the first time, I have had an op-ed piece published in the Sunday New
York Times. (It can be viewed at: http://www.nytimes.com/2007/04/01/opinion/01moss.html.
You must log in to view it...at no charge.)
Basically, I was asked to contribute the op-ed as part of an entire page devoted
to cancer. The impetus seems to have been the unexpected recurrences of the
cancers of both Elizabeth Edwards and White House spokesperson Tony Snow. Unlike
so much of what you read about cancer in the mainstream media, the tone of
the page was rather critical of current directions. Other contributors included
Susan Love, MD, the well-known surgeon and author on breast cancer; Harold
Varmus, MD, Nobel laureate, former director of the National Institutes of Health
and current president of Memorial Sloan-Kettering Cancer Center; David G. Nathan,
the president emeritus of the Dana Farber Cancer Institute; and Shannon Brownlee,
a senior fellow at the New America Foundation. The newspaper later published
ten letters in response, most of them supportive.
I was honored that the Times asked me to join
this distinguished company and submit an editorial comment. (I think they had
seen my December op-ed on the
failure of the war on cancer in the British publication, New
chose to write about the issue of drug patentability and how that affects the
pace of discovery in cancer. This is a topic I first discussed in my book The
Cancer Industry (published as The Cancer Syndrome in
1980), and so I was glad to have an opportunity to revisit the subject and
to reach The New York Times' vast
and influential audience.
The New York Times is the largest metropolitan newspaper in the US, with a
Sunday circulation of 1.6 million. In addition, its website receives 11.6 million
visitors per month and ranks as the number one newspaper site. Needless to
say, the influence of America's "newspaper of record" goes
beyond what the sheer numbers say. In a sense, as many have commented and complained,
the Times has the ability to define the boundaries of a debate, at least in
the United States. Thus, for them to include my critical point of view on the
foundering war on cancer is an indication that times have changed and that
opinion-makers are willing to take a more searching look at where we are going
in the war on cancer.
I wrote that we could make faster progress against cancer by changing the way
drugs are developed. In the current system, if a promising compound can't
be patented, it is highly unlikely ever to make it to market – no matter
how well it performs in the laboratory. The development of new cancer drugs
is crippled as a result. I pointed out that the reason for this problem is
that bringing a new drug to market is extremely expensive. In 2001, the estimated
cost was $802 million; today, it is approximately $1 billion. Incidentally,
this statement generated a few critical emails. There is a school of thought
that the pharmaceutical industry has inflated the cost of developing new drugs
in order to justify sky-high prices. It wasn't my purpose to get in the
middle of that debate. I simply repeated the figures that I believe are most
widely accepted, those that were developed by the Tufts Center for the Study
of Drug Development.
Actually, their 2006 figure for the cost of developing a biotechnology product
is $1.2 billion (Kaitin 2006). But some critics contend that since the data
for the Tufts study is obtained directly from ten drug companies, it is tainted.
It was not my purpose to explore that question in a 600-word column devoted
to other issues. My essential point (with which few would disagree) was that
it is extremely expensive to bring a new drug to market and that such sums
could never be raised by advocates of any treatments that did not have strong
patents on novel compounds.
To ensure a healthy return on their staggering investments, I wrote, drug companies
seek to formulate new drugs in a way that guarantees these watertight patents.
In the meantime, cancer patients miss out on treatments that may be highly
effective and less expensive to boot. I then gave three examples of unconventional
(and relatively less toxic) treatments that I feel have been held back because
of their lack of economic appeal to Big Pharma.
In 2004, Johns Hopkins researchers discovered that an off-the-shelf compound
called 3-bromopyruvate could arrest the growth of liver cancer in rats. The
results were dramatic; moreover, the investigators estimated that the cost
to treat patients would be around 70 cents per day. Yet, three years later,
as the lead researcher wrote to me, no major drug company has shown interest
in developing this drug for human use.
Early this year, another readily available industrial chemical, dichloroacetate,
was found by researchers at the University of Alberta to shrink tumors in laboratory
animals by up to 75%. However, as a U of A news release explained, dichloroacetate
is not patentable, and the lead researcher is concerned that it may be difficult
to find funding from private investors to test the chemical. So the university
has been soliciting public donations to finance a clinical trial.
Finally, the hormone melatonin has repeatedly been shown to slow the growth
of various cancers when used in conjunction with conventional treatments. Paolo
Lissoni, an Italian oncologist, helped write more than 100 articles about this
hormone and conducted numerous clinical trials. I told the Times readers that
when I visited him at his hospital in Monza, Italy, in 2003, he was in deep
despair over the pharmaceutical industry's total lack of interest in
his treatment approach. He has published nothing on the topic since then (although
he has had a dozen publications on other topics).
My basic message was that potential anticancer drugs should be judged on their
scientific merit, not on their patentability. One solution might be for the
government to enlarge the Food and Drug Administration's "orphan
drug" program, which subsidizes the development of drugs for rare diseases.
The definition of an orphan drug could be expanded to include unpatentable
agents that are scorned as unprofitable by pharmaceutical companies. Basically,
I wrote, we need to foster a research and development environment in which
anticancer activity is the main criterion for new drug development. I don't
expect that to happen any time soon, but I am certainly glad that this point
of view has finally been presented to the Times' many influential readers.
Studies Question Accuracy of Many Colonoscopies
Colonoscopy is a reasonably effective way of finding and removing colon polyps,
the benign lesions from which most colon cancers develop. The US Preventive
Services Task Force recommends initiating colonoscopy screening at 50 years
of age for men and women at average risk for colorectal cancer. As a general
rule, people over age 50 should undergo colonoscopy once every five years.
If a doctor has previously found and removed a polyp, that schedule is moved
up to a three-year interval.
However, new concerns have now emerged over the accuracy of many colonoscopies.
The ability of colonoscopy to detect abnormalities ultimately relies on the
vigilance and experience of the operator. The rate of false negatives (i.e.,
missed polyps or colorectal cancers) after colonoscopy is influenced by a number
of factors. For example, who performs the colonoscopy and where it is carried
out can have a major influence on the reliability of the test. University of
Western Ontario researchers have found that colonoscopy is far more likely
to result in a false negative (i.e., cancer is more likely to be missed) when
an internist or family physician performs the test or when it is done in an
office setting. Colonoscopy is far more accurate when done by a gastroenterologist
in a hospital (Bressler 2007).
The senior author of this paper, Dr. Linda Rabeneck, has said: "There
is something different about the practice of colonoscopy in these settings
that gives rise to higher cancer miss rates, a worrisome finding" (Douglas
2007). Of 12,487 patients included in the study, 430 (or 3.4%) had new or missed
cancer within six months to three years of having a colonoscopy. Reducing this
interval to just two years yielded a 2.4% failure rate. An increase to five
years gave a figure of 4.6%. Thus, to be really safe, patients may need to
consider more frequent colonoscopies.
Compared to a colonoscopy performed in the hospital, having the procedure done
in a doctor's office yielded an odds ratio of new or missed colorectal
cancer of 3.07 in men and 1.95 in women. In plain language, this means that
you have a two to three times greater risk of a potentially fatal growth being
missed just by having your colonoscopy done in an office, rather than a hospital!
If you have it done by a family doctor, you nearly double the missed cancer
risk compared to undergoing a gastroenterologist-performed colonoscopy.
A recent study found that the colonoscopy failure rate was higher in the afternoon
than when the procedure was performed in the morning (Sanaka 2006). The reason
was partly because of the all-too-human factor of fatigue among endoscopists.
Some doctors apparently weary of doing one after another of these somewhat
tedious procedures. They tend to miss things when they get tired. This particular
study involved 2,087 colonoscopies, roughly half of which were performed in
the morning and half in the afternoon. The colonoscopy failure rate was 6.5%
in the afternoon compared to 4.1% in the morning, a significant difference
Ideally, performing all colonoscopies in the morning might reduce the number
of repeat procedures. However, this is not feasible given the huge number of
patients undergoing the procedure. The study's authors suggested that
one way to counteract the increased afternoon failure rate would be to ensure
that any patients who are known to be at higher risk for colon cancer were
tested in the morning rather than the afternoon.
A third study found that even among experienced gastroenterologists, the rate
of discovering tumors varies greatly. The time devoted to examining the mucous
lining of the colon – which is performed during the withdrawal of the
instrument – appears to be crucial to the successful detection of abnormalities.
Researchers monitored outcomes among 12 board-certified gastroenterologists.
Data from a total of over 2,000 colonoscopies were evaluated. Gastroenterologists
varied in how long they took to remove the instrument. Some took as little
as 3.1 minutes, while others took as much as 16.8 minutes – more than
five times longer.
The authors saw what they called a "striking, seemingly linear relationship" between
withdrawal time and the rates of polyps and cancers that were detected. The
overall rate of detection of polyps among operators who had relatively slow
withdrawal times was nearly four times as great as the rate among those who
had relatively fast withdrawal times. Slow workers were about three times more
likely to find an abnormality than fast workers. The author of this study (which
was published in The New England Journal of Medicine)
concluded that "a
minimum adequate amount of time for colonoscopic withdrawal can be equated
with quality of colonoscopy" (Barclay 2006).
The takeaway message is this: choose your endoscopist carefully. As a general
rule, pick a board-certified gastroenterologist. Make sure to have the procedure
done in a hospital, not a doctor's office, and insist on having the
procedure done in the morning, not in the afternoon.
As to getting your doctor to slow down and take his or her time in examining
each patient, it is hard to know how laypeople can exert much influence in
that direction. But the next time I go for a colonoscopy, I intend to tell
my gastroenterologist that I have read these three papers, particularly The
New England Journal of Medicine article showing that slower procedures yield
more accurate outcomes. I shall ask him politely to not rush things and to
do the most thorough job possible, even if it takes more time. Hopefully, Dr.
David Lieberman's heartfelt call (in an accompanying New
England Journal editorial) for endoscopists to take this message seriously will have gotten
through by then.
Ralph Moss, PhD
Barclay RL, Vicari JJ, Doughty AS, Johnanson JF, Greenlaw RL. Colonoscopic
withdrawal times and adenoma detection during screening colonoscopy.
N Engl J Med. 2006;355:2533-2541,2588-2589.
Bressler B, Paszat LF, Chen Z, Rothwell DM, Vinden C, Rabeneck L. Rates
of new or missed colorectal cancers after colonoscopy and their risk
factors: a population-based analysis. Gastroenterology. 2007;132:96-102.
Douglas D. Colon cancers missed more often in office setting. Reuters
Health. February 23, 2007. Available at: http://www.nlm.nih.gov/medlineplus/news/fullstory_45711.html
(June 2007: Link no longer available. Try http://uk.reuters.com/article/wtMostRead/idUKCOL36721220070224)
Kaitin KI, ed. Cost to develop new biotech products is estimated to
average $1.2 billion. Tufts Center for the
Study of Drug Development Impact Report. 2006;Nov/Dec;8(6).
Lieberman D. A call to action - measuring the quality of colonoscopy.
N Engl J Med. 2006 Dec 14;355(24):2588-2589.
Sanaka MR, Shah N, Mullen KD, Ferguson Dr, Thomas C, McCullough AJ.
Afternoon colonoscopies have higher failure rates than morning colonoscopies.
Am J Gastroenterol. 2006;101:2726-2730.
Wazana A. Physicians and the pharmaceutical industry: is a gift ever
just a gift? JAMA. 2000;283(3):373-80.