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Risk Communication in a Pharmacovigilance Environment

      Communication, in particular risk communication in the pharmaceutical realm, is the theme for this Specialty Update on pharmacovigilance. This is an underappreciated, yet critical frontier: Who communicates, what is communicated, to whom, how it is received and acted upon, and the degree to which it results in changes in behavioral outcomes. So many of our misunderstandings, missed opportunities, and disasters across the span of business, academic, and political sectors come back to failures in executing on this critical discipline. Whether it is a reflection of a lack of interest, weakness in understanding, poor planning, or something else, it is also an opportunity to shine a light on this topic and make progress.

      Papers in this Specialty Update

      There are 4 papers in this month’s special section. The first paper is a brief report by Winter et al.
      • Winter J.
      • Reetz M.
      • Kerns J.W.
      • et al.
      Changes in asthma maintenance therapy following the 2006 long-acting beta-agonist FDA drug warning.
      that examines the effect of the significant effort by the Food and Drug Administration (FDA) to notify the practicing community about the increased risk of death associated with the use of long-acting β-agonists in the treatment of asthma in adults. Although this episode occurred more than 10 years ago, there has been little subsequent evidence published on the effect of FDA’s public notice on the use of long-acting β-agonists, and even less on the impact on patient outcomes. FDA has an active Risk Communication Advisory Committee, and has published an outstanding user’s guide on the topic.

      Food and Drug Administration. Communicating Risks and Benefits: An Evidence-Based User׳s Guide. http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/ucm268078.htm. Updated July 2, 2015. Accessed February 4, 2017.

      The European Medicines Agency has similarly developed guidance in this arena.

      European Medicines Agency. Benefit-risk communication to medicines users. http://www.ema.europa.eu/docs/en_GB/document_library/Report/2014/12/WC500178511.pdf. Accessed February 1, 2017.

      In fact, regulatory structures of many other industries have also developed guidance or best-practice documents.

      Nuclear Regulatory Commission. Effective risk communication. https://www.nrc.gov/docs/ML0406/ML040690412.pdf. Accessed February 1, 2017.

      World Health Organization. Communication for Behavioral Impact. http://apps.who.int/iris/bitstream/10665/75170/1/WHO_HSE_GCR_2012.13_eng.pdf?ua=1. Accessed February 4, 2017.

      Department of Homeland Security
      Yet, evidence on the outcomes of these efforts is thin. There are significant opportunities to develop and validate methods to assess the effectiveness of risk communication.
      In the second paper, Haque et al.
      • Haque A.
      • Daniel S.
      • Maxwell T.
      • Boerstoel M.
      Post marketing safety surveillance studies – an industry perspective on the changing global requirements and implications.
      review the regulatory shifts in expectations for safety surveillance in 5 countries, with a focus on evolving strategies for post-approval determination of continued favorability of the benefit-risk balance. From their description, there is little congruence among these countries. What will be important in the long term is the development of structures and methods to evaluate and report the outcomes of these efforts.
      In the third article, Varallo et al.
      • Varallo F.R.
      • Hernandez C.
      • Nadai T.R.
      • et al.
      Confounding variables and the performance of triggers in detecting unreported adverse drug reactions.
      document the role of triggers in enhancing detection of adverse drug reactions over and above spontaneous reporting rates in a public general hospital environment in Portugal. Like the use of checklists to reduce the risk of errors when conducting frequently performed processes, such as in hospital operating theaters, triggers serve as checklist reminders for identifying the most frequently reported or most highly suspect adverse events in an intensely busy, highly controlled, and highly regulated environment.
      Finally, I have authored a paper on the issues at the interface of pharmacovigilance and manufacturing.
      • Beninger P.
      Opportunities for Collaboration at the Interface of Pharmacovigilance and Manufacturing.
      Beyond the core pharmacovigilance disciplines of case management, signal management, and benefit-risk management, there is the relationship, or “interface” as I have chosen to call it, between pharmacovigilance and each of the other internal customers of a pharmaceutical research and development enterprise. Clinical development and regulatory affairs have been historically the closest relationships to pharmacovigilance, and medical affairs is fast becoming a tight relationship, as many large pharmaceutical companies tie pharmacovigilance and medical affairs into the same organizational structure and have them report to the Chief Medical Officer.
      Pharmacovigilance’s relationship with manufacturing is usually significantly lower on the radar; however, as I describe, a case can be made for much common ground and convergence of important activities between the 2 disciplines. An assessment of the literature shows that the percent of papers that share the terms pharmacovigilance and manufacturing in the title is in the single digits relative to the numbers of papers published in either discipline alone. This suggests that there is significant opportunity to share philosophies, perspectives, and methodologies between the 2 organizational entities. I have suggested trending, or control charting, as one of those manufacturing methodologies that pharmacovigilance can learn and apply to signal management.

      Risk Communication

      Returning to the theme of this special section, one view of risk management consists of 4 specific tasks: risk identification, risk assessment, risk mitigation, and risk communication. Risk communication is the most difficult of the 4 elements to manage, because, unlike the first 3 tasks, which are largely driven by individuals on one side of the dynamic, risk communication is most heavily dependent on active, bilateral human interaction to be effective, which takes extensive training and experience to execute well.
      Risk communication has gained academic traction in cross-disciplinary fields. Description of case studies has been a standard approach for gleaning lessons learned in many fields.

      Kelay T, Fife-Schaw C, Chenoweth J. Effective Risk Communication: A Guide to Best Practice. https://www.techneau.org/fileadmin/files/Publications/Publications/Deliverables/D6.3.1-2.report.pdf. Accessed February 4, 2017.

      Theoretical approaches include some version of (1) the Risk = Probability × Consequences model
      • Sondalini M.
      Industrial and manufacturing wellness.
      and (2) the Risk = Hazard + Outrage model developed by Sandman.

      Sandman P. http://www.psandman.com/. Accessed February 10, 2017.

      The first model uses a matrix of a range of probabilities (eg, 1 low, 2 medium, and 3 high) versus a range of consequences (eg, 1 mild, 2 moderate, and 3 severe). The resulting 9-box scheme allows the responsible party to focus efforts (eg, available resources) on the issues of highest risk. This scheme works well for manufacturing-related activities.
      The second model, developed by Sandman,

      Sandman P. http://www.psandman.com/. Accessed February 10, 2017.

      expands the definition of risk from a solely mathematically calculable event (Hazard), a focus that is primarily favored by professionals who are experts in scientific or engineering fields, to include the psychosocial context (Outrage) of the event, which is generally experienced and emphasized by the public. How the Risk = Hazard + Outrage model could enhance risk communication in pharmacovigilance is a potentially fruitful area for future research.
      The implications for pharmacovigilance are substantial for both the individual pharmacovigilance professional and for the industry. The individual global pharmacovigilance physician of the future, and increasingly of the present, is likely to require expertise in an expanding range of disciplines: quantitative skills that encompass probability, statistics, and quality; and written and spoken communication skills, including negotiation and crisis management. The industry is likely to come under increasing pressure to support the broader training base, and eventually to expect credentialing of physicians in these disciplines in order to be employed in pharmacovigilance departments and to benefit from greater career opportunities. The European Programme in Pharmacovigilance and Pharmacoepidemiology

      European programme in Pharmacovigilance and Pharmacoepidemiology. https://www.eu2p.org/. Accessed 2017.

      may be a model for how this can be accomplished.
      I welcome reflections on your experiences and insights, and I ask that you consider Clinical Therapeutics as a forum for your future research endeavors.

      References

        • Winter J.
        • Reetz M.
        • Kerns J.W.
        • et al.
        Changes in asthma maintenance therapy following the 2006 long-acting beta-agonist FDA drug warning.
        Clin Ther. 2017; 39: 697-701
      1. Food and Drug Administration. Communicating Risks and Benefits: An Evidence-Based User׳s Guide. http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/ucm268078.htm. Updated July 2, 2015. Accessed February 4, 2017.

      2. European Medicines Agency. Benefit-risk communication to medicines users. http://www.ema.europa.eu/docs/en_GB/document_library/Report/2014/12/WC500178511.pdf. Accessed February 1, 2017.

      3. Nuclear Regulatory Commission. Effective risk communication. https://www.nrc.gov/docs/ML0406/ML040690412.pdf. Accessed February 1, 2017.

      4. World Health Organization. Communication for Behavioral Impact. http://apps.who.int/iris/bitstream/10665/75170/1/WHO_HSE_GCR_2012.13_eng.pdf?ua=1. Accessed February 4, 2017.

        • Department of Homeland Security
        Understanding Risk Communication Best Practices: A Guide for Emergency Managers and Communicators Report to Human Factors/Behavioral Sciences Division, Science and Technology Directorate, US Department of Homeland Security. 2012; (Accessed February 1, 2017)
        • Haque A.
        • Daniel S.
        • Maxwell T.
        • Boerstoel M.
        Post marketing safety surveillance studies – an industry perspective on the changing global requirements and implications.
        Clin Ther. 2017; 39: 675-685
        • Varallo F.R.
        • Hernandez C.
        • Nadai T.R.
        • et al.
        Confounding variables and the performance of triggers in detecting unreported adverse drug reactions.
        Clin Ther. 2017; 39: 686-696
        • Beninger P.
        Opportunities for Collaboration at the Interface of Pharmacovigilance and Manufacturing.
        Clin Ther. 2017; 39: 702-712
      5. Kelay T, Fife-Schaw C, Chenoweth J. Effective Risk Communication: A Guide to Best Practice. https://www.techneau.org/fileadmin/files/Publications/Publications/Deliverables/D6.3.1-2.report.pdf. Accessed February 4, 2017.

        • Sondalini M.
        Industrial and manufacturing wellness.
        Industrial Press, Inc, South Norwalk, CT2016: 69-70
      6. Sandman P. http://www.psandman.com/. Accessed February 10, 2017.

      7. European programme in Pharmacovigilance and Pharmacoepidemiology. https://www.eu2p.org/. Accessed 2017.