We appreciate the opportunity to comment on the FDA’s guidance: “Communications From Firms to Healthcare Providers Regarding Scientific Information on Unapproved Uses of Approved Medical Products, Questions and Answers.”
The National Center for Health Research (NCHR) is a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.
Research indicates that off-label use of medications is common, that physicians prescribing unapproved uses often are unaware that they are doing so, that evidence of safety and efficacy are usually lacking, and that patients are often harmed by off label uses, financially and in terms of their health. That is why it is essential that the FDA provide unambiguous guidance to industry about how to provide information to healthcare providers about unapproved uses of approved medical products.
NCHR agrees with the FDA that any communication between drug firms and healthcare providers regarding scientific information on the unapproved uses of an otherwise approved medical product should be factual and unbiased. However, even when communication is based on high-quality scientific evidence, including randomized, double-blinded controlled superiority trials, the interpretation of the research results can be biased and misleading. That is why all such communication should be subject to regulatory review, as well as clear explanations by the firms to the providers that the product is not approved by the FDA for that purpose, either because the company has not provided evidence to support the off-label use, or because FDA considered any evidence that the company provided to the agency to be insufficient to warrant that off-label indication.
We agree that the FDA should reject the use of scientific communication based on case reports, early-stage development reports, or studies that lack an adequate comparison or control group, even when these limitations are disclosed. Data gathered from these types of studies are insufficient to permit a thorough clinical evaluation for the unintended use of a medical product. Moreover, since not all physicians have expertise in study design and data interpretation, providing such information could easily be misleading or misunderstood.
We strongly support FDA’s proposal to limit the use of presentations to communicate scientific information on the unapproved uses of approved medical products. Because there is rarely enough time to carefully examine the evidence in PowerPoint or other oral presentations, they are unlikely to present information in the full context needed for healthcare providers to interpret the strengths and weakness of the data provided. Presentations may also unintentionally misrepresent or manipulate results, by using figures and graphs that do not fully represent the data. Moreover, the FDA should oppose any communication that uses marketing techniques, since such techniques often unduly influence and bias the audience’s understanding of the risks and benefits of the medical product being considered. All communication should focus on the scientific facts, so that the information will be accurate and understood based on the objective evidence, and healthcare professionals can then accurately share that information with patients. That will enable patients and their providers to make well-informed decisions.
We agree with the FDA that firms should be required to provide a statement identifying that the off-label use of the medical product has not been approved by the FDA and the safety and effectiveness has not been established. A statement acknowledging any serious or life-threatening risks that may be associated with the medical product should also be included, whether the risks have been associated with the approved or unapproved uses. Additionally, a declarations and disclosures statement should be included in these communications that acknowledges investigators who contributed to the design and publication of the study and also had financial ties to the company, whether as employees, consultants, stockholders, researchers, guest speakers, or who received compensation from the firm for any reason. Declarations and disclosures will provide transparency about a financial conflict of interest or the appearance of a conflict of interest that may have affected the design, conduct, or reporting of the research. This will facilitate a healthcare provider’s accurate evaluation of the scientific information provided and awareness of any apparent conflicts of interest or bias.
Lastly, the communication standards specified in this guidance should be consistently and strongly reinforced by the FDA. We recommend that the FDA provides clear instructions encouraging clinicians to report firms that fail to comply with scientific communication standards provided in this guidance. Reporting mechanisms should be made easily accessible and user-friendly for providers and any firms in violation should be publicly reported on the FDA website. This will help ensure that firms incorporate the communication recommendations provided by the FDA and help ensure that clinicians have the information they need to make evidence-based decisions that get past the hype of promotional materials that erroneously purport to be scientific evidence. The bottom line is that transparency in the process and regarding firms that do not comply with the requirements for accuracy and transparency will help safeguard patients from ineffective and unsafe uses of medical products. Given that the FDA frequency distributes press releases to announce the approval of new medical products, it is only right that the FDA be as willing to distribute press releases when companies inappropriately promote unapproved uses or when specific unapproved uses are found to be harmful.