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Monday, April 02, 2012

Immunity to a Cancer in Progress

As Science Tsar of the World, I hereby assign Group A to study the Dendreon science and their vaccine for prostrate cancer. What I want Group A to study is the concept of a cancer vaccine, what they did to prove the mechanism of action, and how they conducted the statistical analysis of the clinical data.

Why is a hedge fund analyst more skeptical than the scientific community? Who is Marie Huber and what is her motivation?

If I, the Science Tsar of the World, want to know more about the Dendreon story I will need to know more about the psychology of the players. I know Dendreons vaccine story and it is bizzarre.
Each dose of Provenge is custom-made. A nurse or technician withdraws white blood cells from a man's arm in a three-to-four hour procedure called leukapheresis.
The cells are shipped to a Dendreon manufacturing facility, where for two days they are incubated with a "fusion protein:" One protein that stimulates the cells' growth and maturation and another called PAP, or prostatic acid phosphatase. PAP is an antigen that studs prostate cancer cells like antennae, pieces of it sticking out of the cells' surfaces.
Dendreon says the patients' white blood cells take up the antigen and within hours their surfaces bristle with fragments of the telltale molecule. The cells are then shipped back to the physician and infused into the patient. A full treatment includes three such procedures, two weeks apart.
Back inside the body, Dendreon claims the modified cells trigger the immune system to produce T cells that kill any cell sporting the PAP antigen — namely, prostate cancer cells.
In principle, that should eliminate the cancer, but Provenge does not shrink either the primary tumor or metastases.
I set the scientists down with the piles of data to sort through. That becomes one piece of the puzzle. I now set my sights on Marie Huber.
She argues that the main reason Provenge seemed to extend survival - a crucial factor in the FDA's decision - was that older men in the study who did not receive Provenge died months sooner than similar patients in other studies.
She raises the possibility the "placebo" they received was actually harmful and made Provenge, known scientifically as sipuleucel-T, look better by comparison.
My scientists are working on the placebo logic / clinical trial design. But Marie... who are you?
In documents JNCI requires authors to sign, she declared no financial conflicts of interest. Neither she nor her former firm nor anyone else she is connected to stands to benefit financially from her analysis, she said. Instead, she says she is motivated to help "vulnerable and desperate patients" - so much so that she gave up her job, salary and health insurance. 
Why did she give up her job for this? Because she cares? How did she get so much traction to her side of the story? An unemployed hedge fund analyst takes on a former $5 billion dollar biotech and people listen? It could have something to do with the unforgiving logical nature of science:

"There is no efficacy in the younger patients, the primary group where you would expect it," said Huber.Since the immune system weakens with age, an immune-based therapy should work better in younger men. Some experts agree."If it was really a vaccine, you'd think younger men would show more response, since they are more immunocompetent," said NCI's Rosenberg.

Then there is the logic of Dendreon:
"We have a lot of data that supports the idea that the product works the way it was designed to," said Dr. Mark Frohlich, Dendreon's chief medical officer. "We're seeing evidence of immune-system activation. The only question is whether the T cells are killing the tumor."
There is support but no verification. Marie Huber has just as much fire power scientifically. Applying Occams Razor, a principle urging one to select among competing hypotheses that which makes the fewest assumptions and thereby offers the simplest explanation of the effect, who should we believe? Do we even need to know who Marie is and what her motivations are? Scientifically, no. Cargo Cult Scientifically we would love to know more about her and why she is so into this issue. 

2 comments:

Anonymous said...

Here you can see her motivations, and what a Feynman fan she is....

http://theprovengetrials.org/files/why.pdf

She thinks the drug is (by occam's razor interpretation of the data) harmful and wants answers to very reasonable questions.

Why isn't saving lives a sufficient motivation?

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