Dosing and compliance?
is commonly asserted that a medicine that has to be taken once a day is more
likely to be taken, and taken correctly, than one that has to be taken in four
doses over the same day.
would agree with that from personal experience. While it may seem obvious, we
get into difficult territory when someone asks the difficult question about
what evidence supports this
assertion. A review of 20 years ago  is the only source
review predates systematic reviews to an extent, but the author tells us that
over 100 articles and chapters were examined, as well as library computer
searches and examinations of cited references. Studies on patient compliance
and dosing of medication were sought.
were 57 such studies, 36 regarding compliance with one agent. We know nothing
about the study design. A variety of different medicines and conditions were
examined in these studies, but 24 examined paediatric, and 32 looked at adult
subjects. Definitions of compliance varied, but included pill counts,
interviews, and presence of drug in body fluids.
26 studies (14 paediatric and 12 adults) there was information relating
compliance to dosing schedule, in studies with sizes from 15 to 705 subjects
(median 96). The results (Figure 1, Table 1) show a distinct tendency for
higher compliance with fewer tablets per day.
Figure 1: Relationship between daily dosing schedule and average compliance
Table 1: Relationship between daily dosing schedule and compliance
|Times a day|
is a serious piece of work for a serious and important topic.
was surprised to find nothing more recent (but that may just be a failure to
find something obvious). It is full of important observations, particularly
about a tendency for elderly patients to make serious errors in dosing.
we have here is a foundation for a contemporary review of this important topic.
It is important for prescribing budgets, as one implication is that a
significant proportion of prescribed medicines are not taken. An average figure
of 40% of tablets not being taken might not be far from modern estimates of
experienced pharmacists. It is also important for the pharmaceutical companies
making once a day medicines, and our response to once a day medicines.
importance of compliance can be seen with statins (Table 2). Benner et al  used
prescription records to study patterns of use in a cohort of 34,501 elderly (65
years or more) patients using statins. They measured the proportion of days
covered (PDC) by drug therapy, and the proportion of patients judged to be
adherent (taking at least 80% of prescribed drug), partially adherent (20-79%
of prescribed drug), or non-adherent (less than 20% of prescribed drug), in
each six-month period for a total of 10 years after initiation of therapy.
Table 2: Adherence to statin therapy over time
patients lost from the partially adherent group moved into the non-adherent
group. Of those who became non-adherent, only 4% had a prescription for another
lipid-lowering drug dispensed, and adherence to that drug was also poor.
Adverse effects rates are low and could account for only a small amount of the
non-adherence. Although this study involved elderly patients from one
geographical area (New Jersey), it is in broad agreement with other studies.
we could do with much more information about what level of compliance, or
concordance, or adherence to therapy exists. We also need to know what to do to
improve it. We also need good solid data on how much prescribed medicine is
- RN Greenberg. Overview of patient compliance with medication dosing: a literature review. Clinical Therapeutics 1984 6: 592-599.
- JS Benner et al. Long-term persistence in use of statin therapy in elderly patients. JAMA 2002 288: 455-461.