Methodology of an ongoing, randomized, controlled trial to improve drug use for elderly patients with chronic heart failure

M.D. Murray et al.

The American Journal of Geriatric Pharmacotherapy

Methodology of an Ongoing, Randomized, Controlled Trial to Improve Drug Use for Elderly Patients with Chronic Heart Failure Michael D. Murray, PharmD, MPH, 1-3 James M. Young, PharmD,4 Daniel G. Morrow, PhD,5 Michael Weiner, MD, MPH, 2,3,6Wanzhu Tu, PhD,2,3,6Shawn C. Hoke, BA,4 Daniel O. Clark, PhD,2,3,6 Kevin T. Stroupe, PhD,7,8 Jingwei Wu, MS, z Melissa M. Deer, MS, OTR,3 "l]na E. Bruner-England, PharmD,4 Kevin M. Sowinski, PharmD, 1 Faye E. Smith, MA, 3 Neil B. Oldridge, PhD,9 Irmina Gradus-Pizlo, MD, 2,m Laura L. Murray, PhD,1~ D. Craig Brater, MD, 2 and Morris Weinberger, PhD12

lOepartment of Pharmacy Practice, Purdue University School of Pharmacy, West Lafayette, 2Department of Medicine, Indiana University School of Medicine, 3Regenstrieflnstitute, 4Wishard Health Services, Indianapolis, Indiana, 5Institute of Aviation, University of Illinois at Urbana-Champaign, Urbana, Illinois, 6Indiana University School of Medicine, Indiana University Center for Aging Research, Indianapolis, Indiana, ZMidwest Center for Health Services and Poficy Research, Hines Veterans Administration Hospital, Hines, aFeinberg School of Medicine, Northwestern University, Evanston, Illinois, 9Center for Urban Population Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, 1°KrannertInstitute of Cardiology, Indiana University School of Medicine, Indianapolis, 11Department of Speech and Hearing Sciences, Indiana University, Bloomington, Indiana, and Z2Oepartmentof Health Policy and Administration, University of North Carolina, Chapel Hill, North Carolina ABSTRACT Background: Medications can improve the functioning and health-related quality of life of patients with chronic heart failure (CHF) and reduce morbidity, mortality, and costs of treatment. However, patients may not adhere to therapy. Patients with complex medication regimens and low health literacy are at risk for nonadherence. Objective: The primary goal of this project is to develop and assess a multilevel pharmacy-based program to improve patient medication adherence and health outcomes for elderly CHF patients with low health literacy. Methods: In this 4-year, controlled trial, patients aged >50 years with a diagnosis of CHF who are being treated at Wishard Health Services (Indianapolis, Indiana) are randomly assigned to pharmacist intervention or usual care. Intervention patients receive 9 months of pharmacist support and 3 months of postintervention follow-up. The intervention involves a pharmacist providing verbal and written education, icon-based labeling of medication containers, and therapeutic monitoring. The pharmacist identifies patients' barriers to appropriate drug use, coaches them on overcoming these barriers, and coordinates medication use issues with their primary care providers. Daily

updates of relevant monitoring data are delivered via an electronic medical record system and stored in a personal computer system designed to support pharmacist monitoring and facilitate documentation of interventions. To measure medication adherence objectively, electronic monitoring lids are used on all CHF medications for patients in both study groups. Other assessments include self-reported medication adherence, results of echocardiography (eg, ejection fraction), brain natriuretic peptide concentrations, and healthrelated quality of life. Health services utilization, refill adherence, and cost data derive from electronic medical records. After completion of this study, the data can be used to assess the effectiveness and costeffectiveness of our intervention. Results: One hundred twenty-two patients have been assigned to receive the intervention and 192 to receive usual care. Conclusions: Our study aims to improve patients' knowledge and self-management of their medication and to improve medication monitoring in a multilevel pharmacy-based intervention. By doing so, we intend that the intervention will improve the health outcomes

AcceptedforpublicationDecember23,2003. Copyright © 2004 Excerpta Medic& Inc.

Volume 2

•

Number 1

1543-5946/04/$19.00

March 2004

The American Journal of Geriatric Pharmacotherapy

M.D. Murray et al.

of elderly patients with CHF. (Am J Geriatr Pharmacother. 2004;2:53-65) Copyright © 2004 Excerpta Medica, Inc. Key words: heart failure, medication adherence, outcomes research.

INTRODUCTION Chronic heart failure (CHF) is a morbid and costly condition that affects -5 million Americans, particularly older adults (aged _>50 years). 1,2 The prevalence of CHF is -300% higher among adults aged 55 to 64 years and _>500% higher among adults aged >75 years compared with adults aged 45 to 54 years. 3 By the eighth decade of life, 10% ofaduhs will have developed CHF. 4 Direct and indirect costs of CHF in the United States have been estimated at $21 billion. 3 These data underscore the need for new strategies to improve the quality of care of CHF patients. Medications provide a central strategy for improving the functioning and health-related quality of life (HRQL) of patients with CHF, reducing morbidity, mortality, and the costs of treatment. ~ Randomized, controlled trials have documented the benefits of 5 drug types--angiotensin-converting enzyme (ACE) inhibitors, 1,6 beta-adrenergic antagonists (betablockers),7-9 digoxin, 1° spironolactone, n and reliably absorbed loop diuretics.12 Moreover, new pharmacologic approaches currently being tested could increase the number of medications used to treat CHF.13 Despite the well-documented efficacy of these medications, patients may not receive prescriptions for these drugs from their physicians, may not tolerate the drugs when prescribed, or may not adhere to a regimen that is likely to be complicated. Poor adherence is exacerbated among patients who are prescribed >5 chronic medications, 14 a situation that is common among CHF patients, who often have comorbidifies that require medication. Health literacy could be another risk factor for poor adherence, is Clearly, any benefits of these medications may not apply to patients with suboptimal adherence levels. The primary goal of this project is to develop and assess a multilevel pharmacy-based program aimed at improving patient medication adherence and health outcomes for elderly CHF patients with low health literacy. In this paper, we describe the methodology being used in an ongoing, randomized, controlled trial in older patients with CHF that will allow us to determine the cost-effectiveness of the study intervention and identify determinants of clinical deterioration of heart failure.

.

I

RESEARCH DESIGN AND METHODS Overview We are conducting a 4-year, randomized, controlled trial to assess a multilevel pharmaceutical care program designed to improve medication adherence using tailored strategies, such as patient education and special medication packaging implemented by a specially trained and equipped pharmacist. Patients with CHF are assigned to the intervention group or the usual care group and followed for 12 months. Patients assigned to the intervention group receive 9 months of active intervention and a 3-month postintervention followup. The intervention includes verbal education, use of icon-based written patient handouts, icon-labeled medication containers, monitoring of drug therapy, and improved communication among patients, pharmacists, and physicians. Primary outcomes include H R Q L and acute exacerbation of CHF. Patients assigned to the usual care group receive no intervention by the study pharmacist. The study protocol was approved by the Indiana University-Purdue University Institutional Review Board. Study Site The study site is the Primary Care Center of Wishard Health Services (Indianapolis, Indiana), a county taxsupported urban teaching medical center located at the Indiana University Medical Center, which includes a 300-bed hospital, 65 outpatient clinics, and the busiest emergency department in Indiana. It serves predominantly inner-city patients. O f >40,000 patients visiting the Primary Care Center, -3000 (-7.5%) have a diagnosis of CHF, most of whom are aged >50 years; 61% are women, and 53% are African American. Most of the prescriptions filled at the Primary Care Center pharmacy are for adult patients. 16 Patient Recruitment Patients are recruited for this study using ResNet (Indianapolis, Indiana), an existing research network that is the only option for recruiting primary care clinic patients into research projects. ResNet was designed to efficiently enroll patients into clinical trials with minimal disruption of the delivery of primary care. A data analyst at the Regenstrief Institute (Indianapolis, Indiana) uses the electronic medical records (see next subsection) to identify potentially eligible patients; these data are then provided to ResNet. A primary function of the data analyst is to filter patients who do not meet inclusion and exclusion criteria, choose not to

M.D. Murray et al.

participate in clinical research, or are already participating in institutional review board-approved research.

Regenstrief Medical Record System We have assessed numerous health care delivery interventions to improve the process and outcomes of care using our electronic medical record system, called the Regenstrief Medical Record System (RMRS). 17,18 The RMRS was developed in modules (eg, pharmacy, laboratory, scheduling) that feed data for archiving into a database module. A network of computer workstations throughout Wishard Health Services (eg, clinics, emergency department, Wishard Hospital) enables online entry of prescriptions and orders by physicians. Computer programs help physicians with their daily care of patients, including retrieval of temporal displays of prescribed drugs, laboratory tests, data from clinical encounters (eg, diagnoses, procedures), vital signs, and body weight. Physicians also use this system for e-mail, MEDLINE searches, and retrieving information from searchable textbooks. For this study, we have created links from the RMRS to the study pharmacist's computer to populate the pharmacotherapy monitoring parameters for CHF (eg, medications, body weight, blood pressure). In addition, the pharmacist uses the integrated system to exchange e-mail with physicians. Furthermore, the RMRS is used as an important source of process and outcome data for this study (eg, prescription data, disease exacerbation, health care utilization, costs of care).

Pharmacist Training A pharmacist who has received multidisciplinary training is responsible for the intervention. The didactic component includes guidelines for the treatment of CHF, principles of pharmaceutical care of older adults, pharmacotherapy of CHF, techniques for communication with older adults, strategies for improving medication adherence, and use of icon-based patient pamphlets. The experiential component includes the use of electronic monitoring of adherence, patient-centered care, interpretation of patient-specific data from the RMRS, strategies for delivering pharmaceutical care in response to patient-specific data, and use of adherence profiles to educate patients. Manuals are being developed to train pharmacists at other sites who wish to develop such a program. We have developed similar training manuals for pharmacists in the past. 19 A multidisciplinary team of study investigators provides 3 training modules. The first addresses the principles of pharmaceutical care of older adult patients

The American Journal of Geriatric Pharmacothera~y

with CHF. Modeled after our recent study of pharmaceutical care of reactive airways disease, 19 this module includes an inpatient rotation in cardiovascular therapeutics with a board-certified pharmacotherapist, an ambulatory rotation with a cardiologist, and assigned readings on the management of CHF, followed by discussion. The second module addresses strategies to educate patients with chronic diseases to improve their adherence, z° The pharmacist meets with a geriatrician to discuss the management of the older adult with CHF; a cognitive psychologist to learn a schema for presenting medication information to older adults; and a behavioral scientist to discuss improving selfmanagement for older adults with chronic diseases,21 the use of the patient education materials, 22,23 and techniques to improve communication with physicians and other primary care providers. The final module addresses policies and procedures at the Wishard Health Services Pharmacy and implementation of the pharmaceutical care intervention fkom the pharmacy.

Randomized, Controlled Trial This randomized, controlled trial is intcnded to test whether our pharmacy-based intervention improves medication adherence and health outcomes. The protocol is designed to broadly address medication use among older adult patients with CHF. Patients are randomly assigned to receive the intervention or usual carc. The intcrvention pharmacist provides pharmaceutical care for patients aged >50 years with CHF, including patient education, icon-based medication packaging, techniques to enhance medication adherence, and the use of a computer-based monitoring program. Patients in the usual care group receive prescription services from pharmacists without special training and without access to educational materials. We chose to randomize more patients to receive usual care than to receive the intervention to provide us with sufficient statistical power to identify the determinants of decompensation of CHF. To prevent contamination among pharmacists within the pharmacy, only the study pharmacist has access to the intervention materials and computer. Because the pharmacist delivers the intervention, there can be no contamination; however, other health care providers will be reminded by the pharmacist intermittently during the study not to make copies or distribute the patient education sheets. For each participant, the intervention lasts 9 months, with follow-up monitoring of study end points continuing through month 12 to assess the effect of the pharmacist intervention.

55

The American Journal of Geriatric Pharmacotherapy

M.D. Murray et al.

Primary health outcomes are H R Q L and exacerbations of CHF resulting in hospitalization. Secondary outcomes are patient satisfaction with health care, patient satisfaction with the pharmacist, and direct health care costs.

Inclusion and Exclusion Criteria Inclusion Criteria Patients are eligible for participation if they are aged >50 years; have a diagnosis of CHF; plan to continue to receive their care and prescriptions at Wishard Health Services; are prescribed an ACE inhibitor, beta-blocker, diuretic, digoxin, or spironolactone; can speak English; have telephone access; have no hearing impediments within the normal speaking range; and have adequate mental status. To assist with the ascertainment of the type of CHF (diastolic or systolic ventricular dysfunction), patients must undergo echocardiography. Exclusion Criteria Patients are ineligible if they are unwilling to do any of the following: respond to H R Q L and medication adherence questions, provide written informed consent that includes permission for investigators to obtain medical records concerning admissions to other hospitals, or take their medications from the medicationevent-monitoring containers (MEMS V TrackCap, AARDEX Ltd., Zug, Switzerland).

Baseline Interview and Randomization to Study Group After patients have provided their informed consent for participation, the project coordinator contacts them to arrange their baseline interview by a research assistant and the pharmacist. After the research assistant completes the baseline interview, the patient is randomized to the intervention or usual care group using a computerized algorithm. We have successfully used such a randomization process in another study of patients with CHF. 24 The pharmacist--who is blinded to the study group--takes medication histories of patients in both the intervention and the usual care groups and explains the electronic monitoring system (MEMS). Patients are provided with an insulated bag designed specifically for the study to hold and protect the MEMS containers. This bag allows easy transport of the containers while the patients are away from home and when they bring the MEMS lids to the pharmacist for data extraction. Patients are instructed that they must take all doses from the MEMS container and carry the con-

tainers with them in the special bag. They are also provided with a laminated card containing procedures and ways to contact the pharmacist and other study personnel. After the medication history and transfer of the medications to the MEMS containers, patients in the usual care group are discharged to conventional care in their regularly appointed primary care clinic. However, for participants in the intervention group, the pharmacist also explains the patient education materials and special labeling. Also, for these patients, the pharmacist uses data from the baseline interview, the medication history, and the computer systems to formulate a tailored intervention strategy. The pharmacist also provides the patient's physician with a list of prescription and nonprescription medications the patient is receiving and meets with the physician, as necessary, to review the formulated patient-centered strategy and discuss any potential problems with the patient's overall drug use pattern, including use of over-the-counter medications, herbal drugs, and alcohol.

Intervention We conducted 2 focus groups (men in 1 group and women in the other) to determine patient preferences regarding the intervention design and to identify potential problems related to content, format, and language in the instructions on patient education materials. Where applicable, we presented participants with a commonly used instruction sheet for comparison. Patient preferences regarding the intervention kit were assessed, including their preferences on all components of the intervention. The results of these focus groups revealed a preference for the patient-centered written medication information compared with standard written information, as well as improved comprehension of the information. 2s That information was incorporated into the final design of the intervention. The intervention is designed to overcome poor communication between patients and providers, incompatible beliefs, and lack of drug monitoring, as well as difficulties with comprehension and memory that are exacerbated by cognitive and literacy limits among older adults (Table I). The intervention addresses these problems by providing information to patients in an easily understood format that explains the importance of adherence. The pharmacist accomplishes these objectives by explicit consultation, patient handouts designed according to theories of cognitive aging and instruction design, and computer-facilitated communication between pharmacist and providers.

M.D. Murray et al.

J The American Journal of Geriatric Pharmacotherapy I

Table I. Components of the intervention. Component

Goal

Methods

Patient education

Provide verbal and written education to improve Verbal patient education; written icon-based patients' understanding of their medications materials (icon-based patient pamphlets and and encourage medication adherence icon-labeled medication containers)

Therapeutic monitoring

Tackle barriers to adherence and p r o v i d e follow-up drug monitoring

Backgrounddata (predisposing, enabling, need, and clinical parameters); MEMS; self-reporting; refill adherence; NewYork Heart Association class; interpreting symptoms of heart failure; reporting changes in symptoms of heart failure; interpreting emergency-department visits or hospital admissions; interpreting changes in body weight; interpreting changes in other clinical data (eg, serum electrolyte concentrations); detecting drug interactions, side effects, and other drug AEs; documenting pharmaceutical care in study computer.

Communication with providers

Assure that patients have adequate trial of treatments in recent guidelines and receive sufficient doses; reduce number of unnecessary medications (including prescribed medications and OTC drugs and herbal products no longer needed); and report side effects and AEs

Contact with physician and nurses in person, by telephone, by paging, and by e-mail; providing follow-up information to physicians and nurses; physician and nurse access to pharmacist by paging

MEMS = medication-event monitoring system; AEs = adverse events; OTC = over-the-counter.

The intervention is also designed to improve patients' understanding of the rationale for their medications and the appropriate use of their medications, as well as to coach them within their belief and value systems to promote adherence. The approach involves the collaborative principles--namely, grounding, monitoring, and collaborative efforts. 21 Rather than emphasizing that patients should take their medications because health care providers deem it appropriate, the intervention is centered on gaining an understanding of patients' predisposing and enabling characteristics and perceived needs within the context of their drug use. This information is then used to design a tailored intervention to promote patients' medication adherence by educating them verbally, using written educational support, 2°,26 monitoring their medication use with an integrated computer system, 16 and coordinating that use with their primary care physicians. 27 Verbal Patient Education Verbal education is aimed at promoting an understanding of how all of the drugs the patients are taking affect their CHF, restructuring their beliefs,2s improv-

ing their medication-taking skills, eliminating medications that reduce the effectiveness of CHF drugs (eg, nonsteroidal anti-inflammatory drugs29,3°), providing patients with feedback about their adherence and the relationship between adherence and symptoms, and explaining the icon-based medication information sheets and their relationship to the icon-labeled medication packaging. Verbal education is organized to be consistent with the medication information sheets, and both verbal and written communications present information in an order consistent with patients' schema for taking medicationsY Training manuals contain scripts that the pharmacists can use in their patient education. Written Icon-Based Materials An educational pamphlet is shown in Figure 1. These materials include medication information sheets formatted according to a multilevel, theory-based approach to designing instructions that includes considerations of content, language, organization, and presentation. 31,32 With regard to content, instructions contain information that patients need and want so they can take their medications accurately. Language

51

The American Journal of Geriatric Pharmacotherapy

M.D. Murray et al.

I

ACE Inhibitors (Pronounced: ACE in-HIB-it-ors)

IDENTIFYING YOUR MEDICATION • T h e ACE Inhibitor label is red. • ACE Inhibitors are u s e d to m a n a g e blood p r e s s u r e a n d chronic h e a r t failure. • T h e t y p e s of ACE Inhibitors are Fosinopril (Monopnl~), Benazepril (Lotensin~), Enalapril (Vasotec~), Lisinepril (Prim'vil®,Zestril*), Quinapril (Accupril®), l ~ n i p r i l (Altace~), Moexipril (Univasc~), a n d Trandolapril (Mavik~).

DI RECTIONS T h e pills in t h e bottle w i t h t h e r e d label are u s e d to d e c r e a s e t h e blood p r e s s u r e a n d s e v e r i t y of chronic h e a r t failure, a n d s h o u l d b e t a k e n continuously. A s k your p h a r m a c i s t ff y o u c a n t a k e t h i s m e d i c a t i o n w i t h food. If y o u forget to t a k e your ACE Inhibitor on time, t a k e it as s o o n a s y o u r e m e m b e r . However, ff it is a l m o s t t i m e for y o u r n e x t d o s e , skip t h e d o s e y o u m i s s e d a n d go b a c k to y o u r r e g u l a r s c h e d u l e . DO N O T DOUBLE-DOSE.

TAKE 1 TABLET AT 8:00 A.M. Q 12 2

L (I

Midnight

4

0

6

8

10 12 2

4

6

8

t

t

I

j

I

~' ,,'

I)

Noon

=1 tablet

10 12

,t

-

Midnight

SIDE EFFECTS Some p a t i e n t s e x p e r i e n c e d i z z i n e s s , h e a d a c h e , low blood p r e s s u r e , n a u s e a , vomiting, diarrhea, fatigue, b a d r a s h or swelling, difficulty b r e a t h i n g , fever or a c o u g h . C o n t a c t y o u r doctor ff t h e s e s y m p t o m s b e c o m e b o t h e r s o m e to you.

NOTES • Before t a k i n g t h e s e m e d i c a t i o n s , m a k e s u r e your doctor a n d p h a r m a c i s t k n o w a b o u t all o t h e r p r e s c r i p t i o n a n d over-thec o u n t e r m e d i c a t i o n s t h a t y o u take.

PLAY TO WIN. W I N FOR LIFE.

Figure 1. Example of patient-centered patient instruction sheet for angiotensin-converting enzyme inhibitors,

.

I

M.D. Murray et al.

considerations involve the use of simple words and syntax that are explicit and minimize the need for inference. The documents have an overall Flesch-Kincaid33 reading ease score of 71 (ie, sixth-grade level). In addition, information should be organized in a way that is consistent with patient preferences for organizing medication information. For example, older adults better understand and remember medication instructions that match their preexisting schema for taking medications. 22 This organization is reinforced with list formats a n d / o r short paragraphs with headers that signal schema categories. With regard to presentation, icons provide an important way to enhance text-based instructions because they are easy to notice, rely less on literacy skills (compared with print), and are explicit, so that they minimize the need for making inferences, which may challenge older adults. 33 The general principle behind this approach is to design instructions to take advantage of older adults' strengths (eg, knowledge) and minimize demands on weaknesses (eg, working-memory capacity). The theme for these materials involves a heart and a bingo game. We chose the bingo motif because many older adults enjoy that game. The overriding themes, Rules to Play By and Rules to Live By, suggest that just as there are rules in bingo that must be followed to win, treatment of C H F has certain rules that must be followed (ie, understanding medications and taking them correctly). We have created medication sheets for the most common drugs used to treat CHF and associated icons with each sheet (Figure 1). At the top of the page is an icon that belongs to that specific drug category: diuretics are indicated by a drop of urine in a black box, ACE inhibitors by the ace of hearts, beta-blockers by a block containing the letter B, digoxin by a purple heart, and spironolactone by a spiral shield (indicating its name and protective effects). 11 The rationale for this design is the reduction of the patient's need to remember long drug names like spironolactone. The sheets are drug-class specific, rather than drugname specific, because patients usually take only 1 drug from a given class. 1 Either the generic or branded drug name may be listed on the label of the prescription container. The dose and time to take each medication are indicated on a timeline icon, which has been found to improve older adults' memory for dose and time information in the laboratory. 34 The individual patient's prescribed treatment is printed on the timeline to indicate the correct time for dose administration. This process requires the pharmacist and patient to actively collabo-

r

The American Journal of Geriatric Pharmacotherapy

rate to create a specific plan for taking the medications when the prescription is filled, thus enhancing the patient's understanding of the adherence task and circumventing potential confusion at home. Patients are also given a calendar that summarizes their plan for taking multiple medications each day. (These medication sheets and calendar were pilot-tested with a group of participants representing the range of education and verbal ability in the target sample to ensure that the materials are easy to understand.) The pharmacist can change the information on the sheets to conform to later changes in the patient's dosing regimen, including verbal changes from the physician.

Icon-Based Labeling of Medication Containers Icon-based labeling of medications creates a pictorial link between the patients' drug sheets and the medication container to which it pertains. The icon-based labels arc made of a glare-free s5 laminated plastic and sized to fit on both the MEMS lid and the medication container. The icon's presence on both the lid and container helps to prevent the patient from inadvertently mixing the lids and containers of different medications. An example of a labeled bottle is shown in Figure 2. In addition to the icon label, a conventional prescription label and relevant auxiliary labels are affixed to the bottle.

Therapeutic Monitoring We developed a software application based on Microsoft Access (Microsoft Corporation, Redmond, Washington) to facilitate the pharmacist's ability to monitor patient care and medication adherence and to document all encounters with patients and their primary care providers. The concepts for this computer system derived from those used in a recent study of pharmaceutical care. 19 This software application is stored on the study pharmacist's computer at the pharmacy. The software has 4 areas: background, medication adherence, body weight, and other therapeutic monitoring parameters (eg, blood pressure, serum electrolyte and creatinine concentrations, liver function tests, documentation). The program uses mnemonic devices to help the pharmacist remember care protocols for medicationrelated problems, monitoring of the patient's response to medications, and management of acute exacerbations. 19 The overriding theme is Care, Help, and Follow (CHF). When medication-related problems are detected, the pharmacist demonstrates that he or she cares about the patient's health (ie, asks how the patient is feeling), helps the patient deal with barriers to appro-

59

The AmericanJournal of Geriatric Pharmacotherapy ] M.D. Murray et al.

The comment and check-box sections of the application permit the pharmacist to document the patient's problems and progress, as well as information related to side effects, other adverse events, distribution and redistribution of patient pamphlets, and other notes relevant to the patient's care and adherence. The pharmacist documents all discussions with the patient and with the patient's physicians. Privacy and security features are imbedded in the system and its software. For example, during working hours when the computer is turned on and the program is running, the pharmacist is required to enter a userspecific password to access the study data. When the pharmacist leaves the computer system or is distracted, a 5-minute log-out automatically closes the program.

Communication with Primary Care Providers

Figure 2. Example of icon-labeled medication container for angiotensin-converting enzyme inhibitors.

pilate use, and then follows or monitors the patient's progress. Data in the pharmacist's computer include the patient's age, body weight, and height; baseline New York Heart Association functional class; ability to see, speak, and hear; medication expectations; comorbidities; and cognitive impairments. Other disabilities, such as those that could interfere with the patient's ability to take medications, are also contained in this section. The name and contact information for the patient's primary care provider is listed. Body weight and blood pressure are displayed graphically using data extracted daily from the RMRS by a data analyst. These data enable the pharmacist to readily identify trends that can be used in communications with the patient's physician. For plotted data, the color green designates that everything is fine, yellow denotes caution, and red signifies potential danger that could require prompt intervention.

=

I

The objectives of communication with primary care providers are to assure that patients have had an adequate supply o f medications that are known to reduce morbidity and mortality in patients with CHF, 1 to assure that patients receive adequate doses of these medications,27,36 to provide feedback to physicians and nurses about patients' adherence patterns (according to MEMS data, patient report, and refill patterns), to discuss strategies to reduce side effects of medications, and to report adverse events. Physicians' prescribing practices can be improved effectively by using direct feedback from pharmacist to physician. 37

Cost-Effectiveness of the Intervention We will use societal and health care system perspectives for the cost-effectiveness analyses. The societal perspective will provide a broad measure of costeffectiveness that will allow us to compare this intervention with similar interventions elsewhere. The health care system perspective will provide information that can be used in resource allocation decisions pertaining to the intervention. We will perform the costeffectiveness analysis by calculating an incremental cost-effectiveness ratio, which reflects the mean expenditure required per unit of effectiveness gained. 38 RESULTS

Based on our sample size calculations, we have randomly assigned 314 patients to intervention (n = 122) or usual care (n = 192). Echocardiographic data are already available for 84% of patients with a diagnosis of CHF who have met inclusion criteria for this study; those without a diagnosis of C H F obtained within 6 months prior to enrollment are to be tested. The data collection scheme is shown in Table IX.39-42 We antic-

M.D. Murray et al.

The American Journal of Geriatric Pharmacotherapy

Table II. Data collection schedule. Measure Predisposing characteristics Demographics, religion, knowledge, attitudes and beliefs, expectations Left ventricular ejection fraction by echocardiography, New York Heart Association functional class 39

Source

Schedule

Research assistant, pharmacist Krannert Institute of Cardiology and Division of Clinical Pharmacology staff Research assistant

Baseline, 6 and 12 months

Research assistant

Baseline 6 and 12 months

Research assistant, RMRS

Baseline 6 and 12 months

Division of Clinical Pharmacology staff and laboratory

Baseline 12 months

Research assistant

In person at baseline, 6 and 12 months; by phone at 2,3, 4, 5, 7, 8, 9, and 10 months

Research assistant

Baseline, 6 and 12 months

Need Kansas City Cardiomyopathy Questionnaire, quality of well-being

Research assistant

Baseline, 6 and 12 months

Medication adherence MEMS lids

Pharmacist

All visits to PCC and 3, 6, 9, and 12 months (+1 wk) In person at baseline and 6 and 12 months; by phone at 3, 6, and 9 months Refills for prescribed drugs

General cognitive resources: speed of processing, working memory Health-specific cognitive resources: health literacy, communication skills, prescription-taking skills Medical/disability-related: New York Heart Association functional class, Kansas City Cardiomyopathy Questionnaire, symptoms, 4° comorbidity from RMRS, disability, vision, hearing Assay for plasma renin and aldosterone and brain natriuretic peptide concentrations Symptoms of heart failure Kansas City Cardiomyopathy Questionnaire

Enabling characteristics Income, distance traveled to health services, transportation, insurance, relationship with providers, support, supervision with medications

Self-reported adherence

Research assistant

Refill adherence

RMRS

Outcomes HRQL: Chronic Heart Failure Questionnaire 41

Acute exacerbation: cardiovascular hospitalization Satisfaction with health care, satisfaction with pharmacy Health care utilization Counts of emergency-department visits, hospitalizations, and physicians' office visits related to CHF and total

Research assistant

RMRS Research assistant RMRS, letters to non-WHS facility

Baseline, 6 and 12 months Baseline

In person at baseline and 6 and 12 months; by phone at 3 and 9 months Monthly Baseline and end of study Monthly and end of study

(continued)

61

I The AmericanJournal of GeriatricPharmacotherapy ] M.D.Murray et al.

Table II. (Continued) Measure Missed days of work or school Self-report Delivery of pharmaceutical care Patient report, documentation of pharmacist's actions, work measurement

Health index to compute quality-adjusted life-years Quality of Well-Being Scale42

Source

Schedule

Research assistant

Monthly

Research assistant, study computer, pharmacist

Patient satisfaction at 6 and 12 months; pharmacist's actions at each prescription fill/refill; work sampling when 25%, 50%, and 75% of patients are enrolled

Research assistant

Baseline, 6 and 12 months

RMRS = Regenstrief Medical Record System; MEMS = medication-eventmonitoring system; PCC = Primary Care Center (Wishard Health Services, Indianapolis, Indiana); HRQL = health-related quality of life; CHF = congestive heart failure; WHS = Wishard Health Services (Indianapolis, Indiana).

ipate that the results of this study will be reported at a later time.

DISCUSSION Morbidity, mortality, and the costs of care have increased over the past decade for older adults with CHF. Surprisingly, this situation has evolved during the same time in which the effectiveness of medications to reduce morbidity, mortality, and costs has become established. A factor contributing to this dilemma could be the increasing complexity of drug regimens for older adults. We presume that most patients are given insufficient help with their medication regimens. Instead, physicians, nurses, and pharmacists visit quickly with patients and spend little time on activities aimed at promoting patients' understanding of their medications, which might improve adherence. Many older adults need assistance with their medications, and multilevel interventions with cognitive, behavioral, and affective dimensions may improve medication adherence.43 However, there are few data from rigorously designed studies to indicate that these interventions improve health outcomes.~,4s We are assessing a pharmacy-based model of care for older adults with CHF using well-tested psychological and behavioral concepts. 46 The model will be tested, in a scientifically rigorous fashion, as a randomized, controlled trial. Such a trial is consistent with the objectives of Healthy People 2010, 47 which are as follows:

,,

I

(1) increasing the proportion of primary care providers, pharmacists, and other health care professionals who routinely review with their patients aged >65 years and their patients with chronic illnesses or disabilities all new prescribed and over-the-counter medicines; (2) increasing the proportion of patients receiving information that meets guidelines for usefulness when their new prescriptions are dispensed; and (3) increasing the proportion of patients who receive verbal counseling from prescribers and pharmacists on appropriate use and potential risks of medications.

Study Limitations Several potential problems exist related to MEMS, but it should be emphasized that no single measure of compliance is superior to other methods. One potential confounder is that informing patients about the function of the MEMS lids could increase adherence with the monitored medications and perhaps other medications as well. Another problem is the possibility that lids could be switched to the wrong medication containers. This problem should be minimized by use of the same drug icon label on both the lid and container. The pharmacist tracks the frequency of lid swapping. For patients in the usual-care group, instead of the icon label for the medication, a colored dot sticker is affixed to the MEMS lid and the container to help keep them matched. Furthermore, if patients already have a routine that works well for them, requiring

M.D. Murray et al.

them to switch to the MEMS lids might actually reduce medication adherence. The availability of multiple ways of tracking adherence (eg, MEMS, selfreporting, and refill adherence data) will be valuable in tracking this problem. Should patients find the use of the MEMS lids too disruptive to their medicationtaking routine, they will be withdrawn from the study. Several limitations affect the generalizability of the study. First, we have a single pharmacist delivering the intervention. However, favorable findings in this study could lead to broader adoption of our study pharmacist's activities and functions into clinical practice. Second, integrating the pharmacist's study computer into a sophisticated electronic information system might limit the generalizability of our findings. However, medical care is increasingly being computerized, and within the next 5 to 10 years, many sites may have similar information systems.

CONCLUSIONS Although the call for more patient information, education, and monitoring is clear, there is litde evidence that such strategies improve adherence and outcomes. Our study aims to improve patients' knowledge and selfmanagement of their medication and to improve medication monitoring in a multilevel pharmacy-based intervention. By doing so, we intend that the intervention will improve the health outcomes of elderly patients with CHF. ACKNOWLEDGMENTS This ongoing study is supported by grants R0I AG19105, R01 AG07631, and R01 HL69399 from the National Institutes of Health (Bethesda, Maryland). Roche Pharmaceuticals (Nutley, New Jersey) provided a complimentary supply o f the diuretic torsemide (Demadex ®) for patients whose physicians prescribed it. Dr. Brater has received honoraria from Roche Pharmaceuticals for previous work. The authors wish to thank Bev Clark for her secretarial assistance. REFERENCES 1. Heart Failure Society of America (HFSA) practice guidelines. HFSA guidelines for management of patients with heart failure caused by left ventricular systolicdysfimction-pharmacological approaches.J Curd Fail. 1999;5:357-382. 2. Jessup M, Brozena S. Heart failure. N Engl J Med. 2003;348:2007-2018. 3. 2004 Heart and Stroke Statistical Update. Available at: http://www.americanheart.org/statistics/biostats. Accessed February 2, 2004.

The AmericanJournal @Geriatric Pharmacotherapy

4. National Heart, Lung, and Blood Institute, National Institutes of Health. Data Fact Sheet. Congestive Heart Failure in the United States: A New Epidemic. Available at: http:/ /www.nhlbi.nih.gov/health /public /heart/ other/ CHF.htm. Accessed February 2, 2004. 5. Gomberg-Maitland M, Baran DA, Fuster V. Treatment of congestive heart failure: Guidelines for the primary care physician and heart failure specialist. Arch Intern Med. 2001;161:342-352. 6. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. NEnglJMed. 1991; 325:293-302. 7. The Cardiac Insufficiency Bisoprolol Study II (CIBISII): A randomised trial. Lancet. 1999;353:9-13. 8. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999; 353:2001-2007. 9. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. US Carvedilol Heart Failure Study Group. NEnglJMed. 1996;334:1349-1355. 10. The effect of digoxin on mortality and morbidity in patients with heart failure. The Digitalis Investigation Group. N EnglJMed. 1997;336:525-533. 11. Pitt B, Zannad F, Remme VfJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N EnglJ Med. 1999;341:709-717. 12. Murray MD, Deer MM, Ferguson JA, et al. Open-label randomized trial oftorsemide compared with furosemide therapy for patients with heart failure. A m J Med. 2001; 111:513-520. 13. O'Connor CM, Gattis WA, Swedberg K. Current and novel pharmacologic approaches in advanced heart failure. Heart Lung. 1999;28:227-242. 14. Murray MD, Darnell J, Weinberger M, Martz BL. Factors contributing to medication noncompliance in elderly public housing tenants. Drug Intell Clin Pharm. 1986;20:146-152. 15. Hussey LC. Overcoming the clinical barriers of low literacy and medication noncompliance among the elderly. J Gerontol Nursing. 1991;17:27-29. 16. Murray MD, Loos B, Tu W, et al. Work patterns of ambulatory care pharmacists with access to electronic guideline-based treatment suggestions. A m J Health Syst Pharm. 1999;56:225-232. 17. McDonald CJ, Overhage JM, Tierney WM, et al. The Regenstrief Medical Record System: A quarter century experience. Int J Med Inform. 1999;54:225-253.

63

The American Journal of Geriatric Pharmacotherapy M.D.Murray et al.

18. Murray MD, Smith FE, Fox J, et al. Structure, functions, and activities of a research support informatics section. J A m Med Inform Assoc. 2003;10:389-398. 19. Weinberger M, Murray MD, Marrero DG, et al. Pharmaceutical care program for patients with reactive airways disease. A m J Health Syst Pharm. 2001 ;58:791796. 20. Lorig KR. Patient Education: A Practical Approach. 2nd ed. Thousand Oaks, Calif." Sage Publications; 1996. 21. Morrow D. Improving consultations between healthcare professionals and older clients: Implications for pharmacists. Int J Aging Hum Dev. 1997;44:47-72. 22. Morrow D, Leirer V, Altieri P, Tanke E. Elders' schema for taking medication: Implications for instruction design. JGerontol. 1991;48:P378-P385. 23. Morrow D, Leirer V, Sheikh J. Adherence and medication instructions. Review and recommendations. J A m Geriatr Soc. 1988;36:1147-1160. 24. Murray MD, Tierney WM, Brater DC. Determining the effectiveness of torasemide and furosemide in heart failure. Design of a randomised comparison using the Regenstrief Medical Record System. Clin Drug Invest. 1998;16:45-52. 25. Morrow DG, Weiner M, Deer M, et al. Patient-centered instructions for medications prescribed for the treatment of heart failure. A m J Geriatr Pharmacother. In press. 26. Lorig KR, Sobel DS, Stewart AL, et al. Evidence suggesting that a chronic disease self-management program can improve health status while reducing hospitalization: A randomized trial. Med Care. 1999;37:5-14. 27. Gattis WA, Hasselblad V, Whellan DJ, O'Connor CM. Reduction in heart failure events by the addition of a clinical pharmacist to the heart failure management team: Results of the Pharmacist in Heart Failure Assessment Recommendation and Monitoring (PHARM) Study. Arch Intern Med. 1999;159:1939-1945. 28. Park DC, Jones TR. Medication adherence and aging. In: Fisk AD, Rogers WA, eds. Handbook of Human Factors and the Older Adult. San Diego, Calif: Academic Press; 1997:257-287. 29. Murray MD, Brater DC. Adverse effects of nonsteroidal anti-inflammatory drugs on renal function. Ann Intern Med. 1990;112:559-560. 30. Murray MD, Lazaridis EN, Brizendine E, et al. The effect of nonsteroidal antiinflammatory drugs on electrolyte homeostasis and blood pressure in young and elderly persons with and without renal insufficiency. A m J Med Sci. 1997;314:80-88. 31. Morrow DG, Leirer VO. List formats improve medication instructions for older adults. Educ Gerontol. 1995; 21:151.

32. Morrow DG, Leirer VO, Andrassy JM, et al. Medication instruction design: Younger and older adult schemas for taking medication. Hum Factors. 1996;38: 556-573. 33. Flesch-Kincaid Index. Available at: http://www. usingenglish.com/glossary/flesch-kincaid-index.html. Accessed December 18, 2003. 34. Morrow D, Leirer V. Designing medication instructions for older adults. In: Park DC, Morrell RW, Shifren K, eds. Processing of Medical Information in Aging Patients: Cognitive and Human Factors Perspectives. Mahwah, NJ: Lawrence Erlbaum; 1999: 249-265. 35. Kline D, Scialfa C. Sensory and perceptual functioning: Basic research and human factors implications. In: Fisk AD, Rogers W, eds. Handbook of Human Factors and the Older Adult. San Diego, Calif: Academic Press; 1997: 27-54. 36. Gattis WA, Larsen RL, Hasselblad V, et al. Is optimal angiotensin-converting enzyme inhibitor dosing neglected in elderly patients with heart failure? A m Heart J. 1998;136:43-48. 37. Avorn J, Soumerai SB. Improving drug-therapy decisions through educational outreach. A randomized controlled trial of academically based "detailing". N EnglJ Med. 1983;308:1457-1463. 38. Gold MR, ed. Cost-Effectiveness in Health and Medicine. 1st ed. New York: Oxford University Press; 1996. 39. New York Heart Association. Diseases of the Heart and Blood Vessels: Nomenclature and Criteria for Diagnosis. 6th ed. Boston, Mass: Little, Brown; 1964. 40. Green CP, Porter CB, Bresnahan DR, Spertus JA. Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: A new health status measure for heart failure. J A m Coll Cardiol. 2000; 35:1245-1255. 41. Guyatt GH, Nogradi S, Halcrow S, et al. Development and testing of a new measure of health status for clinical trials in heart failure. J Gen Intern Med. 1989;4:101107. 42. General health status and quality of life. In: McDowell I, Newell C, eds. Measuring Health: A Guide to Rating Scales and Questionnaires. 2nd ed. New York: Oxford University Press; 1996:380-492. 43. Miller NH, Hill M, Kottke T, Ockene IS. The multilevel compliance challenge: Recommendations for a call to action. A statement for healthcare professionals. Circulation. 1997;95:1085-1090. 44. Roter DL, Hall JA, Merisca R, et al. Effectiveness of interventions to improve patient compliance: A meta-analysis. Med Care. 1998;36:1138-1161.

M.D. Murray et al. t The AmericanJournal of GeriatricPharmacotherapy

45. Haynes RB, Montague P, Oliver T, et al. Interventions for helping patients to follow prescriptions for medications. Cochrane Database Syst Rev. 2000; CD000011.

46. Interventions to Improve Adherence to Medical Regimens in the Elderly. Washington, DC: Center for the Advancement of Health; 1999. 47. Healthy People 2010. 2nd ed. Washington, DC: US Government Printing Office; 2000.

Address correspondence to: Michael D. Murray, PharmD, MPH, Bucke Professor of Pharmacy, Regenstrief Institute, 1050 Wishard Boulevard (RG-6), Indianapolis, IN 46202. E-mail: [email protected]

I

65