Archive for September, 2008
Once you open a can of worms, the only way to recan them is to use a larger can.”
Zymurgy’s law of evolving systems dynamics (?Anon.)
In 1998 a study published in The Lancet implied that the MMR (measles, mumps, rubella) vaccine might be a cause of autism. Suggestions were made that Thiomerosol, a mercury-containing preservative used in some vaccines and other products since the 1930’s was the culprit. Previously, no harmful effects had been reported from Thiomerosol at doses used in vaccines, except for minor local reactions, but because of widespread pressure, Federal Agencies, The American Academy of Pediatrics and manufacturers finally agreed to remove Thiomerosal from vaccines in 1999.
Today, none of the vaccines used in the U.S. to protect preschool children against 11 infectious diseases contain this compound.
The Lancet study ultimately prompted research involving huge numbers of children, including a study of over 500,000 Danish children published in 2002 in the New England Journal of Medicine, which failed to confirm the original findings. Once the question was raised whether the MMR vaccine might trigger autism in some children, even mounting evidence to the contrary failed to allay public fears. The widespread media coverage stemming from the original British report continues to the present day. While the vaccination rate has dropped since the study, the incidence of autism continues to rise.
In February 2004, allegations of research misconduct were raised against the original paper, asserting that the dozen children selected in the study were not randomly chosen, but included children involved in a legal action claiming vaccine injury. This possible conflict of interest was not disclosed to the Editors of the Lancet.Ten of the 13 authors of the research paper issued a partial “retraction.”
In May, 2004 The National Academy of Sciences, Institute of medicine concluded that the available evidence did not support a causal link between between MMR vaccine and autism. Yet the autism MMR affair continues to be the subject of extensive media coverage, although a majority of independent research experts recently concluded there was no evidence of a causal link between vaccines and autism.
To this day, the lawsuits and class action suits against the Government continue, one such suit having been settled as recently as March, 2008. The New York Times reported this month (Sept., 2008) that new teams of researchers from Columbia University, Massachusetts General Hospital, and the CDC have again failed to show any connection between the MMR vaccine and autism, even though the Thiomerasol debate is no longer invoked.
One of the unintended consequences of the autism-vaccine controversy has been a decline in rate of immunizations for measles, mumps, and rubella (MMR) in some regions. Thanks to the debate, measles, a potentially deadly disease is making a big time comeback in the U.S.
Don’t speak through the screen door, you’ll strain your voice.
The idea of screening for disease sound great: discover the disease before symptoms appear, thus allowing an undiscovered condition-cancer, for example-to be treated early, thus saving lives. This philosophy has both a light and a dark side. Does the act of screening create more disease or reveal unexpected but benign conditions that lead to unnecessary and expensive, if not dangerous testing? See this previous blog. Then again do we always achieve what we hope, earlier diagnosis? Another unanswered question: Even if earlier diagnosis is made, when and how often, in the present state of knowledge, does it change the patient outlook for survival? This would seem to be especially pertinent in the diagnosis, for example in case of lung, esophageal, and pancreatic cancers. Yet no one argues the value of screening for cervical or skin cancer and a host of other conditions.
It turns out that “lead time bias” is one of the most pervasive problems in proving that screening does what it promises. This simply means we cannot routinely assume that the patient would have died earlier if screening had not been done. Looking at raw statistics and without long term followup of control patients who had not been screened we often draw the wrong conclusions: We have no consistently reliable way of knowing whether patients discovered at screening live longer than unscreened patients who would have died at the same time. In this case no additional life would have been gained through a screening test which did nothing except advance diagnosis. Indeed, there may be added cost in the form of anxiety as the patient must live with knowledge of the disease for longer.
An interesting example of this problem comes out of disputed research on screening for lung cancer, recently reported in the New York Times. Researchers at Weill Cornell Medical did spiral CT screening of 35,000 people with a history of smoking or occupational exposure. 484 were found to have lung cancer, and most of the tumors were removed. The researchers estimated that 92% with early stage tumors would be alive 10 years later, an amazing survival rate compared to the the 10% who survive that long after diagnosis discovered without screening. This sounds like a medical “slam-dunk case for screening,” but unfortunately there was no control group of patients who did not receive CT scanning; there was no proof that people who are screened die less frequently or live longer than people who are not screened.
To underscore this point, another study published in 2007 analyzing the results of CT screening in over 3,000 patients showed an increased number of small tumors found and the number of surgeries to remove them, but it did not reduce the total number of lung cancer deaths. A possible explanation is that many tumors would not have killed even if left alone, while the truly lethal tumors were not actually caught earlier. As of now, no major organization recommends widespread use of spiral CT screening for lung cancer, although individual patients may choose to have it.
The best hope of showing the effectiveness of lung cancer screening lies in a large federal trial of 50,000 current and former smokers comparing spiral CT screening with standard chest X-rays to see which”saves more lives.” This will take years to complete. The real issue remains, however, whether it will ever be easy to demonstrate that early diagnosis in a large number of conditions, prostate cancer, for example, really prolongs survival unless or until effective new treatments are developed.