Importance and Best Practices of Readability User Testing

The readability of the package leaflets is an essential factor for the safety and rational use of medicines after they are prescribed or dispensed in pharmacies. Many patients rely on package leaflets to answer questions they may have on their own such as how to use the medicinal product correctly.

In the European Union, all medicine packages are required to include a package leaflet. These leaflets must follow a specific format and be written clearly and easy for patients to understand, as set out by regulatory guidelines.

The content of package leaflets in the European Union is guided by the Quality Review of Documents (QRD) template. First published in 1996, the template has undergone several revisions over time. According to the current version (10.4), package leaflets must follow a specific structure, organized into defined sections:

1. What X is and what it is used for
2. What you need to know before you <take> <use> X
3. How to <take> <use> X
4. Possible side effects
5. How to store X
6. Contents of the pack and other information

All medicines marketed within the European Union must include labels and package leaflets that offer clear and easy-to-understand information, helping users to take the medicine safely and correctly. For all marketing authorisations granted after 30 October 2005, the rules outlined in the amended Directive 2001/83/EC must be followed. This means that all package leaflets in Community or national marketing authorisations need to be reviewed accordingly, and information about patient consultation must be included in the application dossier.

One of the most common ways to meet the legal requirement is by conducting “readability user testing” of the package leaflet. This involves checking how well a sample leaflet is understood by a group of selected individuals. User testing is a flexible development tool used to assess whether the content presents the intended information clearly. The test itself could help to identify areas that may be confusing and need improvement. As a result, based on survey results, Marketing Authorisation Holder may improve the leaflet, introduce more patient friendly wording and improve design before submission of new Marketing Authorisation Application.

The results of user testing should be included in Module 1 of the application dossier. Module 1.3.4 should be submitted with new MAA with initial submission. If a readability user testing report is not available, commitment to submit it later during procedure should be submitted. The latest readability user testing report submission for the MRD/DCP new MAA procedures is D160 responses. This should, of course, be agreed upon with the RMS beforehand.

Regulatory Frameworks Guiding Readability Testing

In the European Union, medicinal product package leaflets are governed by regulations designed to ensure that patients can easily read and understand the information provided. The legal basis for this requirement is set out in Directive 2001/83/EC, which states that all leaflets must be clear and understandable, and that this must be verified through consultations with target patient groups.

Further guidance is provided by the European Commission’s “Guideline on the Readability of the Label and Package Leaflet of Medicinal Products for Human Use” (2009) and the “Guidance concerning consultations with target patient groups for the package leaflet” (2006). These documents outline best practices for the layout and language of the leaflet and provide detailed instructions on how to conduct readability user testing.

The Quality Review of Documents (QRD) template, maintained by the EMA, offers a standardized structure for the leaflet and ensures consistency across the EU.

Key Recommendations for Package Leaflet

Based on the regulatory requirements and guidance the following table summarizes key recommendations for creating a clear, accessible, and patient-friendly package leaflet. These best practices reflect the expectations of EU authorities and aim to support both legal compliance and effective patient communication.

Table 1. Recommendations for the package leaflet

Conducting Effective Readability User Testing

To ensure that a package leaflet meets the required standards of clarity and usability, the user testing process must be carefully planned and executed. The goal is to simulate real-world conditions under which patients would read and interpret the leaflet. The process of user testing for PILs involves several critical steps and the participation of various stakeholders.

Preparation of PIL

Pharmaceutical company prepares the PIL based on EMA guidelines.

Selection of participants

Participants should represent the target patient population in terms of age, gender, education, and health literacy. At least 20 participants from the target population are selected.

Mock-Up Creation

Full-colour mock-up of the PIL is prepared for testing.

Testing Procedure

• Questionnaire Design. The questionnaire is the primary tool for assessing comprehension. It should consist of open-ended, product-specific questions that assess whether users can locate and understand key information (e.g., dosage, contraindications, side effects). Questions should be randomized in order, encouraging participants to search through different sections of the leaflet rather than relying on sequence. Usually, 12-15 questions are sufficient. Additionally, general impression questions to gather feedback on layout, clarity, and overall usability should be included.
• Interview Execution. Testing is conducted through structured, one-on-one interviews. This approach allows for direct observation of how participants interact with the leaflet. The process includes pilot testing with 2 participants to refine the questionnaire and identify any major issues. The main testing phase should include at least 10 participants per round. At least two rounds are recommended to validate improvements and confirm consistent comprehension.

Evaluation of Results

At least 90% of participants must be able to locate and understand the key information presented in the leaflet.

Compilation of report

A report is created summarising the consultation process and results.

Submission to Authorities

The report is submitted to EMA or national authorities for final evaluation.

Other important considerations

While readability user testing for EU procedures can be conducted in any EU member state, it’s important to note that for national procedures, some National Competent Authorities (NCAs) may require the testing to be carried out within their own country. Sponsors should verify specific national requirements early in the planning process to ensure compliance. Once a medicinal product is on the market, the package leaflet may undergo changes for various reasons – ranging from updates to safety or efficacy information, to adjustments in layout, design, or dimensions driven by commercial or practical considerations. These changes can impact the readability and usability of the leaflet and therefore may require additional regulatory steps.

National requirements vary significantly. For example, in Poland, even minor changes – such as adjustments to design, dimensions, or text layout – are expected to be submitted to the Polish Medicines Agency (URPL). This reflects a stricter interpretation of national expectations, where even small modifications may necessitate formal approval or additional justification. Therefore, it is essential for MAHs to consult with the relevant NCA early in the process to determine whether submission of a new RUT is required. This is particularly important in national procedures, where local expectations may differ from those in centralized or decentralized procedures. In addition to these national considerations, certain regulatory flexibilities – such as bridging – may be applied in specific cases.

Bridging is a regulatory approach used when two or more package leaflets are sufficiently similar in both content and layout. In such cases, a successful RUT conducted on one leaflet – the “parent” – can be used to support another – the “daughter” – through a bridging report. This allows the MAH to demonstrate compliance with Article 59(3) of Directive 2001/83/EC, which requires that the leaflet be clear and understandable to the average patient. For bridging to be acceptable, the “daughter” leaflet must follow the same design, layout, and writing style as the “parent”. If these elements differ significantly, the bridging proposal is unlikely to be accepted by the competent authority. Bridging is particularly useful when a product has multiple strengths or pharmaceutical forms. Instead of conducting separate RUTs for each version, a single test may be performed for one, while bridging reports are submitted for the others – saving time and resources during the marketing authorisation process.

Maintaining compliance throughout the product lifecycle requires proactive planning, thorough documentation of changes, and close alignment with national regulatory expectations. While bridging strategies can offer a more efficient path to meeting readability requirements, their success depends on strong justification and regulatory acceptability. In this context, the Regulatory Affairs function plays a key role – not only in evaluating the suitability of bridging, but also in identifying the most effective and compliant approach for each specific case.

Conclusion

Readability user testing is a critical step in the development of patient information leaflets, ensuring that essential medical information is communicated clearly and effectively to the intended audience. By adhering to regulatory guidelines and applying structured methodologies – such as participant-based testing, questionnaire design, and iterative evaluation – pharmaceutical companies can demonstrate both compliance and a commitment to patient safety. Ultimately, a well-tested leaflet supports informed decision-making, enhances treatment adherence, and contributes to the safe and effective use of medicinal products.