41. Man, if I were a new cancer patient desperate for information and stumbled across this endless argument, I'd come away more confused and desperate than ever.
Hope y'all can work it out,
Richard Day Gore

Posted at 9:08AM on Apr 26th 2007 by richard day gore

42. Besides richard day gore's inquiry, I've gotten a number of emails asking me to explain what is going on between me and Michelle (hchcec). I'll explain.

Dan Von Hoff was the most prominent member of the 2004 ASCO technology assessment panel on cell culture assays (three hundred or so papers published with the old technology clonogenic assay). For years, he went around the country telling people how the clonogenic assay was the next great thing. If one thought that he was only trying to sell people on the idea that clonogenic assays should be studied in a clinical trial setting, that is totally false. In one of his "mass mailings" he was offering free assays beseeching oncologists to help their patients. This was totally outside of the confines of a clinical trial.

Dan Von Hoff is one of the greatest organizers of clinical trials in the history of clinical oncology. Yet he virtually did not successfully organize and complete a single randomized trial to test "assay directed" versus "physician's choice" chemotherapy. Yet he sold his assay (not as a clinical trial, but as a service to patients) much more aggressively than anyone else has ever done with their own work.

Dan has been going around the country for years, speaking before all sorts of groups, speaking out against the use of cell culture assays in patient management. When his own pet technology was finally discredited, he basically said that if he couldn't do it, then no one else should be able to do it either. I'm glad no one in the private sector took him up on that. Many major attempts were made to get prospective, randomized trials off the ground in the cooperative groups, without success. One should not hold cancer patients hostage if they want to learn their individual tumor's specific biologic characteristics by obtaining and analyzing their fresh tumor tissues before receiving highly toxic chemotherapeutic agents into their body.

The genomic tests can help to find out if the cancer patient will likely have a recurrence if treated with surgery alone. If you aren't likely going to have a recurrence, you don't need chemotherapy. If the test finds them to be a "high risk" patient, then cell culture assays can help see what treatments will have the best opportunity of being successful. Many good surgeons are brow-beating their medical oncologists to look into these tests. It's not just good medicine, it's good economics.

Posted at 4:56PM on May 3rd 2007 by Gregory D. Pawelski

43. The genomic tests can help to find out if the cancer patient will likely have a recurrence if treated with surgery alone.

Absolutuely true! This is exciting and, in the case of breast cancer, the researchers have done excellent prospective trials which have been published in journals like the New England Journal of Medicine. Early and late stage (not yet intermediate) breast cancer treatment can often be guided by these tests. HOWEVER,

"then cell culture assays can help see what treatments will have the best opportunity of being successful."

THE ABOVE STATEMENT is False. There is absolutely no evidence for the above statement. Why? No studies have shown that that prove this is the case. None. Pawelski has yet to link you to any because there are none. This is not rocket science.

"Many good surgeons are brow-beating their medical oncologists to look into these tests. It's not just good medicine, it's good economics."

Brow-beating? Really? So surgeons who have no interest in evidence-based medicine are berating oncologists for not choosing an unproven test? Where are these surgeons?

It's not good medicine because it's unproven, just like essiac tea is unproven. If you want to pay for the test, go right ahead. Just understand that today, we have no evidence at all that it will be of benefit.

You may say, "but hchcec...what's wrong with trying it? Mr. Pawelski tells me that my oncologist is only interested in money he gets from the chemo he offers me. He doesn't really care about me, because Mr. Pawelski told me that I am doomed if I don't try the cell culture assay ." (I'm not making this up.)

If you want everything approved that is unproven, from cell assays to aura healing to applied kinesiology, then medicine is in trouble.

What you should do is read how scientists actually determine benefit and why there have yet to be any quality studies on cell assay testing despite what you hear as proven benefit on this blog.

This exchange is not between hchcec and Pawelski. It is between the purveyors of unproven treatment and legitimate research.

http://www.regence.com/trgmedpol/lab/lab06.html

Still waiting for those studies.......

Posted at 8:01PM on May 3rd 2007 by hchcec

44. Many studies have shown strong correlations between cell culture assay results, chemotherapy response, and patient survival in patients with cancer. Such correlations are the traditional criteria used to evaluate all laboratroy and radiographic tests by the FDA, other regulatory agencies, and the medical profession in general.

The very same people who control the clinical trials, whose entire careers are utterly dependent upon clinical trials, are the same people who say that assays may be good or better than physician's choice, but shouldn't be used unless in the confines of a clinical trial. They call that "the fox guarding the hen house."

The very same people who won't even look at the literature relating to predictive accuracy of cell culture tests and who state that the only relevant studies are those proving that the use of the tests improves outcomes are now very happy to support the use of the gene chip tests based solely on retrospective (not even on prospective) clinical correlations of predictive accuracy.

Prospective, randomized trials of one form of empiric chemotherapy versus another form of empiric chemotherapy have achieved virtually nothing, in that virtually nothing has ever been proven to be better than anything else. Even the NCI "state of the art" website says that it hasn't even been proven that any one treatment is any better than any other.

Hence 85% of academic oncologists give the pill Xeloda (which is simple for them and keeps their chemotherapy administration units open for use by patients participating in clinical trials) while 85% of private practice oncologists are giving infusional chemotherapy because they make their living by giving infusional chemotherapy. So by Michelle's (hchcec) logic, patients should never be treated with any of these empiric regimens, since none of them has been proven to be better than any other regimen.

It is accurate to state that it has not been proven that the use of cell culture assays improves the treatment of "populations" of patients in prospective, randomized trials. It is accurate to state when "individual" patients are treated with drugs active in the assays that they have vastly superior response and survival rates than when they are treated with drugs which are not active in the assays.

Posted at 10:02AM on May 4th 2007 by Gregory D. Pawelski

45. "It is accurate to state when "individual" patients are treated with drugs active in the assays that they have vastly superior response and survival rates than when they are treated with drugs which are not active in the assays."

Meaningless statement without evidence. If you feel persuaded by Pawelski, then try it. No one's stopping you. This blog allows him a forum to state these things without evidence. He wants to throw out the scientific method for anecdotes. There's a major problem with anecdotal evidence.

http://en.wikipedia.org/wiki/Anecdotal_evidence

However, Pawelski dilikes the scientific method so he will settle for anecdotes (this is all you get at the cell assay developer web sites). Of course, as stated numerous times, the cell assay developers rightly state that the scientific method is required to determine if there tests benefit you.

Only one man, on this blog and hundreds of others, will tell you that rigorous science is not needed.

Posted at 4:25PM on May 4th 2007 by hchcec

46. The NCI spent $15 million on a single-cell suspension "fresh" tumor assay with cell proliferation (cell growth) rather than cell death as an endpoint. When that didn't work, they folded their hand and specifically discouraged future applications of cell culture testing in their grant and contract guidelines, dating from the late 1980's. They never supported any drug development work based on primary cultures of three dimensional cell clusters with cell death endpoints, which very nicely recapitulate known disease specific activity endpoints (in other words, what works in the test tube, does work in the human body).

Then later, there were sophisticated programs to discover gene expression microarrays which predict for responsiveness to drug therapy. The NCI has a huge lab working on microarrays to look for patterns of mRNA and protein expression which are predictive of chemotherapy response. They spent 2 years trying to find patterns which correlated using the NCI's various established ovarian "cell lines."

They thought they had something, but when they started to apply them to "fresh" tumor specimens, none of the results in the "cell lines" was applicable to the "fresh" tumors. Everything they worked out in the "cell lines" was not worth anything and they had to start over from square one.

However, the limitations and non-applicability of the NCI efforts, failed to realize that the way to identify informative gene expression patterns is to have a "gold standard" and the (cell-death) cell culture assays are by far the most powerful, efficient, useful "gold standard" to have, adding the potential value of the assays to individualize cancer therapy.

It was routine for the NCI to append statements to grant and contract initiative announcements that applications relating to cell culture assays were strongly discouraged. After failing at his attempt with his own (old technology) clonogenic assay (which hasn't been used by private labs for over 15 years), Dan Von Hoff published a paper in 1990 in which he stated that clinical trials of cell culture assays would never be supported. And the cooperative groups have utterly refused to do the studies. Why should they? Five times as much work for much less (financial) reward.

There was an enormous amount of published, peer-reviewed research documenting the "accuracy" of cell culture assays. Scores of studies in thousands of patients. Based on both response and survival, but all of it excluded from the ASCO and insurance industry reviews. And it's the only evidence existing to validate any other medical test used as an aid in drug selection.

Disallow the introduction of published, peer-reviewed evidence documenting accuracy, while allowing the introduction of hearsay, unstated, undocumented, undescribed, unpublished, unpeer-reviewed non-evidence. While all the time, holding the cancer patient hostage. Again, I'm glad private lab researchers didn't allow that to happen.

I do commend all the good surgeons - the true advocates for the best cancer care of their patients - who do brow beat their medical oncologists to look at assay technology, who encourage surgeons to obtain and analyze fresh tissues for both cellular and genetic testing, who look at the results of these assays very carefully in the context of other known prognostic factors and choose agents based on their profiles. My "hats off" to you.

Posted at 7:27PM on May 4th 2007 by Gregory D. Pawelski

47. Accuracy does not figure among the useful measures for evaluating a clinical test. Pawelski wants his tests approved because they are merely "accurate." The developers of these tests know that this is not enough. Only one person wants a test approved because of accuracy. The fact that there is absolutely no data showing any underlying benefit to this test means nothing to this one individual. It does to the researchers and scientists, but not to the blogger.

Well, yes there was recently one other individual who took Pawelski to task big time on another blog.

"Mr. Pawelski definitely shows a bias, and unfortunately a general misunderstanding of the process of cancer treatment and the payment system surrounding it."

http://www.thehealthcareblog.com/the_health_care_blog/2006/09/physicianspharm.html

I believe this unnerved Mr. Pawelski so much that he not only responded shortly after the posting in November of 2006, but he felt the need to respond 3 more times (with no one else posting) with the latest one 3 days ago. The thread ended in November, but Mr. Pawelski couldn't let it go and felt compelled to add more.

Yet, as we always see, those "scores of studies in thousands of patients, based on both response and survival"......
don't exist.

Where are those studies? ONLY NOW are we seeing prospective studies being performed. Only now. Right now there is no proof that they are of benefit. Are you being held hostage?

Please. Stop with the scare tactics. Frightening cancer patients is just not cool especially when trying to sell them on unproven science.

Posted at 9:15AM on May 5th 2007 by hchcec

48. Ah!, to be continually maligned by some nut who is incapable of addressing the topic at hand and instead launches into a personal attack, usually by ascribing some neurosis that actually applies to them. In Salem, if you said you were not a witch it proved that you were a witch, and if you admitted to being a witch, well then, you were a witch. Like Quackwatch and others, there are certain number of "allrightnicks" who have appointed themselves the arbiters of truth. You just aren't allowed to play in their sandbox (Nah!, Nah!, Nah!, Nah! Nah!). Remember children like this? Obviously, there are a lot of seriously disturbed people in the world.

Posted at 9:51AM on May 6th 2007 by Gregory D. Pawelski

49. Another Pawelski red herring?

I have not attacked him. I have asked for the data. I'm a nut because I ask for proof of the unproven?

Before you tell patients that they are doomed without using your cell assay, show me the data and I will gladly change my tune.

Posted at 1:49PM on May 6th 2007 by hchcec

50. The FDA does adhere to guidelines (unlike some Journals that fail to adhere to guidelines on conflict of interest), and "accuracy" is the guideline for diagnostic laboratory tests (not efficacy). Pehaps her freshman year biology class should have told her that. Just because some unknown person - who doesn't identify themselves - says something is so, doesn't make it so. There is absolutely no credibility in someone who hides behind a symbol.

Perhaps Michelle (hchcec) - or whatever flavor of the month she/he is - should stop using scare tactics to try and intimidate others? I believe most people on this blog recognized the con in her writings. Michelle and hchcec have the very same vile in them. Afterall, preying on the fear of cancer patients can be a wise financial move for drug companies, according to some market analysts.

Michelle reminds me of the old days when white men would proclaim "keeping them bare foot and pregnant and in the kitchen." Seems to me like Michelle (hchcec) still likes to do the same with cancer patients. There are many ways to deal with cancer than the old empiric (one-size-fits-all) paradigm. There are more integrative medicine approaches many patients look into. Ridiculing them on this blog for doing that isn't cool (as she would say).

The last fifteen years has seen a renaissance of the concept of individualized (personalized) chemotherapy in oncology, stimulated by the development of the newer nonclonogenic cell culture assays. These methods are able to overcome the technical limitations associated with older assays, and allow for successful testing of most solid tumor specimens submitted. If Michelle's friend couldn't develop a workable assay of his own, don't try to stop other more knowledgeable scientists who did. And don't make hostages of cancer patients that want to use them.

Posted at 5:27PM on May 6th 2007 by Gregory D. Pawelski

51. Pawelski has yet to link the reader to any data that indicates any benefit from cell culture assays. Yet Pawelski, the internet's most notorious purveryor of this information, tells cancer patients on hundreds of blogs that they are doomed if they don't buy his assay tests.

At this point in time, cell culture assays don't get beyond Level 2 (below)and THAT is even questionable. That's why studies have finally begun.

A Hierarchical Model of Efficacy

Level 1: Techical efficacy

Level 2: Diagnostic accuracy efficacy

Level 3: Diagnostic thinking efficacy

Level 4: Therapeutic efficacy

Level 5: Patient outcome efficacy

Level 6: Societal efficacy

Mr. Pawelski's cell culture assays do not diagnose disease nor do they cure, mitigate, assist with treatment or prevent disease.

Why?

Because the studies haven't been completed yet.

Yet he wants health care providers (ultimately you and me, of course) to pay for these expensive tests for cancer patients with no data to back up therapeutic efficacy.

The anti-science proponents have not and will not win this one. Perhaps, in time, we will see benefit, but we haven't yet. PREDICTIVE ACCURACY is not the reason the FDA approves tests. I have gone over this here exhaustively and will do so again if challenged.

We await the data and studies are ongoing. For Pawelski, it doesn't matter. He believes chemotherapy, not given by his method, kills.

Again, where's the data?

I'll leave you with a common Pawelski internet quote:

"The way she was treated by "one-size-fits-all" cancer treatment should NEVER happen to ANOTHER human being." No wonder he so deeply feels and wants everyone to know that "preying on the fear of cancer patients can be a wise financial move for drug companies."

To a hammer, everything looks like a nail.

Posted at 8:34PM on May 6th 2007 by hchcec

52. Many of the comments posted by Michelle H. (hchcec) have used the fine art of selective quotation to make me appear to hold positions which I do not hold. I suggest readers who may be unnecessarily alarmed by these quotations to read my information in its entirety. A scientific communication should be judged on the quality of its content, not by alarmist Quakewatch attitudes.

Posted at 10:43PM on May 31st 2007 by Gregory D. Pawelski