The ATC Classification and the Defined Daily Dose collectively constitute the WHO methodology for describing and quantitatively evaluating drug consumption. ATC classifies active substances into a five-level hierarchy based on their anatomical site of action, as well as their therapeutic, pharmacological, and chemical properties. The Defined Daily Dose, or DDD, is the technical unit of measurement established for an ATC code for consumption analyses.
The Five Levels of ATC Classification
The first level comprises fourteen main anatomical or pharmacological groups. The second level designates a therapeutic or pharmacological subgroup; the third and fourth levels can express chemical, pharmacological, or therapeutic subgroups. The fifth level identifies the chemical active substance. According to WHO principles, the International Nonproprietary Name is preferably used for the substance name.
The hierarchy allows for the aggregation of drug consumption at the active substance, subgroup, or main group level, depending on the research question. An active substance generally receives one ATC code per medicinal product, with the route of administration and, in individual cases, the strength being relevant. Multiple codes may arise if the same substance is administered via different routes or if different therapeutic applications justify a separate assignment.
The code is not an evaluation of therapeutic equivalence. A common subgroup can be useful for a pharmacological consideration, even if the approved indications, contraindications, or study dosages of the contained active substances differ significantly. Therefore, anyone aggregating ATC groups in an analysis must explicitly justify at which hierarchical level the research question can be meaningfully answered.
DDD as a Unit of Measurement for Consumption Data
The DDD is the assumed average daily maintenance dose of a medicinal product for its main indication in adults. It makes quantities comparable irrespective of price, currency, package size, and strength. DDDs are only assigned to medicinal products with an ATC code. The WHO Collaborating Centre for Drug Statistics Methodology at the Norwegian Institute of Public Health develops and maintains both the classification and the DDD assignments.
From dispensing volumes, prescription data, or consumption data, key figures such as DDD per 1,000 inhabitants per day can be generated. Such key figures show quantity patterns, not directly the number of treated individuals or the quality of a therapy. Changes to a DDD or an ATC code must therefore be considered in time series, as they can affect the comparability of the calculated values.
The assignment of classification and unit of measurement is deliberately coupled methodologically: only the ATC code determines which active substance or medicinal product a DDD belongs to. For combinations or products without a DDD, the rules of the WHO Collaborating Centre must be observed separately. An evaluation must therefore disclose its underlying ATC/DDD version, the data source, and the chosen denominator so that others can correctly interpret the consumption metric.
Distinction from Prescribed and Recommended Dose
The DDD is neither the recommended dosage in the Summary of Product Characteristics nor the actual daily amount taken by a patient. It is a calculated value for drug consumption research. The WHO Collaborating Centre explicitly states that a DDD can be a dose that is rarely or never prescribed because it was derived from several common dosages.
Distinct from this is the Prescribed Daily Dose, PDD. It describes the average prescribed dose based on a representative prescription sample. Especially in children, in renal insufficiency, with individually titrated medicinal products, or for other indications, the PDD can deviate significantly from the DDD. Therefore, a DDD-based evaluation must not replace dosage recommendations for the treatment of individual patients.
Clinical guidelines and Summary of Product Characteristics also serve a different purpose. They align dosage and treatment decisions with the indication, patient group, benefit-risk assessment, and, if applicable, duration of treatment. The DDD precisely abstracts from these individual factors to make aggregated consumption quantities methodologically comparable.
Relevance for clinical trials
In clinical studies, ATC coding primarily assists in the structured evaluation of concomitant medication and in subsequent analyses of drug utilization. The chosen code must match the active substance, dosage form, and, if applicable, the route of administration. For protocol specifications, investigational product dosing, and individual dose adjustments, however, the clinically justified dosage description is decisive, not the DDD.
Full-service CROs like Mediconomics provide support in specifying concomitant medication, assigning active substances to ATC codes, reviewing code changes over study durations, and creating analyzable medication datasets. For secondary analyses, they can define DDD-based metrics and transparently explain their limitations in the statistical analysis plan and the clinical study report.
Frequently Asked Questions (FAQ)
Is the ATC code assigned to a brand name?
The classification focuses on active substances and their therapeutic, pharmacological, and chemical properties. A brand name is therefore not the unit that determines the fifth ATC level.
Why can an active substance have multiple ATC codes?
Different routes of administration or clearly separated therapeutic applications may necessitate a separate classification. The specific classification follows the rules of the WHO Collaborating Centre.
Can the DDD be used for pediatric dosing?
No. By definition, the DDD refers to the assumed average maintenance dose for adults for the main indication. It is not a patient-specific dose recommendation.
Regulatory References
- WHO, ATC Classification — describes the hierarchy and assignment principles of active substance classification.
- WHO, Defined Daily Dose — defines the DDD as a technical unit of measurement for consumption.
- WHO, ATC/DDD Methodology — names the WHO Collaborating Centre as the responsible maintenance body.