kyoto27

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    • Thu Jul 3rd 01:14 AM | Rating: 0 0
      Commented on:
      Cougar Biotechnology: Stalking Prostate Cancer
      Bryan, you say:

      “Both treatments Dendreon's and Cougar's fall short, time to progression for Provenge and no survival statistics for abiraterone.”

      Did Provenge really miss ‘time to progression?’

      The p value for the primary endpoint of cancer progression was p=0.052, barely missing the p=0.050 threshold. For Howard Scher and Maha Hussain, this narrow miss was blown up to be an utter failure. They said that because the p value did not reach 0.050, then all additional data (including survival) should be discarded. Basically, their position was that because the odds of being successful in progression were only 94.8% and not 95.0%, there was no correlation between the two metrics and the 99.0% survival odds should be thrown in the trash.

      And remember, the overall survival p value in 9901 was 0.01, easily beating the p=0.05 threshold. This goes to the crux of the anger of the Provenge advocates. Statistical significance on survival is the "gold standard" by which the FDA judges all oncology treatments, and Provenge met it with flying colors in the 9901 trial.



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    • Wed Jul 2nd 13:17 PM | Rating: 0 0
      Commented on:
      Cougar Biotechnology: Stalking Prostate Cancer
      You say:

      "There is a huge unmet need for an efficacious therapy with minimal side effects that has significant survival benefits. With the dismal performance of Abbott's Xinlay and Spectrum Pharmaceuticals' Sartraplatin, Cougar Biotechnology may take the lion's share."

      With all due respect, the odds right now look appear to tilt more in favor of Dendreon's Provenge taking the 'lion's share' following Provenge's IMPACT trial interim results (this year) or final 2H09. With virtually no side effects, and very significant survival benefits --not to mention a positive FDA AC panel recommendation already in it's pocket, there is very little not to like about Provenge's odds to run the table. And remember, Provenge approval also validates Dendreon's 'platform technology' which opens the door to a paradigm shift in how cancer will be treated in the 21st century.

      We live in exciting times....




      Disclosure: none
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    • Thu Jun 12th 11:26 AM | Rating: 0 0
      Commented on:
      Dendreon's Provenge: Government Agencies Play Hide and Seek With Facts
      The Pharmaco Man said:

      “Sorry, but the data are pretty uncompelling--the vaccine doesn't enhance survival in a statistically significant way.”

      Pharmaco needs to go back to school:


      He asserts that the D9901 study did not attain statistical significance for survival when the final data was released in October 2004. This is an incorrect assertion. The overall survival p value was 0.01, easily beating the p=0.05 threshold. This goes to the crux of the anger of the Provenge advocates. Statistical significance on survival is the "gold standard" by which the FDA judges all oncology treatments, and Provenge met it with flying colors in the 9901 trial.

      In addition, the p value for the primary endpoint of cancer progression was p=0.052, barely missing the p=0.050 threshold. For Howard Scher and Maha Hussain, this narrow miss was blown up to be an utter failure. They said that because the p value did not reach 0.050, then all additional data (including survival) should be discarded. Basically, their position was that because the odds of being successful in progression were only 94.8% and not 95.0%, there was no correlation between the two metrics and the 99.0% survival odds should be thrown in the trash.

      So Pharma Man, the data does suggest it prolongs survival. And the data also suggests our FDA’s decision to de-rail Provenge had nothing to do with good science and a lot do with politics and money. Period. Next?

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    • Tue Apr 22nd 20:09 PM | Rating: 0 0
      Commented on:
      Dendreon: The FDA's Commissioner Doth Protest Too Much!
      “But you can't evaluate cancer vaccines without involving oncologists.”

      Portfolio Manager,

      Why? And why wouldn’t it be more proper to say you cannot involve oncologists who have no training or understanding of the science of immunology or cancer vaccines?
      Let’s be honest, Dr Scher was lost at the Provenge AC and he knew it; and so was Dr Hussein. Not lost in there over the top Cancer Letter crusade , however, was an insight into their well-honed survival instincts, as noted in David Miller’s post above:

      “It took a decade to get the current large Taxotere adjuvant trials started. It was clear from Hussein and Schers' letters they were worried that the approval of Provenge would hurt enrollment of these trials, which they personally and financially benefit from either directly or through their institutions' participation in these trials.”

      So while they treasured their own survival, they trashed the Provenge survival data and the hopes it gave to those with no more hope. Interesting. And says a lot about both of those doctors.
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    • Mon Apr 21st 13:00 PM | Rating: 0 0
      Commented on:
      Dendreon: The FDA's Commissioner Doth Protest Too Much!
      Not so fast Mr Been There.

      The insanity of the FDA's decision is that
      Scher-Hussein would have the world believe that
      because the 9901 Phase III trial had a p-value of p=0.052 when a p-value of p=0.05 is considered statistically significant…that the stellar Provenge survival log-rank p = .01 for D9901 had to also be thrown out!? And let's remember, the p=.01 was on the entire trial, not some subgroup (and the final Cox model improved D9901 from log-rank .01 to Cox .002!).

      It cannot be overly stressed that eight years ago, the sponsors of the Provenge trial chose time to progression as the primary endpoint. They nominally hit it for one trial and missed it with another. If they instead had chosen survival as that single item, then Dr. Scher would not likely have written his letter and Provenge would likely already be on the market.

      As a matter of fact, it was Dr Howard Scher, in a 2007 symposium titled, "Improving Upon Current Standards: The Integration of Novel Therapies in the Treatment of Androgen-Independent Prostate Cancer," sponsored by Novacea, that Howard suggested that when doctors consider whether to prescribe certain treatments, “It may be time we focus less on statistical significance alone, and more on patient benefit.” – MedPage Today, February 26, 2007

      Ironically, this is exactly what the 13 members of the CTGT panel did by voting yes to whether Provenge provided substantial evidence of efficacy.

      How sad that Dr. Scher had it exactly right in February of 2007 when he uttered this line but got it so wrong when he launched his now infamous campaign in The Cancer Letter –which in effect told the 13 members of the CTGT that more time has to be spent on statistical significance and less time on patient benefit.

      So Mr Been There, let’s be clear:

      Biostatisticians would call the Provenge alpha p=.052 “nominally statistically significant.” Laypeople would call it “close enough.”
      Hypothesis-generating? Don't think so.

      So it looks like the real question before the FDA is not whether the agency has the right to study this drug further, but whether immunotherapy treatments need to be judged by a different standard than chemotherapy treatments?

      And sadly, the FDA already knows the answer is yes —as they were told just that at the NIH/NCI workshop they hosted in February 2007


      "Cancer vaccines such as Provenge aim at stimulating the immune system. As that process usually takes at least 8-10 weeks to fully activate, such drugs would not have much of a chance to have impact on TTP."

      So Provenge was measured using standards applied to chemotherapy trials and misses that endpoint by only .002! and the FDA insults all of us by calling that alpha miss a miss...and then throws out all the survival data as Hypothesis-generating?...

      It would be comic tragedy--throwing the baby out with the bathwater if so many lives were not at stake. As it was, the FDA's CRL was an insult not only to good science but also to human life.

      America should not quietly accept this outrage.

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    • Fri Mar 7th 12:26 PM | Rating: 0 0
      Commented on:
      FDA Turns Over Dendreon Documents - Here They Are
      Q to User 161198:

      Provenge had a p-value of .052.
      Are you really suggesting that a p-value of .052 is showing the treatment ‘failed to slow progression?’ To the contrary, a p-value of .052 clearly showed that the treatment slowed progression of symptoms of the disease and, in fact, most biostatisticians would call a p=0.052 level of significance “nominally statistically significant.”

      Why the FDA did not think so in this case is unknown. Especially when you add the stellar survival log-rank p = .01 for D9901 (which was on the entire trial, not some subgroup) the FDA decision becomes what in fact it really was –unprecedented in this terminal disease setting.

      And let’s not forget that the FDA, by virtue of its own revised trial design guidance, has demoted the importance of traditional markers such as TTP, subordinating them to overall survival. Nonetheless, Provenge naysayers continue to trot out TTP like a champion mare when it suits them, knowing that it is an unacceptable endpoint for making an approval decision.

      I’ll let the FDA have the last word:

      “When a study fails to meet its primary endpoints, there's no alpha left for other endpoints analysis. So literally, means from pure statistical point of view, the difference in other endpoints should not be considered statistically significant. Therefore, it is very difficult to interpret the hypothesis test result for overall survival in Study 1.

      So if overall survival is one of the many unspecified endpoints, under testing it is very possible that a p-value of 0.01 was observed just by chance. However, survival is not one of the many, many endpoints that can be randomly selected for testing. Survival is a preferred endpoint for cancer trial. As Dendreon and Dr. Liu just mentioned, this endpoint is reliable, clinically meaningful. This is why we are here seeking advice from the (Provenge) advisory committee meeting.”

      Dr. Bo-Guang Zhen, Ph.D (Division of Biostatistics, FDA )

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    • Thu Feb 14th 12:17 PM | Rating: 0 0
      Commented on:
      Dendreon Clinical Studies Continue to Impress
      A 'thoughtful' observation from an observor of Congress and Biotechland:

      “We find it ironic this word would come down on a day when Congress could find an entire half day to berate a baseball player for taking performance-enhancing drugs. If Roger Clemens is harmed from taking these drugs (assuming for a moment he did), he (a) made his own choices and now has to live with them, and (b) he has more than enough money to buy himself some pretty nice healthcare.

      Contrast that with prostate cancer patients. They don’t get a choice. The FDA took it away from them. It isn’t just one man, it’s thousands—perhaps reaching tens of thousands by the time Provenge is finally on the market.



      Apparently the Senate decides where it will focus based upon not whether the issues are worthy of Congressional attention, but the likelihood of whether they can get their mugs on cable news for a few hours.

      They ought to be ashamed. And we mean really ashamed.”



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