FDA (Food and Drug Administration) Releases Final Guidance on “Dear Doctor” Letters That Omits Controversial Behavior Modification Assessment Provision
On January 22, 2014, the FDA issued finalized guidance on the use, content and form of Dear Health Care Provider (DHCP) letters. While the finalized guidance modifies and removes certain controversial provisions from the November 2010 draft guidance that called for manufacturers to conduct assessments of the impact of some DHCP letters, the finalized guidance retains an expansive definition of the health care providers who should receive such communications.
The January 2014 finalized guidance, Dear Health Care Providers: Improving Communication of Important Safety Information (Final Guidance), provides the U.S. Food and Drug Administration’s (FDA’s) recommendations on when manufacturers should issue a DHCP letter, as well as recommendations on the content and format of such letters. Also sometimes referred to as “Dear Doctor” letters, such communications are used by manufacturers to notify health care providers about new or updated information regarding a drug or biologic. The January 2014 guidance finalizes a draft guidance document the FDA had issued on November 12, 2010 (Draft Guidance). In providing context for its recommendations, the agency explains that past studies of DHCP letters found that “the communication quality of the letters—the extent to which the information is accessible and can be understood—has varied widely,” and that the recommendations set forth in the Final Guidance stem in part from the findings of such studies, the FDA’s own experiences with DHCP letters and the FDA’s “general risk communication experience.”
Purposes and Types of DHCP Letters
As described in the Final Guidance, DHCP letters constitute one mechanism by which manufacturers notify health care providers of new or updated information—often relating to safety considerations—regarding marketed drugs and biologics (collectively referred to herein as drugs). The Final Guidance limits its discussion of the types of DHCP letters to those that are specifically identified in FDA drug regulations (21 C.F.R. § 200.5), but adds that other types of DHCP letters not specifically enumerated in the regulations may nonetheless be guided by the concepts and regulations in the Final Guidance. Appended to the Final Guidance are model letters for the three specific types of DHCP letters discussed.
Important Drug Warning Letters
The first type of DHCP letter discussed in the Final Guidance is an “Important Drug Warning” letter. Manufacturers must use such letters to communicate new safety information relating to “a significant hazard to health” that may “affect the decision to use a drug or require a change in behavior concerning use of the drug (e.g., a specific type of monitoring).” For example, an Important Drug Warning DHCP letter may be used to communicate information regarding “[p]reviously unknown serious or life-threatening adverse reactions,” or the discovery of “a subpopulation in which the drug is contraindicated.” The FDA notes that such letters are designed to convey information that would be included in the “BOXED WARNINGS,” “CONTRAINDICATIONS” or “WARNINGS AND PRECAUTIONS” sections of a product’s labeling.
Important Prescribing Information Letters
The second type of DHCP letter specifically identified in the FDA regulations is an “Important Prescribing Information” letter, used to communicate changes in prescribing information that typically belongs in the “INDICATIONS AND USAGE” or “DOSAGE AND ADMINISTRATION” sections of a drug’s labeling. Important Prescribing Information DHCP letters may address, for instance, a change in a drug’s dosing or dosage regimen that is “intended to minimize risk or improve effectiveness.” The FDA clarifies that an Important Drug Warning letter should be used in lieu of an Important Prescribing Information letter in the event changes to the prescribing information also lead to changes in the information under the “BOXED WARNINGS,” “CONTRAINDICATIONS” or “WARNINGS AND PRECAUTIONS” sections of the drug’s labeling.
Important Correction of Drug Information Letters
Finally, a manufacturer should use an “Important Correction of Drug Information” DHCP letter “to correct false or misleading information or other misinformation in a prescription drug promotional labeling and advertising that is the subject of a Warning letter or other Agency action.” The FDA states that the circumstances under which the agency would require a manufacturer to use an Important Correction of Drug Information letter are beyond the scope of the Final Guidance.
Determining Target Audience
Of particular note, the Final Guidance retains—over objections from several stakeholders—a recommendation from the Draft Guidance that a DHCP letter be sent to not only health care providers who could potentially prescribe the drug at issue (including nurse practitioners and physician assistants with prescribing authority), but any health care provider “likely to” dispense or administer the drug and any other health care provider “who may need to know the information even if they do not prescribe the drug.” As the FDA indicated in a July 9, 2013, Federal Register notice, the agency had received a number of comments objecting to these recommendations in the Draft Guidance “as an expansion of the target audience.” The FDA responded, however, that the proposed recommendations merely clarify the regulatory requirement that manufacturers convey “important information . . . to physicians and others responsible for patient care,” and noted that the recommendations reflect the current reality that “a variety of health care practitioners [are] involved in patient care.” The FDA cites as an example emergency departments or primary care physicians who might not prescribe the drug but who might be involved in the care of patients with adverse reactions to prescribed drugs. Likewise, the FDA states that a DHCP letter relating to a new medication guide should be sent to pharmacists, insofar as they are required to distribute the medication guide upon dispensing the drug at issue to a patient.
DHCP Letter Content and Format
In addition to describing the target audience for DHCP letters, the Final Guidance provides detailed recommendations on the information that should be included in a DHCP letter and how such information should be presented. In describing the content of DHCP letters, the Final Guidance includes recommendations for the details that should be in the three particular types of DHCP letters outlined above. The FDA’s recommendations, which also apply to electronic DHCP letters where relevant, address the content and format of various components of a DHCP letter, including the information on the envelope and letter heading, in the subject line and in the body of the letter. For example, the Final Guidance clarifies that manufacturers should refrain from providing information or details—such as market information and promotional language—that could distract the reader from the more important information in the letter.
Modifications to Assessment Provisions
In addition to objecting to the recommendations in the Draft Guidance regarding the target audience for DHCP letters, stakeholders also criticized the proposal that manufacturers conduct evaluations of the impact of DHCP letters. Specifically, the Draft Guidance called for manufacturers to evaluate the extent to which a DHCP letter resulted in behavior modification by the target audience to the extent such modifications were intended. Additionally, the FDA recommended that manufacturers ascertain the extent to which the target audience received and is aware of the information conveyed in each DHCP letter.
In comments to the Draft Guidance, stakeholders asserted that the recommendations imposed overly burdensome requirements on manufacturers that were beyond the scope of the FDA’s statutory authority and that may have the effect of obscuring the message of DHCP letters by introducing unnecessary additional communications. The FDA conceded the validity of these comments. In the Final Guidance, the agency eliminated the provision that calls for manufacturers to assess the extent to which DHCP letters have the effect of altering the behavior of the target audience as intended. The FDA also revised the recommendation that manufacturers conduct evaluations of the extent to which the target audience received and is aware of the information in a DHCP letter, providing instead that manufacturers should conduct such evaluations “for their own use.” Accordingly, under the Final Guidance, manufacturers are not expected to conduct and submit evaluations of DHCP letters for FDA review. The FDA also advises that if the DHCP letter is part of a risk evaluation and mitigation (REMS) requirement for a drug product, there must be an evaluation plan in place under the REMS.
Consultation With the FDA
The FDA encourages manufacturers to work with the relevant review division of the agency on DHCP letters “to ensure that the letter clearly and accurately reflects both the manufacturer’s and FDA’s understanding of the issue and the action required.” Accordingly, in the event a manufacturer learns of new or updated information regarding a drug, early consultation with the FDA may be useful in determining whether a DHCP letter should be issued, the content and format of any such letter, the appropriate target audience for the letter and when the letter should be distributed in light of the issue to which the letter relates.
Considerations for Stakeholders
The Final Guidance provides useful information on the FDA’s expectations of the type and content of safety information that should be included in DHCP letters. The FDA correctly removed its initial recommendation that, for letters intended to modify behavior in the target audience, manufacturers assess whether the letter modified behavior as intended. The FDA also modified its recommendation that manufacturers ascertain the extent to which the target audience received and is aware of the information conveyed in each DHCP letter, now recommending that manufacturers conduct these evaluations for “their own use.” Finally, the FDA retains its expansive definition of health care providers that should receive DHCP letters to include those non-dispensing providers who “may need to know the information.” In view of the new guidance, drug product manufacturers should carefully evaluate their safety reporting programs and assess the impact of these new recommendations and interpretations, including relating to the target audience for particular drug products.