A new final guidance document issued by the US Food and Drug Administration (FDA) provides recommendations for the pharmaceutical industry on how to develop and conduct self-selection studies in support of non-prescription drug products, more commonly known as over-the-counter (OTC) products.
Self-selection studies are used by regulators to determine whether a consumer can reasonably be expected to-and indeed, shows evidence of-select an OTC product for an appropriate purpose and follow the labeling such that it is used appropriately.
For example, a generic manufacturer of acetaminophen, an OTC analgesic, might conduct studies to show that a typical consumer experiencing a headache would be able to appropriately select acetaminophen as a treatment option, take the product as directed and avoid contra-indications or unapproved uses.
But if the principle of self-selection studies is simple, it is, as many things in regulatory affairs are, more difficult in practice. FDA said its guidance document is intended to recognize that self-selection data may be obtained in "a variety of different ways and that each development program raises distinct issues for which flexibility and creativity is important."
Those studies are particularly important for products that are for new nonprescription indications-sometimes known as an OTC "switch"-for a new target population, are risky to certain subpopulations, or are undergoing a significant labeling change.
FDA explains that these studies should generally be open-label, uncontrolled studies meant to assess absolute, rather than relative, understanding of a product.
Study Design Factors
While FDA is available to consult with sponsors regarding the design of these studies, the agency explained that sponsors should generally:
- State the purpose and objectives of the study.
- Specify a study design that meets the study objectives and calculate the appropriate sample size.
- Use labeling that is as similar as possible to the final drug product label.
- Construct a questionnaire that targets the study objectives.
- Minimize factors that may contribute to a biased study (e.g., sampling, recruitment strategies, leading questions, interviews that bias the responses in a particular direction).
- Enroll a population appropriate for the study objectives.
- Enroll subjects with low and normal literacy skills.
- When necessary, enrich the study with subjects who have relative or absolute contraindications to use of the drug product.
- Consider pilot testing before conducting a large self-selection study.
Some of these factors are somewhat counter-intuitive. For example, FDA advises sponsors to enroll a certain number of patients with "low literacy" skills to determine whether those who are unable to read well are still able to properly use the medication. Educational level, FDA notes, is not a proper proxy for literacy. Sponsors are encouraged to use a validated literacy test like the Rapid Estimate of Adult Literacy in Medicine (REALM) test to assess study subjects for literacy.
The full guidance, which includes information regarding the appropriate sample size and examples of study designs, may be found here.