing. The challenge to researchers,health systems, and payers will be to take the bold stepsneeded to redesign treatment and benefit structures inways that foster the gains suggested here.

From the Center for Practice Management and Outcomes Research, VA Ann ArborHealth Care System; Department of Internal Medicine and Michigan Diabetes Research andTraining Center, Ann Arbor, Mich.

Dr. Piette is a VA Research Career Scientist. The views expressed in this article do notnecessarily reflect those of the US Department of Veterans Affairs.

Address correspondence to: John D. Piette, PhD, Center for Practice Management andOutcomes Research, VA Ann Arbor Health Care System, PO Box 130170, Ann Arbor, MI,48113-0170. E-mail: jpiette@umich.edu.

1. Godley PJ, Maue SK, Farrelly EW, Frech F. 

The need for improved medical managementof patients with concomitant hypertension and type 2 diabetes. 

2. Shah BR, Hux JE, Laupacis A, Zinman B, van Walraven C. 

Clinical inertia inresponse to inadequate glycemic control: do specialists differ from primary care physicians?

Improved care and outcomes among elderlyMedicare managed care beneficiaries with diabetes. 

Diabetes care quality in the Veterans AffairsHealth Care System and commercial managed care: the TRIAD study. 

5. Jackson GL, Yano EM, Edelman D, et al. 

Veterans Affairs primary care organizationalcharacteristics associated with better diabetes control. 

6. Knight K, Badamgarav E, Henning J, et al. 

A systematic review of diabetes diseasemanagement programs. 

7. Krein SL, Klamerus ML, Vijan S, et al. 

Case management for patients with poorlycontrolled diabetes: a randomized trial. 

Disease management and the organization of physician practice. 

9. Choe HM, Mitrovich S, Dubay D, Hayward RA, Krein SL, Vijan S. 

Proactive casemanagement of high-risk patients with type 2 diabetes by a clinical pharmacist: a randomizedcontrolled trial. 

Achieving good glycemic control: Initiation ofnew antihyperglycemic therapies in patients with type 2 diabetes from the KaiserPermanente Northern California Diabetes Registry. 

11. Herman WH, Dirani RG, Horblyuk R, et al. 

Reduction in use of healthcare serviceswith combined sulfonylurea and rosiglitazone: findings from the rosiglitazone earlyversus sulfonylurea titration (RESULT) study. 

12. Piette JD, Wagner TH, Potter MB, Schillinger D. 

Health insurance status, cost-relatedmedication underuse, and outcomes among diabetes patients in three systems ofcare. 

13. Fendrick AM, Smith DG, Chernew ME, Shaw SN. 

A benefit-based copay for prescriptiondrugs: patient contribution based on total benefits, not drug acquisition cost.

The Future of Diabetes Disease Management: Integrating Lessons Learned from Clinical, Health Services, and Policy Research

 To compare rates of cost-related medication underuseand other problems due to medication costs amongDepartment of Veterans Affairs (VA) patients with rates amongpatients with Medicaid, private health insurance, Medicare, and noinsurance coverage.

 A total of 4055 chronically ill patients completed anonline questionnaire regarding cost-related adherence problemsfor medications used to treat 16 chronic illnesses. Respondentsalso reported whether they cut back on necessities due to medicationcosts, increased their debt burden to pay for prescriptions, andworried about how they would pay for their medications.

 Rates of cost-related medication underuse were loweramong VA patients (12%) than among patients with Medicaid(25%; 

 < .0001). In multivariate analyses, patients with Medicare or noinsurance coverage were more likely than VA patients to foregomedication at least once per month due to cost (adjusted oddsratios of 3.4 and 3.9; both 

 &#8804; .001). Patients with Medicare or noinsurance coverage also were more likely than VA patients toforego basic needs to pay medication costs, borrow money to payfor their treatments, and worry frequently about how they wouldpay for their medication.

 The VA's prescription benefits may prevent problemsdue to medication costs. Studies assessing the impact of VAprescription coverage on health outcomes and service use will beneeded to evaluate the cost-effectiveness of VA drug benefit policies.

(Am J Manag Care. 2004;10(part 2):861-868)

Managed care plans and their patients are strugglingwith the burden of skyrocketing prescriptiondrug costs. Patients with chronic illnessesoften have inadequate prescription coverage,

 andmany cut back on medication use due to cost pressures.

 Because medication underuse can lead toincreased morbidity, mortality, and preventable acute-careuse,

 managed care organizations are striving todevelop drug coverage programs that are financiallyviable while ensuring that plan members can afford thetreatments they need.

Department of Veterans Affairs (VA) medical centersoffer more comprehensive medication coverage thanalmost any other payer in the United States. Drugs onthe VA formulary are 100% covered for patients withlow incomes or service-connected disabilities, and otherVA patients pay a $7 copayment for a 30-day prescription.VA patients have no cap on the total cost of theircovered drugs, and most patients who incur $840 ormore in medication costs during a given year have allsubsequent copayments waived. Between 1995 and2001, the number of patients receiving VA outpatientcare increased from 2.8 million to 4.1 million, withmany of these new patients entering the system toaccess prescription drug coverage.

 In the context ofthe current debate over prescription drug costs, theVA's drug coverage policy and its impact on patients'use of prescribed medications provide an importantmodel for inquiry.

 we compared rates of cost-relatedmedication underuse among diabetes patients in 3 VAfacilities to rates among patients with private insurance,Medicare, Medicaid, and no health insurance treated ina county and a university health system. We found thatVA patients were less likely than patients with any othertype of coverage to report medication underuse due tocost. We also found that patients reporting cost-relatedadherence problems had poorer glycemic control, moresymptoms, and worse physical and mental health functioning.These findings suggest that the VA's comprehensivedrug benefits may contribute to the bettertreatment outcomes among chronically ill VA patientscompared with Medicare patients.

 however, all patients were drawn from 5 healthcaresystems, 4 or which were located in NorthernCalifornia. Thus, it remains unclear whether the findingsreflect nationwide patterns of adherence among VAand non-VA patients with chronic illnesses.

The problems chronically ill patients face due tomedication costs extend beyond their treatment adherence.For example, one recent study found that 21% ofMedicare beneficiaries spent less on basic needs tocover the cost of their prescription drugs.

 However, weknow little about the extent to which the VA's prescriptiondrug coverage may buffer chronically ill patientsfrom these other consequences of out-of-pocket treatmentcosts.

Accordingly, we surveyed a nationwide panel ofchronically ill older adults about their problems due toout-of-pocket medication costs. We found that rates ofcost-related medication underuse were high amongindividuals with a variety of chronic health problems.

We also found that more than 22% of patients reportedcutting back on spending for basic needs in response tomedication cost pressures, and that 16% reportedincreasing their debt burden to pay medication costs.

In the current study, we compared rates of cost-relatedmedication underuse as well as other burdens frommedication cost pressures among survey respondentsusing VA care with rates among patients with otherforms of health insurance coverage.

The study was based on surveys completed duringNovember and December 2002 by a nationwide panel ofadults living in the United States. Details about thepanel's sampling approach and recruitment process areavailable elsewhere.

 In brief, panel members wererecruited using random digit dialing; the sampling frameconsisted of the entire US population with an assignedtelephone number. Potential panel members wereoffered WebTV and free Internet access in exchange forcompleting Web-based surveys several times per month.At the time of this study, the panel included over 40 000members.

We used sociodemographic and health status informationabout panel members to identify all 5644 individualsaged 50 years and older who reported takingprescription medication for diabetes, depression, heartproblems, hypertension, or high cholesterol. Thesociodemographic characteristics of these respondentswere similar to those of Americans aged 50 years andolder, as reported in 2000 Census data. For example,the survey and Census populations were similar withregard to the representation of African Americans (8%vs 10%), women (50% vs 54%), married individuals (70%vs 65%), and individuals with household incomes of$20 000 or less (17% vs 23%). Institutional reviewboards approved the study protocol.

Respondents were asked about their use and cost-relatedunderuse of prescription medication for each of16 chronic health problems: arthritis; asthma; chronicback pain or sciatica; diabetes; high cholesterol; chronicobstructive pulmonary disease ("chronic bronchitis,emphysema, or chronic obstructive pulmonary disease");depression; heartburn, acid reflux, or irritablebowel syndrome; atherosclerosis ("blocked arteries inthe heart, angina, or chest pain from heart disease");heart failure; high blood pressure or hypertension;myocardial infarction ("heart attack"); migraineheadache; osteoporosis; stomach or duodenal ulcers;and stroke. On a condition-by-condition basis, participantswere asked: "In the past 12 months, have youever taken less of this medication than prescribed byyour doctor because of the cost?" For the current analyses,respondents were coded as having cost-relatedadherence problems if they reported any medicationunderuse due to cost for 1 or more of their medicationsin the prior year.

Respondents reporting cost-related underuse wereasked how often they engaged in each of the followingbehaviors because of the medication cost: taking fewerpills or a smaller dose, not filling a prescription at all,putting off or postponing getting a prescription filled,using herbal medicine or vitamins when feeling sickrather than taking their prescription medication, or takingthe medication less frequently than recommendedto "stretch out" the time before getting a refill.Participants were coded as foregoing medication at leastmonthly if they reported any of these behaviors "at leastonce per month" due to the cost.

Respondents also were asked about 4 other types ofproblems associated with out-of-pocket medicationcosts: spending less on basic needs such as food or heatto pay medication costs, borrowing money from familyor friends to pay medication costs, increasing creditcard debt to pay for medications, and worrying abouthow to pay for medications at least once per month. Seethe footnotes to Tables 2, 3, and 4 for the wording ofeach item.

For the current study, respondents were groupedinto mutually exclusive categories using a hierarchybased on their primary source of medical insurance.Patients were assigned to the insurance category thatwe expected would be associated with the most generousform of prescription drug coverage. Specifically, weidentified the following patient groups: VA patients,Medicaid patients who did not use the VA, privatelyinsured patients (without VA use or Medicaid),Medicare patients with no other form of health insurance,and uninsured patients. These categories identifysubgroups of patients of particular interest to policymakers(eg, patients with Medicare coverage only) andrecognize that individuals often are unable to identify indetail the provisions of theirprescription drug coverage.

The sociodemographic variableswe examined as possible predictorsof problems due to out-of-pocketmedication costsincluded respondents' race, age,sex, educational attainment,and annual household income.We also examined indices ofpatients' medication cost pressures,including their total numberof prescription medications,total monthly out-of-pocketmedication costs, and numberof chronic health problems.

In initial analyses, we examinedbivariate differences in thesociodemographic characteristicsand medication cost pressuresacross groups of patientsdefined by their primary sourceof health insurance. We thenexamined bivariate associationsbetween insurance type andeach outcome (medicationunderuse, foregoing necessities,borrowing from family orfriends, increasing credit carddebt to pay medication costs,and medication cost worry).Finally, we constructed multivariatelogistic regression modelsto determine the independenteffect of insurance type on eachoutcome, controlling for patients'sociodemographic characteristics(race, sex, age,educational attainment, andincome), number of chronichealth problems, and number ofprescription medications. See

 for the categorization ofordinal and categorical covariates. We included all ofthe covariates in each regression model although somecovariates were not associated with all the outcomevariables, both for consistency and because each of thevariables has been found to be related to medicationadherence problems in prior studies. In all bivariate andmultivariate analyses, we used a standard adjustment tointerpret the 

 values associated with the 4 pairwisecomparisons between VA patients and patients in the 4other insurance categories. Thus, a 2-sided 

 value of.0125 (.05 &#247; 4) was considered equivalent to a nominal

 value of .05 in defining statistically significant differences.

Because our hypothesis was that VA prescription benefitswould lead to lower rates of medication cost problemsby decreasing patients' out-of-pocket costs,out-of-pocket costs were not included as a covariate inour primary multivariate models. Confirmatory analysesincluded models with out-of-pocket costs as acovariate and fitting models limited to men only(because of the high number of male VA patients). In allanalyses, we used sampling weights to adjust the distributionof respondents to match the distribution of theUS population on age, sex, race/ethnicity, education,region, and metropolitan residence, thereby correctingfor oversampling and survey nonresponse.

 TheBureau of Labor Statistics Current Population Surveyfor October 2002 provided data on the distributionof the US population.

A total of 4264 people (76% of the 5644 patients sampled)completed the online informed consent and questionnairein the fall of 2002. We subsequently excluded185 participants because they reported that they wereno longer taking medication for any of the 5 index conditionsand 24 additional patients because they weremissing data on income. The final sample size was 4055.Compared with eligible nonrespondents, respondentsto the survey were more likely to be white (88% vs 81%;

 <.001), to be older (mean age of 65 years vs 63 years;

 <.001), and to have some college education (66% vs60%; 

 < .001). Respondents and nonrespondents weresimilar with regard to sex (

VA patients were more likely to be Caucasian andmale than patients with other insurance types (Table 1).As expected, Medicare patients were older than otherpatients, and most patients with Medicaid coverage hadannual household incomes of less than $20 000 per year.VA patients reported using more prescription medicationsthan patients with private insurance (

 <.0001). For example,a greater proportion of VA patients reported usingcholesterol-lowering drugs (63%) than patients withMedicaid (48%), private insurance (50%), Medicare(46%), or no health insurance (44%; overall 

 = .007).Nevertheless, VA patients reported lower monthly out-of-pocket medication costs than patients with either privatehealth insurance (

Bivariate Relationships Between Insurance Typeand Medication Cost Problems

), less than half asmany VA patients reported foregoing medication atleast once per month due to cost (7%) than patients withMedicaid (20%; 

 <.0001). VA patients alsowere substantially less likely than patients withMedicaid, Medicare, or no health insurance to cut backon necessities to pay medication costs, borrow moneyfrom family or friends to pay for their prescriptions, orworry about their medication costs at least once permonth (

 &#8804;.0002 for each pairwise comparison).

Controlling for patients' disease burden, income,number of prescription medications, and sociodemographiccharacteristics, patients with Medicare coveragewere 2.6 times as likely to report cost-related underuseas VA patients (

 = .001), and patients without anyhealth insurance coverage were 3.2 times as likely to doso (

). The differences between VApatients and those with other forms of health coveragewere even more pronounced when only frequent cost-relatedadherence problems (at least once per month)were considered. Compared with their VA counterparts,Medicare patients were 3.4 times as likely, andpatients with no insurance coverage were nearly 4times as likely, to report frequent medication underuse(both 

In multivariate models, we also observed significantlyhigher rates of other problems due to medicationcosts among non-VA patients compared with VApatients (

). Specifically, patients with Medicareor no insurance were both 2.9 times as likely to reportcutting back on spending for basic needs due to medicationcost pressures, 6.4 and 4.9 times as likely to borrowmoney from family or friends to pay medicationcosts, and 3.2 and 2.8 times as likely to report worryingabout their medication costs at least once per month(all 

 <.001). Rates of other problems due to medicationcosts were similar between VA patients and patientswith Medicaid or private health insurance.

Problems Due to Medication Costs Among VA and Non-VA Patients With Chronic Illnesses

 To review the literature on comorbid depression and diabetes (DM/D) and present a conceptual framework for integrating depression management with diabetes care in a managed care environment.

 Depression affects diabetes management by 1) directly affecting patientsâ€™ health-related quality of life, 2) reducing physical activity levels, 3) limiting adherence to self-care regimens, and 4) impairing patientsâ€™ ability to communicate effectively with clinicians. Small randomized trials suggest that both antidepressant medication and cognitive behavioral therapies (CBTs) or related approaches may improve not only DM/D patientsâ€™ depressive symptoms, but their physical health as well.

 An effective DM/D management strategy should include the following elements: 1) systematic identification of DM/D patients and quality-of-care reviews, 2) proactive patient monitoring between outpatient encounters, 3) intensive efforts to coordinate treatment across providers, 4) increased access to CBT or related therapies addressing patientsâ€™ depressive symptoms and diabetes self care, and 5) an emphasis on promoting physical activity to address both depressive symptoms and physiologic dysregulation. The conceptual framework developed for the care of DM/D patients offers general insights into the management of patients with multiple chronic medical disorders

(Am J Manag Care. 2004;10(part 2):152-162)

Medical care for diabetes is improving in many health systems. The Department of Veterans Affairs,

have reorganized some diabetes services to reflect principles of effective chronic disease management. As a result, they have increased the provision of recommended care processes and improved patients' glycosylated hemoglobin (HbA

) levels–an important intermediate outcome linked to long-term complications such as blindness, limb amputation, and kidney failure.

Nevertheless, nationwide studies report that many diabetes patients continue to have difficulty with self care and experience suboptimal outcomes.

Comorbid medical problems such as depression may be key barriers to achieving treatment gains. Unfortunately, most diabetes management algorithms provide only a limited framework for considering the treatment of comorbid medical conditions. Rather, comorbid conditions usually are addressed under the broad rubric of "tailoring" guidelines to patients' unique needs–a strategy that often fails to conceptually integrate care, prioritize interventions, and identify treatment synergies (ie, treatments that impact more than 1 of the patient&#8219;s comorbid conditions and thus increase treatment value). A more explicit method of identifying priorities for treatment planning could lead to more effective and rational care for patients with comorbid conditions, especially in the context of limited healthcare resources. 

Patients with diabetes and depression (DM/D) comprise a large, costly, and vulnerable subgroup of diabetes patients. The purpose of this paper is to review the literature on comorbid depression and diabetes, and present a conceptual framework for integrating depression management with diabetes care. We discuss the ways in which depression might affect diabetes patients' self-care activities and outcomes, even when health systems offer excellent diabetes-specific treatment. Given the state-of-the-science in DM/D research, an exhaustive quantitative summary of studies addressing specific dimensions of DM/D care (eg, the relative effectiveness of interventions focusing on exercise promotion vs intensive pharmacologic management) is not possible. Nevertheless, we highlight some of the most important literature from relevant fields, examine the treatment implications suggested by the links between these 2 conditions, and suggest ways in which DM/D care may offer general insights into how to conceptualize treatment and manage patients with multiple chronic disorders. 

Like diabetes, major depressive disorder is a common and debilitating illness. Among patients in primary care, 4% to 15% meet criteria for major depression and another 9% to 16% meet criteria for other depressive disorders.

Elderly and poor individuals have particularly high rates of depression, and these groups also are at greatest risk for diabetes and diabetes-related complications. 

Diagnostic and Statistical Manual for Mental Disorders

Depression is twice as common among diabetes patients than in the general population, with 15% to 30% of diabetes patients meeting criteria for depression, depending on whether 

 criteria or high scores on standard depression scales are used to define clinically significant illness.

Evidence is conflicting with regard to whether depression is an independent risk factor for diabetes.

However, depression clearly is more common among diabetes patients–especially those with comorbid conditions.

After an initial episode of depression, patients with diabetes relapse more frequently than other patients.

Depression is a risk factor for hypertension,

and each of these illnesses increases the rate of cardiovascular events among diabetes patients. Although the relationship is complex and may differ for patients with type 1 and type 2 diabetes,

it is clear that depression among diabetes patients is associated with poor glycemic control. 

Patients with DM/D also have higher rates of retinopathy19 and macrovascular complications such as stroke and myocardial infarction (MI) than do nondepressed diabetes patients,

and they report more diabetes- related symptoms.

Patients with major depression respond to antidepressants, depression-specific psychotherapies, or both. Meta-analyses report absolute increases in remission rates of 17% to 39% among patients randomized to receive antidepressants compared with patients receiving placebo.

Antidepressants are as effective among patients with comorbid medical illnesses as they are among patients with major depression alone.

Numerous randomized trials have demonstrated the efficacy of psychotherapies such as cognitive behavioral therapy (CBT) or related approaches (eg, problem- solving therapy) for patients with depression.

Cognitive behavioral therapists work with patients to interrupt self-perpetuating cycles of negative thoughts, low mood, decreased motivation, and inactivity. They also use behavioral techniques to increase pleasurable and productive activities. Depressed patients who receive CBT appear less likely to relapse after treatment is discontinued than patients receiving only antidepressant medication.

In randomized trials, Lustman and colleagues demonstrated that both antidepressant medication and CBT are efficacious for patients with DM/D. In one study, they found that 67% of DM/D patients receiving fluoxetine showed improvement on the Beck Depression Inventory after 8 weeks of treatment compared with 37% of patients receiving placebo.

In a second study, a conservative intent-to-treat analysis showed that 71% of DM/D patients randomized to a 10- week CBT intervention achieved remission, compared with 22% of patients randomized to diabetes education alone (

 < .001); 58% of the CBT patients were in remission at the 6-month follow-up, compared with 26% of controls (

Although there are no large studies indicating that depression treatments for DM/D patients improve medical outcomes, studies by Lustman and colleagues suggest that the treatments may have this important effect. In their CBT study,

these investigators found that patients receiving CBT had substantially better HbA1C levels 6 months after the intervention than did control patients (9.5% vs 10.9%; 

Despite the potential efficacy of depression treatment, DM/D patients are likely to experience significant gaps in their depression care. Providers often fail to detect depression among their patients,

and when depression is identified, depression-specific therapies often are not initiated.

Primary care physicians may be uncomfortable managing depression because they lack treatment expertise or because of time constraints and competing clinical demands. Patients may be unwilling to accept or continue antidepressant treatment because of concerns about stigma or side effects.

Effective CBT therapy often is unavailable because of the lack of adequately trained therapists or limitations on patients' mental health benefits.

Among patients who initiate a course of antidepressant medication, long-term adherence is poor. In a large managed care organization, 28% of patients discontinued their antidepressants within the first month of treatment and 44% discontinued these medications by the third month.

Pharmaceutical claims databases suggest that 30% of patients with private insurance and 70% of patients with Medicaid coverage fill fewer than 4 30-day prescriptions in the 6 months after initiation of antidepressant therapy and thus do not receive an adequate antidepressant trial.

A potential barrier to effective depression management among diabetes patients is the lack of a coherent view of patients' clinical problems that encompasses both disorders. At the system level, this often is reflected by a structural lack of integration between medical and mental health services, with mental health and general medical providers often treating patients in different locations, maintaining separate medical records, and communicating infrequently.

Primary care providers often do not appreciate the importance of aggressive depression management for patients' overall health, and patients often do not draw connections between their depressive symptoms and their ability to manage their diabetes. Despite a good deal of descriptive epidemiology about the confluence of diabetes and depression as well as the availability of effective treatments, there is little consensus regarding the mechanisms linking these 2 conditions or how the care of DM/D patients might be most effectively managed. 

CONCEPTUAL FRAMEWORK FOR THE RELATIONSHIP BETWEEN DIABETES AND DEPRESSION

John D. Piette, PhD

Articles

Impact of Patient Financial Incentives on Participation and Outcomes in a Statin Pill-splitting Program

The Future of Diabetes Disease Management: Integrating Lessons Learned from Clinical, Health Services, and Policy Research

Problems Due to Medication Costs Among VA and Non-VA Patients With Chronic Illnesses

Addressing the Needs of Patients With Multiple Chronic Illnesses

Interactive Voice Response Systems in the Diagnosis and Management of Chronic Disease