Risk Analysis, Vol. 35, No. 7, 2015

DOI: 10.1111/risa.12386

Transparency in Europe: A Quantitative Study 2 ¨ Frederic Bouder,1,∗ Dominic Way,2 Ragnar Lofstedt, and Darrick Evensen3

In recent years, European pharmaceutical regulators have increasingly committed to heightening access to raw safety-related data as part of a wave of transparency initiatives (e.g., providing public Internet-mediated access to clinical trials data). Yet, the regulators—who are under significant pressure—have not yet benefited from a systematic review of this new policy. In seeking to inject much needed evidence, this article explores the effects of new transparency policies designed to promote meaningful communication of risks and benefits to patients. Results of a cross-national European survey with respondents from Great Britain, the Netherlands, Spain, France, Germany, and Sweden (N = 5,648) shed light on how patients and the public are likely to react to the regulators’ new transparency policies. The findings demonstrate clear national variations in how European citizens are likely to react and emphasize the need to develop evidence-based, reasoned transparency policies that integrate benefit-risk communication. The authors conclude by providing six specific recommendations, informed by the study, that seek to improve the European transparency model both within the medical field and across health, safety, and environmental policy domains. KEY WORDS: Cross-national; decisionmaking; Europe; pharmaceuticals; risk communication; transparency

1. INTRODUCTION

style” of decisionmaking, to a new “participatorytransparent” model, which has been accompanied by wider stakeholder participation, a greater emphasis on social and environmental values, and, of particular interest to this study, a trend toward enhanc¨ ing “transparency” (see Lofstedt and Bouder(4) for (1,5–9) a discussion). There is ample evidence that trust—or the lack of it—has been a key driver of this changing policy environment.(4,10–12) In particular, a broadening view recognizes that the traditional elitist and expert-based model is antiquated and no longer able to maintain trust in regulators and industry. This has been reinforced by the belief in the legitimate right to know about the full background of regulatory decisionmaking.(13,14) Although several contributing factors can be identified (e.g., the rise of 24-hour media and the Internet), the impact of drug withdrawals on regulatory discussions and public opinion has offered evidence that the old “consensual style” system no longer works in the medical

Over the past 20 years, the European pharmaceutical regulatory environment has changed profoundly. Similar to other policy domains related to health, the environment, and safety, pharmaceutical regulators at both the EU and national level have become firmly engaged in a more transparent and open model of regulation that ensures greater access to data (e.g., on clinical trials and regulatory decisionmaking) and tackles conflicts of interest.(1–4) Some researchers have described the emergence of “transparency” as part of a shift from an old “consensual 1 Department of Technology and Society Studies, Grote Gracht 76,

6211 SZ, Maastricht, The Netherlands. College London, King’s Centre for Risk Management, Strand London, WC2R 2LS. 3 Oberlin College and Conservatory, A.J. Lewis Center for Environmental Studies, 122 Elm Street, Oberlin, OH, USA. ∗ Address correspondence to Frederic Bouder, Department of Technology and Society Studies, Grote Gracht 76, 6211 SZ Maastricht, The Netherlands; [email protected]. 2 King’s

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C 2015 Society for Risk Analysis 0272-4332/15/0100-1210$22.00/1 

Transparency in Europe field.(13,15) Indeed, often even a single word, such as Thalidomide, Avandia, Vioxx, or Mediator,(16–18) can evoke feelings of distrust and scandal, with some researchers directly linking the Avandia and Cox-2 inhibitor controversies (Vioxx) to calls for transparency.(4,14) Other factors also stand out more in the pharmaceutical sector than in other policy domains, including claims that companies pay too much attention to large profits and marketing rather than to research and development.(16,19–22) In order to demonstrate commitment to the new model, regulatory bodies on both sides of the Atlantic (e.g., the European Medicines Agency [EMA] and the U.S. Food and Drug Administration [FDA]) have agreed to new legislative as well as policy initiatives that set forth increasingly greater public access to data (e.g., safety-related documents) while also actively attempting to tackle conflicts of interest.(23–25) A variety of so-called transparency strategies have been adopted at the European Union (EU) and national level (e.g., Directive 2010/84/EU),(25–27) including:

r Maintaining dedicated web portals to, for examr r r r r r r

ple, provide public access to safety-related data on adverse drug reactions. Publishing recommendations from safety assessments (e.g., periodic safety update reports), lay summaries of risk management plans, and lists of medicinal products being monitored. Introducing public hearings. Establishing a new safety assessment and monitoring committee (i.e., the pharmacovigilance4 risk assessment committee [PRAC]). Disclosing committee meeting agendas and minutes (e.g., from the committee for medicinal products for human use and PRAC). Opening up the regulatory procedure from the beginning by introducing more transparency on urgent safety reviews (including lists of questions, timetables, etc.). Setting up public workshops such as the EMA’s public consultation on transparency that took place in November 2012 and further 2013 and 2014 follow-up consultations. Proposals to proactively release safety-related data.

1211 The regulators argue that these transparency initiatives can achieve many specific objectives and not least the highly desired goal of building trust in national and international pharmaceutical regulatory bodies.(28–30) For instance, the EMA5 published its “transparency policy draft for public consultation” in 2009 and made clear that “transparency is a pivotal element in building trust and confidence in the Agency’s operations” (p. 1).(28) Both policymakers and academics broadly agree that transparency has much potential for the greater good(4) (although see O’Neill).(10) If well managed, it may improve the communication of benefits and risks. Transparency helps to spread knowledge and there is little doubt that it is of fundamental importance from democratic and efficiency perspectives: transparency reassures citizens about the fair and democratic nature of decisionmaking; it consolidates rather than weakens the regulators’ position, as it is received positively by citizens(31–34) (although see Etzioni).(35) However, although both national- and European-level pharmaceutical regulators have enacted a wave of policies that seek to enhance transparency, there has been very little evidence to inform the current debate.(4,36) In particular, no one currently knows whether the types of transparency policy being developed by regulators will achieve its desired goals. Neither the regulators, who have come under increasing pressure, nor the politicians, who are strongly pushing through transparency legislation, have conducted a much needed evidencedbased systematic review.(36) After all, as Heald(37) puts it: different varieties of transparency will have differential effects on the achievement of public policy outcomes. (p. 30)

One area that has received little critical examination centers on the implications of the regulators’ transparency policies for European citizens and patients. In exploring this surprisingly understudied area and injecting much needed evidence into the wider transparency debate, this article explores one central question: What does access to more information (through transparency policies) imply for European pharmaceutical regulators in terms of communicating benefits and risks to patients in a meaningful way?

4 The

World Health Organization defines pharmacovigilance as “the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.”

5 “The

decentralized [EU] agency responsible for the scientific evaluation of [certain] medicines developed by pharmaceutical companies.”

1212 In Europe this fundamental question needs urgent answers as European pharmaceutical regulators are busy implementing major changes from the 2010 pharmacovigilance legislation package (Directive 2010/84/EU). In particular, national-level agencies will be at the front line in implementing transparency initiatives, yet little is known about the impact of the new policies in national settings and especially on patient behavior. In exploring the research question, this article presents the results of a 2013 European survey with a total of 5,648 respondents from six European countries (see Section 4) and that complements the results of an earlier U.S. study conducted by two of the authors in 2011.(38) Specifically, the article conveys preliminary results about how citizens and patients in different European countries are likely to react to the regulators’ transparency initiatives.

2. APPLYING TRANSPARENCY RESEARCH The topic of transparency has received burgeoning academic attention in recent years, resulting in theoretical and increasingly empirical advances.(4,12,35,39,42) Although the modern rhetoric of “transparency” might suggest the term (and concept) is new, several scholars have demonstrated that transparency can be traced back to at least the Enlightenment and especially the writings of Jeremy Bentham.(11,43,44) However, the term “transparency” continues to be defined with little rigor partly because it is used in such a wide variety of issue areas.(4,39) Although debate remains about “what is transparency exactly?”, it is broadly interpreted to “entail conducting affairs in the open or subject to public scrutiny,”(45) or simply being honest.(46) [Transparency] is contrasted with opaque policy measures, where it is hard to discover who takes the decisions, what they are, and who gains and who loses.(46)

A major scholarly advance has involved exploring the multidimensionality of the concept and, notably, the development of various types or varieties of transparency.(37,43,47) In particular, drawing on work by Coglianese,(23) it is possible to distinguish between fishbowl transparency, broadly defined as “the full disclosure of information without explanatory information or contextualization,” and a more reasoned form, which accepts that transparency as information disclosure alone is not a panacea.(4) Fishbowl transparency might include policies such as posting meeting minutes online (e.g., from scientific

Bouder et al. evaluation committees) or publishing safety-related documents (e.g., clinical trial reports or pollution data). The central aim is to “expand the release of information” that can document how regulators or government officials, for instance, come to their risk-related decisions.(23) Information may, in turn, be used by those wishing to (re)analyze data and thus scrutinize regulatory decisions/opinions.(23) In comparison, reasoned transparency policies demand that regulators or government officials “offer explicit explanations for their actions” and, for instance, provide concise, understandable communications such as why a course of action was taken (e.g., in approving a drug or banning a new technology).(23) For instance, releasing thousands of pages of data on the safety of a medicine that might be useful for external “expert” scrutiny (i.e., fishbowl transparency) clearly presents a very different type of transparency to providing concise and well thought through explanations that can be readily digested by the general public or critics (i.e., reasoned transparency). Although both fishbowl and reasoned transparency policies can coexist,(23) theoretical and empirical research has shown how there can be critical unintended or counterintuitive consequences of past “fishbowl” policies.(35–39) These have ranged from how policies can expose the public to how politicians apparently “muddle” and “bicker” through the decision-making process to the public becoming disenchanted with decisionmaking altogether.(42,48,49) Research has also shown how transparency measures can have negative and limited effects on trust (e.g., eroding rather than building trust).(10–12,42) A key contribution from Baroness Onora O’Neill(10,11) explains that demands to enhance transparency can often dazzle decisionmakers, especially with the rise of the Internet and the modern information society,(50) which provides a cheap and easy method of releasing more data into the public domain than ever before. O’Neill(11) argues further that transparency has captivated thinking away from the centuries old requirement of communicating effectively: Transparency mandates disclosure or dissemination, but does not require effective communication with any audience. An emphasis on transparency encourages us to think of information as detachable from communication, and of informing as a process of “transferring” content . . . .” (p. 81)

Yet, despite recent theoretical and increasingly empirical advances, the transparency topic has received surprisingly little critical examination not

Transparency in Europe least from risk scholars. The authors of this study have therefore previously stressed that more studies focusing on regulatory policy do need to be developed both qualitatively and quantitatively to, for instance, test for trust or implications for risk communication.(4,36,38,51) In the medical field (and the focus of this article), only a few studies have critically engaged with the concept of transparency. In 2011, Chrakraborty (51) ¨ conducted two qualitative studies and Lofstedt that examined public perceptions, responses, and behavior toward the FDA 2011 transparency strategies. The study found that posting adverse event reporting signals online could increase public alarm and result in early or inappropriate termination of a medicine. ¨ In 2012, Lofstedt et al.(38) conducted a quantitative Internet survey of 433 physicians and 1,000 American adults and found that there is “significant disagreement between physicians and the public about when medical safety issues should be communicated in the first place” (p. 391). Furthermore, if the public found its medication on the FDA’s adverse event reporting system, then more than a quarter (26%) would stop taking the medicine.(38) Both studies concluded that strategies that do not treat transparency as a critical part of communicating about risks/benefits, side effects, and the safety of medicines are likely to have unintended and possibly even counterintuitive outcomes. However, this research still only represents a small corpus of U.S.-based work. There are many further questions that require much more critical and careful examination. In particular, although there has been research in the U.S. pharmaceutical policy area, there have been few studies exploring how the rise of transparency policies has played out in the European pharmaceutical context. 3. EUROPEAN PHARMACEUTICAL TRANSPARENCY LANDSCAPE European pharmaceutical transparency policies can arguably be traced back to 1995 and the establishment of the European Medicines Evaluation Agency (EMEA).6 The type of policies adopted by the new European regulator set out to build trust and confidence in the pharmaceutical system as well as show “the basis for opinions on how medicines should be used [including] detailed information on Agency scientific assessment work.”(52–54) Since the EMEA first developed what were once considered 6 Renamed

the European Medicines Agency (EMA) in 2004.

1213 innovative and novel policies,(54) regulators at both the national and European level (and increasingly industry) have overwhelmingly adopted transparency policies of the fishbowl variety.(5,33,55) Since 2010, transparency discussions have increasingly been dominated by the full public release of clinical trial data,(26) with some documents providing thousands of pages of safety-related medicine information including a “complete synthesis of the planning execution, and results of a clinical trial.”(56) This trend toward fishbowl types of transparency has been driven by distinct pressure from politicians (e.g., British MEP Glenis Willmott(57) ), academic journal editors,(58–60) and so-called sponsorindependent data miners.(56,61) These groups have provided important arguments as to why regulators and industry should provide greater access to data such as clinical trial reports.(3,4,62) These have ranged from benefits for the biopharmaceutical industry (e.g., reducing duplication effort among trial developers)(30) to ethical and scientific concerns,(63,64) as well as building trust in both national and international pharmaceutical regulatory agencies.(24,26) For example, at a stakeholder meeting, a senior EMA regulator stated that the main aim of the Agency’s new policies on access to documents is to “establish trust and confidence [and] enable independent reanalysis of the evidence used by the EMA scientific committees to determine the benefits and risks of medicines.”(65) Since 2010, this pressure on regulators has become increasingly heated and public. In particular, the Cochrane Collaboration, an international “sponsor-independent” health network that primarily conducts systematic medicine reviews, has been vocal about the need to lift the veil of secrecy, end cover ups, and provide direct access to raw data in order to, for example, reanalyze risk/benefit medicines data.(29,30,61,66) Cochrane has criticized regulators and pharmaceutical companies for not releasing “hidden” clinical trial studies.(67) In October 2007, Cochrane complained to the then European Ombudsman, P. Nikiforos Diamandouros, that the EMA had denied the organization access to documents related to the drugs orlistat and rimonabant, asserting that this was against the public’s interest.(68) The Ombudsman favored Cochrane’s position and recommended the agency disclose the documents as requested, concluding: the agency gave insufficient reasons for its refusal to grant access . . . patient’s welfare should be given priority over concerns for the commercial interests of the drug industry.”(68)

1214 British doctor and writer, Ben Goldacre, has also attacked regulators and industry over not releasing clinical trial data.(63) Spearheaded by the pop science book Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients,(63) Goldacre gathered widespread support in the form of an online petition (alltrials.com), which calls on governments, regulators, and research bodies to implement measures for “all clinical trials to be registered” and the “publication of [all] clinical trial results” whether or not they have positive or negative outcomes.(69) Pressure has also come from a wide variety of other sources.(2,19,70–72) Editors of the British Medical Journal (BMJ), the Lancet, and the Journal of American Medical Association, for instance, have supported full clinical trial data disclosure (and in some cases Cochrane directly), arguing that both regulators and industry must promise greater transparency. For example, Fiona Godlee, BMJ Editior-in-Chief, argues: The main reasons for sharing full clinical trial data are scientific and ethical, with the interests of prescribers and patients at their heart.(73)

Furthermore, Doshi et al.(56) have also been prominent in attacking regulators and industry in their quest to obtain fuller data on pharmaceutical company Hoffman-La Roche’s antiviral Tamiflu, bluntly summarizing in 2012: We challenge industry to either provide open access to clinical study reports or publicly defend their current position of RCT [randomized clinical trials] data secrecy. (p. 2)

In turn, this cumulative pressure caught the attention of both national- and EU-level politicians, who have focused on pressurizing industry and regulators to publish full clinical study reports such as on publicly accessible databases.(57,74) Most notably, in 2014 the Committee on Environment, Public Health, and Food Safety (ENVI) voted on proposed amendments to the 2001 clinical trials directive, the majority of which focus on fishbowl transparency measures (Directive 2001/20/EC).(75) Rapporteur and British MEP Glenis Willmott pushed for full clinical study reports to be published and made publicly available, arguing: A summary of the results is not enough. Summaries written by those that carried out the research can be biased, and make a medicine sound more successful than it really is. Independent researchers need access to the

Bouder et al. results of the trial in order to verify the sponsor’s claims.(57)

In reaction to growing pressures and legislative changes, regulators have increasingly committed to transparency and disclosing raw data, leading to, what might be described as a “tsunami” of fishbowl transparency initiatives.(25–28) A key turning point came at a November 2012 EMA workshop on clinical trial data and transparency where the EMA’s Senior Medical Director, Hans-Georg Eichler, announced that the agency would develop policies on the proactive publication of clinical trial data through setting up “balanced advisory groups” with representatives from the EMA (as a coordinator), patient groups, pharmaceutical industry representatives, research institutions, NGOs, health-care professionals, and academics.(66) As Guido Rasi, EMA Executive Director, announced: Today represents the first step in delivering our vision. We are not here to decide if we will publish clinical-trial data, only how. We need to do this in order to rebuild trust and confidence in the whole system.(66)

European pharmaceutical regulators have since increasingly committed to enhancing transparency. They have overwhelmingly adopted fishbowl types of transparency policy that involve releasing raw safety-related documents and making them publicly available (e.g., posting clinical trial reports online). The regulators’ policies as well as new legislative requirements have and will continue to result in much greater public access to safety-related medicine information, the majority of which was initially developed for expert analysis rather than public consumption. The data also contain uncertain medicines information, with regulators across the Atlantic having lengthy technical discussions about the benefits and risks of individual medicines. For example, at a 2014 Institute of Medicine meeting, FDA Center for Drug Evaluation and Research Director, Janet Woodcock, presented a range of sources of scientific uncertainty that require critical scientific “expert” debate including factors associated with “human biology, . . . the chemistry of the drug, and the research process.”(76) It is therefore of critical importance to understand how the public might react to receiving this information as well as what the regulators’ new fishbowl transparency policies might entail for communicating benefits and risks to patients in a meaningful way.

Transparency in Europe 4. METHOD

1215 Table I. Table Showing Response Rates Broken Down by Sample Countries

4.1. Survey Design In seeking to provide insights into how Europeans are likely to react to fishbowl transparency policies and the subsequent release of uncertain raw medicines data, the authors developed a survey examining the medicines attitudes and opinions of European citizens. To be clear, the survey does not seek to understand public opinions on transparency directly, including whether they are in favor of the regulators’ policies. Rather, the central aim is to understand whether respondents: (1) are aware of the regulators’ activities, (2) want more information on medicines, (3) want safety information before it has been verified scientifically, (4) believe their national governments and health services are effective in communicating about medicines, and to discover (5) how they might respond to more uncertain and complex safety-related medicine information entering the public domain. In turn, understanding the public’s pharmaceutical/medicines attitudes and opinions promises to provide insights into the potential impacts of fishbowl transparency policies. The survey instrument was initiated at Maastricht University and developed together with cognitive psychologists at Dialogik, Stuttgart University, and received informal input from medical experts. The survey contained 16 closed/open questions relating to respondents’ attitudes and opinions toward medicines information, pharmaceuticals, and healthcare. Several questions were modeled on a previous survey examining transparency issues in a U.S. context(38) to enable direct comparisons. For the purposes of this study, only nine questions that relate to the research question are analyzed and discussed, although results relating to other topic areas will be explored in subsequent papers. 4.2. Sample The sample contained a total of 5,648 respondents from Great Britain (GB; N = 1,014), Sweden (N = 1,051), the Netherlands (N = 1,010), Spain (N = 504), Germany (N = 1,008), and France (N = 1,061; see Appendix A). A U.K. polling agency, Ipsos MORI, was subcontracted to recruit respondents using an online panel survey. Respondents were recruited through the polling agency’s online system,

Germany Spain France Netherlands Sweden GB

Invites Sent

Response Rate (%)

5,948 5,363 14,116 11,281 13,395 9,489

15 17 16 24 22 12

which recruits through email lists, banners, website and text ads, co-registration, and search engine methods. The online panel survey also followed strict agency standards, including mechanisms to discourage professional respondents and continually refresh respondents between surveys. A breakdown of response rates per country can be viewed in Table I. The recruitment process also ensured a representative sample for age, gender, and geographic region through screening criteria and respondent profiling (Appendix A). Additional information on educational/professional qualifications, household income, and workings hours was also collected (Appendix A). More details on this process, including translations, can be obtained from the corresponding author on request.7

4.3. Analyzing the Results Respondents’ answers were collected and collated by Ipsos MORI and subsequently analyzed by the authors independently. Statistical analyses were carried out by the authors. This article will present, analyze, and discuss European-level results and national-level variations that most relate to this article’s research question. Further data, such as regional variations in each sample country, will be discussed in a subsequent paper. The key results relating to the research question are divided into six sections in the results and analysis section. The analysis primarily focused on descriptive statistics, including bar charts, pie charts, and tables, to visually display the data as well as significance tests where appropriate.

7 Further

technical information on the sample and recruitment (e.g., on nonprobability samples and representativeness) can also be found on Ipsos MORI’s website: https://www.ipsos-mori.com/

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Table II. Table Showing Respondents Answers to the Question: “Have You Heard of ANSM (France), Bfarm (Germany), AEMPS (Spain), CBG-MEB (Netherlands), MPS (Sweden), MHRA (Great Britain)?”

Yes (%) No (%) Don’t know (%) Sample size (N = 5,648)

Great Britain (MHRA)

Sweden (MPA)

Netherlands (CBG-MEB)

Spain (AEMPS)

Germany (Bfarm)

France (ANSM)

25a 64 11 1,014

67b 24 9 1,051

2c 94 4 1,010

7d 82 12 505

8d 80 12 1,008

15e 84 1 1,061

Note: All superscript letters that differ between nations denote a statistically significant difference (p < 0.05) in the percentage of respondents answering “yes” between those nations (determined by pair-wise comparisons in a generalized linear model with logit link, binomial distribution, and Bonferroni corrections for multiple comparisons).

5. RESULTS 5.1. Awareness of Regulators Respondents were asked whether they had heard of their national regulatory authority (e.g., the Medicines and Healthcare Products Regulatory Agency or “MHRA” in GB) and had to choose “yes,” “no,” or “don’t know” (Table II). The large majority of respondents from GB (64%), the Netherlands (94%), Spain (82%), Germany (80%), and France (84%) said they had not heard of their national authority (Table II). In contrast, only 24% of Swedish sample respondents said they had not heard of their national regulatory authority. 5.2. Popularity and Trustworthiness of Medicine Information Sources Respondents across sample countries were asked what sources of information they use for medicines information and had to choose all that apply from a predetermined list (which was randomized between respondents): “Where would you go in order to find out information about medicines and health alerts?” (Fig. 1). The two most popular options across sample countries were general practitioners (GPs; 64%) followed by pharmacies (52%; Fig. 1). In contrast, pharmaceutical companies (4%) and friends/relatives (who are not medically qualified; 4%) were two of the least popular choices. There were, however, sharp national-level variations, which are likely to account for different governance arrangements within the health-care system. For example, only 30% of respondents in Sweden chose GPs compared to 80% in France or 77% in the Netherlands. Furthermore, the most popular choice in GB was the Internet ˚ (61%) whereas Sweden’s “Sjukvardsupplysningen,”

a Swedish telephone hotline for health-care information, was the most popular (61%) in that nation. Respondents were then separately asked how trustworthy they feel the same predetermined list of information sources are in providing advice on the side effects associated with specific medicines (Fig. 1). They were asked to pick one option from a predetermined five-point Likert scale list for each source of information (Very trustworthy, Fairly trustworthy, Not very trustworthy, Not at all trustworthy, Don’t know; Fig. 1). The list was randomized between respondents and the previous information source question. Across sample countries, respondents said that GPs (85%) and pharmacies (83%) were either “very” or “fairly” trustworthy sources in providing advice on the side effects associated with specific medicines. In contrast, pharmaceutical companies (35%), the media (26%), and “another friend or relative (not medically qualified)” (16%) were either “very” or “fairly” trustworthy sources (Fig. 1). 5.3. Opinions on Effectiveness of Health-Care Services and Government Respondents were asked two questions regarding how effective they consider: (1) their national health-care services (e.g., NHS in GB) and (2) their national governments are in providing members of the general public with information on medicines (Figs. 2a and 2b). For example, in GB respondents were asked: “How effective do you consider the NHS are at providing members of the general public with information on medicines such as a health alert about a flu outbreak?” Respondents had to choose one answer for each question from a predetermined fivepoint Likert scale list (Very effective, Fairly effective, Not very effective, Not at all effective, Don’t Know; Figs. 2a and 2b).

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Fig. 1. Bar chart showing (a) where respondents across Europe (%; N = 5,648) would go to find information on medicines and health alerts. Respondents were asked the question “Where would you go to find information about medicines and health alerts?” and were asked to select all that applied from a (randomized) predetermined list. (b) Shows how trustworthy respondents (%; N = 5,648) felt the same predetermined list of sources of information are in providing them with advice about medicines. Specifically, respondents were asked: “How trustworthy do you feel the following sources are in providing you with advice about medicines?” The bar chart shows the percent of respondents that chose very or fairly for each source of information/advice for both questions.

Fig. 2. Bar charts showing respondents (%; N = 5,648) answers to the questions: (a) “How effective do you consider the NHS (or equivalent) are at providing members of the general public with information on medicines such as a health alert about a flu outbreak?” and (b) “How effective do you consider the government is at providing members of the general public with information on medicines such as a health alert about a flu outbreak?” Notes: Dark shading signifies very effective. Light shading signifies fairly effective. All superscript letters that differ between nations denote a statistically significant difference between those nations (p < 0.05) in the average effectiveness reported by respondents in those nations (determined by pair-wise comparisons in a generalized linear model with identity link, normal distribution, and Bonferroni corrections for multiple comparisons).

The results presented in Fig. 2(a) show that confidence in the effectiveness of national healthcare services across sample countries is moderate, with those saying “very effective” (dark shading) remaining below 10% in all countries, and the total of “very” and “fairly” effective only exceeding 50% in GB. The results presented in Fig. 2(b) show that

confidence in government is even lower—between 20% and 30%—in all countries except GB. 5.4. Public Desire for More Medicines Information Respondents were asked whether they felt that receiving more information on the safety of a

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Table III. Table Comparing National-Level Averages (%; N = 5,648) for the Question: “Do You Think that Receiving More Information on the Safety of a Medicine Would Increase Your Confidence in Taking Medicines?”

Yes (%) No (%) Don’t know (%) Sample size (N = 5,648)

Great Britain*

Sweden

Netherlands

Spain

Germany

France

72a,b 15 13 1,014

60a 16 25 1,051

64a,b 13 23 1,010

80b 12 8 505

65a 16 18 1,008

76a 18 6 1,061

superscript letters that differ between nations denote a statistically significant difference (p < 0.05) between those nations in the percentage of respondents answering “yes” (compared to those responding “no”; “don’t know” responses were excluded; determined by pair-wise comparisons in a generalized linear model with logit link, binomial distribution, and Bonferroni corrections for multiple comparisons).

a All

Table IV. Table Showing European-Level Mean Averages (%; N = 5,648) for the Question: “At What Stage Would You Like Information to be Conveyed to You About a Possible Safety Problem of a Medicine that You Use Or May Use?” When there is a possible sign of a safety problem When the problem has been investigated; not clear if related to the medicine When the problem has been investigated and pharmaceutical company believes it is related to the medicine When the problem has been investigated and the regulators believe it is related to the medicine Don’t know

58% 10% 11%

12% 8%

medicine would increase their confidence in taking medicines: “Do you think that receiving more information about the safety of a medicine would increase your confidence in taking medicines?” They had to choose one answer only: “yes,” “no,” or “don’t know” (Table III). Across sample countries, a mean average of 69% of all respondents said that more information about a possible safety problem would increase their confidence in taking medicines. Little national-level variation was found between sample countries and ranged from 60% of respondents in Sweden to 80% in Spain saying “yes,” receiving more information would increase confidence (Table III). Respondents were then asked at what stage in the scientific evaluation process they desired information on the safety of medicines and had to choose one answer from a predetermined (randomized) list (Table IV). A total of 58% of all respondents said they would like information on a possible safety problem to be conveyed to them “when there is a possible sign of

a safety problem” (Table IV; Fig. 3). In contrast, few respondents said they would prefer information to be conveyed to them “when the problem has been investigated” and (a) “it is not clear whether the problem is related to the medicine” (10%), (b) “the pharmaceutical company believes it is related to the medicine” (11%), or (c) “when regulators believe that the problem is associated with the medicine” (12%; Table IV; Fig. 3). Little variation was found at the national level (Fig. 3). Respondents were then asked a similar question: “At what stage do you think that members of the general public should be informed about a potential medical safety problem with a medicine?” and had to answer from three predetermined answers (Fig. 4). Similar responses were found, with 55% of all respondents saying that the general public should be informed “as soon as a potential medical safety problem has been identified and before a scientific analysis is complete to confirm whether or not there is a problem” (Fig. 4). In contrast, 38% of respondents said they think the general public should be informed about a problem “after a scientific analysis has been undertaken and has confirmed there is a problem” (Fig. 4). Little national variation was found and ranged from 53% of GB respondents to 61% of German respondents choosing option one (before a scientific analysis is complete). 5.5. Public Reactions to Medicines Information Pointing to Safety Problems The final question reported in this article sought to understand what course of action respondents from different nations are likely to take when receiving information that points to a safety problem with a medicine they were taking. Respondents were asked:

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Fig. 3. Bar chart comparing the mean averages across the sample countries for the question (%; N = 5,648): “At what stage would you like information to be conveyed to you about a possible safety problem of a medicine that you use or may use?” Note: All superscript letters that differ between nations denote a statistically significant difference (p < 0.05) between those nations in the percentage of respondents answering “when there is a possible sign of a safety problem” (determined by pair-wise comparisons in a generalized linear model with logit link, binomial distribution, and Bonferroni corrections for multiple comparisons.

If the information you personally receive (via letter, telephone, e-mail, etc) points to safety problems with the medicine you are currently taking, do you think you are more likely . . . to (a) stop taking your medicine (b) reduce your dose of the medicine (c) continue taking your medicine (d) seek additional advice about your medicine (e) don’t know? (Please choose one answer only).

Only 3% of the European-level sample said they would continue to take their medicine (and in effect do nothing) if the information they personally re-

ceive pointed to safety problems with the medicine they are currently taking (Fig. 5).8 Instead, 52% said they would “seek additional advice about the medicine” and 36% said that they would actually “stop taking their medicine” while 4% said they 8 An

important side note with these results is that respondents were unable to select more than one option. Therefore, respondents who said they would “seek additional advice” may indeed continue to take their medicine.

1220

Bouder et al.

Fig. 4. Pie chart showing the European-level mean average (%; N = 5,648) for the question: “At what stage do you think that members of the general public should be informed about a potential medical safety problem with a medicine?”

would reduce their dose (Fig. 5). Furthermore, there were clear and surprising national-level variations (Fig. 5). These variations can divide the European sample countries into two broad categories of “seekers” (who would look for more information) and “stoppers” (who would stop taking their medicine). A total of 67%, 67%, and 48% of respondents in the Netherlands, Great Britain, and Sweden, respectively, said they would most likely seek additional information compared to 39% and 33% of respondents in Germany and Spain, respectively. The “stopping” and “seeking” categories were also the two most popular categories for all sample countries. France was considered “split” on this question with 44% of respondents saying they would stop taking their medicine and 50% saying they would seek additional advice (Fig. 5).

6. DISCUSSION This study set out to explore what access to more information will imply for European pharmaceutical regulators in terms of communicating benefits and risks to patients in a meaningful way. A key result showed that many European citizens are not aware of their national pharmaceutical regulators, with as few as 2% of respondents in the Netherlands having heard of their national regulatory authority (Section 5.1). This suggests that many will therefore not be aware of the regulators’ transparency policies and, indeed, the new publicly available medicines data. In particular, European citizens in the United Kingdom, the Netherlands, Spain, Germany, and France are relatively unaware of or unfamiliar with their authority, with most respondents neither

having heard of them nor being able to demonstrate what they do. This raises important questions about the ability of the regulators’ transparency policies to build public trust.(77,78) Furthermore, these results can be contrasted sharply with results from a U.S. study,(38) which found that no less than 98% of a sample of 1,000 U.S. respondents had heard of the U.S. Food and Drug Administration (FDA), including 94% who could demonstrate that the FDA licenses and approves drugs and 83% who knew that the FDA communicates the benefits/risks of medicines.(38) However, although the mechanisms of fishbowl transparency are poorly understood, recent developments in the pharmaceutical domain have shown that the release of more information into the public domain will be accessed by the public (and scientists/data-miners) through a variety of unexam¨ ined communication channels. For example, Lofstedt and Way(62) (p. 17) describe how anxious Swedish patients actively sought out and obtained a large and complicated safety-related medicine document (a PSUR) for the flu vaccine Pandemrix when concerned about their children’s safety after reading news reports of a possible link with narcolepsy. In turn, many contacted the Swedish Medical Products Agency (MPA) seeking explanations about the complex expert medicines data. Although the consequences of the regulators’ transparency policies remain to be seen and will require further measurement, this example shows how raw safety-related documents, which contain thousands of pages of medicines information and that were initially written for expert rather than public consumption, are indeed likely to be read by patients when released under transparency policies. Furthermore, the survey

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Fig. 5. Comparative bar chart showing the mean averages (%; N = 5,648) for all sample countries for the question: “If the information you personally receive (via letter, telephone, e-mail, etc.) points to safety problems with the medicine you are currently taking, do you think you are more likely to (1) stop taking the medicine (2) reduce your dose of the medicine (3) continue taking your medicine (4) seek additional advice about your medicine (d) don’t know?” The data shows that the countries can broadly be categorized into “seekers,” “stoppers,” and “split” on the issue. Note: All superscript letters that differ between nations denote a statistically significant difference (p < 0.05) between those nations in the percentage of respondents answering “stop taking your medicine” (determined by pair-wise comparisons in a generalized linear model with logit link, binomial distribution, and Bonferroni corrections for multiple comparisons).

showed that the Internet was the third most popular source of information across sample countries despite being a relatively untrustworthy source of information (Section 5.2). This further suggests that the regulators will need to be prepared for an increase in patients asking about unverified safety-related information. In conjunction, other results showed that governments scored relatively low on the scale of trustworthiness compared to health-care professionals and are not seen as effective communicators by a large majority (see Figs. 1, 2a, and 2b ). This is important as a wealth of research has demonstrated that a lack of trust and confidence will make communication much more difficult.(78) Other results in this study present new evidence, based on the 2013 attitudes and opinions of

European citizens, about what is likely to happen when the public receives more unverified and uncertain safety-related medicine data through fishbowl transparency policies (and subsequent unexamined information source mechanisms). The results from this study crucially suggest that if European citizens received safety-related information on unverified safety problems (e.g., as included in documents currently held by the regulators), then the majority from Germany (51%) and Spain (61%) would actually stop taking their medicine over seeking additional advice (the “stoppers”; Section 5.5). In contrast, the majority of respondents from other European sample countries—especially the Netherlands, Great Britain, and Sweden—said they would seek additional information over stopping

1222 taking their medicine (the “seekers”; Section 5.5). These results are more concerning when contrasted with other results suggesting respondents would make these “stopping” or “seeking” decisions based on incomplete evidence. Specifically, the large majority of all respondents said they wanted information before a scientific analysis has been undertaken (55%) and before either the regulators or industry had investigated the problem (58%; Section 5.5). 6.1. Downfall of Prescription Compliance Over the past 20 years, several high-profile drug scares can be directly linked to decisions made on incomplete information. In particular, it took only one article (Nissen and Wolski(79) ) published in the New England Journal of Medicine and four months for 60% of patients taking Avandia (roglitazone)—a type II diabetes drug—to discontinue their medication based on incomplete information.(80,81) The results presented in this study suggest two key consequences based on the attitudes of European citizens. First, “stoppers” (a majority in Germany and Spain) are likely to terminate their medication based on incomplete information, leading to a significant downfall in prescriptions. For Avandia, this became a significant issue as approximately 50% of diabetic patients failed to begin a substitute drug after Nissen and Wolski’s study(79) was published.(80,81) Furthermore, comparing these results with the U.S. study where over a quarter (26%) of respondents (N = 1,000) said they would stop taking their medicine,(38) suggests that the situation in Europe is even more concerning than in the United States. 6.2. GPs and Pharmacies as Main Source of Information Second, “seekers” (especially Dutch, British, and Swedish citizens) are likely to seek additional advice based on incomplete information. More information does not automatically deliver less confusion and better decisions(5) or, as Tsoukas(50) puts it, more information means that there is “de-facto less understanding.” When transparency is just conceived as opening up data (i.e., fishbowl transparency) without being integrated with effective benefit/risk communication, can regulators ensure that the public has access to trustworthy sources? In the Internet age where confusion and misinformation are only one click away, this is very unlikely. Indeed, the Internet in

Bouder et al. general was the third most popular place respondents said they would go to find information on medicines and health alerts (Section 5.2) while simultaneously being one of the least trustworthy sources of information (Section 5.2). Furthermore, the results of this study suggest that GPs and pharmacists are likely to be inundated with difficult questions from concerned patients. Specifically, although there was variation, especially in Great Britain and Sweden, the two most popular places where respondents said they would go to find information on medicines and health alerts were their GP (64%) and the pharmacy (52%; Section 5.2). This supports the results of another recent study conducted by the Irish Medicines Board(82) finding that the general Irish public is most likely to seek advice on new over-the-counter medicines from pharmacists (most popular) or GPs (second most popular). Consequently, are key stakeholders (especially GPs and pharmacists) ready or even equipped to discuss raw data about complex issues with concerned patients? Also, are the regulators ready to explain this raw data to citizens through their most popular sources of advice, which (according to the results of this study) vary considerably between different European countries? For example, in Sweden, GPs were the fourth most popular source of information for medicines and health alerts with as few as 30% of respondents saying they would go to their GP compared to 80% in France (Section 5.2).

6.3. The Importance of National Variation Uneven levels of “seeker” or “stopper” behavior across Europe raise questions about how the current trends toward centralization (through the EMA) may downplay the importance of national variations across Europe. For example, 18% of Dutch compared to 61% of Spanish respondents said they would stop taking their medicine if the information they receive pointed to safety problems (Section 5.5). Among other variations in the survey results, this highlights the importance of national difference in public attitudes toward medicines and possible safety problems with medicines they take. However, it is important to note that this study does not show why there are clear national variations between European countries. There is therefore a need for critical research to be undertaken into explaining reasons for national variations in attitudes toward

Transparency in Europe medicine-related safety problems, including drugtaking behavior and culture. 6.4. Stigmatization of Medicines Drugs that are under investigation for safety concerns also receive significant stigmatization(83) that can even lead to the stigmatization of entire classes of drugs.(14) The impact of the Vioxx controversy on Cox2 inhibitors more broadly provides a clear example of this effect.(14) Risk communication science has shown that “public responses to controversial technologies are often strongly negative. Events, such as accidents or evidence of unsafe conditions . . . , receive extensive and dramatic coverage by the news media. These news stories affect public perceptions . . . [and] one result of these perceptions, avoidance behaviour, is a form of ‘technological stigma’” (p. 715).(83) This is only preventable through a participatory decision process that conveys valuable early information about potential sources of stigmatization and drivers of media amplification.(84) 7. CONCLUSION This study points to significant unintended consequences at the transparency policy implementation stage, which may lead to an increase in risky behavior on the part of the public, such as stopping taking its drugs. The findings also suggest that well thought through risk communication strategies and preparedness will be key to achieving successful transparency initiatives. For instance, are pharmacists and GPs sufficiently equipped to answer varied and difficult questions from concerned citizens? However, in the short term, it is unlikely that the regulators will change their commitment to public disclosure and “fishbowl” transparency. Changing course would mean a major reputation loss at a time when they are under significant scrutiny. Regulators are putting more information into the public domain or soon will (e.g., recommendations from PSUR assessments) with more drastic measures envisaged such as the proposed web-streaming of Committee sessions and plans to proactively release clinical trial data.(27) Nevertheless, the gap between what needs to be done and what is being done shows the importance and value in creating evidence-based initiatives that treat transparency as a form of benefit/risk communication, while highlighting the need to inject further evidence into the debate. This is

1223 particularly important when considering that several European regulatory bodies have begun dividing their organizational activities on “transparency” and “communication” through viewing transparency primarily as releasing data for reanalysis, while “siloing” communication into a separate organizational activity (private communication, 2014). The review of the European transparency landscape (Section 2) suggests that what may be true in the medical context may also apply to other sectors, which calls for a critical assessment of existing data on transparency as well as new studies to explore the relationship between transparency and risk communication. The authors therefore argue that regulators should, as Onora O’Neill(10) warns, avoid becoming “captivated” or “dazzled” by cheap and quick varieties of Internet-mediated transparency that do not take into account evidence-based risk/benefit communication science.(85,86) 8. RECOMMENDATIONS The study strongly suggests that the 2012 Ditchley Transparency Manifesto needs to be put into practice.(87) The objective is to move away from a predominately fishbowl to a more “reasoned” model.(4) Among others, we recommend developing: (1) coordinated interventions, (2) contextualized and nationally sensitive communications, and (3) narratives that present both “up” and “down” sides. We also recommend that regulators gain the support of key third parties and crucially pretest their communication messages. This implies that transparency needs to be coupled with sound evidencebased risk communication at the European and, critically, the national level. Three recommendations have been designed to change the European transparency model beyond therapeutics, and three recommendations have been designed to tackle issues that are more specific to the medical field. To change the European transparency policy model, the authors recommend the following. 8.1. Developing a Stronger Theoretical Understanding of Transparency As briefly discussed in Section 2, major works have been developed by eminent academics, such as Baroness Onora O’Neill and Christopher Hood or Carry Coglianese. We suggest that this effort be stimulated. One proposal could be a followup to

1224 Christopher Hood and David Heald’s 2006 book(39) that directly explores transparency with academics in Europe and North America. The objective would be to push the theoretical understanding of transparency further by, for example, progressing the relationship between transparency and conflicts of interests as well as the impact of transparency on behavior.

8.2. A Conference on Evidence-Based Transparency in the European Commission This conference would link the theory to the practice of transparency. This event should focus on conveying the latest evidence on what works and what does not to the EU Commission. For instance, evidence-based transparency calls for more measurements (e.g., extending the scope of this article such as to other countries and sectors). The conference should cover key sectors where transparency has been put in place, including those related to food, environmental data, and pharmaceuticals. It should also look into the implications of recent policy developments, including at the national level. One such concrete case could be, for example, the consequences of the new pharmacogiliance policy directive, which will result in many more statistics being released (Directive 2010/84/EU). At this stage, only recommendations from PSUR assessments as well as lay summaries of the risk management plan are available. What would “full transparency” imply?(62) At the same time, key actors—including European and national regulatory agencies—need to be very cautious about how they deal with data, as numbers can be distorted and misrepresented (e.g., hostile metaanalyses).

8.3. A Greater Role for Science-Based Risk Communication The need for more risk communication science is becoming urgent. Institutional risk communicators, especially regulators, need to pretest their messages and evaluate when things go wrong while adhering to the most up-to-date risk communication science (see Fischhoff et al.(85,86) for two highly recommended publications). The European Parliament’s committee on the Environment, Public Health, and Food Safety (ENVI) has voted on substantial

Bouder et al. amendments to the 2001 clinical trials directive.(75) The majority involves enhancing fishbowl transparency to “enable the public and independent researchers to analyze the results of clinical trials.”(57,75) The original draft proposal stated that one of the fundamental reasons for these changes is so that Europe can “be a world leader in both patient safety and transparency, in the interest of public trust and good science.”(75) Indeed, stakeholders on both sides of the transparency debate argue that prescribers and patients are of central importance. However, both advocates and opponents have little if any evidence to support their statements on what will happen once the proposed legislative changes come into force.(36) As this study suggests, if not grounded in risk communication science, these proposals may confuse patients about balanced decisions and damage public confidence through ineffective benefit/risk communication strategies that rely on the regulators’ approach of “all we have to do is give them the numbers” or the data-miners’ approach of “all we have to do is get the number right.”(88) The scientific profiles and types of risks at stake should also be considered, both across and within sectors (e.g., pharmaceuticals vs. food). To improve medical risk communication, the authors recommend the following.

8.4. More In-Depth Transparency Studies in the Medical Field A key lesson from this study is that context matters in risk communication. For example, why are more doctors sympathetic to the anti-immunization lobby in Germany than in Sweden? Why do French GPs prescribe more antibiotics than Dutch GPs? Contextualizing information and more reasoned transparency initiatives that go beyond numbers or raw facts are required. The answers to these questions are also often too superficial and insufficient to explain patient behavior when risk information is involved. Developing the right skills to understand how this information will be used (e.g., by the traditional and social media in a specific national context) will support the development of the right narratives to make a positive impact. Furthermore, national variation raises interesting questions about the relationship between culture, medicines, and risk, which will need to be explored further.

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8.5. Establishing a Benefit/Risk Communication Advisory Board at the EMA It is time to revisit the recommendation to establish an external advisory board that focuses on benefits and risks(89) along the lines of the FDA’s Risk Communication Advisory Committee. Unlike PRAC, this board should not be a new committee of the agency. Rather, it should be composed of experts from the risk communication and medical field with a view to integrate benefit/risk communication research into everyday processes. It should have the mandate to bridge medical and communication expertise. It would help to draw and implement lessons from cognitive science to build more robust benefit/risk communications at EU and national levels. To be effective, the setup should maintain a strong link with the risk communication discipline. 8.6. Increase Collaboration Between EMA, FDA, and NCAs on Transparency Transparency is one area where the United States has been at the forefront and the authors are of the view that Europeans should benefit from American trial and error rather than trying to “reinvent the wheel.” On the other side of the Atlantic, significant steps have been taken to refocus transparency measures back to the central aim of communicating effectively. In particular, the FDA’s Risk Communication Advisory Committee both reviews and evaluates research relevant to benefit/risk communication, including those facilities that interactively share risk and benefit data (including data-miners).(90) For

example, the drugs facts box, one of the committee’s most recent initiatives, highlights the importance of communicating benefits and risks effectively and includes a wealth of science-led, evidence-based risk communication research that enables the public to make better-informed, independent judgments on complex risk information.(85,86,91) ACKNOWLEDGMENTS In conducting research on risk communication and transparency, materials, assistance, and advice were provided by the Dutch Medicines Evaluation Board (CBG-MEB), Roche, Biogen Idec, the EMA, the Irish Medicines Board, the U.K. MHRA, and the Swedish Medical Products Agency (SMPA). The survey conducted by Ipsos and Dialogik was funded by Roche under a subcontract. Funding for writing the article was supported by Maastricht University. Findings were presented by the authors at the pharma and transparency “Ditchley 3” meet˚ ing at Krusenberg Herrgard, Sweden, on June 5, 2013. We are grateful for the comments and advice received from the participants at these meetings. We are grateful to the following individuals, who have provided us with materials, or who have commented on an earlier draft of this article: Prof. Ortwin Renn (Stuttgart University), Dr. James Smith (Roche), Ms. Sonia Gupta (Ipsos), Mr. Matthew Webster (Ipsos), Mr. Ross Connell (Ipsos), Mr. Cole Stirling (Ipsos), and Mr. Piet Sellke (Dialogik), as well as officials at CBG-MEB, EMA, U.S. FDA, MHRA, and SMPA. All the remaining errors remain our own.

APPENDIX A: ADDITIONAL DEMOGRAPHIC DATA

Table A1. Table Showing Gender and Age Demographic Data (%) for All Six Sample Countries

Sample Size Gender (%) Age (%)

Male Female 18–24 25–34 35–44 45–54 55–64

Great Britain

Sweden

The Netherlands

Spain

Germany

France

1,014 49.2 50.8 13.5 20.6 24.9 21.2 19.8

1,051 50.2 49.8 13.8 20.3 23.2 20.4 22.4

1,010 50.4 49.6 13 19.8 25.1 22.8 19.3

504 50.2 49.8 13.1 26 24.8 19.8 16.3

1,008 50.6 49.4 13.1 18.8 26.5 22.9 18.8

1,061 49.8 50.2 13.9 21.6 23 22.3 19.2

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Bouder et al. Table A2. Table Showing Respondents’ Estimated Average Number of Working Hours for All Six Countries (%)

Working Hours (%)

Great Britain

Sweden

The Netherlands

Spain

Germany

France

52.3 15.5 7.5

52.4 12.7 1.2

42.3 21.3 10.7

46.6 10.3 4.8

55.8 15.5 6.7

59.1 9.4 3.6

2.8 1.5

8.4 2

4 1.4

15.1 8.3

4.7 0.7

4.6 2.1

9.8 4.4 6.3

9.7 9.4 4.2

4 7.1 9.3

1.4 10.5 3

7.4 7.3 1.9

12.9 6.1 2.2

Working 30 hours or more a week (full-time) Working 8–29 hrs a week (part-time) Not working (under 8 hrs) — housewife/houseman Not working (under 8 hrs) — unemployed Not working (under 8 hrs) — unemployed (not registered but looking for work) Not working (under 8 hrs) — retired Not working (under 8 hrs) — student Not working (under 8 hrs) — other (inc. disabled)

Table A3. Table Showing Respondents’ Estimated Average Household Income for All Six Sample Countries (%) Estimated Average Household Income (%) Band 1 (GB: under £10,000; Swe: under 100,000 kr; NL, De, Fr: under €10,000; Sp: under €14,000) Band 2 (GB £10,000–£20,000; Swe: 100,000–200,000 kr; NL: €10,000–€25,000; Sp: €14.001–€30,000; De, Fr: €10,000–€20,000) Band 3 (GB: £20,000–£30,000; Swe: 200,000–300,000 kr; NL: €25,000–€40,000; Spain: €30,001– €55,000; De, Fr: €20,000–€30,000) Band 4 (GB: £30,000–£40,000; Swe: 300,000–400,000 kr; NL: €40,000–€55,000; SP: €55,001– €85,000; De, Fr: €30,000–€40,000) Band 5 (GB: £40,000–£50,000; Swe: 400,000–500,000 kr; NL: €55,000–€70.000; SP: €85,001–€115,000; De, Fr: €40,000–€50,000) Band 6 (GB: £50,000–£75,000; Swe: 500,000–750,000 kr; NL: €70,000–€100.000; Sp: €115,001–€140.000; De, Fr: €50,000–€75,000) Band 7 (GB: Over £75,000; Swe: over 750,000 kr; NL: over €100,000; Sp: over €140,000; De, Fr: over €75,000) Don’t know

Great Britain

Sweden

The Netherlands

Spain

Germany

France

8.5

6.9

12.1

28

14.6

10.9

18.7

13.8

20.5

35.7

14.4

21.2

19.9

17.9

21.9

17.7

14.9

19.8

13.5

16.2

10.7

3.8

14.3

16.2

11.8

10.4

6.1

0.2

8.5

10.3

10.5

15.6

3.7

0.4

10.7

6.8

3.5

6.1

1.1

0.6

5.1

1.7

2.1

3.4

5.6

13.7

17.6

2.7

Note: Income “bands” vary between countries. Please contact the corresponding author if you require a more detailed breakdown of educational qualifications in the sample countries.

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Table A4. Table Showing Which Regions Respondents Are from in Great Britain, Sweden, and the Netherlands (%) Great Britain (%) North & Yorkshire North West Midlands South West & Wales South East & Anglia London Scotland

Sweden (%) 12.8 11.5 16.2 13.6 23.4 13.6 8.9

The Netherlands (%)

Northern Sweden (Norrland) Central Sweden (Mellansverige) Stockholm ¨ Western Sweden (Vastsverige) ¨ Southern Sweden (Sodra Sverige)

9.8 25.3 21.1 20.3 23.5

North and East Netherlands West Netherlands South Netherlands

31.2 47 21.8

Table A5. Table Showing Which Regions Respondents Are from in Spain, Germany, and France (%) Spain (%) Madrid and Central East South and Canarias

Germany (%) 26 28.8 25.6

France (%)

Nielsen I (Hamburg, Bremen, Schleswig-Holstein, Lower Saxony) Nielsen II (North Rhine Westphalia) Nielsen III (a & b; Hesse, Rhineland-Palatine, Saarland) Nielsen IV (Baden-Wuerttemberg) Nielsen V (a & b; Barvaria) Nielsen VI (Berlin, Mecklenburg-Western Pomerania) Nielsen VII (Thuringia)

16 21.4 26.6 15.1 4.5 8.5 7.9

Paris region North West North East South West South East

19.5 22.6 23.6 11 23.3

Table A6. Table Showing Respondents’ Educational/Professional Qualifications (%) Education/Professional Qualifications (%) GCSE/O-level/CSE or equivalent Vocational qualifications A-level or equivalent Bachelor degree or equivalent Masters/PhD or equivalent No formal qualifications Still studying Other Don’t know

Great Britain

Sweden

The Netherlands

Spain

Germany

France

17.3 8.8 24.7 32.4 10.1 3.1 2.1 1.1 0.6

6.9 13.2 44.1 19.1 7.8 1 4.4 2.9 0.7

12.2 48.7 – 20.6 8.7 3.3 3.6 2.7 0.3

2.2 7.9 37.9 24.2 27.2 0.6 – – –

37.2 11.2 20.9 26.9 1.7 0.2 1.7 – 0.2

3.3 19 18.6 34 19.9 0.7 3.1 1.3 0.1

Note: Sample country education systems vary in Europe. Please contact the corresponding author if you require a more detailed breakdown of educational qualifications in the sample countries.

REFERENCES ¨ 1. Lofstedt RE, Bouder F, Wardman J, Chakraborty S. The changing nature of communication and regulation of risk in Europe. Journal of Risk Research, 2009; 14(4):409–429. 2. Hampton T. European drug agency under fire. Journal of the American Medical Association, 2012; 306(6):593–595. 3. EMA. European Medicines Agency Policy on the Handling of Conflicts of Interests of Scientific Committee Members and Experts. European Medicines Agency, 2012. ¨ 4. Lofstedt RE, Bouder, F. New transparency policies: Risk communication’s doom? Pp. 73–90 in Arvai J, Rivers III L (eds). Effective Risk Communication. Oxon and New York: Earthscan from Routledge, 2014.

5. Vogel D. National Styles of Regulation: Environmental Policy in Great Britain and the United States. Ithaca, NY: Cornell University Press, 1986. ¨ 6. Lofstedt RE, Vogel, D. The changing character of regulation: A comparison of Europe and the United States. Risk Analysis, 2001; 21(3):399–416. 7. European Commission. European Governance—A White Paper. Brussels: European Commission, COM (2001) 428 Final, July 25, 2001. 8. Cabinet Office. Risk: Improving Government’s Capability to Handle Risk and Uncertainty, Strategic Unit Report, 2002. Available at: http://webarchive.nationalarchives.gov.uk/±/ http:/www.cabinetoffice.gov.uk/media/cabinetoffice/strategy/

1228

9. 10. 11. 12.

13. 14.

15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25.

26.

27.

28. 29. 30.

assets/su%20risk%20summary.pdf, Accessed on September 4, 2014. ¨ Lofstedt RE. Risk communication and management in the twenty-first century. International Public Management Journal, 2004; 7:335–346. O’ Neill O. A Question of Trust: The BBC Reith Lectures. Cambridge: Cambridge University Press, 2002. O’Neill O. Transparency and the ethics of communication. Pp. 75–90 in Hood C, Heald D (eds). Transparency: The Key to Better Governance? Oxford: Oxford University Press, 2006. Grimmelikhuijsen SG, Meijer AJ. The effects of transparency on the perceived trustworthiness of a government organization: Evidence from an online experiment. Journal of Public Administration Research and Theory, 2012; 24(1):137–157. ¨ Lofstedt RE. Risk Management in Post-Trust Societies. Basingstoke: Palgrave/Macmillan, 2005. ¨ Lofstedt RE. The impact of the Cox-2 inhibitor issue on perceptions of the pharmaceutical industry: Contents analysis and communication implications. Journal of Health Communication, 2007; 12(5):471–491. Avorn J. Powerful Medicines: The Benefits, Risks and Costs of Prescription Drugs. New York: Knopf, 2004. Abraham J. Science, Politics and the Pharmaceutical Industry. London: Routledge, 1995. Bryner R, Stephens T. Dark Remedy: The Impact of Thalidomide and its Revival as a Vital Medicine. Cambridge, MA: Basic Books, 2001. Mullard A. Mediator scandal rocks French medical community. Lancet, 2011; 377:890–892. Angell M. The Truth About Drug Companies: How They Deceive Us and What to Do About It. New York: Random House, 2004. Goozner M. The 800 Million Dollar Pill: The Truth Behind the Cost of New Drugs. Berkeley, CA: University of California Press, 2004. Greider K. The Big Fix: How the Pharmaceutical Industry Rips Off American Consumers. New York: Public Affairs, 2003. Kassirer JP. On the Take: How Medicine’s Complicity with Big Business Can Endanger Your Health. New York: Oxford University Press, 2005. Coglianese C. The transparency president? The Obama administration and open government. Governance, 2009; 22(4):529–544. Hamburg MA, Sharfstein J. The FDA as a public health agency. New England Journal of Medicine, 2009; 360:2493– 2495. EMA. The European Medicines Agency Road Map to 2015: The Agency’s Contribution to Science, Medicines, Health. European Medicines Agency, 2010. Available at: http://www. ema.europa.eu/docs/en_GB/document_library/Report/2011/ 01/WC500101373.pdf, Accessed on September 4, 2014. EMA. European Medicines Agency Policy on Access to Documents (Related to Medicinal Products for Human and Veterinary Use). London: European Medicines Agency, November 30, 2010. EMA. Special Topics: Transparency. Web Portal of the European Medicines Agency, 2013. Available at: http://www.ema. europa.eu/ema/index.jsp?curl=pages/special_topics/general/ general_content_000526.jsp&mid=WC0b01ac0580050108, Accessed September 17, 2013. EMA. The EMEA Transparency Policy Draft for Public Consultation. London: European Medicines Agency, June and September 2009. Eichler H-G, Abadie E, Breckenridge A, Leufkens, H, Rasi, G. Open clinical trial data for all? A view from regulators. PLOS Medicine, 2012; 9(4): e1001202. ´ Eichler H-G, Petavy F, Pignatti F, Rasi G. Access to patientlevel trial data—A boon to drug developers. New England Journal of Medicine, 2013; 369(17):1577–1579.

Bouder et al. 31. Hood C. What happens when transparency meets blame avoidance? Public Management Review, 2007; 9(2):191–210. 32. Treaty of Lisbon (2007/C 306/01). Official Journal of the European Union, Volume 50, 2007. 33. Coglianese C, Kilmartin H, Mendelson E. Transparency and Public Participation in the Rulemaking Process. Submission to the Office of Information and Regulatory Affairs. Transparency and Public Participation Task Force, 2009. Available at: http://reginfo.gov/public/jsp/EO/fedRegReview/ Penn_Law_comments.pdf, Accessed September 17, 2013. 34. Curtin D. Transparency executive power. Pp. 204–246 in Curtin D (ed). Executive Power of the European Union. New York: Oxford University Press, 2009. 35. Etzioni A. Is transparency the best disinfectant? Journal of Political Philosophy, 2010; 18(4):389–404. ¨ 36. Lofstedt RE. Transparency at the EMA: More evidence is needed. Therapeutic Innovation and Regulatory Science, 2013; 47(3):299–300. 37. Heald D. Why is transparency about public expenditure so elusive? International Review of Administrative Sciences, 2012; 78(1):30–49. ¨ 38. Lofstedt RE, Bouder F, Chakraborty S. Risk communication and transparency: A quantitative study. Journal of Health Communication, 2013;18(4):391–396. 39. Hood C, Heald D. (eds). Transparency. The Key to Better Governance? London: Proceedings of the British Academy, 2006. 40. Roberts A. Dashed expectations: Governmental adaptation to transparency rules. Pp. 107–126 in Hood C, Heald D (eds). Transparency. The Key to Better Governance? London: Proceedings of the British Academy, 2006. 41. Fung A, Graham M, Weil D. Full Disclosure: The Perils and Promise of Transparency. Cambridge MA: Cambridge University Press, 2007. 42. Grimmelikhuijsen SG. Transparency of public decisionmaking: Toward trust in local government? Policy and Internet, 2010; 2(1):Article 2. 43. Hood C. Transparency in historical perspective. Pp. 3–23 in Hood C, Heald D (eds). Transparency. The Key to Better Governance? London: Proceedings of the British Academy, 2006. 44. Roberts J. No one is perfect: The limits of transparency and an ethic for “intelligent” accountability. Accounting, Organizations and Society, 2009; 34(8):957–970. 45. Florini A. Does the Invisible Hand Need a Transparent Glove? The Politics of Transparency. Washington, DC: Annual World Bank Conference on Development Economics, 1999. 46. Birkinshaw P. Freedom of information and openness: Fundamental human rights? Law Review, 2006; 58:177–218. 47. Meijer A. Understanding modern transparency. International Review of Administrative Sciences, 2009; 75(2):255–269. 48. Curtin D, Meijer AJ. Does transparency strengthen legitimacy? Information Polity, 2006; 11:109–123. 49. Bovens MAP, Wille A. Deciphering the Dutch drop: Ten explanations for decreasing public trust in the Netherlands. International Review of Administrative Sciences, 2008; 74:283– 305. 50. Tsoukas H. The tyranny of light: The temptations and paradoxes of the information society. Futures, 1997; 29:827– 843. ¨ 51. Chakraborty S, Lofstedt RE. Transparency initiative by the FDA’s Centre for Drug Evaluation and Research (CDER): Two qualitative studies of public perceptions. European Journal of Risk Regulation, 2012; 1:57–71. 52. EMA. European Public Assessment Reports: Background and Context. European Medicines Agency, 2014. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/ medicines/general/general_content_000433.jsp&mid=WC0b01 ac058067fa25, Accessed September 4, 2014.

Transparency in Europe 53. Sauer F. European Medicines Evaluation Agency is ahead of national licensing authorities. BMJ, 1998; 317:1078. 54. Abbasi K, Herxheimer A. The European Medicines Evaluation Agency: Open to criticism. BMJ, 1998; 317: 898. 55. OECD. Ethics in the Public Service, Current Issues and Practice. Public Management Occasional Papers No. 14. Paris: Organisation for Economic Co-operation and Development, 1996. 56. Doshi P, Jefferson T, Del Mar C. The imperative to share clinical study reports. Recommendations from the Tamiflu experience. PLOS Medicine, 2012; 9(4): e1001201. 57. Willmott G. Labour MEP’s Campaign to Open Op Clinical Trials Takes Giant Step Forward. Glenis Willmott MEP, 2013. Available at: http://www.gleniswillmott.eu/labourmeps-campaign-to-open-up-clinical-trials-takes-giant-stepforward/, Accessed September 17, 2013. ¨ 58. Lofstedt RE. European Medicines Agency—More transparency needed. Lancet, 2010; 375:1753. 59. Hampton T. European Drug Agency under fire. JAMA, 2011; 306(6):593–595. 60. Groves T, Godlee F. The European Medicines Agency’s for sharing data from clinical trials. BMJ, 2013; 346:f2961 doi: 10.1136/bmj.f2961. 61. Gøtzsche P. European Governments should sue Roche and prescribers should boycott its drugs. BMJ, 2012; 345: e7689. ¨ 62. Lofstedt R, Way D. Transparency and trust in the European pharmaceutical sector: Outcomes from an experimental study. Journal of Risk Research, 2014. Available at: http://dx.doi.org/10.1080/13669877.2014.919517, Accessed September 4, 2014. 63. Goldacre B. Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients. London: Harper Collins, 2012. 64. Godlee F. Clinical trial data for all drugs in current use. BMJ, 2012; 345:e73. 65. EMA. Access to Clinical Trial Data and Transparency: Workshop Report. European Medicines Agency, 2012. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/ Report/2012/12/WC500135841.pdf, Accessed September 4, 2014. 66. Gøtzsche P. Roche continues to drag its feet on access to Tamiflu data. BMJ, 2013; 346:f3001. 67. Gøtzsche P, Jørgensen A. Opening up data at the European Medicines Agency. BMJ, 2011; 342:d2686. 68. European Ombudsman. Case Decision of the European Ombudsman Closing His Inquiry into Complaint 2560/2007/BEH Against the European Medicines Agency. European Ombudsman, 2010. Available at: http://www.ombudsman.europa.eu/ en/cases/decision.faces/en/5459/html.bookmark, Accessed September 17, 2013. 69. All Trials. All Trials Registered; All Trials Reported, 2013. Available at: http://www.alltrials.net/, Accessed September 4, 2014. 70. Smith R. Transparency: A modern essential. 2004; BMJ, 328:1136. 71. Garattini S, Bertele V. Europe’s opportunity to open up on drug regulation. BMJ, 2010; 340:842–843. 72. Barbui C, Baschirotto C, Cipriani A. EMA must improve the quality of its clinical trial reports. BMJ, 2011; 342:d2291. 73. Godlee F. Promises of transparency? Hold the applause. BMJ, 2013;346:f1513 74. HoC (UK House of Commons). Government Must Take Action to Tackle Lack of Clinical Trial Transparency, Say MPs. UK Parliament, 2013. Available at: http://www.parliament.uk/ business/committees/committees-a-z/commons-select/scienceand-technology-committee/news/130916-clinical-trials-reportpublished/, Accessed September 4, 2014.

1229 75. ENVI (Committee on the Environment, Public Health and Food Safety). Draft Report on the Proposal for a Regulation of the European Parliament and of the Council on Clinical Trials on Medicinal Products for Human Use, and Repealing Directive 2001/20/EC. European Parliament, 2013. Available at: http://euapm.eu/wp-content/uploads/2013/04/EuropeanParliament-Draft-Report-on-Clinical-Trials-Directive.pdf, Accessed September 17, 2013. 76. IOM. Characterising Uncertainty in the Assessment of Benefits and Risks of Pharmaceutical Products—Workshop in Brief. Washington, DC: National Academies Press, 2014. 77. Kasperson RE. Four questions for risk communication. Journal of Risk Research, 2014; 17(10):1233–1239. 78. Tuler SP, Kasperson RE. Social distrust and its implications for risk communication. Pp. 91–107 in Arvai J, Rivers III L (eds). Effective Risk Communication. Oxon and New York: Earthscan from Routledge, 2014. 79. Nissen S, Wolksi K. Effect of rosiglitazone on the risk of myocardial infarcation and death from cardiovascular causes. New England Journal of Medicine, 2007; 356(24):2457– 2470. ¨ 80. Lofstedt RE. Risk communication: The Avandia case, a pilot study. Expert Review of Clinical Pharmacology, 2010; 3(1):31– 41. 81. Saul S. VA limits Glaxo drug widely used for diabetes. New York Times, NY, October 18, 2007. 82. IMB. Consumer Views on Sourcing Information on Medicines: National Survey. Irish Medicines Board, 2010. Available at: http://www.lenus.ie/hse/handle/10147/96670, Accessed September 17, 2013. 83. Flynn J, Peter E, Mertz CK, Slovic P. Risk, media and stigma at Rocky Flats. Risk Analysis, 1998; 18(6):715–727. 84. Kasperson RE, Jhaveri N, Kasperson JX. Stigma and the social amplification of risk: Toward a framework of analysis. Pp. 9–27 in Slovic P, Flynn J, Kunreuther H (eds). Risk, Media and Stigma: Understanding Public Challenges to Modern Science and Technology. Oxon and New York: Earthscan, 2004. 85. Fischhoff B, Brewer NT, Downs JS. Communicating Risks and Benefits: An Evidenced-Based User’s Guide. US Department of Health and Human Services, Food and Drug Administration, 2011. Available at: http://www.fda.gov/downloads/ AboutFDA/ReportsManualsForms/Reports/UCM268069. pdf, Accessed September 17, 2013. 86. Fischhoff B. The sciences of science communication. Proceedings of the Academies of Sciences of the United States of America, 2013; 110 (Suppl 3):14033–14039. doi: 10.1073/pnas.1213273110. ¨ 87. Lofstedt RE, Bouder F. The Ditchley Transparency Manifesto. Therapeutic Innovation and Regulatory Science, 2012; 46(1): 7. 88. Fischhoff B. Risk perception and communication unplugged: Twenty years of research. Risk Analysis, 1995; 15:137–145. 89. Bouder F. Benefit/Risk Communication by the European Medicines Agency: A Study of Influential Stakeholders’ Expectations and Attitudes. European Medicines Agency, 2011. Available at: http://www.ema.europa.eu/docs/en_GB/ document_library/Report/2011/05/WC500106865.pdf, Accessed June 26, 2013. 90. USFDA. Risk Communication Advisory Committee. US Food and Drug Administration, 2013. Available at: http:// www.fda.gov/AdvisoryCommittees/CommitteesMeeting Materials/RiskCommunicationAdvisoryCommittee/default. htm, Accessed September 17, 2013. 91. Schwartz LM, Woloshin S. The drugs facts box: Making informed decisions about prescription drugs possible. Pp. 233– 242 in Gigerenzer G, Muir Gray JA (eds). Better Doctors, Better Patients, Better Decisions Envisioning Health Care 2020. Cambridge, MA: MIT Books; 2011.