The 2018 European Meeting of the International Society for Medical Publication Professionals (ISMPP) was held in London on 23–24 January and attracted nearly 300 delegates; the highest number of attendees to date. The meeting’s theme was ‘Advancing Medical Publications in a Complex Evidence Ecosystem’ and the agenda centred around data transparency, patient centricity and the future of medical publishing. Delegates were treated to two keynote addresses, lively panel discussions, interactive roundtables and parallel sessions, and also had the chance to present their own research in a poster session.
A summary of the second day of the meeting is provided below for those who could not attend. A summary of the first day of the meeting can be found here.
Evolving transparency requirements in a complex multi-stakeholder environment
Fresh from the previous day’s discussion of Shire’s Open Access policy, Chris Rains (Shire) took to the podium as moderator of day two’s first session panel, which comprised Trish Groves (The BMJ), Andy Powrie-Smith (European Federation of Pharmaceutical Industries and Associations; EFPIA), Anne-Sophie Henry-Eude (European Medicines Agency; EMA), Katherine Tucker (Roche), Rafal Swierzewski (European Cancer Patient Coalition), Stuart Spencer (The Lancet) and Slavka Baronikova (Shire). Over the course of the next 90 minutes, the speakers discussed the changing transparency landscape in medical communications.
Trish Groves gave the opening presentation, starting with a fitting nod to the duration and visibility of presenter interests, citing a recent study into the insufficiency of presentation disclosures. Groves then began in earnest with an introduction to open science; comprising not just the availability of manuscripts, but access to data, methodology and the peer review process. Indeed, narrow disclosure of research endeavours wastes much of the effort involved in clinical studies, leading to unnecessary duplication or confounding reinterpretation. However, Groves warned that providing context remains essential, and that isolated ‘data dumps’ are not the answer. The importance of data sharing has been recognised in the recent International Committee of Medial Journal Editors (ICMJE) updates and is also reflected in regulator and industry policy initiatives from EMA, EFPIA and The Pharmaceutical Research and Manufacturers of America (PhRMA), and internationally with data sharing statements being issued by WHO, UN and G7. In Europe these visions are expected to be at least partly addressed by the EU open science cloud – mandating open access to all EU-funded research on a central publishing platform. Groves concluded with a summary of the recent BMJ Open consensus statement on sharing and reuse of individual participant data from clinical trials, highlighting recommendations to promote discoverability of shareable data through being “as open as possible and as closed as necessary” to protect patient privacy and reduce the risk of misuse.
Andy Powrie-Smith was next to the stage, opening with a discussion of the emerging cultural considerations that necessitate improved data sharing. He cited a public loss of confidence in institutions and a preference for self-directed data analysis and interpretation. Yet every call for openness is met with conflicting patient privacy and data deletion requests. How can we share more, while adequately addressing the fears inherent in doing so? EFPIA–PhRMA principles incorporate the needs of enhanced sharing between researchers as well as trial participants and the public. Examining the implementation of these principles finds that the majority of pharmaceutical companies have policies in place to facilitate and regulate data requests, and that most (80%) requests from qualified individuals are approved. Yet the uptake in data availability is relatively low, and the majority of requests focus on using data to conduct novel analyses. There is “no reverse gear” for transparency though, Powrie-Smith noted, as he considered the continuing progress of data transparency alongside key requirements of collaboration, confidentiality and consistency that will ensure its increasingly successful implementation.
The next presentation was led by Anne-Sophie Henry-Eude who outlined the existing EMA policies, some passive, some proactive, through which data are made available, and focused specifically on the Clinical Data Publication (CDP) policy. Henry-Eude described the journey to approval for this policy, the documentation collected under its remit, and its long-term aim to clarify the drug approval process and improve public confidence in it. As part of the CDP guidance, anonymisation of clinical reports to protect patient identification and sensitive company information was emphasised. Yet it was notable that over the past year, of >3,000 published documents, applicants proposed a substantially higher level of redaction than was eventually deemed necessary by the EMA. The presentation concluded with an examination of the high rates of user download activity, indicating a clear interest and enthusiasm for these data.
Katherine Tucker presented the next section, and examined the shift from historically poor data sharing, to an increased openness and an emphasis towards “building in” transparency at the core of research, considering all the eventual uses and audiences. Trial registration and documentation are standard today, yet disclosure of individual patient-level data remains voluntary, with a fragmented ecosystem of reporting databases, and a historical lack of standardisation that has impaired the practicality of meta analysis. Academic research lags much further behind, but projects like VIVLI are aiming to address these gaps. From the Roche perspective, Tucker provided an overview of the challenges inherent in retrospectively identifying patient-level data, and a commitment to the FAIR (Findable, Accessible, Interoperable, Reusable) principles aimed at enhancing automated data retrieval and supporting its reuse by individuals. Ultimately, Tucker concluded that collaboration has been key to getting where we are today, and continued partnership will be essential to further development.
The session was brought to a close by Rafal Swierzewski, who represented the frequently neglected patient perspective in clinical research. Patient data are created by patients, and should be for patients, yet the myriad of research stakeholders has evolved a complex range of data sources to service the differing analytical focuses or capabilities of each audience. These do not lay a simple path for accessible patient research and education. There is a clear call from patient groups to distil the complexity of the obscure health data environment into one of transparency and ease of access. The session finished with a call to remember that patients are at the core of all research, and that there can be a shocking lack of acknowledgement or involvement of patients throughout, echoing the European Cancer Patient Coalition’s call to action: “nothing about us, without us.”
Speed research: part 2
Following day one’s speed research session, day two saw three more ISMPP members take to the stand to report on their groups’ research findings, which were also presented in poster form during the meeting.
Henrike Resemann (Costello Medical) got proceedings underway with a summary of her team’s findings on the ‘Reporting of Delphi methods to achieve consensus on guidelines in rare diseases’. The group conducted a pragmatic literature review of publications reporting the development of consensus guidelines, via the Delphi method, for the diagnosis or management of rare diseases. Analysis of 11 evaluable publications revealed that the Delphi method is often not reported comprehensively and that key methodological details are omitted:
- 91% did not report an agreement threshold
- 45% did not report a consensus threshold
- 45% did not report methods for collecting panellist feedback
- 36% failed to report the number of statements assessed.
There was also variation in study design, with three studies failing to conduct a literature review, and only two using a systematic literature review to inform guideline development. Resemann pointed out that, due to a lack of RCTs, consensus guidelines are of particular importance for the management of rare diseases; therefore the need for rigour is pertinent.
Next up, Anna Georgieva (Excerpta Medica) described her team’s research on the question ‘Should we consider patients in communication plans?’. The team surveyed 100 patients and 50 caregivers in the US. Interestingly, they found that 45% of respondents were familiar with medical journal articles, with 49% finding these articles from journals directly (60% found them via a general internet search and 12% via PubMed). Respondents reported that medical publications helped them to be involved in clinical decision-making and aided discussions with their healthcare professional (51 and 45%, respectively). In spite of this uptake, patients and caregivers reported challenges in accessing journal articles, including the use of jargon and a lack of clarity around how an article’s conclusions relate to patients. Georgieva suggested that publications professionals have a responsibility to ensure data is presented in a way that is understandable to patients. She emphasised that “research begins and ends with a person”; medical publications have the potential to empower patients, but only if information is presented in a clear, relevant and accessible way.
Finally, Anne-Clare Wadsworth (Envision Pharma Group) reported on her team’s efforts to assess ‘Patient involvement… or not? Analysis of “Patient involvement” statements in clinical trial publications in The BMJ’. The BMJ has required the inclusion of a patient involvement statement in publications since 2014 and also includes a patient review step for articles reporting clinical trials. The team analysed clinical trial publications in The BMJ from 2015 to 2016 and looked in further detail at the level of ‘patient involvement’. Of the 52 publications analysed, 25% did not include any patient involvement, or even thank patients in the publications’ acknowledgements. While 58% did thank patients, and 40% involved patients in disseminating results to trial participants, rates of patient involvement in study design and conduct were low (<20%), and only one article included a patient as an author. Overall, patient involvement was described as “visible but variable” and the authors threw down the gauntlet to publications professionals to increase collaboration with patients and patient advocacy groups.
Keynote address: patients know best
The first of the 2018 keynote talks was delivered by Dr Mohammad Al-Ubaydli (UCL Centre for Health Informatics & Multiprofessional Education; CHIME), founder and CEO of Patients Know Best (PKB), a social enterprise which aims to help patients understand their personal health records (PHRs) and collaborate with clinicians.
Speaking from personal experience, Al-Ubaydli explained that patients are very aware of their unique medical situation. He recognised that providing more control over PHRs could both empower patients and foster a productive shared care approach to disease management. These factors led to the foundation of PKB, which securely stores patient-controlled records, while providing access via web-enabled devices.
Al-Ubaydli went on to explain that putting the patient in control of their PHR allows it to be shared more easily across healthcare services, researchers, charities and patient advocacy groups. Moreover, the digital platform allows letters, such as appointments, laboratory results and discharge summaries, to be sent electronically, providing secure information storage while reducing costs. Online access to clinical laboratory results can both reduce unnecessary telephone calls and the need for face-to-face appointments, and as Al-Ubaydli argues, may also reduce unplanned emergency admissions by allowing health deteriorations to be spotted earlier. He also highlighted the growing importance of patient devices and apps which record clinically useful data, and the ability of PKB to integrate with these to allow home monitoring of parameters such as blood pressure, body weight and blood glucose. Finally, Al-Ubaydli raised the point that with PKB, digital care plans can be viewed and edited by all relevant parties, which may increase patient engagement and adherence.
The address was followed by a lively audience question and answer session in which Al-Ubaydli argued that the major bottle neck for the use of this type of e-system is the transfer of power from the doctor to the patient. He speculated on the impact that an accessible digital system could have on translational delay and spoke about how the platform could be utilised by patients who may not have previously been able to advocate for themselves.
Following this keynote address and a break for lunch delegates had the opportunity to attend two of four parallel sessions, each summarised below.
Patient involvement in research and communication: opportunities and challenges
Continuing the theme of patient centricity, this parallel session bought representatives from a medical communications agency, a patient advocacy group, the pharmaceutical industry, and publishing together to debate issues relating to patient involvement in research and communications.
Karen Wolley (Envision Pharma Group) kicked things off by presenting data from research investigating the extent of patient involvement in clinical trials, with a focus on patient authorship and data sharing. In an evaluation of 52 clinical trial articles published 2015–2016 in The BMJ, only one had a patient co-author. However, it was noted that while the sample was limited, this patient-authored paper outperformed the other 51 articles in terms of Altmetric attention score, number of tweets and Twitter followers. She highlighted that the public tweets more than healthcare professionals about JAMA Patient Pages and about related scientific articles. She advocated that patients can and should affect publications and noted that sufficient time and resources are needed for high-quality research that earns the trust of patients.
Antonio Ciaglia (International Alliance of Patients’ Organizations) went on to describe how patients are not just users, data suppliers or beneficiaries, but are willing participants. From a patient’s perspective early engagement in research is as important as late engagement and ensuring research is properly communicated to its primary beneficiaries is essential. He concluded that this requires cross-stakeholder effort and all parties to understand the value of patient involvement.
Rachel Jones (Admedicum), asserted that it is the duty of the pharmaceutical industry to help patients piece information together. She described how patients can play a role in research and publications as well feeding back into outcomes and affecting strategic planning, and discussed an example of a patient-authored paper. She described how patients can better inform pharmaceutical companies and reduce costs but explained that there is a lack of clarity around how the industry can engage patients. She concluded that, “the biggest risk is not taking risk”.
Finally, Dr Sophie Cook (UK Research Editor, The BMJ) provided an overview of The BMJ’s commitment to involving patients. The publisher launched its patient partnership strategy in 2014, aimed at making patient partnership integral to the publishing model, including patient and carer editors as members of the editorial team. She described the opportunities for patient participation in the generation of both commissioned and unsolicited content, including authorship, peer review and dissemination. She reported that editors and patients have found the strategy extremely valuable and would encourage other journals to take the same approach.
The session ended with a dynamic panel discussion. It was acknowledged that patient authorship is still in its infancy but is a realistic goal for publications where there is a strong rationale for involving patients. Such publications should be set up for success and minimise potential harm for the patient. The utility of the GRIPP2 reporting checklist was discussed and a show of hands demonstrated the widespread support for more specific guidelines on patient involvement to be included in GPP4.
The growing importance of RWE: what does it mean for publication professionals?
Richard White (OxfordPharmaGenesis) was joined by fellow panellists Witold Wiecek (Analytica LASER) and Sajan Khosla (AstraZeneca) in steering delegates through the evolving landscape of real world evidence (RWE).
Wiecek began by explaining that real world data (RWD) are collected in a routine care setting and RWE is derived from analysis of these data. RWD take many forms, such as data from registries, claims databases, pragmatic RCTs, or bridging studies (that combine data with modelling). RWE can be used to build upon the information provided by RCTs by looking at clinically relevant outcomes and comparators in a real clinical setting, rather than a controlled environment, and in the heterogenous population seen in clinical practice.
Wiecek described how factors such as the increasing complexity of the treatment landscape in many therapy areas, the growing availability of RWD, technological advances in data analysis, and increasing interest among payers and regulators, are combining to drive improvements in the quality and quantity of RWD. He also outlined how RWE is now generated across the drug life cycle, for example in:
- post-authorisation safety and efficacy
- cost-effectiveness models
- outcomes-based agreements with payers
- adaptive licensing.
Sajan Khosla then presented an industry perspective on the generation of RWE. He outlined how RWE can be used to address evidence gaps and highlighted the importance of building a clear RWE strategy, flagging RWE Navigator as a useful resource. Khosla emphasised that publications play a fundamental role in the dissemination of RWE.
Richard White delved further into the challenges of publishing RWE. While some of these are linked to the unpredictable nature of RWE (eg with respect to timelines for data generation), White also flagged the potential risk of scope ‘drift’. Furthermore, discrepancies exist with respect to the knowledge base of key stakeholders: while RWD analysis experts are often unfamiliar with publications processes and guidelines, peer reviewers at many journals may not be familiar with RWE study methodology. These challenges are further exacerbated by the fact that some journals do not publish RWE. Scepticism around RWE also persists in some quarters of the academic community, but the panel felt that new FDA guidelines and the publication of robust RWE studies, such as the Salford Lung Study and CVD-REAL, will see this change.
Facing the challenges of publishing unfavourable, negative, equivalence or non-confirmatory data
Karen Mittleman (Sanofi), Danielle Sheard (Costello Medical) and Jan Seal-Roberts (ADIS) bought together their perspectives from the pharmaceutical industry, medical communications agencies, and publishing to offer delegates advice on how to publish data types that some journals have traditionally deemed unattractive. They opened the session by emphasising that ‘difficult data’, such as inconclusive or negative results, are not the same as ‘bad data’ which are generated from non-scientifically sound or poorly performed studies.
Mittleman then reminded the audience of the pharmaceutical industry’s ethical obligation to publish and disseminate data from all clinical trials and highlighted that all studies involving human participants should be registered on a publicly accessible database, as set out in the Declaration of Helsinki. Mittleman shared some of the difficulties around publishing phase 1 healthy volunteer studies, including a lack of interest and motivation among authors. She also pointed out how this early research may contain commercially confidential information, which can impact the timing of publication, and suggested grouping phase 1 studies for publication closer to product launch could be a potential solution.
Research into rare diseases can also generate valuable, but difficult-to-publish data. Such studies frequently involve small sample sizes and do not follow a RCT design. Moreover, for each rare disease there is often a limited pool of knowledgeable peer reviewers. Sheard, who specialises in publishing this type of research shared her tips for success. She suggested highlighting the novelty of the study and its potential impact on the clinical management of patients. When choosing a journal, Sheard recommended working with authors to make a realistic first choice, as this can save time by preventing multiple cycles of submission and rejection. She also recommended sending a pre-submission enquiry to the journal, but cautioned that a positive response does not guarantee acceptance.
This advice was seconded by Seal-Roberts, who also recommended ensuring that publication strategies include journals to target should a trial provide inconclusive or negative data. She asserted that confirming this plan with lead investigators early on helps to manage expectations. Finally, she reminded delegates that even if study results are unfavourable, honesty, transparency and clear reporting are still vital.
The Learning Room
Delegates with less than three years’ experience were offered the opportunity to attend ‘The Learning Room’, a session for those new to medical publishing that was successfully introduced to the program at the ISMPP EU 2017 meeting. In this session, moderated by Steven Walker (Stgilesmedical), seven experienced speakers delivered short, high-quality talks on a diverse range of topics, and answered questions relating to their areas of expertise.
Keynote address: the impact of Brexit
Andy Powrie-Smith (EFPIA) presented the final keynote address on the potential impact of ‘Brexit’ on the scientific and pharmaceutical industries, delivering an interesting, and sometimes rather daunting, overview of the sector-specific issues that will need to be addressed before the UK officially leaves the EU in March 2019.
- There are 1,500 UK-sponsored EU clinical trials currently taking place; half of these will be ongoing post-March 2019 when the UK formally leaves the EU. How these will be regulated is not yet known.
- There are 400 centrally authorised products with UK licence holders and 4,000 centrally authorised UK-held marketing authorisations (MA) for medicines that will require transfer to the EU.
- There are 12,000 centrally authorised MA that will require a separate MA in the UK in order for these drugs to be legally prescribed to patients in the UK once it leaves the EU.
- Ongoing cooperation on the regulation of medicines will need to be secured post-Brexit.
Trade and supply
- Millions of patient packs of medicines are supplied from the UK to the EU every month with a similar number moving in the opposite direction.
- To avoid delays in the supply of these products, a bespoke and comprehensive free trade agreement between the UK and the EU may be required.
- Science and medicine are both very mobile industries. Brexit is already thought to have had an impact on recruitment in these areas due to the uncertainties around the movement of people once the UK leaves the EU.
- Currently, the UK is one of the largest recipients of EU funding for research.
Intellectual property (IP)
- The current IP framework and incentives have allowed investment in new medicines across the EU. It will therefore be important to have a UK IP framework in place following Brexit.
Powrie-Smith concluded that, in an era where media coverage of Brexit may have led to an increased distrust of experts in favour of a populist narrative, it is important for the medical industry to simplify and humanise its communication with society.
Following this informative keynote address, and after a successful and thought-provoking 2 days the 2018 European meeting of ISMPP drew to a close.
By Aspire Scientific, an independent medical writing agency led by experienced editorial team members, and supported by MSc and/or PhD-educated writers