Archives of Internal Medicine: Clinical Practice Guidelines No Harm But Ban Industry Science Anyway

As science continues to advance and medical discoveries persistently make our lives healthier and better, a number of critics are concerned about the rare and potential harms that can come from industry-physician collaboration.  Despite the decades of progress that industry-physician innovation has given to millions of Americans, critics of such partnerships are concerned with the “potential” for bias.  As a result, instead of encouraging collaboration to find cures for diseases, they would rather waste resources, time and money investigating biases and conflicts of interest (COIs), which are so subtle that a microscope could not detect.

A recent example of these wasted resources investigating “subtle” bias or “potential COIs” was a study that examined the most recent American College of Cardiology (ACC) and American Heart Association (AHA) guidelines through 2008.  Clinical practice guidelines (CPGs) serve as standards of care in practice, quality improvement, and reimbursement.  The authors of the study, published in the Archives of Internal Medicine, noted that “the extent of COIs in cardiology guideline production has not been well studied.  One of the authors is outspoken industry critic and professed COI expert Eric Campbell, PhD.

Background

 “CPGs have become a fixture in clinical medicine and 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.” Additionally, “CPGs play a prominent role in quality improvement initiatives and have an emerging role in national policy to guide reimbursement and serve as the standard of care in medical malpractice cases.”

Consequently, the authors believed that COIs in the formation of CPGs may be especially significant because “improper bias in the CPG production process can have a potentially more widespread adverse effect on patient care than individual practitioners’ COIs.”  As a result, the authors looked at the recent ACC and AHA guidelines, which included documented disclosures of COIs, explicitly listed the companies and institutions involved in each COI for each author and reviewer, categorized the COIs by type into at least 4 categories (receipt of research grant; receipt of honoraria or being on a speaker’s bureau [honoraria/speaker’s bureau]; owning stock or having other type of ownership [stock/other ownership]; or being a consultant or member of an advisory board [consultant/advisory board]), and indicated whether the COI is moderate or significant in magnitude (defined as >$10 000 or <$10 000, respectively).

Using disclosure lists and the categories above, the authors cataloged COIs for each participant on the guidelines committees and noted that an “Episode” described an instance of participation in 1 guideline by 1 person.

Findings

In the 17 guidelines, the authors found 651 episodes of participation by 498 individuals. A total of 277 of the 498 individuals (56%) reported a COI. Over half of the episodes (365 of 651 [56%]) involved a COI. The most common form of COI was consultant/advisory board, followed by research grant, honoraria/speakers’ bureau, and stock/other ownership.

Role as guideline committee member (vs peer reviewer) was associated with COI (63% vs 51%), as was role as chair/co-chair/first author (81% vs 55%). Only 105 of the 498 individuals (21%) were involved in 2 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.

Of the guidelines the authors analyzed, 6 included information characterizing COIs as modest vs significant.  In these guidelines, there were 232 episodes, of which 150 involved COIs. Modest COIs were reported in 125 of 232 episodes (54%), whereas significant COIs were reported in 68 of 232 episodes (29%).

Disclosures

The article also discussed the “recent trend toward increased disclosure in guidelines production” and reviewed a number of studies that looked at disclosure in guidelines committees. The authors first noted that disclosure may not be effective because a busy clinician may not have the time or prioritize reading pages of disclosures at the end of guideline recommendations.  As a result, some have recommended that, “agencies that sponsor guidelines could mandate that guideline committee members have no COIs related to the guideline they are creating.”  AHA/ACC’s and CMSS policies reflect this rule, as does the Institute of Medicine report on Conflicts of Interest in Medical Research, Education, and Practice, and the AGREE criteria involve similar recommendations.

Another recommendation is to require members to abstain from voting on issues related to their COIs while participating in the discussion.  The problem with this recommendation, as many have noted, is that “excluding or limiting individuals with COIs is unrealistic because there simply are not enough experts without COIs.” Additionally, excluding members with COIs is unnecessary.  For example, in 2006, an article in the Journal of the American Medical Association (JAMA) examined this issue.

The study examined a total of 221 meetings held by 16 FDA advisory committees.  Overall, the study reported that the meeting-level analysis did not show a statistically significant relationship between conflict rates and voting patterns. In other words, the researchers tested for a relationship not between conflict of interest and yes votes on a drug but between conflicts of interest and votes for the interest of a pharmaceutical company. Moreover, the research indicated that the exclusion of advisory committee members and voting consultants with conflicts would have produced margins less favorable to the index drug in the majority of meetings, but this would not have changed whether the majority favored or opposed the drug.

The reality is, as the authors acknowledge, “relationships with industry bring a breadth of perspective and experience, especially if individuals have relationships with multiple different companies.” As the authors also recognized, “these individuals may be less conflicted than those with fewer industry affiliations.”

Discussion

In shifting the focus on COIs in medicine towards participants in the production of guidelines, the authors highlighted “several controversial episodes involving COIs in guideline production that have surfaced in recent years.”  However, the authors clearly overemphasize these incidents, since they are extremely rare.  Nevertheless, the authors assert that their findings are a “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.”

What is problematic about this article is that the authors admit that, “the actual degree to which any individual may be influenced by any specific type of COI (or even a specific dollar amount) is impossible to assess.”  If this is true, then why waste the time, money and resources trying to assess them?  Why demonize and scrutinize valuable relationships and partnerships that have improved medicine and health care in America for decades?  The only answer we know of is that the authors of this article and other critics make their own livings criticizing the hard work, innovations, and discoveries of others.

Critics and the authors of this article fail to realizes that “individuals with a long history of working on guidelines and with industry may be well equipped to handle COIs and promote the best interests of clinical care over the interests of industry affiliations.”  In fact, the authors recognize that, “it may even be preferable to include individuals who have access to the most up-to-date advancements through industry ties, especially in a rapidly advancing and technology- driven field such as cardiology. Otherwise, guidelines may quickly become out of date.”

Commentary

In response to the article, Steve Nissen, MD, published comments regarding COIs in CPGs.  Nissen similarly emphasized the important role that CPGs play in the practice of medicine.  His commentary over exaggerates the findings from the study and he asserts that disclosure of relationships is not sufficient to ensure the independence and scientific integrity of the CPG document. As a result, Nissen asserted that “a promotional speaker and stockholder is inherently biased and should never be permitted to serve as a CPG writer.” 

If we are to ban all those who work with industry as Dr. Nissen suggests, this would ban him from participating in trials, Nissen’s own voice would be silenced, and his vast research and consulting experience would be summarily discounted.   

Of course Dr. Nissen fails to look in the mirror on this one.  If he is so passionate about this issue he should resign from the guidelines committees he serves on.

Conclusion

This “research” makes no attempt to determine the accuracy of the guidelines as that would require hard work.   No one is denying that the current guidelines are in any way skewed in a particular direction or inaccurate.  So we ask question why worry about a problem that does not exist.

What is especially disconcerting about the series that the editor solicited commentaries from only one point of view the view that physicians working with industry should not participate in guidelines committees.  Those who believe that relationships with industry and being on guidelines committees allows for the best scientists to participate were never allowed a voice in the Archives.