LINKING MICRO AND MACRO UTILIZATION DATA EuroDURG Meeting, Prague, June 8, 2001

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LINKING MICRO- AND MACRO- UTILIZATION
DATAEuro-DURG Meeting, Prague, June 8, 2001

• John Urquhart, MD, FRCP(Edin)
• Pharmaco-epidemiology Group
• Maastricht University,
• Maastricht, Netherlands

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MAIN SOURCES OF PHARMACO-EPIDEMIOLOGIC DATA
MACRO
MARKET
SEMI-MICRO
PHARMACY
MICRO
PATIENT
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Definitions at the MICRO level of Ambulatory
Pharmacotherapy - 1

• Acceptance -- does the patient accept or not the
  recommended treatment?
• Execution -- how well does the patient execute
  the recommended regimen?
• Discontinuation -- when does the patient stop
  taking the medicine?

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Definitions at the MICRO level of Ambulatory
Pharmacotherapy -2

• Acceptance -- ?dichotomous
• Execution -- continuous
• Discontinuation -- ?dichotomous

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Definitions at the MICRO level of Ambulatory
Pharmacotherapy -3

• Adherence is a useful overall term, subsuming
• Acceptance,
• Execution, the quality of which is called
• compliance
• the extent to which the actual dosing history
  corresponds to the prescribed drug regimen
• Discontinuation
• The length of time between acceptance and
  discontinuation is called
• persistence

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PRESENT VIEWS ABOUT COMPLIANCE ARISE FROM A
METHODOLOGIC REVOLUTION

• Electronic monitoring methods, introduced in the
  late 1980s, revealed that pre-electronic methods
  grossly overestimated compliance
• histories
• diaries
• returned tablet counts, canister weights
• drug levels in plasma (white-coat compliance)
• These methods allow patients easily to censor
  evidence for delayed or omitted doses.

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25 YEARS OF DEVELOPMENTS IN ELECTRONIC MONITORING

• quick overview

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1976 500 each (1200 today)
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1986 400 each
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1991 250 each
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2000 80 each
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(No Transcript)
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Transition from punctual to erratic
holiday
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WHITE-COAT COMPLIANCE--taking the medicine just
before the scheduled visit
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RELATIONSHIP BETWEEN ADHERENCE AND VIROLOGIC
FAILURE IN HIV INFECTION
94
75
WITH VIROLOGIC FAILURE
50
36
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PRESCRIBED DOSES TAKEN
?1/3 lt70 ?1/3 gt95








Paterson, , et al., Ann Int Med 133 21-30, 2000
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Patterns of compliance in medically unselected
patients 1 patient in ca. 6...

• punctual dosing
• ?all doses taken but slightly erratic timing
• 5-20 of doses omitted, but never more than 1 at
  a time

• many doses missed has a drug holiday 3-4 times
  /yr
• many doses missed has at least 1 drug
  holiday/mo.
• takes few or no doses, but presents as compliant

rule of sixes
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Similarity of dosing patterns between fields

• Compliance appears to be more or less independent
  of
• drug
• disease
• prognosis
• symptoms
• The usual patterns of poor partial compliance
  prevail in asymptomatic diseases, treated with
  convenient drugs without attributable
  side-effects
• Compliance is mostly a patient-attribute, rather
  than a disease- or drug-attribute.

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BJR 3560-5, 1996
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Effect of typical compliance patterns on refill
intervals 60-day prescription
of prescriptions in category
Median 71days
Mean 78 days--4.7 refills/yr, not 6
Days needed to empty a 60-day prescription

100
80-89
60-69
40-49
20-29
90-99
70-79
50-59
30-39
10-19
of prescribed doses taken
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Role of Prior Selection - 1

• 30-40 of medically unselected patients will
  substantially underdose, per the rule of sixes
• medically unselected means that the patients
  have had
• no prior medical treatment
• the usual interactions with a
  physician-prescriber and a pharmacy-dispenser

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Role of Prior Selection - 2

• Patients who have failed to respond to a prior
  course of rationally-prescribed drug treatment
  will include more than the usual proportion of
  poor/partial compliers
• EXAMPLE Burnier Brunner found that 53 of
  hypertensives who had been escalated to triple
  therapy without responding, were clinically
  unrecognized poor compliers

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Role of Prior Selection - 3

• Patients who have responded well to a prior
  course of rationally-prescribed drug treatment
  will include more than the usual proportion of
  good compliers
• EXAMPLE de Geest found poor compliance in 5 of
  patients with severe heart failure who had
  endured a long wait for a suitable heart and then
  had successfully received a cardiac transplant

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Role of Selection by Compliance in a Prior
Course of Medical Treatment
good-enough
not good- enough
unselected
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Role of Selection by Compliance in a Prior
Course of Medical Treatment
good-enough
not good- enough
unselected
cardiac transplant recipients
drug refractory hypertension
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SHIFTING GEARS ...

• We turn to
• PERSISTENCE

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WHAT DO WE KNOW ABOUT PERSISTENCE?

• Example statins in Quebec
• median persistence 173 days
• 33 persistence at 1 year
• despite full reimbursement optimal convenience,
  side-effect profile, efficacy
• Similar stories in hypertension and other
  chronic-use medicines
• Major public health disappointment - but not
  widely recognized...

Catalan LeLorier, Val Hlth, 3 417, 00
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HUGE CHASM BETWEEN PUBLIC HEALTH OBJECTIVES AND
REALITY

• A fortnight ago the US National Heart, Lung
  Blood Institute issued revised guidelines on
  treatment of lipid disorders
• The guidelines would result in statin treatment
  of ca. 20 of people over age 40
• To realize the goals of this program, median
  persistence should be 20 years, not 6 months
• Closing that huge chasm has huge economic
  implications

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COMMON-SENSE BASICS ABOUT PERSISTENCE

• Persistence increases one dose at a time
• The link between compliance and persistence is
  the patients confidence in the values of ...
• the treatment program
• correct compliance with the dosing regimen
• continuation
• Regular review of the patients dosing history is
  a natural way to achieve two desirable goals...
• assure satisfactory compliance
• reinforce the importance of correct, ongoing
  dosing

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WHO PAYS?

• Lengthening persistence proportionally increases
  the manufacturers revenues
• Gross margins on premium-priced medicines
  (2-4/day or more) are gt80
• One added year of persistence with a 3/day
  product returns ?800 in gross margins
• In commercial quantities, electronic monitors
  with a 2-year lifetime now cost ?50.
• A good economic return is possible, IF indeed
  compliance is a main link to persistence.

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SOME CONSEQUENCES OF SHORT PERSISTENCE WITH
DRUGS INDICATED FOR LONG-TERM USE

• high ratio of new to refill prescriptions but
  slow or no growth in the total market
• heavy promotional expenses
• poor cost-effectiveness
• resources wasted on both diagnostics and drugs
• short persistence is in no-ones interest

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PERSISTENCE

• High priority topic linking
• micro- and macro-aspects of
• drug utilization research

COMMENTS urquhart_at_ix.netcom.com 500 paper
bibliography of published studies based on
electronic monitoring www.aardex.ch