Regulatory Use

Here are some published case studies of MedDRA use by regulatory authorities.

Evaluation of the use of algorithmic SMQs in safety signal detection

The objective of this study, was to evaluate important quantitative and qualitative criteria of algorithmic SMQs to reflect their performance in the identification of relevant cases.  The authors reviewed the adverse event (AE) datasets of 107 New Drug Applications and Biological License Applications submitted to the U. S. Food and Drug Administration, with respect to the accuracy and precision of seven of the ten algorithmic SMQs. Their findings support the value of algorithmic SMQs and temporal assessments to improve specificity when retrieving appropriate cases, and to reduce overestimating of event incidence that sometimes results from the identification of the same case by the narrow and broad algorithmic terms of an SMQ.  It was recommended that a temporal assessment be considered for some SMQs, because “a better understanding of the pattern of onset AEs can help provide guidance for case retrieval for safety signal detection.”  The authors suggest, “As the popularity of SMQs used to screen for safety signals grows, we recommend revisiting and refining their term lists.”  This publication provides an important objective, empirical evaluation of the performance of algorithmic SMQs, a confirmation of their value in the identification of cases of interest for pharmacovigilance, and specific recommendations for their ongoing enhancement to increase their efficiency and productivity for data safety mining.

Tieu C, Breder CD.  A Critical Evaluation of Safety Signal Analysis Using Algorithmic Standardised MedDRA Queries. Drug Saf. 2018 Aug 16.

Use of MedDRA in Characterising Medication Errors

This article presents the results of a study that characterises spontaneously reported cases of medication errors in EudraVigilance over the period 2002–2015. A total of 147,824 potential case reports was identified for review using the Standardised MedDRA Query (SMQ) for medication errors. Events were further categorised by MedDRA term, geographical region, patient age group, and Anatomical Therapeutic Chemical classification system of suspect medicinal product(s). Potential reasons for the steady increase in medication errors during the observation period were discussed. The authors noted that, since 2005, there has been a significant expansion of the MedDRA hierarchy which now uses a conceptual approach to cover a broad range of medication errors. In addition, the authors emphasised the value of Medication errors (SMQ) in the identification of medication errors in a pharmacovigilance database: “The release of the MedDRA SMQ for medication errors has been an important milestone to improve the detection and retrieval of medication errors in EudraVigilance.”

Newbould V, Le Meur S, Goedecke T, Kurz X. Medication Errors: A Characterisation of Spontaneously Reported Cases in EudraVigilance. Drug Saf. 2017 Jul 11

Use of SMQs in Safety Evaluation of Regulatory Submissions

The authors state that “the present study is the first one, to the best of our knowledge…to characterize patterns in SMQ use and impact in the generation of regulatory decisions in the review of NDA and BLA submissions to the United States Food and Drug Administration.” Hepatic toxicity, cardiac toxicity, central nervous system toxicity, and hypersensitivity were the most common safety concerns that were subject to SMQ evaluation, and the utility of SMQ use relevant to labeling and postmarketing requirements is demonstrated in this review of regulatory submissions. The authors conclude that “the SMQ is a well-recognized tool with increasing importance for the analysis of safety profiles, which could be effectively used in making regulatory decisions.”

Chang LC, Mahmood R, Qureshi S, Breder CD. Patterns of use and impact of standardised MedDRA query analyses on the safety evaluation and review of new drug and biologics license applications. PLoS One. 2017 Jun 1;12(6):e0178104

Analysis of SMQs for Signal Detection

The EMA researchers in this study compared the timing of onset of a known safety signal (hyperglycaemia) for a marketed product using various MedDRA term levels (PT, HLT, HLGT) and for SMQ Hyperglycaemia/new onset diabetes mellitus. Proportional reporting ratios (PRRs) over time (“dynamic PRRs”) for each term level and for the SMQ were calculated and used for the comparison. The researchers reported that a significant PRR was found using SMQ Hyperglycaemia/new onset diabetes mellitus earlier than for any other term level studied. The study highlighted the potential for SMQs to be used early on in signal detection for risk management, and that further research in this area would be useful.

Newbould V, Halsey N, Tsintis P, Lerch M, Mozzicato P. Standardised MedDRA® Queries: Analysis of their signal detection capability. 22nd ICPE Meeting; 2006 Aug; Lisbon, Portugal; Abstract 87.

MedDRA Used by Regulatory Safety Officers to Monitor Vaccine Safety

During the H1N1 influenza outbreak in the USA in 2009, safety officers from the US Centers for Disease Control and Prevention (CDC) and US FDA monitored the Vaccine Adverse Event Reporting System (VAERS) for adverse events following immunisation with the H1N1 vaccine. Signs and symptoms in submitted adverse event reports were coded using MedDRA for the VAERS database. Using trends in reporting proportions (for reports with selected MedDRA terms), advanced signal detection methods (data mining) and clinical review of received reports, the safety officers concluded in their analysis that AE profile of the H1N1 vaccination was consistent with that of seasonal influenza vaccines.

Vellozzi C, Broder KR, Haber P, Guh A, Nguyen M, Cano M et al. Adverse events following influenza A (H1N1) 2009 monovalent vaccines reported to the vaccine adverse event reporting system, United States, October 1, 2009–January 31, 2010. Vaccine 2010 Oct 21;28(45):7248-55.

MedDRA Used by Regulatory Authority to Monitor Reports of Drug-Induced Hepatotoxicity

The Serbian regulatory authority performed a retrospective observational study of spontaneously reported adverse drug reactions recorded in their database from January 1995 to December 2008.  MedDRA was used to identify cases of hepatobiliary disorders; these reports were also studied for the types of drugs involved. The regulatory authority researchers concluded that anti-infective drugs, nervous system drugs, and herbal products were the most common drug classes reported for hepatotoxicity in Serbia. They also identified a need for additional education about adverse drug reactions and enhanced reporting by health care professionals in their country.

Petronijevic M, Ilic K, Suzuki A. Drug induced hepatotoxicity: data from the Serbian pharmacovigilance database. Pharmacoepidemiology and Drug Safety 2011 April;20:416-23.