Application of Real-Time Global Media Monitoring and 'Derived Questions' for Enhancing Communication by Regulatory Bodies: The Case of Human Papillomavirus Vaccines

"[M]edicine safety and public trust into underlying surveillance systems could benefit from listening more systematically to the public, identifying and challenging misleading or missing information and addressing what different population groups may want and need to know for making informed choices and using medicines safely and effectively."

The benefit-risk balance of vaccines is regularly debated by the public, but the utility of media monitoring for regulatory bodies is unclear. To explore this, a media monitoring study was conducted at the European Medicines Agency (EMA) concerning human papillomavirus (HPV) vaccines during a European Union (EU) referral procedure assessing the potential causality of complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS) reported to the authorities as suspected adverse reactions.

As the authors of this paper explain, media attention to vaccine issues may increase in cases of information on a new vaccine, an epidemic of a virus for which there is not yet a vaccine, or the occurrence of a new vaccine-related concern. Regulatory bodies may be put in the spotlight, as they are in charge of vaccines licensure, safety surveillance, continuous benefit-risk assessment and, if needed, risk minimisation or other regulatory action. They also need to inform the public about the outcome of their assessments and provide advice on safe and effective use of vaccines. Listening is described here as a fundamental element of a communication model that envisions communication as integrating with vaccine safety assessment and trust-building strategies. Listening mechanisms available to regulatory bodies include directly interacting with members of the public (e.g., through working groups, public hearings, information contact points), conducting or reviewing research (e.g., surveys), and media monitoring. The latter is the focus of the present research.

When in July 2015 a EU referral procedure was initiated for HPV vaccines, the EMA decided, given frequent media debates about vaccines, to conduct and evaluate medicinal product-specific media monitoring to support preparations for communicating with the public about the assessment and outcome of the referral procedure. The assessment of HPV vaccines was considered a specifically important test case for media monitoring, as a public debate with a wide range of topics about these vaccines had already accompanied their licensure and launch in 2006. Cases of CRPS and POTS symptoms occurring after HPV vaccination had been reported to the authorities. The assessment was carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the EMA's scientific committee responsible for monitoring and assessing safety issues for human medicines in the EU and providing recommendations for risk minimisation or other regulatory action as necessary.

To evaluate the utility of media monitoring in real life, prospective real-time monitoring of worldwide online news was conducted from September to December 2015 with inductive content analysis, generating "derived questions". With this approach, concerns, information needs, and expectations towards regulatory bodies that have been discussed in the public domain explicitly, implied, raised due to a lack of knowledge, or anticipated to be raised once more information has been published, have been expressed in the form of specific questions in scientific language and with reference to regulatory policies and procedures. Examples of derived questions include: "What is the knowledge on the benefit and effectiveness of HPV vaccines?" and "What is the likely magnitude of underreporting?" Question formats are familiar to those in the scientific-regulatory domain and seemed to be an effective way to provide feedback from the public domain to those in charge of assessing medicines or defining messages on assessment outcomes.

A cumulative review of the weekly media content analyses was performed by one of the researchers in the month prior to the scheduled finalisation of the PRAC assessment for supporting the preparations of the communication for the EU referral outcome. Specifically, 4,230 news items (3,737 news stories and 493 blog posts) originating from 2,124 media outlets were identified, containing personal stories and scientific and policy/process-related topics. Identified concerns, information needs, and expectations of the public were used to derive questions from the media content. Explicit and implicit concerns were identified, including those raised due to lack of knowledge or anticipated once more information would be published. The 50 derived questions were generated and categorised into 12 themes. The evaluation was performed through the validation of the predictive capacity of these questions against journalists' queries, review of the EMA's public statement, and feedback from EU regulators.

The media content analysis (after applying the inclusion criteria) identified patterns over time: While many debates remained nationally contained, some topics "travelled", in particular between Scandinavian countries and those countries with active parents' groups, such as Demark, Ireland, and the United Kingdom (UK). There was also a change in focus; in particular in Denmark, the debate moved from presenting personal stories to additionally including scientific and policy-related points. There were increasingly references to scientific publications on safety aspects, and overall the debate turned from questioning vaccine safety as such to doubting the trustworthiness of the data, the pharmaceutical industry as a data source, and the integrity of the regulatory and other public health bodies in collecting and assessing data. Some debates claimed that the EMA and its scientific committees do not exercise separation between pre- and post-authorisation decision-making and rely on data provided by industry rather than requiring data from independent sources. This led to including in the respective weekly considerations for communication preparations that regulatory bodies should be prepared to answer in detail how they ensure the legally demanded independence of their work and manage potential conflicts of interests and how the pharmaceutical industry is inspected for their compliance with legal requirements.

In addition to the theme categorisation and identifying patterns of flow and focus over time, the media content analysis allowed for an understanding of some of the motivations and expectations of parents. The parents who expressed their opinions in the media considered the information they had received on vaccine risks in general as insufficient. Parents who suspected that their daughters had been harmed by HPV vaccination mainly wanted to provide case information to the authorities, obtain support and treatment within the governmental health insurance, and remedy the lack of respect their daughters feel that they experience in relation to their condition. Some also requested ending the HPV vaccination programme or wanted other parents to be provided with information about the ongoing EU referral review prior to giving an informed consent to vaccination. Giving special attention to respectfully acknowledging the health status of the patients, regardless of what the outcome of the EU referral would be, was therefore added to the considerations for preparing communication.

The users of the media monitoring results were the EMA communication department, the PRAC, and the EU member states. Through the media monitoring, the media office of the EMA communication department became aware of emerging issues which needed attention. The weekly media monitoring reports and the derived questions were circulated within the EMA and to the PRAC. The medical writers of the EMA communication department stated that they were guided by the derived questions as to which information items from the assessment to include proactively in the summary of PRAC recommendations, i.e., the public statement on the PRAC outcome for website publication and dissemination to the EU regulatory network, its international partners, relevant patient and healthcare professional organisations, and journalists. The derived questions guided these colleagues further as to which information to include in the talking points, prepared for the EMA itself as well as for the authorities in EU member states, to enable prompt provision of accurate and consistent information in response to external requests, including those from journalists. The talking points were also used by senior EMA colleagues to prepare for attending a discussion on HPV vaccines at the Danish parliament in December 2015. The identification of the pattern of the public debate becoming increasingly focused on scientific and policy-related points, particularly in Denmark, was considered to be especially helpful for these preparations. In short, providing the media monitoring findings to assessors and communicators resulted in: (1) confirming that public concerns regarding CRPS and POTS would be covered by the assessment; (2) meeting specific information needs proactively in the public statement; (3) predicting all queries from journalists, although in some instances the level of detail of the questions was not anticipated; and (4) altering the tone of the public statement reflective of the fact that the evaluation identified words intended to express commitment and diligence towards patients with CRPS and POTS and to acknowledge the seriousness of what they were experiencing.

The study demonstrated the potential utility of media monitoring for regulatory bodies to support communication proactivity and preparedness, intended to support trusted safe and effective vaccine use. Derived questions seem to be a familiar and effective format for presenting media monitoring results in the scientific-regulatory environment. It is suggested that media monitoring could form part of regular surveillance for medicines of high public interest. Future work is recommended to develop efficient monitoring strategies for that purpose. Further evaluation could include studying how the outcome of the EU referral procedure on HPV vaccines was reported in the news and social media, whether public concerns persisted and were discussed in the light of the assessment by PRAC, or whether journalists felt satisfied by the information published by the EMA in terms of scope, format, and language. Correlations between information from regulatory bodies, media coverage and vaccination rates among the population could establish the impact of communication by regulatory bodies on medicines use behaviours.

The following principles and actions on communication are recommended in general for any stakeholder assessing vaccines (e.g., regulatory and public health authorities, industry, or academia) and for Accelerated Development of VAccine benefit-risk Collaboration in Europe (ADVANCE) in particular:

• Efficient media monitoring should be built into the process of vaccine benefit-risk monitoring, and benefit-risk assessment should ensure the provision of responses to all safety concerns, including those debated in the public domain.
• Explanations on methods for benefit-risk monitoring and assessment should be provided in a language understandable to the public, and should be developed and ideally be tested with a view to explaining how the method works and how robust the results are.
• Given that conflicts of interests are a major concern voiced by the public, procedures to ensure unbiased monitoring and assessment as well as, if applicable, the mechanisms of public-private partnership (PPP) governance models (as envisaged by ADVANCE as one option for a future platform for vaccine benefit-risk monitoring) need to be proactively communicated to the public.