Subjective methods usually used to assess
patient compliance in drug trials or medical prac-
tice grossly overestimate patient compliance.
Reliable measurements of drug exposure in ambu-
latory patients require methods that make it diffi-
cult for patients to censor evidence for delayed or
omitted doses. Electronic monitoring has emerged
as the gold standard method for measuring drug
exposure in ambulatory patients. One mission of
pharmionics-guided measurements is to acceler-
ate and improve clinical developments of new
drugs for ambulatory patients. Another mission
is to improve clinical outcomes of ambulatory
pharmacotherapy. The basis for doing both is the
provision of full and reliable knowledge of drug
exposure.
27.2 Introduction
A major reason for poor compliance is simple
negligence. Neither good intention nor a profes-
sional levelof understanding of medicine and phar-
macology competes well for priority in busy lives:
35–40% of well-informed, cooperative patients
frequently delay or omit scheduled doses. The
resulting range and patterns of drug intake are
remarkably similar, essentially irrespective of
drug, disease, prognosis and even symptoms. Yet,
although the dosing patterns are similar, their med-
ical and economic consequences vary widely,
depending on drug, disease and severity of disease
and comorbidity. Thus is created varying needs for
intervention, which, to be cost-effective, requires
proper targeting to those patients who stand to
incur big problems and high costs if their poor
compliance is not improved, or other steps taken
to minimize its consequences.
Thus, two very basic factors are (a) reliable
detection of poor compliance and (b) reliable mea-
surement of the consequences of steps taken to
improve it. Given that clinical identification of
poor compliance is so strongly biased toward
underestimation, electronic monitoring, done in
real time, is now the accepted standard.
Several levels of feedback of dosing history data
to patients probably have future roles. A basic man-
euver can be audible or visual status alerts for
patients. A more intensive approach is modem- or
pager-mediated error alerts forprofessionalswilling
to assume responsibility for pharmaceutical care.
Obviously, the latter must be focused on well-
defined, high-risk situations, in which the conse-
quences of delayed or omitted doses are severe
and costly, and actions taken are cost-effective.27.3 What does ‘compliance’
mean?Prior to the methodological advances, patient com-
pliance had only a vague definition: ‘following the
instructions of the health care provider’. With the
advent of electronic monitoring methods,
described below, it became practical to use a defi-
nition of compliance that has pharmacological
meaning, in terms of drug exposure: ‘the degree
for correspondence between the actual time history
of dosing and the prescribed regimen’. The time
history of dosing expresses drug exposure, not only
in quantity but also in respect to the timing of
individual doses. In order to get full therapeutic
benefit from the drug, with least toxicity, certain
standards must be met in respect to the quantity of
drug taken and the timing of doses. Each drug,
depending on its pharmacokinetics and pharmaco-
dynamics, has its own standards, which are scien-
tifically definable in properly conducted dose-
response studies.27.4 Methods of evaluating
complianceThere are two categories, direct and indirect.Direct
The most basic, direct method is to measure the
concentration of drug in plasma; unfortunately, this
method is usually biased because in most instances
its reflection of prior dosing history is limited only
to a day or two prior to the time that blood is drawn
for the analysis. These problems arise because356 CH27 PATIENT COMPLIANCE: PHARMIONICS, A NEW DISCIPLINE