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The GLSP (Good Clinical Summary Practice) recommendations for creating and disseminating lay summaries (LS) of clinical trials. The LS aim to provide objective and clear information on trial results to sponsors, trial participants, and the general public. Pediatric studies may require child-focused versions of LS. LS should be coordinated with publication plans and regulatory requirements. Patient contributions are valuable in LS planning and review. Complex trials may require different LS approaches. Once final trial data are available, a person experienced in clinical trial result presentation should prepare the LS draft.
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Document history: Date of adoption by the expert group on Clinical Trials 9 July 2021 Date of publication 4 October 2021
This “Good Lay Summary Practice” (“GLSP”) provides recommendations on how to prepare, write, translate, and disseminate summaries of clinical trial results in lay language. This is a mandatory requirement laid out in Regulation (EU) No. 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use^1 (“EU CTR”) and a transparency obligation to all trial participants and the interested public.
The GLSP is organised in two parts. Part 1 is a GLSP Quick Guide and Part 2 is the full GLSP Handbook. The GLSP Quick Guide contains core extracts from the GLSP Handbook and may serve as an overview of the recommendations offered in the Handbook. Since the intention of the GLSP is to provide practical recommendations and strive for good lay summary practices, professionals directly involved in lay summary projects are encouraged to read the full handbook to benefit from the detailed recommendations. The GLSP recommends clinical trial sponsors to organise the lay summary process (“LS process”) in four steps: planning, development, translation, and dissemination. A stepwise approach will help sponsors with their proactive planning and execution and will ensure a high quality of the lay summary (“LS”). However, unless otherwise stated, the order in which information is presented in the GLSP does not necessarily drive a linear process with a set order of priorities. Company or research institutional standard operating procedures (SOPs) and other considerations may require activities to be performed in another sequence. The four steps and related core activities are depicted in the flowchart below with further defined input and output. It is recommended that the trial sponsor determines which output or deliverables may be desired before a next step is initiated. For easy navigation, both the Quick Guide and the Handbook are organized in the same way. Throughout the GLSP, the use of the word “must” refers to legal requirements, as laid out in the EU CTR, whereas the use of the word “should” refers to optional recommendations (anchored in ethical obligations and best practices). To further aid this distinction, mandatory requirements under the EU CTR are marked with a “§” icon throughout the GLSP. In addition, to easily identify recommendations on paediatric LS, a paediatric icon is added to relevant text sections. The Appendices offer supplemental information. Appendix 1 contains additional useful considerations and information related to each step of the LS process. A list of glossaries is included in Appendix 2 and a number of additional guidance references are presented in Appendix 3.
ADR Adverse Drug Reaction AE Adverse Event AESI Adverse Event of Special Interest CDC Centers for Disease Control and Prevention CSR Clinical Study Report CTCAE Common Terminology Criteria for Adverse Event Reporting CTIS Clinical Trials Information System CTR Clinical Trial Regulation EEA European Economic Area EFGCP European Forum for Good Clinical Practice EFPIA European Federation of Pharmaceutical Industries and Associations EMA European Medicines Agency EPF European Patients’ Forum EU European Union EUPATI European Patients’ Academy on Therapeutic Innovation FDA Food and Drug Administration GLSP Good Lay Summary Practice ICF Informed Consent Form ICH International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use IMI Innovative Medicines Initiative IPPOSI Irish Platform for Patient Organisations, Science and Industry IRB/IEC Institutional Review Board/Independent Ethics Committee LS Lay Summary LPLV Last Participant/Patient Last Visit MDR Medical Device Regulation EU 2017/ MedDRA Medical Dictionary for Regulatory Activities MRCT Multi-Regional Clinical Trials NAP National Academies Press PhRMA Pharmaceutical Research and Manufacturers of America PIS Patient Information Sheet QA Quality Assurance QC Quality Control R&D Research and Development SAE Serious Adverse Event SAR Serious Adverse Reaction SME Small and Medium-sized Enterprise SOP Standard Operating Procedure US United States WAI Web Accessibility Initiative WHO World Health Organization
In line with the EU CT Expert Group’s Recommendations, a well written LS should normally be accessible by young people from the age of 12 years upwards^4. Sponsors of paediatric studies are encouraged to consider developing a child-focused version of the LS for younger trial participants in addition to the version for the parents or legal representatives, particularly where they have already developed an Assent for the paediatric patient’s information about trial participation. LS recommendations in this document apply to aggregate clinical trial results only; therefore, return of individual patient-level data to a given trial participant is out of scope. Although some shared principles may apply, other types of result information to lay audiences, such as plain language summaries of journal publications and conference abstracts, are out of scope. Considering the terms “plain language” and “lay language” as synonyms, the GSLP has adopted the definition of plain language from 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"^5. The GLSP is the result of a roadmap and consultation process integrating the experience and recommendations from more than 60 industry, academia, patient and not for profit organisations from within and outside of the EU in collaboration with Competent Authority and Ethics Committee representatives of the EU Commission Expert Group on Clinical Trials, which are committed to clinical trial result transparency and the development and dissemination of factual, non-promotional, and reader-friendly lay summaries. In addition to the EU CT Expert Group Recommendations (entitled “Summaries of Clinical Trial Results for Laypersons. Recommendations of the expert group on clinical trials for the implementation of Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use”^4 ), the GLSP takes into consideration the recommendations from TransCelerate BioPharma on “Layperson Summaries of Clinical Trials”^6 and from the Multi-Regional Clinical Trials (MRCT) Draft FDA Guidance on Provision of Plain Language^7.
Timing of the Lay Summary Planning of the LS should start at the time of protocol preparation. LS planning including translations (where applicable) should be aligned with the preparation of the Patient Information Sheet (PIS) and the Informed Consent Form (ICF), since these documents partly share content and readership. A coordinated approach across these documents can reduce duplication of effort or discrepant use of plain language terminology. When planning the LS, its dissemination should be coordinated with the publication plans for the clinical trial results in general but also with the regulatory requirements for posting trial results on databases such as EU Clinical Trials Register^8 , the EU Portal (mandatory upon implementation of the EU CTR), or on others such as ClinicalTrials.gov. For multinational and multicentre trials, LS dissemination should be coordinated across all trial sites, and if distribution is planned via investigational sites, access to
information for all participating patients should be considered in the interest of fairness. For additional recommendations on the timing of the LS, refer to Section 2.1 in the GLSP Handbook. Lay Summary Production Planning LS development and dissemination approaches may differ, e.g., according to the type of clinical trial or resource capacity of the sponsor. Sponsors should develop a standard operating procedure (SOP) for their LS approach. Use of a LS template (e.g., in line with the EU CT Expert Group’s Recommendation) can aid efficient and consistent preparation of LS. It may be helpful to pre-fill the template with general information on the trial and the endpoint presentation structure, and hence create an outline ‘shell’ document, in advance of trial results availability. However, once available, the sponsor must present the main objectives and overall results of the clinical trial^1. The EU Portal provides an option for uploading of interim scientific summary of trial results but does not anticipate this option for a LS of interim results. Should the protocol foresee an interim analysis with uploading of the results to the publicly available EU Portal, and the sponsor plan the preparation of a LS, such LS availability and planned dissemination should be presented in the Patient Information Sheet/Informed Consent Form. Potentially available local restrictions to such dissemination should be respected. Complex clinical trials (e.g., basket, umbrella, or platform trials) can contain separate parts that constitute individual clinical trials, or they can be characterised by extensive prospective adaptations. For these complex designs, the end of trial definition(s) applicable to individual parts and the results- sharing strategy should be carefully planned. Planning should foresee that the chosen approach will be addressed in the Patient Information Sheet/Informed Consent Form and reviewed during amendments. To enable adherence to the LS finalisation timelines, the LS review process needs to be efficiently planned. According to the sponsor’s SOP other stakeholders may be involved in the LS review process, e.g., scientific/statistical experts, patient representatives, legal and medical communication experts and/or investigators. Their involvement and tasks should be well defined and logistically structured. At the time of LS finalisation, it is recommended that the sponsor’s content owners document their approval of the LS. Having finalised and “locked” the LS content in source language, the document can then be entered into the EU Portal, and potentially further translated and disseminated. When trial sites are located outside the EU, the sponsor will need to track local LS requirements to ensure regulatory compliance. For additional recommendations on Production Planning for the LS, refer to Section 2.2 in the GLSP Handbook. Cost Implications Generally, but especially for resource-limited sponsors from academia, charities, or Small Medium-sized Enterprises (SME), planning of the process and resources required for production and dissemination of a LS should begin with budgeting at the time when a research proposal for a clinical trial is submitted to a funding source. Budget implications such as patient involvement in the LS process, costs of standard or special patient population communication tools, and for translations and/or dissemination beyond the CTIS need to be factored in at the proposal stage. For additional recommendations on Cost Implications, refer to Section 2.3 in the GLSP Handbook. Stakeholder Communication If direct dissemination of the LS to trial participants is planned, investigators should be made aware of their roles pertaining to the LS as early as possible and the contractual conditions agreed.
Element 2: Name and contact details of the sponsor. Sponsors may need to establish procedures, specifying how to handle public contacts based on the information provided in the LS. National regulatory guidance and local law may need to be consulted regarding the provision of topics concerning medical information. Element 3: General information about the clinical trial. In addition to the information recommended by the EU CT Expert Group (including trial rationale, objectives, location, timing), an explanation of the trial design may be helpful. This may include information on the type of randomisation, treatment arms, use of placebo, titration of medication, wash-out periods, and long-term follow up (where appropriate). Simple diagrams may be a helpful way to communicate trial design, particularly where multiple treatment groups/phases are concerned. Element 5: Investigational medicinal products used. The trial treatments should be named as in the protocol and trial registration. When describing investigational products and comparators, sponsors should not provide promotional information. Repetitive use of compound code names may impair readability. The route of administration should be stated together with the treatment regimen. Element 7: Overall results of the clinical trial. The LS must include the overall results of the trial. The sponsor must present the main objectives and overall results of the clinical trial^1. According to the “Clinical Trials Regulation (EU) No 536/2014 DRAFT Questions & Answers” document, this means that the LS should reflect at a minimum the results of the primary Element 4: Population of subjects (trial participants). This should include main demographics and selection criteria. Care should be taken not to inadvertently identify specific individuals, particularly in trials involving rare diseases. Where there are differences in the numbers of randomised and treated trial participants, information should be presented clearly to avoid confusion. As far as possible, the numbers should align with the number of trial participants referred in the results section. Any differences should be explained in a simple way in the relevant section. Element 6: Description of adverse reactions and their frequency. Adverse reactions must be clearly defined and presented with their frequency. The EU CT Expert Group Recommendations specify that serious adverse reactions should be listed first, followed by other common adverse reactions listed by frequency given in numerical terms and percentages. It should be made clear that these are the results of a single clinical trial. A detailed discussion of safety information in the LS is provided in Section 3.5 of the GLSP Handbook.
endpoint(s) and potentially also patient-relevant secondary endpoints^10. Since no broadly accepted definition for “patient-relevant” exists, sponsors may prefer to limit results presentation to the primary endpoint(s). However, if sponsors plan to select and include patient-relevant secondary endpoints, it is recommended that these endpoints are defined according to an established, documented framework for endpoint selection across all the sponsor’s trials, ideally as early as trial finalisation but prior to availability of interim results, and no later than database look. Secondary endpoints may lack statistical power and presenting such endpoints should therefore aim to avoid lay readers placing undue emphasis on these results^6. Independent of the sponsor’s choice on endpoint presentation a reference link to the complete list of outcomes in the scientific Summary of the Clinical Trial Results (Annex IV) in the EU Database should be included in the LS^4. Additional safety data important to the overall results of the trial should complete the presentation of overall results. Element 9: Indication if follow-up clinical trials are foreseen. Publicly available information about related trials should be provided and sponsors should ensure that the information disclosed is non-promotional. Reference literature should be chosen with caution, providing general sources of information only such as public databases or clinical trial registries. Sponsors may decide to combine the information given on this element with another element, e.g., “comments on outcome.” Element 10: Indication where additional information could be found. This section may provide links to other websites deemed helpful (including industry- based websites and academic websites) or public trial registries. Sponsors need to make sure readers will not unintentionally be exposed to promotional content, or selective presentation of data, via such links. Competencies to Enable Good Lay Summary Development Depending on available resources, the LS can be prepared by a team or an individual, however, a variety of competencies (knowledge, skills, and attitudes) are helpful to prepare a suitable LS. These are: Scientific knowledge Familiarity with the reference and source documents (e.g., PIS/ICF, scientific Summary of the Results, CSR, or full set of structured trial results) Disease and patient/trial participant population characteristics Clinical research methodology Terminology and judgement on safety results Element 8: Comments on the outcome of the clinical trial. This section should state whether the results are applicable to a specific population and should describe the most important limitations. Sponsors should reinforce that the LS reflects the outcome of one single trial and that other trials may show other results or other outcomes.
Layout and Design of Lay Summaries Layout and design are as important as the wording in a LS. Appearance and attractiveness of the LS have a strong impact on whether it may be read at all. The use of headings and descriptive sub-headings, of adequate white space and reduction of unnecessary imagery like logos can help the lay summary appear reader-friendly and accessible. Choice of columns, page breaks and colours can help provide a more attractive structure of the pages in a LS. Further points to consider are presented in Table 3.6 in the GLSP Handbook. Well-chosen and clearly designed graphics or visuals can enhance comprehension of the text^4. Graphics designed with the audience in mind can be powerful in supporting and facilitating the processing of numbers in the text. In general, bar graphs are recommended for comparison across groups and pie charts for numerical proportions. Infographics or pictorial representation can also be useful. Figure 3. offers examples of how numbers can be presented graphically. Section 3.6 in the GLSP Handbook provides further recommendations. Review and User Testing of the LS A LS review by different stakeholders involved in the clinical trial (patient(s), medical monitor, statistician, etc.) is recommended to ensure completeness and accuracy of the LS in all aspects. In resource-limited settings this should at least be envisaged for the LS template. While not mandatory, it is good practice to user test the LS with individuals who are not involved in the trial and unfamiliar with clinical research methodology. Clear instructions on tasks expected from the test persons and a well-prepared feedback process are essential. For additional recommendations on review and user testing of the LS, refer to Section 3.7 in the GLSP Handbook.
Availability of a LS in patients’ native language is an important element of fair access to information. While the EU CTR does not request translations, the EU CT Expert Group Recommendations suggest that as a minimum, the LS should be provided in the local official language(s) of each of the countries where the trial took place, matching the languages employed in the Patient Information Sheet/Informed Consent Form^4 (“PIS/ICF”). Where resources allow, sponsors should consider preparing an English version if the trial did not include the Republic of Ireland or Malta to allow greater accessibility across the EU and globally. Thorough review of the LS before translation, a well-managed translation process, and use of glossaries and pre-defined terminology are helpful for achieving successful translation of LS. Technology and linguistic skills could be leveraged. Even with limited resources or budget, proactive planning and management will facilitate the quality, timeliness, and adequacy of LS to the target audience. The translated LS versions should be made available as soon as possible, ideally in parallel to the release
For additional recommendations on translation of the lay summary and a step-by-step translation process, refer to Section 4 in the GLSP Handbook and Table 7.7 in Appendix 1.
The importance of consistently and reliably presenting the results of all clinical trials in easily understandable language to the public and in particular to trial participants, has also been recognised by global stakeholders involved in patient engagement^11 ,^12. Lay summaries (“LS”) can serve multiple purposes ensuring transparency, knowledge sharing and trust building towards clinical research benefiting current and future clinical trial participants. However, the practice of patient involvement in the lay summary process with the purpose of supporting sponsors’ efforts to better meet patients’ and the public’s needs has not yet been consistently established. Sharing and presenting best practices among different stakeholders should facilitate patient engagement as well as the development and dissemination of LS. 1.1 Purpose & Scope of the Good Lay Summary Practice The EU CTR does not call for LS on non-interventional studies or medical device trials. However, the recommendations provided in the GLSP can be useful in the preparation of LS for such studies, albeit considering that some EU CTR-defined elements may not apply, e.g., the required timelines for preparation of LS. The EU Clinical Trial Regulation (“EU CTR”) 536/2014, Article 37 requires the public dissemination of trial results presented in lay language through the EU Database, a core element of the EU “Clinical Trials Information System” (“CTIS”), at the time of availability of the scientific Summary of Clinical Trial Results^1. Article 37 of the EU Clinical Trial Regulation (EU) No. 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use requests the sponsor to prepare a summary of clinical trial results written in a manner that is understandable to laypersons for interventionalclinical trials with medicinal products in adult and paediatric populations conducted in the EU/EEA^1. The content required in such lay summary is listed in Annex V of the EU CTR.
Suggestions for structure and presentation of the content of lay summaries are provided in the “Recommendations of the expert group on clinical trials for the implementation of Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use: ”Summaries of Clinical Trial Results for Laypersons”^4 (“EU CT Expert Group Recommendations”). This Good Lay Summary practice (“GLSP”) expands on these recommendations and takes into consideration the recommendations from TransCelerate BioPharma on “Layperson Summaries of Clinical Trials”^6 and from the Multi-Regional Clinical Trials (MRCT) “Draft FDA Guidance on Provision of Plain Language Summaries”^7. The GLSP Handbook provides detailed recommendations for best practice in terms of planning, preparation, translation, and dissemination of high-quality lay language summaries of results from clinical trials with medicinal products: The GLSP provides recommendations for building an LS infrastructure and processes with the aim to enable all sponsors to generate and disseminate objective and understandable information on clinical trial results. The GLSP contains recommendations on how to enable patient engagement throughout the LS process although it is acknowledged that sponsors’ resource and infrastructure constraints can limit a routine involvement of patients in the different steps. The GLSP gives recommendations for LS dissemination aiming to inform trial participants and the general public to ensure fair access to information for all. The GLSP recognises and addresses the need for specific skills and strategies for LS on paediatric trials and highlights the limited experience available so far. LS recommendations in this document apply to aggregate clinical trial results only; therefore, return of individual patient-level data to a given trial participant is out of scope. Although some shared principles may apply, other types of result information to the lay audience, such as plain language summaries of journal publications and conference abstracts, are out of scope. 1.2 Target Audience for the Good Lay Summary Practice The target audience for the GLSP constitutes professionals who have been assigned the responsibility to plan, develop, review, translate, disseminate and/or upload LS to the EU Database, as well as stakeholders who wish to offer LS outside of the mandatory EU CTR requirements.
It should become clear from the recommendations in this GLSP that plain or lay language is not only about how written content is understood by non-scientists or lay persons but also about the structure, organisation and visual means applied in the LS communication process.
Planning of the LS should commence during protocol development or even at preparation of a research proposal and related budget. Careful and proactive planning is strongly encouraged to ensure timely delivery of a high-quality and compliant LS. 2.1 Timing of the Lay Summary Early in the trial, LS planning should be aligned with the preparation of the Patient Information Sheet (PIS) and the Informed Consent Form (ICF) since these documents partly share content and readership. A coordinated approach across these documents can reduce duplication of effort or discrepant use of lay language terminology. If the documents are prepared by different writing teams, planning and collaboration between these teams should be enabled. The dissemination of LS should be coordinated with the publication plans for the clinical trial in general but also with the regulatory requirements for posting trial results on databases such as the EU Clinical Trials Register^8 , the EU Portal and Database (mandatory upon implementation of the EU CTR), or others such as ClinicalTrials.gov. For multinational and multicentre trials, LS dissemination should be According to EU CTR, Article 37, the LS must be submitted to the EU Database no later than 12 months from the protocol-defined end of the clinical trial in adults, 6 months in paediatric studies, and up to 30 months for non-therapeutic Phase 1 trials. More detailed rules about the publication of clinical trial results can be found in “Functional specifications for the EU portal and EU database to be audited - EMA/42176/2014”^3. If the summary of results cannot be reported within these timelines for scientific reasons, the summary of results shall be submitted as soon as possible. In that case the approved protocol shall specify when the results are going to be submitted. Deferral of the publication timelines can be requested for approval by the EU Member States concerned either in the initial trial application or as a substantial modification. This requirement applies in all concerned EU Member States irrespective of the trial outcome and is consistent with the timing of the Summary of the Clinical Trial Results submission. In line with the EU Expert Group on Clinical Trials Recommendations, a well written LS would normally be accessible by young people from the age of 12 years upwards 4 . Sponsors of paediatric studies are encouraged to consider developing a child- focused version of the LS for younger trial participants in addition to the obligatory version for the parents or legal representatives^14 , particularly where they have already developed an Assent for the paediatric patient’s information about trial participation.
coordinated across all trial sites, and if distribution is planned via investigational sites access to information for all participating patients should be considered in the interest of fairness. Finally, proactive planning of translations is important for successful results communication in the local languages of patients participating in global, regional and local trials matching the languages employed in the PIS and ICF. 2.2 Lay Summary Production Planning The LS production process requires early and efficient planning to enable all required contributions from different stakeholders in time for meeting the LS completion and submission in line with the respective legal obligations. LS development and dissemination approaches may differ, e.g., according to the type of clinical trial or resource capacity of the sponsor. Sponsors should develop a Standard Operating Procedure (“SOP”) on their organisation’s LS planning, development, review, translation, and dissemination process. In line with the EU Expert Group on Clinical Trials Recommendations^4 , use of a LS template can aid efficient and consistent preparation of LS. It may be helpful to pre-fill the template with general information on the trial and the endpoint presentation structure, and hence create an outline ‘shell’ document, in advance of database upload and trial results availability. Once final trial data are available, a person experienced in clinical trial result presentation and lay language should prepare the LS draft. This draft should be reviewed by the sponsor’s trial team which is familiar with both the trial conduct and the results and which will also review the Summary of Clinical Trial Results, the Clinical Study Report (CSR) or full set of structured study results and/or publication. According to the sponsor’s SOP, other process stakeholders may be involved in the review process, e.g., scientific/statistical experts, patient representatives, legal and medical communication experts and/or investigators. Quality control on the final LS should be carried out by other stakeholder(s) than the LS author to ensure the accuracy of the content against the source data. At any review step, tailored checklists and review instructions will provide helpful guidance to reviewers. Should the final version of the CSR not yet be available at the time the LS writing starts, advanced draft versions may be used. However, in such cases the content of the final LS should be checked against the final version of the CSR or full set of structured study results. In addition, final consistency checks between the scientific Summary of the Results of the Clinical Trial and the LS need to be ensured. Some countries may have national requirements for local posting of LS, and – if outside the EU - also may have different specifications for LS content and format. Thus, sponsors need to track local requirements to ensure regulatory compliance. This will also apply to new sites from additional countries joining after trial initiation. It will generally be the intention to generate a single master version of the LS for all countries. In cases in which country-specific requirements cannot be The EU Portal will accept LS to be uploaded in a PDF file format. This entails materials suitable for print which include text and figures as well as cartoons but excludes videos and animations at the current stage of the technical system. Recommendations in this GLSP are focused mainly on written content and cartoons, e.g., for paediatric trial result LS, to convey storytelling that would be compliant under the EU CTR. However, sponsors are free to develop videos and animations in their LS for separate dissemination.
