MedDRA and SMQs
MedDRA and SMQs: MedDRA (Medical Dictionary for Regulatory Activities) is a globally standardized medical terminology developed by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). It is used in regulatory submissions, clinical trials, and post-marketing surveillance to describe adverse drug reactions (ADRs), medical conditions, and therapeutic indications in a uniform and structured manner.
MedDRA helps standardize the way medical terms are recorded and reported, making it easier for healthcare providers, pharmaceutical companies, and regulatory agencies to monitor drug safety and track adverse events across different regions and languages.
1. Structure of MedDRA
MedDRA has a five-level hierarchical structure, which allows for flexibility in the level of detail provided for coding and analyzing medical events:
1. System Organ Class (SOC): The highest level of the hierarchy, grouping terms by organ system or etiology (e.g., Cardiac disorders, Nervous system disorders).
2. High-Level Group Term (HLGT): More specific groupings within SOCs (e.g., Cardiac arrhythmias, Neurological disorders).
3. High-Level Term (HLT): A further breakdown of medical events (e.g., Atrial arrhythmias, Seizures).
4. Preferred Term (PT): The standard term used to describe a specific medical condition or adverse reaction (e.g., Atrial fibrillation, Epileptic seizure).
5. Lowest-Level Term (LLT): The most specific terms, often synonyms or colloquial expressions of the PT (e.g., AF for Atrial fibrillation, Seizure attack for Epileptic seizure).
Example of MedDRA Hierarchical Structure:
System Organ Class (SOC): Nervous system disorders
High-Level Group Term (HLGT): Neurological disorders NEC
High-Level Term (HLT): Seizure-related disorders
Preferred Term (PT): Epileptic seizure
Lowest-Level Term (LLT): Seizure attack
MedDRA’s flexible structure allows pharmacovigilance professionals to report adverse events at different levels of specificity, depending on the available information.
2. Standardized MedDRA Queries (SMQs)
Standardized MedDRA Queries (SMQs) are pre-defined sets of MedDRA terms that are grouped together to assist in identifying specific medical conditions or safety issues. SMQs are developed to support signal detection and data analysis in pharmacovigilance by grouping related terms that may indicate a common underlying condition, even if different terminology is used.
SMQs are particularly useful for:
Signal Detection: Identifying new safety signals for drugs.
Case Retrieval: Searching databases for cases related to specific medical issues (e.g., liver injury, cardiovascular disorders).
Data Analysis: Analyzing safety data in clinical trials and post-marketing surveillance.
Each SMQ is designed to be flexible, allowing for broad or narrow searches:
Broad SMQ: Captures all potential cases related to the medical condition of interest, but may include some false positives.
Narrow SMQ: Focuses on specific cases and minimizes false positives, but may miss some relevant cases.
Examples of SMQs:
Liver-Related Investigations, Signs, and Symptoms: This SMQ would include terms related to liver function tests, jaundice, and liver disorders.
Anaphylactic Reaction: This SMQ contains terms for identifying cases related to allergic or anaphylactic reactions.
Cardiac Arrhythmias: Includes terms for detecting cases of irregular heartbeats or arrhythmias, such as atrial fibrillation or ventricular tachycardia.
Example of an SMQ: Liver-Related Investigations, Signs, and Symptoms
This SMQ is designed to capture cases of liver injury or dysfunction and includes MedDRA terms related to:
Liver function test abnormalities (e.g., elevated liver enzymes, ALT increased).
Clinical signs (e.g., jaundice, hepatomegaly).
Liver disorders (e.g., hepatitis, liver failure).
The SMQ can be used for signal detection in clinical trials or post-marketing surveillance to identify drugs that may cause liver damage.
3. How SMQs Are Used in Pharmacovigilance
Case Identification: Pharmacovigilance professionals can use SMQs to retrieve cases from safety databases (such as the FDA’s FAERS or the WHO’s VigiBase) that might indicate a common underlying adverse reaction.
Signal Detection: By grouping related MedDRA terms, SMQs help identify potential safety signals by highlighting patterns in adverse event reporting. For example, an SMQ for acute renal failure would include terms such as kidney failure, renal impairment, and elevated creatinine, allowing for comprehensive data analysis.
Data Analysis: SMQs are particularly useful when analyzing large datasets from clinical trials or real-world data. They allow for targeted searches of specific safety concerns, such as identifying all adverse events related to hemolytic anemia or acute pancreatitis.
4. Example of SMQ Application in a Study
Case Example: Study on Drug-Induced Liver Injury (DILI)
Objective: To detect cases of drug-induced liver injury (DILI) in a clinical trial database using the Liver-Related Investigations, Signs, and Symptoms SMQ.
Steps:
1. Define the Scope: The pharmacovigilance team selects the broad version of the SMQ for liver-related issues to capture a wide range of potential liver-related adverse events.
2. Run the Query: The SMQ is run against the clinical trial database to retrieve cases where MedDRA terms related to liver function (e.g., ALT increased, bilirubin increased, hepatitis) are present.
3. Narrow the Search: To focus on more specific cases of DILI, the team applies the narrow version of the SMQ, which excludes less specific terms.
4. Analyze the Results: The retrieved cases are analyzed to determine if there is a potential safety signal related to the drug being studied. The broad SMQ results are compared with the narrow SMQ results to assess the balance between sensitivity and specificity.
This use of the Liver-Related SMQ helps identify potential liver injury signals, ensuring that the study drug’s safety profile is thoroughly evaluated.
5. Benefits of Using SMQs in Pharmacovigilance
Efficiency: SMQs streamline the process of searching and identifying related adverse events, saving time and reducing the manual effort required to comb through safety data.
Standardization: By using pre-defined sets of terms, SMQs ensure that pharmacovigilance professionals are consistently identifying the same types of cases across different studies and databases.
Improved Signal Detection: SMQs improve the sensitivity of signal detection by grouping related terms together, which might otherwise be missed if terms are evaluated individually.
Regulatory Compliance: SMQs are recognized by regulatory authorities (such as the FDA, EMA, and PMDA) and are often required in the submission of safety data for drugs undergoing clinical trials or in post-marketing surveillance.
Conclusion
MedDRA and Standardized MedDRA Queries (SMQs) are critical tools in pharmacovigilance for ensuring the consistency and accuracy of adverse event reporting and drug safety data analysis. MedDRA provides a structured way to code medical events, while SMQs allow for the efficient identification of safety signals by grouping related terms. Together, they enhance the ability of healthcare providers, regulatory authorities, and pharmaceutical companies to monitor drug safety, detect potential risks, and ensure patient safety.