Here, we comprehensively investigated drug company perspectives on current risk communications for drug safety. To our knowledge, this is the first such study conducted in Japan.
The response ratio of 70% was considered sufficient to ensure the external validity of the survey results, and was additionally strengthened by the following considerations. More than 10 of the targeted companies are considered to be currently inactive or to have reduced post-marketing pharmacovigilance activities because their products are generic, legacy, or licensed out to other companies, and accordingly might not have responded to the survey. Foreign capital companies account for 25.6% of all member companies of the JPMA (Japan Pharmaceutical Manufacturers Association 2013), which is consistent with the ratio of domestic to foreign capital among the firms responding to this survey. Responses were predominately from large-scale companies with more than one thousand regular employees, which account for the majority of pharmaceutical companies selling newly developed pharmaceutical products in Japan. Many respondents appeared to be sufficiently experienced in the area of pharmacovigilance to provide adequate answers.
Contents
To be successful, messages for risk communications need to convey a balance of multiple conflicting requirements: they need to be written in a clear, simple and comprehensive manner on topics that are relevant and important, and yet at the same time they need to be brief (Seligman and Osborne 2009; Mazor et al. 2005). We found that many companies prioritized the strength of evidence and place a high value on comprehension, probably because of their intent to ensure the credibility of the message. This appears to reflect the principle that the effectiveness of risk communication depends on the creditability of the message (Bahri and Harrison-Woolrych 2012b). Aspects at the next ranking level, ‘Stratification of patients with regard to harm’ and ‘Number of people affected by harm’, likely include the expectation of behavioral changes in medical practice as a consequence of the communication. This question lacked an option of ‘mention of what should be done differently’ since the Media Doctor rating criteria lack it; nevertheless, the comments of several respondents regarding the question on the creation of messages emphasized the importance of the outcome of message transmission, indicating that pharmaceutical companies are likely to next focus on the effectiveness of message transmission. The EU and US guidelines clearly recommend that communication plans include the assessment of effectiveness, such as quantification of behavioral changes, survey of comprehension, and reductions in adverse event reporting (Edwards and Chakraborty 2012; The US Food and Drug Administration 2009; European Medicines Agency 2013). The Japanese regulations for the provision of DHCP letters, in contrast, requires a pharmaceutical company to assesses only the distribution of the communication materials to medical institutions and practitioners in the communication plan. Unlike the EU and US plans, therefore, the Japanese communication plan does not address ‘true effectiveness’ (Pharmaceuticals and Food Safety Bureau 2011a). The introduction of risk management planning in Japan, although delayed until April 2013, urges the Japanese regulatory community to change the poor methodology of the current method of assessing communication practices (Pharmaceuticals and Food Safety Bureau 2012).
Targets
Stakeholders and the message to be communicated in risk communications vary depending on the type of harm/risk. Communication with the most prioritized targets, physicians and pharmacists, was considered mostly successful, indicating that drug companies focused intensively on these two occupations, as evidenced by the considerable time allocated to them shown in the other question item. Patients were rated as third; however, risk communication with patients was rated as less successful than that with the reference in-company division in this survey. Drug companies in Japan communicate with patients in an indirect and unidirectional fashion via healthcare professionals, patient-oriented handouts, and corporate websites. Direct-to-consumer advertisements are legally prohibited, and drug company activities and publications directed to patients are strictly regulated. Given the comparatively small work-time allocation to patients, the high prioritization given to patients as communication targets in this survey therefore likely represents corporate policies and conceptual but unsubstantial patient-oriented attitudes.
We found the lower ranking of the regulatory authority as a communication target to be inconsistent with the finding that the regulatory authority received the largest work-time allocation. Pharmaceutical companies are required to consult the regulatory authority when commencing regulatory actions involving risk communication activities which target healthcare professionals and the public. We speculate that the drug companies may be concerned about being seen as excessively authority-oriented, with a view to subsequent publication of the survey results. Additionally, risk communications with the regulatory authority were all rated successful or better. We speculate that respondents might have censored their responses by selecting the socially “harmless” answer ‘successful’ to telegraph that they had no particular concerns in their relationship with the regulatory authority.
Measures
Generally, DGPs obtained a good appraisal, particularly in terms of readability and contents. As respondents pointed out, however, they are poorly recognized by the public; in a survey of 1,707 people who had undergone a regular physical examination, for example, only 2% had experienced accessing a DGP and only 15% were in fact actually aware of them, and an initiative to attract patient attention to this material is therefore warranted (Suka 2011). Consistent with the US medication guides, the scope of drugs requiring the preparation of DPGs is limited (The US Food and Drug Administration 2011). However, more than half of respondents supported extension of the preparation of DGPs to all prescription drugs, as does the UK Patient Information Leaflet (Committee on Safety of Medicines 2005). In Japan, prescription drugs are dispensed with a consumer medication information (CMI) sheet, which includes a small picture of the drug in its dosage form and a brief description of its usage, dosage and adverse reactions. These are prepared by the dispensing pharmacy, which primarily sources them from non-authorized drug information databases maintained by private claims reimbursement computer system vendors. In this regard, a survey of the US CMI sheets reported that the contents were of low quality, and urged their improvement (Kimberlin and Winterstein 2008; Raynor et al. 2007). In contrast, DGPs provide several pages of rich and detailed content for patient self-instruction and are developed by the supplying pharmaceutical company and reviewed by the regulatory authority at the expense of national insurance subscribers and patients, although many are currently in disuse. Utilization of DGPs as legitimate source documents for the preparation of CMIs at dispensing pharmacies is strongly recommended. Achieving this will require that all information in individual DGPs for all prescription drugs become publicly available through an official online database with easy accessibility using the Standard Generalized Markup Language.
Our survey respondents also positively noted the efficiency and effectiveness of drug information websites run by the pharmaceutical companies. Although some respondents expressed concerned that the information posted on company-run websites is likely to be partial and one-sided (Davis et al. 2007), one study reported that lay people considered that the credibility of information on regulatory agency and pharmaceutical company websites was comparable (Kim 2011). The low usability of the PMDA website noted in our survey appears to result from its tangled, multiroute, multistep path from the home page to target information, and from the awkwardly organized, overlapping information and PDF regulatory documents attached to many webpages. This should be improved by usability testing from the perspective of the public, without influence by the regulatory perspective (Bahri and Harrison-Woolrych 2012b; European Medicines Agency 2013). The significance and importance of internet use in searching and querying drug information was shown in our separate surveys, which found that 37.4% of community pharmacists had utilized company-run websites and that 43% of people who received regular health checkups had had a chance to browse for drug information on the Internet (Suka 2011). The very major importance of official, integrated, and strategic web–based provision of drug information should therefore be acknowledged. The EMEA websites may be referenced as sophisticated examples, and the EU is also planning to establish a single consolidated online database for drug information (European Medicines Agency 2013).
The respondents appreciated the significance of direct communication of risk information by the regulatory agency, especially in case of emergency. Current Japanese regulatory advisories, including revision of label information, issuance of DHCP letters, and other safety notifications often require intensive and sometimes contentious preliminary discussion, followed by tough negotiation before agreement between the regulatory authority and pharmaceutical company is reached. These likely represent the most resource-consuming tasks on both sides. The risk communication measures implemented by drug companies under the strict oversight of the regulatory agency may therefore take considerable time until the dispatch of key risk messages can proceed, which might in turn impair the timeliness of risk mitigation actions, and also compromise the effectiveness and transparency of communications. Indeed, in July 2011, coincidentally after the close of this survey, the PMDA launched a new website “On information concerning the risks of drugs under evaluation” within its “Pharmaceuticals and Medical Devices Information Homepage”, similar to the Drug Safety Communication by the US FDA (Pharmaceuticals and Food Safety Bureau 2011b; Seligman and Osborne 2009). Further effective utilization of direct and rapid communication by the regulatory agency is desirable.
The media were recognized as and expected to play an essential role in emergency risk communications by the pharmaceutical company side. This expectation was in contrast to the lower success rating for communications targeted to mass media, and the smaller resource allocation to them. The effectiveness of risk minimization activities such as DHCP letters is reportedly influenced by whether the risk receives wide media publicity (Weatherby et al. 2001; Urushihara et al. 2011; Waller et al. 2006). However, the legitimate role of the media in risk communications has been questioned as their interests differ from those of pharmaceutical companies and regulatory agencies. If the media is conceived of as a public organ of society, rather than a private institution that seeks mere demagoguery and sensation, then its provision of well-balanced, evidence-based media coverage of safety issues may be expected to maximize benefits and ameliorate harms for patients and the public, although admittedly this remains an ongoing challenge (Bahri 2010; Waller et al. 2006). The advantage of the UK’s scientific media in improving the quality of reporting of drug information via the general media should be acknowledged (Czarnecki 2008; Mebane 2005).
Safety risk management planning was eventually implemented in April 2013 in Japan, following the issuance of local guidance for risk management plans for pharmaceuticals in April 2012, which supplements the ICH E2E “pharmacovigilance planning” guideline (Pharmaceuticals and Food Safety Bureau 2012). Most global companies have therefore already experienced the development and implementation of safety risk management plans, whereas domestic companies likely have little or no such experience. More than half of the respondents in this survey agreed with disclosure of the outlines of risk management plans, mostly owing to a likely grudging acceptance of transparency. Disclosure of safety risk management plans is planned to commence in 2013 and is also expected to facilitate understanding and cooperation with practitioners and patients. However, as our respondents noted, tailoring the information to the expected audience is essential, given its potential to both maximize the effectiveness of the information and minimize anticipated confusion among patients as well as healthcare professionals (Bahri and Harrison-Woolrych 2012b).
Limitations
The results of this survey likely represent the partial and one-sided views of the responding pharmaceutical companies, and comprehensive and impartial investigations among other important stakeholders should accordingly follow. Owing to the anonymity of the study process, it was not possible to identify non-responding companies and thereby determine the extent of selection bias. The possibility exists that only those companies which actively express their opinion on a routine basis dominated this survey results. This survey did not target generic drug makers since they generally rely on the marketing authorization holders of the original drugs and do not play a central role in risk communication activities. Further, the answers derived from the survey may be biased toward those considered socially desirable, out of concern of criticism after the publication of this survey and subsequent to internal review within companies before the answers were returned. Even considering the above limitations, the high return rate appears sufficient to ensure representativeness in Japan, although the results would not be applicable to companies located in other countries, which have different medicosocial national systems.