PHARMA/POLICY/POLITICS: November comes after September

Interesting article in the WaPo about the impact of the donut hole in Part D on the Senior vote. I think it will matter, it will hurt the Republicans and the signs seems to be point that way in one House race in Florida. Of course whether it will matter enough to push the House over to the Democrats is another matter. But the most interesting stat in the article is buried on the second page.

Perhaps playing in Klein’s benefit: More seniors are finding themselves
in the doughnut hole as the election approaches. The Institute for
America’s Future, a group calling for the closure of the gap,
calculated that, on average, seniors who enrolled in the benefit at the
beginning of the year would have fallen into the doughnut hole on Sept.

So this problem will get worse all the way up to election day, and the greed fest known as the Medicare Modernization Act (of which to be fair the greed of big Pharma was only one small part) may play a factor. And if it does, the obvious change that the Democrats would now put in the bill would be negotiated pricing.

That was not what Pharma wants, but of course it’s a maybe and the CEOs of big Pharma who pushed the bill through are leaving their posts and leaving the potential consequences to their successors. My guess is that those successors will wise up and figure out how to cut a more reasonable deal so that they are not so squarely in the gun sights when the nation has a real debate about health care costs in a few more years.


35 replies »

  1. NCI’s Failure at assay-directed therapy
    Good review papers exist on cell culture assays and are increasingly appreciated, understood and applied by the private sector and European clinicans and scientists. The literature on these assays have not been understood by many NCI investigators and by NCI-funded university investigators, because their knowledge was almost always geared towards an assay technique (cell-growth) that hasnt’ been used in private labs for over fifteen years now.
    NCI studies never determine if “fresh” tumor assays worked. All of the considerable literature which supports the use of these assays in patient management has been based on true “fresh” tumor (non-passaged) cell assays.
    Some years ago, NCI made an attempt to study “assay-directed” therapy of lung cancer. The study was a failure because it was done with established permanent cell lines (instead of fresh cells), which have been conclusively proven to have no predictive value at all with respect to the clinical activity spectrum. The result was a dismal 11% response.
    The NCI used “cell lines” because the major expertise of the investigators who carried out any study was in the creation of cancer cell lines, and they wanted to see if they could perform assays on these cell lines to use in patient therapy. The results showed they were able to test successfully only 22% of specimens received, including only 7% of primary lesions.
    This contrasts with a 75% overall success rate reported by earlier investigators who used the same assay system in “fresh” tumor and a routinely obtained >95% success rate using improved (cell death) methods available today.
    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.
    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. Dan Von Hoff published a paper around 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.
    And the fact that “proving” efficacy in one situation would do nothing to prove efficacy in any other situation. This is why the FDA demands clinical trials data showing efficacy for each and every indication relating to drugs.
    Let’s say a plan assay-directed clinical trial in relapsed NSCLC proves efficacy. All we prove is that it improves things for one small indication. Relapsed NSCLC, not ovarian cancer. And it gets worse. The year after the close of the study, two new drugs become available and the assay-directed clinical study only proves efficacy with the old drugs. It doesn’t prove efficacy involving the new and improved drugs. A constantly moving target. So then you say, just go out and get a grant to do another one.
    Sounds like the Twilight Zone.

  2. Favorable local coverage decision (LCD) regarding Medicare payment for Cell Culture Assay Test
    Cell culture assay technology has been clinically validated for the selection of optimal chemotherapy regimens for individual patients. It is a laboratory analysis based on tumor tissue profiling that uses fresh human tumor biopsy or surgical specimen to determine which drugs or combinations of chemotherapeutic agents have the highest likelihood of response for individual cancer patients. Individualized assay-directed therapy is based on the premise that each patient’s cancer cells are unique and therefore will respond differently to a given treatment. This is in stark contrast to standard or empiric therapy, which chemotherapy for a specific patient is based on average population studies from prior clinical trials.
    ASCO’s 2004 tech assessment focused on an older cell-growth assay method and not on a newer cell-death method, which is the most relevant biological measure. Their panel made no attempt to distinguish cell-death from cell-growth techniques. Their conclusions simply did not apply to cell-death assays. In fact, cell-death assay results have consistently correlated with response, time to progression, and overall survival.
    The ASCO paper focused solely on a lack of prospective, randomized clinical trials proving superior outcomes with assay-directed therapy, a standard not met by ER/PR testing, HER2 protein or gene analysis, or any other clinical test in cancer medicine, and has seldom been met by even the eimpiric chemotherapy treatments supported by ASCO. Were they to apply the standard measure of predictive test accuracy, the results of their analysis would have been much different and in favor of the use of cell-death assays in clinical practice.
    This omission was so significant that Medicare contractor, National Heritage Insurance Company which spent six months reviewing everything about the cell culture assay, including all of the ASCO arguments, and upon reviewing all available information, approved Medicare coverage for the tests. They made the courageous decision to reverse trend and noted that the ASCO paper had failed the consider any of the many studies which support the predictive accuracy of cell death-based in vitro chemosensitivity testing.
    The decision had been made that the assay is a perfectly appropriate medical service, worthy of coverage on a non-investigational basis. What is of particular significance is that they are finally abandoning the artificial distinction between “resistance” testing and “sensitivity” testing and are providing coverage for the whole FDA-approved kit.
    Cell cuture assay tests based on cell-death have proven very effective in identifying novel treatment combinations for a variety of cancers. It is unfortunate that ASCO had not carried out studies to assess the value of cell-death assays, because they can and do accurately predict clinical outcomes and define novel chemotherapeutic synergies. In many cases, these same tests have induced highly durable remissions in patients whom current medical literature have deemed otherwise hopeless.
    (Note) Medicare coverage is available for Chemosensitivity (Resistance) Testing for a tumor specimen from a Medicare patient obtained anywhere within the United States, but submitted for testing by one of the approved laboratories located within California.
    Source: http://www.medicarenhic.com/cal_prov/policies.shtml

  3. I once thought Michelle A. had a particular agenda, but now I feel she’s flakier than first perceived (a blog groupie). Excuse Me!

  4. Notice, the logical fallacy:
    Argument By Repetition (Argument Ad Nauseam):
    if you say something often enough, some people will begin to believe it, i.e. reposting the same fallacious premise presumably in hopes it will have that effect.
    It’s an endless mantra from him and the “alternative” medicine crowd.
    Here’s what I mean:
    “Michelle harps on the fallacy that assay tests have no proof. What “proof” does “one-size-fits-all” cancer treatment have?”
    This is it. This is what he has to resort to to prove to nonbelievers that his assays show benefit. He has to criticize “”one-size-fits-all” cancer treatment.” You might believe, as he has stated, that if YOU get the treatment another earthling has received, without individualization, hang it up. Sort of a To Quoque fallacy.
    “It hasn’t been proven that most things medical oncologists do make any difference at all.”
    Oy. Notice no data, again. Just over-the-top comments without meaning OTHER than to stoke fear in the patient who reads his words.
    (An aside: Just my opinion…. “nice legacy”.)
    Brings back memories of the ol’ Condi mushroom cloud comment.
    “If that is a reason, patients should never have any x-ray studies or laboratory tests performed..”
    This is, again, fallacious. I’ve given a nice response to this above when I wrote discussed bile acids. (Search this page for “bile”.)
    But, then he states in the NEXT PARAGRAPH:
    “could be obtained by monitoring treatment results with history, physical, and simple blood tests.”
    So no labs should be performed unless you want want to do lab tests.
    Huh? This is much like saying “I never borrowed his car.
    It already had that dent when I got it.”
    Finally, one often sees this in the post of the alties and Mr. Pawelski:
    His posts can be categorized, in general, is a classic Fallacies of Presumption because they creates the presumption that the true premises are complete.
    Most dogs (assays) are friendly and pose no threat to people who pet them. Therefore, it would be safe to pet the little dog that is approaching us now.
    That type of car (one-size fits all) is poorly made; a friend of mine has one, and it continually gives him trouble.
    We sometimes see this fallacy committed in scientific research whenever someone focuses on evidence which supports their hypothesis but ignores data which would tend to disconfirm it. This is why it is important that all experiments can be replicated by others and that the information about how the experiments were conducted be released. Other researchers might catch the data which was originally ignored.
    Mr. Pawelski offers no evidence that assays offer any benefit greater than one-size-fits-all. What he does do, and this must be made clear, is simply attack one-size-fits all (all those cars are bad)and claim superiority for assays (“go ahead, pet my dog – he’s like all the others”).
    But, somehow, you probably knew that. The government knows it. Industry knows it. And the assay scientists know it.
    THAT is precisely why they won’t be approved until they show some, any, benefit.
    Until then, I’ll reserve my opinion.

  5. Michelle harps on the fallacy that assay tests have no proof. What “proof” does “one-size-fits-all” cancer treatment have? It hasn’t been proven that most things medical oncologists do make any difference at all. First-line chemotherapy of many types of tumors. Second-line chemotherapy of virtually all types of tumors. High-dose chemotherapy of breast cancer.
    What is the standard Michelle tries to apply to cell culture assays, as the most appropriate situation? Proof? There are precious few treatments available for cancer beyond surgery and radiation therapy for local control. Cell culture assays are a test, not a treatment. You may “try” to argue proof beyond reasonable doubt against the use of cell culture assay tests, but the weight of currently available evidence argues in favor of their use. Of course, ASCO doesn’t want that evidence included in their “closed” tech assessements.
    It has never been shown, with any laboratory or radiographic test, that the use of the test improves treatment outcome compared with “physician’s choice” treatment. If that is a reason, patients should never have any x-ray studies or laboratory tests performed, because they have never been proven to improve outcomes. This goes for estrogen receptors, DNA analysis, bacterial culture and sensitivity tests, CA-125 levels, CT scans, MRI scans, bone scans, and every other test. It even goes for the practice of making a tissue diagnosis before definitively treating the cancer.
    An entire generation of academic oncologists has been trained in the paradigm of the empiric, randomized trial to select the best regimen for the average patient and an entire generation of practicing oncologists have been trained to use these empiric regimens in the management of their patients. Trained to make extensive use of expensive, latest-generation radiographic tests and second-look surgeries to measure tumors before and during therapy to monitor and document “response” or “progression,” despite the absence of even a shred of evidence that such radiographic and surgical documentation does anything at all to improve outcome beyond that which could be obtained by monitoring treatment results with history, physical, and simple blood tests.
    I don’t believe Michelle has a clue what is done, how it is done, the rationale, the data, the practicality, or anything else about cell culture assay tests. I wouldn’t expect her to. Before she accuses me of doom and gloom with cancer patients, I don’t think a single randomized clinical trial in any solid tumor cancer should be performed until someone can claim at least an 80% response rate.

  6. What’s interesting is that Mr. Pawelski and I would like to see more effective treatments for cancer.
    The trouble arises when there is mere speculation treated as fact, a speculation that creates fear in patients he claims to help.
    He has finally softened his certitude:
    my point with respect to cell culture assay testing is to educate patients that such techniques exist, and MIGHT be very valuable.
    (This is a needed change in his blog posts.)
    Yet, in the same post he says:
    “The way she was treated by “one-size-fits-all” cancer treatment should NEVER happen to ANOTHER human being.”
    (A lot of certitude there.)
    I mean, this is a ridiculous statement that lacks any understanding of the disease process. I could imagine every patient getting blood cultures and urine cultures for bacterial growth every time symptoms crop up and a WBC rises. Boy, would that bankrupt us.
    He throws out the scientific method because he thinks we are so “tumor different” that it’s absurd to treat with the knowledge we have gained over decades and yet refuses to acknowledge that, in fact, cancer is a very difficult disease to treat. That is why we are making such inroads into early detection. Those in the know KNOW that prevention is very key. Why do we tell nurses and docs to wash their hands in the hopsital to prevent transmission of infectiion? Why do we tell people to quit smoking? Why do we tell patients with ovarian cancer family histories to get an oophorectomy, get a BRCA 1?
    OK, so he’s talked to noted authorities. This is another logical fallacy called Appeal to Misleading Authority.
    Authority A believes that P is true.
    Therefore, P is true.
    I highly recommend the section entitiled “Exposition”
    for a discussion of this fallacy. You will see this fallacy time and time again on medical blogs. And this is but one of many, especially in a number of Mr. Pawelski’s posts.
    This is precisely why his assays are unapproved. A beginner’s understanding of logical fallacies will see this and those versed in the scientific method may not be able to name the fallacies, but they know them and make correct decisions based on them.
    I recommend reading all posts on health blogs with a level of skepticism, not cynicism, but skepticism, especially those emotionally charged, as his often are…. THE reason of why he started on this path in the first place.
    (As an aside, I also cared for my loved one for 6 years until she died in our home. I was very grateful for having those incredible last years with her.)
    Fortunately, as we know, very few people read these blog posts or any particular blog regularly. And, decisions made based on them are probably nil. However, Mr. Pawelski posts on many blogs and newsfeeds and he has been unchallenged for years. So, I am one who has thrown down the gauntlet. Why? I probably wouldn’t have started, but he reminds me so much of alternative medicine posters who take it upon themselves to create fear in those looking for help. His proclamations of doom bring back memories of my loved one who, for a time, chose to not undergo treatment, in favor of alternative methods that went to the “heart of cancer treatment.” Well, you can imagine what happened by putting off treatment.
    Mr. Pawelski’s statements of “authority” and barrage of postings appear to the unitiated and the vulnerable as statements of fact. And, they respond to these, yet are very unaware of the fallacies that exist.
    So, I’ll continue to respond to him and I’ll let the scientists who toil in the field daily respond to the assay merchants.
    Again, until any assay benefit data is available, despite what you may here from bloggers about accuracy, one-size-fits-all, yada yada yada, proclamations, all you are hearing are warnings that you are doomed and empty promises from an imagined white knight.

  7. I assured Matt that I am not gaining any financial benefit by promoting this technology (let alone selling anything). On the internet, my point with respect to cell culture assay testing is to educate patients that such techniques exist, and might be very valuable. Especially when active chemoagents are limited in a particular disease, it makes more sense than ever to test the tumor first.
    I was a spouse/caregiver to an ovarian cancer patient. I became intensely interested in cancer medicine by virtue of working through, enduring and surviving my wife’s illness. I’ve gotten a street education by virtue of voluminous reading and hundreds of hours of past and continued, ongoing personal communication with noted authorities in the field.
    Matt is right. The way my wife was treated for her cancer inspired my interest in this subject. The way she was treated by “one-size-fits-all” cancer treatment should never happen to another human being.

  8. Well done the two of you for keeping this up!
    Meanwhile, I don’t know anything about the science of all this but I do know that a) there is clear evidence of overuse of chemotherapy by oncologists who are definitely incented to use drugs by the way they get paid, and b) the NEJM study on OncotypeDX Testing suggests that if we looked at the subject more closely instead of dismissing it out of hand, we might discover more. So I wouldn’t be so certain, either.
    If Greg is gaining any financial benefit by selling this test I’m sure he’d tell us. His interest in the subject as far as I’m aware is because of his wife’s treatment during her chemotherapy.
    The Quackwatch article Micelle cites claims that there’s no evidence, it doesn’t claim that it’s quackery. IT reminds me a little of the emdical marijuana debate where the Feds say there’s no evidence from clinical trials, but then ban the trials!
    Good luck to both of you.

  9. The greatest poison in all the world is an overdose of certitude. You certainly have that Michelle A. I’ve got to had it to you, you certainly have it.

  10. 1.I don’t work for oncologists.
    2.There’s no evidence that individualized chemotherapy assays are good science because there is no science.
    3.No evidence of lives saved if pretesting was incorporated. None.
    4.”The objective of pre-testing is to provide the patient with more options to discuss with their oncologist and to bring about multimodality approaches to IMPROVE the probability of a successful outcome.”
    No evidence. None.
    5.”having a lot of tools (drugs) available and making use of various assay tests can match treatment to the patient.”
    Completely unproven with respect to chmotherapy assays. No benefit has ever been shown.
    That’s why this assay blogger is incorrect again. He repeats the mantra over and over and gets nowhere, evidenced by the fact that his assays are unproven and unapproved.
    While he loves to create fear in cancer patients (hard to believe a human would do that, isn’t it?) and loves to point out on blog after blog that you, the cancer patient are “doomed” as he has said, the research continues and we’ll know in the future whether his unproven assays have any merit whatsoever.

  11. I understand your frustration Michelle A., when good science (individualized treatment) trumps bad science (one-size-fits-all). There is seldom a “standard” therapy which has been proven to be superior to any other therapy. Even NCI admits that.
    The respected cancer journals are publishing articles that identify safer and more effective treatment regimens, yet few oncologists are incorporating these synergistic methods into their clinical practice. Cancer patients often suffer through chemotherapy sessions that do not integrate all possibilities.
    Chemotherapy drugs have a high rate of failure because they usually kill only specific types of cancer cells within a tumor or the cancer cells mutate and become resistant to the chemotherapy. Cancer chemotherapy could save more lives if pre-testing were incorporated into clinical medicine.
    It is impossible to design a single chemotherapy protocol that is effective against all types of cancer. The oncologist might need to administer several chemotherapy drugs at varying doses because tumor cells express survival factors with a wide degree of individual cell variability.
    The objective of pre-testing is to provide the patient with more options to discuss with their oncologist and to bring about multimodality approaches to improve the probability of a successful outcome.
    I know your bosses cannot come to grips with this. Perhaps you can educate them? The best chance for discovering the right formula is having all the drugs available to oncologists, and allow creativity and insight and the “Art of Medicine” enter into the process. A “standard” therapy would not be for everyone, but having a lot of tools (drugs) available and making use of various assay tests can match treatment to the patient.

  12. “They’re here, you’ll just have to get use to it!”
    Is this your NYAH, NYAH! moment?
    As our boy, Dubya says, “Bring it on!”
    But let’s not do it from blind faith, as he likes to run the country, but from evidence of benefit, from which tests are approved. Unfortunately, assay researchers, as opposed to the typical assay blogger who likes to say, “Honey, you will die without my assay,” know that research, is required to show benefit.
    Yes, we’ve already addressed the stale “accuracy is good enough” fallacious myth and that is why these apoptosis tests are not approved….yet. (I’ll give you that, OK.) All we have are testimonials from these pushers of unapproved technology, prominently displayed on their web sites. We need not go into the utter ridiculousness of testimonials. Most schooled in science laugh at this.
    For a very good look at testimonial value, read “The Value of Testimonials” here:
    So, here we are again, awaiting any research on the benefit to mankind of apoptosis assays. Until then, I will reserve my opinion unlike the typical assay blogger who, hopefully unsuccessfully, tries with all his might to create fear in cancer patients that they are, as one has been known to say, “doomed.”
    I mean, isn’t that all he’s doing, anyway? He thinks he benefits them, but there is not a lick of data to say so. Because of this he makes unsubstantiated statements that all those hard at work on cancer are charlatans.
    But, his assay pushers aren’t. He does say,
    “These private companies are successfully achieving what the NCI and American universities could not and would not do – the introduction of these tests into the mainstream practice of American cancer medicine.”
    Notice, he wants them introduced with no evidence of benefit. Hmmmm. Yet, there is benefit for some, isn’t there?

  13. Michelle A. Your oppositition to cell culture assays has been erected to protect the paradigm of the best empiric treatment for the average patient, as identified in traditional clinical trials. This opposition served to protect the paradigm of drug selection with consideration of the spread between wholesale cost and reimbursement. As we have seen, the conventional approach is not working.
    It is extraordinary difficult to prove the efficacy of chemotherapy in general and of specific drug regimens in particular in studies of empiric-directed chemotherapy. Only with extremely large studies has it been possible to document that chemotherapy of any type produces survival advantages compared to no chemotherapy at all, in many clinical situations.
    The private sector laboratories offering cell culture assays as a patient service have been able to make considerable progress in improving the assay technologies and in building databases which improve the interpretation of raw assay results. This progress has been possible because clinicians have wanted to have the information provided by the tests.
    This is a tribute to the genius of the American private enterprise system. Small companies, supported by venture capital, private and institutional investors, the sweat equity of their founders, and an occasional Small Business Innovative Research Grant. These private companies are successfully achieving what the NCI and American universities could not and would not do – the introduction of these tests into the mainstream practice of American cancer medicine.
    They’re here, you’ll just have to get use to it!

  14. “There are a number of scientists from respected research facilities across the United States that say much of what is known to be true about cancer is false.”
    Who? What’s false? What’s true?
    “Many of the basic assumptions and theories that are driving most of today’s cancer research are false.”
    Really? Data please.
    “..clinical trials of cancer drugs are failing with painfully predictable regularity.”
    Really? What’s failure?
    “Some researchers say…”
    Who? YOU? You’re a researcher? I doubt it.
    “Drugs have been made to target and kill cancer cells.”
    You have so little understanding of cancer physiology and the difficulty in treating disease. Your comments are flip, disrespectful, and lacking in evidence.

  15. We have produced an entire generation of investigators in clinical oncology who believe that the only valid form of clinical research is to perfrom well-designed, prospective randomized trials in which patients are randomized to receive one empiric drug combination versus another empiric drug combination. Cancer patients can’t wait another ten years to learn what is already known.
    There are a number of scientists from respected research facilities across the United States that say much of what is known to be true about cancer is false. Many of the basic assumptions and theories that are driving most of today’s cancer research are false. There has been almost no improvement in the cure of most types of metastatic cancers over the last thirty years.
    Despite the media hype about the breakthroughs, clinical trials of cancer drugs are failing with painfully predictable regularity. “Chronic control” has replaced “cure” as the goal of many in the research community. Some researchers say insufficient consideration has been given to the requirements for the “cure” of cancer without significant toxicity to the patient and without severe side effects.
    Most cancer research has focused on discovery of the differences between cancer cells and normal cells. The hope has been that these differences can provide a basis for understanding and targeting cancer cells. Drugs have been made to target and kill cancer cells. But the truth is that despite these drugs, patients continue to suffer and die of cancer at virtually the same rate. What is known is that the conventional approach is not working.

  16. Mr. Pawelski:
    So what?
    So treatment hasn’t improved for a difficult-to-treat disease. From this I guess an illogical person would say, “well, Mr. Pawelski’s breakthrough must do a better job.”
    However, logic is on the side of the scientist. So the inference is false.
    Here are some logical fallacies in the presentation put forth by the typical (I think there actually is only one) cell assay blogger:
    *Appeal to impending acceptance
    I consider this to be a subtype to the argument from authority, because it attempts to invoke the authority of future belief and acceptance. Many peudosciences, such as creationism, ESP, and UFOlogy, claim that broad acceptance is right around the corner. This is a logical fallacy (the argument from authority) coupled with an assumed premise (that of future acceptance).
    *Argument from authority
    The basic structure of such arguments is as follows: Professor X believes A, Professor X speaks from authority, therefore A is true. Often this argument is implied by emphasizing the many years of experience, or the formal degrees held by the individual making a specific claim.
    *Argument from Conspiracy or anti-authority
    This is the converse of the argument from authority, and basically states that a claim is false because it is held and promoted by an authority. This occurs often in the context that the official government position must be false because it’s the official government position. This is more properly considered a subtype of ad-hominem logical fallacy, arguing that the government must be wrong because they habitually lie or engage in cover-up conspiracies.
    *Appeal to Fear
    The appeal to fear is an argument from consequences, but in this case the consequences are individually relevant – an outcome to be personally feared. For example, assay proponents often argue that you should accept the claims of their unproven methods for if you reject them you risk death.
    *Tu quoque
    Tu quoque translates to “you too.” This is an attempt to justify wrong action because someone else also does it (two wrongs make a right). “My evidence may be invalid, but so is yours.” This fallacy is frequently committed by proponents of various alternative medicine modalities, who argue that even though their therapies may lack evidence some mainstream modalities also lack evidence. We se this in his attempt to fire back at the critics of assays by condemning their research, but of course, he avoids the fundamental problem, they have no research on benefit at all…yet.
    FINALLY (but certainly, not complete)
    *Confusing absence of evidence with evidence of absence
    This fallacy cuts both ways. In other words, one might assume that absence of evidence is a compelling argument against the reality of a claim or phenomenon. On the other hand, however, one might dismiss the absence of evidence as having no significance – as not being evidence of absence.
    In reality, the absence of evidence can only be properly considered in the context of how likely it is that evidence should exist. You must therefore consider how thoroughly evidence has been looked for, and if the tools and techniques employed are capable of finding evidence.
    There are tools to find evidence and those studies have begun. Until then, I reserve my opinion.
    It’s logical.

  17. Other than ASCO, GOG’s history of establishing treatment standards for ovarian cancer, including platinum therapy trials and again with combination Taxol/platinum trials, have a lot to be desired. Landmark meta-analysis published in the 90’s, described that it has NOT been shown that platinum-based combination therapy is superior to single agent alkylator therapy. Yet many would maintain that not to treat an ovarian cancer patient with platinum is tantamount to malpractice. This position cannot be supported, and is, in fact, refuted by prospective, randomized clinical trials.
    The largest ever international clinical trial of treatments for ovarian cancer concluded that standard initial chemotherapy drug treatments for women with ovarian cancer are equally as effective adding the drug paclitaxel (Taxol) to those treatments, and also cause fewer side effects. The study’s results suggest that, for initial treatment of women with ovarian cancer, widely used standard drugs are equally as effective as treatments that include paclitaxel and, on balance, standard treatments such as carboplatin may be considered the preferred treatment as they have fewer side effects.
    At the end of the day, the only clear conclusion possible after more than 20 years of these cooperative group trials of empiric chemotherapy in ovarian cancer is that there is no clear and meaningful advantage associated with any form of therapy ever examined in these trials.

  18. “The traditional criteria ever used to evaluate laboratory tests has been the predictive accuracy of the test.”
    Again, not true. Not sure how much he really knows about microbiology, physiology, the disease process, etc.
    A simple example:
    The U.S. Food and Drug Administration (FDA) has granted Diazyme 510(K) clearance to market its Enzymatic Total Bile Acids (TBA) Assay Kit for the quantitative determination of total bile acids in human blood samples.
    Must be because it’s “accurate,” his favorite, and only buzzword.
    But, is THAT why we examine bile acids, just to say “hey, we have bile acids here!”
    Well, nope.
    Total bile acids is a well known bio-marker for diagnosis of liver diseases. Serum total bile acids are elevated in patients with acute hepatitis, chronic hepatitis, liver sclerosis, and liver cancer. Total bile acids levels are found to be the most sensitive indicator for monitoring the effectiveness of interferon treatment of chronic hepatitis C patients. Moreover, total bile acids tests are also widely used to screen pregnant women for the condition of obstetric cholestasis, a disease that is caused by elevated total bile acids in the bloodstream of pregnant women. This poses and risks to the unborn baby including stillbirth, premature labor and bleeding. The frequency of obstetric cholestasis is found to be 1 in 100 pregnant European women, and 1 in 10 pregnant South American women. Cholestasis treatment includes the drug Urso.
    Well, look at that.
    -We have a disease process that can be identified by elevated bile acids.
    -We have an accurate tool to allow us to make decisions about treating diseases caused by elevated bile acids.
    -This can be monitored to look for resolution or worsening.
    -We have treatment for disease cause by elevated bile acids.
    So we have a test that monitors an established disease process WE KNOW that causes problems and WE KNOW that has solutions.
    Unfortunately, we see nothing like this at all from chemotherapy cell culture assays. Why? Because there is absoutely no evidence that his assays do anything whatsoever to legitimately, unerringly, diagnose a disease process and can be of any help in affecting the treatment protocol. We have no data to back up his claims that the disease process will be altered by his tests. We know addressing bile acids will because we know a lot about bile acids. We know it’s beneficial to have results WNL and it’s detrimental not to.
    We have no such evidence at all that his assays are of any benefit.
    He wants us to pay for his unproven tests. But, it’s not going to happen. It may in due time, but that will occur, as the real scientists know who work quietly in the background, away from the blogosphere, when scientists make the decision.
    Blogging it into existence ain’t happening.

  19. From someone who has no understanding about cell culture assays, I can understand that Michelle A. doesn’t know that the assay is approved. They have been extensively validated for predictive accuracy. The traditional criteria ever used to evaluate laboratory tests has been the predictive accuracy of the test.
    The needed change in the “war on cancer” will not be on the types of drugs being developed, but on the understanding of the drugs we have. The system is overloaded with drugs and underloaded with the wisdom and expertise for using them. Something the randomized clinical trial hasn’t been able to do.

  20. Ad hominem man is back! Pawelski backs up his pronouncements with…
    that’s right, no evidence.
    But, then again, there is no evidence of assay benefit and THAT is why they aren’t approved.
    Of course, a lack of evidence never stops some people from emotionally charged declarations.

  21. Matthew,
    According to a WSJ editorial this morning about the Medicare prescription drug program, the VA has only included 19% of the drugs approved by the FDA since 2000 for inclusion in its formulary. While I suppose this is one way to control costs, it does not look like an especially attractive model for nationwide replication. I also wonder how this squares with Genentech’s successful strategy of convincing hospitals in the 1980’s that they would be wise to use expensive Activase if they wanted to avoid being sued if they didn’t.

  22. I’m beginning to believe that Michelle really has no understanding about cell culture assays at all. I can accept that. She just loves to blow smoke for the sake of blowing smoke. It would be fruitless to re-adjust her misalignment.
    The much needed reforms to the system which are currently ongoing are occurring over the opposition of a profession which is vastly more concerned with protecting the selfish monetary interests of its members than in promoting the well-being of cancer patients.
    ASCO has never felt the need to perform clinical trials to determine whether or not treatment outcomes and patient satisfaction are altered by profit incentives, although the joint Harvard/Michigan and Patterns of Care studies have documented it.
    One of the great overlooked achievements in cancer research was the brilliant work of a scientist named R. Schrek in the 1960s. He was perhaps the father of cell culture assays, as Judah Folkman is to angiogenesis. Dr. Schrek worked at the Hines VA hospital in Chicago, right up to his death at the age of 87 (in 1995).
    In his published work of over 30 years ago, there are obvious clues to a practicable testing method which should have been developed, long ago, to improve clinical research and drug selection in clinical patients. But, the drugs available in the 1960s were not all that great, and no one knew of the importance of a biological concept now known as apoptosis during the 60s, when Schrek published his work.

  23. “And there are obviously lots of situations where a rational oncologist and patient would conclude that the evidence from an accurate test would be of help to guide treatment.”
    There is no evidence of
    1. lots of situations
    2. irrationality
    3. help
    “No other lab test in history has anything other than evidence of “accuracy” to either commend it or condemn it.”
    Ridiculous statement without data.
    The truth:
    [G. Pawelski] is simply mistaken in suggesting that diagnostic accuracy indices (sensitivity, specificity, and positive and negative predictive values) are sufficient for establishing a test’s utility. As outlined by the Institute of Medicine,1 tests are clinically useful only if the information they produce leads to patient management changes that improve outcomes, such as longer survival, better quality of life, or fewer adverse events. Clinical utility can be determined by mapping a causal chain from diagnostic accuracy through changes in management to impact on outcomes.2 There is a lack of clarity about how CSRA results influence management decisions and there is insufficient evidence documenting their effect on patient outcomes.3 Similarly, one of the articles that Dr Nagourney cites on gene expression profiles in childhood leukemia concludes, “If patients are found to have a gene-expression profile that is predictive of a poor response to one or several chemotherapeutic agents, should those agents be omitted from their treatment? Not yet.”4
    (Familiarizing one’s self with the IOM’s position paper is a good idea.)
    Mr. Pawelski loves to make cancer patients feel fear, fear that they are “doomed”, as he often says, and that his assays may save them.
    Luckily, the researchers are doing the research quietly without preying on vulnerable patients.

  24. Michelle keeps “spinning” the same old inadequate and misleading arguments that the assays are unproven. The so-called “expert ASCO review” is a sad reflection on the incompetence of “closed” review panels. The tech reviewers failed to realize that they were evaluating a laboratory test and not a treatment.
    ASCO should honest and evaluate and report the “accuracy” of these assays. They should correctly note the lack of proof of “efficacy,” but at least evaluate and report the accuracy. The tests have been proven accurate. And there are obviously lots of situations where a rational oncologist and patient would conclude that the evidence from an accurate test would be of help to guide treatment.
    No other lab test in history has anything other than evidence of “accuracy” to either commend it or condemn it. If BC/BS and ASCO applied the same criteria to evaluate all laboratory tests as they applied to review cell culture assay testing, there would be absolutely zero laboratory or radiographic tests available to assist physicians in the management of cancer patients.

  25. Michelle,
    While I have no expertise to even offer an opinion as to whether these tests have any value or not, I would like to point out that CMS currently spends $650 billion per year between Medicare and its share of Medicaid. In that context, $1.4 billion might be worth investing on a pilot or experimental basis to see if enough expensive drug regimens can be eliminated by more precisely targeting patients most likely to benefit from them. If it turns out to be money poorly spent, stop spending it. If it saves the system a meaningful amount of money, keep doing it and continue to refine and improve the science.

  26. What does help is the truth, and the truth is, science requires some level of certitude.
    The cell culture assays this gentleman promotes have yet to show any evidence of benefit.
    He wants the 700,000 new Medicare cancer cases per year to get at least one cell culture assay at, let’s say, $2000 a pop.
    That’s $1,400,000,000 for an unproven test.
    But, wait. How can we afford this unproven test? Don’t the rich need tax cut extensions?

  27. Professing that there is no proof of this and no proof of that with cell culture assays, I feel that Michelle is a victim of her own certitude.
    I know the phrase “membership has its privileges” but that doesn’t help the health and welfare of cancer patients.

  28. “There should be an expansion of reimbursement to promote even greater utilization and development of laboratory-based mechanisms for improving the match between tumors and an ever-increasing number of partially effective and very expensive drug therapies.”
    Reimbursement is not for development. Now he wants insurance cos. to fund biotech development.
    “How Michelle blatantly misleads the public is that the traditional FDA criteria ever used to evaluate laboratory tests has been the predictive accuracy of the test, not efficacy.”
    In fact, this is not the case at all.
    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
    At this point in time, cell culture assays don’t get beyond Level 2 and THAT is even questionable. That’s why studies have finally begun.
    The FDA has responded to the industry by stating:
    The definition of a device is set forth at section 201(h) of the Federal Food,
    Drug and Cosmetic Act (the act) (21 U.S.C. 321(h)). It provides in relevant part:
    ‘‘The term ‘device’ * * * means an instrument, apparatus, implement, machine,
    contrivance, implant, in vitro reagent, or other similar or related article,
    including any component, part, or accessory, which is intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation,
    treatment, or prevention of disease, in man or other animals.
    Mr. Pawelski’s cell culture assays do not diagnose disease nor do they cure, mitigate, assist with treatment or prevent disease.
    Because the studies haven’t been completed yet.
    Yet he wants healthcare 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.

  29. How Michelle blatantly misleads the public is that the traditional FDA criteria ever used to evaluate laboratory tests has been the predictive accuracy of the test, not efficacy.
    Clinical efficacy is the basis for approving new cancer drugs. The vast majority of clinical trials performed are ones that test one chemotherapeutic regimen against another. And the result looked for in these trials is tumor response (shrinkage). Tumor shrinkage should not be the criteria for approving cancer drugs.
    The criteria of laboratory assay efficacy, as opposed to laboratory assay accuracy sounds reasonable, but it is unprecendented with regard to any other laboratory test ever evaluated. If ASCO wants to change the criteria that has always been established, they’re going to have to re-evaluate all the other laboratory tests used in the selection of treatments for cancer patients.
    Oncologists have been documented to use reimbursement (payment to the oncologist) as the most important criterion for selecting between the large array of otherwise equally acceptable regimens. Laboratory and diagnostic tests are a tool for the oncologist. The oncologist should take advantage of all the tools available to him/her to treat a patient.
    There should be an expansion of reimbursement to promote even greater utilization and development of laboratory-based mechanisms for improving the match between tumors and an ever-increasing number of partially effective and very expensive drug therapies.

  30. I agree with Barry in his interpretaion of the facts in reality (and laud the concept of CMS using QALYs for expensive drug coverage), but my point is that this has a political component–which may (just may) play out in November.
    And you can be sure that a single large monopsonistic pharmaceutical buyer would get much better prices, and control its budget much better than the private market has done. You need only look at the VA for an example. Pharma knows this, which is why the MMA was created the way it was!
    Meanwhile the economics of Rx dispensing are complicated, but Walgreen has a minimum $10 dispensing fee. I buy a generic there that costs $10 for a 30 day supply(i.e. the drugs themselves are almost free) If I buy a 3 month supply at Walgreens online it still costs only $11. So the likely answer is that 90 day generics will become common in stores at around $10-15–which will be similar to the Wal-Mart price

  31. Barry has a good point in regards to CMS lobbying for a change in the law to allow it to specifically consider cost in determining whether or not to cover some of the ultra expensive biotech cancer drugs. Patients, physicians, insurance carriers, and the FDA are all calling for predictive tests that allow for rational and cost-effective use of these drugs.
    There are molecular tests (like Oncotype DX) that can often prevent more costly and unnecessary chemo treatment by helping doctors pick patients who really need it. In breast cancer, that would be approximately 20 – 30% of patients. There are other tests that do this for lung cancer and ovarian cancer. For those that do need treatment, there are cellular tests (like EGFRx) that can test these molecularly-targetd drugs and can identify patients who benefit most from these “smart” drugs, by determining their efficacy. And it can identify situations in which it is advantageoue to combine targeted drugs with other types of cancer drugs.
    The FDA has approved the predictive accuracy of these diagnostic tests, but it’s a question, will the CMS pay for using them to solve some of the problems confronting a healthcare system that is seeking ways to best allocate resources? There should be an expansion of reimbursement to promote even greater utilization and development of laboratory-based mechanisms for improving the match between tumors and an ever-increasing number of partially effective and very expensive drug therapies.

  32. Peter – I doubt it. Wal-Mart is only offering this deal in the Tampa, FL market to start and will not roll it out to all of Florida until January, 2007. I have no idea when nationwide rollout will occur. This effort is clearly a loss leader for Wal-Mart on a fully allocated basis intended to help build traffic for the rest of the store. While they may buy the pills for $2.00 or so, their estimated cost to fill is between $6-$10 per prescription. Walgreens has the lowest cost to fill in retailing which outsiders estimate at $5.00 because it fills many more prescriptions per day (250-300 or more in most stores) than any other retail pharmacy chain. By contrast, many supermarket pharmacies fill 100 per day or fewer, but they feel they need to have a pharmacy to be a full service supermarket. If they didn’t, they would sell fewer very profitable health and beauty aids, and some customers may not shop in their store at all.

  33. So, is Walmarts move to sell $4 prescriptions in Florida an attempt to influence the elections by numbing the donut hole?

  34. There are several things worth noting here. First, the estimate of 3.4 million seniors who will reach the doughnut hole this year amounts to fewer than 10% of enrollees, and many of those will likely incur only a few hundred dollars of cost while in it as compared to the potential maximum doughnut hole exposure of $2,800. Second, many of the Part D options in the marketplace cover the doughnut hole at a reasonable premium, and more will do so next year.
    With respect to drug pricing, fully 20% of all prescriptions filled are among those that Wal-Mart will start to offer in Florida for $4.00 per 30 day supply. Industrywide, over 50% of all prescriptions are already generics, and numerous high selling drugs are going off patent over the next couple of years.
    On the issue of the government negotiating prices, it is unclear to me how much it thinks could be saved vs the current system unless it has price controls or dictated prices in mind. If, like Medicaid, it is contemplating a relatively small margin above the average manufacturer’s price (AMP), it will likely be disappointed. For the retail pharmacies to stay in business, they need to be paid a reasonable professional fee to cover the salary and benefits of their pharmacists and techs, store rent, information systems costs, etc. Walgreens recently negotiated an agreement with Medicaid in Louisiana that will pay it 5% above AMP plus a professional fee of $10 for brands and $15 for generics. So, a very low cost generic medication that has an AMP of $2.00 for a 30 day supply, Walgreens would receive $2.10 for the pills plus $15 for its professional fee or $17.10 altogether. For a brand name drug with an AMP of $100, it would be paid $110 plus $10 professional fee or $120. Believe it or not, prescription drugs as a category of healthcare costs are actually growing 1-2% slower this year (and probably next) than healthcare costs overall, in part, because of the generics boom.
    If CMS is really interested in saving money on drugs, I suggest it lobby for a change in the law to allow it to specifically consider cost in determining whether or not to cover some of the ultra expensive biotech cancer drugs that manage to win FDA approval and then get priced at thousands of dollars per dose. I think introducing QALY metrics would make sense in these situations, and I hope CMS wins the authorization to do so sooner rather than later.