Conflicts of Interest in Cardiovascular Guidelines

More than half of authors and reviewers of cardiovascular clinical practice guidelines have at least one conflict of interest (COI), according to a study in Archives of Internal Medicine. Todd Mendelson and colleagues analyzed the 17 most recent ACC/AHA guidelines through 2008 and found that 56% of the participants reported a COI. The most common COI was being a consultant or a member of an advisory board.

The authors concluded that “although restricting participation may prevent some qualified individuals from serving in the guidelines production process, we found that a large percentage of individuals with guidelines experience reported no disclosures, suggesting there is a substantial pool of potential
guideline writers and reviewers without COIs.”

In an accompanying commentary, Steve Nissen writes that the authors”raise disturbing questions about the independence and reliability of CPGs in cardiovascular medicine” and that “the depth and breath of industry relationships… are extraordinary.” Nissen also notes that “professional societies and their leadership are often plagued by the same commercial relationships as the CPG-writing committees.”

As might be expected, Nissen pulls no punches in his discussion of the topic:

The depth and breath of industry relationships reported in this article are extraordinary. Unexpectedly, financial ties between companies and CPG authors include relationships extending far beyond scientific collaboration. More than half of CPG writers served as promotional speakers on behalf of industry, and a substantial number actually held stock in companies affected by the CPG. For example, one-third of the writers of the percutaneous intervention CPG actually owned stock in companies affected by the CPG. Even if we were to accept the premise that scientific involvement by authors is reasonable, no conceivable logic can defend the practice of including promotional speakers and stockholders on CPG writing committees. Participants in speaker’s bureaus essentially become temporary employees of industry, whose duty is the promotion of the company’s products. Such relationships are so antithetical to the academic mission that many medical schools have now forbid such relationships for their faculty. To allow such individuals to write CPGs defies logic.

In response to the Archives article and an IOM report on CPGs,  the AHA and the ACC issued a statement (reprinted below) pointing out that the the AHA and ACC had “refined their policies in 2010 to require even more stringent management of relationships with industry, to align with the Council of Medical Specialty Societies (CMSS). Thus the data within and the conclusions drawn by the article do not reflect the reality of the guidelines development process today.”

Sanjay Kaul sent the following comment to CardioBrief:

I agree with the core message from both the authors and the editorialist. However, in fairness, the information predates the changes implemented by the ACC/AHA Task Force for Clinical Practice Guideline Committee to minimize the conflicts and relationships with industry which are now more stringent. For example, the chair(s) of the Writing Committee is(are) not allowed to have any conflicts (financial or otherwise), and no more than 50% of the writing committee is allowed to have any COIs.

What is not known to many is that the Task Force did attempt to implement some of the steps recommended by the authors and the editorialist during the development of the 2007 focused update on unstable angina guidelines. It was an unmitigated disaster and the guidelines had to be redone, thereby delaying their release.

The ACC/AHA Task Force has a difficult challenge to limit the biases and the conflicts of interest of the guideline writing committee. These are not just limited to financial conflicts but also include intellectual biases and conflicts. In my experience, the best advice often comes from expert “consumers” rather than expert “generators” of information and evidence. One of the recommendations I have for the task Force in this regard is to limit the participation of the principal investigators of guideline-relevant clinical trials in writing guidelines. They should be invited to offer their expert opinion (as part of the peer review), but not allowed to “engineer” the guidelines. Although, the Task Force does a good job in assembling a panel with a broad spectrum of expertise in evidence appraisal, benefit-risk assessment, and clinical decision making, in my opinion, there is room for further improvement.

Here is the press release from JAMA:

Conflicts of Interest are Prevalent Among Writers, Reviewers of Cardiovascular Clinical Practice Guidelines

CHICAGO – An analysis of recent clinical practice guidelines for cardiology finds that of nearly 500 individuals involved in the development of these guidelines, more than half reported a conflict of interest, according to a report in the March 28 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

“Clinical practice guidelines (CPGs) have become a fixture in clinical medicine. Though individual clinical trials have meaningful impacts on patient care, CPGs are often adopted as the standard of care and taught as such in training programs at all levels. CPGs also play a prominent role in quality improvement initiatives,” according to background information in the article. “Although conflicts of interest (COIs) are found in all spheres of medicine, their role in the formation of CPGs may be especially significant. Improper bias in the CPG production process can have a potentially more widespread adverse effect on patient care than individual practitioners’ COIs.” The extent of COIs in cardiology guideline production has not been well studied.

Todd B. Mendelson, M.D., M.B.E., of the University of Pennsylvania, Philadelphia, and colleagues examined the 17 most recent American College of Cardiology/American Heart Association guidelines through 2008. Using disclosure lists, the researchers cataloged COIs for each participant as receiving a research grant, being on a speaker’s bureau and/or receiving honoraria, owning stock, or being a consultant or member of an advisory board. The researchers also cataloged the companies and institutions reported in each disclosure. “Episode” describes one instance of participation in one guideline by one person. “Individual” describes one person who may be involved in multiple episodes. “Company” describes a commercial or industry affiliation reported by an individual in a single episode.

In the 17 guidelines, the researchers found 651 episodes of participation by 498 individuals. On average, each individual participated in 1.31 episodes. A total of 277 of the 498 individuals (56 percent) reported a COI. Over half of the episodes (365 of 651 [56 percent]) involved a COI. The most common form of COI was consultant/advisory board, followed by research grant, honoraria/speakers’ bureau, and stock/other ownership. The percentage of episodes involving a COI ranged widely across guidelines, from 13 percent (2 of 15 episodes) to 87 percent (13 of 15 episodes).

“Role as guideline committee member (vs. peer reviewer) was associated with COI (63 percent vs. 51 percent), as was role as chair/co-chair/first author (81 percent vs. 55 percent). Only 105 of the 498 individuals (21 percent) were involved in two or more guidelines. The percentage of individuals reporting a COI was higher among individuals with more episodes of participation, and the number of episodes of participation was associated with both presence of COIs and number of COIs,” the authors write.

There were 510 commercial companies involved in the 17 guidelines, with a wide range in the number of companies reported to be involved in different guidelines (average, 38 companies; range, 2-242 companies). In contrast, there were only 18 noncommercial organizations reported to be involved in COIs. The researchers identified the commercial company involved in the greatest number of COIs in each guideline. One specific company was reported by more individuals than any other company in seven of the 17 guidelines.

“Our finding that most episodes of guidelines participation involve COIs, and that most individuals involved in producing guidelines report COIs, is a cause for concern. These findings are a particular cause for concern given the fact that many of the newest ACC/AHA guideline recommendations are based more on expert opinion than on clinical trial data. However, our findings of the average number of companies (38) and the range of numbers of companies (2-242) reported per guideline are perhaps less salient than the finding that a few companies were most reported in multiple different guidelines, and that one company was most reported in seven of 17 guidelines,” the authors write.

“In conclusion, CPGs play an increasingly influential role in the practice of medicine. COIs are prevalent but vary widely in recent ACC/AHA guidelines. Individuals with greater involvement in CPGs reported more COIs. Although restricting participation may prevent some qualified individuals from serving in the guidelines production process, we found that a large percentage of individuals with guidelines experience reported no disclosures, suggesting there is a substantial pool of potential guideline writers and reviewers without COIs.”
(Arch Intern Med. 2011;171[6]:577-584.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Commentary: Can We Trust Cardiovascular Practice Guidelines?

In an accompanying invited commentary, Steven E. Nissen, M.D., of The Cleveland Clinic Foundation, writes that the findings of this study “raise disturbing questions about the independence and reliability of CPGs in cardiovascular medicine.”

“Why have professional societies allowed such extraordinary levels of commercial influence to infiltrate CPG committees? Professional societies and their leadership are often plagued by the same commercial relationships as the CPG-writing committees. Pharmaceutical and medical device companies provide large amounts of the financial support for the education and advocacy efforts of professional societies. Such relationships have created a dependency that is difficult to terminate because the leadership of professional societies is reluctant to antagonize their financial benefactors. The extent to which such financial ties bias the selection of CPG chairs and writers is unknown, but it certainly raises appropriate concerns. The revelations reported in the current article highlight troubling concerns that must be urgently addressed. If we fail as a profession to police our CPG process, the credibility of evidence-based medicine will suffer irreparable harm.”
(Arch Intern Med. 2011;171[6]:584-585.)

Here is the ACC/AHA comment:

American College of Cardiology/American Heart Association Media Comment:

Institute of Medicine makes recommendations on producing trustworthy guidelines

Organizations also acknowledge Archives of Internal Medicine Article

DALLAS, March 28, 2011 — Few issues are more important to the American College of Cardiology and the American Heart Association than translating scientific evidence into guidelines and performance measures for healthcare providers, a process we have been engaged in for several decades. The use of these evidence-based guidelines has been proven to improve the quality of care and actual outcomes for patients. We applaud the IOM for its new report and share its position that it is critical that no commercial or any other bias can be allowed to influence the development of clinical practice guidelines.

The new Institutes of Medicine report, “Clinical Guidelines Practices We Can Trust,” published March 23, 2011, cites the American College of Cardiology and American Heart Association’s standards for guideline development as being almost perfectly aligned with their recommendations.

Both the AHA and ACC also appreciate the focus on the issue in the Archives of Internal Medicine article by Mendelson et al, which analyzes the disclosure of relationships with industry in joint guidelines developed by the American College of Cardiology and American Heart Association between 2004 and 2008.

Both the American College of Cardiology and the American Heart Association have long had strict policies for preventing any undue influence of industry. In 2004-2008, these policies relating to practice guidelines included the requirements that:

• All writing panel members must verbally disclose all relevant relationships with industry at every meeting and conference call.
• Individual panelists with a relationship with industry were held responsible to recuse themselves from any matter relevant to their relationship.
• All disclosures would be published as an appendix to each guideline.
• Multiple tiers of reviewers assured the lack of bias of each guideline document.

As the Archives article states, the American College of Cardiology and the American Heart Association refined their policies in 2010 to require even more stringent management of relationships with industry, to align with the Council of Medical Specialty Societies (CMSS). Thus the data within and the conclusions drawn by the article do not reflect the reality of the guidelines development process today.

Updated practices include these additions:

• The Chair of the guidelines writing panel may not have any relevant relationships with industry.
• In addition to the Chair, a majority (at least 50 percent) of guidelines writing committee members must not have any relevant relationships with industry.
• A writing committee member may not draft a recommendation nor any text nor vote on any recommendation that is relevant to any of their industry relationships.
• Members of the final approving bodies of both ACC and AHA, Science Advisory Coordinating Committee and the Board of Trust respectively, also must recuse themselves from voting if they have a relevant relationship with industry.

For determining eligibility to serve on a writing committee, a person is considered to have a relevant relationship IF:

– The relationship or interest relates to the same or similar subject matter, intellectual property or asset,topic, or issue addressed in the document; or

– The company/entity (with whom the relationship exists) makes a drug, drug class, or device addressed in the document, or makes a competing drug or device addressed in the document; or

– The person or a member of the person’s household has a reasonable potential for financial, professional or other personal gain or loss as a result of the issues/content addressed in the document.

The American College of Cardiology and the American Heart Association remain fully committed to transparency in the development of all our guidelines. We will continue to look closely at our policies regarding relationships with industry and welcome public dialogue that may help us continue to enhance our practices in the future.