The US Food and Drug Administration (FDA) has released a final guidance that aims to clarify the agency's requirements for information contained within "Dear Healthcare Provider" (DHCP) letters.

Background

The letters-so-named because they often begin with that exact salutation-are usually bulk mailings sent out by a manufacturer when it has been made aware of a serious problem with a drug or biologic, or when there is a need to provide updated information to the healthcare provider about the drug or biologic's use.

Despite the name, some DHCP letters are sent via email, and FDA notes that many are available on the Internet on the manufacturer's website.

But as FDA notes, three factors have been problematic for manufacturers:

• When a DHCP letter should be sent
• What information should be included in a DHCP
• How information should be organized, formatted and presented within a DHCP

"FDA regulations describe the process for mailing important new information about drug products (21 CFR 200.5), but do not provide instructions on the format and content of the actual letter," FDA explained. "Nor do the regulations provide information on electronic or other means of communication."

The result, FDA said, has been a wide gap in the quality of the letters with respect to how well they communicate their intended information. Regulators said they believed guidance on the format and content of the letters would "help improve the effectiveness of DHCP letters in communicating drug information," thereby benefiting patient safety.

The Guidance

To bridge the gap between regulations and best practices, FDA has released a final guidance, Dear Health Care Provider Letters: Improving Communication of Important Safety Information.

The guidance recommends that manufacturers work closely with the appropriate FDA review divisions to determine the need for a DHCP, the presentation of information within the DHCP, the target audience for the DHCP and the timeframe for distribution of the DHCP. For example, a manufacturer of an innovative pharmaceutical product would work with the Office of New Drugs (OND).

"In addition to providing a broader range of input into the content of the letter, such consultation could help ensure FDA's concurrence that the content of the letter is not in some way false or misleading," regulators wrote in the guidance.

When would a DHCP need to be sent? FDA's guidance explains that, "In most cases, the information relates to an important safety concern that could affect the decision to use a drug or require some change in behavior by health care providers, patients, or caregivers to reduce the potential for harm from a drug." Other DHCPs may be sent as part of a Risk Evaluation and Mitigation Strategies (REMS) plan, or to notify a healthcare provider about a pending drug shortage or to correct misleading advertising.

Three Types of Letters

Three types of letters are available to manufacturers, depending on the type of information that needs to be conveyed.

Important Drug Warning Letters are those required under 21 CFR 200.5(c)(1), and are those concerning "a significant hazard to health" requiring a change in the way in which a drug is used. FDA notes that information in these letters would typically be added to the drug's WARNING, CONTRAINDICATIONS, or WARNINGS AND PRECAUTIONS portions of its labeling.

Important Prescribing Information Letters are those under 21 CFR 200.5(c)(2), and are used to communicate important changes that are less serious in scope than those communicated in an Important Drug Warning Letter. "An Important Prescribing Information letter ordinarily is used to convey important changes to the INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION sections of the prescribing information," FDA wrote. A DHCP letter should not be used to announce new indications, "even an important one," FDA added.

Finally, Important Correction of Drug Information Letters are those required under 21 CFR 200.5(c)(3) to correct false or misleading advertising or promotional information

Content Recommendations

The guidance goes on to explain the various content recommendations for DHCP letters.

FDA said it recommended a six-part outline for writing DHCP letters:

1. state the purpose of the letter, along with a concise description of the issue (paragraph 1)
2. summarize actions that should be taken to address the issue, if any (paragraph 2)
3. describe the new information (interior paragraphs)
4. explain how this changes any existing practices or information (interior paragraphs)
5. state the action the healthcare provider must take in response to the new information (interior paragraphs)
6. include information about how to report new information or contact FDA or the manufacturer (final paragraph)

Letters should be clear, concise and no more than two pages while containing "sufficient detail to meaningfully inform the target audience," FDA said. It should also avoid discussion of "noncritical information," it added. Contact information for the manufacturer should also be contained within the DHCP letter

Other recommendations include:

• informative paragraph headings
• vertical lists with bullets or numbering, where appropriate
• text emphasis techniques to draw attention to major points (e.g., bold font, larger font, italics)
• minimum 12-point font
• easily readable font based on the type of media used (e.g., serif or sans serif)
• use of upper and lowercase letters (i.e., avoid all caps)
• adequate spacing and leading (i.e., letters should not touch within lines; lines of text should not touch one another)
• use of white space to delineate paragraphs and organize text

The same recommendations also apply to DHCP letters distributed electronically, FDA said.

Other Recommendations

Other recommendations made by FDA include:

• Repeat the heading from the outside envelope on the inside letter, as they may become separated after receipt of the letter.
• For DHCPs distributed by email, the letter should be in the body of the message, and not included as an attachment.
• The DHCP letter should be directed to all healthcare providers who are likely to prescribe, dispense or administer the drug, as well as all others who "need to know the information," such as nurses with prescribing authority or emergency department technicians who might treat the adverse event described in the letter.
• The subject line of the letter should contain the drug names (proprietary, established) and a concise description of the information within the letter. It may also contain a characterization of the nature of the problem ("life-threatening," "serious"), but should exclude any "vague terms" regarding the incidence of the problem ("rare").
• The impact of DHCP letters should be assessed, either for the manufacturer's own use or as a part of a REMS plan.

Specific examples of an approved DHCP letter are included within the guidance.

 

Dear Health Care Provider Letters: Improving Communication of Important Safety Information

Focus: Communicating Important Drug Safety Messages: the Dear Health Care Provider Letter