Patterns of use and impact of standardised MedDRA query analyses on the safety evaluation and review of new drug and biologics license applications

Lin Chau Chang, Riaz Mahmood, Samina Qureshi, Christopher D. Breder

Research output: Contribution to journalArticle

Abstract

Purpose: Standardised MedDRA Queries (SMQs) have been developed since the early 2000's and used by academia, industry, public health, and government sectors for detecting safety signals in adverse event safety databases. The purpose of the present study is to characterize how SMQs are used and the impact in safety analyses for New Drug Application (NDA) and Biologics License Application (BLA) submissions to the United States Food and Drug Administration (USFDA). Methods: We used the PharmaPendium database to capture SMQ use in Summary Basis of Approvals (SBoAs) of drugs and biologics approved by the USFDA. Characteristics of the drugs and the SMQ use were employed to evaluate the role of SMQ safety analyses in regulatory decisions and the veracity of signals they revealed. Results: A comprehensive search of the SBoAs yielded 184 regulatory submissions approved from 2006 to 2015. Search strategies more frequently utilized restrictive searches with "narrow terms" to enhance specificity over strategies using "broad terms" to increase sensitivity, while some involved modification of search terms. A majority (59%) of 1290 searches used descriptive statistics, however inferential statistics were utilized in 35% of them. Commentary from reviewers and supervisory staff suggested that a small, yet notable percentage (18%) of 1290 searches supported regulatory decisions. The searches with regulatory impact were found in 73 submissions (40% of the submissions investigated). Most searches (75% of 227 searches) with regulatory implications described how the searches were confirmed, indicating prudence in the decision-making process. Conclusions: SMQs have an increasing role in the presentation and review of safety analysis for NDAs/BLAs and their regulatory reviews. This study suggests that SMQs are best used for screening process, with descriptive statistics, description of SMQ modifications, and systematic verification of cases which is crucial for drawing regulatory conclusions.

Original languageEnglish (US)
Article numbere0178104
JournalPLoS One
Volume12
Issue number6
DOIs
StatePublished - Jun 1 2017

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new drugs
Licensure
Biological Products
statistics
Safety
Pharmaceutical Preparations
Statistics
drugs
United States Food and Drug Administration
safety assessment
decision making
Databases
public health
Drug Approval
screening
industry
Public health
Decision Making
Industry
Screening

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Patterns of use and impact of standardised MedDRA query analyses on the safety evaluation and review of new drug and biologics license applications. / Chang, Lin Chau; Mahmood, Riaz; Qureshi, Samina; Breder, Christopher D.

In: PLoS One, Vol. 12, No. 6, e0178104, 01.06.2017.

Research output: Contribution to journalArticle

Chang, Lin Chau ; Mahmood, Riaz ; Qureshi, Samina ; Breder, Christopher D. / Patterns of use and impact of standardised MedDRA query analyses on the safety evaluation and review of new drug and biologics license applications. In: PLoS One. 2017 ; Vol. 12, No. 6.
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