1. You may want to look at virtualtrials.com about a Chemosensitivity assay for any malignant brain tumors. Chemosensitivity testing might help you find the best option. It's an idea worth looking into.

http://virtualtrials.com/trialdetails.cfm?id=96100226

Posted at 1:26AM on Sep 24th 2006 by Gregory D. Pawelski

2. One may get the impression that this a clinical trial because of the name of the URL.

It, in fact, is not a trial, as the trial author indicates. The cost to you is also not clearly indicated.

There is no evidence that you will benefit from what you are paying for. Of course, no one should stop you from attempting to gather information from this assay test, but one should know that:

1. There is no evidence that this method benefits survival
2. Studies have just begun on chemosensitivity testing and clinical benefit.

Posted at 12:44PM on Sep 24th 2006 by Michelle

3. There have been over 40 publications in peer-reviewed medical literature showing correlations between cell-death assay test results and the results of clinical chemotherapy in thousands of patients. In every single study, patients treated with drugs active in the assays had a higher response rate than the entire group of patients as a whole. In every single study, patients treated with drugs inactive in the assays had lower response rates than the entire group of patients. In every single study, patients treated with active drugs were much more likely to respond than patients treated with inactive drugs, with assay-active drugs being 7 to 9 times more likely to work than assay-inactive drugs. A large number of peer-review publications also reported that patients treated with assay-tested 'active' drugs enjoyed significantly longer survival of cancer than patients with assay-tested 'negative' drugs.

By investing a little time on the phone speaking with the lab directors, you should have enough knowledge to present the concept to your own physician. At that point, the best thing is to ask the physician, as a courtesy to the patient, to speak on the phone with the director of the laboratory in which you are interested, so that everyone (patient, physician, and laboratory director) understand what is being considered, what is the rationale, and what are the data which support what is being considered.

These labs will provide you and your physician with in depth information and research on the testing they provide. They follow careful quality controlled methods that adhere to College of American Pathologists and Clinical Laboratory Improvement Amendments (CLIA) guidelines.

The norm is to use chemotherapy that is randomized or standardized in relation to the target organs or tumor origins. Because tumors originate from a wide variety of genetic backgrounds, most cancer cases have become unsuited to the use of such standardized chemotherapy. Since no single drug or combination has been found to be optimal for cancers of all origins, developing a good and clinically practical drug selection system is no less important than the discovery of new drugs or how to put them into the body.

Upgrading clinical therapy by using drug sensitivity assays can improve the conventional situation by allowing more drugs to be considered. There "are" better ways of treating cancer patients than what has always been the standard. Cutting-edge techniques can often provide superior results over tried-and-true methods that have been around for many years.

Posted at 5:04PM on Sep 24th 2006 by Gregory D. Pawelski

4. In examining just one malignancy, I will quote from the the designer of the ew ovarian trial:

"Fruehauf and Alberts state that "the Gynecologic Oncology Group has approved the concept of performing a trial to assess assay directed therapy for patients with platinum resistant epithelial ovarian cancer" and that this decision is "partially on the basis of the recent article by Loizzi et al, demonstrating a significant survival advantage for ovarian cancer patients who were treated with assay assisted therapy."4 As the individual who conceived the trial design to be employed in the Gynecologic Oncology Group study, I must clearly state that the genesis of this concept was absolutely not a claimed survival advantage in this, or any other, retrospective analysis of any chemotherapy sensitivity or resistance assay system. In fact, it is precisely because of the unsubstantiated claims, comparing any assay-directed therapy to a historical control population (described in detail in the excellent ASCO review), that it is critically important for carefully considered, well-designed, prospective trials to be conducted to determine the clinical utility of this technology."

This is a summary of the statement:

Evidence from available studies is insufficient to conclude that in vitro chemosensitivity testing leads to improved patient management or health outcomes. The majority of studies reported no survival benefit associated with chemotherapy based on chemosensitivity assays when compared to chemotherapy based on standard regimens or clinical indicators. The level of evidence includes properly controlled randomized trials that show no substantial difference between patient groups receiving in vitro selected drugs as compared to regimens chosen by specialty physicians.

YET, THEY ARE OPEN TO ASSAY UTILIY. WHY?

although there is not yet any compelling
evidence that CSRAs should be integrated into routine oncology
care, the rationale for their development has increased.
When few chemotherapeutic options are available
and the array of choices is limited, the potential impact of
CSRAs is also circumscribed. Over the past decade, a large
number of new therapeutic agents (eg, oxaliplatin, irinotecan,
multiple monoclonal antibodies) have been US Food
and Drug Administration approved and the array of choices
facing oncologists has grown ever more complex. The
increasing number of choices makes the rational basis for
developing CSRAs even more compelling. This is particularly
true for those advanced malignancies with short
median survival. A review of several large clinical trials
demonstrates that, in the absence of CSRAs, the clinical
efficacy of different chemotherapy regimens is very similar.
17 For diseases with short median survival, patients
often do not maintain the functional status necessary to
receive more than one chemotherapeutic regimen and
thus selecting the regimen with the greatest chance of
inducing a response is indeed an important goal.
Although the Working Group finds no circumstance
in which chemotherapy sensitivity and resistance assays
should be obtained to make treatment recommendations
in routine clinical practice, this view should not be misconstrued
to suggest that this strategy lacks opportunity for
further research, particularly with newer therapies. As laboratory
techniques become more automated and high throughput
analyses become easier to obtain and interpret, better
assays will be developed. The in vitro approach to determining
drug sensitivity and resistance continues to have great potential
to spare patients the morbidity of ineffective chemotherapy
regimens. Evaluation of these technologies within the context
of appropriate research studies should be strongly encouraged
within the oncology community.

This excellent review and statement can be found here:

http://www.jco.org/cgi/reprint/JCO.2004.05.065v1.pdf

Again, pay for the test if you like. We can agree on that. But, we still need good research, no matter what model one wants to use. Let's see some, any, good evidence of significant survival advantage as compared to traditional methods.

Posted at 5:54PM on Sep 24th 2006 by Michelle

5. With the absence of effective laboratory tests to guide physicians, many patients do not even get a second chance at treatment when their disease progresses. Spending six to eight weeks to diagnose treatment failure often consumes a substantial portion of a patient's remaining survival, not to mention toxicities. In cases where there are several equivalent treatments available, patients can benefit from cell culture assay results as a supplement to other clinical data when deciding on a treatment option.

Drug sensitivity assays do not harm patients in any way except in terms of cost. But having some foreknowledge of a given chemo agent's expected result before its administration would benefit the individual patient. The cost of drugs is enormous. Patients are followed with serial CT scans, MRI's and even Pet Scans, just to see if a tumor is growing or shrinking. Not to mention the hospitalizations for toxicity, bone marrow tranfusions, etc. The point is, the cost of ineffective therapy is truly enormous and assay-testing is particularly good at identifying ineffective therapy.

Oncologists prescribe patients one standard empiric chemotherapy regimen after another, until they find one that works. This often can expose patients to the side effects of chemotherapy, without showing any cancer-killing results. Every cancer patient should have his/her own unique chemotherapy trial based on consultation of pathogenic profiles and drug sensitivity testing data. Research and application of drug sensitivity assays are being encouraged by growing patient demands, scientific advances and medical ethics. Drug sensitivity tests are not a luxury but an absolute necessity, and a powerful strategy that cannot be overlooked.

In light of the precious little in the way of guidance from clinical trials with respect to best empiric therapy (where the only thing that has been proven to correlate with treatment decisions is reimbursement to the prescribing oncologist) and the importance of basing cancer treatment at least in part on patient preferences, it is entirely reasonable to support judicious application of laboratory tests which have been well characterized with respect to test accuracy.

Posted at 7:08PM on Sep 24th 2006 by Gregory D. Pawelski

6. "In cases where there are several equivalent treatments available, patients can benefit from cell culture assay results as a supplement to other clinical data when deciding on a treatment option."

There is no evidence of this.

"Every cancer patient should have his/her own unique chemotherapy trial based on consultation of pathogenic profiles and drug sensitivity testing data."

There is no evidence that this is beneficial.

"Drug sensitivity tests are not a luxury but an absolute necessity, and a powerful strategy that cannot be overlooked."

This has yet to be proven.

"it is entirely reasonable to support judicious application of laboratory tests which have been well characterized with respect to test accuracy."

Fine. But, there is no evidence that there is any benefit over standard treatment protocol.

As indicated above:

"it is precisely because of the unsubstantiated claims, comparing any assay-directed therapy to a historical control population (described in detail in the excellent ASCO review), that it is critically important for carefully considered, well-designed, prospective trials to be conducted to determine the clinical utility of this technology."

You can keep repeating the mantra over and over and over, but I'll be here to also inform:

We need the data. Studies are just beginning. To tell a cancer patient that he or she is doomed without it, as you have said before, is extreme and just doesn't hold water.

Posted at 11:03PM on Sep 24th 2006 by Michelle

7. The activity for gemcitabine + platinum was first recognized as a treatment for ovarian cancer by Dr. Robert Nagourney. In November 1995, he received emergency approval from the FDA to use the Platin plus Gemcitabine combination to treat a late-stage ovarian cancer patient who had failed all conventional therapies. His research team used a cell-death endpoint assay. His discovery of the two-drug combination for treating ovarian cancer led to a national trial conducted by the Gynecologic Oncology Group, and was finally approved by the FDA in 2006, eleven years later.

Individualized testing of the gemcitabine + platinum combination began in the mid-1990s. The contribution of Dr. Nagourney in terms of recognizing the synergistic effects of this combination had been very important in getting clinical trials with this regimen started in a broad spectrum of cancers. Many thousands of cancer patients were helped by this, long before these clinical trials ever started. Many patients received treatment with this regimen because of individualized testing long before any clinical trials in their particular disease types had ever been published.

The idea is that a cancer patient is here today. And every one can have his/her own unique chemotherapy trial based on consultation of pathogenic profiles and drug sensitivity testing data, or they can wait years before clinical trials are ever started, let alone finished. Telling a cancer patient that he/she needs to wait until clinical trails are completed is doom and gloom, and doesn't hold water. They need help today, not years from now.

Posted at 2:05AM on Sep 25th 2006 by Gregory D. Pawelski

8. Gemzar was approved in 1996 but was made available to doctors for the treatment of pancreatic cancer patients in a "TIND" study (Treatment Investigational New Drug study) in 1995.

Two clinical trials conducted by the drug's sponsor, Eli Lilly and Co., suggested that gemcitabine (Gemzar) may effectively treat this cancer.

Dr. Nagourney claims that it was HIS work in 1995 that led to THE studies that then led to the approval of this cancer fighter for ovarian cancer. All press releases about said association come not from an independant source, but from Dr. Nagourney himself.

The IND designation was given for treatment of pancreatic cancer, months before the use in this ovarian patient he speaks of. So, this chemotherapeutic agent had already been seen as valuable.

In fact, gemcitabine was studied in ovarian patients in 2001, two years before publication of the Nagourney trial.

Thus,the statement,

"the contribution of Dr. Nagourney in terms of recognizing the synergistic effects of this combination had been very important in getting clinical trials with this regimen started in a broad spectrum of cancers,"

lacks evidence.

Dr. Nagourney likes to toot his own horn, but there is no evidence that HIS assay LED to approval of gemcitabine in ovarian cancer.

Finally, the statement,

"Telling a cancer patient that he/she needs to wait until clinical trails are completed is doom and gloom,"

is insensitive and again, infers that assay testing is a lifesaver. At this point in time, this is just plain wrong.

Mr. Pawelski goes completely unchallenged on this and hundreds of blogs and newsfeeds.

It's time for some rational discourse.

Posted at 8:24AM on Sep 25th 2006 by Michelle

9. Some people can be "fast" and "loose" saying there is no proof with cell culture assay tests. Where's the "proof" with clinical trials? Efficacy is not proof.

The problem with current approaches to cancer therapy are they are too often ludicrously ineffective and progress over the past 20 years has too often been virtually non-existent, when a 2,000 patient prospective randomized trial produces a significant improvement in median survival which translates out to an 18.4 month median survival versus a 17.1 month median survival and that means that everyone should receive the treatment producing the 18.4 month survival, even when the next three trials fail to confirm this advantage.

Presently used chemotherapy drugs have a high rate of failure. This was brought out in a January 10, 2002 issue of the New England Journal of Medicine, when it was noted that while new chemotherapy regimens "appear" to be improving survival, when these same regimens are tested on a wider range of cancer patients, the results have been very disappointing. In other words, oncologists at a single institution may obtain a 40% - 50% response rate in a tightly controlled study, but when these same chemotherapy drugs are administered in a real world setting, the response rates decline to only 17% - 27%.

The percentage of patients that must respond to a drug before it is approved varies from as high as 80% to as low as 20%. Thereafter, it is used routinely for all patients with the same form of cancer, though unfortunately a drug that helps one person does not necessarily mean it will help all patients with the same diagnosis. God forbid you have a medical oncologist that really does believe in the one drug(s) fits all patients. And the response rate for FDA approval of Taxol........a measly 30%. Imagine if a patient knew beforehand that Taxol had only a 30% response rate, would that patient take the drug? This is all part of the "informed consent".

Having a good tumor-drug match not only would improve survival rates, it would be cost-effective, and the high cost of the newer cancer therapies reinforces the necessity of choosing the right therapy the first time around.

I'll be here to correct Michelle A's misinformation about cell culture assays.

Posted at 4:32PM on Sep 25th 2006 by Gregory D. Pawelski

10. "I'll be here to correct Michelle A's misinformation about cell culture assays."

Unfortunately, Mr. Pawelski gave me a red herring, a distraction from the fact that there is no evidence that cell culture assays are of benefit. His red herring: attack chemotherapy regimens routinely used by virtually all onologists worldwide.

It's alright to attack traditional treatments, as cancer is a very difficult disease to treat and we are only now able, with new technology, just made available, to look at how cancer cells function and grow. But, he does not address the fundamental questions about assay benefit.

Jenny Heumann Senior Public Affairs Manager, American Society of Clinical Oncology states, in response to criticism of the ASCO recommendations:

CRITICSM:

"-- The goal of these assays should not be to determine sensitivity/specificity, but to demonstrate through prospective trials that such assays can be employed to change treatment for the better."

RESPONSE:
"To date, there are insufficient data for such a demonstration."

Now, Mr. Pawelski may again bring out his hypothesis that they "want to keep approval at bay so office oncologists can profit," but this will be another red herring.

But, I can't help myself. What the heck. I'll quote Mr. Heumann again:

"The [ONCOLGISTS FOR INDIVIDUALIZED THERAPY]fail to acknowledge explicitly their own overt conflicts of interest as providers and marketers of assay services."

Ouch. (Sorry. I shouldn't have brought it up, because this is my red herring I'm throwing out there. Again this has nothing to do with the fact that there is no evidence that cell culture assay testing will benefit you at this time.)

For a further rebuttal of the individualized therapy oncologists see:

http://www.medicalnewstoday.com/medicalnews.php?newsid=14009

One of the logical fallacies used by proponents of unsubstantiated claims is the THE APPEAL TO PROBABILITY. Often used in conjunction with other fallacies, it assumes that because something could happen, it is inevitable that it will happen. This is flawed logic, regardless of the likelihood of the event in question. The fallacy is often used to exploit paranoia (in this case, among vulnerable cancer patients.)

Until research is available on claims of benefit for any diseases, one should be aware of this common logical fallacy among benefit proponents and "call them on it."

I think it's very fair and it does not involve attacks on the person.

Posted at 8:11PM on Sep 25th 2006 by Michelle

11. The most important progress made in the field of cell culture assays during the past 20 years had taken place in the private sector, with more European and Japanese clinicians and scientists taking the lead. There is a substantial amount of published, peer-reviewed literature to establish that existing assays are capable of identifying both poor prognosis and good prognosis therapies, with good prognosis therapies being about seven-fold more likely to work than poor prognosis therapies.

However, the literature is complex and cannot be intelligently interpreted without an understanding of Bayes' Theorem (a statistical concept) and a host of biological and pharmacological concepts. This literature is not understood by many NCI investigators and by NCI-funded university investigators, except maybe for M.D. Anderson investigators who have recently taken a new look at how to evaluate new medicines and treatments for cancer by adoption of the Bayesian method of science in 100 cancer-related phase I and II clinical trials being planned or carried out.

The NCI failed in its attempt years ago, to study assay-directed therapy of lung cancer on its own. Their expertise was in establishing permanent cell lines and they only tested tumors after first culturing them to amplify their cell number (these were all passaged, grown up, multiplied, replated). The result was that their assay evaluability rate for primary lung cancers was only 11% (a very dismal result).

The second problem they had is that they were selecting subpopulations. Subsequent work showed that you get different results when you test "passaged" cells compared to primary "fresh" tumors. The third problem is that the ability to get lung cancer to actually grow is an independent marker for virulent disease. It was actually the single greatest negative predictor for survival in one of the studies.

So the NCI concluded that it was too much trouble and not all that useful. If they couldn't get it to work at NCI, then of course no one can do it. That was the attitude thereafter. One of the physicians that worked on these studies now knows and readily grasps the limitations and non-applicability of the NCI efforts.

And again, more recently, 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'd worked out in the cell lines was not worth anything and they had to start over from square one. A simple gesture to their colleagues in the private sector could have saved a lot of aggravation.

Critics of cell culture assays demand proof that use of the test improves clinical outcome. This has never been demonstrated for any laboratory or radiographic test, in any specialty of medicine, and certainly not in cancer medicine. No one has ever shown that managing patients with the benefit of any laboratory or radiographic test has been shown to improve treatment outcome, compared to treatment of patients without benefit of the knowledge provided by test results. So they are presenting a standard which is entirely without precedent. It is also a standard which has not been applied by the FDA.

Posted at 12:51AM on Sep 26th 2006 by Gregory D. Pawelski

12. Mr. Pawelski has no evidence of the NCI data other than copying and pasting from Dr. Wiesenthal's site from which he quotes often without attribution.

If he does, he should present it here for discussion.

In looking at the data on

“Cell-Death” Assays. Taken together, the
evidence from 6 studies on these 3 cell-death
assays is insufficient to permit conclusions
about the relative effects on health outcomes
of assay-guided and empiric treatment. Two
studies show significantly better response rates
for assay-guided therapy, but intention-to-treat
analysis of results is unavailable for one of
these. Two other studies show nonsignificant
trends favoring assay-guided treatment and
2 more studies show no substantial difference
between groups. Only 1 of 6 studies found a
significant increase in survival with assayguided
therapy, in a study with no comparison
of groups on baseline characteristics. Two
studies provide limited information on baseline
characteristics, but it is insufficient to permit
thorough assessment of the comparability of
groups. None of the 6 studies used randomization
and none reported on adverse events."

http://www.bcbs.com/tec/vol17/17_12.pdf

It's time for the community to do the studies. And they have just begun. Until then, the vast majority of researchers in the field have not made the statements one sees in the blogging community. They choose to wait for the data, real data to show benefit. They are finally performing the scientific work required.

Posted at 1:49PM on Sep 26th 2006 by Michelle

13. In a cell culture assay, the concept is to obtain a biopsy of a patient's cancer and isolate the cancer cells from the biopsy, culture these cells in the laboratory, and test them to determine if they are likely to be "sensitivity" or "resistant" to different forms of chemotherapy.

There are two main endpoints for these tests. The first endpoint is whether the drugs prevent the cells from reproducing themselves. These are called "cell-proliferation" assays. The second enpoint is whether the drugs kill the cells. These are called "cell-death" assays.

There was tremendous interest in the cell-proliferation assays between 1979 and 1983. At the same time, an alternative endpoint of cell-death was coming into being. However, there was a critical New England Journal of Medicine editorial exposing the problems with the "cell-proliferation" endpoints. The importance of Apoptosis, the programmed cell-death as an important mechanism of action of anticancer drugs, did not come into existence until five years later, in 1988.

As the NCI investigators and NCI-funded academic oncology investigators failed in their research attempts to understand this technology, research into this field was largely driven into the venture capital-backed private sector. Ultimately, a very large and compelling body of evidence emerged to document the predictive accuracy of the drugs "active" in the assays likely to work in the patient than drugs "inactive" in the assays, and patients treated with drugs "active" in the assays enjoy a significant survival advantage over patients treated with drugs "inactive" in the assays.

While individual oncologists have made extensive use of the assays in their practices, and are convinced of their clinical utility, the so-called "official" oncology lead organizations have not supported the use of these outside the setting of clinical trials. That's a no-brainer. For institutions that make a living predominately from clinical trials, what else are they going to say?

As some would like to point out the 2004 ASCO reviews of the use of these assays in oncology practice, the conclusions were inaccurate and misleading. After 20 years of prospective, randomized clinical trials to identify the best treatments to give to the average patient, there has been absolutely no progress. The whole system existed to serve the clinical investigators and the clinical oncologists, but not to serve the best interests of the cancer patients. But I don't know whoever anointed ASCO? However, like the AMA, doctors are mostly not "members of the club." Most doctors are intelligent, free-thinking individuals that do have the health and welfare of the patient in mind.

Posted at 3:39PM on Sep 26th 2006 by Gregory D. Pawelski

14. Conspiracy theories aside:

"Members of the ASCO working group would have liked more than anyone for these assays to be shown to be ready for “prime time.”
Several of the investigators participating in the ASCO review spent years of their careers trying to develop truly clinically useful assays, and thus did not reach these conclusions lightly."

http://www.medicalnewstoday.com/medicalnews.php?newsid=14009

Again, there is absolutely no proof, not a lick of evidence, that oncologists treat patients "to serve the clinical investigators and the clinical oncologists."

These are adhominem statements that lack evidence. I see it all the time in the alternative medicine community where alternative advocates claim physicians poo poo their "treatments" so physicians can make all the money. This is presented with no data to back these claims. It's like if you say it enough, maybe some will believe it. Unfortunately, no headway is made as no scientific data is presented.

Unfortunately, the passion exhibited by assay promotion in blogs has done little to further the cause over the past decade. It's only now that true researchers realize good data is required before claims are made. They work quietly in the background and we should start to know soon if there is any benefit at all from this method. It will be truly great if there is benefit. Those studies are just now beginning.

Sure, their sites are filled with testimonials, but do you read of the lack of success there? Of course not. No one holds them to that because only now is legitimate research beginning to occur.

Again, be aware of THE APPEAL TO PROBABILITY. Often used in conjunction with other fallacies, it assumes that because something could happen, it is inevitable that it will happen. This is flawed logic, regardless of the likelihood of the event in question. The fallacy is often used to exploit paranoia (in this case, among vulnerable cancer patients.)

Until research is available on claims of benefit for any diseases, one should be aware of this common logical fallacy among benefit proponents and "call them on it."

They may make you very anxious that your treatment will not help you. Cancer is difficult to treat. That is true. But to offer a fanciful notion as truth is not helpful and perhaps worse.

Posted at 5:26PM on Sep 26th 2006 by Michelle

15. There are two types of cell culture assays, one that determines whether a drug stops a cancer from growing (cell-growth) and one that determines whether a drug kills (cell-death) the cancer outright. The ASCO report looked at the cell-growth tests, and not at the cell-death tests, that are a better predictor of whether a drug will work.

As Michelle points out in her referrals, the ASCO panel says the cell-death tests weren't included in the review because, to them, there weren't any reliable studies assessing them. Even with the cell-growth analysis, many studies cited in the ASCO report showed twice as many patients who were given assay-directed therapy responded to treatment, compared to patients who were given empiric-directed therapies.

The researchers claim that the studies didn't show that using the tests helped people live longer than those prescribed a "standard" treatment, however, they cannot claim that "standard" treatments helped people live longer than those that used "assay-directed" treatments.

ASCO is attempting to impose an entirely new standard for the evaluation of medical tests. The previous standard always used to evaluate any type of medical test has always been the correlative and predictive "accuracy" of the test. How well does a Bacterial Culture and Sensitivity Test predict for clinical success or failure of penicillin therapy?

Not only is test accuracy (not efficacy) the established standard for evaluating every single test used in medicine, it is also the precise standard used by the FDA in approving a test kit for these assays. The FDA didn't require proof of efficacy (as it has never required proof of efficacy for any medical tests).

Eighty percent of academic oncologists and thirty-five percent of private practice oncologists are ordering the $3,600 OncotypeDX test, at a time when it had only been shown to be accurate (and not efficacious) and only in a retrospective study in which all assays were done not under real world situations, but by a single "crack" lab team in the space of two weeks. There are no studies planned of assay directed treatment versus non-assay directed treatment. All that are being planned are studies to confirm the predictive "accuracy" prospectively.

Why are lung cancer oncologists performing gene mutation tests to determine whether or not patients should be treated with erlotinib, in the absence of any studies in American patients showing survival correlations and with the absence of any studies showing that using the test make a difference in treatment outcomes. Name a single laboratory test which has ever been shown to improve treatment outcomes. Why is it appropriate to specifically exclude test accuracy as a factor to evaluate cell culture drug resistance tests when test accuracy is the only factor used to evaluate every single other type of medical test.

Posted at 11:00PM on Sep 26th 2006 by Gregory D. Pawelski

16. I'll just take respond to one comment here as it's late.

The Oncotype DX Recurrence Score has been shown to predict the likelihood of distant recurrence and the benefit of chemotherapy.

Oncotype DX represents the first diagnostic multi-gene expression test commercially available that has clinical evidence validating its ability to predict the likelihood of cancer recurrence, the likelihood of patient survival within 10 years of diagnosis and the likelihood of chemotherapy benefit.

Accuracy is not the reason it was approved in California.

The assays Mr. Pawelski always refers to, as of yet, show no benefit.

Technology Evaluation Center (TEC) Criteria:

The Blue Cross and Blue Shield Association and Kaiser Permanente use the five criteria below to assess
whether a technology improves health outcomes such as length of life, quality of life and functional ability.
1. The technology must have final approval from the appropriate governmental regulatory
bodies.
• This criterion applies to drugs, biological products, devices and any other product or procedure that
must have final approval to market from the U.S. Food and Drug Administration or any other federal
governmental body with authority to regulate the technology.
• Any approval that is granted as an interim step in the U.S. Food and Drug Administration's or any
other federal governmental body's regulatory process is not sufficient.
• The indications for which the technology is approved need not be the same as those which Blue
Cross and Blue Shield Association's Technology Evaluation Center is evaluating.
2. The scientific evidence must permit conclusions concerning the effect of the technology on
health outcomes.
• The evidence should consist of well-designed and well-conducted investigations published in peerreviewed
journals. The quality of the body of studies and the consistency of the results are
considered in evaluating the evidence.
• The evidence should demonstrate that the technology can measure or alter the physiological
changes related to a disease, injury, illness, or condition. In addition, there should be evidence or a
convincing argument based on established medical facts that such measurement or alteration affects
health outcomes.
• Opinions and evaluations by national medical associations, consensus panels, or other technology
evaluation bodies are evaluated according to the scientific quality of the supporting evidence and
rationale.
3. The technology must improve the net health outcome.
• The technology's beneficial effects on health outcomes should outweigh any harmful effects on
health outcomes.
4. The technology must be as beneficial as any established alternatives.
• The technology should improve the net health outcome as much as, or more than, established
alternatives.
5. The improvement must be attainable outside the investigational settings.
When used under the usual conditions of medical practice, the technology should be reasonably
expected to satisfy TEC criteria #3 and #4.

http://www.harvardpilgrim.org/pls/portal/docs/PAGE/PROVIDERS/MEDMGMT/STATEMENTS/ONCOTYPEDX_POLICY7.05.PDF

As far as his referral to bacterial C&S an approval based on accuracy alone? I will address these next as the analogy is incorrect.

But, it's time for bed.

Posted at 12:39AM on Sep 27th 2006 by Michelle

17. ASCO Recommendations on Adjuvant Chemotherapy for Stage II Colon Cancer

Al B. Benson III, Deborah Schrag, Mark R. Somerfield, Alfred M. Cohen, Alvaro T. Figueredo,Patrick J. Flynn, Monika K. Krzyzanowska, Jean Maroun, Pamela McAllister, Eric Van Cutsem,Melissa Brouwers, Manya Charette, and Daniel G. Haller (JCO Vol 22; No. 16; Aug. 15, 2004)

Conclusion

Direct evidence from randomized controlled trials does not support the routine use of adjuvant chemotherapy for patients with stage II colon cancer. Patients and oncologists who accept the relative benefit in stage III disease as adequate indirect evidence of benefit for stage II disease are justified in considering the use of adjuvant chemotherapy, particularly for those patients with high-risk stage II disease. The ultimate clinical decision should be based on discussions with the patient about the nature of the evidence supporting treatment, the anticipated morbidity of treatment, the presence of high-risk prognostic features on individual prognosis, and patient preferences. Patients with stage II disease should be encouraged to participate in randomized trials.

The ASCO study showed no evidence of benefits for (empirically-selected) adjuvant chemotherapy in Stage II colon cancer, but even in the face of a negative study, said it was OK for individual oncologists and patients to make the decision whether or not they want to be treated.

And Schrag, two weeks previously the second author on another ASCO study showed no evidence of benefit for (empirically-selected) adjuvant chemotherapy in Stage II colon cancer, but even in the face of a negative study, said that it was OK for individual oncologists and patients to make the decision whether or not they want to be treated. She wouldn't tell her colleagues not to give chemotherapy if they really wanted to. And she's talking about a treatment; not just about a test. The question gets asked in randomized studies. She does a big meta-analysis and still gets a negative result. But still says, well, OK, you can use it if/when you really want to, if it's OK with your patient. Efficacy has been tested and refuted, but it's still OK to use treatment which has been proven to be non-efficacious.

Posted at 12:55AM on Sep 27th 2006 by Gregory D. Pawelski

18. Finally, Mr. Pawelski now reports on a statement and decision based on evidence-based research. This is what scientists do.

Now, his claim that:

"Efficacy has been tested and refuted, but it's still OK to use treatment which has been proven to be non-efficacious."

is partially right. It IS OK to use adjuvant chemotherapy, but he then makes the mistake of saying that it is "non-efficacious" when, in fact, that is not at all what ASCO says. This is why one must, as the authors of this blog and ALL good health blogs and newsfeeds, must state a disclaimer. (This blog does it prominently at the top.)

THIS IS WHAT THEY STATE (and was unfortunately, left out from the auhor's post):

"Direct evidence from randomized controlled trials does not support the use of adjuvant chemotherapy, even for patients with high-risk stage II colon cancer. Patients and oncologists might reasonably be reluctant to choose adjuvant therapy because of this lack of direct evidence of benefit. However, patients and oncologists who are prepared to take the risk of accepting the results from stage III disease as adequate indirect evidence of benefit are justified in considering the use of adjuvant chemotherapy in stage II disease, provided that they understand that the magnitude of benefit as measured in absolute improvement in survival, is small. Patients who have had a complete resection can be reassured that adjuvant treatment for typical stage II disease does not improve 5-year survival by more than an absolute 5%. Whether smaller incremental improvements in survival can be derived from treatment remains open to question."

http://www.guideline.gov/summary/summary.aspx?doc_id=5298&nbr=3621

Some may want that 5% chance when there is no chance without treatment. And, this is a statement from 2 years ago. Now we have more data from those dastardly clinical trials with new conclusions:

http://patient.cancerconsultants.com/colon_cancer_treatment.aspx?id=689

Mr. Pawelski has stated that chemotherapy assays should be approved when the data on survival is not available at this time. Yet, much data on survival IS available on stage II colon cancer and chemotherapy and NOW physicians and patients can make sound decisions based on that data. Hopefully, in the future, decisions can be made on treatment based on cell culture assays, but the time is not yet here and to constantly inform patients on hundreds of blogs and newsfeeds that treatment for cancer will prove worthless for them unless they try this unproven therapy is, well....you know how I feel.

Posted at 9:14AM on Sep 27th 2006 by Michelle

19. The reviews that Michelle A. brings up simply reiterates the same old inadequate and misleading arguments. Once again, the reviewers failed to realize that they are evaluating a laboratory test and not a treatment. All laboratory tests are evaluated on the basis of test accuracy and no laboratory test in the history of cancer medicine has ever been shown in clinical trials to improve the results of therapy. Why is it appropriate to specifically exclude test accuracy as a factor to evaluate cell culture assay tests when test accuracy is the only factor used to evaluate every single other type of medical test?

The so-called "expert review" is a sad reflection on the incompetence of "closed" review panels. Critics say "until we get sound scientific data, approval will not occur." But all of the "sound scientific data" was excluded from analysis. So point of fact, the reviewers completely misunderstood the studies.

Critics say "in vitro chemosensitivity assays, including but not limited to the histoculture drug response assay or a fluorescent cytoprint assay are considered investigational." The National Medicare policy, dating from 1981 is that assays, specifically described as (and therefore limited to) the Human Tumor Stem Cell Assay and Fluorescent Cytoprint assay, are considered "investigational." Neither of those assays have been used in the clinical management of patients in a non-investigational setting for more than 15 years. National Medicare currently has no national coverage policy relating to the technologies which are in current use, leaving it to local coverage decisions.

I ask any readers to ask themselves if they had acute leukemia or chronic lymphocytic leukemia (two diseases where NCI currently identifies a number of different drug regimens as being equally likely to be active if chosen by the flip of a coin, would they not want to avail themselves of a simple laboratory test (performed on a simple blood or bone marrow specimen) which could help them avoid receiving a treatment which was likely to be a death sentence, when a large number of otherwise equal by coin flip regimens could be chosen instead?

As ASCO points out, because the number of available chemotherapeutic agents has increased enormously over the past few years, the emphasis on the rationale for these assays has never been stronger. But institutions that make a living predominately from clinical trials, no wonder ASCO has not supported the use of cell culture assays outside the clinical trial. Don't want to disturb the income flow. Academic center-based oncologists derive personal profit from the implementation of clinical trials. The same people who maintain that assay-directed therapy should not be used until "proven" in prospective randomized clinical trials, are the same people who control the clinical trials system, the grant review study sections, and the journal editorial boards.

This implies the academic center-based oncologists' fair share of collective guilt. They are misguided in not recognizing that they are trying to mate notoriously heterogeneous diseases into one-size-fits-all treatments. They devote 100% of their clinical trial resources into trying to identify the best treatment for the average patient, in the face of evidence that this approach is non-productive. However, such unsuccessful experiments will never be viewed as such by the thousands of people whose careers are supported by these experiments.

Posted at 9:29AM on Sep 27th 2006 by Gregory D. Pawelski

20. "would they not want to avail themselves of a simple laboratory test (performed on a simple blood or bone marrow specimen) which could help them

No proof of this.

"But institutions that make a living predominately from clinical trials, no wonder ASCO has not supported the use of cell culture assays outside the clinical trial. Don't want to disturb the income flow.."

No proof of this.

"However, such unsuccessful experiments will never be viewed as such by the thousands of people whose careers are supported by these experiments."

AGAIN, good thing blogs have disclaimers. The implication by this lone blogger who posts comments like this to hundreds of blogs and newsfeeds (do a Google search on "Pawelski and cancer"), not only lacks any proof (of course, he prefers tests be approved without proof), is inflammatory, and I, must say, has to cause tears in the eyes of those who not only have to fight this disease, but have to have constantly read his posts all over the cancer blogs about the fact they, as he has stated, are "doomed."

I can't keep up with him, but hopefully some who may come to THIS blog will get to see some rebuttal of the unproven statements.

BTW, always look for the adhominem fallacy when you get people angry enough.

An ad hominem argument, also known as argumentum ad hominem (Latin, literally "argument against the person") involves replying to an argument or assertion by attacking the person presenting the argument or assertion rather than the argument itself. It is a logical fallacy.

This is what happens when claims are made about GREEDY scientists rather than addressing any of the facts. Often this happens when someone has felt, whether right or wrong, slighted at some point in his or her life.

As the rhetoric heats up, the ad hominem becomes:

ad personam

Ad hominem abusive (also called argumentum ad personam) usually and most notoriously involves insulting one's opponent, but can also involve pointing out factual but damning character flaws or actions. The reason that this is fallacious is that — usually, anyway — insults and even damaging facts simply do not undermine what logical support there might be for one's opponent's arguments or assertions; argumentum ad personam short-circuits these potential arguments from logic in favor of a direct attack on the opponent's authority (as can be seen here on the attack on physicians and scientists.)

The study of logical fallacies in the field of science is valuable. It allows one to view facts as they are and to decrease emotion and promote healthy discourse.

It would be nice if we saw this in the political realm today.

See if you can identify fallacies in bloggers' posts, including mine.

Posted at 10:21AM on Sep 27th 2006 by Michelle