Drug Safety

, Volume 36, Issue 7, pp 557–564 | Cite as

The Impact of Direct Healthcare Professional Communication on Prescribing Practice in the UK Hospital Setting: An Interrupted Time Series Analysis

  • Sarah K. Thomas
  • James Hodson
  • Graham McIlroy
  • Annjeet Dhami
  • Jamie J. ColemanEmail author
Original Research Article



Direct Healthcare Professional Communications (DHPCs) aim to quickly disseminate information to key healthcare professionals to inform practice and minimize patient harm. The Medicines and Healthcare products Regulatory Agency (MHRA) issues warnings and alerts to communicate safety information effectively in the UK.


To investigate the impact of MHRA DHPCs on prescribing practice in the secondary-care setting, looking specifically at a drug-drug interaction–the concomitant use of clopidogrel and proton pump inhibitors (PPIs) [as omeprazole]–and a drug-disease contraindication–the use of conventional (typical) antipsychotics in dementia.


The effects of the MHRA DHPCs were analysed using segmented binary logistic regression of interrupted time series. This allowed for the detection of any significant changes in prescribing practice occurring after the MHRA warnings were issued, whilst controlling for the baseline period.


Of the patients concomitantly prescribed clopidogrel and omeprazole on admission, the rate at which omeprazole was substituted for either another PPI (with the exception of esomeprazole), or for a histamine H2-antagonist showed a significant step-change increase after the DHPC was issued. The modelled rate increased from 5.1 % in the month directly before the intervention to 25.1 % in the following month (odds ratio [OR] 6.18; p < 0.001). However, the action taken in the switching of therapy was not always consistent with the advice from the current MHRA warning. The rate of typical antipsychotic prescribing in patients with dementia was declining significantly by 3.9 % per quarter prior to the DHPC being issued (OR 0.970; p = 0.035). No significant step-change was detected immediately after the DHPC (p = 0.962). However, the rate of decline increased significantly in the post-warning period to 12.3 % per quarter (OR 0.938; p = 0.006).


This study has shown that DHPCs issued by the MHRA as warnings are associated with changes in prescribing practices in secondary care. However, their impact is variable depending on the intervention described by the warning. A national initiative to ensure patient safety information is effectively translated into practice and the effect of the warning continues beyond the period of the issue would be beneficial.


Dementia Clopidogrel Omeprazole Esomeprazole Interrupted Time Series 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We would like to thank the Data Analysts, David Westwood and Mariam Afzal, for obtaining the information from the PICS and LORENZO systems in order to carry out this research.

Statements of contribution

All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. All authors contributed to the writing of the manuscript, the interpretation of data, and approved the final version.

Competing interests

Jamie Coleman is a member of the Pharmacovigilance Expert Advisory Group of the MHRA. The views expressed in this study are, however, his own.


This work was funded by the National Institute for Health Research (NIHR) through the Collaborations for Leadership in Applied Health Research and Care for Birmingham and Black Country (CLAHRC-BBC) programme. The views expressed in this study are not necessarily those of the NIHR, the Department of Health, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham or the CLAHRC-BBC Theme 9 Management Steering Group.

Conflict of interest

Sarah Thomas, James Hodson, Graham McIlroy, Annjeet Dhami and Jamie Coleman have no conflicts of interest to declare that are directly relevant to the content of this study.


  1. 1.
    Department of Health. Building a safer NHS for patients: implementing an organisation with a memory. 2001. Accessed 30 Mar 2012.
  2. 2.
    European Medicines Agency. 2012. Accessed 7 May 2012.
  3. 3.
    Medicines and Healthcare products Regulatory Agency. Medicines and medical devices regulation: what you need to know. 2008. Accessed 7 May 2012.
  4. 4.
    Wagner AK, Chan KA, Dashevsky I, Raebel MA, Andrade SE. Elston Laffata J, et al. FDA drug prescribing warnings: is the black box half empty or half full? Pharmacoepidemiol Drug Saf. 2005;15(6):369–86.CrossRefGoogle Scholar
  5. 5.
    Piening S, Reber KC, Wieringa JE, De Graeff PA, Haaijer-Ruskamp FM, Mol PGM. Impact of safety-related regulatory action on drug use in ambulatory care in the Netherlands. Clin Pharmacol Ther. 2012;91(5):838–45.PubMedCrossRefGoogle Scholar
  6. 6.
    Ruiter R, Visser LE, van Herk-Sukel MP, Geelhoed-Duijvestijn PH, de Bie S, Straus SM, et al. Prescribing of rosiglitazone and pioglitazone following safety signals: analysis of trends in dispensing patterns in the Netherlands from 1998 to 2008. Drug Saf. 2012;35(6):471–80.PubMedCrossRefGoogle Scholar
  7. 7.
    Carracedo-Martínez E, Pia-Morandeira A, Figueiras A. Impact of a health safety warning and prior authorisation on the use of piroxicam: a time-series study. Pharmacoepidemiol Drug Saf. 2012;21(3):281–4.PubMedCrossRefGoogle Scholar
  8. 8.
    Dorsey ER, Rabbani A, Gallagher SA, Conti RM, Alexander GC. Impact of FDA black box advisory on antipsychotic medication use. Arch Intern Med. 2010;170(1):96–103.PubMedCrossRefGoogle Scholar
  9. 9.
    Kales HC, Zivin K, Kim HM, Valenstein M, Chiang C, Ignacio RV, et al. Trends in antipsychotic use in dementia 1999–2007. Arch Gen Psychiatry. 2011;86(2):190–7.CrossRefGoogle Scholar
  10. 10.
    Action Against Medical Accidents. Adding insult to injury: NHS failure to implement patient safety alerts. 2010. Accessed 28 May 2012.
  11. 11.
    Dusetzina SB, Higashi AS, Dorsey ER, Conti R, Huskamp HA, Zhu S, et al. Impact of FDA drug risk communications on health care utilization and health behaviors: a systematic review. Med Care. 2012;50(6):466–78.PubMedCrossRefGoogle Scholar
  12. 12.
    Medicines and Healthcare products Regulatory Agency. Clopidogrel and proton pump inhibitors: interaction. 2009. Accessed 10 Mar 2012.
  13. 13.
    Medicines and Healthcare products Regulatory Agency. Conventional (typical) antipsychotics: increased mortality in dementia. 2008. Accessed 7 Mar 2012.
  14. 14.
    O’Donoghue ML, Braunwald E, Antman EM, Murphy SA, Bates ER, Rozenman Y, et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Lancet. 2009;374(9694):989–97.PubMedCrossRefGoogle Scholar
  15. 15.
    Rassen JA, Choudhry NK, Avorn J, Schneeweiss S. Cardiovascular outcomes and mortality in patients using clopidogrel with proton pump inhibitors after percutaneous coronary intervention or acute coronary syndrome. Circulation. 2009;120(23):2322–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Charlot M, Ahlehoff O, Norgaard ML, Jørgensen CH, Sørensen R, Abildstrøm SZ, et al. Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study. Ann Intern Med. 2010;153(6):378–86.PubMedCrossRefGoogle Scholar
  17. 17.
    Tentzeris I, Jarai R, Farhan S, Brozovic I, Smetana P, Geppert A, et al. Impact of concomitant treatment with proton pump inhibitors and clopidogrel on clinical outcome in patients after coronary stent implantation. Thromb Haemost. 2010;104(6):1211–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Douglas IJ, Evans SJW, Hingorani AD, Grosso AM, Timmis A, Hemingway H, et al. Clopidogrel and interaction with proton pump inhibitors: comparison between cohort and within person study designs. BMJ. 2012;10(345):e4388.CrossRefGoogle Scholar
  19. 19.
    Neubauer H, Engelhardt A, Kruger JC, Lask S, Borgel J, Mugge A, et al. Pantoprazole does not influence the antiplatelet effect of clopidogrel-a whole blood aggregometry study after coronary stenting. J Cardiovasc Pharmacol. 2010;56(1):91–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Zuern CS, Geisler T, Lutilsky N, Winter S, Schwab M, Gawaz M. Effect of comedication with proton pump inhibitors (PPIs) on post-interventional residual platelet aggregation in patients undergoing coronary stenting treated by dual antiplatelet therapy. Thromb Res. 2010;125(2):e51–4.PubMedCrossRefGoogle Scholar
  21. 21.
    Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009;180(7):713–8.PubMedGoogle Scholar
  22. 22.
    Pezalla E, Day D, Pulliadath I. Initial assessment of clinical impact of a drug interaction between clopidogrel and proton pump inhibitors. J Am Coll Cardiol. 2008;52(12):1038–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Gilard M, Arnaud B, Cornily J-C, Le Gal G, Lacut K, Le Calvez G, et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol. 2008;51(3):256–60.PubMedCrossRefGoogle Scholar
  24. 24.
    Yasuda H, Yamada T, Sawada S, Endo Y, Inoue K, Takeyama Y, et al. Upper gastrointestinal bleeding in patients receiving dual antiplatelet therapy after coronary stenting. Intern Med. 2009;48(19):1725–30.PubMedCrossRefGoogle Scholar
  25. 25.
    Ho PM, Maddox TM, Wang L, Fihn SD, Jesse RL, Peterson ED, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA. 2009;301(9):937–44.PubMedCrossRefGoogle Scholar
  26. 26.
    Ray WA, Murray KT, Griffin MR, Chung CP, Smalley WE, Hall K, et al. Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study. Ann Intern Med. 2010;152(6):337–45.PubMedCrossRefGoogle Scholar
  27. 27.
    Medicines and Healthcare products Regulatory Agency. Clopidogrel and proton pump inhibitors: interaction–updated advice. 2010. Accessed 7 May 2012.
  28. 28.
    Nightingale PG, Adu D, Richards NT, Peters M. Implementation of rules based computerised bedside prescribing and administration: intervention study. BMJ. 2000;320(7237):750–3.PubMedCrossRefGoogle Scholar
  29. 29.
    Lankshear A, Lowson K, Weingart SN. An assessment of the quality and impact of NPSA medication safety outputs issued to the NHS in England and Wales. BMJ Qual Saf. 2011;20(4):360–5.PubMedCrossRefGoogle Scholar
  30. 30.
    Chief Medical Officer. Safety first: a report for patients, clinicians and managers. London: Department of Health; 2006.Google Scholar
  31. 31.
    Wagner AK, Soumerai SB, Zhang F. Segmented regression analysis of interrupted time series studies in medication use research. J Clin Pharm Ther. 2002;27:299–309.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Sarah K. Thomas
    • 1
    • 2
  • James Hodson
    • 1
    • 2
  • Graham McIlroy
    • 1
  • Annjeet Dhami
    • 1
  • Jamie J. Coleman
    • 1
    • 2
  1. 1.The Medical School, College of Medical and Dental SciencesUniversity of BirminghamBirminghamUK
  2. 2.University Hospitals Birmingham NHS Foundation TrustBirminghamUK

Personalised recommendations