Conflict of interest is an acknowledged, and largely unavoidable, factor in the development of drug compendia. Growing awareness of this fact has led to the adoption of policies and procedures in both the public and private sectors designed to minimize and control the influence.

However, because the stakes are so high and the potential for conflict arguably will always be present, new and more effective policies and procedures will have to be put in place over time. The public benefits if the compendia fairly and accurately assess the state of the evidence for a particular indication, but even in those cases, there should be meaningful conflict-of-interest policies in place.

An April 2009 technology assessment commissioned by the Agency for Healthcare Research and Quality explores concerns that conflict of interest may potentially influence the production and content of current drug compendia. The assessment, “Conflict of Interest in the Production of Drug Compendia,” was not a critique of existing compendia. Instead, its goals included identifying potential areas for improvement, systematic approaches to understanding conflict-of-interest-related bias in drug compendia and refinements to the compendia system that would increase the amount of accurate, timely, unbiased and complete evidence available for us as a reference for clinical decision-making.

Compendia information on drugs, their effectiveness, safety, toxicity and dosing are frequently used to determine whether a medication has a role in the treatment of a particular disease. These roles include both therapeutic uses approved by the U.S. Food and Drug Administration (FDA) and off-label indications. Policy enactments have also resulted in use of the compendia to inform reimbursement decisions made by the Centers for Medicare & Medicaid Services (CMS) and other third-party payers.

A conflict of interest exists when an individual or corporate entity possesses more than one motivation for trying to achieve an objective. According to a formal definition in the New England Journal of Medicine in 1993, “A conflict of interest is a set of conditions in which professional judgment concerning a primary interest (such as a patient's welfare or the validity of research) tends to be unduly influenced by a secondary interest (such as financial gain).”

Seven months after the release of the AHRQ assessment, which was conducted by the Duke University Evidence-Based Practice Center based on a CMS request, CMS adopted a rule change to address the issue. The Agency revised the Medicare Improvements for Patients and Providers Act of 2008 (MIPPA) to include a sentence which requires compendia to have “a publicly transparent process for evaluating therapies and for identifying potential conflicts of interest.”

Duke’s evaluation of the therapeutic and off-label roles of drugs included a description of compendia processes, delineating points at which conflict of interest may arise. It also lays out an ethical framework for evaluating the potential presence and influence of conflict of interest in compendia.

The study also included the results of an investigation into the policies and practices of four specific compendia with regard to conflict of interest, and talks about the adequacy of compendia approaches to address conflict of interest, problems with conflict of interest that have been reported and opportunities for minimizing conflict of interest in the compendia to ensure an objective and impartial system.

While acknowledging that compendia play a vital role in our health care system, the AHRQ assessment suggests that a survey of practicing clinicians would be instructive. Looking at the ways clinicians use the compendia, which compendia they consult and with what frequency could provide important guidance for future activities.

Other areas of opportunity for improving the compendia through managing conflict of interest include:

• Standardization of disclosure processes, including reporting of conflicts and more consistent limits on the level of financial conflict of interest that is allowed
• Greater standardization of the rules regarding evidence to be included in the compendia
• Development of a process for secondary evidence review, such as an “enhanced evidence-based practice center” structure designed to achieve rapid-cycle synthesis and to produce updated reviews.

In the practice center structure, highly qualified teams of experts, specially trained in evidence review and synthesis, would prepare evaluations and continuously modify as new evidence emerges. Simultaneously, teams of content experts would consider those reviews for relevance to clinical practice and comparative effectiveness-based decision-making, and would provide recommendations that would be updated based on the latest developments and findings.

And perhaps most important would be the existence of a continuing and open public dialogue regarding the importance of recognizing and reducing conflicts of interest, while also acknowledging that some level of conflict will always exist and that these conflicts do not necessarily always erode safety or intent.