Validation of statistical signal detection procedures in eudravigilance post-authorization data: a retrospective evaluation of the potential for earlier signalling.

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/14160
• EU PAS number:
  EUPAS1594
• Study ID:
  14160
• Official title and acronym:
  Validation of statistical signal detection procedures in eudravigilance post-authorization data: a retrospective evaluation of the potential for earlier signalling.
• DARWIN EU® study:
  No
• Study countries:
  United Kingdom
• Study description:
  OBJECTIVE: To evaluate whether statistical signal detection in spontaneous reporting data can lead to earlier detection of drug safety problems and to assess the additional regulatory work entailed. METHODS: Using the EudraVigilance post-authorization module (EVPM), a screening procedure based on the proportional reporting ratio (PRR) was applied retrospectively to examine if regulatory investigations concerning ADRs could have been initiated earlier than occurred in practice. During the same time period (Sep03 - Mar07), the number of PRR-based signals of disproportionate reporting (SDR) that arose in a predefined set of products was calculated and evaluated to determine the number requiring investigation. RESULTS: In 191 chemically different products, 532 adverse reactions were added to the summary of product characteristics during the study period. Of these, 405 were designated as important medical events (IMEs) based on a comprehensive predefined list. Of the IMEs, 217 (53.6%) were identified earlier by the statistical screening technique, 79 (19.6%) were detected after the date at which they were raised by standard pharmacovigilance (PhV) methods and 109 (26.9%) were not signalled during the study period. 1561 SDRs requiring further evaluation were detected during the study period, giving a ratio of 7.2 assessments for each signal pre-empted. The mean delay between the discovery of signals using the statistical methods in the EVPM and established methods in the 217 cases detected earlier was 2.45 years. A review resulted in clear explanation for why the statistical method had not pre-empted detection in all but 77 of 188 cases. CONCLUSIONS: The form of statistical signal detection tested in this study can provide significant early warning in a large proportion of drug safety problems, however, it cannot detect all safety issues more quickly than other PhV processes and hence it should be used in addition to, rather than as an alternative to, established methods.
• Study status:
  Finalised

Research institution and networks

Institutions

European Medicines Agency (EMA)

Study timelines

Date when funding contract was signed

Actual: 01/12/2006

Study start date

Actual: 05/03/2007

Date of final study report

Actual: 01/06/2010

Sources of funding

EMA

Regulatory

• Was the study required by a regulatory body?:
  Yes
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable