Good Lay Summary Practice
FAQ
What is the big change has taken place for clinical trials in the EU?

The key recent change for clinical trials is the legislation governing them. The EU has effectively moved from an EU Directive to an EU Regulation for clinical trials on medicinal products for human use. The EU Clinical Trials Directive, in effect since 2004, has thus been replaced by the EU Clinical Trials Regulation 536/2014.

This new Regulation contains a particular Article (no. 37) that states that sponsors must not only report the results of trials, whether they were successful or not, but that they must also provide a lay summary of these results.

A Regulation is directly applicable and does not require national implementation. It is automatically in force in all EU member states (plus Norway, Iceland, and Liechtenstein) and has the same legal effect in each of these countries.

What is the goals of Clinical Trial Regulation?

Key goals of the Regulation are increasing transparency, efficiency, and cooperation in clinical trials’ performance and information throughout the EU. Lay summaries is just one part of this overarching goal.

What are the expectations mentioned in the Regulation?

Lay Summaries are now a legal requirement for all clinical trials that have at least one trial site in the EU.

Article 37 of the Regulation states:

“… irrespective of the outcome of a clinical trial, within one year from the end of a clinical trial in all Member States concerned, the sponsor shall submit to the EU database a summary of the results of the clinical trial… accompanied by a summary written in a manner that is understandable to laypersons.”

Who is expected to produce these lay summaries?

Both commercial and non-commercial sponsors who have run a trial in at least one EU country are obliged to produce an accompanying lay summary.

This expectation applies thus to both pharmaceutical companies as well as investigators running trials while working in non-corporate settings, for academia, universities, university hospitals, charities, or NGOs.

About how many trials are carried out in the EU per year?

According to the information provided by EMA, there are more than 3,000 clinical trials with medicinal products authorised per year in the EU.

Watch this introductory video by the European Medicines Agency (EMA) herehttps://youtu.be/0nQ2ABHa9L0

What are the key deliverables for sponsors according to the Regulation?

Lay summaries must be uploaded to EU portal 12 months after the end of the study. LSLV, which means “last subject last visit”, is usually considered the end of study. But for studies in children, the sponsor has only 6 months to upload the lay summary.

Content of the lay summaries must follow the legal requirements, should consider the available GLSP guidance, and be strictly non-promotional.

The sponsor should apply a consistent approach for lay summaries across all studies. Sponsors should form a dedicated team for the lay summaries process, including plain language experts.

In detail, what does the Regulation say the language summary must contain?
The Clinical Trials Regulation, Annex V, page 71, lists the essential elements of the lay summary.
It states:
The summary of the results of the clinical trial for laypersons shall contain information on the following elements:
1. Clinical trial identification (including title of the trial, protocol number, EU trial number and other identifiers);
2. Name and contact details of the sponsor;
3. General information about the clinical trial (including where and when the trial was conducted, the main objectives of the trial and an explanation of the reasons for conducting it);
4. Population of subjects (including information on the number of subjects included in the trial in the Member State concerned, in the Union and in third countries; age group breakdown and gender breakdown; inclusion and exclusion criteria);
5. Investigational medicinal products used;
6. Description of adverse reactions and their frequency;
7. Overall results of the clinical trial;
8. Comments on the outcome of the clinical trial;
9. Indication if follow up clinical trials are foreseen;
10. Indication where additional information could be found.
Lay Summaries: What are they What are they not
Lay Summaries must be:
  • developed using the method of plain language communications: easy to understand
  • a summary of clinical study results for participants/for all clinical trials with at least one trial site in the EU
  • short, factual, non-promotional
  • express appreciation to participants
  • submitted in one EU language but also available in all languages of the trial
  • have a ready age of about grade 8 (meaning eight years of formal schooling)
  • linked one study only (not a summary of two or more studies)
  • hosted on the CTIS portal and potentially on the sponsors website
 
Lay Summaries ARE not:
  • publication-associated plain language summaries (PLS): i.e., peer-reviewed/ peer-oriented publications and/or congress material
  • standalone plain langue summaries of publications (PLSPs): full-length secondary publications that translate a primary manuscript, and may include the patient voice or patient authors.
Who is the target audience of the lay summaries?
  • The general public: lay summaries should be understandable to everybody, whether patient; carer, or a lay person in the public.
  • Trial participants: lay summaries should be provided in all languages of the trial participants
  • Patient organizations
  • Pharmaceutical companies
  • Other research sponsors
  • Anybody involved in medical care
What are the key benefits of sharing and disseminating lay summaries?
  • Reaching the "general public": patients, carers, scientists, healthcare practitioners, clinical researcher organisations; media, and citizens.
  • Building the public trust in clinical research and pharmaceutical development.
  • Empowering patients.
  • Boosting transparency: improved transparency in reporting clinical trials results, a transparency obligation to all trial participants and the interested public.
  • Reducing "waste" (wasted efforts) in research, estimated by The Lancet in  2014 to be as high as 85%.
  • Increasing the general understanding of the value of patient and public involvement and non-expert engagement.
  • Contributing to citizens understanding of diseases and treatments.
  • Facilitating shared decision-making.
  • Improving health literacy, which leads to improved health outcomes.
  • Mitigating misinformation.
  • Raising awareness about research findings (so new audiences can find them)
Where are we in the timeline?

Timeline: When did the new Regulation come into effect

This Regulation came into effect in January 2022, after the launch of the EMA’s Clinical Trials Information System, an online portal designed to aid the dissemination of such summaries. After a one-year transition, from 31 January 2023, the use of CTIS was mandatory.

https://euclinicaltrials.eu/about-this-website/lang=en

 

Timeline: From 31 Jan 2022 to 31 Jan 2023, how did sponsors use the CTIS

The Clinical Trials Information System (CTIS) was launched on 31 January 2022, starting the clock for the one-year transition time for sponsors of clinical trials.

During the first year of the transition period, clinical trial sponsors could choose whether to submit an initial clinical trial application in line with the Clinical Trials Directive or under the Clinical Trials Regulation, via CTIS. Both were possible.

The last date for sponsors to submit initial clinical trial applications under the Clinical Trials Directive was 30 January 2023.

Information on individual clinical trials initiated before 31 January 2022 can be found in the European Union Clinical Trials Register: https://www.clinicaltrialsregister.eu/ctr-search/search

 

Timeline: From 31 Jan 2023 to present, where must trials and summaries be submitted

Since 31 January 2023, all initial clinical trial applications in the European Union (EU) must be submitted via the Clinical Trials Information System (CTIS).

Since then, the use of CTIS became mandatory for all clinical trial applications in the EU. For trials authorised under the Clinical Trial Directive, sponsors can continue to perform their clinical trial  under the regime of the Clinical Trial Directive, until the end of the transition period on 30 January 2025.

CTIS is now the single-entry point for sponsors and regulators/ethics committees of clinical trials for the submission and assessment of clinical trial application dossiers.

The CTIS is structured in two restricted and secured workspaces (sponsor workspace and authority workspace) and a public website.

 

Where can one find updates on the CTIS?

EMAs “CTIS newsflash” contains key updates on the latest developments, including system improvements, and links to useful reference materials.

To sign up for a newsletter giving updates on CTIS progress, write to <CTIS.communicationema.europa.eu>

You can read past issues of “CTIS newsflash” here.

What will motivate sponsors to produce lay summaries in consultation with patients and lay members of the public?

Good Clinical Practice: a foundation of all biomedical research

Involving patients in a consultative way in all aspects of clinical trials is a central aspect in the new Good Clinical Practice (GCP) framework, presented in the ICH E8(R1) guideline on “General considerations for clinical studies”. One of the “Critical to Quality Factors” raised there: The reporting of the study results is planned, comprehensive, accurate, timely, and publicly accessible. Study sponsors need to adhere to GCP throughout their work and ensure that publicly accessible result reports are presented in a lay-friendly way.

EudraLex: providing lay summary recommendations within the regulatory framework for clinical trials

Importantly, the GLSP Guidance was adopted by the Clinical Trials Expert Group (CTEG, a working group of the European Commission). In a crucial and remarkable step, on 4 October 2021, the Good Lay Summary Practice Recommendations were published in EudraLex: a collection of rules and regulations that govern the EU pharmaceutical development.

What is the influence and impact of EudraLex EudraLex is the collection of rules and regulations governing medicinal products in the EU. These regulations aim to ensure that medicinal products are safe, effective, and of high quality, and that they are marketed and distributed in a manner that protects public health.

How were the EFGCP and EFPIA situated to drive the development of the Good Lay Summary Practice Roadmap Initiative and the resulting guidance?

The European Forum for Good Clinical Practice (EFGCP) is the leading European multi-stakeholder forum where science, quality, and ethics meet to promote Good Clinical Practice in clinical research and development. EFGCP is a non-profit organisation established by and for individuals with a professional involvement in making medicines and medical devices available to patients.

The European Federation of Pharmaceutical Industries and Associations (EFPIA) serves as the voice of the research-based pharmaceutical industry operating in Europe. EFPIA’s mission is to create a collaborative environment that enables our members to innovate, discover, develop, and deliver new therapies and vaccines for people across Europe, as well as contribute to the European economy.

Joining forces to create the GLSP Initiative, EFGCP and EFPIA convened 60 participants from EU and US pharma companies, contract research organizations (CROs), academic institutions, patient organisations, and not-for-profit organisations to create the GLSP Roadmap Initiative with the aim to jointly develop the best practice framework for lay summary planning, preparation, translation and dissemination with involvement of patients in all steps. Their contributions will help to ensure availability of trial result communication that is interesting and meaningful for patients and the public.

Through information and education of all stakeholders in GLSP, the compilation of all available and updated information on this website, and multi-stakeholder discussions in conferences and workshops the GSLP Roadmap Initiative strives to globally implement this transparency standard..

What does the future hold for clinical trial lay summaries, beyond the EU?

Outside the European Union there is no  legislation on lay summaries. The US Food and Drug Administration (FDA) encourages the production of “plain language summaries”, but this is not legislated. The trend in citizen science is to promote plain language in science and to increase health literacy among the public, both of which lead to better outcomes: better health results for people.

What exactly is plain language?

Plainlanguage.gov, an official website of the United States government, states:Plain language is communication that your audience can understand the first time they read or hear it.

According to the Plain Language Association International:

“A communication is in plain language if its wording, structure, and design are so clear that the audience can easily find what they need, understand what they find, and use that information.”

Note that the Clinical Trial Regulation does not define the needs and conditions for lay summary translations. In CTIS a lay summary in one language is required to be submitted within 1 year after end of the trial. But there is an option to upload more language versions with an undefined timeline.  GLSP states that lay summaries should be provided in all languages of the trial participants (so they can understand the results of the trial that they took part in).

Where can I see examples of lay summaries done by pharmaceutical companies?

As the Regulation is relatively new, it will take a while to find lay summaries on the CTIS portal. Especially larger pharma companies voluntarily prepare lay summaries since several years. But there is no global central place where lay summaries can be found. In the meantime, you can consult Trialsummaries.com, to see how some sponsors are preparing lay summaries in anticipation of the changes.

Where can I find more information about reading levels and tools for assessing readability?

The GLSP recommends reading age about Grade 8 thus 12 years of age.

 

3.4 Writing and Presentation of the Lay Summary

One of the most demanding steps in the LS production process is authoring and presenting the LS in a way which meets the needs and literacy levels of the target audience. Efforts should be made to prepare LS which are understandable for the general public as of the age of 12 years. In contrast to scientific writing, which is designed for a narrow professional community, the LS should address the public at large and thus make the summary understandable, readable, and accessible for a heterogenous lay audience with no scientific knowledge...

 

Eight years of schooling is believed to correspond to a person of 11 or 12 years of age (assuming one starts school around 5 of 6 years of age). But please note that it is more polite and less stigmatising to refer to approximate years of schooling, than to a person’s age.

For paediatric trial summaries, however, the GLSP Guidance recommends three age ranges: up to 8, 9-11, 12-17 (adolescents). 

Many tried and tested tools are available:

Flesch Reading Ease (FRES)

The FRES is widely used. It checks average sentence and word length. Gives a score from 0–100 (higher score = text is easier to read). Ideal score is between 70 to 80 (equivalent to school grade level 8).

Flesch-Kincaid Readability Score (FKRS)

The FKRS is widely used. It translates the 0–100 from the previous tool score to a grade reading level. Ideal score is 7 or 8, scores of 12 or more are too difficult for most people to understand.

Gunning Fog

The Gunning Fog checks average sentence length and number of words of 3 or more syllables. Ideal score is 7 or 8, scores of 12 or more are too difficult for most people to understand.

 

Simple Measure of Gobbledygook  (SMOG)  Index

The SMOG Index measures number of sentences and words of 3 or more syllables. Gives a grade reading level. Thus the recommended score for school grade 7 or 8 level would be a score of 7 or 8.

 

Note that the SMOG is recommended by Cochrane Collaboration, an independent international organization that produces high-quality and accessible systematic reviews to inform evidence-based health decision making.

 

Other tools: the New Dale–Chall Readability Formula (NCDRF)

Read-able: webfx.com/tools/read-able/

TheWriter.co.uk readability:  https://www.thewriter.co.uk/tools/readability

Readability Formulas: https://www.readabilityformulas.com/free-readability-formula-tests.php  which enables you to run as many as seven scores at once

See also: PFMD How-to Guides for Patient Engagement, p. 37 for the development of plain language summaries of publications.

https://www.plainlanguagesummaries.com/pfmd-how-to-guide-plain-language-summaries/,

 

How should sponsors go about the planning, development, translation, and dissemination of lay summaries?

As advised in the GLSP guidance, sponsors need a consistent approach for lay summaries across all studies, a dedicated team including plain language experts, and to keep patient involvement integrated in their strategies for lay summaries: planning, developing and writing, translation, and dissemination.

Planning

  • Plan for the entire lay summary process and create a Standard Operating Procedure (SOP) that covers writing, review, and dissemination of lay summari