Lexi-Drugs Off-Label Uses Policy

Lexi-Drugs includes information pertaining to uses of a drug that have not been recognized as approved by the U.S. FDA in the “Use: Off-Label” field of some drug monographs. Lexi-Drugs is not exhaustive of all off-label uses, does not include extensive statistical analysis, and is not intended for use in establishing global drug policies. It is intended to aid the health care professional in quickly identifying published literature regarding a specific drug use. Use of off-label content should help enable a clinician to determine if a specific off-label use is rational. The primary literature for the specific off-label use should be reviewed prior to patient-care decisions.

Stimulus for identifying potential off-label content includes:

  • Routine Wolters Kluwer Clinical Drug Information surveillance
  • Monitoring of the National Library of Medicine's 119 premier or core journals
  • Unbiased, evidence-based clinical practice guidelines
  • Internal drug monograph review
  • Drug-specific literature search done internally for updating purposes
  • External contributor's use in a practice setting
  • Client request

Evaluation of an Identified Off-Label Oncology Use

Internal clinical editors (subject matter experts in oncology) initially assess the potential off-label request through a primary literature review. Once a potential off-label oncology use for a medication is identified, an internal oncology pharmacist will review the supporting literature, assess and evaluate the evidence, and assign an evidence rating and strength of recommendation for inclusion into Lexi-Drugs based upon the scales below. The off-label use content is reviewed by 4 additional panel members composed of internal and external experts. Each panel member independently reviews and votes on the level of evidence rating and strength of recommendation for inclusion into Lexi-Drugs and identifies any conflicts of interest. Five panel members without a conflict of interest need to participate in the vote. To be listed in Lexi-Drugs, agreement is required from at least 3 of the 5 panel members regarding its inclusion and level of evidence rating. If the panel does not attain a majority vote in favor of an off-label addition, it will not be added to the database. If any member of the review panel has additional details for discussion, a conference call will be arranged to review the off-label use and determine/resolve the disposition of it.

Level of Evidence Scale

Levels of evidence do not pertain to the drug’s place in therapy as compared with other agents.

A Consistent evidence from well-performed randomized, controlled trials or overwhelming evidence of some other form (eg, results of the introduction of penicillin treatment) to support off-label use. Further research is unlikely to change confidence in the estimate of benefit.
B Evidence from randomized, controlled trials with important limitations (eg, inconsistent results, methodologic flaws, indirect, imprecise); or very strong evidence of some other research design. Further research (if performed) is likely to have an impact on confidence in the estimate of benefit and risk and may change the estimate.
C Evidence from observational studies (eg, retrospective case series/reports providing significant impact on patient care); unsystematic clinical experience; or potentially flawed randomized, controlled trials (eg, when limited options exist for condition). Any estimate of effect is uncertain.
G Use has been substantiated by inclusion in at least one evidence-based or consensus-based clinical practice guideline.

Strength of Recommendation for Inclusion into Lexi-Drugs for Oncology Off-Label Use

Strong (for proposed off-label use) The evidence persuasively supports the off-label use (ie, Level of Evidence A
Equivocal (for proposed off-label use) The evidence to support the off-label use is of uncertain clinical significance (ie, Level of Evidence B, C). Additional studies may be necessary to further define the role of this medication for the off-label use.
Against proposed off-label use The evidence either advocates against the off-label use or suggests a lack of support for the off-label use (independent of Level of Evidence). Additional studies are necessary to define the role of this medication for the off-label use.

Removal of an Off-Label Oncology Use from Lexi-Drugs:

Off-label uses that are already incorporated within the database will be moved into the “Use: Labeled Indications” section if the use gains approval from the FDA. Identification of an off-label use that is no longer supported may occur through literature surveillance and review. This would initiate a similar process where an internal oncology pharmacist reviews and assesses the supporting literature. The off-label use content is reviewed by 4 additional panel members composed of internal and external experts. Each panel member independently reviews and votes on the removal of the off-label use. Five panel members without a conflict of interest need to participate in the vote. To be removed from Lexi-Drugs, a consensus of agreement for removal is required from at least 3 of the 5 panel members. The off-label use will be removed from the off-label use field and may be placed in the “Use: Unsupported” field. If the panel does not attain a majority vote in favor of removal of off label use, it will not be removed from the database. If any member of the review panel has additional details for discussion, a conference call will be arranged to review the off-label use and determine/resolve the disposition of it.

Conflict of Interest Policy

Content to which this Policy applies is developed, published, and licensed jointly by Clinical Drug Information, LLC and Wolters Kluwer Clinical Drug Information, Inc., which are referred to collectively in this Policy as "Wolters Kluwer Clinical Drug Information."

Wolters Kluwer Clinical Drug Information is committed to minimizing conflicts of interest and ensuring public transparency in the provision of reliable, unbiased, evidence-based information on drug use to support a variety of diverse decisions made across the health care spectrum. This policy provides important information about potential conflicts of interest that may be involved in developing Lexicomp®, Medi-Span®, and Facts and Comparisons® offerings.

Conflicts of interest can arise when individuals who work for, or are engaged on behalf of, an organization engage in activities that interfere, or appear to supersede, the interests of that organization, its customers, or individuals and entities who may be affected by use of the organization's offerings. Of particular concern to Wolters Kluwer Clinical Drug Information are activities and interests that could impact, or may appear to impact, patient outcomes or the validity of evidence selection, literature evaluation/interpretation, and content development. This policy covers business judgment and decision-making activities involving evidence selection, literature evaluation/interpretation, and content development at Wolters Kluwer Clinical Drug Information. This policy does not address all conflict of interest concerns that may be applicable or relevant to Wolters Kluwer Clinical Drug Information.

This policy applies to all Wolters Kluwer Clinical Drug Information locations and all individuals engaged in evidence selection, literature evaluation/interpretation, and content development, regardless of location or employment or contractor status (collectively, "Wolters Kluwer Clinical Drug Information Personnel").

Summary Statement on Conflicts of Interest Management Objectives

Wolters Kluwer Clinical Drug Information is committed to minimizing conflicts of interest and ensuring public transparency in the provision of reliable, unbiased, evidence-based information on drug use to support a variety of diverse decisions made across the health care spectrum. Wolters Kluwer Clinical Drug Information utilizes a range of internal and external expertise in the development of content, including specifically the selection and interpretation of indications and evidence for review. This policy provides information on Wolters Kluwer Clinical Drug Information's management of activities and interests that could impact, or may appear to impact, professional judgment concerning patient welfare or the validity of evidence selection, literature evaluation/interpretation, and content development. Collectively, this policy, and any associated procedures and disclosure documentation, help promote the goal of developing the content of Lexicomp®, Medi-Span®, and Facts and Comparisons® offerings with integrity, objectivity, and impartiality.

Potential Conflicts of Interest in the Development Process

Conflicts of interest can arise when individuals who work for, or are engaged on behalf of, an organization, are engaged in activities that interfere, or appear to supersede, the interests of that organization, its customers or individuals, and entities who may be affected by use of the organization's offerings.

Due to the nature of Wolters Kluwer Clinical Drug Information's content development process, and the structure of the health care system generally, Wolters Kluwer Clinical Drug Information Personnel, and their spouses, partners, or minor children, may engage in activities with, have affiliations to, or have financial ties to entities with commercial interests in the content developed for Lexicomp®, Medi-Span®, and Facts and Comparisons® offerings. Common activities and interests that could result in a conflict might include:

  • Previous employment or leadership positions at a pharmaceutical company
  • Direct financial interests in a pharmaceutical company (eg, stock or equity ownership)
  • Patents related to particular drugs or treatments that are the subject of services performed for Wolters Kluwer Clinical Drug Information
  • Performance of an advisory or consultant role to a pharmaceutical company
  • Performance of an advisory or consultant role to a governmental agency with regulatory power over drugs or treatments that are the subject of Wolters Kluwer Clinical Drug Information content that the Wolters Kluwer Clinical Drug Information Personnel are providing content development services concerning
  • Receiving financial sponsorship from a pharmaceutical company for research
  • Previous or existing employment or financial interests with a Wolters Kluwer Clinical Drug Information competitor or its subsidiaries

Not all activities, affiliations, or financial relationships are problematic. There may be activities, affiliations, and interests that pose no conflict at all, or may preclude contribution to the content development process entirely, as well as interests to which the extent of any real or perceived conflict can be minimized through disclosure or other management efforts. Potential decision points in which conflicts of interest may arise within Wolters Kluwer Clinical Drug Information’s content development process include, but are not limited to:

  • Decisions regarding review of potential content, including, but not limited to, items such as drugs, topics, recommended dosages, and indications
  • Decisions on intervals for content updates
  • Selection of evidence to review
  • Evaluation of the quality of evidence
  • Interpretation of evidence and formation of conclusions

In general, conflicts of interest are most likely to arise when Wolters Kluwer Clinical Drug Information Personnel or their spouses, partners, or minor children have financial ties to pharmaceutical drug sponsors. Regardless of the situation, however, Wolters Kluwer Clinical Drug Information Personnel are required to disclose all situations in which a real, potential, or perceived conflict of interest may result from their or their spouse's, partner's, or minor children's activities, affiliations, or financial ties to entities with commercial interests in the content developed for Lexicomp®, Medi-Span®, and Facts and Comparisons® offerings.

Conflicts of Interest Disclosure Requirement

All Wolters Kluwer Clinical Drug Information Personnel involved with Wolters Kluwer Clinical Drug Information's content development process are required to make a formal, written disclosure of real, potential, or perceived conflicts of interest related to themselves or their spouses, partners, or minor children and Wolters Kluwer Clinical Drug Information content development. Such written disclosure will be collected on the Wolters Kluwer Clinical Drug Information Conflicts of Interest Disclosure Statement. Information will be collected from WK Personnel:

  • Prior to providing service to Wolters Kluwer Clinical Drug Information
  • Annually following engagement of services performed for Wolters Kluwer Clinical Drug Information
  • Upon any change in circumstances during the engagement of services that presents a real, potential, or perceived conflict of interest

Wolters Kluwer Clinical Drug Information Personnel are required to disclose all situations in which a real, potential, or perceived conflict of interest may result from their or their spouse's, partner's, or minor children's activities, affiliations, or financial ties to entities with commercial interests in the content developed for Lexicomp®, Medi-Span®, and Facts and Comparisons® offerings.

Compendia Transparency Document

View the new off-label uses and ones removed from the database.

View