The Medical Dictionary for Regulatory Activities (MedDRA) Terminology
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is a unique organization that brings together national regulatory authorities and the pharmaceutical industry to discuss scientific and technical aspects of drug registration. As of January 2021, the ICH has united 43 regulatory parties and regional harmonization initiatives, important regional and international industry associations, and other relevant parties . The ICH facilitates and recommends the use of MedDRA through all phases of a medicine’s life cycle, from clinical trials to post-marketing surveillance. The use of MedDRA by all pharmacovigilance stakeholders is required in the European Union (EU) for the “classification, retrieval, presentation in EU Summary of Product Characteristics (SmPC), risk–benefit evaluation and assessment, electronic exchange and communication of pharmacovigilance and medical product information” [2, 3], and is also required by the United States (U.S.) Food and Drug Administration (FDA) for clinical trial safety reporting by all commercial pharmaceutical sponsors . Hence, the Council for International Organizations of Medical Sciences (CIOMS) MedDRA Labeling Groupings (MLGs) Expert Working Group (EWG) proposal for MLG Preferred Term (PT) grouping in medical product information is limited to usage of MedDRA and no other coding terminologies.
The CIOMS MLG EWG envisions that MLGs, which are groupings of near synonymous MedDRA PTs that convey substantially similar clinical concepts, will simplify the product information and enhance safety communication to healthcare providers via the product label. MLGs are intended to communicate an adverse reaction (AR) in a manner that is expected to give the most accurate and understandable description of an adverse reaction in the product label to the healthcare provider.
MedDRA provides several levels of PT groupings, but these can be inadequate to clearly communicate safety information to the healthcare community. For labeling purposes, it is generally recommended that ARs be represented as either individual or grouped terms [2, 4, 5].
The MedDRA PTs noted in this manuscript are from MedDRA version 24.0. Due to the high granularity of MedDRA, which has over 24,000 PTs in version 24.0, several PTs may be available within this terminology to represent highly similar clinical concepts. However, groupings within MedDRA, such as High Level Terms (HLTs), can be inadequate to clearly communicate safety information in product labels. For example, the HLT Gastrointestinal and abdominal pains (excl oral and throat) includes PTs that might not be appropriate to include in the concept “Abdominal pain,” such as the PTs Oesophageal pain and Visceral pain. In addition, other parts of the MedDRA hierarchy, such as the HLT Gastrointestinal signs and symptoms NEC, contain other PTs that one might want to include with abdominal pain, such as the PT Abdominal discomfort. In order to capture relevant PTs from both HLTs, one could consider combining the two HLTs. However, the latter HLT also includes PTs such as Mastication disorder and Hiccups, which would likely not be considered sufficiently relevant to the concept of abdominal pain.
The need to combine similar PTs was previously discussed by MedDRA’s expert forum called the “Blue Ribbon Panel” in 2005 and subsequently at the ICH MedDRA Management Board. The ICH MedDRA Data Retrieval and Presentation: Points to Consider document  also discusses the importance of displaying and grouping medically related concepts when presenting estimates of the occurrence of an AR.
The need to group similar ARs is also addressed in regulatory guidance texts [2, 5, 7]. For instance, U.S. FDA Guidance for Industry states that “Events that are reported under different terms in the database, but that represent the same phenomenon (e.g., sedation, somnolence, drowsiness) should ordinarily be grouped together as a single adverse reaction to avoid diluting or obscuring the true effect” . “Similarly, reactions that represent a syndrome complex should ordinarily be grouped together under an appropriate heading to avoid obscuring the full range of respective symptoms” .