Timid medical research

Cancer research is sometimes criticized for being timid. Drug companies run enormous trials looking for small improvements. Critics say they should run smaller trials and more of them.

Which side is correct depends on what’s out there waiting to be discovered, which of course we don’t know. We can only guess. Timid research is rational if you believe there are only marginal improvements that are likely to be discovered.

Sample size increases quickly as the size of the effect you’re trying to find decreases. To establish small differences in effect, you need very large trials.

If you think there are only small improvements on the status quo available to explore, you’ll explore each of the possibilities very carefully. On the other hand, if you think there’s a miracle drug in the pipeline waiting to be discovered, you’ll be willing to risk falsely rejecting small improvements along the way in order to get to the big improvement.

Suppose there are 500 drugs waiting to be tested. All of these are only 10% effective except for one that is 100% effective. You could quickly find the winner by giving each candidate to one patient. For every drug whose patient responded, repeat the process until only one drug is left. One strike and you’re out. You’re likely to find the winner in three rounds, treating fewer than 600 patients. But if all the drugs are 10% effective except one that’s 11% effective,  you’d need hundreds of trials with thousands of patients each.

The best research strategy depends on what you believe is out there to be found. People who know nothing about cancer often believe we could find a cure soon if we just spend a little more money on research. Experts are more sanguine, except when they’re asking for money.

Cancer moon shots

M. D. Anderson Cancer Center announced a $3 billion research program today aimed at six specific forms of cancer.

  • Acute myeloid leukemia and myelodysplastic syndrome (AML and MDS)
  • Chronic lymphocytic leukemia (CLL)
  • Lung cancer
  • Melanoma
  • Prostate cancer
  • Triple negative breast and ovarian cancer

These special areas of research are being called “moon shots” by analogy with John F. Kennedy’s challenge to put a man on the moon. This isn’t a new idea. In fact, a few months after the first moon landing, there was a full-page ad in the Washington Post that began “Mr. Nixon: You can cure cancer.” The thinking was the familiar refrain “If we can put a man on the moon, we can …” President Nixon and other politicians were excited about the idea and announced a “war on cancer.” Scientists, however, were more skeptical. Sol Spiegelman said at the time

An all-out effort at this time would be like trying to land a man on the moon without knowing Newton’s laws of gravity.

The new moon shots are not a national attempt to “cure cancer” in the abstract. They are six initiatives at one institution to focus research on specific kinds of cancer. And while we do not yet know the analog of Newton’s laws for cancer, we do know far more about the basic biology of cancer than we did in the 1970’s.

There are results that suggest that there is some unity beyond the diversity of cancer, that ultimately there are a few common biological pathways involved in all cancers. Maybe some day we will be able to treat cancer in general, but for now it looks like the road forward is specialization. Perhaps specialized research programs will uncover some of these common patters in all cancer.

Related links

Scientific opposition to the war on cancer

On December 9, 1969 the Washington Post ran a full-page ad that began

Mr. Nixon: You can cure cancer.

If America could put a man on the moon, she should be able to cure cancer. And why not? Well, because cancer research isn’t rocket science. (Actually, rocket science isn’t science; it’s engineering.) The science necessary to put a man on the moon was well known; the science necessary to cure cancer was not.

President Nixon was eager to comply with the request for massive funding for cancer research. However, many scientists were opposed to the idea. Cancer researcher Sol Spiegelman, for example, believed such a push was premature.

An all-out effort at this time would be like trying to land a man on the moon without knowing Newton’s laws of gravity.

James Watson warned

… we must reject the notion that we will be lucky. … Instead we will be witnessing a massive expansion of well-intentioned mediocrity.

How many scientists today would argue against a funding increase for their area of study?

Quotes taken from Emperor of all Maladies

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Breast cancer stem cells identified

From the article Proverbial new “Twist” in Breast Cancer Detection:

… scientists at Johns Hopkins … have shown that a protein made by a gene called “Twist” may be the proverbial red flag that can accurately distinguish stem cells that drive aggressive, metastatic breast cancer from other breast cancer cells.

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Bayesian clinical trials in one zip code

I recently ran across this quote from Mithat Gönen of Memorial Sloan-Kettering Cancer Center:

While there are certainly some at other centers, the bulk of applied Bayesian clinical trial design in this country is largely confined to a single zip code.

from “Bayesian clinical trials: no more excuses,” Clinical Trials 2009; 6; 203.

The zip code Gönen alludes to is 77030, the zip code of M. D. Anderson Cancer Center. I can’t say how much activity there is elsewhere, but certainly we design and conduct a lot of Bayesian clinical trials at MDACC.

Update: After over a decade working at MDACC, I left to start my own consulting business. If you’d like help with adaptive clinical trials please let me know.

More clinical trial posts


Seth Godin has a blog post this morning in which he says

Smoking a pack a day for twenty years is a great way to be sure you’ll die early.

The point of his post was not the dangers of smoking. His point was that “What we do in the long run, over time, drip by drip” matters more than what we do sporadically and I certainly agree. But I disagree with Seth’s comment on smoking.

Smoking certainly cuts your life short on average. But smoking is like playing Russian roulette: Most of the time, you’re OK. Most smokers do not get lung cancer. Smoking does not ensure that you’ll die early. And that may be why smokers ignore warnings. They can point to plenty of fellow smokers who were not killed by smoking. For example, if I wanted to smoke I could point out that my parents smoked and did not die of smoking-related causes. (Another smoker in my family, however, did die of lung cancer.)

People are most strongly motivated by consequences that are immediate and certain. Given a choice between the certain pleasure of enjoying a cigarette now versus a risk of lung cancer years from now, smokers choose the former.

It’s not very effective to tell someone, especially someone young, that if they smoke they will get lung cancer. For one thing, it’s not true: they probably will not get lung cancer. But they do increase their chances of cancer, and even more so their chances of emphysema, heart disease, etc. Still, those are probabilities of future events. Teenagers may be more motivated by the thought of their fingernails turning yellow or their clothes stinking.

Update: I want to be clear that I’m not defending smoking. I couldn’t wait to move out of the smoke-filled house I grew up in. Nor am I trying to down-play the health risks of smoking. The harmful effects are extraordinary well established. As Fletcher Knebel said back in 1961, smoking is the leading cause of statistics. Half a century later we’re still spending money on studies to confirm what we already know.

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Killing too much of a tumor

The traditional approach to cancer treatment has been to try to eradicate tumors. Eliminating a tumor is better than shrinking a tumor, so this approach makes sense. But if you try to eradicate the tumor and fail, you may leave the patient worse off. If you kill 90% of a tumor with some treatment but leave 10%, the remaining 10% is resistant to that treatment. You may have made the tumor more deadly by removing the weaker portions that were suppressing its growth. This explains why cancer treatments sometimes appear to be quite successful, dramatically reducing the size of tumors, without improving survival.

Sometimes one treatment will shrink a tumor as much as possible as a prelude to another treatment, such as shrinking a tumor with chemotherapy prior to surgery. But if only one treatment is being used, the situation may be like the old saying that you don’t want to wound the king. If you’re going try to kill the king, you’d better succeed.

In a recent interview on the Nature podcast, Robert Gatenby of Moffitt Cancer Center advocates an alternative approach, treating cancer as a chronic disease. Instead of killing as much of a tumor as possible, it may be better to kill as little of tumor as necessary to keep it under control. Patients would continue to take anti-cancer treatments for the rest of their lives, just as patients with heart disease or diabetes take medication indefinitely.

Related post: Repairing tumors

Down’s syndrome and cancer

The most recent Nature podcast (21 May 2009) has a news story about Down’s syndrome and cancer. Most types of cancer are much less common among people with Down’s syndrome. Since Down’s syndrome is caused by an extra copy of chromosome 21, researchers naturally want to know whether a gene on that chromosome is responsible for the reduced incidence of cancer. The podcast interviews researchers from two promising studies of candidate genes.

Here is the abstract of the medical paper discussed on the podcast.

Related post: Cartoon guide to cancer research