A study participant participates in a clinical trial, contributing invaluable data to understanding the safety and efficacy profile of a drug. Yet, patients, despite risking their lives by participating in a clinical trial, don’t usually get to know the outcome of the clinical trial.
In the spirit of transparency, the EU Clinical Trials Regulation 536/ 2014 ((EU CTR Article 37) mandated that sponsors should submit a transparent, simplified summary of clinical trial results, the lay summaries (plain-language summaries (PLSs)) within a year of a trial being completed for studies in adults, and within six months of trial completion for studies in a pediatric population. The PLSs need to be provided in all EU languages for countries in which the study has been conducted and have to be submitted, along with the summary of the clinical trial results in the designated central EU portal and database (The Clinical Trials Information System (CTIS)).
The regulation came into effect on 16 June 2014 and is being rolled out in a phased manner. As the CTIS is expected to go live in December 2021, as was indicated by the European Medicines Agency (EMA) in June 2020, the submission of lay summaries on this portal for all new trials will then become mandatory. Some sponsors publish lay summaries on their own websites, as well as on portals such as TrialSummaries.com.
This rule is applicable to all interventional phase I to phase IV trials, involving at least one site in the EU regions. As per Article 27, it is also important that the informed consent form informs patients that the lay summaries will be made available in the designated central EU portal and also clarifies potentially when they would be made available.
The purpose of lay summaries is to explain the results of a clinical study in simple language, so that study participants and the general public can understand the study results. Lay summaries are strictly non-promotional, factual and objective documents that complement other forms of clinical study disclosure, but do not replace them. Ten elements need to be included in lay summaries as per Annex V of the EU CT Regulation, and this is the responsibility of the sponsor. They need to incorporate principles of health literacy, numeracy and cultural literacy, use simple, unambiguous language and an engaging tone. Health literacy is defined as the degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions. As per the EU CTR regulation, readability needs to be targeted at a literacy proficiency level of 2–3 on the International Adult Literacy Survey scale, which implies that the lay summary should be easily understood by people 12 years of age and older. Yet, it is important that the language used does not talk down to the audience. One needs to understand for what patient population are lay summaries being developed, and use relevant, culturally sensitive language. The language and style used for populations of different ages and different cultures would need to be different.
While the EU requires the translation of the PLS into all European languages in the countries where the trial is being conducted, it is important to start with a well-structured Master PLS, presenting the overall study results and the primary endpoints of the study by treatment group. It is strongly recommended that inputs be sought from a panel, including patients, patient advocates, as well as healthcare professionals to ensure that the information is easily comprehensible to patients and strikes the right tone as well. Translating lay summaries requires the use of skilled linguists with clinical expertise so as to ensure that the scientific integrity of the results is not lost. The Translation Memory (TM) that is used should be configured to customer terminology to ensure consistency and accuracy. In addition to forward and backward translations, a comparative review by an independent linguist, and a clinical review by a subject matter expert, add value. Customer review may also be included as a part of the process.
The language assets that have been created should be updated in a repository, and libraries could be created per therapeutic area, to enhance both quality and efficiencies. While Machine Translation drive efficiencies, linguistic sensitivity and style result from the use of professional, skilled translators. It is said that a picture speaks a thousand words – visual imagery adds significant value and drives retention as well. The length of the document is also important – one wants to ensure that all relevant information has been shared, and all scientific jargon explained. That could run into many pages. Yet, how many patients would like to read a 10 to 20-page long document? Understanding the statistical relevance of trial outcomes can in itself be challenging to a scientific audience; trying to explain it to a lay audience is even more so. The challenge for scientific writers lies in simplifying detailed scientific content and communicating it in an engaging, yet non-promotional and a concise manner – that is no small ask!
The entire process should use experienced in-country, native linguists and companies should establish a PLS strategy, in alignment with their clinical development plan. PLS templates, style guides and glossaries need to be created and integrated with the TM.
The EU has clearly taken the lead in clinical trial transparency. In the US, the FDA does not mandate the submission of lay summaries, though it is strongly encouraged by the FDA. The Multi-Regional Clinical Trials (MRCT) Center at Harvard Return of Results Workgroup published two documents in 2015, the Return of Results Guidance and the Return of Results Toolkit. While the former is a practical guide to returning results and outlines the challenges involved, the latter, in addition to providing templates and toolkits, provides suggestions for translating endpoints into lay language, and shares some practical examples as well. The Center for Information and Study on Clinical Research Participation (CSICRP), in 2011, piloted programs with Pfizer and Eli Lilly wherein trial results were reproduced into lay summaries. Over 90% of volunteers were satisfied with their level of understanding, resulting in the FDA recommending that the CISCRP program should be adopted industry-wide. In January 2018, Scott Gottlieb, MD, announced a pilot to be run by the FDA, to improve public access to drug approval information. As the outcome of this pilot, the FDA published the posted portions of pivotal clinical study-related summaries of nine recently approved NDAs on Drugs@FDA.
The world is demanding transparency – as an industry it is our responsibility to share scientific knowledge in the simplest manner possible. It is our duty to patients and to the public to convey understandable information, drive transparency, and build trust.
About CSOFT Health Sciences
CSOFT Health Sciences provides end-to-end medical translations for all phases of the product lifecycle, from pre-clinical to post-launch. We also specialize in market access consulting, medical writing, and CTD/eCTD submissions with the FDA, EMA, and NMPA. Our operations are compliant with ISO 17100 and certified in ISO 9001:2015 and ISO 13485:2016, ensuring our customized solutions meet the rigorous regulatory requirements of global submissions.
CSOFT International is a leading provider of cross-border communications for enterprises seeking growth in global markets. Our expertise in localization, documentation, and branding encompasses a full range of end-to-end content and consulting services that we deliver in over 250 languages. With a focus in health sciences and smart technology, we work closely with our clients to deliver precision solutions to the challenges of engaging markets, consumers, and regulatory environments worldwide.