Thursday, August 10, 2006

Disclosing Conflicts of Interest: A Story Involving JAMA, Harvard Medical School, Baxter International, Cytyc

We have recently posted about cases in which JAMA (see post here) and the journal Neuropsychopharmacology (see post here) published articles whose authors did not fully disclose conflicts of interests that might have influenced what they wrote. Dr Cathy DeAngelis, the Editor of JAMA, just wrote an editorial calling for fuller disclosure of such conflicts of interest (full citation: DeAngelis CD. The influence of money on medical science. JAMA 2006; )

Some key quotes:
There can be no doubt that editors of peer-reviewed medical journals must always place the interest of patients above all else. Every published article eventually can and should affect patient care. Therefore, all articles that we publish must be ethically sound, valid, reliable, and credible (ie, reflective of work that is performed, written, reviewed, and edited in a manner that is unencumbered by financial pressure). With that in mind, it is important to discern the necessary and honest interests of for-profit companies from the potentially corrupting influence of commercial interests.

In some instances, the marketing goal of a company dominates the scientific aspect of the company-funded research. There have been a number of high-profile examples of such research irregularities involving for-profit companies, such as the refusal to provide all study data to the study team, reporting only 6 months of data in a trial designed to have 12 months of data as the primary outcome; incomplete reporting of serious adverse events; and concealing clinical trial data showing harm.

For-profit companies also can exert inappropriate influence in research via control of study data and statistical analysis, ghostwriting, managing all or most aspects of manuscript preparation, and dictating to investigators the journals to which they should submit their manuscripts.

How do editors preserve the integrity of their journals while ensuring that they serve as vehicles for dissemination of scientific information that could help clinicians provide better care for their patients? First and foremost is to ensure that all published articles are scientifically sound and as objective and unbiased as possible by using rigorous peer review and careful editorial evaluation. Another important aspect is to ensure that readers are aware of the authors' financial relationships and potential conflicts of interest so that these readers can interpret the article in light of that information.
Most remarkable about this editorial was that in it Dr DeAngelis singled out the Harvard Medical School.
Because we are so adamant and open about disclosure of financial interests, it is not surprising that we are being made aware of nondisclosures by authors and by readers. Somewhat surprising was that 3 consecutive cases of nondisclosures, all of which raised the interest of the mainstream press, involved authors from Harvard Medical School. To his credit, the dean of Harvard Medical School has informed me of his plan to send a letter enclosing the disclosure requirements for JAMA (plus our July 12, 2006, editorial) and those for the New England Journal of Medicine to all 8000 Harvard Medical School faculty members. In addition, he indicated that he will work with his faculty to enhance Harvard Medical School's current policies on financial relationships with for-profit companies (Joseph B. Martin, MD, PhD, oral communication, July 18, 2006).
A news article in the Boston Globe actually reported that Dr DeAngelis called Dr Martin and said, "Joe, do something with your kids." "Kids" here refers to the distinguished faculty of the Harvard Medical School.

In my humble opinion, it's good that some of the pervasive conflicts of interest in health care are starting to get more public scrutiny. Although disclosure of conflicts of interest do not negate all the problems they cause, full disclosure would at least make all aware of the scope of the problem

That's where the irony comes into this story. Dr Martin, in addition to his day job at Harvard, is a member of the board of directors of Baxter International, which describes itself as "a global healthcare company that, through its subsidiaries assists healthcare professionals and their patients with treatment of complex medical conditions including hemophilia, immune disorders, kidney disease, cancer, trauma and other conditions." Dr Martin is also a member of the board of directors of Cytyc, which makes a variety of diagnostic and therapeutic devices for use in gynecology. Dr Martin's official Harvard on-line biography does not mention these affiliations. Dr Martin did report these affiliations when writing, for example, an article for the New England Journal of Medicine about academic collaboration with industry (Moses H, Braunwald E, Martin JB, Their SO. Collaborating with industry — choices for the academic medical center. N Engl J Med 2002; 347(17):1371-5.) How Dr Martin simultaneously manages his fiduciary responsibilities to maximize financial results for the stock holders of Baxter International and of Cytyc and his leadership responsibilities at the Harvard Medical School is not clear.

So it would seem that full disclosure about conflicts of interest in health care really should begin at home.


Anonymous said...

I agree with this wholeheartedly. I think this has just as much to do with pride, arrogance, and short-sightedness as it does with the ignorance that many of the involved authors are claiming.

I'm very glad that Dr. DeAngelis and the other journal editors are standing firm on this one. It's important. Despite what often seems to be generally accepted, our advanced degrees to not make us wiser or put us above the rules.

I realize I'm being harsh, but it seems beyond ridiculous to me that my colleagues appear unable and/or unwilling to reveal who is lining their pocketbooks. If you aren't willing to talk about your funding stream in public, then maybe you shouldn't have taken the money.

With all that said, I do understand the hesitation and concern here. I realize that there is grey area with the whole issue and that there aren't any clear cut standards. I also realize that the average layperson isn't going to appreciate the nuances of the relatively complicated funding process. Instead, the reader may see a pharmaceutical company's name on the study and question or even write off the findings. Since we can be assured that this will happen at least to some degree, it puts the burden on us to do an even better and more thorough job as researchers so that our work stands on its own merit regardless of who is signing our checks. I don't think that's asking too much.

Anonymous said...

The August 10, WSJ article Lipitor Shows Limited Benefit for Stroke reveals that the doctor selected to review the latest Lipitor findings by The New England Journal of Medicine has financial ties to Pfizer. 11 study co-authors have financial ties to Pfizer.

Co-author Justin A. Zivin finds the results no better than aspirin.

Pfizer's spin was this is breaking new ground and another plus for statins.

Steve Lucas

Anonymous said...

I was so mad about the ivory-tower one-sidedness of this editorial, that I wrote the following, which I offer for your edification and amusement:

Dear Dr. DeAngelis:

As someone who has spent nearly 30 years analyzing data within for-profit healthcare companies, I found your editorial, “The Influence of Money on Medical Science”, insulting to me and other members of my profession.

You begin with the implication that the interests of patients are protected only within the academic setting. I assure that patients who use pharmaceuticals and medical devices that have been touched by my work are as much my patients as they are yours. Concern for patients is build into the DNA of any successful healthcare company. I can cite the Johnson and Johnson credo, which led to this company’s exemplary behavior during the Tylenol tragedy, as a good example of this.

I know that my concern for “my” patients is shared by all of my colleagues in the drug-information industry with whom I have discussed this topic. We provide knowledge regarding treatment effectiveness and safety with the full knowledge that lives will be affected, including our own and those of our loved ones, as well as the population at large. Our work involves the interpretation of incomplete and ambiguous data, without the benefit of hindsight. By the way, if you could watch my industry colleagues struggle to get the employees of academic medical centers to fill out case report forms for critical studies completely and correctly, you might conclude that the greater concern for patients lay on the for-profit side of the fence.

We are also pragmatists, who know that the truth comes out eventually. Even if we didn’t have our high ethical standards, and were motivated by pure greed, where is the profit in getting an unsafe drug approved? We know that if the FDA doesn’t expose an unsafe or ineffective product, our competitors will, to the ruin of the product line and perhaps the company.

Your article is also highly selective in its reporting of “research irregularities”. The Korean stem-cell research case was missing from your list, because it took place within an academic setting. The perverse incentives within the systems for advancement in academic medicine have been widely discussed, and are no less encouraging of unethical behavior than the profit motive within industry. In 2005 the endowment of Harvard University was over $25 billion. Can you seriously claim that money has less of a motivating role within academic research and academic medicine?

I was glad to hear that a company within the pharmaceutical industry had decided not to submit studies to JAMA, in response to your insult selectively aimed at their biostatistics professionals. It certainly does mean something other than a fear that flaws will be uncovered in their work. It means that they value their employees, and object to the implication—now an explicit statement—that they are less “intelligent, creative, and experienced” than their academic colleagues. Is there any data to support this assertion? In writing those words, was there any thought to how it might affect the vital partnerships between industry and academic researchers, on which the safety and care of “our” patients depend?

Had JAMA instituted a requirement for an independent statistical analysis of all studies, whether sponsored by industry, government, or academia, I am certain the company would have cooperated. Come to think of it, that’s not a bad idea. Maybe the financial disclosure rules should be modified, too, so that tenure-track academic researchers are required to state the difference in salary between Full Professor and Assistant Professor at their institutions.

Anonymous said...

Harvard might attract criticism if they were seen to be "allowing their faculty CV pages to be used to promote commercial entities" though, as well, and indeed their faculty might be criticised individually if they were seen using their academic pages to promote their companies. It is possible the Prof got the balance right, particularly nowadays with Google to help.