Final FDA Guidance Clarifies Formatting and Content Requirements of “Dear Doctor” Letters without Requiring Behavior Tracking Evaluations
On January 23, 2014, the United States Food and Drug Administration (“FDA”) released a final guidance entitled Dear Health Care Provider Letters: Improving Communication of Important Safety Information, 75 Fed. Reg. 3827 (“Final Guidance”), availablehere, in which the Agency provides recommendations regarding when to issue a Dear Health Care Provider (“DHCP”) letter, what information to include in a letter, how to organize the information, and how to format letters for ease of access by health care providers.
Emphasizing effective and prompt communication goals, the FDA encourages pharmaceutical and biologics manufacturers to consult with the Agency “to ensure that the letter clearly and accurately reflects both the manufacturer’s and FDA’s understanding of the issues and the action required,” including a determination of the following:
Whether a DHCP letter is needed to convey new or important information;
How to format and present the new information;
How to define the target audience; and
When a DHCP letter should be sent.
The Final Guidance explains that the Agency decided to draft and publish a guidance document on DHCP letter formatting and content issues based on the results of a 2005 study, which found “a correlation between the quality or perceived quality of a DHCP letter and the extent to which physicians perceived the new information as important. Letters that were evaluated as clearer, more concise, better organized and formatted and that focused on the most important aspects of the new safety information were considered more effective in communicating the new information.” Mazor KM, Andrade SE, Auger J, Fish L, Gurwitz JH, 2005, “Communicating Safety Information to Physicians: An Examination of Dear Doctor Letters,”Pharmacoepidemiol Drug Saf., 14 (12):869-875 (emphasis added).
Types of DHCP Letters.
FDA regulations (21 C.F.R § 200.5) provide for three types of DHCP letters to “notify health care providers about new or updated information about a drug,” and the first two categories fall within the scope of the Final Guidance.
- Important Drug Warning Letters convey “new information that ‘concerns a significant hazard to health’ (21 C.F.R § 200.5(c)(1)) and therefore could 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).” This type of letter incorporates “Boxed Warnings,” “Contraindications,” and “Warnings and Precautions.” Such letters must be accompanied with envelopes marked: IMPORTANT DRUG WARNING.
- Important Prescribing Information Letters convey “important changes to the prescribing information other than those changes that are described in an Important Drug Warning Letter,” such as information in the “Indications and Usage” and “Dosage and Administration” sections. Such letters must be accompanied with envelopes marked: IMPORTANT PRESCRIBING INFORMATION.
- Important Correction of Drug Information Letters are sent to healthcare providers “to correct false or misleading information and other misinformation in prescription drug promotional labeling and advertising that is the subject of a Warning Letter or other Agency action,” and while the Final Guidance provides recommendations as to the formatting of such letters, the circumstances relating to when the FDA would require a correction letter are outside the scope of this guidance document. Such letters must be accompanied with envelopes marked: IMPORTANT CORRECTION OF DRUG INFORMATION.
The FDA recommends that the above-referenced headings be repeated on each letter in a similar format because the envelope may be separated from the letter before reaching its intended recipient.
A manufacturer’s DHCP letter “should be directed to all health care providers who are likely to prescribe, dispense, or administer the drug, as well as others who need to know the information. The letter should be directed to the full range of health care providers who could prescribe the drug, including nurse practitioners and physician assistants who have prescribing authority.” The Final Guidance further explains that DHCP letters should be sent to health care providers who have an interest in the information but do not prescribe the product. An example includes “the emergency departments or primary care physicians might not routinely prescribe the drug that is the subject of a DHCP letter, but might be providing care for patients with a drug-induced adverse reaction described in the letter.” DHCP letters should also be sent to pharmacists when a letter “announces the introduction of a new medication guide” and the pharmacist is required to distribute the guide to patients.
The Final Guidance suggests that “to effectively communicate new information,” a DHCP letter should clearly indicate:
The purpose of the letter;
The new information;
Any existing information that has changed; and
Any actions a health care provider should take in response to the new information.
The FDA recommends that letters “be clear, concise, and contain sufficient detail to meaningfully inform the target audience.” Letters should “not exceed two pages” and should “avoid discussion of non-critical information that could obscure the more important information.”
The Final Guidance details Agency recommendations relating to font sizes, headings, paragraph-by-paragraph descriptions of the issues, rationales for changes, quoting verbatim language from prescribing information or providing a summary if the new information is lengthy, descriptions of patient populations, and drafting a concluding paragraph with FDA and manufacturer contact information. The following information should not be included in DHCP letters:
Market information, including number of prescriptions or approvals;
Extensive details about clinical study designs;
Safety review panel information;
Future investigation information unrelated to safety; or
Promotional language or presentations.
For ease of reference, the Final Guidance attaches three model letters as examples of formatting and content of Important Drug Warning, Important Prescribing Information, and Correction of Drug Information letters to health care providers.
Tracking Behavior Modifications and Success of Letters.
The Final Guidance recommends that manufacturers “should conduct an evaluation, for their own use, of the extent to which the target audience received the DHCP letter and is aware of the information that was communicated in the letter.” (emphasis added).
Originally, the November 2010 draft guidance (“2010 Guidance”) introduced two tracking models for manufacturers to use to assess the impact of DHCP letters, evaluating (1) receipt and conveyance of information contained, and (2) modifications to behavior. First, to measure the letters’ overall effectiveness, the 2010 Guidance proposed that manufacturers “conduct an evaluation of the extent to which the target audience received the DHCP letter and is aware of the information that was communicated in the letter.” Second, for letters intended to modify behavior, the 2010 Guidance suggested that manufacturers actively monitor the extent to which the letters succeed in changing provider and prescriber behavior.
Nine of the eleven public comments to the 2010 Guidance asserted that the proposal would be “overly burdensome [and] beyond the Agency’s statutory authority.” 78 FR 41065 (July 9, 2013). For example, in its January 11, 2011 comments to the FDA, the Pharmaceutical Research and Manufacturers of America (PhRMA), a trade group representing biopharmaceutical researchers and biotechnology companies in the United States, explained that a proposal requiring an evaluation of patient behavior would “unnecessarily increase the number of correspondence regarding the letters and dilute the impact of the important information in the letters themselves.” See Correspondence from PhRMA to FDA re: Comments on Docket No. FDA-2010-D-0319 (Jan. 11, 2011),available here.
Based on the comments and submissions, the FDA eliminated the recommendation that manufacturers evaluate changes in behavior, and on July 9, 2013 (“2013 Guidance”), the FDA released proposed modifications to the 2010 Guidance document, which we discussed in detail here. The 2013 Guidance revised the monitoring language to suggest that “manufacturers conduct an evaluation for their own use, of the utility of the letters and their success in reaching the target audiences.” 78 FR 41065 (July 9, 2013) (emphasis added).
The Final Guidance now recommends that manufacturers shouldconduct an evaluation for the manufacturer’s own use. This is a departure from the active monitoring requirements suggested in the initial 2010 Guidance, and the Final Guidance replaces and clarifies the success language of the 2013 Guidance modifications with an assessment of the target’s ultimate awareness of the information. The Final Guidance does not instruct or recommend that manufacturers submit evaluations to the FDA.