FDA-compliant label comprehension studies are a critical part of the U.S. Food and Drug Administration (FDA) clearance process for over-the-counter (OTC) drugs and medical devices. These studies help ensure that consumers can safely and effectively use nonprescription products based solely on their labeling—without guidance from a healthcare professional. To support this, the FDA provides formal guidance on how to design and conduct label comprehension studies that meet regulatory expectations.
For pharmaceutical and medical device companies, understanding and applying FDA guidance on label comprehension studies is essential—especially when pursuing FDA 510(k) clearance for OTC products. In this article, we outline key recommendations and best practices to help ensure your label comprehension study meets regulatory expectations.
What Are Label Comprehension Studies?
Label comprehension studies evaluate how well consumers understand the labeling of nonprescription medical products, such as OTC drugs and medical devices. Labeling includes all consumer-facing materials, such as the outer retail packaging (e.g., container or box), the Drug Facts label, and the Instructions for Use (IFU).
These studies assess whether individuals can accurately interpret key label information—such as dosage instructions, warnings, and intended use—and apply that understanding to make self-directed decisions in hypothetical use scenarios without assistance from a healthcare provider.
Label comprehension studies are often a required component for securing FDA 510(k) clearance of OTC drugs and medical devices. They help validate that labeling effectively communicates critical safety and usage information to consumers. To achieve compliance, manufacturers must design studies that align with FDA regulatory standards and collect data that demonstrates real-world comprehension.
FDA Regulatory Basis for Label Comprehension
The FDA’s authority to regulate label comprehension studies is grounded in the Federal Food, Drug, and Cosmetic Act. This legislation sets the legal foundation for OTC product labeling requirements and consumer safety. It specifically mandates that drug and device labels must be written in a way that an ordinary consumer can read and understand under typical purchase and use conditions—without supervision from a licensed healthcare provider.
The FDA’s Guidance for Industry: Label Comprehension Studies for Nonprescription Drug Products outlines key expectations for designing effective studies. While this document offers important direction, it does not replace a formal FDA review. However, following the guidance significantly improves your chances of obtaining pre-market clearance for OTC products.
How to Design an FDA-Compliant Label Comprehension Study
Designing an effective label comprehension study involves several key components: clearly defining study objectives, selecting a representative participant population, and developing a structured questionnaire to assess understanding. Statistical considerations, such as determining sample size and defining success criteria, are also essential. In the following sections, we’ll break down each element of the study design process in detail.
Defining Communication Objectives for FDA Studies
Before launching a label comprehension study, manufacturers must identify what a typical consumer needs to understand to use the product correctly without professional assistance. These are known as communication objectives—the critical concepts that labeling must convey clearly. Focus your study on testing the sections of the label that communicate these key messages; not all labeling elements need to be evaluated.
Primary communication objectives—those tied to the most significant clinical risks—should be explicitly defined in the study protocol before the research begins. For each objective, the research team should set a target comprehension rate based on the clinical importance of the concept being tested. These objectives often serve as the basis for defining the study’s primary endpoints.
A self-selection study, often conducted alongside a label comprehension study, evaluates whether consumers can determine if an OTC drug or medical device is appropriate for their use. This decision is based on the product labeling—such as the outer packaging or website—and the individual’s personal health history.
Selecting a Representative Study Population
Recruiting a demographically diverse and representative study population is critical to ensuring that findings reflect real-world OTC product users. This includes participants across a range of age groups, racial and ethnic backgrounds, geographic locations, and especially varying literacy levels. Including individuals with low health literacy is particularly important, as these products are used without professional guidance.
To ensure appropriate representation, participant literacy should be assessed during recruitment using validated tools such as the Rapid Estimate of Adult Literacy in Medicine (REALM) or the Test of Functional Health Literacy in Adults (TOFHLA/S-TOFHLA). Education level alone is not a reliable indicator of health literacy and should not be used as a substitute for direct assessment.
Planning for Statistical Rigor and Comprehension Metrics
Critical statistical elements—such as sample size calculation and predefined success criteria—must be clearly outlined in the study protocol to meet FDA expectations and ensure valid interpretation of results.
Primary endpoints—derived from your communication objectives—serve as the key metrics for evaluating consumer comprehension of critical labeling information. These endpoints define the success criteria for your study, often requiring a specific proportion of participants to accurately interpret essential concepts. Sample size should be calculated to ensure statistical validity across relevant subgroups, including those with varying literacy levels.
A robust data analysis plan is equally important. This includes calculating comprehension accuracy rates, evaluating subgroup performance, and, where applicable, analyzing qualitative data from open-ended or root cause questions to identify patterns in miscomprehension.
All statistical considerations—such as endpoint definitions, success thresholds, and analysis methods—should be documented in the study protocol prior to launching the study, forming a foundation for FDA-aligned research design.
Designing Effective Questionnaires for Label Testing
Designing an effective questionnaire is critical to accurately assess label comprehension. Questions should be clearly worded, free of ambiguity, and directly tied to critical label elements such as intended use, dosage, contraindications, and warnings. To meet FDA standards, all content must be easily understood by individuals across a range of literacy levels.
A well-structured questionnaire often includes a mix of closed-ended questions—like multiple-choice or true/false—for quantifiable analysis, along with open-ended questions or hypothetical scenarios to explore participant reasoning. However, open-ended responses must be carefully categorized and interpreted.
When a participant misunderstands a key concept, follow-up questions should be used to identify the root cause. This type of root cause analysis is essential for pinpointing specific areas of label content that may require revision for greater clarity and consumer understanding.
Standardized Label Formats and IFU Testing
The FDA provides a standardized Drug Facts label format for OTC drugs to enhance readability and ensure consistency across products. Adhering to this format is essential, as it directly supports consumer comprehension. If you choose to deviate from the standard layout, you must provide a clear justification in your submission. All labeling content—including the OTC product box and Instructions for Use (IFU)—should be user-tested and refined for readability across various literacy levels prior to study implementation.
Best Practices for Study Implementation and Environment
Conducting a successful label comprehension study requires careful attention to participant recruitment, study setting, and environmental control. Each element plays a critical role in ensuring reliable, FDA-aligned results.
- Recruitment: Select a demographically diverse sample that reflects your product’s intended OTC user population. Include variation in age, ethnicity, region, and—most importantly—literacy level. Use targeted outreach strategies across locations and media channels to engage representative participants. If conducting a self-selection study, be sure to include individuals for whom the product may not be appropriate to evaluate their ability to make informed decisions.
- Study Setting: Choose a study format that simulates real-world product use. In-person designs are ideal when participants need to physically handle labels or Instructions for Use (IFUs), while virtual formats may work well for products typically purchased or used online. In remote studies, consider mailing physical materials to participants in advance.
- Controlled Environment: Whether remote or in-person, the study environment should be quiet, comfortable, and free from distractions to ensure participants can fully concentrate on the labeling materials. Ask participants to silence electronic devices and minimize interruptions during the session.
By thoughtfully managing recruitment and study conditions, you increase the reliability and regulatory relevance of your comprehension data.
Ensuring Data Accuracy and Audit-Ready Documentation
Reliable data collection is foundational to a successful label comprehension study. Use standardized forms or secure digital tools to capture participant responses in real time, reducing the risk of transcription errors. Implement verification procedures—such as double-entry systems or automated checks—to maintain data integrity. Regular audits of your data collection process can help identify inefficiencies, ensure accuracy, and strengthen your overall quality assurance approach in alignment with FDA expectations.
Analyzing Results to Improve Label Clarity
After the study concludes, data analysis should focus on determining whether a diverse group of typical consumers can understand and apply key labeling information accurately. Use your predefined success criteria—typically the percentage of correct responses to each primary endpoint—to evaluate comprehension performance across the full study population and relevant subgroups.
While quantitative results offer clear benchmarks, qualitative data such as open-ended responses or participant feedback can reveal deeper insights into labeling challenges. Identifying patterns in misinterpretation and conducting root cause analysis helps uncover areas of confusion and guides potential improvements to the label or Instructions for Use (IFU), ultimately strengthening your product’s regulatory readiness.
What to Include in an FDA-Ready Label Comprehension Report
The final study report should provide a thorough, transparent account of your methodology, findings, and takeaways. Key components of a comprehensive report may include:
- Executive Summary: Provide a brief overview of the study’s objectives, methodology, key findings, and conclusions.
- Study Objectives and Design: Clearly state the study’s goals, target population, and design process.
- Demographic Breakdown: To show the representativeness of the study population, break down the participants’ demographics, including age, gender, race/ethnicity, geographic location, and literacy levels.
- Data Analysis and Results: This section presents the primary endpoints, statistical analyses, and interpretation of responses and comprehension rates.
- Discussion and Conclusion: If needed, evaluate the findings and note any comprehension challenges or recommendations for label modifications.
- Appendices: Provide supporting materials like data tables, summaries, or analyses.
A thorough report not only demonstrates your study’s rigor but also helps position your label for FDA clearance by showcasing evidence-based design decisions.
A thorough, well-documented report demonstrates the rigor of your label comprehension study and strengthens the case for FDA clearance. It not only reflects your commitment to regulatory compliance but also showcases the care taken to ensure consumer safety. By following FDA guidance and reporting best practices, you position your product—and your organization—for successful market entry. For teams seeking expert support, partnering with an experienced research firm like SoundRocket ensures every element of the study, from protocol to final report, meets the highest standards.