Category: Medicine, Drugs & Devices

By Steven Milloy
June 06, 2003, FoxNews.com

The media and stock market are again atwitter with news of another supposed cancer breakthrough. Avastin (search), a drug developed by biotech giant Genentech (search), reportedly extended the median survival time of terminally ill colon cancer patients in a clinical trial by 4.7 months.

The news was formally released at last weekend’s meeting of the American Society of Clinical Oncology (search) (ASCO). The price of Genentech stock has risen by about 65 percent since mid-May when the news began leaking.

One biotech analyst said annual sales of Avastin could reach $2 billion as almost 150,000 Americans are diagnosed with colon cancer and 57,000 die from it every year.

And based on headlines such as the Los Angeles Times’ “New Drug Combinations Effective on Colon Cancer,” the Avastin claims sound exciting.

But since cancer breakthrough news is usually more smoke than fire, a closer look is warranted — especially since Avastin wasn’t effective in an earlier breast cancer trial.

It’s too bad a closer look isn’t possible.

Detailed information in standard study form about the Avastin trial isn’t available — not from the Duke University Medical Center, whose news release claimed Avastin’s efficacy was “proved,” and not from Genentech, whose market value increased by $15 billion on the news.

Both were happy to be contacted about the study, no doubt expecting more giddy and gullible reporting. But no detailed write-up was available. The Genentech spokesperson couldn’t even say when a study might be published.

Only a brief study summary or abstract was available, one omitting or glossing over key information and basic questions about the trial.

The trial involved 925 patients. About 800 patients were either given Avastin plus a standard chemotherapy or the chemotherapy alone. Another 100 patients were given Avastin in combination with another standard chemotherapy.

The abstract only contains results for the 800-patient treatment group. What happened in the 100-patient treatment group? Was Avastin effective there, too? If so, why not report it?

Avastin reportedly increased survival time by almost five months. But that claim relies on the major assumption that at the beginning of the trial, patients in the Avastin group, on average, had a similar expected survival time as patients in the chemotherapy-alone group.

Individual study subjects, though, likely had different types of colon cancer and were at different stages in the progression of their colon cancers. If the Avastin treatment group was, on average, at an earlier stage of colon cancer or had less aggressive colon cancers and metastases, it wouldn’t be surprising that their survival time is longer.

The researchers apparently hoped that random assignment of subjects to the Avastin and non-Avastin treatment groups would equalize the expected survival times of the treatment groups at the trial’s beginning.

This may have worked, but we just don’t know. Without some information about, and validation of the assumption, the touted results are based on a huge leap of faith.

The trial was multicenter in nature, meaning that patients were treated at several locations around the country. Such decentralization may give rise to a phenomenon known as “multicenter bias,” where the results from one study center may be skewed because of some systematic difference in the conduct of its part of the trial.

We can’t tell whether multicenter bias occurred in the Avastin trial because the data weren’t reported by a study center.

I asked lead researcher Herbert Hurwitz whether the study was peer-reviewed. He said it was reviewed by a committee of ASCO — the group putting on the medical conference where the results were announced.

But how could the committee perform a credible review with only the superficial abstract? No reputable journal would publish results without more. We must also wonder if the committee was truly objective since ASCO may have been eager to have such headline-grabbing claims announced at its annual meeting.

One final reason for requiring something more than “science by press conference” is that the biological mechanism by which Avastin is supposed to work, the blocking of blood vessels in tumors (anti-angiogenesis), hasn’t really panned out yet.

Based on studies in laboratory animals, anti-angiogenesis drugs were first touted several years ago in a front-page New York Times article that caused dramatic speculation in biotech stocks. But subsequent studies in humans have disappointed and biotech stock prices collapsed.

Given the huckster-ish history of anti-angiogenesis drug claims, Genentech and Hurwitz should realize more than a vague abstract is needed to show Avastin works. A detailed study would be a start, followed by more clinical trials.

Proven effective or not, terminally-ill cancer patients shouldn’t be denied Avastin or any other potentially helpful drug they are willing to try on their own dime. But cancer treatments shouldn’t be hailed until they are actually proven to work.

Steven Milloy is the publisher of JunkScience.com, an adjunct scholar at the Cato Institute and the author of Junk Science Judo: Self-defense Against Health Scares and Scams (Cato Institute, 2001).

By Steven Milloy
August 2, 2002, FoxNews.com

Women have been scared during the last several weeks with new studies about alleged health risks from hormone replacement therapy (HRT). This scare contrasts starkly with the preceding decades of HRT being touted as the fountain of youth.

What should women and their physicians believe? Past hype? Recent hysteria?

Neither.

HRT, originally estrogen alone and later estrogen in combination with progestin, was approved in 1942 by the Food and Drug Administration to relieve the short-term symptoms of menopause such as night sweats and hot flashes.

Two decades later, though, HRT began being touted as a wonder drug for many long-term health concerns of women, not just menopausal symptoms. HRT mania was kicked off by Dr. Robert Wilson’s 1966 book Feminine Forever. Unknown at the time, the book was financed by Wyeth-Ayerst, the leading manufacturer of HRT.

Studies appeared in the scientific literature touting HRT as reducing bone loss, the risk of heart disease and the risk of some cancers.

But anyone who paid attention to the data rather than the hype would have known that these studies didn’t at all demonstrate HRT to be a panacea.

The studies invariably reported weak statistical correlations between HRT use and long-term health benefits — and that’s with the study populations biased in favor of the reported results.

The study populations taking HRT tended to be comprised of thinner, wealthier and better-educated women under physician care. It is not surprising that these women were healthier than the women in the “control” groups.

Myths about the long-term benefits of HRT nevertheless took hold. Premarin, the most popular HRT made by Wyeth-Ayerst, was recently used by about 12 million women in the U.S. at a cost of about $180 per year.

Or it used to be so widely used.

Early July saw a rash of epidemiologic (human population) studies allegedly linking HRT with a variety of health risks. “NIH says type of hormone therapy hurts instead of helping women’s hearts and causes breast cancer,” headlined The Associated Press.

The New York Times quoted a female physician stating, “I may have taken my last pill this morning.”

But the most notable of the recent studies reported that, among 8,506 estrogen-plus-progestin HRT users, there was only a 29 percent increase in heart disease occurrence. The result was barely statistically significant, meaning there’s a worrisome possibility it was a fluke.

The study reported only a 26 percent increase in breast cancer occurrence. That result wasn’t statistically significant.

The study’s reported results for other health concerns were of similar magnitude and statistical significance — that is to say, weak.

But you don’t have to accept my characterization of such results.

As the National Cancer Institute points out: “In epidemiologic research, [risks of less than 100 percent] are considered small and usually difficult to interpret. Such increases may be due to chance, statistical bias or effects of confounding factors that are sometimes not evident.”

In other words, these results should be treated as preliminary — particularly until they are replicated many times by independent researchers. That’s just Scientific Method 101.

Moreover, these women were only studied for five years and previous studies report contradictory results. It seems the panic is premature.

David Sturdee, former chairman of the British Menopause Society, once said: “A lot of nonsense is talked by those who say HRT is the best thing since sliced bread. Equally, I am incensed by the idea that all HRT is unsafe. Some women feel undue pressure either to take HRT or not to.”

What kind of pressure? Wyeth-Ayerst pressed women to take HRT. Now others are trying to scare women about HRT.

Pharmaceutical manufacturer Eli Lilly promoted HRT fears in the fall of 1997 as it awaited approval of it rival drug, raloxifene (Evista).

Lilly placed full-page advertisements in women’s magazines that ominously read, “Many women have serious worries about a possible link between estrogen replacements and cancer.” The implication was that Evista didn’t increase cancer risk.

Lilly even touted preliminary studies reporting a slight decrease in cancer risk among Evista users.

This marketing-by-scaremongering was eventually brought to a halt by a federal judge who issued an injunction against Lilly touting research that did not prove Evista prevented breast cancer.

No one disputes the short-term benefits of HRT for menopausal symptoms. Moreover, there is no substitute for it. But HRT’s supposed long-term benefits and risks so far seem to have more to do with unscrupulous marketing than science.

by Steve Milloy
October 6, 1999, JunkScience.com

I hate to admit it. But I’m at that age where prostate cancer enters the mind – especially since my father just completed a course of radiation treatment for his prostate cancer.

Prostate cancer is the most commonly diagnosed cancer among U.S. men. And at about 40,000 annual deaths, it is the second deadliest behind lung cancer. Prostate cancer is the male version of breast cancer. It’s not preventable and early detection is the key to survival. But – and it’s a big “but” – controversy has arisen over early detection.

The prostate is a chestnut-sized gland in the make pelvic area. It plays a role in generating seminal fluid that helps transport sperm. For unknown reasons, the gland can enlarge and cancer can develop. Some cancers are fatal. Some aren’t. While most prostate cancer occurs in older men, it can strike younger men as well. Half of prostate cancer deaths occur in men over the age of 75. Fewer than 5 percent of deaths occur in men who were under 60 at diagnosis.

Until about 10 years ago, prostate cancer was detected by a technique euphemistically named the “digital rectal exam.” But rectal exams often don’t catch cancers until after they have spread – at which point it may be too late to cure. Then came the PSA test, a blood test that measures the level of prostate specific antigen. PSA is usually elevated in men with prostate cancer, but can also be elevated, usually to a lesser degree, in men with benign prostate growth.

The PSA test did wonders for diagnosing prostate cancer. The number of men diagnosed with prostate cancer in 1985 was about 85,000. By 1996, the number diagnosed had jumped to almost 320,000. Sounds great right? It was early detection we needed and early detection we got. But maybe not.

Though more prostate cancer is being detected now than 10 years ago, it’s not that more men are getting prostate cancer. It’s just that more prostate cancer is being detected by the PSA test. Not all prostate cancer is fatal. In older men, prostate cancer can be slow-growing so that they will die with it, not of it.

An elevated PSA test does not automatically mean that cancer is present. Like the digital rectal exam, a PSA a test can erroneously indicate prostate cancer and erroneously fail to detect a prostate cancer. So while the screening may lead to life-extending diagnosis and treatment, it can also lead to treatment of cancers that don’t need to be treated – or even cancer that a man may choose not to treat. Treatment may cause urinary incontinence or impotence.

Several years ago, controversy arose over whether routine screening for prostate cancer.

The American College of Physicians says that routine prostate-cancer screening “is not for everyone” and that it is “a complex decision that patients should make after talking to their physician, understanding the risks and benefits, and coming to an informed, individualized decision. A urologist said in the British Medical Journal that [PSA testing] “merely Promotes Stress and Anxiety.”

But the American Urology Association and the American Cancer Society recommend that, annual PSA testing be done annually beginning at age 50, and earlier for men at high risk. The developer of the PSA test, Dr. William J. Catalona, professor and chief of urology and the Washington University School of Medicine says “PSA testing has exhibited all the features of an effective cancer-screening tool.” But note that he didn’t say it saves lives. Why? Because there’s no proof it has.

The National Cancer Institute criticized the American Cancer Society in 1992 for acting hastily in recommending routine screening without waiting for proof that mass screening reduces mortality. The ACS’ chief medial officer offered the weak defense that “Physicians and the public are demanding to be told what to do.”

Until recently, there have been no controlled studies on whether PSA testing reduces the prostate cancer death rate. The first clinical trial to examine the value of PSA screening, released in May 1998, reported that PSA screening led to a 69 percent reduction in prostate cancer death rates. While sounding impressive, researchers immediately raised questions about potential bias in the study data. Men who agreed to be screened may have been healther than those who did not agree.

Now, a new study in the Oct. 6 Journal of the National Cancer Institute reports that PSA levels may mean something entirely different than originally thought.

So what do you do? How do you choose between the American College of Physicians and the American Urological Association? Does it help to know that the ACP recommendation is “evidenced-based”? The ACP examined and reviewed more than 40 studies to determine the potential benefits of screening, the complication rate of treatment, and the balance of benefits harms and costs. In contrast, the AUA recommendation represents a consensus of expert opinion. Evidence vs. expert opinion? Wouldn’t you think expert opinion would be based on evidence? Confused? As my father-in-law, a prominent south Florida urologist said, “Urologists have the most experience, but they also have the most to gain from routine screening.”

What do urologists have to gain? You decide. PSA testing costs about $100. An elevated PSA could lead to more testing or a biopsy costing around $1,500. The prostate testing market is worth about $200 million to $300 million annually. Until recently, the developer of – and the leading cheerleader for – the PSA test, William Catalona, was receiving $1 million per year “to study the effectiveness of the PSA test,” largely from Hybritech, a pharmaceutical firm that manufactures the PSA test.

Recently, Catalona criticized the American College of Physicians for recommending against routine screening in favor of physicians and patients discussing the potential benefits and known harms of screening diagnosis and treatment and making individual decisions. Catalona wrote “This sounds reasonable but is impractical because busy doctors lack time for long discussions.”

Prostate cancer can be life-threatening. If your physician doesn’t have the time to discuss your options, get a new doctor. And whatever you do, don’t fall for the unproven and undeciphered PSA test.

Steve Milloy is the publisher of JunkScience.com.