E-DRUG: The terms compliance and patient (cont)
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The proponents of the term 'concordance', which came out of a UK group
sponsored jointly by the Pharmaceutical Society and MSD, would undoubtedly
be pleased to hear that 'concordance' has become the preferred term in
place of 'compliance' or 'adherence', or 'fidelity', which was the term
that Alvan Feinstein used in what I think was the first-ever study that
sought to quantify drug exposure in an ambulatory drug trial. (The Dutch
have a nice term, 'therapie-trouw', which more or less means 'faith with
the therapy' ... 'trouw' being a term loosely related to the English word
'troth'.)
In any case, the principal difficulty with the British conception of
'concordance' is that it seems oblivious to the fact that many drug
regimens have strong scientific support, and cannot be widely deviated from
without loss of effectiveness or, in some instances, overt hazard, due,
e.g., to 'rebound' effects, which some drugs have. The underlying
scientific issue is the definition of an optimal regimen for administration
of the drug, and what the limits are in respect to deviations from the
recommended timing and/or quantity of drug to be taken. As it happens, the
one class of drugs for which this information is very well defined is the
class of drugs that has the most extensive use-experience, namely the
combined estrogen-progestin oral contraceptives.
There were a series of studies done during the 1980's in which placebo
pills were substituted, in properly randomized & controlled fashion, for
active pills, in order to determine how long one could delay the next pill
before breakthrough ovulation occurred, signifying that contraception had
halted.
These studies, which were mostly done in women who had had a prior tubal
ligation and so were not at risk of unwanted conception, although they
still ovulated, were reviewed by John Guillebaud at the time that their
conclusions were translated into oral contraceptive labeling in both the UK
and the US, under the rubric: 'what to do if you miss pills'. Guillebaud's
summary is published in: Guillebaud J. Any questions. Brit Med J 307: 617.
1993.
The instructions in the UK inform patients that if they are more than 12
hrs late in taking their once-daily pill they should take the missed pill
as soon as they recognize that they've missed it, keep on taking the pills
at the usual time, and institute the use of back-up barrier contraception
for the next 7 days. There are analogous instructions for what to do when
yesterday's pill was forgotten, and today's pill was forgotten and now it
is some time later in that same day, plus when day before yesterday's pill
was forgotten, yesterday's pill was forgotten, and now, today, all this
comes to light.
If more than 2 pills have been missed, the instruction is
to discard the pill pack, institute use of barrier contraception, and await
the next menstrual period and start out on a new pill-pack.
So here, for the pharmaceuticals with the most extensive use-experience, we
have precise, scientifically well-supported evidence showing that there is
relatively little latitude for forgotten pills. It would be an unwise
caregiver who, in the name of 'concordance' and a desire to accommodate to
a woman's perceived needs for a less rigid regimen, negotiated a regimen
for oral contraceptives that was substantially wide of the limits defined
by these studies.
Since 1994 there have been, by my count, 6 placebo-substitution studies
done with antihypertensive drugs, and 1 done with the three leading SSRI
antidepressants. Thus, the logic of the programmed lapse in dosing is
spreading and will hopefully bring to these other fields of chronic
ambulatory pharmacotherapy information of the quality and format we have
for the oral contraceptives on 'how much compliance is enough', which is
basically defined by how long one can allow to elapse between doses before
some kind of trouble occurs -- lack of efficacy, rebound effects, emergence
of drug resistant micro-organisms or the like..
So, however much one wishes to accommodate to the woman who would prefer to
take 7 oral contraceptive pills at once, coincident with her Saturday night
bath, the underlying science does not support her doing so without
nullification of the contraceptive efficacy she presumably desires.
Another facet of the terminology question is that the Index Medicus of the
National Library of Medicine in the US indexes papers under the term
'compliance', irrespective of whether the authors use the term 'adherence'
or 'concordance' or 'asyoulikeit'.
What this field needs is not an arcane debate about terminology, but
concerted effort to push drug regulators to demand information of the
quality we have for the combined oral contraceptives, so that we all know
how much compliance/adherence/concordance/asyoulikeit is enough. Only then
can one negotiate with patients about how best to adapt the drug regimen to
their needs, without being either far more demanding than necessary, or so
loose as to undermine efficacy.
John Urquhart
John Urquhart, MD, FRCP(Edin)
Professor of Pharmaco-epidemiology, Maastricht University, Maastricht NL
Chief Scientist, AARDEX/APREX, Zug CH & Union City, CA, USA
Professor of Biopharmaceutical Sciences, UCSF, San Francisco
Email: urquhart@ix.netcom.com [added by moderator; WB]
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