MedDRA (Medical Dictionary for Regulatory Activities) coding is a critical requirement in pharmacovigilance. MedDRA coding is a skill and in many cases medical judgments have to be made about how to code. So everyone should be trained in coding and up to date on the MSSO guidelines (https://www.meddra.org/training-materials).
MedDRA Definition: MedDRA is a clinically-validated international medical terminology used by regulatory authorities and the regulated biopharmaceutical industry. The terminology is used through the entire regulatory process, from pre-marketing to post-marketing, and for data entry, retrieval, evaluation, and presentation.
- It is a standardized medical terminology developed by ICH to facilitate sharing of regulatory information internationally for drugs, vaccines and drug- device combination products.
- MedDRA contains terms for medical conditions (signs, symptoms, diseases, syndromes, diagnoses), indications, investigations, medical and surgical procedures, medical, social, family history medication errors, product quality issues, device-related issues, product use issues, pharmacogenetic terms, toxicologic issues, and standardized queries.
- MedDRA Management Committee: governance body providing technical and financial oversight of the MedDRA terminology and the MedDRA maintenance organization. ICH MedDRA Points to Consider Working Group: develops guides for harmonized MedDRA usage (coding and retrieval guidelines). MSSO (Maintenance and Support Services Organization): contracted by ICH to maintain, develop and distribute MedDRA.
- MedDRA is updated by the MSSO twice yearly. The first annual release in the spring includes changes to all levels in MedDRA (if any occur). The second release in the autumn is minor and only includes changes to terms at the PT and LLT levels (e.g., new terms, spelling changes, non-current LLTs). Currently we are on version 22. The next version, 22.1 will be out in September 2019.
- See their website for more detail: www.meddra.org.
- MedDRA is already in wide usage with more than 3,700 subscribing organisations around the world including numerous regulators.
MedDRA coding uses in Pharmacovigilance:
- Coding is process of converting investigators’ “verbatim” terms to standardized “Preferred Terms” (PT)
- Standardization allows sorting of AEs and grouping of like events.
- PT used to calculate incidence of AE in signaling, PSUR / DSUR document preparation. For Example, clinical trials are increasingly conducted internationally. Much of the clinical information gathered in trials – such as disease and disorders present; medical, social and family history; signs and symptoms observed; as well as adverse events and adverse drug reactions – can be accurately and efficiently communicated using MedDRA. This allows such data to be pooled, compared and analysed across trials, regardless of linguistic barriers.
- For example if we receive the case with below information then all highlighted information has to be coded with MedDRA. Sample Narrative: A 75-year-old male receiving Drug X for rheumatoid arthritis developed symptomatic aortic valve stenosis. The patient’s medical history is significant for colon cancer and cigarette smoking. He underwent an aortic valve replacement and developed a sternal wound infection three days post-surgery.
- MedDRA support for electronic submissions. Each MedDRA term is assigned a unique 8-digit numeric code. Codes can fill certain data fields in e-submission types (E2B: ICSR- Individual Case Safety Reports, eCTD: e-Common Technical Document).
- These associated numerical code remains the same irrespective of the language. Thus, for example, a user of the French version can understand the results from the user of the Japanese version through their identical numerical codes. This multilingual approach allows most users to operate in their native language which promotes accuracy and precision of assigning codes.
MedDRA Structure:
MedDRA can be used to analyse individual medical events (e.g., Influenza) or issues involving a system, organ or etiology (e.g., Infections) using its hierarchical structure.
It has 5 levels and is hierarchical totalling over 80,262 terms:
System organ classes (SOCs): 27 terms
Higher level group terms (HLGTs): 337 terms
Higher level terms (HLTs): 1,737 terms
Preferred terms (PTs): 23,708) terms
Lowest level terms (LLTs): 80,262 terms
- “Lowest Level Terms” (LLTs): reflects how information is reported by reporter (verbatim). It is most specific and most accurate to the reported term.
- “Preferred Terms” (PTs) are single concepts for symptoms, signs, disease diagnoses, therapeutic indications, investigations, surgical or medical procedures, and medical, social or family history characteristics.
- Related PTs are grouped together into over 1,700 “High Level Terms” (HLTs) based upon anatomy, pathology, physiology, etiology or function. HLTs are in turn linked to over 330 “High Level Group Terms” (HLGTs).
- Finally, HLGTs are grouped into 27 “System Organ Classes” (SOCs) which are grouped by etiology (e.g., Infections and infestations), manifestation site (e.g., Gastrointestinal disorders) or purpose (e.g., Surgical and medical procedures).
- There is also a SOC accounting for social circumstances.
The most common levels used in PV practice are the LLT and PT levels. These terms are all medical terms compared to reporters’ terms (“verbatim terms”) which may or may not be medical – vomiting or throwing up or barfing for example.
While selecting LLT term we need to be very accurate and it must reflect actual reporter term. A single letter difference in a reported verbatim text can impact the meaning of the word and consequently the term selection. For example, if reported term is lip sore then we need to select LLT of ‘lip sore’ which goes to PT of ‘Lip pain’, if reported verbatim is Lip sores then we need to select LLT of ‘Sores lip’ which has PT ‘Cheilitis’.
If no direct LLT match with verbatim term available in MedDRA then medical judgement is required to select the closest LLT to reported term.
MedDRA has multi-axiality meaning that the representation of a medical concept in multiple SOCs or a PT can be associated with more than one HLT (axis) with a primary axis and one or more secondary axes. For example, the PT Influenza represents an important respiratory tract problem as well as an infection. For this reason, each PT is assigned to a primary SOC, but may also be assigned to one or more secondary SOCs. The multiaxial structure of MedDRA supports signal detection and signal monitoring. The PT Influenza is primary to the SOC Infections and infestations, but this PT is also secondary to the SOC Respiratory, thoracic and mediastinal disorders.
SMQ – Standardised MedDRA Query:
- SMQs are validated, pre-determined sets of MedDRA terms grouped together after extensive review, testing, analysis and expert discussion.
- A SMQ can be wide in reach, such as Taste and smell disorders, or specific, such as the SMQ on Agranulocytosis.
- Currently, more than 100 SMQs have been created. Additional SMQs are created as the need arises.
- SMQs are complex and varied in concept. Some SMQs are a simple set of PTs while other SMQs are hierarchical containing subordinate SMQs.
- SMQs can include “narrow” and “broad” terms. Narrow terms are those that are highly likely to represent the condition of interest. For example, the PTs Pancreatitis acute and Pancreatitis haemorrhagic are narrow terms for the Acute pancreatitis (SMQ) whereas the PT Blood bilirubin increased is a broad term. Not all instances of increased blood bilirubin are indicative of acute pancreatitis. SMQ retrievals may be limited to narrow terms if desired.
- SMQs may also be used to further support signal detection and monitoring.
The next post in MedDRA learning series will be on MedDRA term selection principles and tricky coding issues.
