For Immediate Release: 4 P.M. ET February 5, 2002
Contact: DMS Communications (603) 650-1492
Dartmouth Research Examines the Value of Cancer Screening
HANOVER, NH - As people consider the merits or drawbacks of cancer
screening, a Dartmouth Medical School study weighs in with some new
observations, based on a statistical analysis of past trials, that may help
put cancer screening in better perspective.
The conventional way deaths were classified may have caused
misclassifications that biased study results in favor of screening,
Dartmouth researchers demonstrated. They suggest an additional method of
tallying all deaths to help avoid the misinterpretations that can lead
investigators to overestimate or underestimate the value of cancer screening.
The findings are reported in the Feb. 6 issue of the Journal of the
National Cancer Institute by Dartmouth Medical School professors William C.
Black, MD, of radiology and of community and family medicine, and H.
Gilbert Welch, MD, of medicine and of community and family medicine, and
former medical resident David Haggstrom, MD.
Classifying the cause of death by specific disease is the most widely
accepted procedure in randomized trials that assess cancer screening.
However, two biases--sticky-diagnosis bias and slippery-linkage
bias--affect such classification and can alter the assessment of screening
value, the researchers found.
The validity of disease-specific mortality assumes that the cause of death
can be accurately determined. An alternative end point, all-cause
mortality, depends only on an accurate determination of deaths and when
they occur; therefore it is unaffected by misclassifications in the cause
People making decisions about screening want to have pertinent information
about what it means for them, explained Black, a member of a national
expert panel that assesses cancer evidence. He uses the shark analogy
popular among his peers. Instructions and aids to protect yourself from a
shark attack are meaningless if you don't go in the water.
Similarly, people have to understand how likely they are to be at risk for
certain cancers when they decide to be screened for them. "They should be
asking their physicians if this screening intervention is likely to
increase their life expectancy," Black says. And their physicians hope
screening studies take as much information as possible into account.
He and his colleagues compared the two mortality groups in 12 randomized
studies of cancer screening for which both disease-specific and all-cause
mortality could be determined. These trials involved screening for cancer
of the breast, colon or lung.
In five of the 12 trials, the two mortality end points suggested opposite
effects of screening. The researchers attributed these discrepancies to the
two forms of bias that affect cause of death classifications.
In one form, called sticky-diagnosis bias, deaths from other causes in the
screened group are falsely attributed to cancer because that cancer was
detected by screening. This type of misclassification influences the
disease-specific mortality results against screening.
In the second form, called slippery-linkage bias, deaths from the screening
process or subsequent treatment are falsely attributed to other causes. For
example, if an invasive evaluation causes a patient to have a fatal heart
attack, the death may be attributed to a heart attack rather than to the
disease being tested for. This misclassification tilts the disease-specific
mortality results in favor of screening.
Both forms of bias affected the randomized screening trials, according to
the analysis, but the Dartmouth researchers argue that slippery-linkage
bias had a larger effect. The concept of "slippery linkage" has been hinted
at before but never previously defined, notes Black, who says he and his
colleagues are among the first to investigate the impact of this bias.
Integrating both types of mortality classification can help avoid flaws in
screening assessment, according to the researchers. They conclude that
all-cause mortality should always be analyzed and reported along with
disease-specific mortality to ensure that major harms or benefits of
screening are not missed due to misclassification in the cause of death.
"All-cause mortality also puts the magnitude of expected benefit from
screening into an appropriate perspective for prospective decision making,"
For additional information, contact William Black at (603) 650-5846 or by
J Science, 3/03
Source: Finmeccanica, Inc.
Weizmann Institute of
Science report, 10/03
Integrative Cancer Therapies, 3/06
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