JunkScience.com

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.