Part VI, the public summary of the risk management plan
Part VI of the EU risk management plan condenses the whole plan into summary tables for the public assessment report and a public summary in lay language. One text has to serve expert and lay readers at once, in summaries limited to a few hundred words. The public summary stands beside the other public documents about the same medicine, and the European Medicines Agency turns it into the summary it publishes and updates. Feedback from the agency's pilot suggested that the summary did not reach or serve its lay readers well, and the second revision of the guidance shifted its audience, cut its contents and left questions open.
Part VI and its two sections
Part VI summarises in abridged form the most important information compiled in the complete plan and so provides the essence of the medicine's overall safety profile. It is prepared as part of the plan and presents the safety concerns in plain language, so that the public can later understand the medicine's safety concerns and the associated risk management system. Part VI supports the overall goal of transparent, concise and high-level communication of all relevant data and information.
In the agency's template, Part VI has two sections. Section VI.1, Elements for summary tables in the European public assessment report, gives tabular overviews of the medicine's safety concerns and of the related pharmacovigilance and risk minimisation measures, which are copied from the main body of the plan and incorporated into the assessment report of the Committee for Medicinal Products for Human Use (CHMP) and the public assessment report at the time of authorisation. One account draws those tables from Parts I, III, IV and V. Another draws them from Module SVIII and Parts III, IV and V.
Section VI.2, Elements for a Public Summary, is the publicly available scientific summary of the plan, written for the lay reader. Risk management plans have to include a lay summary of safety concerns. Such a summary describes how the important risks of a medicine are being managed or will be managed. The summaries in Section VI.2 cover the epidemiology of the disease, the treatment benefits of the drug, the unknowns relating to those benefits, and the safety concerns. A summary of the risk minimisation measures, which puts the medicine's risks in the context of the treatment benefits, has to be provided too, along with the planned post-authorisation development plan where there is one. For medicines with additional risk minimisation measures proposed or in place, a further summary in lay language informs the public about those measures. Once the plan is approved, the agency uses Section VI.2 as the basis for the summary it publishes on its website, so lay wording is required. Section VI.2 is also partly incorporated into the public assessment report's summary for the public, in its summary of treatment benefits, and is published as a stand-alone document.
The requirements and detailed instructions for Part VI are in Module V of the good pharmacovigilance practices (GVP) and in the agency's template on its risk management plan webpage. More and more medicines have published summaries, and examples are on the agency's website. Useful sources of information for writing Part VI are:
- the EU Pharma Package, Regulation (EU) No 1235/2010 and Directive 2010/84/EU
- the agency's risk management plan webpage, including GVP Module V on risk management systems (Revision 1), the agency's plan template and the questions and answers on the plan summary
- the agency's webpage of public summary examples
- the website of the Pharmacovigilance Risk Assessment Committee (PRAC)
- the CHMP website
Origin of the public summary
The public summary, Section VI.2, came into existence with the 2012 EU Pharma Package (Regulation (EU) No 1235/2010 and Directive 2010/84/EU) and its accompanying transparency initiative, which aimed to enhance public information on the processes around a medicine's authorisation, its efficacy and its safety. It was introduced with the new GVP legislation. Another account dates the EU's introduction of Section VI.2 to 2013. Publishing the public summary is one of the requirements of the European pharmacovigilance legislation, Regulation (EU) No 1235/2010 and Directive 2010/84/EU, and a further step towards increased transparency and public access to relevant information on medicines.
Besides providing as much information as possible to other health authorities, marketing authorisation holders, investigators, healthcare professionals and others, the agency also strives to inform the general public better. The public summary is part of that drive to improve information about medicines for the general public. The agency's goal is to involve patients more and to give them all the relevant information available for a specific medicine, in the case of the public summary in a language tailored to patients' needs. The published lay summaries were meant to explain to the general public how the European regulatory authorities make decisions about the safety of medicines, and to make those decisions more transparent.
The plan, and especially its public summary, became a widely discussed topic in pharmacovigilance. A large number of questions arose, many of them about the summary's content, but also about the new process the plan needed, which has to allow for transparency on the one hand and data protection on the other. The introduction of the summary caused great discussion and concern in an industry very willing to provide information to patients but more experienced with producing complex scientific information for regulatory authorities.
Publication by the agency
The agency started publishing summaries of the plan in March 2014, in a one-year pilot phase for medicines authorised under the centralised procedure. Another account has the agency publish its first summary for the public of the plan of a newly authorised medicine in November 2014, for Neuraceq. That summary describes what is known and not known about the medicine's safety and states what measures will be taken to prevent or minimise its risks. The agency was to pilot the publication of summaries for all newly centrally authorised medicines during 2014 and at a later stage to start producing them for previously authorised medicines. Eventually all centrally authorised medicines were to have a public summary.
The pilot set out to confirm interest and usefulness for stakeholders, to confirm the target audience, to improve format and content based on the needs and expectations of the readership, and to streamline the process for preparing and updating the summaries. During the pilot, the agency collected feedback from patients, healthcare professionals and industry associations. Revision 1 of the plan template and of GVP Module V was a minor one, and it did not include results from the pilot, which had just started at that time.
Once the plan is submitted to the agency, the assessment procedure starts, and with it the review of the public summary. After a positive opinion has been issued, the agency transfers the relevant information from Part VI of the approved plan to its own summary template and revises the text according to agency style, format and naming conventions. The marketing authorisation holder then receives the summary and is given the opportunity to review it, with a focus on content-related issues only. The review takes only a few days, and the holder should be prepared for a quick turnaround. The holder should also consider whom to include in the review. It might be advisable to include not the entire multidisciplinary team that contributed to the plan but only the relevant Part VI authors, such as drug safety, epidemiology, medical and regulatory, and to add representatives from the legal and communications departments and management. The holder then returns consolidated comments to the agency, which finalises the summary for release on its website.
The summary is always subject to change. Unlike the other documents in the submission dossier, the plan is a living document, updated continuously throughout a medicine's life cycle as knowledge about the medicine's benefits, risks and overall safety profile increases. Whenever there are significant changes to the plan, meaning a change in the benefit-risk profile, the summary is updated as well.
The summary among the other public documents
Patient-friendly documents such as the summaries of the European public assessment report (EPAR) and the package leaflet are already available from the agency. The EPAR summary explains for lay people what the medicine is, how it works, how it has been studied, what it is used for, what its benefits and risks are, and why and how it was approved; in other words, it explains the scientific and regulatory context of the medicine. Tables from the first section of Part VI feed into the EPAR summary. The package leaflet contains instructions for the patient on the actual use of the medicine, such as how to take it properly, its administration and dosage, and its anticipated side effects, and so places the medicine in the context of everyday use and daily medical practice. The package leaflet and the EPAR summary present key information on the benefits and the risks of a medicine in lay language. The summary of the plan provides yet another angle on the medicine. It introduces the concept of risks related to a medicine, which neither the EPAR summary nor the package leaflet covers. It complements the public-friendly information already available in the agency's EPAR summaries. It is intended to provide a context for the medicine's risk-benefit evaluation and to complement the public assessment report and the package leaflet with information on the medicine's safety concerns and the related post-authorisation studies. The three documents thus complement each other and provide a complete picture of a medicine's safety profile.
The summary of the plan is written in lay language and summarises the information in the plan, which is a long, complex and partly very technical document. It is intended for readers who would like to know more about the risks related to a medicine, in the context of its benefits, and how these risks are handled. It includes:
- a brief overview of epidemiology, meaning how common the disease is and which parts of the general population it affects
- a summary of the treatment benefits, based on the main studies conducted
- a description of the unknowns of the treatment benefits, in the populations not studied
- a tabular summary of the important risks and how they are managed
- a tabular overview of missing information that needs to be collected
- any additional measures to be taken as required as part of the marketing authorisation
- a list of planned studies to provide more information on the medicine's safety and benefits
- a tabular overview of updates to the plan
The audiences of the public summary
For many medicines the summary has been made publicly available on the agency's website, for regulators, industry and healthcare professionals as well as for patients. Section VI.2 can be regarded as one of the key challenges for the medical writer, as it represents the public face of the plan and should be a useful resource for patients and physicians. A lay summary of a risk management plan can be challenging to write, and however much it is needed, the effort is wasted if it does not reach or connect with its intended audience.
From a regulator's perspective, communicating a medicine's important risks and the associated risk minimisation measures to the public is in itself a form of risk minimisation, and may also be a valuable tool for healthcare professionals and patients in deciding for or against the use of a medicine. So it is crucial that the target audience can understand the complex benefit-risk information presented, which means taking the health literacy of the readership into account. For the summaries in the format set by Revision 1 of the plan template and of GVP Module V, medical writers normally aim at a literacy level of 11 to 12 years old or below.
In the one-year pilot phase, the target audience for Section VI.2 was stated as the lay audience. An update from the agency was to amend it to a primary audience of stakeholders with a professional interest in medicines and a secondary audience of members of the public, among whom the summary should be understandable to those looking for more information on medicines who may not be familiar with medical terminology. The summaries were expected to be consulted by stakeholders with a professional interest in medicines and to be a useful resource for members of the public who would like more information about their medicines. The expanded audience creates a significant challenge for medical writers, as the primary and secondary audiences are likely to have very different levels of health literacy, numeracy and interest, and different motivations for seeking the information. The wording of the two descriptions acknowledges this implicitly: the primary audience, with a professional interest, would be expected to understand medical terminology, while the secondary audience is clearly stated not to be expected to be familiar with it.
Serving experts and lay readers in one text
The public summary's purpose is twofold: it is supposed to summarise all relevant information for regulators and, at the same time, to make the medical context, the benefits, the unknowns and, most importantly, the safety concerns clear to the lay reader. Authoring Part VI means meeting two demands at once: the information must be medically accurate and convey all the relevant information needed for a medicine's authorisation, while it should be written so that a lay reader can understand it. With a single text, the writer has to reach experts and lay readers, two audiences with very different needs, and writing for both at once poses new challenges for medical writers. The format of the summary aims to provide condensed, clear and understandable information on elements of the plan, which is very challenging for medical writers because the plan is a long, complex and quite technical document. The major challenge is to tailor the complex information on the most relevant aspects of the plan to a heterogeneous audience of healthcare professionals, industry stakeholders, and patients and patient organisations, while ensuring correctness, accuracy and clarity. Reaching both audiences can be a challenge in regulatory writing, since conveying correct and exact medical information can prove difficult if medical terminology is to be avoided.
The writer serves as an interface between the expert functions that contribute to the summary and the lay readership, and in most cases the content those functions provide has to be translated into lay language. So the writer is often caught between two opposite positions: the expert contributing to the plan is often concerned that important medical information will be lost with lay language and may be reluctant to omit medical terms, while the agency requires lay language so that the information is also accessible to the general public.
Lay language within word limits
The summaries in Section VI.2 run to 50 to 300 words, depending on the number of indications. The guidance imposes word count constraints on most of the lay overviews in the summary, which makes the task even more challenging. Conveying correct and exact medical information without medical terminology is especially difficult when the word count is limited, which means that explaining medical terms or using both medical and lay terms is not an option.
Some subsections of Section VI.2 are particularly difficult to write in lay language, such as the epidemiology of the disease being treated, the clinical benefits of the drug, and the more in-depth discussion of the important identified risks and the important potential risks. The epidemiology section naturally incorporates numerical presentations of incidence and prevalence data, both of which are difficult concepts to explain to lay readers. Discussions of a drug's benefits and risks or harms are often supported by statistical information, and risk information in particular is usually given in numerical terms. Simply providing these numbers is not sufficient for the lay audience: an understanding of what the numbers mean has to be conveyed, so that the risks, benefits, incidence and prevalence can be put into context.
The problem is conveying the summary's information to a lay audience, and particularly to readers with difficulty reading. In the UK, for example, 16% of adults (7.1 million people) are functionally illiterate: they can understand short, straightforward texts on familiar topics but have problems reading information from unfamiliar sources or on unfamiliar topics. One account gives the average reading age in the UK as below 14 years, which shows how challenging it is to explain the risks and harms of treatments as a risk management plan lays them out. Another gives it as 11 years.
What the pilot found
The pilot covered over 80 summaries and confirmed a wide interest from different audience groups and the need to improve format and contents to meet their demand and expectations. The introduction of the public summaries was generally perceived as a positive measure to improve transparent communication and to contribute to a more patient-centred drug development process. But format, requirements and lay language, combined with the complex contents, impose inherent limitations, and these raise two questions: how the requirements and the format can be adjusted to fulfil the needs of the targeted readership, and whether the lay public is really the appropriate audience.
Industry welcomed the transparency initiative, but its general perception was that, if the summary is mainly intended for patients, it should be improved and further adapted to meet that audience's needs. Industry critically questioned the suitability of the summary in its format at the time, on three counts:
- It provides no definitions of identified risks, potential risks and missing information.
- It does not explain how it complements the summary of product characteristics, the package leaflet and the public assessment report, or how the concepts in those documents differ, such as important risks against side effects.
- It does not explain the pharmacovigilance and risk minimisation processes, such as post-authorisation plans and risk minimisation measures, with which the audience is not familiar.
In that context, a summary containing numerous important risks and gaps in knowledge may lead to unjustified concern and to the misleading perception that a product is more hazardous than it actually is, and that its risks outweigh its benefits.
Patients' feedback further challenged the format and language. They criticised a lack of clarity, context and definitions, and considered the summary hard for patients to understand because of its complex and technical contents. Among the public, knowledge and understanding of drug development, medicine safety monitoring and health authority activities are generally limited, so it appears that the summaries are not perceived as a useful communication tool and do not effectively reach their target audience.
Despite the intention behind the lay language requirements, it is doubtful that the summary is in fact widely used. It also does not provide the basic definitions needed to understand its contents and its relationship to the other publicly available documents, so it is questionable whether it fulfils the criteria for effective, transparent communication.
The public assessment report summary, the package leaflet and the summary of the plan give different perspectives on a medicine's safety profile, but the differences in their concepts, such as the distinction between side effects and risks, might not be obvious to the lay audience. Although the summary is to be written in lay language with a focus on patients, it is still a very technical document and not very reader-friendly; lay audiences will not be familiar with the definitions of risk, important risk, potential risk or identified risk, for instance.
The summary in Revision 2 of GVP Module V
Four years after its first introduction, the summary was undergoing a major revision based on feedback from all stakeholders, in line with the transparency initiative and the agency's efforts to improve the communication of clinical and safety information. With GVP Module V under revision and the pilot feedback still being analysed, changes to the plan's content, process requirements and target audience could be expected. Those working in pharmacovigilance awaited the revision of the summary with their own open questions: whether the original concerns would be addressed, whether they would still be asked to produce a single document that satisfies healthcare professionals and the general public at once, and whether the summary would achieve its aim of increasing transparency for the lay audience.
The revision of the summary had three main targets for transparent communication:
- Format, contents and structure should be simplified, with the focus on the summary of safety concerns, risk minimisation measures and the planned post-authorisation development plan.
- While the package leaflet and the public assessment report summary are the main primary source of information on a medicine's benefits and risks for patients, the summary should address an audience interested in additional background safety information provided in the package leaflet.
- A plain-language approach should be used, without avoiding technical terms.
With Revision 2 of GVP Module V, the summary moves towards a rather professional audience and people seeking additional information, possibly with a slightly higher health literacy level, though it should still follow plain-language principles to facilitate readability by the general public. The draft guidance states that the audience is very broad, and that to satisfy its different needs the summary should be written and presented clearly using a plain-language approach, which does not mean that technical terms should be avoided. It adds that the document should clearly explain its purpose and how it relates to other information, in particular the product information: the summary of product characteristics, the package leaflet and the labelling. It states that the summary should contain:
- the medicine and what it is used for
- a summary of safety concerns and missing information
- routine and additional risk minimisation measures
- additional pharmacovigilance activities
In March 2017 the guidance on drafting risk management plans was revised, with significant changes to how the lay summary in Part VI should be written. The revised guidance likewise states that the audience is very broad and that the summary should be written and presented clearly using a plain-language approach.
Although the revised summary considered many of the stakeholders' comments, it still does not seem to fully meet the needs of its diverse target audience. Its contents are now very concise and limited to safety concerns, pharmacovigilance activities and risk minimisation measures, and the public assessment report tables have been removed, as have the overviews of disease epidemiology and treatment benefits. Sections on safety concerns, risk minimisation measures and pharmacovigilance activities would not pose any difficulty for medical writers producing documentation for a regulatory authority. Removing the descriptions of the drug's efficacy and of the epidemiology simplifies the lay summary for the medical writer to produce, but it makes it very difficult for the reader to understand the benefits of the drug and the impact of the disease in general. Standard text has been proposed to define identified and potential risks but not missing information, and the importance of a risk is still not defined. Context is given with regard to the public assessment report, the summary of product characteristics and the package leaflet, but there is still no explanation of how side effects or adverse events, the terms those documents use, differ from important risks, the term the summary uses. Routine and additional risk minimisation measures and routine pharmacovigilance activities are defined, but additional pharmacovigilance activities, the post-authorisation studies, are not explained. In line with the objectives of template and process simplification, the proposed format maps the summary's contents to the full plan. This gives the impression that its content is mainly taken verbatim from the body of the plan, and it raises the question of who should prepare the summaries in the new format: the pharmaceutical company, or the health authority when it prepares the reader-friendly summaries.
Questions left open
Apart from the challenges in writing the summary, process-related questions remained unanswered, as is expected for a new procedure. Publication applied only to centrally authorised medicines, although Part VI is needed for every plan, whatever the authorisation procedure. No detailed guidance was available for medicines authorised under the mutual recognition, decentralised and national procedures, and information on national publication strategies, if any were in place, was sparse. The agency's template text is tailored to centrally authorised medicines and is not always suitable for the other procedures, so the marketing authorisation holder depends on national authorities' feedback on local requirements and on whether deviations from the template text are permitted or even required. An official lay term glossary and style guide for Part VI, available to all marketing authorisation holders for writing the summary's lay texts, would be helpful. Because third parties can request plans under the transparency initiative, data protection needs careful consideration when writing the plan and especially Part VI; patient identifiers, for example, should not be used.
Revision 2 of GVP Module V addresses many questions and concerns that had been raised, but four questions remain.
- The summary is available only in English, which not everyone in the EU or EEA is able to understand. Besides that language barrier there is an information barrier: most people are likely not aware that a summary of a risk management plan, the plan itself or the agency's website exists, and so do not have access to the information. So it is unclear whether the summary can reach the lay audience at all.
- Even if plain language is used, and assuming the patients speak English, it is unclear whether they will be able to understand the information and consequently make appropriate decisions.
- It is unclear whether transparency requires showing all the details of the risk management process to an audience with low health literacy and no understanding of such processes.
- It is unclear whether the focus should be shifted even more to patients' needs and readability, whether user testing would help meet those needs and create a more reader-friendly document, or whether separate summaries should be created for lay readers and expert readers.
Since the EU Pharma Package was implemented in 2012, regulators and marketing authorisation holders have gained experience with the plan and its summary. Open questions remain, though, and the new process is still evolving, so medical writers will continue to face the challenge of meeting the needs of all stakeholders in a dynamic and transforming environment. As a document that must address different needs and interests and cover complex medical information, the summary has a major impact on how a medicine is perceived, and further interaction and exchange between all the parties involved will likely be needed to reach the common goals of effective communication, transparency and patient safety.