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Pharmacist Organization Evaluates Evidence for "Off-Label" Medication Use

October 1, 2008 -- An enhanced process for evaluating and publishing evidence for “off-label” uses of medications has been launched through a collaborative initiative with the Foundation for Evidence-Based Medicine (FEBM) and the American Society of Health-System Pharmacists (ASHP), which publishes AHFS Drug Information (AHFS DI). AHFS DI is recognized by the U.S. Congress as an official compendium for establishing medical acceptance of off-label uses of drugs.

This enhancement to AHFS DI’s long-standing evidence-based process allows applicants to submit a formal application for the consideration of an “off-label” use of a medication by AHFS DI. As part of this process, AHFS DI determines whether the proposed use of the drug is considered medically acceptable, based on existing scientific evidence. The collaboration is expected to be used mostly to evaluate new uses of cancer drugs.

Use of a medication is considered “off-label” if it is prescribed to treat a condition other than what was approved by the Food and Drug Administration (FDA). “Increasing the speed of these evaluations is especially important for cancer medications, because developments in the field can move quickly and because of the urgent needs of patients who have not responded to existing therapies,” said Gerald McEvoy, ASHP assistant vice president of drug information and Editor-in-Chief of AHFS DI. Because AHFS DI is an official compendium of drug information recognized by Congress, the information it publishes on medically acceptable uses is relied upon by Medicare and Medicaid to determine reimbursement eligibility.

The Final Determination includes information critical to the prescribing decision, including a rating of the strength of the evidence, the grade of the recommendation, and disclosure of any possible conflicts of interest among the committee members.

This process supplements AHFS DI’s existing activities to evaluate evidence for off-label use of medications by allowing a formal application for consideration to be made by a petitioning organization. The partnership between AHFS DI and FEBM follows a user-fee model, similar to the Prescription Drug User Fee Act that is employed by the FDA. Applications are submitted to FEBM for consideration of an off-label use and a user-fee is paid by the submitter to FEBM. FEBM has contracted with AHFS DI to perform the determinations as part of its federally recognized compendial activities. The determinations will be posted on and available to the public.

Strict firewall polices are in place between AHFS staff and outside applicants, to prevent any undue influence. FEBM is the sole entry point for the application process and receives the applications and communicates with the applicants.

This initiative meets key characteristics identified by the Centers for Medicare & Medicaid Services (CMS) Medicare Evidence Development and Coverage Committee (MedCAC) as desirable for compendia that review drugs used to treat cancer, including:

  • Organization by drug or biologic
  • Provision of a summary of the pharmacologic characteristics and dosage regimens,
  • Detailed description of the evidence reviewed for each drug listing,
  • Use of pre-specified published criteria for weighing evidence,
  • Use of a prescribed published process for making recommendations public,
  • Transparent process for evaluating evidence for therapies,
  • Explicit identification of “not recommended” and “not fully established/equivocol” findings when appropriate,
  • Explicit listing and recommendations regarding therapies, including sequential use or combination in relation to other therapies, and
  • Process for public identification and notification of potential conflicts of interest, with established procedures for managing recognized conflicts.
In addition to publishing the Determination in a codified fashion using levels of evidence and grades (strengths) of recommendation, the Determination explicitly states whether the use it is medically accepted or not and includes a narrative summary to clarify the recommendation to facilitate consistent interpretation of the Determination.

The review process for consideration of a new use for an oncology medication begins with an application to FEBM, which is reviewed by AHFS DI and evaluated by an expert review panel consisting of oncologists, oncology pharmacists, and oncology nurses. The panel’s “Final Determination” is published on the AHFS DI Web site,, and reflects the consensus vote and comments from the AHFS Oncology Expert Committee. The determination will be revised as emerging evidence becomes available.

Source: Foundation for Evidence-Based Medicine and American Society of Health-System Pharmacists

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