It has been a busy week for new guidance and draft notices from the regulators, and this latest one is new draft guidance for Label Comprehension Studies for Non-prescription (over the counter) drug products.

The Food and Drug Administration (FDA) often requires sponsors to conduct label comprehension studies that are designed to evaluate proposed nonprescription drug product labeling. This guidance is intended to provide recommendations to industry on conducting label comprehension studies. A label comprehension study is a tool that can be used for assessing the extent to which consumers understand the information conveyed by proposed nonprescription drug product labeling and then apply this information when making hypothetical drug product use decisions.

When designing and conducting a label comprehension study it is important to:

• Clearly state the purpose of the study
• Identify the communication objectives (the important concepts that need to be understood by the consumer)
• Enroll a demographically diverse population with varying levels of literacy
• When necessary, enrich the study with subjects who have specific characteristics that are relative or absolute contradiction to the use of the drug product
• Specify a study design that meets study objectives and calculate the appropriate sample size
• Construct a questionnaire that targets the communication objectives
• Use test labeling as close as possible to the final product label
• Minimize factors that may contribute to a biased study
• Compare different versions of the label to study the effect of variations in working and information location on comprehension.

Study Objectives

Primary Communication Objectives: the information that has the greatest clinical significance, target understanding should be 90% or greater. (indications, dose and dose interval, contraindications, warnings, and drug interactions, and when to stop taking the product)

Secondary Communication Objectives: Address areas of less critical importance and 80% or higher understanding is the target. (general health information)

Self Selection: the decision consumers make to use or not use a drug product based on reading the information and applying their own personal medical history.

Study Populations

The study should include all subjects who could potentially use the drug product, regardless of their age, sex, underlying medical conditions, and use of concomitant medications. The study should test label comprehension in a general population whether or not individuals express interest in using the drug product.

Label comprehension studies also should enroll a low literacy cohort. This low literate population should represent a range of low literacy below an 8th grade reading level.

Statistical Considerations and Data Analysis

The primary endpoints should be the endpoints capable of capturing the most relevant and convincing data on consumer comprehension of the critical label elements.

Based on the clearly defined primary endpoints, the study protocol should also specify what criteria determine success for the study. These success criteria should be related to the predefined target level of comprehension for the primary communication objectives.

Sample Size Considerations

The number of subjects in a label comprehension study should be large enough to provide a reliable answer to the primary communication objectives. Sizing of such a study should be based on the success criteria.

Questionnaire Design

The questionnaire design should: 1) clearly reflect the communication objectives of the study; and 2) optimize the validity and interpretability of the information collected. Wording, question structure, and question sequences significantly affect the validity and interpretability of the data collected.

• Questions should assess specific objectives
• Simple vocabulary should be used
• Questions would be direct, specific and unambiguous
• Different types of questions should be used, open, closed etc
• Closed questions should be validated with open-ended probing questions (e.g. please explain your answer)
• if answers are incorrect, open ended probing questions should be issued to investigate the cause of the error
• Leading question should be avoided
• Multiple choice should be clear and only one correct answer (include I don’t know)

Guidance is also provided on location, conduct of the study, data analysis and final reporting and interpretation.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug  development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.