Conflicts of interest: Finally a formula that solves it!

It is now difficult to know what to do with the information provided in the disclosure section of journal articles.  I am puzzled as to how are we supposed to train residents and fellows into how to incorporate this information into the decision making process.  After all, we want the readers to formulate impressions about disclosures so that they attain objectivity about content.  And objectivity is about measurement.  So how is one supposed to do so?  Until now no one knew for sure.

As background I would suggest we needed a simplified statistical system for an audience who is known on occasions to struggle with stats.  For example many very smart colleagues still struggle with the significance of the p value.  Less than 0.05 Biblical!  Anything else discard immediately...  Let alone understanding a Bonferroni correction.

So to try to solve this problem I tackled a recent paper in the NEJM where C1 inhibitor deficiency is successfully treated by a new intervention (one of 3 papers in the same issue).  (Zuraw et al N Engl J Med 2010; 363:513-522August 5, 2010).  By the way congratulations to the authors on such important study.  (This comment is about the irony of disclosures not the value of their paper, which is truly outstanding).  The methods did not tell me how to account for the disclosures (Top figure).  So if you look at the results section there were 1006 words.  The disclosure text was almost as long (798 words).  There must be a way!  After many hours I took it upon myself to calculate the significance of disclosures and suggest the following formula for correction.

For the sake of providing due credit I thought about the "CANDAB correction" which is an acronym with the first letter of some of the most intense pharmascolds. (HINT:  Solving this is much simpler than my formula).  So here it is finally! Do this for every author.  X stands for the age of the author, y is the net compensation received in the last 12 months and n is the number of times they have participated in CME or consulting.  You add it all and move the p value as many decimal points as the result shows to know the truth. 

 Late breaking news: I heard JAMA will include automatic computation in their website.

Guest Blog: Real Influence, Pharma or Insurers?

With the recent proposal to repeal the so-called Massachusetts “gift ban” (referred to from this point as the “interaction ban”), I asked myself who stands to gain the most from such bans? Is it the consumers or patients?  Is it the physicians or their practices? Is it the federal or state governments?  Nope. Sadly, it is the insurers who gain the most, at the expense of patients. 

The argument for interaction bans is that generics will save money over name-brand medicines, which are being “unnecessarily” or “irrationally” prescribed (as defined by whom?). What is forgotten is who wields the most influence over the decision to prescribe a medication. The public is convinced that it is the physician, and, actually, that would make sense.   More recently savvy public relations campaigns and advocacy efforts have convinced legislators (and the public, so the advocates claim) that it is the Pharma rep that controls prescribing. In reality, it is the insurance companies.

Insurance company actuaries decide which drugs are on the formulary (what they will cover) and which one is a preferred name-brand medicine (cheaper co-pay), based on benefit-to-the-bottom-line calculations.  Ironically, some generics are not even on a formulary list and are NOT preferred over name brands. Consequently, these decisions, which are based on the whim of the insurer, dictate whether a patient has access to a medicine, not their physician, and definitely not the Pharma rep.

Does an intelligent Congressman or Senator really believe that a patient will blindly order a name brand drug when generics are available?  What would they do in that situation?  Why would they think the general public will be so eager to simply accept a costly name-brand medicine when money could be saved? Are Congress members so far removed from reality?  Some of my patients have to decide to forgo either food or medications.  I hope Congress members realize they lacked the proper infomation about the situation and correct their version of reality!

For example, it is already extremely challenging to get a name-brand medicine when it is medically necessary.  Many states have laws that mandate generic interchange (substitution when the active ingredient is the same); physicians must fill out prior authorizations, which are labor-intensive and represent uncompensated work; and pharmacies are pushing cheaper alternatives due to higher profit margins for them.

Among all these competing forces, where is the logic, or evidence, that a patient can walk into a physician’s office and end up with an unnecessary and expensive bottle of pills solely because of a Pharma rep?  Only in the minds of idealistic social science researchers who claim that a pen with a name brand label will overcome all these obstacles. Sadly, the true issue at hand is that many physicians will or cannot perform the extra work to obtain a name brand drug when it is safer or works better than a generic because of the extra time or staff involved with the myriad paper-work, which is a real cost-driver of health care.

So the next time you hear of the egregious cases of Pharma exerting their control by ‘wining and dining’ physicians, take a moment to consider who really stands to gain by the proposed solutions and whether patients have even entered into the equation.

Edison Wong, MD

Physiatrist, Massachusetts 

WHO and Conflict of Interest; Chan versus Godlee

Without base, or substance, the WHO has come under fire for not having disclosed financial ties of some of its advisers regarding the influenza pandemic of last year.  It turns out the BMJ published an accusatory article, and accompanying editorial.  These accusations will persist in the blogosphere, despite very forceful and rightful fight back by Dr Chan (WHO director) and colleagues.  It seems that the BMJ editors are only is interested in self promotion of an agenda that has no basis.  If no influence is found (which will not be) then the WHO should press on with a request for a retraction, or at the very least an apology.

It is worth noting that criticisms for those who work with industry come  from people like Dr. F Godlee, who has no track record in having worked ever with industry. A quick Pub Med search reveals that most of her publications are commentaries while on editorial boards, and little in the way of original research.  One can easily conclude that her agitation and suspicion arises from a fundamental lack of understanding of the process of research involving industry.

NIH Proposes New Conflict of Interest Regulations

The original NIH regulations went into effect in 1995. At that time we were fairly early into the avalanche of allegations that financial “conflicts of interest” promoted research corruption and were just emerging from a spate of high-profile scientific misconduct incidents. Therefore, one might cut the NIH some slack for some of the disingenuous aspects of its policy.


First, I put “COI” in quotes, because it is a meaningless framing bias that ignores the fact that interests are only perfectly aligned in anthills and that the pejorative use of “conflicts” emphasizes potential risks over potential benefits (otherwise there would be no need to disclose, manage or eliminate them). If you accept the frame, it puts you in the impossible position of disproving a negative (“I am not a crook”). It gets worse when you stretch the rules to cover “appearance” of conflict, because appearance is reality in politics, not science and because it is totally subjective. “Appearance” is invoked frequently in the proposal (I assume it was in the original as well).


What is striking and focuses the discussion is the title of the document: “Responsibility of Applicants for Promoting Objectivity in Research for which Public Health Service Funding is Sought and Responsible Prospective Contractors.” The assumption is that COI detracts from “objectivity in research.”


There was no evidence in 1995 that this assumption is true, and no evidence has emerged in the intervening 15 years. In fact the totality of evidence of “corruption” due to FCOI has shifted almost totally to marketing, not research – and that evidence is vanishingly weak.


I am unaware of a single case of research misconduct that involved industry-related FCOI. The approach to research misconduct has been to maintain a narrow definition of misconduct, investigate allegations thoroughly, and punish the convicted. We do not “manage” (and we can’t eliminate) misconduct. It is therefore bizarre that we have allowed a prophylactic regime to permeate biomedical research – instead of ticketing speeders, we ban fast cars.


The ramping up of regulation in the absence of substantive evidence that we need it is, of course, the fallout from demagoguery exercised by certain politicians abetted by COI critics and the media – and by the failure of rank and file researchers to resist.


The proposed regulations represent a stimulus plan for COI bureaucracy and the “COI experts” who encourage it. The emphasis on appearance empowers the type II error


At a time when the NIH budget is flat and the investment pipeline is seized up due to the recession, why would we divert energy and scarce resources into the minute compilation of who is being paid how much and speculate on what constitutes a “significant” COI – even a FUTURE COI -- “that COULD effect the design, conduct or reporting of research?”


Prior to 1995, commercial influence permeated biomedicine exponentially, and only good things happened. Investigators were free to mingle with industry, and research superstars deservedly made a lot of money. Medical research is not immune to opportunity costs and the emerging compliance culture will hurt progress – and patients.