By Ogan Gurel MD. You can email Dr. Gurel at gurel@aesisgroup.com and view his blog at http://blog.aesisgroup.com/.

A New York Times article published this weekend “Market Forces Cited in Lymphoma Drugs’ Disuse” presents a fascinating (and sobering) window on how financial incentives and other market factors can drive some drugs – despite strong indications of efficacy – from reaching patients. The article discussed the situation with respect to the lymphoma drugs Bexxar and Zevalin but the issue extends beyond these specific drugs. And it is important enough for the health of nations to consider in more detail.

Why should this be so and what are the broader implications?

Market Forces Drive the Adoption of New Pharmaceuticals and Medical Technology

While Medical Director at the healthcare consultancy and intelligence firm - Sg2 and clinical lead on literally dozens of hospital consulting projects, we had the opportunity to advise both clinical and executive management on emerging technologies and the implications of these for their institutions. The core offering of such projects was to provide information on new technologies and their potential clinical and business impact. An important task, however, was also to assess the “adoption dynamics” at that hospital and its respective market. A technology is of little strategic impact if it is to be adopted only marginally by the physicians in that community. Among other sources of information, we would conduct physician interviews; one such interview (back in 2003) was very memorable. Here’s how the interview went:

Interviewer: “Let me ask you about another technology.”

Dr. Jones
(name changed): “Sure.”

Interviewer: “Virtual colonoscopy. CT colonography, if you will. What do you think of that technology?”

Dr. Jones: “Great technology!”

Interviewer: “Really? Why?”

Dr. Jones: “Great technology!”

Interviewer: “… Any particular reason why?”

Dr. Jones: “It’s going to be a real money-maker.”

… awkward silence as the consultants around the table as well as the CEO of the hospital (also in attendance) glance at each other …

Interviewer: “I see. Why do you say that?”

Dr. Jones: “Well. It’s obvious.” – looking over at the CEO for approval.

Interviewer: “OK. Let’s move on to another technology”

I must say that having done hundreds of such interviews, this was an anomaly as the majority of doctors are – and must be - guided by their professional ethics rather than whether a particular technique will be a “money-maker” for them. The interview stood out nevertheless and certainly no one is so naïve to believe that money doesn’t play a role in clinical decisions and even if only marginally, it can have a substantial effect.

The Case of CT Colonography vs. Optical Colonoscopy

By way of background, CT colonography (or virtual colonoscopy) is a relatively new technique by which an imaging test – specifically a CT scan - is used to produce a picture of the internal anatomy of the large intestine in the hope (or rather hopefully not) of finding any signs of colon cancer. Radiologists – as evidenced by Dr. Jones’ enthusiasm – are the ones who review such studies and are thus reimbursed for them. Virtual colonoscopy has been considered by some to be a replacement for more conventional (and invasive) colonoscopy. While this statement is not entirely true, it is a fact that gastroenterologists (and to a lesser extent general surgeons) are the ones who order, perform and get paid for conventional colonoscopies and thus could be potentially threatened by the onslaught of radiologists on their turf.

[By the way, for the latest guidelines on colon cancer screening, see: the American Cancer Society or the National Guideline Clearinghouse.]

Interestingly, at the end of 2003 and early 2004, two articles were published in the nation’s leading medical journals – the Journal of the American Medical Association (JAMA) and the New England Journal of Medicine (NEJM) - comparing CT colonography with conventional (optical) colonoscopy.

As you can see from the two articles, nearly opposite conclusions – one in favor, the other against virtual colonoscopy– had been reached. Guess which article was written by gastroenterologists and which by radiologists? (Incidentally, for a posting on bias in clinical trials, see the article: “Subtle But Powerful, Publication Bias Goes Beyond Financial Incentives” which highlights how bias in studying expanding indications for erythropoietin - a controversial topic which has hit the headlines this past year - may have been evident as early as 1989).

Thus, the points raised by the New York Times article in which the drugs Bexxar (marketed by GlaxoSmithKline) and Zevalin (by Biogen Idec) were considered to be vastly underutilized for their indications should not be surprising.

“Non-Hodgkin’s lymphoma is the fifth most common cancer in the United States, with 60,000 new cases and almost 20,000 deaths a year. But fewer than 2,000 patients received Bexxar or Zevalin last year, only about 10 percent of those who are suitable candidates for the drugs.”

What is significant though is that in contrast to screening technologies – where definitive evidence can be challenge or near-impossible to obtain – well-defined treatment protocols for highly fatal diseases should provide relatively clearer answers. On the other hand …

“One reason is that cancer doctors, or oncologists, have financial incentives to use drugs other than Bexxar and Zevalin, which they are not paid to administer. In addition, using either drug usually requires oncologists to coordinate treatment with academic hospitals, whom the doctors may view as competitors … But the drugs have run into an obstacle that so far has been impassable. Because they are radioactive, they are almost always administered in hospitals, not doctors’ offices. As a result, doctors are not paid by Medicare and private insurers for prescribing them …”

The obvious implication of all this – which is the cornerstone of pharmaceutical marketing theory & practice - is that physician education and adoption is critical to building a market for drugs – whatever may be the degree of efficacy that these drugs may have been shown to have. An understanding of physician adoption dynamics absolutely requires an understanding of the “turf” and financial compensation issues involved. With respect to the latter, it should be borne in mind that this article is not intended as a critique of physician motivations per se. Two things must be considered – one that physicians, highly trained and as responsible for the welfare of others as they are, certainly deserve to be well compensated and it is only rational that they would seek such compensation and second, that systemic bias may confound what would otherwise be an objective appraisal on the basis of professionally determined patient benefit. All these, however, are issues beyond the scope of this article.

There are other, more surprising implications – especially concerning recent FDA reform proposals – which I’d like to briefly address.

Implications for FDA Reform

Previous postings (see: FDA: Tortoise, Hare or Something Else and FDA Reform Redux: On Business Models, Regulatory Reform and Safety) have proposed that in order to speed drugs through approval with greater confidence concerning their safety, the FDA should increase the rigor of the safety requirement while pulling back on the (Kefauver-Harris 1962) requirement for demonstrated efficacy. Decreasing the efficacy requirement (as is the case in many regulatory environments, including the EMEA in Europe) means that the market (namely the academic, clinical, payor and patient communities) should work out the efficacy of drugs given the assurance, of course, of strongly documented safety. This FDA reform proposal was, predicated of course, on the idea that information flow in our present internet age is much freer than it was in 1962. Efficacy information can be rapidly shared among all segments of the market and we have less to worry about “snake oils” propagating themselves without recourse in a highly efficient (from an information standpoint) market.

What the New York Times article – supplemented by the points above – imply is that while information flow may be fluid, there still are substantial barriers (namely the financial biases mentioned above) to free information interchange. As the article would seem to indicate, some oncologists may not necessarily want to know about certain evidence and in this end, the mantra of evidence-based medicine may be falling on deaf ears.

On the surface, then, the financial biases that cloud efficacy judgments should invalidate the FDA reform proposal (e.g. more on safety, less on efficacy) presented in my previous blog pieces. Ironically, though, one could say that the existence of these financial biases actually supports the FDA reform proposal even more strongly. Namely, if billions are being spent on efficacy trials in the hopes of building up an edifice of evidence based medicine, and yet market factors are what ultimately determine clinical practice, then one could surely say that those dollars are, to some extent, wasted. Hence, strengthening the efficacy component of FDA approval will likely have little effect on these market distortions. Free information interchange is, in this respect, of more value than the imprimatur of FDA efficacy approval.

The solution, then, lies in maximizing information flow and minimizing financial and market distortions. That’s a difficult problem which we’ll address in a later blog entry. In the meantime, any suggestions?

As all well know, Adam Smith propounded the free-market system in his famous “An Inquiry into the Nature and Causes of the Wealth of Nations.” While most would argue for the ascendancy of free-market economies in allocating resources and benefits in modern societies, one thing should be clear: by definition, in the absence of the free flow of information, a free-market system is only an illusion. If we delude ourselves in this way, there will be no concordance between the health and wealth of nations.

Ogan Gurel, MD MPhil
gurel@aesisgroup.com

Dr. Ogan Gurel is chairman of the Aesis Group which provides consulting services in the life sciences and healthcare sectors to clients that have included biopharma/medtech companies, hospitals & health systems, private equity firms, venture capital groups and hedge funds. Presently, he is also a Board Director at FireFly Medical and Chief Medical Officer at BlueBob Analytics. As a healthcare technology expert and futurist, he has been a frequent conference speaker worldwide, addressing the issue of emerging technologies and their impact on the future of healthcare with particular focus on convergent medical technologies including medical nanotechnology. Ogan’s commentaries have been published in prominent publications, including the Wall Street Journal and he is a regular columnist for Midwestbusiness.com, a juror for the 2007/2008 Medical Design Excellence Awards and an Adjunct Associate Professor of bioengineering at the University of Illinois at Chicago. Ogan’s scientific work has been published in the peer-reviewed literature and has received numerous awards; he has taught at several universities including the Columbia University College of Physicians & Surgeons, Roosevelt University, Princeton University and Harvard Medical School. For a more complete bio, you can download a PDF or click here. You can email Ogan by clicking here and view his blog at http://blog.aesisgroup.com/.