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Fair And Impartial ASCO Tech Assessments? Give Me A Break!!!
posted by Gregory D. Pawelski on 06 Aug 2007 at 7:50 amA so-called ASCO expert panel did a tech assessment on cell culture assays tests which included only three investigators who had ever worked in the field of cell culture assay technology: Dan Von Hoff, Anne Hamburger, and a German named Hanauske who worked with Von Hoff in San Antonio and then returned to Germany to continue using Von Hoff's methods (which were Hamburger and Salmon's methods). All three were old line "Human Tumor Stem Cell" (clonogenic) assay workers, who, along with Salmon, convinced the oncologic community that clonogenic assays were the only valid approach to chemosensitivity testing (no one had ever heard of apoptosis back then). The clonogenic assay failed and it dragged down the whole field of inquiry along with it. So basically, the panel consisted of various oncologists who knew nothing about the technology and data, along with three proponents of a long-ago discredited approach which had nothing to do with the technologies (assays with cell death endpoints), and with no one at all who understands anything at all about the newer technologies and published data pertaining to them.
In the tech assessments, the authors invented a brand new criterion for validating a laboratory test. The existing standard had always been the "accuracy" of the test. This is true for every single test used in cancer medicine, from estrogen receptors to bacterial culture and sensitivity testing to panels of immunohistochemical stains to diagnose and classify tumor to Her2/neu and CA-125 to MRI scans, CT scans, PET scans and on and on. Yet they never even attempted to review the voluminous literature which defined the "accuracy" of cell death assays, and instead restricted their analysis to a consideration of papers which tried to address the issue of whether the use of the assays actually improved patient outcomes. They lumped together the old and long abandoned technologies (clonogenic assay, subrenal capsule assay, etc.) with the cell death assays. And yet, even in their own review, there were five studies with cell death assays and patient outcomes that were improved in four of the five studies and one negative study wasn't even relevant, because the authors did their tests on subcultured cells (as opposed to "fresh" tumor cultures) and tested the cells in monolayers (as opposed to three dimensional cell clusters). They ignored all studies having to do with "accuracy," the criteria used in tech assessments of all previous laboratory and radiographic tests, and only included studies dealing with "efficacy," a standard never met by any laboratory or radiographic test.
Were they to have reviewed studies showing that the use of estrogen receptor improved treatment outcomes, they would have found no publications at all. Were they to have reviewed papers showing that the use of panels of immunohistochemical stains to subclassify tumors improved treatment outcomes, they would have found no publications at all. Were they to have reviewed studies showing that treatment outcomes were improved through the use of MRI scans or PET scans or CT scans to monitor growth and shrinkage of tumors (for the purpose of influencing the decision to continue the same chemotherapy or to change chemotherapy), as opposed to simply following patients with history, physical, simple plain radiographs, and simple lab tests, they would have found no publications at all.
A "valid" tech review would have started with the published "accuracy" of the tests, and would have included in excess of 2,000 published correlations, in all types of neoplasms from acute leukemia to breast cancer to ovarian cancer to colon cancer and so forth, every single one of which showed that patients treated with drugs "active" in the assays had significantly higher response rates than patients treated with drugs which were "inactive" in the assays. They would have noted a half dozen papers which also showed that patients treated with drugs "active" in the assays also enjoyed significantly longer survivals. They would have made note of the preliminary studies which supported the concept that the use of the assays influenced treatment decisions which resulted in superior outcomes. A "valide" technology assessment would have concluded that the weight of the available evidence supports the decisions of individual oncologists to make at least selective use of these assays in their clinical practices.
What is it that ASCO is saying? Cell culture assays should not be used outside the confines of a clinical trial setting. The same people who maintain that assay-directed therapy should not be used until proven in prospective randomized clinical trials, are the same people whose entire careers are utterly dependent upon mega-trials funded by pharmaceutical companies (that, plus fees from speeches they give for these companies), are the same people who control the clinical trials system, the grant review study sections, and the journal editorial boards. Why else would they want this technology tested under the clinical trial setting?
Opponents of cell culture assay testing can blow all the smoke screens they want, but the fact is that every single time advocates for cell culture assays have been given fair consideration by an impartial, non-ASCO adjudication, the decision has been made that this testing is a perfectly appropriate medical service, worthy of coverage on a non-investigational basis. It is only when ASCO or the insurance industry has been appointed itself as the judge/jury/prosecutor/defense rolled into one and not invited input from all "relevant" parties that the decisions have been unfavorable.
| No Benefit To Chemo Assays. |
| posted by hchcec on 06 Aug 2007 at 7:51 pm |
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I don't understand the anger with ASCO. This excellent organization is comprised of hard working scientists and physicians who work daily to find better ways to treat cancer patients. I'm not sure why this internet blogger, who doesn't possess a scientific background and who has never treated a patient or worked in a laboratory is so disgruntled. Perhaps he bears a grudge for some perceived wrongdoing. Maybe he's had a bad experience with chemotherapy, like believing taxol causes brain cancer, or something odd like that.
His marketing of cell assays over the internet has done nothing over many years to change anybody's mind. It certainly creates fear in cancer patients that scientists do not have their best interest in mind. There's a demonization which is certainly displaced. His anger should be directed toward the developers of the tests he is marketing over the internet for they have not produced any evidence of benefit , yet they want your money. No national Medicare guidelines for its use, no insurance company coverage, NOT due to some conspiracy, but simply because his tests are not proven to benefit cancer patients. The "accuracy myth" is just that: a myth. Accuracy, efficacy and timeliness are three goals that must be achieved by the FDA. One should not be compromised for the other. He knows this. To determine whether assay-guided treatment results in overall different outcomes than empiric treatment, it is important to take into account response rates, survival, and adverse effects. These effects may be assessed by decision analysis or comparative trials. Pawelski, years ago, wanted us to buy his clonogenic test without research. It failed. More tests over the years. "Buy them." They failed. And, now he wants you to buy the latest and greatest. There's no evidence they are of any benefit, either. What's next? Maybe they will help. But, we don't know that at all and you'll have to pay $3500 to the marketers of these tests to find out. "Major questions remain unanswered, such as how best to select patients who benefit from these tests and whether patients receiving assay-selected chemotherapy show better response than those receiving best current therapy." You mention studies. Let's see them , Pawelski. I'd like to do a statistical analysis of them. Could you show these supposed beneficial studies to your readers? Your test hasn't been approved. Is it because these studies don't really hold up under real honest-to-goodness analysis? Where are they? Hey. I'll criticize ASCO, too, if I believed your beneficial studies actually exist. |
| Open And Impartial ASCO Tech Assessment Is The Answer |
| posted by Gregory D. Pawelski on 07 Aug 2007 at 7:21 am |
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An "open" and "impartial" ASCO tech assessment will give you all the proof in the world Michelle. Each and every time advocates for cell culture assays have been given an "open" and "impartial" adjudication the decision has been made that this testing is a perfectly appropriate medical service, worthy of coverage on a non-investigational basis. But what is ASCO afraid of? Protecting their financial holdings? They won't be able to get their little gold stars for writing a "paper?"
Numerous venerated scientific journals have been caught with scientific misconduct. Caught withholding crucial data. Exaggerating drug safety. Falsifying results. Medical knowledge grows not in the direction that best improves the health and welfare of patients but toward profit incentive. It has gotten so out of hand that some individual scientists are manipulating their findings. A Journal of the American Medical Association report found that clinical studies funded by drug companies are three times more likely to conclude that the sponsor's drug is the treatment of choice, compared to studies of the same drug that was not commercially funded. Most of the evidence in what physicians believe to be "evidence-based" medicine is more informercial than science. There is no better cautionary tale than the "buyer be ware" when it comes to drug development. I will not dignify any of Michelle's slanderious accussations about me with an answer. She is very good at the fine art of selective quotation to make me appear to hold positions which I do not hold. That's her problem. I do have to range the web to combat misinformation about cell culture assays. I do challenge conventional cancer medicine. It has all the faults in the world to be challenged. I do suggest to readers who may be unnecessarily alarmed by her quotations to read my information in its entirety. A scientific communication should be judged on the quality of its content, not by alarmist Quackwatch attitudes. |
| No Studies, Again |
| posted by hchcec on 08 Aug 2007 at 5:15 am |
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Where are your studies? What do you fear by not posting your studies. Shouldn't we see those studies before we buy your $3500 product?
Where are they? Attack the scientific method all you want, but show us your PROOF that your test has any benefit. We're waiting..... |
| What Is The Issue With Cell Culture Assay Tests? |
| posted by Gregory D. Pawelski on 08 Aug 2007 at 2:19 pm |
|
As with any other laboratory tests in cancer medicine, the determination of the efficacy of cell culture assays is based on clinical correlations (comparisons of laboratory results with patient response). That is, above-average drug effects in the cell culture assays correlate with above-average drug effects in the patient, as measured by both response rates and patient survival. The standard of retrospective correlations between treatment outcomes and laboratory results is sufficient in the case of all laboratory tests.
The markers ER and Her2/neu correlate with and predict for tumor response and patient survival. Imagine if these laboratory tests may only be judged on the basis of the proven ability of the tests to improve treatment outcomes in clinical trials in which patients are managed with and without the information provided by the tests? In other words, judged only by studies in which comparisons are made of the treatment outcomes of groups of patients managed with the benefit of the information provided by these tests, compared to the treatment outcomes of patients managed without benefit of the information provided by these tests. You'd say, "Wait a minute, neither the ER nor the Her2/neu tests are ready for prime-time players." That's what ASCO and private insurers are doing with cell culture assay tests. Michelle is trying to invent a brand new criterion for validating a laboratory test. The existing standard has always been the accuracy of the test. This is true for every single test used in cancer medicine, from estrogen receptors to bacterial culture and sensitivity testing to panels of immunohistochemical stains to diagnose and classify tumor to Her2/neu and CA-125 to MRI scans, CT scans, PET scans and on and on. PET scans were not apporved because they saved lives in a controlled clinical trial that compared the outcome of patients who received care with or without the benefit of a PET scan. They were approved because their performance characteristics (sensitivity/specificity) are reporducible, favorable and provide useful information to treating physicians. Cell culture assays have performance characteristics that are reproducible, favorable and provide useful information to treating physicians. In an effort to establish treatment guidelines, even the chair of the Community Oncology Alliance's QSP Committee states that ASCO has technology assessments that are very limited and updates which are not timely (and as we now know, not 'open'). The only tech reviews that were negative for cell culture assays were the "closed" reviews (e.g. BC/BS and ASCO), where they never even attempted to review the voluminous literature which defined the accuracy of cell death assays. But the two "open" reviews by NHIC Medicare and California Blue Shield where everyone had the chance to present their data and make their case, were both quite positive. There is an inherent conflict of interest when organizations that provide guidelines for treating a disease also receive funding from corporations that benefit financially from the recommended treatment. In the "closed" ASCO tech assessment, they lumped together the old and long abandoned technologies (clonogenic assay, subrenal capsule assay, etc.) with the cell death assays. And yet, even in their own review, there were five studies with cell death assays and patient outcomes that were improved in four of the five studies and one negative study wasn't even relevant, because the authors did their tests on subcultured cells (as opposed to "fresh" tumor cultures) and tested the cells in monolayers (as opposed to three dimensional cell clusters). They ignored all studies having to do with accuracy, the criteria used in tech assessments of all previous laboratory and radiographic tests. Even the ASCO tech review specifically stated that it excluded from coverage papers which only related to test accuracy and there were no other tests which had ever been judged on anything other than accuracy. Were they to review studies showing that the use of estrogen receptor improving treatment outcomes, they would have found no publications at all. Were they to have reviewed papers showing that the use of panels of immunohistochemical stains to subclassify tumors improved treatment outcomes, they would have found no publications at all. Were they to have reviewed studies showing that treatment outcomes were improved through the use of MRI scans or PET scans or CT scans to monitor growth and shrinkage of tumors (for the purpose of influencing the decision to continue the same chemotherapy or to change chemotherapy), as opposed to simply following patients with history, physical, simple plain radiographs, and simple lab tests, they would have found no publications at all. A valid tech review would have started with the published accuracy of the tests, and would have included in excess of 2,000 published correlations, in all types of neoplasms from acute leukemia to breast cancer to ovarian cancer to colon cancer and so forth, every single one of which showed that patients treated with drugs "active" in the assays had significantly higher response rates than patients treated with drugs which were "inactive" in the assays. They would have noted a half dozen papers which also showed that patients treated with drugs "active" in the assays also enjoyed significantly longer survivals. They would have made note of the preliminary studies which supported the concept that the use of the assays influenced treatment decisions which resulted in superior outcomes. The technology assessment should have concluded that the weight of the available evidence supports the decisions of individual oncologists to make at least selective use of these assays in their clinical practices. If the so-called respectible Journals (the ones that fail to adhere to guidelines on conflict of interest) won't publish articles because they have a lock-up on information, don't lay blame on me. If trials show that an assay-directed group actually did better than a physician's choice group, but because these are small and non-randomized studies, it is concluded that efficacy hasn't been proven. No one has ever said or represented that cell culture assays have been proven to be efficacious in randomized trials, just that the tests are accurate and that accuracy has always been the standard used to evaluate tests. 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 also 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. But, just because trials may have never been done, this should not be the reason for an medical oncologist to refuse to have the tests performed. There is so much misinformation about the cell culture assay tests being perpetuated. All the important progress in cell culture assays has come outside of NCI-sponsored university-based research and it strikes at the heart of the standard NCI/university clinical research paradigms. That's why many doctors have not yet made the effort to learn about this. Because of the efforts of a dedicated private sector and the availability of media such as the Internet, the NCI and NCI-oriented institutions will soon find themselves in the position of having to make the effort to learn and to be forced to provide sound reasons if they choose not to use these tests in the management of individual patients. If you cannot understand this Michelle, you never will. Why is ASCO afraid of having an "open," "ambiguous," and "transparent" tech assessment? One like NHIC Medicare did. Let ASCO bring it on! |
| What Is The Issue With Cell Culture Assay Tests? |
| posted by Gregory D. Pawelski on 09 Aug 2007 at 5:49 am |
|
As with any other laboratory tests in cancer medicine, the determination of the efficacy of cell culture assays is based on clinical correlations (comparisons of laboratory results with patient response). That is, above-average drug effects in the cell culture assays correlate with above-average drug effects in the patient, as measured by both response rates and patient survival. The standard of retrospective correlations between treatment outcomes and laboratory results is sufficient in the case of all laboratory tests.
The markers ER and Her2/neu correlate with and predict for tumor response and patient survival. Imagine if these laboratory tests may only be judged on the basis of the proven ability of the tests to improve treatment outcomes in clinical trials in which patients are managed with and without the information provided by the tests? In other words, judged only by studies in which comparisons are made of the treatment outcomes of groups of patients managed with the benefit of the information provided by these tests, compared to the treatment outcomes of patients managed without benefit of the information provided by these tests. You'd say, "Wait a minute, neither the ER nor the Her2/neu tests are ready for prime-time players." That's what ASCO and private insurers are doing with cell culture assay tests. Michelle is trying to invent a brand new criterion for validating a laboratory test. The existing standard has always been the accuracy of the test. This is true for every single test used in cancer medicine, from estrogen receptors to bacterial culture and sensitivity testing to panels of immunohistochemical stains to diagnose and classify tumor to Her2/neu and CA-125 to MRI scans, CT scans, PET scans and on and on. PET scans were not apporved because they saved lives in a controlled clinical trial that compared the outcome of patients who received care with or without the benefit of a PET scan. They were approved because their performance characteristics (sensitivity/specificity) are reporducible, favorable and provide useful information to treating physicians. Cell culture assays have performance characteristics that are reproducible, favorable and provide useful information to treating physicians. In an effort to establish treatment guidelines, even the chair of the Community Oncology Alliance's QSP Committee states that ASCO has technology assessments that are very limited and updates which are not timely (and as we now know, not 'open'). The only tech reviews that were negative for cell culture assays were the "closed" reviews (e.g. BC/BS and ASCO), where they never even attempted to review the voluminous literature which defined the accuracy of cell death assays. But the two "open" reviews by NHIC Medicare and California Blue Shield where everyone had the chance to present their data and make their case, were both quite positive. There is an inherent conflict of interest when organizations that provide guidelines for treating a disease also receive funding from corporations that benefit financially from the recommended treatment. In the "closed" ASCO tech assessment, they lumped together the old and long abandoned technologies (clonogenic assay, subrenal capsule assay, etc.) with the cell death assays. And yet, even in their own review, there were five studies with cell death assays and patient outcomes that were improved in four of the five studies and one negative study wasn't even relevant, because the authors did their tests on subcultured cells (as opposed to "fresh" tumor cultures) and tested the cells in monolayers (as opposed to three dimensional cell clusters). They ignored all studies having to do with accuracy, the criteria used in tech assessments of all previous laboratory and radiographic tests. Even the ASCO tech review specifically stated that it excluded from coverage papers which only related to test accuracy and there were no other tests which had ever been judged on anything other than accuracy. Were they to review studies showing that the use of estrogen receptor improving treatment outcomes, they would have found no publications at all. Were they to have reviewed papers showing that the use of panels of immunohistochemical stains to subclassify tumors improved treatment outcomes, they would have found no publications at all. Were they to have reviewed studies showing that treatment outcomes were improved through the use of MRI scans or PET scans or CT scans to monitor growth and shrinkage of tumors (for the purpose of influencing the decision to continue the same chemotherapy or to change chemotherapy), as opposed to simply following patients with history, physical, simple plain radiographs, and simple lab tests, they would have found no publications at all. A valid tech review would have started with the published accuracy of the tests, and would have included in excess of 2,000 published correlations, in all types of neoplasms from acute leukemia to breast cancer to ovarian cancer to colon cancer and so forth, every single one of which showed that patients treated with drugs "active" in the assays had significantly higher response rates than patients treated with drugs which were "inactive" in the assays. They would have noted a half dozen papers which also showed that patients treated with drugs "active" in the assays also enjoyed significantly longer survivals. They would have made note of the preliminary studies which supported the concept that the use of the assays influenced treatment decisions which resulted in superior outcomes. The technology assessment should have concluded that the weight of the available evidence supports the decisions of individual oncologists to make at least selective use of these assays in their clinical practices. If the so-called respectible Journals (the ones that fail to adhere to guidelines on conflict of interest) won't publish articles because they have a lock-up on information, don't lay blame on me. If trials show that an assay-directed group actually did better than a physician's choice group, but because these are small and non-randomized studies, it is concluded that efficacy hasn't been proven. No one has ever said or represented that cell culture assays have been proven to be efficacious in randomized trials, just that the tests are accurate and that accuracy has always been the standard used to evaluate tests. 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 also 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. But, just because trials may have never been done, this should not be the reason for an medical oncologist to refuse to have the tests performed. There is so much misinformation about the cell culture assay tests being perpetuated. All the important progress in cell culture assays has come outside of NCI-sponsored university-based research and it strikes at the heart of the standard NCI/university clinical research paradigms. That's why many doctors have not yet made the effort to learn about this. Because of the efforts of a dedicated private sector and the availability of media such as the Internet, the NCI and NCI-oriented institutions will soon find themselves in the position of having to make the effort to learn and to be forced to provide sound reasons if they choose not to use these tests in the management of individual patients. If you cannot understand this Michelle, you never will. Why is ASCO afraid of having an "open," "ambiguous," and "transparent" tech assessment? One like NHIC Medicare did. Let ASCO bring it on! |
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