MedDRA and Labelling

MedDRA AND LABELLING

‘Best practices’ guidelines on the use of MedDRA for labelling have been published by the MSSO (MedDRA Maintenance and Support Services Orga-nization, 2005). They propose three tiers of product labelling: the Company Core Data Sheet (CCDS) for use by the manufacturer and for interacting with regu-latory agencies; information for the prescriber; and information for the patient. The MSSO states that it does not foresee a role for MedDRA in any form of patient-oriented product information.

For the CCDS, it is proposed in the MSSO docu-ment that MedDRA should be used in narrative and tabular presentations of information, but that flexibil-ity is required, as MedDRA may not be applicable in some sections, such as for indications or dosage. In the adverse reaction section of the CCDS, the MSSO proposes the use of MedDRA, generally at the PT level, but with HLTs, HLGTs and/or SMQs or similar groupings to represent particular conditions, if needed.

The guidelines suggest that, in the CCDS, it might be possible to supplement PTs with lists of corre-sponding LLTs, to assist in judging listedness and to facilitate automated expectedness determination. However, it is made clear that such lists are no substi-tute for medical judgement, and that it may be neces-sary to review additional case-level information in order to provide context in deciding upon listedness or expectedness.

For product information directed at the health professional, the MSSO recommends the use of famil-iar medical words and logical groupings, supple-mented by specific MedDRA terms or groupings. They point out that the specificity of MedDRA may be problematic when summarising data in a clini-cally meaningful way and that prescribers may not be familiar with MedDRA conventions. Hence, it may be necessary to translate MedDRA terms into more familiar and understandable medical terms. Again, it may be appropriate to use MedDRA group terms, or SMQs, or ad hoc groupings may be needed. One example of such a grouping would be the use of a single term for thrombocytopenia to include PTs for the medical condition (e.g., PT Thrombocytopenia) with those for the corresponding laboratory findings (e.g., Platelet count decreased).

Existing regulatory guidance on the use of MedDRA in the Summary of Product Characteristics in the EU can be found in Volume 2 of the Notice to Applicants, published by the European Commis-sion (European Commission Enterprise Directorate General, 1999). Draft amendments to these guidelines have been issued and are awaiting the outcomes of consultation at the time of writing (Proposal for Revi-sion of a Guideline on Summary of Product Character-istics Committee for Medicinal Products for Human Use, 2005). Despite the possibility that these may change in due course, it is worth summarising the proposed SPC guidelines as an indication of current EU regulatory thought on the use of MedDRA.

The present and proposed SPC Guidelines propose the use of MedDRA in Section 4.8, Undesirable effects, with a table of ADRs according to MedDRA SOC, listed in accordance with the International SOC Order. ADR descriptions should be based on the most suitable representation within MedDRA, usually PTs, but sometimes the use of LLTs or exceptionally group terms may be appropriate. Within each SOC, ADRs should be ranked under headings of frequency. In addition, the proposed guidance states that, as a general rule, any ADR in the SPC should be assigned to the most relevant SOC related to the target organ. For example, the PT Liver function test abnormal should be assigned to the SOC Hepatobiliary disorder rather than to the SOC Investigations.

The proposed SPC Guidelines include an Annex devoted to the use of MedDRA. This states that a pragmatic approach to the location of terms should be taken in order to make the identification of ADRs simpler and clinically appropriate for the reader. Thus, it may be helpful on some occasions to use secondary SOC locations of some MedDRA PTs, or to use loca-tions that do not accord with MedDRA architecture. The example is given for the terms Liver function test abnormal, Hepatitis and Hepatic encephalopathy – it would be acceptable to include them all under the ‘Hepato-biliary disorders’ SOC, instead of distribut-ing the reactions among ‘Hepato-biliary disorders’, ‘Nervous system disorders’ and ‘Investigations’ SOCs as dictated by their primary location in MedDRA.

The Annex then suggests that it is acceptable to adapt names of group terms if this makes their mean-ing more transparent, for example HLT Genitouri-nary tract disorders NEC could be presented without ‘NEC’ (not elsewhere classified). ADR terms should be expressed in natural word order, such as ‘Intersti-tial pneumonia’ not ‘Pneumonia interstitial’. Also, the most widely recognised term for a particular condition should be used, for example the LLT ‘Churg Strauss syndrome’ might be more appropriate than the PT ‘Allergic granulomatous angiitis’.

With regard to estimating frequency of occur-rence of adverse events from studies, the proposed guidelines state that appropriate levels of MedDRA should be used in order to group together clinically related conditions in a meaningful way. For exam-ple if ‘postural dizziness’, ‘exertional dizziness’ and ‘unspecified dizziness’ were each reported by 2% of patients, this might be represented in the SPC as ‘Dizziness’ occurring in 6% of patients (assuming that only one report of dizziness applied to each patient). It may also be appropriate to use ad hoc groupings, or to adapt MedDRA group terms, for example reports of ADRs represented as PTs ‘Diarrhoea’, ‘Diarrhoea aggravated’, ‘Loose stools’, ‘Stools watery’, ‘Intesti-nal hypermotility’ could not really be represented as standard MedDRA groupings, which comprise three separate HLTs – ‘Diarrhoea (excl infective)’, ‘Gastrointestinal spastic and hypermotility disorders’ and ‘Faeces abnormal’. To make the SPC relevant and comprehensible to clinicians, the condition might simply be represented as ‘Diarrhoea’.