Thus, the physician who has a reliable measure
of the patient’s dosing history can interpret the
patient’s response to the drug in far more realistic
manner than the physician who can only guess at
the patient’s actual drug intake. Such guesses are
usually skewed toward overestimating patients’
actual drug intake. Obviously, the prescriber’s per-
ception of the drug’s reliability and overall value
will be diminished by patients who appear to the
prescriber to be nonresponders but who in fact have
taken too little drug to produce a clinically useful
response (Vanhoveet al., 1955; Milgromet al.,
1996). For example, Burnier and Brunner found
that slightly over half the patients referred to their
hypertension clinic for evaluation of ‘drug refrac-
tory hypertension’ turned out to be clinically
unrecognized non-compliers, whose noncompli-
ance only came to light when the first step in
their diagnostic evaluation was 60 days of electro-
nic monitoring of their intake of each of the three
antihypertensive drugs that most of them had been
prescribed by their primary physician (Urquhart,
1991; Burnieret al., 2001).
Another facet, obviously, is to deal with the
patient whose compliance has been substandard
and take effective action to make as much improve-
ment as possible in drug intake, and to switch, if
necessary, to the agent whose therapeutic actions
are least influenced by lapses in dosing. These are,
of course, new issues that have previously not been
considered in drug evaluation, for the simple rea-
son that reliable measures of patient compliance
have not previously been available. The potential
roles of pharmacists, nurses and other health pro-
fessionals remain to be defined as this new infor-
mation and its implications become available and
integrated into clinical thinking.
Needless to say, the economic consequences of
poor compliance will sooner or later attract serious
attention of insurers and other payors for health-
care. Prescription drugs, after all, are a principal
interventional arm of modern medicine, and their
actions are invariably dose- and time dependent, so
their ineffective or suboptimal dosing represents an
inefficiency in medical care that is potentially
remediable. In considering this prospect, one
should recall the words of one of the pioneers in
compliance research, Stefan Norell, who wrote in
1980: ‘... the aim of ‘‘improving’’ compliance is
not to achieve perfect agreement between behavior
and prescription, but to increase compliance only
to the level where the satisfactory outcome of
treatment is assured. In practice, however, this
level is often unknown...’.
Awakening to these realities has already begun,
as several pharmaceutical firms are making promo-
tional claims for products, based on their having an
exceptional degree of ‘forgiveness’ for the more
common errors in compliance: delayed doses,
skipping a single dose and skipping two sequential
doses.27.14 What are the facts
which demonstrate
the importance
of compliance?There are various perspectives from which to
answer this question.Science
Every study done with reliable measures of
patients’ actual drug exposure in both trials and
practice shows a marked skewtoward underdosing.
A prominent finding is the ‘holiday’ pattern of
dosing – sudden halts in dosing, followed by a
sequence of days during which no doses are
taken, followed by an abrupt resumption of dosing.
First described by Prof. Michael Kass and his
colleagues in patients with sight-threatening glau-
coma (Kasset al., 1986; Crameret al., 1989, 1990),
the medical and economic consequences were pro-
jected by Urquhart and Chevalley already in 1988.
Of particular concern are drugs with hazardous
‘rebound’ effects when dosing suddenly halts. In
1990, Psatyet al. reported a four- to six-fold
increased risk of incident coronary heart disease
in poorly compliant hypertensive patients pre-
scribed the most widely used beta-blockers. This
class of drugs has long been known to have hazar-
dous rebound effects, but the presumption always
had been that it was matter of concern only when366 CH27 PATIENT COMPLIANCE: PHARMIONICS, A NEW DISCIPLINE