By Deborah Collyar, Mat Stevens, and Catina O’Leary
The European Medicines Agency (EMA) now requires Plain Language Summaries (PLS) for clinical trials with sites in the European Union (EU),1 and other countries have followed suit with regulations or statements that support the EMA regulations. While the FDA has no current regulations for PLS, they fit into the Patient-Focused Drug Development (PFDD) guidance documents (1–4, both final and planned).2 In addition, given the FDA’s push for plain language in clinical trial informed consent forms and drug labeling, it seems likely that the FDA will adopt PLS regulations soon.3
Many companies have already incorporated PLS into their transparency, data disclosure, or medical writing processes. With all the time, effort, and money that is being dedicated to writing PLS, it would be unfortunate if they did not return value to the intended audiences and to each company.
While PLS are prioritized to meet the needs of trial participants who expect summary results, those participants are not the only audience for these materials.3,4 Patients (and their family members) are also interested in the information offered by PLS once they receive a diagnosis for a medical condition. Patient advocacy groups (PAGs) use them to keep track of advances to keep their communities informed. Healthcare providers also use PLS to stay up-to-date and find new information for patients. By providing useful PLS for all these intended audiences, companies can achieve benefits from their PLS investments.
Efforts to create PLS are necessary, but not sufficient to make them effective. A PLS can do more than simply check a box on a form to meet regulatory guidelines. An effective PLS provides participants with feedback they need about expectations from a trial while providing the sponsor with valuable insights into their patient communities.
People not only want to know more about the trial results but also want to use the information in their decision-making processes. Through audience testing and survey processes associated with close to 100 PLS, Health Literacy Media (HLM), a non-profit health communications company, has assessed what people expect in PLS. Across summaries, patients and caregivers respond that the most important factors people hope to understand from the PLS include treatment effects and adverse events, followed closely by who was in the study and how closely the study participants match their individual characteristics.
Why Test PLS Before Publishing Them?
Providing quality tested PLS conveys why a clinical trial is important (using non-promotional language) while building goodwill, developing potential relationships, and solidifying value by showing patient communities the sponsor wants to better understand and fit patient needs.
While more resources such as skills training and staff time are needed as sponsors develop a PLS process that includes user testing, it also builds important informational resources for future clinical trials. Testing language in the PLS can help build a database for how to communicate complex topics across the entire clinical trial process. Planning an effective PLS process requires time and effort to build a framework that collects and disseminates information. Knowledge gained from each PLS improves this process and reduces the resources it requires in the future. For instance, HLM spent more time on the first two PLS completed than on the next 20.
Sponsors who have invested in PLS testing are also beginning to reap the rewards of a more streamlined development, protocol, and clinical trial flow.5 This testing can help create patient input for protocol development and can touch many departments to help achieve their goals, including:
- Legal, regulatory, and compliance
- Research and development
- Clinical operations and clinical trials operations
- Statistics and data management
- Project management and medical writing
- Medical affairs and communication5
PLS testing helps identify key barriers that may inadvertently cause misconceptions and potential resistance to companies and their products. Testing helps identify confusing language and concepts. Testing also offers suggestions to bridge language that covers different cultures and how they perceive the information. This can include unintended word choices and colloquial idioms that can creep into common practice, or how people may interpret icons and colors differently across countries and cultures.
PLS testing discovers what matters to patients and PAGs, and this information can help future trial efforts meet FDA PFDD requirements (e.g., Patient-Reported Outcomes, more patient-focused endpoints, broader eligibility criteria, relevant trial procedures). It also helps sponsors learn what specific patient groups know and what they expect to see. For instance, patients with rare diseases and relevant PAGs may be more interested in daily movement and functionality (e.g., Duchenne muscular dystrophy) while others may be keen to discuss biomarkers and endpoints (e.g., lung cancer).6,7
Sponsors who test PLS with patients and their representatives may also improve public opinion of the company, which can currently be as low as 25%.8 Using testing results to aid future recruitment can also improve the whole research development pipeline. PLS testing results can also help inform future documents such as informed consent forms (ICF) and recruitment/retention materials as well as development plans, FDA/EMA meetings and reviews, and protocol development.
Evolving Practices For Testing PLS
Planning helps define goals for each PLS and for the PLS process to make them as valuable as possible to all audiences while becoming more cost-effective. At a minimum, relevant patient and caregiver audiences can be found for each disease or medical condition. Testing with diverse patient representatives also maximizes the variety of perspectives from patient communities and loops back to future development. Healthcare providers also find PLS useful. If the sponsor plans to post PLS on public websites, they should also consider how the public may interpret their content.3,4,10
Some of the most helpful methods for PLS testing include one-on-one interviews and patient panels. Both methods offer important insights and differ in the resources they require. For instance, one-on-one interviews can help identify confusing language and content that can be misinterpreted. They can also explore the causes of these issues in a safe, comfortable environment that allows honest, critical feedback. One-on-one interviews may be especially important as a method to understand feedback from community members who may not share in a group setting because they feel less comfortable with their reading or science literacy levels. One-on-one interviews require considerable staff time to conduct and analyze their feedback.
Patient panels, like one-on-one interviews, can identify harder-to-understand sections of a PLS, providing more general feedback in less time. The quality of the panel’s feedback often depends on the facilitator’s skills, and they require panelists to share similar backgrounds to encourage sharing and avoid dissonate feedback. This means it may be necessary to hold multiple panels to ensure coverage from communities of color and other traditionally under-represented groups. It is important to note that if the same panel is used across multiple PLS, panelists often become “experts” over time, resulting in feedback that is different from the intended audience for the PLS.
For either method, data from these processes provide deep insights into concepts that are fundamental to public communication of clinical research. For instance, HLM has found that people almost always assume that the adverse events listed in a PLS are caused by the trial’s treatments, no matter how much it explains otherwise. HLM has also gathered data on differences between how the public and research community define certain health terms. For example, people often define inflammation by the noticeable symptoms (such as swelling, redness, and heat) while researchers define it as an immune system response.9 This often leads to confusion in a PLS, especially regarding autoinflammatory diseases. Testing that finds these kinds of miscommunication can prevent further misperceptions and lead to greater public receptivity.
Optimize Returns On The PLS Process
PLS require an investment to create clinical trial result summaries that are understandable and usable to trial participants and broader audiences. Companies can get a return on this investment by testing PLS with intended audiences to ensure they provide needed and useful information. PLS test results can also inform and improve future clinical trials and procedures by creating protocols that consider patient needs and preferences, decreasing the time it takes to recruit, enroll, and retain participants through the trial. It may also possibly lead to smoother commercial market acceptance and reimbursement. Clinical trials that are designed with patient experience may result in higher levels of patient participation, engagement, satisfaction, and trust over time.
- Regulation (EU) 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC  OJ L158/1, Article 37.
- United States, Food and Drug Administration. “FDA Patient-Focused Drug Development Guidance Series for Enhancing the Incorporation of the Patient’s Voice in Medical Product Development and Regulatory Decision Making” 87 Fed. Reg. 39101-39103 (June 30, 2022).
- “Draft FDA Guidance on Provision of Plain Language Summaries.” MRCT Center, Sept. 7 2017, https://downloads.regulations.gov/FDA-2017-D-5478-0001/attachment_1.pdf.
- “Good Lay Summary Practice.” Clinical Trials Expert Group, 2021, https://health.ec.europa.eu/system/files/2021-10/glsp_en_0.pdf.
- National Academies of Sciences, Engineering, and Medicine. 2020. Health literacy in clinical research: Practice and impact: Proceedings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/25616.
- Contesse, Marielle G et al. “Development of Duchenne Video Assessment scorecards to evaluate ease of movement among those with Duchenne muscular dystrophy.” PloS one vol. 17,4 e0266845. 13 Apr. 2022, https://doi.org/10.1371/journal.pone.0266845.
- "Biomarker Testing." LUNGevity, 2021, https://www.lungevity.org/for-patients-caregivers/navigating-your-diagnosis/biomarker-testing.
- Brenan, Megan. “U.S. Business Sector Average Rating Worst since 2008.” Gallup.com, Gallup, 15 Sept. 2022, https://news.gallup.com/poll/400835/business-sector-average-rating-worst-2008.aspx.
- “Immune Response: Medlineplus Medical Encyclopedia.” MedlinePlus, U.S. National Library of Medicine, https://medlineplus.gov/ency/article/000821.htm.
- www.trialsummaries.com. Accessed 10/1/22.
About The Authors:
Deborah Collyar founded the Patient Advocates in Research (PAIR) international communication network in 1996, "where research meets reality," and consults with health and medical research communities. She has been a leader in patient engagement and advocacy since her first cancer diagnosis and applies her business leadership, IT, and communication skills to bridge gaps between scientists, medical providers, governments, and patients.
Mat Stevens is the clinical trial & science communications program manager at Health Literacy Media (HLM) and has worked in public science communications for more than 12 years. He holds bachelor’s degrees in both chemistry and science education.
Catina O’Leary, Ph.D., LMSW, is the president & CEO at Health Literacy Media (HLM), a health literacy-focused nonprofit organization based in St. Louis, Missouri.