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Exploring the Potential Routine Use of Electronic Healthcare Record Data to Strengthen Early Signal Assessment in UK Medicines Regulation: Proof-of-Concept Study

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Abstract

Introduction

Electronic healthcare record (EHR) databases are used within pharmacoepidemiology studies to confirm or refute safety signals arising from spontaneous adverse event reports. However, there has been limited routine use of such data earlier in the signal management process, to help rapidly contextualise signals and strengthen preliminary assessment or to inform decisions regarding action including the need for further studies. This study explores the value of EHR used in this way within a regulatory environment via an automated analysis platform.

Methods

Safety signals raised at the UK Medicines and Healthcare products Regulatory Agency (MHRA) between July 2014 and June 2015 were individually reviewed by a multi-disciplinary team. They assessed the feasibility of identifying the exposure and event of interest using primary care data from the Clinical Practice Research Datalink (CPRD) within the Commonwealth Vigilance Workbench (CVW) Longitudinal Module platform, which was designed to facilitate routine descriptive analysis of signals using EHR. Three signals, where exposure and event could be well identified, were retrospectively analysed using the platform.

Results

Of 69 unique new signals, 20 were for drugs prescribed predominately in secondary care or available without prescription, which would not be identified in primary care. A further 17 were brand, formulation, or dose-specific issues, were related to mortality, were relevant only to a subgroup of patients, or were drug interactions, and hence could not be reviewed using the platform given its limitations. Analyses of exposure and incidence of the adverse event could be produced using CPRD within the CMV Longitudinal Module for 32 (46%) signals. The case studies demonstrated that the data provided supporting evidence for confirming initial assessment of the signal and deciding upon the need for further action.

Conclusions

CPRD can routinely provide useful early insights into clinical context when assessing a large proportion of safety signals within a regulatory environment provided that a flexible approach is adopted within the analysis platform.

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Acknowledgements

The authors would like to thank Olutoyin Agbaje, Claire Davies, Temitope Ibitoye, and Jenny Wong for the comments they provided within early stages of the pilot and on the output from the three case studies, and Arlene Gallagher for providing additional expertise on the use of CPRD data.

Author information

Authors and Affiliations

  1. Vigilance and Risk Management of Medicines, MHRA, 151 Buckingham Palace Road, London, SW1W 9SZ, UK

    Katherine Donegan, Rebecca Owen, Helena Bird, Brian Burch, Alex Smith & Phil Tregunno

Authors
  1. Katherine Donegan
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  2. Rebecca Owen
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  3. Helena Bird
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  4. Brian Burch
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  5. Alex Smith
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  6. Phil Tregunno
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Contributions

The study was planned and led by KD, PT and RO. Preliminary screening of the DECs included was conducted by PT, RO and BB, with additional assessment support from KD, HB and AS for the second stage of the review. The three case studies were conducted by HB, BB and AS with input from KD. The paper was drafted by KD with contributions from all authors.

Corresponding author

Correspondence to Katherine Donegan.

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Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Access to the CVW Longitudinal Module was provided by Commonwealth Informatics Inc. The CVW Longitudinal software is engineered by Commonwealth Informatics, Inc., and builds on research performed by the Uppsala Monitoring Centre.

Conflict of interest

At the time of the study, all authors (Katherine Donegan, Rebecca Owen, Helena Bird, Brian Burch, Alex Smith, and Phil Tregunno) were employed by the MHRA, which is an Executive Agency of the Department of Health, but have no conflicts of interest that are directly relevant to the contents of this study. The MHRA has statutory responsibility to monitor the safety of medicinal products on the UK market, and the study was undertaken independently of the Department of Health.

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Donegan, K., Owen, R., Bird, H. et al. Exploring the Potential Routine Use of Electronic Healthcare Record Data to Strengthen Early Signal Assessment in UK Medicines Regulation: Proof-of-Concept Study. Drug Saf 41, 899–910 (2018). https://doi.org/10.1007/s40264-018-0675-x

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  • DOI: https://doi.org/10.1007/s40264-018-0675-x

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