GE: Don't Know Much About Radiation Safety, Don't Know Much About Physics

Don't know much about history

Don't know much biology
Don't know much about a science book
Don't know much about the french I took.
(Wonderful World, sung by Sam Cook)

This is becoming the theme song for executives of health care corporations.  We have posted about a series of cases in which major health care corporations suddenly seemed unable to carry out their core business functions, a phenomenon I am going to start calling "core business incompetence."  Some recent examples:
-  Baxter International apparently failed to check the purity of heparin it bought from a foreign supplier; the contaminated heparin resulted in approximately 81 deaths. (See post here.)
-  A major Genzyme manufacturing facility had multiple quality problems, resulting in the production of a very expensive, but contaminated biologic medication. (See post here.)
-  Three Johnson and Johnson manufacturing facilities had multiple quality problems, resulting in the production of contaminated batches of over-the-counter medications for children. (See post here.)
-  Aetna made mathematical errors in computing the rates it proposed charging; WellPoint made computer errors that exposed sensitive policy-holder information.  (See blog post here.)

Manufacturing pure, unadulterated medicines is a core function of a drug company.  Correctly calculating policy-costs and correctly handling patient data are core functions of health insurance companies.  But in the above cases, three large pharmaceutical companies and two large insurance companies could not perform these core functions competently.

Radiation Sickness from CT Scans
In the last few days, more details of what appears to be another example of core incompetency afflicting a major health care organization has surfaced.  The details were reported by Walt Bogdanich in the New York Times. Here is the summary:

When Alain Reyes’s hair suddenly fell out in a freakish band circling his head, he was not the only one worried about his health. His co-workers at a shipping company avoided him, and his boss sent him home, fearing he had a contagious disease.

Only later would Mr. Reyes learn what had caused him so much physical and emotional grief: he had received a radiation overdose during a test for a stroke at a hospital in Glendale, Calif.

Other patients getting the procedure, called a CT brain perfusion scan, were being overdosed, too — 37 of them just up the freeway at Providence Saint Joseph Medical Center in Burbank, 269 more at the renowned Cedars-Sinai Medical Center in Los Angeles and dozens more at a hospital in Huntsville, Ala.

The overdoses, which began to emerge late last summer, set off an investigation by the Food and Drug Administration into why patients tested with this complex yet lightly regulated technology were bombarded with excessive radiation. After 10 months, the agency has yet to provide a final report on what it found.

But an examination by The New York Times has found that radiation overdoses were larger and more widespread than previously known, that patients have reported symptoms considerably more serious than losing their hair, and that experts say they may face long-term risks of cancer and brain damage.

So not to mince words, in this sad case, many patients seem to have been subject to radiation poisoning from a diagnostic x-ray procedure (not from radiation therapy for cancer.)  Most people (and physicians) may have not previously thought that radiation poisoning was a possible harm from a single diagnostic CT scan.

A Design Failure?

Moreover, it appears that the radiation poisoning did not result from some freak accidents or malfunction:

The review also offers insight into the way many of the overdoses occurred. While in some cases technicians did not know how to properly administer the test, interviews with hospital officials and a review of public records raise new questions about the role of manufacturers, including how well they design their software and equipment and train those who use them.

Also,

None of the overdoses can be attributed to malfunctions of the CT scanners, government officials say.

At Glendale Adventist Medical Center, where Mr. Reyes and nine others were overdosed, employees told state investigators that they consulted with GE last year when instituting a new procedure to get quicker images of blood flow, state records show. But employees still made mistakes.

As a result, hospital officials said, a feature that technicians thought would lower radiation levels actually raised them. Cedars-Sinai gave a similar explanation.

'There was a lot of trust in the manufacturers and trust in the technology that this type of equipment in this day and age would not allow you to get more radiation than was absolutely necessary,' said Robert Marchuck, the Glendale hospital’s vice president of ancillary services.

A GE spokesman, Arvind Gopalratnam, said the way scanners were programmed was 'determined by the user and not the manufacturer.' GE, he added, has no record of Glendale seeking its help setting up the new procedure in 2009.

Most of the known overdoses, including the biggest, occurred on scanners made by GE Healthcare. At two hospitals that use Toshiba scanners — Los Angeles County-U.S.C. and South Lake in Florida — officials said the manufacturer suggested machine settings that ultimately produced too much radiation. Representatives of Toshiba agreed to be interviewed in their California office but abruptly canceled.

In particular,

To this day, no one at Cedars-Sinai knows who programmed the scanners that delivered the overdoses, officials there say. But in written statements to The Times, hospital officials said they had figured out how they might have occurred.

Normally, the more radiation a CT scan uses, the better the image. But amid concerns that patients are getting more radiation than necessary, the medical community has embraced the idea of using only enough to obtain an image sufficient for diagnosis.

To do that, GE offers a feature on its CT scanner that can automatically adjust the dose according to a patient’s size and body part. It is, a GE manual says, 'a technical innovation that significantly reduces radiation dose.'

At Cedars-Sinai and Glendale Adventist, technicians used the automatic feature — rather than a fixed, predetermined radiation level — for their brain perfusion scans.

But a surprise awaited them: when used with certain machine settings that govern image clarity, the automatic feature did not reduce the dose — it raised it.

As a result, patients at Cedars-Sinai received up to eight times as much radiation as necessary, while the 10 overradiated at Glendale received four times as much, state records show.

GE says the hospitals should have known how to safely use the automatic feature. Besides, GE said, the feature had 'limited utility' for a perfusion scan because the test targets one specific area of the brain, rather than body parts of varying thickness. In addition, experts say high-clarity images are not needed to track blood flow in the brain.

GE further faulted hospital technologists for failing to notice dosing levels on their treatment screens.

But representatives of both hospitals said GE trainers never fully explained the automatic feature.

In a statement, Cedars-Sinai said that during multiple training visits, GE never mentioned the 'counterintuitive' nature of a feature that promises to lower radiation but ends up raising it. The hospital also said user manuals never pointed out that the automatic feature was of limited value for perfusion scans.

A better-designed CT scanner, safety experts say, might have prevented the overdoses by alerting operators, or simply shutting down, when doses reached dangerous levels.

Summary: Core Incompetence
To summarize, GE diagnostic CT scan machines apparently were designed so that they could deliver so much radiation that their use could cause radiation sickness. The machines had no built in safeguards to limit the dose of radiation. Users, that is, X-ray technicians, could program the machine so as to deliver dangerous radiation doses, but GE did not warn them that this was the case, nor provide a machine feature that would give a real-time warning of incipient overdose.

Thus it appears that GE, which has been described as "the world’s biggest maker of health care imaging and information technology systems," failed in its core function of designing and manufacturing safe diagnostic x-ray machines. (Presumably the same might be said of Toshiba, but the NY Times report does not include so much detail about problems with its machines.)

A straightforward explanation of the magnitude of the core incompetence was provided by one of the patients who got radiation sickness:

To Mr. Heuser, it is unconscionable that equipment able to deliver such high radiation doses lacks stronger safety features.

'When you are in a car and it backs up, it goes beep, beep, beep,' he said. 'If you fill the washing machine up too much, it won’t work. There is no red light that says you are overradiating.'

It really seems like we are seeing an epidemic of core incompetence by major US health care corporations.

I can only speculate about why this occurring. One explanation is that the organizations may be lead by people who do not understand the health care context, and do not understand the scientific, engineering, and technical issues involved with core competence. Many health care corporations have come to be lead by people with no experience or background in relevant areas.

For example, the current, and often acclaimed CEO of GE is Jeffrey Immelt, who "earned a B.A. degree in applied mathematics from Dartmouth College in 1978 and an M.B.A. from Harvard University in 1982." The leader of GE Healthcare is John Dineen, who "is a graduate of the University of Vermont where he earned Bachelor's degrees in biology/genetics and computer science," and "joined GE in 1986 as a telecommunications engineer."

Another, even more speculative explanation is that many major US and global health care organizations seem to have been infected with the virus of putting short-term financial results ahead of everything else, leading to cutting of costs and particularly human expertise in the areas most core to the organizations' functions, and pushing for hurried results even at the expense of clear thinking, carefully engineering, and consideration of the effects on patients and other humans of the resulting mistakes.

Hopefully, further investigation will reveal more about what went wrong in this case. Meanwhile, I say again, again, again,...

As long as "imperial CEOs" can continue to get extremely rich while presiding over incompetence and stupidity, if not worse), we can expect the foolishness to continue. Meanwhile, the foolishness drives up costs and drives down quality of health care for the poor suffering patients, let alone the physicians and other health care professionals who must deal with it.

To really reform health care, we need to provide incentives for competent, honest leadership, and make that leadership accountable for its shortcomings.

Postscript - Why the Rush to Aggressive Treatment?

The NY Times article described the rush to get one of the afflicted patients to the CT scan:

on the morning of July 4, when a 52-year-old executive producer of films, H. Michael Heuser, arrived in the emergency department with stroke symptoms.

A 'code brain' was immediately called, signaling a life-or-death situation. A blood clot in the brain can be dissolved with medicine, but doctors must do it within several hours, before brain cells die from a lack of oxygen. So Mr. Heuser was rushed into a room with several CT scanners, where he underwent one brain perfusion study and at least one more later. A CT perfusion scan, which lasts about 45 seconds, can identify a stroke through a series of blood flow images.

Mr. Heuser did have a stroke, from which he would recover. But other parts of his body inexplicably began to break down.

However, there is no clear evidence that such a rapid and drastic approach is really that good for patients. A recently updated Cochrane review concluded: "In patients with acute ischaemic stroke, immediate anticoagulant therapy is not associated with net short or long-term benefit. Treatment with anticoagulants reduced recurrent stroke, deep vein thrombosis and pulmonary embolism, but increased bleeding risk. The data do not support the routine use of any the currently available anticoagulants in acute ischaemic stroke." However, many physicians seem to advocate the drastic approach based on some controlled trials that showed at best small improvements in average neurological function for patients receiving rapid anti-coagulation (and which were done before anyone thought about radiation sickness as a possible harm of the approach.) Once again, an aggressive, technological, expensive approach, possibly advocated by people who stood to gain financially from it, may not be as advantageous as it appears.

BLOGSCAN - Evidence? We Don't Need No Stinkin' Evidence

The New York Times recently reported on the rush to use advanced CT scans for cardiologic diagnosis, in the absence of much evidence that this expensive technology works. Merrill Goozner on GoozNews, and Matthew Holt on the Health Care Blog offered some pithy comments. My jaw dropped at this quote in the Times article:

It's incumbent on the community to dispense with the need for evidence-based medicine.

As Goozner wrote, when self proclaimed experts (perhaps key opinion leaders) are convinced they are right, they don't need no stinkin' evidence.

ADDENDUM (2 July, 2008): Dr Wes also weighed in, with considerable skepticism. His post is an excellent primer about how the test is actually done, its drawbacks, and the lack of evidence supporting its use except in special circumstances.

Smoked Out: Funding Lung Cancer Screening Research with Tobacco Money

A few weeks ago, we posted about conflicts of interest affecting a widely publicized study of using CT scans to screen for lung cancer. The study, basically a large case-series, was susceptible to multiple kinds of study bias that challenged its validity. Yet its authors used this limited and flawed data to strongly advocate such screening. Two lead study investigators, Dr Claudia Henschke and Dr David Yankelevitz of Weill Medical College of Cornell University, held multiple patents on technology used for the screening, and had licensed one patent to General Electric, a manufacturer of CT scans, and exchanged another for rights in a start-up manufacturer of lung biopsy devices. They did not disclose these conflicts in the articles they published describing study results, including one in the New England Journal of Medicine. We noted that perhaps these conflicts were related to the investigators' great enthusiasm for CT scan based lung cancer screening that went well beyond the data from their study.

Since then, the plot has thickened. A follow up article in the Cancer Letter(1) noted that the New England Journal of Medicine article which failed to disclose the authors' patents and licensing agreement also was a vehicle for continuing medical education (CME). Ethics rules for US CME require full disclosure of all authors' conflicts of interest. Futhermore, the authors had given multiple CME talks. Their disclosure of these conflicts was inconsistent across these talks. Thus, on the GoozNews blog, Merrill Goozner announced that "The Center for Science in the Public Interest later this week will ask the ACCME [Accreditation Council for Continuing Medical Education] to order all the CME providers where Henschke failed to disclose to send proper disclosures to anyone who participated in those activities."

Henschke and Yankelewitz wrote a letter to JAMA in which they acknowledged they had failed to disclose "potential conflicts of interest" in a previous JAMA article and letter.(2) The letter was rather defensive, in my humble opinion, declaring that "The license agreement was between General Electric and Cornell, the institution listed on the title page. A portion of the royalties are distributed to both of us and to the other co-inventors pursuant to Cornell policy, which in turn is consistent with the Bayh-Dole Act." The letter also asserted the authors' very narrow interpretation of conflicts of interest, "we believe that none of the patent applications or the license agreement played any role in the design of the study, interpretation of the data, or drafting of the publications in JAMA and therefore did not disclose them."

A recent AP article noted that even getting to Henschke and Yankelevitz to write this much was not easy.

Dr. Catherine DeAngelis, editor in chief of JAMA, the Journal of the American Medical Association, said she contacted Henschke months ago after others pointed out patents not disclosed in a July 2006 study. DeAngelis said Henschke didn't believe the patents were relevant to the research and resisted disclosing them.

'We'd been working with Dr. Henschke trying to get her to write a letter of apology — which is our policy — and to take responsibility,' DeAngelis said. 'It was not easy to get her to do anything.'

But you ain't seen nothing yet.

This week, Gardiner Harris writing in the New York Times revealed that the same study which was reported in the New England Journal of Medicine article(3), was substantially funded by money from a tobacco company.

Small print at the end of the study, published in The New England Journal of Medicine, noted that it had been financed in part by a little-known charity called the Foundation for Lung Cancer: Early Detection, Prevention & Treatment. A review of tax records by The New York Times shows that the foundation was underwritten almost entirely by $3.6 million in grants from the parent company of the Liggett Group, maker of Liggett Select, Eve, Grand Prix, Quest and Pyramid cigarette brands [Vector Group Ltd].

Moreover, Henschke and Yankelevitz could hardly deny knowing about this source of their funding. They were the ones running the foundation.

Dr. Henschke was the foundation president, and her longtime collaborator, Dr. David Yankelevitz, was its secretary-treasurer.

It turns out that the leadership of Weill Medical College of Cornell University were in on this.

Dr. Antonio Gotto, dean of Weill Cornell, and Arthur J. Mahon, vice chairman of the college board of overseers, were directors.

The Cornell leadership denied that the intent was hiding tobacco money. On the other hand, the purpose of the foundation, other than to serve as a conduit for this money to the research project, was not exactly clear.

In an e-mail message, Drs. Henschke and Yankelevitz wrote, 'It seems clear that you are trying to suggest that Cornell was trying to conceal this gift, which is entirely false.'

'The gift was announced publicly, the advocacy and public health community knew about it, it is quite easy to look it up on the Internet, its board has independent Cornell faculty on it, and it was fully disclosed to grant funding organizations,' they wrote, adding that the Vector grant represented a small part of the study’s overall cost. The foundation no longer accepts grants from tobacco companies, they wrote.

In the Vector press release, Dr. Henschke was quoted as saying that, thanks to the Vector grants, 'we have raised the initial funding needed to support this important research and data collection on the effectiveness of spiral CT screening.'

Dr. Gotto said in an interview that Dr. Henschke, Dr. Yankelevitz and another colleague set up the foundation initially without the university’s approval, which he said faculty members are allowed to do. He and Mr. Mahon joined the board some weeks or months after its creation to ensure that the Vector grants were handled correctly, he said.

'If we had been approached, we would not have set up the foundation,' Dr. Gotto said. 'We would have accepted the gift directly. We think we behaved honorably. There was no attempt to set up a foundation to hide tobacco money.'

Days earlier, Andrew Ben Ami, assistant secretary of the foundation, said in an interview he would not disclose the source of the charity’s financing at the request of the university.

In another interview before Dr. Gotto agreed to speak, Mr. Mahon, another foundation director, said he did not know the source of the funds.

Note that the Foundation for Lung Cancer: Early Detection, Prevention, & Treatment seems quite obscure. It has no web-site. Its address and email address, as reported by SourceWatch, are for Dr Henschke's office. What it has done other than transfer tobacco money to the research project is unknown.

You just can't make this stuff up.

So we have yet another case which illustrates how pervasive is the web of conflicts of interest that entangles physicians, researchers, academic medical institutions, and industry. Moreover, the web increasingly appears to involve not only industries that make products meant to do patients more good than harm, that is drugs and medical devices, but also industries whose products have no medical use, and even now tobacco, certainly one of the major man-made health scourges.

So this case has actually produced some outrage. Per the New York Times article,

Prominent cancer researchers and journal editors, told of the foundation by The Times, said they were stunned to learn of Dr. Henschke’s association with Liggett. Cigarette makers are so reviled among cancer advocates and researchers that any association with the industry can taint researchers and bar their work from being published.

'If you’re using blood money, you need to tell people you’re using blood money,' said Dr. Otis Brawley, chief medical officer of the American Cancer Society. The society gave Dr. Henschke more than $100,000 in grants from 2004 to 2007, money it would not have provided had it known of Liggett’s grants, Dr. Brawley said.

Also,

Dr. Jerome Kassirer, a former editor of The New England Journal of Medicine and the author of a book about conflicts of interest, said he believed that Weill Cornell had created the foundation to hide its receipt of money from a cigarette company. 'You have to ask yourself the question, ‘Why did the tobacco company want to support her research?’' Dr. Kassirer said. 'They want to show that lung cancer is not so bad as everybody thinks because screening can save people; and that’s outrageous.'

The case also illustrates the messiness of relationships among researchers, academic medical leaders, and industry. As Gardiner Harris wrote in the NY Times,

Universities are responsible for policing conflicts of interest and, in many cases, the required disclosures of their faculty. But Weill Cornell shared in the proceeds of Dr. Henschke’s patent and pending patents, and university officials were on the foundation board.

'We have a very strict oversight policy' for conflicts of interest, Dr. Gotto of Weill Cornell said. He dismissed any suggestion that the university could not police and benefit from faculty members’ financial deals.

But Dr. Kassirer said, 'The problem is that universities, because they’re so conflicted themselves, ignore the conflicts of interest of their faculty.'

To illustrate Dr Kassirer's last point, a quick Google search revealed that Dr Gotto, in addition to being dean of the medical school, is a top leader of two pharmaceutical companies. He is on the board of directors of Aegerion Pharmaceuticals and of Arisaph Pharmaceuticals. So where do his interests lie? - promoting the integrity of the medical school, promoting more funding to the medical school, promoting the profits of these two companies, or promoting the interests of the power elite who simultaneously can run medical schools and run health care corporations? Who can tell?

And that is, as we have said before, the curse of conflicts of interest in health care. Conflicts lead to confused thought, speech, and action. One cannot tell what interests lie behind the speech and actions of the conflicted. So clinical research designed, implemented, analyzed, and discussed by the conflicted rather than leading to further clarity about how to care for patients, just leaves us in a fog of doubt.

But financial ties to various industries, regardless of the conflicts they produce, fuel academic medical institutions and universities who want their faculty to become "taxpayers" rather than teachers and researchers (see post here). Such funding may be one reason why administrators now outnumber faculty in higher educational institutions. Such funding fuels the imperial pretensions of their leadership (see post here). So the universities will not give up their conflicts without quite a fight. But it's time for that fight to start.

ADDENDUM (28 March, 2008) - See also comments by Merrill Goozner on Gooznews, and by Gary Schwitzer on the Schwitzer Health News Blog.

References

1. Goldberg P. NEJM says Henschke conflicts irrelevant; propriety of granting CME questioned. Cancer Letter 2008; 34: 1.
2. Henschke CI, Yankelevitz DF. Unreported financial disclosures. JAMA 2008. (Link here.)
3. The International Early Lung Cancer Action Program Investigators. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006; 355: 1763-1771. (Link here.)

Cancer Screening, CT Scans, and Patent Applications

We are getting to this story a bit late, but perhaps can provide some new insight.

In 2006, an article that supported the value of CT scans to screen for lung cancer caused quite a stir. [The International Early Lung Cancer Action Program Investigators. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006; 355: 1763-1771. Link here.]

The article reported a case series of over 30,000 patients who were entered into a program using annual CT scans to screen for lung cancer. Over 10 years of enrollment, 484 patients were found to have cancer. The investigators estimated the10-year lung-cancer specific survival of these patients was 80%, concluding "annual spiral CT screening can detect lung cancer that is curable."

A few days later, the article's lead author, Dr Claudia Henschke, was quoted in the New York Times as not understanding why CT screening was not the standard of care, "'I don’t get what the resistance is,' Dr. Henschke said. To her, it is a matter of simple logic: the earlier cancer is found, the better the odds of a cure. CT finds lung cancer early. So why not use it?"

In line with that sentiment, advocacy for widespread screening using CT scanning has continued under the auspices of the Lung Cancer Alliance. (See their news release, "Lung Cancer Alliance stands behind CT screening for lung cancer" from last fall.) The LCA asserted, "the mounting evidence which continues to mature from the largest international, protocol-driven screening effort (I-ELCAP) [is] showing that CT screening in a high risk population has the potential to reverse the current 15% five year survival rate." Furthermore, as reported in the May 4, 2007 edition of the Cancer Letter, legislation providing funding for screening using I-ELCAP protocols has been introduced in several state legislatures.

Of course, this seems to be another example of the introduction of an expensive, high-technology intervention that could save lives, but once again driving up the already staggering cost of health care. But these sorts of advances seem inevitable, don't they?

Maybe not. Dr Henschke's enthusiasm for screening seemed to go well beyond the data her study provided. In fact, the multiple flaws of the study were nicely summarized in a special article in the Archives of Internal Medicine [Welch HG, Woloshin S, Schwartz LM et al. Overstating the evidence for lung cancer screening: the International Early Lung Cancer Action Program (I-ELCAP) study. Arch Intern Med 2007; 167: 2289-2295. Link here.]

• A Case-Series, not a Randomized Controlled Trial - Because the study did not contain a control group, it is impossible to tell whether its apparently favorable results were due to the intervention, to the selection of patients with unusually good prognoses, or to chance. As Welch et al put it, "The I-ELCAP study design is a case series. Because there was no control group, readers cannot know what would have been observed in the absence of screening."
• Lead-Time Bias - The major result of the NEJM study was that patients with cancer seemed to live longer after their diagnosis than experience suggests is the norm for lung cancer patients. However, this could have been due to lead-time bias. Per Welch et al, "because survival is measured from the time of diagnosis, any screening test that advances the time of diagnosis will bias the measure of survival—the lead-time bias." For example, consider a person who developed cancer at age 60, was diagnosed at age 65, and died at age 66. His survival after diagnosis was one year. But if he had been diagnosed at age 60, and died at age 66, his survival after diagnosis would have been six years, but his life-span would not have been altered.
• "Overdiagnosis Bias" - This means that more intensive efforts at diagnosis may reveal cases of disease with more favorable prognoses. For example, it is well known that some patients who appear to have early prostate cancer will never have progressive disease. But detecting such patients by screening will not improve their survival. Welch et al noted that previous studies that used chest x-rays to screen for lung cancer demonstrated improved survival after diagnosis, presumably as a result of combined lead-time and overdiagnosis biases, since overall survival was not improved in patients who were screened compared to controls.
• Failure to Assess Harms of Screening and Subsequent Treatment - Welch et al noted problems with how the I-ELCAP study assessed deaths due to surgical treatment of cancer. The study also failed to report adverse effects of invasive diagnostic efforts for patients who had positive CT scans, most of whom did not prove to have cancer. For example, needle biopsy of lesions found by CT scan can cause pneumothorax (lung collapse), but these events were not reported in the NEJM article.

Also, a series of letters to the editor of the NEJM brought up similar concerns, plus additional flaws, e.g., although the I-ELCAP study reported 10-year disease specific survival, it only followed patients for a median of 40 months, and less than one-fifth of subjects were followed for five years or more. A response by lead author Henschke and two other authors failed to reassure. It first seemed to simply deny the importance of lead-time bias,

Screening for cancer is supposed to provide for lead time in diagnosis and treatment. A bias is introduced when one compares relatively short-term survival rates as of diagnosis to assess the effectiveness of treatment with lead time relative to treatment without lead time. We did not do this.

Henschke et al also seemed to misunderstand overdiagnosis bias. They responded to the relevant critique by asserting that all cases of cancer were confirmed by pathology. This begged the question, because pathological diagnosis does not necessarily determine whether a tumor will progress.

Finally, they seemed to deny that randomized controlled trials are necessary to assess screening programs.

Berg and Aberle remark that our study had no comparison group, but unlike interventional research, diagnostic research does not inherently require a comparison, much less a comparison group. The attainable frequency of diagnoses of stage I tumors can be assessed only in the framework of screening, and our principal diagnostic result was the 85% frequency of diagnoses of clinical stage I tumors among all diagnoses. The principal interventional result was the 92% cause-specific 10-year survival rate after prompt treatment of stage I tumors. The relevant comparison group would consist of patients who received early diagnoses but were treated late, principally to learn about the timing of deaths from lung cancer.

Every scientist tends to be an enthusiast about his or her own work, but I was struck by how Henschke et al seemed to shrug off their study's obvious methodologic problems.

(It might seem to be beating a dead horse, but I found even more problems with the I-ELCAP article beyond those noted above: failure to describe the clinical characteristics of the patient population; not blinding assessment of whether deaths were cancer-related; failure to have a credible method to verify that patients who did not have a positive CT scan did not have cancer; and failure to report loss to follow-up.)

More concerns about the origins of the I-ELCAP investigators' enthusiasm, which seems to have infected such groups as the Lung Cancer Alliance, were raised by a new report in the Cancer Letter, (from Jan 18, 2007, but not available without a subscription, and just made available to me last week),

The leaders of a research consortium that advocates computed tomography scanning to detect early-stage lung cancer have built an estate of 27 patent applications worldwide covering technologies and methods of screening.

According to publicly available databases, the leaders of the International
Early Lung Cancer Action Project are listed as inventors on patent applications
and one issued U.S. patent that cover innovations in lung cancer screening,
from clinical trial methodology, to software for interpretation of scans, to
technology of biopsy needles.

The first of these patent applications was submitted on April 11, 2000. In the U.S., group leaders are listed as inventors on one patent and 10 published applications. At least one of the inventions has been licensed by General Electric, a maker of CT scanners, and, in another instance, patent rights were reportedly exchanged for stock of a start-up company that markets lung biopsy devices.

Disclosure statements that accompanied the publications by the group’s leaders didn’t reflect these activities as potential conflict of interest, a literature
search shows.

Furthermore,

Both GE and Cornell declined to disclose the details of a licensing agreement covering Henschke’s and Yankelevitz’s inventions.

'We do have a license agreement with the Cornell Research Foundation for certain CT lung cancer patents,' Corey Miller, a spokesman for GE Healthcare Americas,
said to The Cancer Letter.

'The researchers—Henschke and Yankelevitz— have received some royalty payments from GE for a computer algorithm equation that they developed to detect lung cancer on diagnostic scans,' Miller said. 'That is, as far as I know, the extent of our relationship with those two.'

Note that the 2006 NEJM article included no disclosures of conflicts of interest.

Finally, the Cancer Letter noted that I-ELCAP investigators have worked actively with the Lung Cancer Alliance to promote screening.

As they spar with skeptics, I-ELCAP scientists work closely with LCA, a group that advocates for screening former and current smokers in accordance with I-ELCAP protocols.

So here we go again. Flawed research that supports an expensive, high-technology intervention for which millions of people would be eligible appears in a major journal. The intervention is hyped in news articles, and by a grass roots patient advocacy group. Politicians soon jump on the bandwagon. Citing the potential for saving lives, enthusiasts ignore the flaws in the data that started it all. Only much later do we find out that the researchers who wrote the flawed study may stand to make money if the high-technology intervention is widely adopted.

At the minimum, this case suggests that academic medicine's current method of managing conflicts of interest through disclosure is not working well. Further, in the absence of such disclosure, it seems that individual clinical decisions and public policy may too often be based on apparently unbiased research that in fact is being purveyed not merely by enthusiasts, but by people who may make more money when the results turn out a certain way.

People have been wringing their hands about ever rising health care costs for a long time. Expensive high-technology interventions are often cited as responsible, but not further addressed, apparently due to the assumption that their costs are an inevitable reflection of their advantages. Yet maybe this is not so inevitable. We may have placed to much credence in research that exaggerated the value of high tech gizmos because it was done by by people who stood to gain from the sale of such gizmos.

At the very least, we need to make sure we know when clinical research to evaluate screening methods, diagnostic tests, drugs, or devices was done by people with financial interests in their success. It might be, however, that the only way to get unbiased evaluations of drugs and devices is to have the evaluation done by people who have no financial interest in the results turning out one way or the other.

See this editorial in the Boston Globe by Dr Jerry Kassirer, and this post in the WSJ Health Blog for earlier discussion of what the Cancer Letter revealed.

ADDENDUM (11 March, 2008) - See also previous comments after publication of article by Welch et al by Merrill Goozner in GoozNews blog.

The Imaging Test Pre-Certification Blues

The Philadelphia Inquirer reported on the movement towards more restrictions on imaging tests by managed care organizations. Independence Blue Cross (of Pennsylvania) has noted that their payments for "diagnostic radiology" grew by 57% from 2001 to 2003. So on October 1, the company will begin to require that physicians obtain authorization before ordering (apparently all) outpatient diagnostic imaging tests. Aetna Inc. has required pre-certification for "high-technology diagnostic imaging" in the Philadelphia area for two years. Horizon Blue Cross Blue Shield of New Jersey started requiring pre-certification on January 1.
The Inquirer noted some down-sides of pre-certification, including adding to the bureaucratic burden on physicians, and the possibility that pre-certification will lead physicians to forego tests that would actually benefit patients. One physician noted that the pre-certification requirements are overly broad, not particularly targeted on specific kinds of over-use, and appear to be meant to discourage testing across the board, "pre-certification is meant as something of a roadblock to ordering imaging."
I was particularly fascinated by an aside in the article about the amounts Blue Cross is paying for imaging tests: $500 - $700 for CT scans, $700-$900 for MRIs, and $2000 for PET scans.
We had posted here about how generously insurers and managed care organizations reimburse for diagnostic imaging tests,. This article suggests that the cost to a hospital or radiology center of doing a CT scan is now only about $102 per procedure. So at least 80% of Blue Cross reimbursement for CT scans is pure profit for the owners of CT scanners. The reimbursement rates of CT scans in Philadelphia seem to be yet another example of "Wooden-Headed Health Care Reimbursement."
If health insurers and managed care companies are so concerned about health care costs, inquiring minds want to know why they keep paying so lavishly for imaging servicies? And why oh why don't managed care organizations and insurers bargain down reimbursement rates for these procedures to something more reasonable?
This cost-cutting approach would make a lot more sense than their continuing heavy-handed efforts to heap bureaucracy on doctors to discourage them from ordering radiology procedures.

The Costs of Computer Based Medical Technology

My take on Arnold Kling's article on the "Myth of Massive Health Care Waste" has generated quite a bit of discussion on Kling's EconBlog, here. What generated the most interest was the question of whether the cost of computer based medical technology was too high. (The example used was the CT scanner.)
Some of the main conceptual points raised were:

• One needs to separate the costs of the equipment and its maintenance from the other costs incurred by hospitals or offices in doing CT scans, and these, in turn, need to be separated from the actual price of CT scans
• Hardware costs need to be adjusted for inflation, but more important, the increasing capabilities of the hardware need to be taken into account

Some striking opinions were:

• "I think you'll find that in real dollars, the price of CT equipment and technology as well as the cost per procedure has dropped substantially...."
• "The PC hardware is a small part of the technology."
• "GE Medical dominates the market and can charge pretty much what it wants."
• "as quality/performance rises, 'prices' don't necessarily fall continually...."
• "If high fixed costs are the problem, more volume (more patients, more procedures) will lower the cost per procedure."
• "I was part of a design team for a CAT scanner.... I proposed many approaches that would have saved quite a bit in both hardware and software costs without reducing functionality, reliability, and performance. I was frequently met with the answer, 'We want it to be expensive.' The medical technology marketplace is a perverse marketplace. There are too many docs involved in the process and they don't respect anything unless it's expensive."

To make this discussion a bit more data driven, I was able to find some about the economics of CT scans over time. [Stockburger WT. CT imaging, then and now. Radiology Management, November/December, 2004. On the web here.]
From 1974 to 2004, the list price of a CT scanner has gone up faster than inflation (from $385K to $2200K, 471% increase, versus 342% increase in consumer price index). So has the acquisition cost ($385K to $1600K, 416%). However, revenue obtained per CT scan has gone up even faster (the Medicare payment for a CT scan of the head without contrast increased 700%.) Finally, and perhaps most importantly, the amount to be made by CT scanning facilities has risen even faster, because, as noted above, it is now possible to do more CT scans per unit time. In 1974, by my calculations, the typical profit of a single-scanner facility would have been $56700 in 1974 dollars. In 2004, it would have been $577,900 in 2004 dollars! Even adjusted for inflation, that's a big increase (1030% unadjusted, 298% adjusted for inflation)!
So, to summarize, my hypothesis that the costs of CT scanners over the last 30 years have become exaggerated in the face of the vast increase in computer performance/ price, given that the "C" in CT stands for computer, remains unproven. However, there is anecdotal evidence (from the comments above) that suggests that these prices may have been artificially elevated by a less than competitive marketplace plus the industries interest in wanting it to be expensive.
More importantly, the data from the article above suggests the larger problem. Despite the rise of managed care and of government efforts to contain costs, reimbursement for CT has risen faster than costs and inflation, and given that CT scans can be done more and more quickly, which raises volume while it further reduces the fixed costs associated with each scan, the amount of money made by CT scan facilities has risen even faster.
So the big question remains. If managed care was supposed to restrain costs by using a more business-like approach, and more attention to the economic issues, why has it so massively failed to restrain these sorts of costs?