Diagnostics Turned Upside Down

New recommendations question old assumptions about diagnostic screening, and stir up a political hornet’s nest.

Physicians have for years debated and refined their recommendations regarding diagnostics and screening procedures. That’s inevitable, as the science behind diagnostics and the etiology of disease improves. But given the current climate of healthcare reform, concern about rising healthcare costs and charges of “death panels,” the debates have taken on a particularly strident tone.

Things bubbled over in November, when the U.S. Preventive Services Task Force revised its recommendations regarding mammography. Sponsored by the Agency for Healthcare Research and Quality, the task force is an independent panel of private-sector experts in prevention and primary care. It is charged with assessing the evidence for the effectiveness of a broad range of clinical preventive services, including screening, counseling and preventive medications; making recommendations about which preventive services should be incorporated routinely into primary medical care; and identifying a research agenda for clinical preventive care.

The task force suggested that routine mammograms begin at age 50 rather than 40; that women receive the test every two years rather than annually; and that education on breast self-examination be eliminated. The task force acknowledged that mammography does indeed detect cancers that otherwise would go undetected among women in their 40s. But more than 1,900 women have to be screened for a decade to save a single life, it said. The risks presented by false-positive test results, over-diagnosis, unnecessary biopsies and even surgical procedures – not to mention anxiety – outweigh the benefits of screening for women in that age group, the task force concluded.

Just days later, the American College of Obstetricians and Gynecologists revised its recommendations on Pap smears. Its self-proclaimed “evidence-based guidelines” now call for women to receive their first Pap smear test at age 21. ACOG’s prior recommendation had called for testing to begin three years after a woman’s first sexual intercourse or age 21, whichever came first. The college also now recommends that women aged 21 to 30 – at least those who are absent certain risk factors – should undergo the test every two years instead of annually, with the belief that screening at less frequent intervals not only decreases costs, but avoids unnecessary interventions.

Prostate, colorectal screening
November’s developments weren’t the first time in the recent past that controversy flared over changes in suggested screening and diagnostics protocols. In March 2009, for example, a study by the National Cancer Institute, published in the New England Journal of Medicine, found that while blood tests for prostate-specific antigen (PSA) identify cancer, they don’t save more men’s lives in the first 10 years of follow-up.

It’s true that U.S. death rates from prostate cancer have fallen about 4 percent per year since 1992, five years after the introduction of PSA testing, pointed out the magazine’s editor. “At the same time, practice guidelines cite the unproven benefit of PSA screening, as well as the known side effects, which largely reflect the high risks of overdiagnosis and overtreatment that PSA-based screening engenders.”

Prior to that, in October 2008, the U.S. Preventive Services Task Force recommended against routine screening for colorectal cancer in adults aged 76 to 85, and against any screening in adults older than 85. (That said, the task force supported screening for colorectal cancer using fecal occult blood testing, sigmoidoscopy, or colonoscopy in adults aged 50 to 75.)

The panel acknowledged that screening for colorectal cancer detects early-stage cancer and adenomatous polyps, and reduces cancer mortality in adults aged 50 to 75. But it also concluded that the benefits of detection and early intervention decline after age 75. The potential complications associated with flexible sigmoidoscopy and colonoscopy – such as perforation of the colon, major bleeding and cardiovascular events – outweigh the benefits for men over 75.
What’s more, the task force concluded that for adults older than age 85, “there is moderate certainty that the benefits of screening do not outweigh the harms.”

Cancer death rates down
Ironically, the questions about cancer screening were raised just as a report showed that the cancer death rate for men and women combined fell 1.6 percent per year during the period from 2001 to 2006. The findings came from the Annual Report to the Nation on the Status of Cancer, 1975-2006, Featuring Colorectal Cancer Trends and Impact of Interventions (Risk Factors, Screening, and Treatment) to Reduce Future Rates, published in December 2009 in the American Cancer Society journal Cancer. It was authored by researchers from the American Cancer Society, the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries.

According to the report, colorectal cancer death rates have been falling since 1984 in men and since 1975 in women, with a more marked decline in recent years. What’s more, the researchers concluded that with increased screening rates and control of certain risk factors (such as smoking and lack of physical activity), Americans could see a 36 percent decline in colorectal cancer death rates by 2020.

And ACOG, in its November guidelines regarding Pap smears, acknowledged that cervical cancer rates have fallen more than 50 percent in the past 30 years in the United States, due to the widespread use of the Pap test. “The majority of deaths from cervical cancer in the United States are among women who are screened infrequently or not at all,” said the association.

More harm than good?
Statistics such as these beg the question, “How is it possible that screening can be so effective, yet cause more harm than good?” Is it possible that, when it comes to screening for diseases such as cancer, less is more?

The question was raised in March 2009, when the results of the PSA study were released. “Serial PSA screening has at best a modest effect on prostate-cancer mortality during the first decade of follow-up,” concluded the New England Journal of Medicine. “This benefit comes at the cost of substantial overdiagnosis and overtreatment. It is important to remember that the key question is not whether PSA screening is effective, but whether it does more good than harm.”
In its breast-cancer recommendations, the U.S. Preventive Services Task Force pointed out that 80 percent to 90 percent of abnormal screening mammograms or clinical breast examinations are false-positives, which may lead to unnecessary follow-up procedures, such as a breast biopsy, not to mention anxiety.

But, as was suggested with prostate cancer, more problematic is the possibility of overtreating breast cancer, according to the task force. “Some experts view the over-diagnosis and treatment of ductal carcinoma in situ (DCIS) as a potential adverse consequence of mammography,” according to the authors. “[M]any women in the United States are treated aggressively with mastectomy or lumpectomy and radiation. Given the dramatic increase in the incidence of DCIS in the past two decades (750 percent) and autopsy series suggesting that there is a significant pool of DCIS among women who die of other causes, screening may be increasing the number of women undergoing treatment for lesions that might not pose a threat to their health.”

In its revised recommendations regarding Pap tests, the American College of Obstetricians and Gynecologists pointed out that although the rate of human papillomavirus (HPV) infection is high among sexually active adolescents, invasive cervical cancer is very rare in women under age 21. “The immune system clears the HPV infection within one to two years among most adolescent women,” wrote the authors. “Because the adolescent cervix is immature, there is a higher incidence of HPV-related precancerous lesions (called dysplasia). However, the large majority of cervical dysplasias in adolescents resolve on their own without treatment.”

Unnecessary interventions can be harmful, added Alan G. Waxman, M.D., University of New Mexico, who headed the document developed by ACOG’s Committee on Practice Bulletins – Gynecology. A significant increase in premature births has recently been documented among women who have been treated with excisional procedures for dysplasia, he said. “Adolescents have most of their childbearing years ahead of them, so it’s important to avoid unnecessary procedures that negatively affect the cervix,” said Waxman in a statement. “Screening for cervical cancer in adolescents only serves to increase their anxiety and has led to overuse of follow-up procedures for something that usually resolves on its own.”

A new way of looking at cancer
That some cancers or precancerous lesions are best left untreated may be a radical concept for Americans to accept, but it could affect the future of diagnostic screening in this country.

“What has been learned is that while some cancers are aggressive, many are indolent, and may lie dormant or even regress in some patients,” says John Blackwood, vice president and general manager of Beckman Coulter’s immunoassay business center. “That’s not intuitively obvious to patients. Historically, for any cancer, the idea has always been, ‘Cut it out.’

“But what we are learning – and this is very true especially in the molecular diagnostics space – is that cancer is a heterogeneous disease. Not all cancers are the same. So the question goes from, ‘Does the patient have cancer?’ to, ‘If they do, what is the likelihood that that specific cancer will spread or cause significant disease?’ That’s where cancer diagnostics is going today and in the future.”

But until technology can yield definitive answers about the potential end results of a disease, some tough decisions will have to be made. And the patient himself or herself will have to be involved.

“Patients have to educate themselves in some fairly complex topics, because some of this comes down to – with imperfect knowledge – best estimates and probability,” says Blackwood. “Patients will ultimately have to decide quite a bit by themselves.” Some may simply refuse to accept a doctor’s recommendation of watchful waiting. “Everyone has to stay abreast of the current information, and the patient is the key stakeholder.”

The politization of diagnostics
Coming as they did while Congress was engaged in a nasty debate about healthcare reform, perhaps it was inevitable that the recommendations of the U.S. Preventive Services Task Force and ACOG would raise the ire of some, who accused the government, in particular, of raising doubts about diagnostics in an effort to cut costs.

As if anticipating an attack by lawmakers embroiled in the healthcare reform battle, the American Clinical Laboratory Association last September released a report making the case that screening and diagnostic laboratory tests for such conditions as diabetes, cervical cancer, drug-resistant infections and metastatic colon cancer are both clinically and economically sound.

“Despite the extensive role of laboratory medicine in informing medical decision-making, in 2007, spending on Part B laboratory services was $6.8 billion, or just 1.6 percent of total Medicare expenditures, and 2.3 percent of national healthcare spending,” pointed out the association. What’s more, by detecting disease at the earliest stages, even before symptoms occur, laboratory medicine can help patients and their doctors chart an effective disease management strategy.

‘Damaging new guidelines’
Another organization – the Access to Medical Imaging Coalition – issued this statement immediately following the release of the task force’s mammography recommendations: “Damaging new guidelines released today by the U.S. Preventive Services Task Force opens the door for private insurers and Medicare to deny important mammography services to women and should be rejected outright.” The coalition represents a number of professional medical societies as well as imaging manufacturers.

Soon thereafter, a panel of breast imaging experts expressed outrage at the task force’s recommendations at the 2009 Radiological Society of North America conference. “There were no radiologists, surgeons, oncologists – no one specializing in breast cancer,” said Mary Mahoney, M.D., director of breast imaging at the University of Cincinnati Medical Center and chair of the RSNA Public Information Committee.

“It’s hard for me to believe the task force thought about the implications of these guidelines,” added Daniel Kopans, M.D., a senior radiologist in the Breast Imaging Division at Massachusetts General Hospital and a professor of radiology at Harvard Medical School, Boston. “If they had used the actual available data and not computer modeling, by their own estimates, mammography screening would be appropriate for women in their 40s.”

On the other hand, the American College of Physicians attacked those who, it said, were politicizing the issue. “The USPSTF is a highly regarded, credible and independent group of experts that performs this role, on a purely advisory basis, to the Department of Health and Human Services, as it relates to interventions to prevent or detect diseases,” said Joseph W. Stubbs, M.D., FACP, president of the American College of Physicians, in a statement. “As is often the case with evidence-based reviews, the USPSTF’s recommendations will not always be consistent with the guidelines established by other experts in the field, by professional medical societies, and by patient advocacy groups.

“Such differences of opinion, expressed in a constructive and transparent manner so that patients and their clinicians can make their own best judgment, are important and welcome. It is not constructive to make ill-founded attacks on the integrity, credibility, motivations, and expertise of the clinicians and scientists on the USPSTF.”

Concluded Stubbs, “ACP urges Congress, the administration, and patient and physician advocacy groups to respect and support the importance of protecting evidence-based research by respected scientists and clinicians from being used to score political points that do not serve the public’s interest.”

Naivete a factor
“In my opinion, the task force was, I think, a little naïve thinking that if they just issued an evidence-based recommendation, looking at randomized controlled data, people would buy into it, because it is the rational thing to do,” Richard Bankowitz, M.D., chief medical officer, Premier healthcare alliance, told the Journal of Healthcare Contracting. “I think they underestimated the political and social and economic fallout. It was badly timed, because of the healthcare reform debate, when people are scared about access to care.

“Patients want to feel empowered,” continued Bankowitz. “They feel that doing something is better than nothing. So there are other interests involved besides just scientific interests.”

That said, “women will undergo needless biopsies or even surgery” because of false positives, said Bankowitz. “Every time you do an invasive procedure, there are risks – of infections or scars. It’s small, but real. So you really do need to examine the tradeoffs.

“And when we’re talking about screening exams for cancer, the real question is, ‘Does [screening] actually impact the survival of the patient. There’s no doubt that in some of these cases, you can find things earlier. The question becomes, ‘Do you just increase the time between diagnosis and death, because you’ve diagnosed [disease] earlier, or do you actually extend life?’ That’s what the task force was trying to answer.”

Scrutiny is OK
The hubbub surrounding the new recommendations didn’t surprise Tom Schwieterman, M.D., director of research and development for Midmark, the Versailles, Ohio-based manufacturer of medical diagnostics and furniture. After all, not only do the recommendations raise suspicions in some people’s minds about the government’s motives, they also question the status quo of healthcare delivery. And sometimes physicians don’t like that.

“I am the son of a doctor, and a doctor myself, formerly practicing in the trenches,” he says. “But I also have a software engineering degree, [which challenges me to] look at entire systems and determine how best to analyze problems. When I brought those two perspectives to bear on healthcare, it was phenomenal to me how much legacy thinking – ‘It’s just done this way’ – is built into the system.”

Comparative effectiveness and evidence-based studies demand that providers stop and ask themselves, “Is the way we’ve done things for 50 years the way we should keep doing them?” says Schwieterman. “People love the intimacy of the doctor/patient relationship, the personalization of care. It’s hard to go to 30,000 feet and say, ‘Maybe we shouldn’t do rectal exams after age 70.’

“To me, the elephant in the room is the difference between one-on-one patient management, and population-based management,” says Schwieterman. “I understand that greater than 80 percent of [breast] biopsies turn out to be negative. On the flip side, I understand how every woman wants to be screened at every interval they and their doctor feel is appropriate.”

Evidence-based medicine and practice guidelines force doctors to think differently about the way they manage their patients, says Schwieterman. And that’s a good thing. “But I hope that the guidelines based on evidence-based medicine and comparative-effectiveness studies are simply that – guidelines. Always, from my mind, [a course of treatment] should end up being the decision of the doctor and the patient. Medicine is both art and science. Trying to put the whole equation on the science (that is, evidence-based guidelines) is a mistake.”

As the science gets better, the art should get better too, adds Blackwood. “It’s about optimizing healthcare delivery,” he says. “That means making sure the right people get the right test and the right treatment at the right time.

“It’s trying to understand a specific person’s cancer and their situation and risk profile, and the genetic makeup of their cancer,” he says. “With that knowledge, decision-making can change. That’s what I mean about optimizing delivery. That’s true personalized medicine.”

The quandary for contracting executives
While the industry may be approaching the age of personalized care, it’s not there yet. Molecular diagnostics is still relatively new, and certainly hasn’t reached point-of-care status. Given the status of medicine today, and the healthcare debate raging in Congress and across the country, how does the contracting executive evaluate and acquire diagnostic supplies and equipment? Deliberately.

Contracting executives responsible for ambulatory care sites should know that most evidence-based guidelines call for more, not less, diagnostic testing, says Schwieterman. Spirometry, for example, is probably underutilized in the ambulatory environment today, he says. Sleep apnea is still underdiagnosed. And more patients are pre-diabetic than are being effectively treated and managed. “So it’s possible that in certain categories, doctors will practice good evidence-based medicine by using more devices than they do today,” he says.

Even if third-party payers back off of reimbursing for certain tests, that doesn’t mean patients will stop demanding them, adds Tim Dumas, a Raleigh, N.C.-based clinical laboratory scientist and lab consultant. “If people have to pay out-of-pocket, they will.” Many people know of others for whom early detection of a cancer or other disease was critical for that person’s well-being. So if a person is told that a $50 PSA test can clear up the possibility of cancer, “I’ll plunk down $50 to get my prostate checked,” he says.

And the concept of screening and disease prevention still holds a lot of merit, adds Tim Hanahan, director of sales, physician office, bioMérieux. “What you look for in medicine is change,” he says. “Did [a test result] go up or down? That’s simplifying it, but that’s what you’re looking at.” Regular screening – whether it be PSAs or mammograms – gives doctors that long-term view and helps them devise a treatment plan.

Harbinger?
The fierce opposition to the task force’s recommendations on mammography – particularly the charges that it could lead to something akin to death panels – may be a harbinger of things to come, said Bankowitz. “It’s pretty sobering. If we have this kind of emotional response, where we have two very good, randomized controlled trials (which are the gold standard), what is going to happen when we have lesser-grade evidence from clinical effectiveness studies?

“But I remain optimistic. Hopefully we can understand that not every dollar spent on healthcare is spent on something that’s needed. There is waste involved.”
The challenge, of course, is to find it.

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