Results tagged “conflict of interest” from Pathophilia
Like GSK, Lilly, and Merck, Pfizer has begun to publicly disclose its payments to US docs for their advising and speaker services, as of yesterday.* However, unlike the other companies, Pfizer is revealing how much money it has given to fund US-based clinical trials (ie, research grants).
During the second half of 2009, the world's biggest drug firm shelled out $19.8 million to 4500 health care professionals ($4400, on average, per HCP) and $15.3 million to 250 academic or other research groups ($61,200, on average, per group). Pfizer provides a friendly graph (below) and also notes that it invests about $7 billion in R&D and spends about $1.3 billion to bring a drug to market.
Individual Pfizer payments are available here, with a database that is browsable and searchable. However, the payment information, like that from other companies, is not easily downloadable, as yesterday's NYT notes.
According to a Pfizer spokesperson, also by way of the NYT, the disclosures (or at least most of them) are mandated by an "integrity agreement" between Pfizer and the federal government. The agreement was struck as part of a settlement in re Pfizer's off-label promotion of drugs (like Wyeth's Neurontin [gabapentin]).
HCP = health care professional (including nurse practitioners and PAs).
* "Meals, business travel expenses and educational items that are greater than or equal to $25 in value, and where the aggregate amount paid to an individual health care professional is greater than or equal to $500 in a calendar year."
The famous (or infamous) NEJM meta-analysis of rosiglitazone (Avandia; GSK) studies by Nissen and Wolski—who concluded that the drug increases the risk of MI—initiated a flood of articles in the medical literature, most of which were opinion pieces.* As logic would dictate, the authors of these articles either 1) favored the continued use of Avandia (denying that the drug increases MI risk); 2) recommended discontinuation of Avandia (stating that the drug increases MI risk); or 3) were neutral on the subject (stating that there is insufficient evidence to make a recommendation).
Given these widely differing opinions, physicians at the Mayo Clinic recently assessed these response articles to determine whether the opinions offered might be associated with the authors' relationships to pharma generally and the manufacturer of Avandia specifically. Their findings were reported yesterday in the BMJ.
What is most surprising in the Mayo assessment is the relative lack of disclosure among the 202 articles discovered. (Note: The authors excluded the many follow-up articles written by Nissen.) Only 108 (53%) provided a conflict of interest (COI) statement, despite the fact that all were published within the last 3 years (ie, during the burgeoning Age of Transparency). While 9 of 10 original research articles provided a COI statement, only 43% of the 91 letters, editorials, or commentaries and 59% of the 101 reviews, meta-analyses, or guidelines offered COI statements.
Consequently the Mayo physicians were obliged to search the Interweb for the remaining authors' potential COIs. They then determined that 90 (45%) articles were written by authors with COIs, but that only 69 (77%) of these articles provided a COI statement. In 3 articles, the authors declared no COI, but a web search revealed otherwise.
Among the 180 unique authors that were counted, the largest percentage (44%) were neutral on the subject of whether Avandia increases the risk of MI; 17% claimed no increased MI risk, and 36% concluded that Avandia increases the risk of MI. The COI breakdown is tabulated below.
|
COI |
No MI Risk |
Neutral |
MI Risk |
|
General, % |
94 |
38 |
28 |
|
Avandia, % |
87 |
24 |
20 |
|
Actos, % |
65 |
30 |
22 |
The Mayo docs concluded that authors who came down on the side of no increased MI risk were significantly more likely to have relationships with pharma in general, the manufacturer of Avandia (GSK), and the manufacturer of Avandia's main competitor, pioglitazone (Actos; Takeda).
A similar pattern was discovered when considering whether authors recommended the continued use of Avandia.
|
COI |
Favor Use |
Neutral |
Disfavor Use |
|
General, % |
88 |
40 |
26 |
|
Avandia, % |
81 |
26 |
24 |
|
Actos, % |
73 |
26 |
26 |
It is important to note that the possible influence of a pharma relationship wasn't limited to opinions on Avandia. Of the 29 articles that "strongly recommended" using Actos over Avandia, 86% were written by individuals who had a COI with the manufacturer of Actos.
Although the BMJ study is intriguing (in its narrowly focused sort of way), a big problem with it, in my mind, is that the authors failed to acknowledge the distinction between the COIs of pharma employees and those of academics.*** The former is expected (and expected to be highly influential), while the latter is the primary concern when it comes to preserving the integrity of the medical literature and mitigating any undue influence that pharma might have on medical practice. Unfortunately the BMJ authors neglected to make the distinction and stratify their assessments accordingly.
* The interim analysis of Home et al, which concluded no increased risk of MI with rosiglitazone use, also instigated its share of published responses, albeit it to a lesser extent than the meta-analysis by Nissen and Wolski.
** A direct competitor of Avandia. Actos actually has a cardiopotective effect, according to a randomized, controlled trial by Dormandy et al (2005).
*** Another big problem: Implicit within the study is that a relationship with pharma is necessarily a negative influence, rather than an indicator of greater knowledge of a drug's activity and associated clinical data.
The popular and continuing backlash against the pharmaceutical industry and its potential influence on the practice of medicine (and the practice of academic medicine, in particular) led to a number of notable events this year.
The most tangible is legislation dictating pharma and physician conduct—specifically, the Massachusetts Health Code Bill, which bans pharma gifts and meals to Massachusetts physicians and requires them to report pharma payments for their consulting and speaking services. The legislation is in the spirit of the updated PhRMA Interaction Code, which goes into effect January 1 and bans non-educational gifts—like branded pens, notepads, and stress balls—from pharma or medical-device companies to healthcare professionals.
A prime issue informing these actions is whether pharma money biases the treatment recommendations of key opinion leaders in academia. Notable academic psychiatrists specifically* were caught in the crosshairs of anti-pharma bulldog Senator Chuck Grassley, the national press, and interested bloggers, who charged that these influential physicians failed to report the payment of hundreds of thousands of dollars from pharma.
Another important factor is whether pharma currently holds undue influence over the content of continuing medical education (CME) that it supports financially. Some pharma companies (eg, Lilly), without withdrawing CME support altogether, have agreed to publicly disclose their CME funding to outside groups in a show of conscientiousness and in response to a request from Senator Grassley. Others (ie, Pfizer) cut off direct CME grants to medical education communications companies (MECCs), a probable PR move that is based on the perception of (and not so much actual) bias in MECC-produced CME specifically.
And if academic isolation from pharma is not possible (or very smart), then transparency is next to godliness. This year, the web site of The Cleveland Clinic began disclosing information about its physicians' financial ties to industry; although specific dollar amounts and research funding from pharma are not currently provided. In addition, the University of Pennsylvania recently reported that it will create a searchable web site that discloses the industry relationships of its physicians.
Straggling behind in this anti-pharma zeitgeist is the nearly toothless Accreditation Council for CME (ACCME), the accreditor of CME providers and, like many a bureaucracy, an apparent fan of abstruse verbiage. This year, the ACCME promised to enhance its monitoring and surveillance of CME production (by increasing its fees) and proposed harsh limits on CME production that demonstrated little practical forethought.
* Namely Joseph Biederman of Harvard, Alan Schatzberg of Stanford, and Charles Nemeroff of Emory.
In the spirit of the transparency zeitgeist, the University of Pennsylvania health system (my postgrad alma mater) will create a searchable web site that discloses the industry relationships of its physicians. The web site is scheduled to launch in the spring of 2009, according to the Philly Inquirer, and follows the example of the Cleveland Clinic, which most recently began providing information about its physicians' financial ties to industry.
The types of potential conflicts to be posted by Penn are not specified; however, the institution has a longstanding reputation for being relatively pristine, providing few (if any) opportunities for its residents and faculty to interact with pharma.* My estimation, if history is any guide, is that there will be little to disclose. Penn already bans its staff from accepting industry gifts, meals, and even drug samples, and the institution does not allow its name to be posted on pharma-supported CME.
Although the Cleveland Clinic discloses pharma-related royalties, equity interest holdings, and speaker or consulting fees (>$5000) received by its physicians, it fails to provide other, potentially relevant information like research grant support or actual dollar amounts received by faculty. For instance, the web page for Steven Nissen—head of cardiology, harsh critic of Vytorin (ezetimibe/simvastatin; Merck/Schering-Plough), and apparent lover of Crestor (rosuvastatin; AstraZeneca)—discloses no "applicable" financial relationships and reports that he donates all honoraria or consulting fees directly to nonprofit organizations. But other sources (eg, here) indicate that Nissen has received research support—life's blood for any academician—from a number of companies, including AstraZeneca.
* From 1986-1991, I never saw a drug rep in the Department of Medicine or Neurology, and I knew of noone who collaborated with industry on research at the time.
