The defined daily dose (DDD) is a statistical measure of drug consumption, defined by the

World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of ...

(WHO) Collaborating Centre for Drug Statistics Methodology. It is defined in combination with the

ATC Code The Anatomical Therapeutic Chemical (ATC) Classification System is a drug classification system that classifies the active ingredients of drugs according to the organ or system on which they act and their therapeutic, pharmacological and chemical ...

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 The therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes ...

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.WHO Collaborating Centre for Drug Statistics Methodology (WHOCC)
DDD Definition and general considerations
/ref> The WHO's definition is: "The DDD is the assumed average

maintenance dose In pharmacokinetics, a maintenance dose is the maintenance rate g/hof drug administration equal to the rate of elimination at steady state. This is not to be confused with dose regimen, which is a type of drug therapy in which the dose gof ...

per day for a drug used for its main indication in adults." The Defined Daily Dose was first developed in the late 1970s.

Assignment

Before a DDD is assigned by the WHO Collaborating Centre for Drug Statistics Methodology, it must have an

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. The formula for determining the dose is: #If there is a single recommended maintenance dose in the literature, this is preferred. #If there are a range of recommended maintenance doses then ##If the literature recommends generally increasing from initial to maximum dose provided it is tolerated, pick the maximum dose. ##If the literature recommends only increasing from an initial dose if not sufficiently effective, pick the minimum dose. ##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%.WHO Collaborating Centre for Drug Statistics Methodology (WHOCC)
Application for DDD alterations
/ref>

Limitations

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). 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 Combination therapy or polytherapy is therapy that uses more than one medication or modality. Typically, the term refers to using multiple therapies to treat a ''single'' disease, and often all the therapies are pharmaceutical (although it can also ...

, or due to differences in

drug metabolism Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set o ...

between individuals or

ethnicities An ethnic group or an ethnicity is a grouping of people who identify with each other on the basis of shared attributes that distinguish them from other groups. Those attributes can include common sets of traditions, ancestry, language, history, ...

(

genetic polymorphism A gene is said to be polymorphic if more than one allele occupies that gene's locus within a population. In addition to having more than one allele at a specific locus, each allele must also occur in the population at a rate of at least 1% to gen ...

). 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. 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, whereas changes in the actual daily dose prescribed for a population may often occur. For example, the Recorded Daily Dose (RDD) of

simvastatin Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease elevated lipid levels. It is also used to decrease the risk of hear ...

in Canada in 1997 was only 8% different to the DDD, but by 2006 it was 67% different. In 2009, the DDD of several

statin Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Low ...

s were updated, with simvastatin changing from 15mg to 30mg. 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.

Use and misuse

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.WHO Collaborating Centre for Drug Statistics Methodology (WHOCC)
Use of ATC/DDD
/ref> 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." 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. For example, an analysis of statin use in the Ontario Drug Benefit Program, 2006-07. The average ''cost per DDD'' of

rosuvastatin Rosuvastatin, sold under the brand name Crestor among others, is a statin medication, used to prevent cardiovascular disease in those at high risk and treat abnormal lipids. It is recommended to be used together with dietary changes, exercise, ...

was 21% more expensive than

atorvastatin Atorvastatin is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a first-line treatment. It is taken by mouth. Common ...

($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. 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". 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".

Example

If the DDD for a certain drug is given, the number of DDDs used by an individual patient or (more commonly) by a collective of patients is as follows.

Drug\ usage\ (in\ DDDs) = \frac

For example, the analgesic (pain reliever) paracetamol has a DDD of 3 g, which means that an average patient who takes paracetamol for its main indication, which is pain relief, uses 3 grams per day. This is equivalent to six standard tablets of 500 mg each. If a patient consumes 24 such tablets (12 g of paracetamol in total) over a certain span of time, this equals a consumption of four DDDs.

Drug\ usage\ (in\ DDDs) = \frac = 4

References

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External links