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Dosing and compliance?


It 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. Bandolier 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 obvious assertion. A review of 20 years ago [1] is the only source Bandolier could find.


The 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.


There 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.

In 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

Percent taking tablets
Times a day
Mean (SEM)
73 (6)
70 (5)
Three times
52 (7)
Four times
42 (5)


This is a serious piece of work for a serious and important topic. Bandolier 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.

What 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.

The importance of compliance can be seen with statins (Table 2). Benner et al [2] 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

Partially adherent

Most 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.

Clearly 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 wasted.


  1. RN Greenberg. Overview of patient compliance with medication dosing: a literature review. Clinical Therapeutics 1984 6: 592-599.
  2. JS Benner et al. Long-term persistence in use of statin therapy in elderly patients. JAMA 2002 288: 455-461.

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