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
Dec 18, 2015
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
00
2525
5050
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
60
50
40
30
20
10
0
Pa
tie
nts
ta
kin
g s
tati
ns
(%
)
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
nu
ing
th
era
py
at
48
-mo
nth
fo
llo
w-u
p (
%)
0
10
20
30
40
50
60
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
5050
7575
100100
No (n=278)No (n=278) Yes (n=65)Yes (n=65)
Prescribed statin at dischargePrescribed statin at discharge
Tak
ing
sta
tin
at
foll
ow
-up
(%
)T
akin
g s
tati
n a
t fo
llo
w-u
p (
%)
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.
-54 -59-67
-51-44
-108
-70
-110
-48 -51 -54-41
0 1 0 1
-140-120-100-80-60-40-20
020
CHD Diabetes High Risk Low Risk
Total Cholesterol TriglycerideLow Density Lipoprotein High Density Lipoprotein
Ch
ang
e at
Fo
llo
w-u
p
Ch
ang
e at
Fo
llo
w-u
p
fro
m B
asel
ine
fro
m B
asel
ine
**
††
**PP<0.001; <0.001; ††PP=NS; =NS; ‡‡PP=0.001.=0.001.
****
†† †† ††
**
††
****
** **
††
‡‡
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).