In Keillor’s fictional Lake Wobegon, all the women are strong, all the men are good-looking, and all the children are above average. At the much less bucolic FDA, some scientists and doctors are fighting with administrators over approval of radiological devices, and the administrators are fighting back by monitoring the staffers’ personal e-mail.

Meanwhile, the FDA announced a tentative deal with medical device makers that would double its user fees in exchange for a faster and more transparent device-review process.

So, kind of a roller-coaster week.

Last week began with the news that six former and current FDA staffers, including two doctors and an MD/PhD, had filed a lawsuit alleging that the agency had spied on their nonwork e-mail, which the staffers had accessed through work computers. The suit also charges that the FDA fired or otherwise retaliated against them for leaking documents to Congress and the press.

Science magazine has a good summary of the situation, including a link to the lawsuit. What’s most significant for the medical community and the public is the viciousness of the infighting as FDA managers push for approval of radiological devices against the advice of their own medical and scientific experts.

The Washington Post points out:

Most of the devices the scientists and doctors questioned have received approvals only in the past two years, making it difficult to evaluate whether the fears that the FDA scientists and doctors expressed were valid.

Against that backdrop, the FDA announced on Wednesday the user-fee agreement, which is intended to speed up that very same approval process for medical devices. DOTmed News quoted Stephen Ubl, president of the Advanced Medical Technology Association trade group, as saying:

We believe this agreement is a potential game changer for the FDA, for industry, and, most importantly, for patients and the American economy.

The FDA said the agency would collect $595 million, plus adjustments for inflation, in user fees over five years, allowing it to hire more than 200 full-time-equivalent workers. “The FDA and the industry expect that the agreement in principle would result in a reduction in average total review times,” said the agency’s announcement.

Great. But the FDA has to do a better job in balancing the legitimate economic and political pressure to get useful devices approved with its duty to make sure that the devices are indeed useful as well as safe.

The Washington Post story quotes one of the lawsuit plaintiffs as saying a team of FDA experts three times recommended against approving a computer-aided imaging device for detecting breast cancer. Each time, the plaintiff said, middle managers agreed. Then, after the third rejection, a senior manager approved the device.

Something’s wrong, and adding more money and more staff won’t fix it.

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Related seminar: Radiology Review Course

University of Pennsylvania engineers coated iron oxide nanoparticles with glycol chitosan, a sugar-based polymer that reacts to acids. The sugar keeps the particles from binding or being absorbed by the body, but this particular formulation allows them to become ionized in acidic environments and thus attracted to such areas.

Enter the Warburg effect: Most healthy cells are aerobic, getting energy primarily from oxygen, but cancer cells are anaerobic, getting energy from glucose and turning it into lactic acid. Cancer cells also disrupt the blood flow around them, making it harder for the body to clear away the acid.

So acid-attracted iron oxide nanoparticles will cluster around tumors and make them stand out on MRI images. Said Andrew Tsourkas, PhD, who did the research along with graduate student Samuel H. Crayton:

One of the reasons we like our approach is that it hits a lot of tumors; almost all tumors exhibit a change in the acidity of their microenvironment.

Dr. Tsourkas, an associate professor of bioengineering at Penn’s School of Engineering and Applied Science, was quoted in a Penn news release. The research was published in the December 27 issue of ACS Nano.

The new coating could work well for other uses too, Dr. Tsourkas said:

You can take any nanoparticle and put this coating on it, so it’s not limited to imaging by any means. You could also use it to deliver drugs to tumor sites.

It gets better: The more malignant a tumor, the more it disrupts blood vessels, and therefore the more aciditic its environment. So the new nanoparticles do a good job differentiating malignant from nonmalignant tumors.

That could particularly benefit patients getting an MRI scan as a secondary breast cancer screen. MRI’s high sensitivity but low specificity can work against it, as Dr. Tsourkas explained: “The screening detects a lot of tumors, but many of them are benign. Having a tool like ours would allow clinicians to better differentiate the benign and malignant tumors.”

That explains why the research was funded partly by the Department of Defense Breast Cancer Research Program (yes, such a thing exists).

Related seminar: CT/MRI of the Abdomen and Pelvis

Breast-cancer researcher Mina Bissell, PhD, explained:

Our data show that at lower doses of ionizing radiation, DNA repair mechanisms work better than at higher doses. This nonlinear DNA damage response casts doubt on the general assumption that any amount of ionizing radiation is harmful and additive.

Dr. Bissell, who holds the title of distinguished scientist at the Berkeley Lab’s Life Sciences Division, was quoted in a lab news release. The findings have particular significance for those who undergo such low-dose medical imaging procedures as mammograms.

The lab revealed the results of its research in a freely available study published online Monday in Proceedings of the National Academy of Sciences.

The decreased risk at low doses derives not from the amount of damage caused by the radiation but rather from how the body fixes the damage. The researchers found that after low doses of radiation, the body repairs double-strand DNA breaks (meaning the double helix is completely severed) on site. It’s a relatively simple procedure with relatively little chance of error.

But as doses increase, creating more double-strand breaks, the broken strands congregate at “radiation-induced foci” (RIF), which are aggregations of repair proteins. With lots of repairs going on at once, the opportunities for mistakes increase.

“We hypothesize that, contrary to what has long been thought, double-strand breaks are not static entities but will rapidly cluster into preferred regions of the nucleus we call DNA repair centers as radiation exposure increases,” said Sylvain Costes, PhD, a biophysicist who led the study.

“As a result of this clustering,” Dr. Costes said, “a single RIF may reflect a center where multiple double-strand breaks are rejoined. Such multiple repair activity increases the risks of broken DNA strands being incorrectly rejoined, and that can lead to cancer.”

The researchers are looking into whether their results, achieved with a single human breast cell line, will hold up with different lines and different breast cells. Stay tuned.

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Related seminar: ALARA — CT (As Low As Reasonably Achievable)

B.C. Wang, PhD, studies molecules. (He’s Ramsey-Georgia Research Alliance Eminent Scholar in Structural Biology at the University of Georgia in Athens). X-ray crystallography—bombarding molecules’ crystalline forms with X-rays—reveals the position of chemical bonds and other important properties.

However, large molecules, which are especially important in drug development, don’t handle X-rays as well as small molecules do. In a University of Georgia news release, Dr. Wang explained:

A macromolecular crystal can only withstand a certain amount of X-ray dose before it is destroyed as a result of radiation damage. Obtaining accurate and complete diffraction data sets of these crystals is very important.

So Dr. Wang and his team tried doing several low-power scans of the same crystals (specifically, bovine insulin crystals) instead of a single higher-power scan. The weaker scans delivered the same total radiation dose as the single higher-power scan would have. They also produced much better data than the single scan. For details, see the study, published online this month (open access) in the journal Foundations of Crystallography.

Adapting this technique to human imaging could produce better-quality scans while reducing radiation exposure, though Dr. Wang cautions that such applications will not be ready for clinical use anytime soon.

Of course, there will be problems to overcome. For one thing, bovine insulin molecules are generally better at holding still than people are. And Dr. Wang’s team uses X-ray data in a different form from the familiar human X-ray image. But, obviously, such multislice technologies as CT have overcome similar issues.

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It comes from the Medical Imaging & Technology Alliance (MITA), a trade group for makers of medical imaging equipment. So perhaps it’s not so surprising.

MITA said in a Wednesday news release that, according to its own analysis of Medicare data, spending on imaging for each Medicare beneficiary has decreased 13.2 percent since 2006. In addition, the release said, imaging utilization per beneficiary decreased by 3 percent in 2010. Spending for Medicare services other than imaging has increased by 20 percent since 2006, and overall utilization increased by 2 percent in 2010, MITA said.

David Fisher, MITA’s executive director, said the reduction in imaging spending and use may be harming Medicare patients:

It is unsettling to see these accelerating declines in Medicare beneficiaries’ use of medical imaging services during a time of tremendous advances in imaging and radiation therapy technologies, which have become increasingly integral to medical best practices and early disease detection. This disconnect raises serious concerns about whether or not patients are receiving the care they need.

Somehow, we can’t see the congressional “super committee” bursting out of its phone booth, or its locked meeting room, or wherever it’s been thrashing out deficit-reduction proposals, and saying, “Sure, cut spending on Social Security, the military, our salaries, and everything else, but we really need to increase Medicare spending on imaging.”

Still, as MITA points out, imaging reimbursements have been cut seven times in six years, with payments for such services as bone density screenings, arm and leg artery X-rays, and brain MRI reduced by more than 60 percent. And further cuts have been proposed. Are Medicare patients in fact now getting second-rate care … well, maybe that’s too strong; let’s say suboptimal care in terms of imaging?

MITA also quotes John A. Patti, MD, chair of the American College of Radiology Board of Chancellors, as saying, “Current evidence, including this analysis, debunks the myth that imaging is significantly overused and somehow responsible for escalating health-care costs.”

Dr. Patti adds:

According to these data, the goal of bending the cost curve has indeed been achieved for medical imaging. Any further reductions would represent socially irresponsible policy.

Of course, the fact that a piece of legislation might be socially irresponsible has never stopped Congress before.

Related seminar: Radiology Review Course

We’ve written previously about the mess in the province, where an examination of the work of four radiologists eventually involved checking 14,000 scans.

Doug Cochrane, MD, chairman of the British Columbia Patient Safety & Quality Council, led the investigation. He said the independent radiologists who reviewed the scans found serious problems with interpretations only of CT scans, and not of mammograms, ultrasounds, or ordinary X-rays.

Doesn’t sound too reassuring, does it? Especially because Dr. Cochrane said the review team found “discrepancies” in up to 17 percent of the CT scans. However, he said, as quoted by the Vancouver Sun:

No one died as a direct result of an imaging misinterpretation.

Health officials did say three people died indirectly, apparently as a result of delays or errors in treatment. As Dr. Cochrane said, “Delays in treatment occurred. Changes in treatment occurred. Tests were repeated. There were additional interventions and procedures because of these errors.”

At least some of the radiologists apparently were learning how to read CT scans on the job. At least one took a two-week course in CT interpretation.

In some cases, the investigation found, doctors working with the four radiologists observed inept behavior but did not promptly report it. The report said staff at Powell River General Hospital in Powell River were “aware of deficiencies in scanning processes and interpretation” from the time the scanner was commissioned, but feared reprisals if they voiced concern.

Dr. Cochrane and Health Minister Mike de Jong announced procedures designed to prevent future errors through improved oversight and monitoring, including better checking of credentials. Compensation for affected patients and their families is being discussed, de Jong said.

Joan Graham, whose father, John Moser, died of cancer in a British Columbia hospital after an incorrectly interpreted CT scan, called the report “spin doctoring.” She found the lapses in monitoring and reporting infuriating:

To me, this is something that should have been elementary. You wouldn’t check people’s credentials?

None of the four radiologists apparently has been disciplined. Two are no longer working in Canada, and one is working in Ontario, where, according to the Sun, “authorities have been made aware of the concerns.”

One of the four radiologists is still working in British Columbia—but within his area of expertise, according to de Jong.

Heidi Oetter, MD, registrar of the College of Physicians and Surgeons of British Columbia, the provincial licensing and regulatory body for doctors, said that radiology is particularly prone to competency problems because it depends on constantly evolving technology and “whiz-bang machines.”

Yep. Those newfangled gadgets’ll confuse you every time, by cracky. Better we should all stick to X-rays, right?

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Robert Smith, PhD, was appalled at a loud cheer when an announcement at a medical meeting heralded just such a milestone. “Several of us were just shaking our heads in disbelief,” he said, “because it makes absolutely no sense whatsoever to put a 100-year-old woman through a mammogram.”

And Dr. Smith, as director of screening for the American Cancer Society, is a screening hawk. “As long as a patient is in good health and a candidate for treatment, they are a candidate for screening indefinitely,” he told Sandra G. Boodman for a story headlined: “Concern Is Growing That The Elderly Get Too Many Medical Tests.” The article was published jointly by Kaiser Health News and The Washington Post.

The article cites such excesses as a virtual colonoscopy for a 99-year-old woman. And such tragedies as the case of a theretofore healthy 78-year-old man who underwent radiation treatment for prostate cancer—a disease that typically progresses too slowly to seriously bother, let alone kill, someone of that age—and was left impotent and incontinent.

How old is too old for screening or other imaging tests? Do we side with Dr. Smith, who thinks that underscreening is more of a problem than overscreening, even among the elderly? Or with Mark Klein, MD, a Washington, DC, radiologist, who said:

The most important thing on any referral is the date of birth. The game is not finding things. It’s can you improve mortality? And if you do find something, it’s very hard for a doctor to say, ‘Don’t do anything.’

Pamela Davis, MD, a family-practice physician and director of the Family Medicine Residency Program at Northridge Hospital Medical Center in Northridge, California, discovered that when a doctor does say “Don’t do anything,” the patient may not react well. When she told a healthy, active 86-year-old woman that mammograms and colon cancer tests were no longer necessary “at your age,” the woman became furious and responded:

You doctors just want to save money to spend on the young people and just let us old folks die.

The woman was Dr. Davis’s mother.

When Dr. Davis wrote about the experience in a Los Angeles Times article, the doctor received a flood of angry responses, some from fellow physicians, accusing her of the same thing.

Money is always a consideration. Money being made from imaging procedures, ever-growing amounts of money being spent on health care, money not being spent by insurance companies.

However, Dr. Davis would certainly spend any amount of money, from her pocket or any other, if she thought it helpful for her own mother. What’s best for individual patients of whatever age will certainly vary. Reasonable, well-intentioned people will argue about screening and other tests for the elderly.

However … maybe we can all agree that a centenarian doesn’t need a mammogram, and work back from there.

Related seminar: Review for Practicing Radiologists

The numbers are certainly dramatic. The study, published online August 1 in Annals of Emergency Medicine, analyzed a sample of 447,011 U.S. emergency department visits from 1992 through 2006, using National Hospital Ambulatory Medical Care Survey data.

The study found that from 1996 through 2006, the percentage of adult patients with appendicitis who received a CT scan increased from 6.3 percent to 69 percent. For children, the increase was from 0 percent to 59.8 percent.

Lead researcher Daniel S. Tsze, MD, is director of the pain management and sedation program at Morgan Stanley Children’s Hospital of New York-Presbyterian in New York. He told Reuters Health that the probable main reason for the huge increase was simple: CT is the most accurate test for appendicitis.

But is it overused? We don’t know, because we don’t know how the increase in scans correlates with patient outcomes. Because of the cost and the risk of radiation exposure, particularly for children, CT shouldn’t be used when patients’ symptoms very clearly point to appendicitis, Dr. Tsze said. Those patients should go straight to the operating room.

In less clearcut situations, CT can clearly help narrow down the diagnosis. Dr. Tsze said:

There are definitely situations where it’s indicated. But I don’t think it’s indicated in every case.

In some instances, he said, a thorough physical exam and a look at the patient’s medical history may be enough. Ultrasound can provide an alternative scan that’s free of radiation danger, but it’s not as accurate as CT. If an ultrasound were inconclusive, some patients would then get a CT scan anyway. Running two scans for a significant percentage of patients could get costly. And the patients, most of whom would be suffering considerable abdominal pain, wouldn’t appreciate the extra time it would take.

So we need some research on patient outcomes with and without CT. Right now, as Dr. Tsze put it, “With appendicitis, we just don’t know yet.”

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• The process is fundamentally flawed and should be scrapped;
• Even though it hasn’t actually approved any unsafe or ineffective devices;
• And the organization has no specific recommendations for a replacement process.

Can you blame the FDA for responding, in effect, “Um, thanks, guys; we’ll keep your suggestions in mind”?

In September 2009, the FDA asked the Institute of Medicine (IOM), a federally chartered but independent advisory group, for its thoughts about the FDA’s 510(k) clearance process for medical devices (including imaging machines). The 510(k) process allows certain products to be quickly cleared for sale and use if they are substantially equivalent to devices already on the market.

Last Friday, the IOM finally announced its report. It said the FDA had asked two questions: “Does the current 510(k) process protect patients optimally and promote innovation?” “If not, what legislative, regulatory, or administrative changes are recommended?”

To the first question, the IOM responded:

The IOM finds that the current 510(k) process is flawed based on its legislative foundation. Rather than continuing to modify the 35-year-old 510(k) process, the IOM concludes that the FDA’s finite resources would be better invested in developing an integrated premarket and postmarket regulatory framework.

In other words, the FDA should expend its “finite resources” on asking Congress, including a House of Representatives that is virulently suspicious of government regulation, for a new regulatory framework. Good luck with that.

And why should the FDA embark on this suicide mission? Are bad devices slipping through? Well, no. Using italics for emphasis, the IOM declared: “The committee is not suggesting that all, many, or even any medical devices cleared through the 510(k) process and currently on the market are unsafe or ineffective.”

As for the second question, the IOM listed a set of criteria for a new device-approval process: it should “be based on sound science,” “be clear, predictable, straightforward, and fair,” etc.

The IOM did not, however, propose an actual process. One IOM committee member, William W. Vodra, JD, former senior counsel at Arnold & Porter law firm, said proposing a new process was “well beyond our mandate,” according to HealthImaging.com.

Apparently, “what legislative, regulatory, or administrative changes are recommended?” does not constitute a mandate to recommend legislative, regulatory, or administrative changes.

In essence, the IOM suggested not-really-a-solution for not-quite-a-problem.

The FDA said it would take public comments about the IOM report. In the news release, you can almost hear Jeffrey Shuren, MD, director of the FDA’s Center for Devices and Radiological Health, speaking through clenched teeth:

We appreciate the IOM’s report on the 510(k) program, and agree that the public should continue to feel confident in the medical devices on the market today. … FDA believes that the 510(k) process should not be eliminated but we are open to additional proposals and approaches for continued improvement of our device review programs.

We suspect that the next time the FDA asks the IOM for advice will be never.

Related seminar: Radiology Review

The accused doctor, Mansukhlal Mavji Parmar, MB BCh BAO, helped trigger a widespread, and still ongoing, investigation of radiology practices in the Canadian province. In February, the province’s health services minister said that two radiologists had interpreted scans for as many as 3,400 patients without proper credentials or experience. Dr. Parmar was later identified as one of the two.

Sophia Hilleren underwent a hemicolectomy in May 2010 because doctors thought she had colon cancer. According to a lawsuit she filed in British Columbia Supreme Court on July 19, that diagnosis was based in part on Dr. Parmar’s misreading of her CT scan.

After the surgery, the suit says, doctors found that she did not have cancer. Another radiologist re-read Hilleren’s scans and found no abnormalities, according to the suit. In June of this year, the suit says, Hilleren received a letter from the Vancouver Coastal Health Authority saying that Dr. Parmar’s reading of her scan had been “misleading.”

The lawsuit names as defendants Dr. Parmar, the provincial health authority, and Dr. Parmar’s supervisor, whom it does not identify. The suit charges that:

Due to the negligence of the defendants, the plaintiff underwent unnecessary surgeries and … will be on medications for the rest of her life.

The suit says that Hilleren will likely suffer from diarrhea and malnutrition, as well as stress, anxiety, depression, nausea, and continual cramps. She is seeking damages for, among other things, pain and suffering, costs of future care and medication, and loss of income.

Hilleren’s lawyer told CTV News that he had not been able to find Dr. Parmar to serve him with the suit. CTV said Dr. Parmar was no longer practicing in British Columbia and could not be reached for comment.

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