The defined daily dose (DDD) is a statistical measure

of drug consumption, defined by the World Health Organization (WHO)

Collaborating Centre for Drug Statistics Methodology. It is defined in
combination with the ATC Code drug classification system for grouping
related drugs. The DDD enables comparison of drug usage between
different drugs in the same group or between different health care
environments, or to look at trends in drug utilisation over time. The DDD is
not to be confused with the therapeutic dose or Prescribed Daily
Dose (PDD), or Recorded Daily Dose (RDD), and will often be different to
the dose actually prescribed by a physician for an individual person.[1]
The WHO's definition is: "The DDD is the assumed average maintenance
dose per day for a drug used for its main indication in adults."[1] The
Defined Daily Dose was first developed in the late 1970s.[2]
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Assignment[edit]
Before a DDD is assigned by the WHO Collaborating Centre for Drug
Statistics Methodology, it must have an ATC Code and be approved for
sale in at least one country. The DDD is calculated for a 70kg adult, except
if this drug is only ever used in children. The dose is based on
recommendations for treatment rather than prevention, except if prevention
is the main indication. Generally there is only one DDD for all formulations
of a drug, however exceptions are made if some formulations are typically
used in significantly different strengths (e.g., antibiotic injection in a hospital
vs tablets in the community). The DDD of combination tablets (containing
more than one drug) is more complex, most taking into account a "unit
dose", though combination tablets used for high blood pressure take the
number of doses per day into account.[1]
The formula for determining the dose is:[1]
1. If there is a single recommended maintenance dose in the literature,
this is preferred.
2. If there are a range of recommended maintenance doses then
1. If the literature recommends generally increasing from initial to
maximum dose provided it is tolerated, pick the maximum dose.
2. If the literature recommends only increasing from an initial dose
if not sufficiently effective, pick the minimum dose.
3. If there is no guidance then pick the mid point between the
dose range extremes.
The DDD of a drug is reviewed after three years. Ad hoc requests for
change may be made but are discouraged and generally not permitted
unless the main indication for the drug has changed or the average dose
used has changed by more than 50%.[3]

Limitations[edit]
The DDD is generally the same for all formulations of a drug, even if some
(e.g., flavoured syrup) are designed with children in mind. Some types of
drug are not assigned a DDD, for example: medicines applied to the skin,
anaesthetics and vaccines. Because the DDD is a calculated value, it is
sometimes a "dose" not actually ever prescribed (e.g., a midpoint of two
prescribed tablet strengths may not be equal to or be a multiple of any
available tablet).[1] Different people may in practice be prescribed higher or
lower doses than the DDD, for instance in children, people with liver or
kidney impairment, patients with a combination therapy, or due to
differences in drug metabolism between individuals or ethnicities (genetic
polymorphism).[1]
Although designed primarily for drug utilisation research, data using the
DDD can only give a "rough estimate" compared with actually collecting
statistics on drug use in practice.[1] The DDD is often use for long term
research and analysis of drug utilisation trends over time, so changes to
the DDD are avoided if possible,[3] whereas changes in the actual daily
dose prescribed for a population may often occur.[4] For example, the
Recorded Daily Dose (RDD) of simvastatin in Canada in 1997 was only 8%
different to the DDD, but by 2006 it was 67% different. In 2009, the DDD of
several statins were updated, with simvastatin changing from 15mg to
30mg.[4]
The DDD is based on the maintenance dose, but in practice patients in a
population will be on a mix of initial and maintenance doses.[4]

Use and misuse[edit]

The DDD can be used as the basis for calculating various indicators of drug
utilisation. The indicator DDD per 1000 inhabitants per day can suggest
what portion of a population are regularly using a drug or class of drugs.
The indicator DDD per 100 bed days estimates on average how many
inpatients are given a drug every day in hospital. The indicator DDDs per
inhabitant per year can be used for drugs normally prescribed for short
treatment duration (e.g., antibiotics) to indicate the average number of days
in a year a person may take that treatment. The extent to which estimates
using DDD reflect actual clinical practice depends on how close the DDD is
to the typical prescribed dose in that country or setting and at that point in
history.[5]
Because the primary purpose of the ATC/DDD system is drug consumption
measurement, the WHO recommend caution when considering its use for
cost analysis: "DDDs, if used with caution can be used to compare, for
example, the costs of two formulations of the same drug."[5] So, the cost
per DDD of an extended-release tablet taken once a day compared with a
standard tablet taken twice a day, may indicate the extended-release tablet
costs much more to treat the same condition.
In contrast, using DDD to compare the cost of different drugs or drug
groups is "usually not valid" according to the WHO. They recommend that
"DDDs are not suitable for comparing drugs for specific, detailed pricing,
reimbursement and cost-containment decisions". The DDD may not
necessarily compare well with the actual prescribed daily dose, and two
drugs in the same ATC group may not be equally effective at their Daily
Defined Dose.[5]
For example, an analysis of statin use in the Ontario Drug Benefit Program,
2006-07. The average cost per DDD of rosuvastatin was 21% more
expensive than atorvastatin ($1.14 compared to $0.94), which would
suggest the shift at the time from prescribing atorvastatin to prescribing
rosuvastatin would result in increased costs to the healthcare budget. Both
had a DDD at that time of 10mg, but 10mg was not the only dose
prescribed. For example, atorvastatin once daily at 10mg, 20mg, 40mg and
80mg was prescribed 45%, 36%, 16% and 3% of the time respectively. If
one compared cost per unit (daily tablet) then rosuvastatin was instead
24% cheaper than atorvastatin ($1.44 vs $1.90), and if one compares cost
per RDD (recorded daily dose) then rosuvastatin was 26% cheaper than
atorvastatin ($1.43 vs $1.93). An erroneous conclusion of a healthcare
budget cost increase arises in this case from using cost per DDD. At the
time, the RDD of rosuvastatin was similar to its DDD (12.6 mg vs 10mg),
but the RDD of atorvastatin was twice its DDD (20.6 mg vs 10mg). The
DDD of atorvastatin was revised in 2009 to 20mg.[4]
The Canadian Patented Medicine Prices Review Board analysed the use of
DDD for drug utilisation and cost analysis and offered recommendations.
They particularly concentrated on the problems that occur when the
Recorded Daily Dose (RDD) observed in the population deviates more than
minimally from the Defined Daily Dose. They conclude that the DDD
methodology "should generally not be used to interpret Canadian drug
utilization; should generally not be applied in cost analyses; and should
generally not be applied in policy decisions".[4] The Board recommend that
provided the agreement between DDD and RDD is known and minimal,
then a cost per DDD "can provide a rough idea of the treatment cost" but
"caution should still be used, as misinterpretation of the results based on
the DDD methodology may still occur". If the agreement between DDD and
RDD is unknown or a significant disagreement is known, then the DDD
methodology "should not be used in cost analyses". In all cases, the Board
state "The DDD methodology should not be used in guiding policy
decisions regarding reimbursement, therapeutic substitution and other
pricing decisions".[4]