Patient and Provider Non-Adherence to Therapy in Prevention and

Treatment of Disease: Problems and Solutions

Ned Ferguson, M.D.

Professor of Medicine

Preventive Cardiology

Section of Cardiovascular Medicine

DefinitionsAdherence: The extent to which a person’s behavior corresponds with agreed recommendations from a healthcare provider; also called compliance

Persistence: The duration of treatment (ie, the length of time a patient fills his/her prescriptions)

Benner JS et al. JAMA. 2002;288:255-261.Insull W. J Intern Med. 1997;241:317-325.World Health Organization. World Health Organization; Geneva, Switzerland. 2003.

Nonadherence to Therapy: A Major Challenge

Nonadherence (aka noncompliance, nonpersistence, etc) is a major problem

Within 1 year, ~50% of patients overall discontinue use of drugs

An additional ~35% discontinue treatment within 2 years

National Council on Patient Information and Education, 1997.National Council on Patient Information and Education, 1997.

Adherence to Chronic Therapy

Courtesy: Ockene IS; Source: IMS Health data, 1996.Courtesy: Ockene IS; Source: IMS Health data, 1996.

00

1010

2020

3030

4040

5050

6060

7070

8080

9090

100100

11 22 33 44 55 66 77 88 99 1010 1111 1212

Pat

ien

ts (

%)

Pat

ien

ts (

%)

ACE-Inhibitor Statin

MonthMonth

Combining 2 Antihypertensive Agents

In 1 Pill Enhances Persistence

19%*19%*

**PP<0.05 vs. fixed-dose combination<0.05 vs. fixed-dose combination Dezii C. Dezii C. Managed CareManaged Care. 2000;(Suppl 2):6-10.. 2000;(Suppl 2):6-10.**PP<0.05 vs. fixed-dose combination<0.05 vs. fixed-dose combination Dezii C. Dezii C. Managed CareManaged Care. 2000;(Suppl 2):6-10.. 2000;(Suppl 2):6-10.

Lisinopril/HCTZ combination pill (n=1644) Lisinopril and diuretic in separate pills (n=624)

5050

6060

7070

8080

9090

100100

00 11 22 33 44 55 66 77 88 99 1010 1111 1212Months

Per

sist

ence

(%

)P

ersi

sten

ce (

%)

69%69%

58%58%

Persistence* with Diabetes Therapy Declines When Patients Are Prescribed 2 Pills Instead of 1

55%55%

29%**29%**

58%58%

*Defined as continuous months of drug use. ***Defined as continuous months of drug use. **PP<0.05 vs. monotherapies.<0.05 vs. monotherapies.Data on file. Bristol-Myers Squibb Company.Data on file. Bristol-Myers Squibb Company.

Metformin aloneMetformin alone Sulfonylurea aloneSulfonylurea alone Metformin and sulfonylurea in separate pillsMetformin and sulfonylurea in separate pills

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2525

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7575

100100

11 22 33 44 55 66 77 88 99 1010 1111 1212

MonthsMonths

Per

sist

ence

(%

)P

ersi

sten

ce (

%)

Jackevicius CA et al. JAMA. 2002;288:462-467.

Adherence Lowest When Therapy Was Preventive

100

90

80

70

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40

30

20

10

0

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nts

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)

Cohort study using linked population-based administration data from Ontario, Canada (N=143,505).

Conlin PR et al. Clin Ther. 2001;23:1999-2010.

Initial Therapy Choice InfluencedLong-term Persistence

Pa

tie

nts

co

nti

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th

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48

-mo

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10

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ARB ACE inhibitor CCB Thiazide diuretic-Blocker

Retrospective, records-based, cohort study of patients on antihypertensive medication using the Merck-Medco Managed Care LLC Research Convenience Sample database (N=15,175).

Cheng JWM et al. Pharmacotherapy. 2001;21:828-841.

Patient Reasons for Nonadherence

4%

1%

1%

2%

3%

6%

7%

7%

14%

55%

Don’t think it’s necessary all the time

Hate taking

Don’t like being dependent

Drugs give me side effects

Don’t think drugs are working

Too expensive

Don’t like being told what to take

Just forget

Other

Supply will last longer

Prospective, open-label, interview-based study in metropolitan New York area pharmacies (N=821).

Don’t think it’s necessary all the time

What Research Shows About Patterns of Adherence

Remember, nonadherence begins early and persists

Patients must actively decide to adhereMany factors influence adherence

Monane M et al. Am J Hypertens. 1997;10:697-704.

More Frequent Physician Visits Improved Adherence

0.80

1.00

1.20

1.40

1.60

1.80

2.00

2.20

2.40

2.60

1-3 4-7 8+

Physician visits in last 120 days

Ad

her

ence

≥80

% (

OR

)

Retrospective study of elderly (aged 65 to 99 years) members of the New Jersey Medicaid and Medicare populations (N=8643).

Data on file. Pfizer Inc., New York, NY.

Number of Concurrent Medications

Influenced Adherence

0.00

0.50

1.00

1.50

2.00

2.50

3.00

0 1 2 3-5 6+

Number of other prescription medications

Ad

he

ren

ce

≥8

0% (

OR

) P<.0001

P<.0001

P<.0001 P<.0002

Retrospective cohort study in a large managed care population (N=8406).

Data on file. Pfizer Inc., New York, NY.

Concurrently Starting 2 Medications Improved Adherence

0.80

0.90

1.00

1.10

1.20

1.30

1.40

1.50

1.60

1.70

1-30 days 31-60 days 61-90 days

Time between start of antihypertensive and lipid-lowering therapies

Ad

he

ren

ce

≥8

0% (

OR

)

Retrospective cohort study in a large managed care population (N=8406).

Monane M et al. Am J Hypertens. 1997;10:697-704.

Using Multiple Pharmacies Negatively Affected Adherence

0.30

0.40

0.50

0.60

0.70

0.80

0.90

1.00

1.10

1 >1

Pharmacies used in last 120 days

Ad

he

ren

ce

≥8

0% (

OR

)

Retrospective study of elderly (aged 65 to 99 years) members of the New Jersey Medicaid and Medicare populations (N=8643).

The Case for Improving Adherence Improved adherence can lead to:

Higher rates of treatment success Fewer diagnostic procedures Fewer hospitalizations Lower mortality rates

Benner JS et al. JAMA. 2002;288:255-261.Insull W. J Intern Med. 1997;241:317-325.World Health Organization. World Health Organization; Geneva, Switzerland. 2003.

Strategies for Success

Adherence: A Multilevel Problem

The Individual/PatientThe Healthcare ProviderThe Healthcare SystemThe Social-Environmental Context

Adapted from: Miller NH, Hill M, Kottke T, Ockene IS. Adapted from: Miller NH, Hill M, Kottke T, Ockene IS. Circulation.Circulation. 1997;95:1085-1090. 1997;95:1085-1090.

Summary of Implications for Adherence Intervention ProgramsIntervene EARLY in therapyInteract OFTEN KNOW your patientTARGET interventionsEDUCATE patientsPRESCRIBE regimens with a high probability of adherence

ENCOURAGE close relationships

Adherence: Patient Factors

Knowledge, attitudes, skillsOrganic factors (memory, cognitive-information

processing)Self-efficacyDecision-making processes – discountingCo-morbidities/complexity of therapeutic regimenIndividual resources

Aronow HD et al. Arch Intern Med. 2003;163:2576-2582. Avorn J et al. JAMA. 1998;279:1458-1462.Bloom BS. Clin Ther. 1998;20:671-681. Dezii CM. Manag Care. 2000;9(suppl):S2-S6.Monane M et al. Am J Hypertens. 1997;10:697-704. Newell SA et al. Prev Med. 1999;29:535-548.

Prescribe: Regimens with the lowest appropriate pill burden Drugs with reduced dose frequencies Drugs with favorable side-effect profiles Drugs with a lower cost Before hospital discharge

Remind patients by letter and/or phone to refill prescriptions

Recommended Strategies From Several Studies: Prescribing Practices

1

Medicaid Study: Time Interventions to the Advantage of Adherence

Reach patients within the first 3 months of therapy or sooner, if possible

After 6 months, attitudes about therapy are formed

Benner JS et al. JAMA. 2002;288:255-261.

2

Retrospective claims analysis of elderly members of the New Jersey Medicaid and Pharmaceutical Assistance to the Aged and Disabled programs (N=34,501).

Adherence: Provider Factors

Counseling skillsInvolvement of patients in decision-making/plan

of careTime constraintsKnowledge, awareness, adherence to clinical

practice guidelines Individual vs. team-provider approach

Provider Level – Problems

Problem-solving skillsSelf-monitoringRelapse prevention strategies Prompts/reminder systems

Mail/telephone Medication containers

Social supportRealistic/appropriate goalsReward system

Provider Level – Problems

Number of daily doses

Number of medications

Occurrence and severity of side effects

Incompatibility with patient’s daily routine

Inadequate physician-patient communication

Cost

Russell M. Russell M. Behavioral Counseling in Medicine: Strategies for Modifying At-Risk Behavioral Counseling in Medicine: Strategies for Modifying At-Risk Behavior.Behavior. New York, NY: Oxford Press; 1986. New York, NY: Oxford Press; 1986.

Provider Level – Problems

Studies show clinicians generally cannot reliably predict which patients will be adherent

Clinicians consistently overestimate patient adherence

Physicians tend to believe adherence is solely the patient’s responsibility

Adherence: Societal Factors

Example: ObesityFood used to be expensive – now it’s cheapPhysical activity used to be cheap – now it’s

expensive

Social Learning Theory: Albert Bandura

Behavior is learned and can be unlearnedPeople learn best by active participationPeople need to believe they can change

(self-efficacy)

Bandura A. Bandura A. Social Foundations of Thought and Action: A Social Cognitive TheorySocial Foundations of Thought and Action: A Social Cognitive Theory . . Englewood Cliffs, NJ: Prentice Hall; 1986.Englewood Cliffs, NJ: Prentice Hall; 1986.

Health Belief Model

People are more likely to take action if they believe:

They’re vulnerable or susceptible to consequence of a behavior

They’re capable of change Benefits of change will outweigh costs

Rosenstock I, in Glanz K et al, eds. Rosenstock I, in Glanz K et al, eds. Health Behavior and Education: Theory, Research and Health Behavior and Education: Theory, Research and Practice.Practice. San Francisco: Jossey-Bass; 1990. San Francisco: Jossey-Bass; 1990.

Stages of Change

Adapted from: Prochaska J, DiClemente CC. Adapted from: Prochaska J, DiClemente CC. J Consulting Clin Psych.J Consulting Clin Psych. 1983;51:390. 1983;51:390.

PrecontemplationPrecontemplation

ContemplationContemplation

ActionAction

MaintenanceMaintenance

Relapse

Summary of Principles from Theories and Models of ChangeIndividuals need to have adequate information

Individuals need to believe in their ability to make changes and have positive expected outcomes

Individuals need skills, support, resources

Interventions need to be tailored to the individual or organization and its social context

Patient Level – Solutions

Counseling

Use questions related to 5 content areas:

Desire and motivation to change behavior

Past experiences with the behavioral change

Factors that inhibit the change (barriers)

Resources for change (strengths)

Plan for change and follow-upCourtesy: Ockene IS.Courtesy: Ockene IS.Ockene IS, et al. Ockene IS, et al. J Am Coll CardiolJ Am Coll Cardiol; 2002;40:630-638.; 2002;40:630-638.

Provider Level – Solutions

Simplify the regimenAsk about adherence at every visitLook at the refill dates!!Tailor regimen to patient’s lifestyle

and needs, and to patient’s willingness/desire to be challenged

Involve patient as partner in treatmentProvide clear written and oral instructionsUse behavioral strategies (reminder systems,

cues, self-monitoring, feedback, reinforcement)

Courtesy: Ockene IS.Courtesy: Ockene IS.Ockene IS, et al. Ockene IS, et al. J Am Coll CardiolJ Am Coll Cardiol; 2002;40:630-638.; 2002;40:630-638.

Physician Adherence Management

“How do you remember to take your medicine?”“As is the case with many patients, do you ever

miss or forget a dose?”“How do you remember to take your medication

on weekends or while traveling?”“What do you think you could do to avoid missing

doses?”“Might any future events interfere with taking your

medication?”

Clinician uses problem-solving approach based on questioning the patient in a nonjudgmental manner

Insull W. J Intern Med. 1997;241:317.

Self-reported AdherenceLevel of adherence reported by patient, in interview or questionnaire

Frequently overstated Sample questions:

Do you ever forget to take your medicine? Are you careless at times about taking your medicine? When you feel better, do you sometimes stop taking

your medicine? Sometimes if you feel worse when you take the

medicine, do you stop taking it?

Choo PW et al. Med Care. 1999;37:846-857. Morisky DE et al. Med Care. 1986;24:67-74. Wang PS et al. Pharmacoepidemiol Drug Saf. 2004;13:11-19.

Adherence: System-Based Factors

Extent to which the healthcare system facilitates or impedes provider’s adherence-related activities

Organizational structures and processes Organizational priorities Need to extend financial horizon –

5-year vs. 6-12 month outlook

Systems Level – SolutionsCreate an environment/office system supportive

of preventive interventions

Establish tracking and reporting systems

Optimize multidisciplinary team approach

Implement education, training programs for provider

Establish appropriate reimbursement for providers

Courtesy: Ockene IS.Courtesy: Ockene IS.Ockene IS, et al. Ockene IS, et al. J Am Coll CardiolJ Am Coll Cardiol. 2002;40:630-638.. 2002;40:630-638.

Midwest Heart Specialists’ Experience

Cardiology practice in Naperville, Illinois started physician-directed, nurse-managed lipid clinic in 1985

All new patients see medical director, then lipid nurseLipid nurse reviews lab results, educates patient

on NCEP lipid goals and step II dietAfter diet trial, patient has repeat lipid profile and

appointment with lipid physician for individualized treatment plan

Electronic medical record tracks patientsNurses provide ongoing education, phone consultationIntense compliance effort through phone calls, postcards

Brown AS, et al. Brown AS, et al. Am J Cardiol. Am J Cardiol. 2000;85:18A-22A.2000;85:18A-22A.

Midwest Heart Specialists’ Experience

97% of patients have LDL-C level in their charts71% are at their LDL-C goal29% not at goal have average LDL-C of 105

mg/dL

Brown AS, et al. Brown AS, et al. Am J Cardiol. Am J Cardiol. 2000;85:18A-22A.2000;85:18A-22A.

Easily Implemented Steps for All Practices

Have nurse flag date of last lipid measurement on Post-It atop patient’s chart

Measure lipids upon diagnosing a patient with hypertension, diabetes, other conditions

Designate 1 nurse or other staffer to handle basic lipid and hypertension education and phone calls, clearly defining what issues warrant notifying physician

Use paper or electronic methods for quick calculation of Framingham 10-year risk

Use preprinted index cards or other form to provide each patient with his or her lipid and blood pressure levels and goals

Specific Challenges in Adherence to Long-Term Medication Regimens Most effective interventions are complex

and labor intensive: Usually require multiple approaches and

follow-up supervision

Even effective interventions may have only modest effects

Full benefits of long-term medications cannot be realized at currently achievable levels of adherence: More innovative approaches are needed

McDonald HP, et al. McDonald HP, et al. JAMAJAMA. 2002;288:2868-2879. . 2002;288:2868-2879.

In-Hospital Initiation of Lipid-Lowering Therapy for Patients CHD: The Time is NOW Therapy more likely to be

Initiated by physician Continued by physician long term

Patients Less likely to be concerned about side effects

and monitoring More likely to view therapy as essential (heart medication) More likely to adhere (lower discontinuation rates) More likely to achieve LDL-C<100 mg/dL

Early event reduction in ACS patients not missed

Fonarow GC, et al. Fonarow GC, et al. CirculationCirculation. 2001;103:2768-2770.. 2001;103:2768-2770.

3-year follow-up3-year follow-up

In-Hospital Prescribing of Statin Improves Long-Term Compliance

Muhlestein JB, et al. Muhlestein JB, et al. Am J CardiolAm J Cardiol. 2001;87:257-261.. 2001;87:257-261.

PP<0.0001<0.0001

40%

77%

00

2525

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7575

100100

No (n=278)No (n=278) Yes (n=65)Yes (n=65)

Prescribed statin at dischargePrescribed statin at discharge

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Prevention Clinic Approach Improves Lipid Profiles

All drugs/combinations: >80% success to reach goal ATP III Success rate with statins: 97% Success rate with statin and niacin: 100%

Thomas HD, et al. Thomas HD, et al. NC Med JNC Med J. 2003;6:263-266.. 2003;6:263-266.

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Total Cholesterol TriglycerideLow Density Lipoprotein High Density Lipoprotein

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Other Successful Prevention Clinic Models

Collaborative care 417 patients (66% CHD) Baseline: 45% no therapy, 29% on statins 3d year: 41% on monotherapy, 56% on

combination therapy 62%-74% reached singular lipid goals

Pharmacist-managed LDL-C goals at enrollment vs 12 mo: <100 mg/dL (ASCVD or DM): 24% vs 63% <130 mg/dL (>2 RF): 42% vs 79% <160 mg/dL (<2 RF): 59% vs 93%

Physician-directed, nurse-managed

National average vs clinic: Lipid-lowering meds: 39% vs 100% LDL-C documentation: 44% vs 97% LDL-C goals reached: 11% vs 71%

Ryan MJ Jr, et al. Ryan MJ Jr, et al. Am J CardiolAm J Cardiol. 2003;91:1427-1431; Cording MA, et al. . 2003;91:1427-1431; Cording MA, et al. Ann PharmacotherAnn Pharmacother. . 2002;36:892-904; Brown AS, Cofer LA. 2002;36:892-904; Brown AS, Cofer LA. Am J CardiolAm J Cardiol. 2000;85:18A-22A; Sueta CA, et al. . 2000;85:18A-22A; Sueta CA, et al. Am J CardiolAm J Cardiol. 1999;83:1303-1307.. 1999;83:1303-1307.

A Prevention Clinic Offers: Enhanced patient compliance with therapy

Aggressive treatment and follow-up, including combination therapy

Aggressive lifestyle and risk factor modification

Multifaceted team approach (diet, exercise, medication)

Continuous patient education (handouts, tapes, classes)

Constant reinforcement (frequent visits, calls, mailers)

A Prevention Clinic’s Keys to Success Are:A Prevention Clinic’s Keys to Success Are:

Summary

Patient Barriers to Adherence with Treatment Recommendations Lack of access to care Psychological dysfunction, such as depression, alcohol

abuse Cognitive impairment Societal issues (lack of education, cultural beliefs and

habits) Failure to recognize severity of condition Failure to recognize the need for chronic therapy Distrust of long-term medication safety Lack of understanding goals and benefits of therapy Asymptomatic nature of dyslipidemia Lack of immediate benefits from medication regimen Polypharmacy (costs, complexity, fear of side effects)

Strategies for Improving Patient Adherence Seeking continuing education of health care professionals on

principles and implementation of evidence-based guidelines Implement a team approach to preventive care Ask about patient adherence at every visit Be aware of pharmacy refill dates Simplify the regimen if possible (fewest number of pills and

simplest dosing schedule, tailored to the patient’s lifestyle) Involve patient as active partner in treatment goals and

regimen Use proven behavioral modification tools (reminder systems,

prompts for health care professionals; in-office and home educational tools for patients; clear verbal and written instructions)

Physician Barriers to Adherence with Guidelines Time pressure/constraints Reimbursement issues Overestimation of patient adherence Underestimation of the consequences of

undertreatment Belief that adherence is solely the patient’s

responsibility Discomfort in discussing risk factors with patients Lack of knowledge of evidence-based practice

guidelines (awareness differs by physician type: primary care, OB/GYN, cardiologists)

Delay in rapid and effective dissemination of new clinical trial results to health care professionals

Physician Barriers to Adherence with Guidelines (cont’d)

Focus on single risk factors, not the global picture Gender issues (risk prevention is driven by

misperceived lower risk in women even though calculated risk is equivalent to men)

Underdeveloped counseling skills Failing to involve patients in decision-making and care

plan Lack of perceived effectiveness of attempts to change

lifestyle Individual vs. team-provider care Lack of referral to specialty care, eg, preventive

cardiology clinic, cardiac rehabilitation program, diabetes nurse educator, smoking cessation program

References1. Jackevicius CA, Mamdani M, Tu JV. Adherence with statin

therapy in elderly patients with and without acute coronary syndromes. JAMA. 2002;288:462-467.

2. Ellis JJ, Erickson SR, Stevenson JG, et al. Suboptimal statin adherence and discontinuation in primary and secondary care populations. Should we target patients with the most to gain? J Gen Intern Med. 2004;19:638-645.

3. Ockene IS, Hayman LL, Pasternek RC, et al. Task Force #4—Adherence issues and behavior changes: achieving a long-term solution. J Am Coll Cardiol. 2002;40:630-640.

References (cont’d)4. Roter DL, Hall JA, Kern DE, et al. Improving physicians’

interviewing skills and reducing patients’ emotional distress: a randomized clinical trial. Arch Intern Med. 1995;155:1877-1884.

5. Fonarow GC, Gawlinski A, Moughrabi S, et al. Improved treatment of coronary heart disease by implementation of a Cardiac Hospitalization Atherosclerosis Management Program (CHAMP). Am J Cardiol. 2001;87:819-822.

6. Smaha LA. The American Heart Association Get with the Guidelines program. Am Heart J. 2004;148:S46-S48.

References (cont’d)7. Mason CM. The nurse practitioner’s role in helping

patients achieve lipid goals with statin therapy. J Am Acad Nurse Pract. 2005;17:256-262.

8. Osterberg L, Blaschke T. Adherence to Medication. N Engl J Med 2005;353:487-97.

9. Ferguson EE. Physician and Patient Nonadherence: How to Improve Therapy and Outcomes. Lipid Letter 2005;5:1-8 (available at www.eslm.org).