Medical Dictionary for Regulatory Activities (MedDRA)
05 May 2018
MedDRA is a standard medical terminology used to facilitate sharing of regulatory information. MedDRA contains all the terms for signs, symptoms, diagnosis, syndromes, social conditions/circumstances and laboratory tests, however names of drugs or devices, description of terms or severity is not included in MedDRA. It was developed by the International Conference on Harmonization of Technical Requirements (ICH) for Registration of Pharmaceuticals for Human Use in the 1990s. It is maintained by Maintenance and Support Services Organization (MSSO). MedDRA is used for data entry, retrieval and evaluation of safety information, both during the development and post-marketing phases of the products. There are other established terminologies like WHOART (WHO Adverse Reaction Terminology) and CO-START (Coding Symbols for a Thesaurus of Adverse Reaction Terms). However, the ease of use with more data retrieval options in MedDRA has led to its growing use throughout the world, which has resulted in it becoming an integral part of safety reporting and monitoring process.
New version of MedDRA is released twice every year in March and September. MSSO also releases the list of events (important medical events) along with the release of each new version of MedDRA. These events present in the list are considered as core serious events. Referring this list helps in determining the seriousness of an event when it is not provided by the reporter. With the release of MedDRA version 19.0, the MSSO also has developed two lists of pediatric and gender adverse event terms. Such type of a separate list would be useful in improving the quality of adverse event terms coding benefitting pharmacovigilance activities. Although these newly generated lists are not part of any regulatory requirement, they would be help users to have a common understanding for coding; users can modify this list as per their requirements. This list can be found on the MSSO website. MedDRA points to consider document which is released along with each new version provides detailed guidance on the coding of adverse events with examples.
Access to MedDRA is available free of charge to regulatory authorities, non-profit organizations, direct patient care providers, educational institutes. and at an annual subscription fee to commercial users.
Apart from the English language, MedDRA is also available in Chinese, Dutch, French, Czech, German, Italian, Hungarian, Portuguese, Spanish and Japanese. MedDRA terms are assigned a unique numeric code which is assigned to its corresponding translated term in each MedDRA language. This allows accurate submission of similar information in any or all the languages.
MedDRA comprises of five levels of hierarchy, arranged from specific to general. The most specific level, the Lowest Level Terms (LLTs), comprises of more than seventy thousand terms which facilitates information communication.
Preferred Term (PT) is a single unique medical concept for a disease, symptom, sign, diagnosis, investigation, therapeutic indication, medical, social or family history characteristic and surgical or medical procedure. Each LLT is always linked to only one PT.
Related PTs are grouped together in High Level Terms (HLTs) based on pathology, etiology, physiology, function and anatomy. Similarly, related HLTs are linked to High Level Group Terms (HLGTs).
Further, High Level Group Terms are grouped into System Organ Classes (SOCs) based on purpose, manifestation site and etiology. Apart from this, there is also a system organ class to contain issues related to products and social circumstances.
The system organ classes (SOCs) allows a term to be reflected in more than one system organ class which allows its retrieval and presentation using different data sets.
Standardised MedDRA Queries
Standardised MedDRA queries (SMQ) is a tool used for the retrieval of coded data while investigating drug safety issues. It is maintained during each new release of MedDRA. New standardized MedDRA queries are created as and when required. It was introduced by the CIOMS working group, and further developed in collaboration with MSSO and various authorities and companies. MedDRA contains a large number of PTs and it is difficult to group events which indicate the presence of the condition that typically presents itself through different PTs. SMQs are designed to solve this concern. SMQ has different degrees of search criteria- for e.g., narrow search SMQ will retrieve PTs with greater certainty and broad search SMQ will retrieve the PTs with greater certainty along with the PTs which merely indicate the condition possibly with a different origin. E.g. Narrow SMQs for the condition lactic acidosis would be lactic acidosis, blood lactic acid increased and hyperlactetaemia; and Broad SMQs would be lactic acidosis, blood lactic acid increased hyperlactetaemia, acid base balance abnormal, acidosis, anion gap abnormal, anion gap increased, blood bicarbonate abnormal, blood bicarbonate decreased, blood gases abnormal, blood lactic acid abnormal, blood pH abnormal, blood pH decreased, coma acidotic, metabolic acidosis, PCO2 abnormal, PCO2 decreased, urine lactic acid increased, kaussmaul breathing. SMQ is based on the medical concept, hence it can provide consistent and specific safety data, and it also provides users flexibility to retrieve safety data based on their need.
Thus, MedDRA is a tool which allows for straightforward as well as sophisticated analyses. Proper coding of the term through MedDRA would be very useful in analyzing the aggregate data during signal detection and PSUR. Consistent and appropriate coding would be helpful when larger datasets or datasets of longer period are to be analyzed. SMQ is a powerful tool which is used to understand the safety of a drug during pre- and post- marketing period.