July 25, 2007
Provenge -- Again
So much has been written about the experimental prostate cancer drug Provenge that I have hesitated until now from getting into the morass. It's a fascinating tale that involves conflicts of interests, Wall Street insider trading, serious questions about the drug's efficacy, and Washington lobbying. Note what I didn't put on that list: the science behind the drug.
Rather than add my own two cents, let me point you to a few places where you can read about it. First, though, let me give my bottom line: two influential oncologists raised legitimate questions about whether the limited clinical trials completed so far warranted fast approval for the drug. But because at least one of them was involved in running a late stage clinical trial for a rival therapeutic approach for prostate cancer, frustrated investors and some groups in the prostate cancer patient advocacy community raised howls of protest on internet bulletin boards and on Capitol Hill. There have even been anonymous death threats hurled at the two physicians, according to published reports.
But let's place the blame where it ought to be in this scientific fiasco. The FDA had no business appointing scientists testing a rival drug for another firm onto an advisory committee evaluating Provenge. Oncology is a field where the agency could easily find other clinicians willing to analyze these data who did not have conflicts of interest.
It doesn't matter if these scientists were right (and, based on my quick reading of the data, they had a good case). Eliminating conflicts of interest isn't about keeping industry shills off these committees. It's about making sure the process of evaluating new drugs and devices is FAIR. The FDA should eliminate these conflicts of interest so that everyone involved -- patients, doctors, companies, scientists, investors and the public -- believes the process has been fair and evenhanded, and the end result dictated by the science.
Unfortunately, at this hour, the conference committee considering FDA reform legislation is leaning against strict limits on conflicts of interest on FDA advisory committees. It appears that no matter many times the current system fails, Congress just can't get up the gumption to "just say no" to industry influence over this regulatory agency.
The earliest accounts of the Provenge saga appeared in The Cancer Letter, which is subscription only. Dr. Roy Poses on Health Care Renewal in June provided a good rundown on the press coverage. Today, Maggie Mahar offered her long take on the situation on the Century Foundation website. A shorter version ran on the Health Care blog. The latter is worth looking at since you can get a flavor for the Provenge proponent arguments by reading the comments that have poured in.
Posted by gooznews at July 25, 2007 09:34 PMMr. Goozner,
On behalf of current and future PCa patients, Thank You! for your article on the Provenge Conflict of Interest (COI) controversy. Drs. Scher and Hussain, 2 of the naysayers at the March 29th FDA Advisory Committee (AC) meeting, based on internet research, have COI’s and Dr. Howard I. Scher of Memorial Sloan Kettering in NYC apparently has an unbelievable amount of Undisclosed ones as shown below.
Scher reported only 3 COI's to the FDA per his filing to them in late February available at the FDA website which appears to be composed of ownership of 2 stocks and 1 competing industry interest.
Internet research shows the following for Scher thus far:
1. NOVACEA: grants & research support; STUDY CHAIR of DN-101
2. GPB BIOTECH: financial conflict of interest per Scher in MedPage
3. PHARMION: financial conflict of interest per Scher in MedPage
4. SANOFI-AVENTIS: grants & research support
5. BRISTOL MYERS SQUIBB: consultant, grants & research
6. MILLENNIUM PHARMCEUTICALS: grant of research support
7. COUGAR BIOTECHNOLOGY: principal investigator; advisory board;
8. INNOVIVE PHARMACEUTICALS: principal investigator
9. INFINITY PHARMACEUTICALS: principal investigator
10. BIOGEN-IDEC: jointly held stock with spouse
11. PFIZER: jointly held stock with spouse
12. GENTA: scientific advisory board (as of March 6, 2007; since removed from web, but cached)
13. DEPARTMENT of DEFENSE: Principal Investigator PC Clinical Trials-P1 and P2
14. PROQUEST INVESTMENTS: consultant, scientific advisory board; Limited Partner FINANCIAL interest
15. MEDIVATION, INC: principal investigator MDV3100
There appears to be a significant and disturbing difference between his 3 disclosures to the FDA and the alleged 15 COI's found so far on the internet. It seems incomprehensible for someone with the training and education Scher has to "forget" so many apparent COIs… that is simply beyond all reasonableness and suggests intentional dishonesty or deceit.
Even more disturbing is the FDA's Office of Inspector General and other government departments to whom this information has been supplied apparent failure to investigate these charges that Scher has more COI's than he disclosed to them. When such information is provided and such allegations of potential federal law violation is involved, any ordinary citizen has the right to expect our government to investigate such allegations timely and thoroughly.
As a "temporary government employee" at the FDA, he is obligated, under Federal law, to provide full and complete disclosure. If he didn't, he may have the potential for liability for law violation(s) as well as for providing false data to the FDA under which he secured a waiver in order to participate on the Provenge AC meeting March 29th.
You also mentioned the alleged "threats" Drs. Scher and Hussain reported in both the media and to ASCO where they sought--and obtained--body guards at that Chicago meeting. It seems, indeed, strange that no one has reported seeing these allegedly threatening emails or letters first-hand nor has it been reported that either doctor has notified the police or other authorities of such alleged bodily threats against them. Had such threats come via email, it is more than a simple matter for law enforcement to easily track down the alleged perpetrators. Why hasn't anyone seen these alleged threats and why aren't law enforcement agencies pursuing them to insure Scher and Hussain's security? Are they even real?
The true tragedy in the Provenge folly is the 27,050 men--according to the American Cancer Society and the National Institutes of Health--who will succumb to their TERMINAL prostate cancer in the next 12 months alone! It appears interim data will be at least 12 additional months away. In the event it takes the full 2 or 3 years for the complete data to be submitted to the FDA and for the FDA to act, the Death Tally will be between 54,000 and 81,000 men who will die prematurely from the FDA's current actions.
Is it no wonder patients, families and advocates are making this cause known to media, Congress and the FDA? Such a horrendous death toll, if noted nightly in the media as the Iraq war casualties are, would create a firestorm and clamor from the general public as well for this product to be released to those suffering such TERMINAL cancer.
That is 82 men each and every day, 24 hours per day and 7 days per week.
Provenge satisfied 100% of the 17 voting members (including Scher and Hussain) of the March 29th FDA AC meeting that it is "substantially safe" and 13 of those 17 positively voted that Provenge shows "substantial evidence of efficacy".
The only FDA approved alternative treatment for these TERMINAL men is Taxetore, a horrible chemotherapy of which 50% or more men refuse to take it because of the horrible side-effects of this treatment and it's reported that 1 to 2% of those who do take it die from the treatment--not their cancer.
Again, Thank You! for your honesty and integrity in reporting this situation. I trust you'll continue to look into the allegations being made against Scher and report--either way--to keep your readers appraised of what you find.
you shills are forgetting provenge did not meet any endpoints of the trials. you arent concerned with pc suffering and are only embarrassing yourselves.
Posted by: red at July 28, 2007 07:44 PMMerrill--
I agree completely that the FDA paved the way for all of the confusion over Provenge by putting someone on the panel who had a financial interest in the outcome.
Regarding the threats against the doctors who
voted no, those threats were verified by both
Sloan-Kettering Hospital and the organizers of the cancer conference. (See the New York Times, June 3 or June 4). Sloan-Kettering's spokesperson specifically said that one e-mail was headlined "Your murder."
(Frank F. knows this because he also commented on my piece on the healthcareblog where we discussed this issue of whether anyone else saw the threats in the thread. The fact that he repeats
the accusation that the doctors fabricated the threats seems typical of the way those who are unhappy about the FDA decision repeat the same
misinformation over and over again.)
Maggie,
You state above, "I agree completely that the FDA paved the way for all of the confusion over Provenge by putting someone on the panel who had a financial interest in the outcome."
Also significant in the matter of Dr. Scher's conflicts of interest is the fact that Dr. Scher was granted a waiver by Dr. Randall Lutter to participate in Dendreon's FDA advisory panel for Provenge because an individual with lesser conflicts of interest was unavailable. How truthful is that assertion? The above statement appears to be a complete fabrication. Placing Dr. Scher on the Provenge advisory panel, regardless of his financial interest in the outcome, appears to have been intentional, calculated and irrelevant.
Why were Dr. Scher and Dr. Hussain allowed to vote on the Provenge advisory committee, much less participate, given their substantial conflicts of interest? According to Pat Harley, Consumer Safety Officer at the Center for Biologics Evaluation and Research (CBER), the advisory panel for Provenge was initially planned to be composed of only of the CBER employees.
Who at the FDA leaked these confidential internal letters written by Dr. Scher, Dr. Hussain and Dr. Fleming to The Cancer Letter?
Did anyone ask Dr. Scher, Dr. Hussain or Dr. Fleming to write their letters to the FDA? Did Dr. Scher, Dr. Hussain and Dr. Fleming receive any assistance in the development of their letters?
Are the policies, processes, and procedures within the FDA adequate to address what appears to be an egregious example of conflicted interests on the part of Dr. Scher?
As Dr. Benett so elequently stated, Dr. Scher’s participation in the Provenge advisory panel is akin to a defendant's own sibling participating on a jury resulting in a hung jury decision. Knowing of Dr. Scher’s close professional relationship to ProQuest Investments, how is the public to believe that the FDA made the correct decision? Surely you can see the travesty of his participation in this matter. Such conflicts of public and personal interest jeopardize the legitimacy of one proclaiming to act on behalf of the public’s best interests.
red, this is one shill who is proud to advocate for the "terminal" prostate cancer patients who've come to the end of the line and have, but 2 "life and death" choices currently:
a. do nothing and die sooner--approx. 18 months, but likely have a good quality of life;
b. take Taxetore and suffer the horrible consequences of that awful chemo regime that also includes hospitalization, added drugs to rebuild red- and white blood cell counts, nausea, hair loss, weakness, fatigue, immune suppression, etc. with a poorer QoL.
Where's their ability--in consult with their doctors--for another choice like Provenge--voted 17-0 as being reasonably safe--with a good likelihood of extending their lives for added months (some trial participants have experienced years) with a good QoL?
You do realize AIPC cancer victims are terminal, have likely been castrated chemically or surgically, irradated, chemo-ed to near death, hospitalized, chance a 1-2% death by chemo--not their cancer-- and are on their last legs weak ill and just wanting to see a child or grand-child get married or graduate from college or celebrate another birthday, wedding anniversary or family milestone spending time with those whom they love... quality time.
Add in they've also likely lost their libido, experience ED, have incontinence and see their breasts grow--and if they have testicles left having not had them surgically removed yet, see them shrink--with loss of masculine muscle mass, but with a likely gain in both water (edema) and fatness from the decreased testosterone levels and increased female hormone levels.
As a man, these horrify me and I do not have prostate cancer at this time, but have a bunch of brothers and we have a poor family history regarding PCa--at least 1 of us will become a PCa victim sooner or later--likely sooner at our ages.
The cancer medical professionals--this year and from organizations both government and private such as NIH & FDA--agree judging immunotherapy by chemo standards is wrong!!!
Even the FDA's Pazdur and others have publicly stated "Survival is the gold standard" so missing Time To Progression or other surrogate endpoints is meaningless. Either the PCa patient is alive or dead... no equivocation about that, is there? Either the PCa patient lived 18 months or more (or less)... Nothing equivocal about that, is there?
The Provenge trials "end points" that you proudly proclaim as being missed were designed almost 10 years back and are based on chemo standards--now known to be next to useless for immunotherapy--as you either know or, if you're acquainted with PCa, should know. Either way, your post is disingeneous.
Maggie, even if I stipulate Scher & Hussain received death threats, my question remains WHY, if they were so worried as to required bodyguards at ASCO (and possibly elsewhere), have they NOT called the police and reported these alleged death threats. Cops can easily trace such emails... the media gladly bally-hoos the allegedly threats because it's "sensational" and makes good ink/talking points; where's the media follow-up on the police reports and the actions to catch these criminals????
Equally as weak is your assertion that a Sloan-Kettering spokesperson said what a headline was in 1 email. That doesn't verify and prove in the least as to having actually seen such email, does it? Scher could have told them that was the subject in conversation. Again, my disbelief stems not whether or not such email was received, it stems from the to-do being made about it/them by Scher and Hussain and the media without having a police report made in an attempt to catch the culprit(s). Why not? Are they afraid of making a "false" police report which is a law violation?
And, Maggie, I listed above 15 COI for Scher; there are links available to verify each allegation. Yet, you neglected to ever acknowledge --both here and at your own blog--the unbelievably large quantity of such COI--15 [Fifteen] found so far vs the 3 [three]he reported to the FDA; above you wrote in the singular as if it was just ONE, single COI... it's NOT!!!!!
Those wishing to join in advocating for PCa patients and their families (and possibly for themselves in the future) are reminded that September is PC Awareness. Get a prostate screening and nag someone you love to do likewise. When caught early, treatment is less severe and more successful.
Additionally, PCa advocates will peacefully rally at the FDA in Washington on Sept 18th starting about 10 a.m.. Those wishing more info or to help PCa patients should check out "A Right To Live" at arighttolive.com
Thanks, Mr. Goozaner, for providing another forum for bringing this topic to the public's forefront for the benefit of prostate cancer victims!
Posted by: Tony F at August 1, 2007 07:10 PMred, this is one shill who is proud to advocate for the "terminal" prostate cancer patients who've come to the end of the line and have, but 2 "life and death" choices currently:
a. do nothing and die sooner--approx. 18 months, but likely have a good quality of life;
b. take Taxetore and suffer the horrible consequences of that awful chemo regime that also includes hospitalization, added drugs to rebuild red- and white blood cell counts, nausea, hair loss, weakness, fatigue, immune suppression, etc. with a poorer QoL.
Where's their ability--in consult with their doctors--for another choice like Provenge--voted 17-0 as being reasonably safe--with a good likelihood of extending their lives for added months (some trial participants have experienced years) with a good QoL?
- continued in next post -
Posted by: Tony F at August 1, 2007 07:12 PMred, this is one shill who is proud to advocate for the "terminal" prostate cancer patients who've come to the end of the line and have, but 2 "life and death" choices currently:
a. do nothing and die sooner--approx. 18 months, but likely have a good quality of life;
b. take Taxetore and suffer the horrible consequences of that awful chemo regime that also includes hospitalization, added drugs to rebuild red- and white blood cell counts, nausea, hair loss, weakness, fatigue, immune suppression, etc. with a poorer QoL.
Where's their ability--in consult with their doctors--for another choice like Provenge--voted 17-0 as being reasonably safe--with a good likelihood of extending their lives for added months (some trial participants have experienced years) with a good QoL?
You do realize AIPC cancer victims are terminal, have likely been castrated chemically or surgically, irradated, chemo-ed to near-death, hospitalized, chance a 1-2% death by chemo--not their cancer-- and are on their last legs weak ill and just wanting to see a child or grand-child get married or graduate from college or celebrate another birthday, wedding anniversary or family milestone spending time with those whom they love... quality time.
Add in they've also likely lost their libido, experience ED, have incontinence and see their breasts grow--and if they have testicles left having not had them surgically removed yet, see them shrink--with loss of masculine muscle mass, but with a likely gain in both water (edema) and fatness from the decreased testosterone levels and increased female hormone levels.
As a man, these horrify me and I do not have prostate cancer at this time, but have a bunch of brothers and we have a poor family history regarding PCa--at least 1 of us will become a PCa victim sooner or later--likely sooner at our ages.
The cancer medical professionals--this year and from organizations both government and private such as NIH & FDA--agree judging immunotherapy by chemo standards is wrong!!!
Even the FDA's Pazdur and others have publicly stated "Survival is the gold standard" so missing Time To Progression or other surrogate endpoints is meaningless. Either the PCa patient is alive or dead... no equivocation about that, is there? Either the PCa patient lived 18 months or more (or less)... Nothing equivocal about that, is there?
The Provenge trials "end points" that you proudly proclaim as being missed were designed almost 10 years back and are based on chemo standards--now known to be next to useless for immunotherapy--as you either know or, if you're acquainted with PCa, should know. Either way, your post is disingeneous.
Maggie, even if I stipulate Scher & Hussain received death threats, my question remains WHY, if they were so worried as to required bodyguards at ASCO (and possibly elsewhere), have they NOT called the police and reported these alleged death threats. Cops can easily trace such emails... the media gladly bally-hoos the allegedly threats because it's "sensational" and makes good ink/talking points; where's the media follow-up on the police reports and the actions to catch these criminals????
Equally as weak is your assertion that a Sloan-Kettering spokesperson said what a headline was in 1 email. That doesn't verify and prove in the least as to having actually seen such email, does it? Scher could have told them that was the subject in conversation. Again, my disbelief stems not whether or not such email was received, it stems from the to-do being made about it/them by Scher and Hussain and the media without having a police report made in an attempt to catch the culprit(s). Why not? Are they afraid of making a "false" police report which is a law violation?
And, Maggie, I listed above 15 COI for Scher; there are links available to verify each allegation. Yet, you neglected to ever acknowledge --both here and at your own blog--the unbelievably large quantity of such COI--15 [Fifteen] found so far vs the 3 [three]he reported to the FDA; above you wrote in the singular as if it was just ONE, single COI... it's NOT!!!!!
Those wishing to join in advocating for PCa patients and their families (and possibly for themselves in the future) are reminded that September is PC Awareness. Get a prostate screening and nag someone you love to do likewise. When caught early, treatment is less severe and more successful.
Additionally, PCa advocates will peacefully rally at the FDA in Washington on Sept 18th starting about 10 a.m.. Those wishing more info or to help PCa patients should check out "A Right To Live" at arighttolive.com
Thanks, Mr. Goozaner, for providing another forum for bringing this topic to the public's forefront for the benefit of prostate cancer victims!
Posted by: Tony F at August 1, 2007 07:22 PMred, this is one shill who is proud to advocate for the "terminal" prostate cancer patients who've come to the end of the line and have, but 2 "life and death" choices currently:
a. do nothing and die sooner--approx. 18 months, but likely have a good quality of life;
b. take Taxetore and suffer the horrible consequences of that awful chemo regime that also includes hospitalization, added drugs to rebuild red- and white blood cell counts, nausea, hair loss, weakness, fatigue, immune suppression, etc. with a poorer QoL.
- continued below -
Posted by: Tony F at August 1, 2007 07:23 PM