Medical Dictionary for Regulatory Activities (MedDRA®)

Medical Dictionary for Regulatory Activities (MedDRA^®)

INTRODUCTION

MedDRA is a structured vocabulary of medical and other terms relevant to the development and use of medicines in man. It was designed for use in the phar-maceutical industry/regulatory environment, ostensi-bly to support all stages of the regulatory process concerning human medicines. It began life in the early 1990s as a refinement of the, then new, dictionary developed for the UK regulatory agency’s ADROIT (Adverse Drug Reaction On-line Information Track-ing) post-marketing safety database. Developed by an international committee of regulators and industry staff, the new terminology had its first incarnation as MEDDRA (Medical Dictionary for Drug Regulatory Affairs) in 1993, then being nurtured and transformed by the International Conference on Harmonization (ICH) M1 Expert Working Group into the subtly renamed MedDRA (Medical Dictionary for Regula-tory Activities) (Brown, Wood and Wood, 1999).

Its release to an expectant public as an international ICH-approved standard took place in March 1999. By this time, its ownership had been taken over by the International Federation of Pharmaceutical Manufacturers Associations (IFPMA), with over-sight by a Management Board answerable to ICH. However, the interface with users, who purchase access rights through a system of licensing, is via the MedDRA Maintenance and Support Services Organ-isation (MSSO) and the corresponding, but distinct, Japanese Maintenance Organisation (JMO). The work of these bodies is undertaken on a commercial basis – currently by Northrop Grumman Mission Systems (for MSSO) and the Japanese Pharmacopoeia (for JMO). The MSSO and JMO release to subscribers updated versions of MedDRA (currently) every 6 months on a CD or by Internet download (MedDRA Maintenance and Support Services, 2005).

Guidance for the use of MedDRA has been devel-oped by the MSSO: this comprises an Introductory Guide that is provided with MedDRA to subscribers, as well as guidance on some specific contentious issues, including version control and use of MedDRA in labelling. In addition, ICH-endorsed guidelines on term selection (MedDRA^® Term Selection, 2004) have been issued by a joint industry-regulators work-ing group (‘Points to Consider’ guidelines), and this body has also published draft guidance on database searches and presentation (MedDRA^® Data Retrieval and Presentation, 2004). Another working group, under the aegis of CIOMS, is developing standardised pharmacovigilance search strategies (SMQs, 2005).

MedDRA SUBSCRIPTIONS

MedDRA is available only on payment of a subscrip-tion to the MSSO or JMO, although this is free for regulatory authorities. The usual type of subscrip-tion involves the ‘core service’ (MedDRA Mainte-nance and Support Services, 2005); this provides for use throughout a company and its wholly owned subsidiaries. The core service supplies the subscrib-ing company with two updated versions of MedDRA each year, together with the facility to request up to 100 changes per month to MedDRA. Changes that are accepted by the MSSO are posted on their website and are available in the next version of the terminology.

The Core Service subscriptions are based on the annual revenue of the company, as published in the annual report. The annual subscription charges in 2005 range from $3825 for a company with revenue under $1 million to $92 292 for a company with more than $5 billion annual revenue. It does not take a mathematical expert to appreciate that there is some significant disproportion at play here!

MedDRA CONTENTS

The MedDRA terminology contains more than 60 000 terms for medical conditions, syndromes, diagnoses, clinical signs, symptoms, laboratory and clinical investigations and social circumstances. It thus differs from dictionaries such as COSTART, HARTS and WHO-ART, which are more than an order of magni-tude smaller and principally composed of adverse reaction terms. However, MedDRA does contain most (if not all) of the terms from these adverse reaction dictionaries, as well as most terms from the Interna-tional Classification of Diseases ICD9 and its clini-cal modification, ICD9-CM. The intention was that the terms from these other dictionaries and classifica-tions are retained in MedDRA at the data entry level (Lowest Level Term, LLT) to facilitate transfer of previously coded data from an existing safety database to a database using MedDRA – so-called ‘legacy data migration’. It should be appreciated that, although these terms from other dictionaries are present in MedDRA, they do not retain their original relation-ships and hierarchical locations.

Thus, for example, in WHO-ART, the Preferred Term (PT) Cholesterol crystal emboli is located in the Platelet, bleeding and clotting disorders System Organ Class (SOC). In MedDRA, Cholesterol crystal emboli is a LLT under the PT Fat embolism, located in the Injury, poisoning and procedural complica-tions SOC.

MedDRA does not include terms for drug or device names (unless, exceptionally, these represent a typical medical diagnosis, such as Digoxin toxicity). It does not provide definitions of terms (and hence perhaps does not strictly comply with the dictionary defi-nition of a dictionary!). It does not include demo-graphic terms, such as those describing gender, age or race – unless these are a component of a discrete medical condition, such as Infantile spasms or Breast cancer male. MedDRA also does not include numeri-cal expressions, although there are again some excep-tions such as Type II hyperlipidaemia, nor does it provide measures of severity. Once more, there are some exceptions, as in Severe mental retardation or Grade 1 hypertensive fundus. The implication is that MedDRA is intended for use with a database that can capture information about drug name, patient demographics and disease severity independently of MedDRA itself. It should be noted that MedDRA is limited to human experience: animal pharmacol-ogy and toxicology and veterinary terms are outside its scope.