Background and Summary

The United States Food and Drug Administration (FDA) focuses on regulating the approval of prescription drugs rather than regulating the prescribing practices of physicians. Therefore, the use of medications for indications beyond those formally evaluated is allowable in medical clinical practice.

Gold Standard Inc. drug information databases and products contain FDA-approved or “labeled” information. This approved drug information for given drug products serves as the foundation, or back-bone, of our electronic drug compendia.

The full and ultimate use of a drug is rarely evident at the time of initial FDA-approval or marketing. The discovery and clinical adoption of new uses for marketed drugs or for investigational drugs often precedes FDA-approval of such uses. In some cases, as in treatments for rare diseases or for underserved populations, there may be substantial literature evidence and/or clinical experience, yet little financial incentive, for a manufacturer to pursue FDA approval. A 1996 GAO report (Prescription Drugs, Implications of Drug Labeling and Off-Label Use) showed that off-label use is substantial in situations where satisfactory treatment is not available and that there are lower rates of off-label use when there is an effective therapy.

An expected role of any drug compendia for off-label listings is to consolidate published scientific literature for educational ease of the user and for quick navigation to appropriate documentation. Our team of medical professionals recognizes the importance of emerging therapies that promote medical advancements in the treatment of human disease and health conditions. The exclusive inclusion of only “labeled” information within our compendia would limit the utility and scope of our products to clinicians. Gold Standard Inc. drug information products also include unapproved or “off-label” indications and other data for drug therapy that is outside the scope of the FDA-approved labeling. The ability to reference this information is critical to the healthcare professionals we serve.

The Editorial Staff at Gold Standard Inc. is committed to a legacy of providing unbiased, comprehensive drug information that is accurate, clinically-relevant, and current. In order to represent such best practices in drug therapy, the editorial team follows a policy for content style and production, which includes a specific policy regarding off-label data.

Identifying Off-Label Data

Off-label data are included in our drug information content when identified as a clinically-relevant or emerging treatment by the Editorial Staff. Off-label data are primarily identified and selected by the Editorial Staff for inclusion in the database through regular and comprehensive review of:

• Primary published literature
• New or updated national practice guidelines
• Surveillance of other accepted sources of medical information (e.g., FDA, CDC, NIH communications)
• Dialogue with customers or other external reviewers of our content

Off-label information may be included in the monographs of FDA-approved drugs, investigational drugs, or dietary supplements.

Research of Off-Label Data

The members of the Editorial Staff conduct a thorough search of the primary literature and other accepted sources of information to identify relevant, published information, including negative or equivocal findings. Searches ensure that relevant and timely publications are considered.

Clinical Review and Database Edits

After the research is completed, the evidence is reviewed and independently evaluated by the assigned Editorial Staff member. If the documentation is deemed sufficient to warrant inclusion, the data undergo peer-review for inclusion into our content. The documentation for the off-label data includes supporting references of the best-quality evidence available from our research, and will often include a summary of the level of quality of the supporting evidence in descriptive fashion. All off-label (i.e., non-FDA-approved) indications, dosage, or related data are clearly designated within the content of our products.
In the evaluation of the research available, the following are considered:

• The impact (benefits and risks) of the therapy on the disease/condition (e.g., emerging treatment, response vs. conventional therapy, optional use when there is approved therapy failure, etc.)
• Patient safety

Patient safety is an especially important consideration for users of the provided Gold Standard Inc. data. Despite sufficient literature evidence that may justify an off-label practice, the lack of FDA-approval for that use means that the drug is not given the same degree of scientific scrutiny as for an approved indication. Scientific evidence documenting the efficacy of off-label use in routine practice settings often does not replicate the depth and breadth of the evidence the manufacturer is required to provide the FDA to receive drug approval for a specific indication. In addition, the population of use or the indication may be so different from the approved indication that extrapolating safety data from the approved documents can be an erroneous presumption.

Unsupported or inconclusive data are qualified. For example, unsupported or refuted indications are often reported only in the Description section of the drug monograph for completion and will not usually be found in the Indications or Dosage sections.

Please note that the Editorial Staff adheres to the Consumer Medication Information (CMI) Guidance of the FDA with regard to the production of Patient Information Documents (i.e., MedCounselor Sheets). With rare exceptions, the MedCounselor Sheets of Gold Standard Inc. refrain from noting specific off-label uses to consumers.

Peer-Review and Conflict of Interest

Please see the Editorial Policy Summary. Editorial Policy governs all clinical drug data production at Gold Standard Inc. A peer-review process is ensured via the editorial policy and our electronic drug data production systems. All editorial staff members must comply with the Gold Standard Inc. Editorial Conflict of Interest Policy.

External Review

Occasionally, the internal Editorial Staff Management determines the documentation of off-label data to be controversial or, in some cases, equivocal or indeterminate. In these cases, the data may be sent for external review and validation to a member of the external Gold Standard Inc. Editorial Consultant Board, or to a Board member within other Elsevier publishing efforts who exhibits expertise in the area of question.

Date Last Reviewed: July 25, 2007