For 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 Scientist.) I 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 of 2.1%.

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).

Recommendations
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
www.cancerdecisions.com

References
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.