New Requirements for Lay Language Summaries of Clinical Trials Are Here—Are You Prepared?
Chi Pakarinen
Patient Engagement and Multi-stakeholder Collaborations
Jo Dewhurst
ICON, Plc.
Dan Bilodeau
ICON, Plc.
Solange Corriol Rohou
Sheila Khawaja
World Alliance for Pituitary Organizations

ay language summaries—sisters to Plain Language Summaries—focus on summarizing clinical trial results in an understandable way to provide increased transparency to the patients and interested general public. The European Clinical Trial Regulation now requires sponsors to provide a lay summary of clinical trials in a set time period following the trial end. To support sponsors, a guidance cocreated and endorsed by the European Commission aims to help implement organizational capabilities to write and share lay summaries.

Lay language summaries (LS) are meant to inform trial participants and the public about clinical trial results in an easy-to-understand manner. Recognizing the need for and importance of providing accessible and understandable summaries of clinical trial results to patients and the interested public, a multistakeholder Roadmap Initiative to Good Lay Summary Practice (in collaboration with the Clinical Trial Expert Group of the European Commission) cocreated the Good Lay Summary Practice (GLSP) recommendations that were published in EudraLex in October 2021 (GLSP, 2021). Although LS and Plain Language Summary (PLS) are often used interchangeably, PLS is generally used to refer to summaries of scientific publications and conference and other presentations, whereas LS is generally used in the context of summaries of clinical trial results.
About the EU Clinical Trial Regulation

Since 2014 when the European Union (EU) Clinical Trials Regulation (CTR) No 536/2014 was released, sponsors have had to provide LS results of clinical trials to increase clinical trial transparency, although this requirement came fully into effect only in January of this year (EMA 2021, EUR-Lex 2014, EU 2014). This LS is required to be done in a format understandable to laypersons and the public at large. This dissemination is facilitated by the European Medicines Agency’s (EMA) Clinical Trials Information System (CTIS) that was launched at the end of January 2022. Sponsors are required to submit a LS (Annex V of the CTR) and a technical summary (Annex IV of the CTR) of the results of all new Phase I through IV interventional clinical trials.

For clinical trials in adults, sponsors will be required to post a LS and a technical summary within 12 months of the end of the trial, up to 30 months for nontherapeutic Phase 1 trials and 6 months for pediatric trials. Implementation of the CTR will go through a 3-year phase-in. In the first year, LS submission will be optional, while after the second and third years, it will become mandatory for new trials.

What Are the Main Components of a Lay Summary?

Creating a LS involves incorporating complex, technical information from regulatory documents into a short summary using nonpromotional and unbiased language. These summaries are generally written at a 6th-to-8th-grade United States (US) reading level (about 12 years of age) while avoiding the use of medical terminology and industry jargon. LS is not only about how written content is understood by nonscientists or laypersons but also about the structure, organization, and visual means applied in the LS communication process.

The EU CTR Annex V lists the 10 key elements that must be included in the LS, i.e., the clinical trial identification, name and contact details of the sponsor, general information about the trial, trial population, investigational medicinal products used, description of adverse reactions and their frequency, overall results of the trial, comments on the outcome of the trial, indication if follow-up clinical trials are foreseen, and indication where additional information can be found.

Lay Summaries as the Connecting Factor Between Stakeholders

Increased transparency in communication with patients builds and maintains public trust in and awareness of health research (i.e., through scientific publications) and clinical trials. In a digital world where information is increasingly accessible to the public, life science companies as well as other stakeholders within the health ecosystem should consider the patient empowerment that comes from and with transparency initiatives.

The availability of a LS at the end of the clinical trial process provides not only closure, but also valuable information that may change the course of a participant’s disease journey. Summaries cocreated and/or reviewed by the patient community help to ensure that the LS focuses on or includes information that is important to the community.

Patient involvement and engagement initiatives, including cocreation and dissemination of LSs, may also increase participant recruitment and retention in clinical trials. Healthcare professionals may also find LSs extremely valuable for communicating current clinical findings of a particular treatment option to their patients.

Similarly to LSs, PLSs—which are increasingly expected by scientific journals (e.g., Elsevier,1 Future Science Group,2 and Sage Journals3)—provide the public and patient community an access point to scientific information in an understandable way. This helps lower the barrier for the public to be informed of scientific advances as well as become more involved in health research if they so choose. These PLSs can also be shared by healthcare professionals with their patients to inform them of new or relevant research.

Several tools and guidance documents have been created to lower the barrier for creating PLSs. Some examples include:

Read more about PLS in the April issue of Global Forum here.
Despite the increased awareness of and requirements for LSs, clinical trial participants typically do not receive results of their clinical trial, although they wish to have them. A 2019 survey found that 85% of participants were willing to participate in clinical research, while 68% of those surveyed said a summary of trial results was the most important information they would like to receive (CISCRP 2019). Yet, nearly 61% of participants did not receive a summary of their trial’s results, with 39% noting that they never received a follow-up response from anyone (CISCRP 2019).

Many countries in which LSs for clinical trials are not yet explicitly required, such as the US, have nonetheless shown awareness of and support for LS development. Moreover, companies which are used to operating globally have already started sharing results with their trial participants, through the investigators and/or specific websites.

Cocreated Guidance to Set up Organizational Lay Summary Capabilities

The GLSP “provides recommendations on how to prepare, write, translate, and disseminate summaries of clinical trial results in lay language” in a Quick Guide, as well as a full Handbook format, with detailed instructions for each step of the process and accompanying templates (see Figure 1) (GLSP 2021). The GLSP guidance builds on the initial one released in 2017 by the EU commission and on the experience gained so far by sponsors.
Flowchart of the lay summary process
Figure 1. Flowchart of the lay summary process. (Source: GLSP 2021)
When building LS capabilities, sponsors should consider creating LS templates for consistency, flexibility, and compliance with local laws and regulations. A collaborative effort (including relevant patient advisors) will be key in prioritizing finalized data sets. Discussion of key messaging ahead of clinical study report finalization can help sponsors meet the 12-month EU deadline for LSs and incorporate information that is important to the patient community. This increases transparency and involves patients in drug research and development beyond the traditional clinical trial design scope and helps increase not only collaboration, but also trust between the stakeholders. This could even facilitate participant trial enrollment and retention.

Considerations for LSs for Pediatric Studies

When the EFGCP/EFPIA Roadmap Initiative to GLSP started in 2019, experience of LSs for pediatric studies was still limited. Since then, experience has increased, and as part of GLSP dissemination activities, it was decided to use it to assess whether additional pediatric-specific recommendations for the drafting of pediatric LSs could be identified. The future will tell us more as this work will include young patients’ representatives (i.e., Young Patients Advisory Groups, etc.).