Tuesday, September 02, 2008

Dr Marcia Angell on Reforming a "Broken System" of Clinical Research

This week's Journal of the American Medical Association (3 September, the paper version of which seems to arrive early at my house) is notable for having three commentaries on relationships among physicians, academic medicine, and industry. One, by David Rothman and Susan Chimonas, seemed rather optimistic, while two, by Dr Arnold Relman and by Dr Marcia Angell, were quite dark.

The latter [Angell M. Industry-sponsored clinical research: a broken system. JAMA 2008; 300: 1069-1071. Link here when available] should be required reading for anyone who worries about the issues we raise on Health Care Renewal. Dr Angell provided an excellent summary of how commercial "sponsors" have come to dominate clinical research, and thus ensure that the resulting studies favor their vested interests. My only criticism of her summary of the data was that it may actually have been too optimistic. For example, Dr Angell focused almost exclusively on pharmaceutical companies' influence on research, while the problem is even larger. Biotechnology companies, device manufacturers, and multiple miscellaneous commercial suppliers of health care goods and services also may influence research. Dr Angell's admittedly extensive list of the kinds of relationships among researchers and industry (grant support, paid consulting, service on speakers' bureaus and advisory panels, and stock ownership) was incomplete, leaving out, for example, the even more acute conflicts of interest generated by service on companies' boards of directors and service as companies' officers.

But those are quibbles. Most striking was Dr Angell's summary:

Looking at this picture altogether, it would be naive to conclude that bias is only a matter of a few isolated instances. It permeates the entire system. Physicians can no longer rely on the medical literature for valid and reliable information. This is the conclusion I reluctantly reached toward the end of my 2 decades as an editor of the New England Journal of Medicine, and it has been reinforced in subsequent years. Clinicians just do not know anymore how safe and effective prescription drugs really are, but these products are probably nowhere near as good as the published literature indicates.

I am afraid I must concur, and also concur with her summary of the effects of the substitution for valid clinical research of pseudo-evidence favoring the vested interests of "research" sponsors:

Physicians learn to practice a very drug-intensive style of medicine.

Physicians are also led to believe that the newest, most expensive brand-name drugs are superior to older drugs or generics, even though there is seldom any evidence to the effect because sponsors do not usually compare their drugs with old drugs at equivalent doses.

Physicians learn to use drugs for off-label uses without good evidence of effectiveness.

Keep in mind that the same considerations apply to devices, so that physicians also learn to practice a test- and procedure-intensive style of medicine; are led to believe that the newest tests, devices, and procedures are superior to older ones without any evidence comparing the new to the old; and physicians learn to extend the use of tests, devices, and procedures far beyond what the evidence would support.

In addition, I agree with Dr Angell's advocacy of an independent body that would administer all clinical trials of drugs. Dr Angell suggested it be an Institute within the NIH. I think it might be possible to form a not-for-profit body that would be independent of government that would do the same thing. Furthermore, that body, or another in parallel should also administer all clinical trials of diagnostic tests, devices and procedures, for analogous reasons.

Finally, Dr Angell urged academic investigators and their institutions to "be at the forefront of efforts to reform the system of clinical research and not leave it to the government and legal profession." However, as Dr Angell previously noted, a majority of medical school faculty have financial ties to drug, device, biotechnology and other health care companies, as do a majority of department chairs. As we have noted, some top leaders of academic medicine serve also as top leaders of for-profit health care corporations (see this post), and other corporations whose products have profound effects on health, even tobacco companies (see this post). Many academic leaders make a small fortune working on the side for such companies. It may be too much to expect that such leaders would be at all interested in reforming a system that has so effectively lined their pockets. For better or worse, we may need a wholesale change in the leadership of academic organizations before we can expect any real cooperation from them in transforming clinical research from being mainly a marketing exercise to once more being real clinical science.

ADDENDUM (5 September, 2008) - See also comments by Dr Howard Brody on the Hooked: Ethics, Medicine and Pharma blog.


Anonymous said...

While in general I agree with Dr. Angell's comments (which are not her first on this issue) and yours, looks like Boston Scientific got a big surprise in its recent stent vs. bypass study, doesn't it. There had been hints of this result in previous studies. One can't say they suppressed the results, can we? We can only wish for more of these comparative effectiveness studies - probably no stent company will fund any more of this particular type!

bev M.D.

Bruce Grant said...

40 years ago, when I first began my career, the physicians I worked with in academic medicine prided themselves on a culture of independence from commercial influence. The few physicians on faculty who had significant relationships with industry, as clinical investigators, were considered somewhat declassé and subtly looked down on.

It's worth noting that the chief source of funding for medical education and training at that time was our government -- through Hill-Burton funding, Federal medical student and resident capitation, NIH grants, and so on.

Were one to plot the rise of industry influence over academic medicine and clinical research it would reveal a rather neat inverse-proportion relationship to societal funding of these enterprises so vital to society as a whole.

The 1980s tide of Reaganomics -- propelled by slogans like "It's your money" and "Government is the problem" -- left academic medicine not-so-high...but very dry for funding. Faculty appointments started to become contingent on funding one's own salary and expenses, and hospital administrators began to speak of "taxpayers" (staff and faculty with their own sources of funding) and "welfare recipients" (those without).

It was into this vacuum that industry money began to flow -- not just in academic medicine but in academia in general -- generating a new culture of industry friendliness and leading to today's sorry state.

If one wants to lay blame for the corruption of a once incorruptible profession one should look to those who made it susceptible to corruption by impoverishing it.

A society gets the healthcare system it pays for. And if it doesn't pay for it, it gets the healthcare system someone else has (bought and) paid for.

MedInformaticsMD said...

If one wants to lay blame for the corruption of a once incorruptible profession one should look to those who made it susceptible to corruption by impoverishing it.

I still also hold to blame those who became corrupt. That's a personal choice.