Patient Adherence: some basics not in the WHO report

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Patient Adherence some basicsnot in the WHO
report

• John Urquhart, MD, FRCPE, FRSE
• Chief Scientist, AARDEX Ltd
• Professor (wos) of Biopharmaceutical Sciences,
  UCSF
• Emeritus Professor of Pharmaco-epidemiology,
  Maastricht Univ
• urquhart_at_ix.netcom.com

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Janus, the God of Adherence Research Looking
simultaneously at two very different disciplines
Human behavior
Treatment outcomes
reasons
consequences
Basic to both Clear Definitions Reliable
Measurement
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Graphical display of definitions
Persistence
Percent
Osteoporosis (N1173)
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Sources of variance in drug response
manufacturing distribution
prescribing
dispensing
patient adherence
Pharmacokinetics
Pharmacodynamics
drug response
Harter Peck, Ann NY Acad Sci, 618 563-571,
1991
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Patients vary usually the dosing interval and
keep the dose constant
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Variable adherence Variable concentration
of drug in plasma
Periodic loss of effectiveness emergence of drug
resistance occasional toxicity
Concentration (ng/ml)
Days on treatment
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Assessing drug exposure
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Basic principle of electronic monitoring (EM)
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Chronology plot
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Chronology plot
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Chronology plot
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BJR 3560-5, 1996
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RELATIONSHIP BETWEEN PROTEASE INHIBITOR INTAKE
AND VIROLOGIC FAILURE IN HIV INFECTION
Portrait of a more forgiving drug
94
75
WITH VIROLOGIC FAILURE
50
36
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?1/3 95
PRESCRIBED DOSES TAKEN
Paterson, , et al., Ann Int Med 133 21-30, 2000







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Conception Rates (/year) with two methods of
steroidal contraception
Rate in non-contracepting, sexually active women
80
Source, A Century of Family Planning, MMWR,
Dec. 1999
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Migraine prevention twice daily dosing
Persistence
Persistence
Compliance
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Different pharmaco-economics of persistence and
compliance

• Persistence
• Half of starting patients have stopped dosing
  within 6-30 months
• Achievement of intended persistence has the
  potential to treble revenues
• Compliance
• Typical patterns of missed doses result in a 20
  delay in prescription refills and thus a 20
  shortfall in revenues
• NOTE added pharma revenues go mostly to the
  bottom line because of largely fixed overheads

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Problems with patient-reported doses
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Clinically unrecognized underdosing
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"Well controlled" Phase II study35 patients
55 of the residual variability in PK can
become useful informationwhen the dosing history
is knownVrijens et al. IAS Paris 2003
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Viral load observation
31000 182 113 49 132 49 49
212 49 49
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Making it simple for the patient
Patient adherence
Viral Load
Patient care
Model
Probability of no change
Probability to improve
Timing error
Probability to déteriorate
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Need for a new discipline Pharmionics

• Pharmionics is the discipline concerned with
  quantitative assessment of what patients do with
  prescription drugs
• It is akin to avionics in the control of flight
• ion -- to go the going of the drug (or the
  plane)
• Wheres it headed?
• Is it going the way it should?
• What can we do to correct it?
• How well did the correction succeed?

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With pharmionics
Prescribed dosing regimen
pharmionics
Actual dosing history
pharmacokinetics
Actual time-course of drug concentration in blood
pharmacodynamics
Actual time-course of drug actions in the body
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Without pharmionics
Prescribed dosing regimen
pharmionics
Assumed dosing history
Often wrong
pharmacokinetics
Assumed time-course of drug concentration in
blood
pharmacodynamics
Assumed time-course of drug actions in the body
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Some conclusions

• Much of the usual variance in results of clinical
  studies can be improved by using EM-compiled vs
  assumed dosing histories
• noise becomes signal
• The clinical/economic impacts of partial
  compliance short persistence are drug- and
  disease-specific
• Pharmionics is the missing link in the
  biopharmaceutical sciences.
• None of this in the WHO report on adherence