FDA Issues Guidance on “Dear Healthcare Provider” Letters

“Dear Healthcare Provider” (DHCP) letters are mailings (either regular or electronic) sent by a drug manufacturer who has been made aware of a serious problem with its product or when the manufacturer needs to provide updated information on the use of the product. The FDA drafted Guidance about DHCP letters to address three areas of concern raised by manufacturers:

• When a letter should be sent.
• What information should be included in a letter.
• How the information presented in the letter should be formatted and presented.

Manufacturers are encouraged to consult with the appropriate FDA division to determine that the letter: (a) reflects both parties’ understanding of the issue and the action required; (b) identifies the appropriate audience; and (c) identifies the timeframe and means of communication of the letter.

There are four cases where a DHCP letter may be used to provide notification to healthcare providers (HCPs) about important new or updated information on a particular drug:

1. an important safety concern that could affect a HCP’s decision to use a drug or impact behavior.
2. Risk Evaluation and Mitigation Strategy (REMS), which may be required to inform the target audience about the implementation of a new or modified REMS or to provide additional required safety information about the product.
3. drug shortages.
4. corrections to misleading information.

There are three types of DHCP letters available:

1. Important Drug Warning (21 CFR 200.5(c)(1))
Conveys important new safety information that “concerns a significant hazard to health” that could affect the decision to use or cause a change in behavior (e.g., monitoring). Used when information is being modified in the Boxed Warnings, Contraindications, or Warnings and Precautions section of the full Prescribing Information (PI).

2. Important Prescribing Information (21 CFR 200.5(c)(2))
Conveys important changes to the Indications and Usage and Dosage and Administration sections of the PI. May communicate: (a) change in the indication and usage to minimize risk, improve effectiveness or convey a limitation of the product indication; (b) change to the dose or dosage regimen; or (c) change in the drug supply to address a drug shortage issue. This type of letter may not be used to announce a new product indication.

3. Important Correction of Drug Information (21 CFR 200.5(c)(3))
Used to correct false or misleading information or other misinformation in drug promotional labeling and advertising that is the subject of a Warning Letter or other Agency action.

The Guidance recommends that the following information be provided at or near the beginning of the letter to effectively communicate the information:

• Provide the purpose of the letter and a description of the issue in the opening paragraph.
• Contain in the interior of the letter:
  • A description of the new information.
  • An explanation of how the changes impact existing protocols or treatment decisions.
  • Action steps, if any, for the HCP to take in response to this information.

Further recommendations are that the letters be no more than two pages in length, be “clear and concise and contain sufficient detail to meaningfully inform the target audience,” and not include any “noncritical information” (e.g., promotional language or claims).

The FDA Guidance recommends the following when developing the content and format of the letter. These recommendations apply whether DHCP letters are distributed by regular or electronic mail:

1. Include the heading of the letter on the outside of the envelope, and repeat this information on the inside letter in the event they become separated.
2. Include all HCPs who are likely to prescribe, dispense or administer the drug and may include others who need to know the information (e.g., pharmacists) as the target audience.
3. Include the name of the drug (propriety and established name) in the subject line.
4. Include a brief summary of the information for Important Drug Warning and Important Prescribing Information letters so HCPs can understand the nature and management of the problem and actions taken to address the issue.
5. Include the following in subsequent interior paragraphs for Important Drug Warning and Important Prescribing Information letters:
   1. Attributes of affected patient populations.
   2. Summary of the information that is the basis for the revised information and the limitations of that information.
   3. Mechanism of the adverse reaction and whether additional research is being done to understand the adverse reaction.
   4. Whether the event is common to the drug class.
   5. Further discussion of the indication.
6. Include the following for Correction of Drug Information Letters:
   1. Purpose of the letter (e.g., to correct false or misleading claims).
   2. Statement of the information that was subject of the FDA Regulatory Action.
   3. Where and how the incorrect information was disseminated.
   4. A description of the actual false information and a description of why it was false or misleading.
   5. The corrected information.
   6. The approved indication, including limitations to use, risk and safety information.
   7. Reference to full Prescribing Information (which must be enclosed in the letter) and the appropriate medication guide or patient information.
   8. Statement that the letter is not intended to be a complete statement of benefits and risk associated with use of the product.
7. Include information in the final paragraph on how to report new cases of adverse reaction or other safety issue and contact information for the company and FDA.

The Guidance recommends that all manufactures assess, for themselves, the impact of the letter on the target audience to measure awareness of the information that was communicated. The Guidance, which may be accessed by clicking here, contains specific examples of approved letters.