For those of you who haven’t been following the comments and overall discussion, my post on the lawsuit against the FDA and some key individuals who were part of the non-approval of Provenge in May generated a lot of attention from some people who are both knowledgeable and vocal about this issue. While the specific therapy is for prostate cancer, rather than the lung cancer that more of my readers are focusing on, there are some general issues here that I think merit discussion.
I don’t have a firm answer here about whether the non-approval of Provenge was inappropriate or not, but my views based on new information provided by participants here have changed. My perspective at the time I wrote the post a couple of weeks ago was more entrenched in a general trust in the system and some people who I know as leaders in their fields. Nothing about the FDA decision required me to change my frame of mind or general beliefs about these individuals or the FDA as an institution. At this point, I’ve learned more about the data behind the Provenge trial, the mixed messages that were generally quite favorable leading up to the actual decisions, and the potentially significant conflicts of interest. And while I haven’t concluded that there were economic and/or petty ego motives behind the FDA decision, I’m much less convinced of my prior assumption that the system works well with the only real guiding forces being the strength of the data and the benefits for the population.
We all tend to filter data and interpret information through the prism that reinforces what we already believe/understand. Like everyone else, I have to struggle to remain open-minded about what I think I know and receptive to new findings that should force me to question my interpretations. At ASCO 2007, new data were available that indicates that consolidation chemo for stage III NSCLC doesn’t improve survival (reviewed here). This contrasts with some limited information we had before, and also with my approach and understanding of the best way to treat patients in this setting. Nevertheless, it’s important to recognize when the weight of the evidence should make us step back, re-evaluate, and say that there’s a better conclusion to make. At the end of the day, it’s the converts from a different way of thinking who are more compelling than the people who always maintained the same beliefs. Thus, the politician who switches parties or the tobacco executive who testifies against his former company is more convincing than listening to a person who has always toed the same party line.
I still think the language of the lawsuit against the FDA was bitter and at several points unprofessional, and that anger can undermine some of the legitimacy of the issue. But I have come to appreciate, really just with a recent volley of communication with several vocal, thoughtful, and articulate participants, that there may be good reason to examine the process by which these important FDA decisions of access to medical interventions are made. While I find it unsettling to think that there could be motivations other than the best interests of the cancer community undermining the process (to which some readers may think, “of course! how naive!” – but at least part of me is an optimist), we can at least hope that a careful review will either improve confidence or demonstrate that our institutions and current processes are too fallible to be entrusted with such important stakes.
I am not yet concluding that the FDA decision on Provenge was motivated by financial conflicts of interest or ego and pride, but I have been shaken of many of my presumptions that there is little reason to question the inner workings of the process. I will be following this story closely and with a more jaded view.
posted by Dr. West @ 10:18 am link to this post
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August 12th, 2007 at 9:12 pm
If you want to get Provenge approved for use in this country, just reformulate to include lead, bisphenol A, nicotine, and a sprinkle of botulism.
But seriously, we are paying a lot of tax monies that are going to a lot of different governmental bodies which are littered with conflicts of interest and cronyism. I’m afraid that even the FDA is probably not immune. I think it’s time for some meaningful change.
Jim
August 13th, 2007 at 8:52 am
Oh Plueeeeeze Doc! Let this engineer educated you on that which is intuitively obvious to the most casual observer. The combined net worth of the ten largest pharmaceutical companies (not counting biotech companies) is 1.1 trillion dollars (yes that’s T for trillion) and they have the largest lobby per capita in dollars in Washington D.C. than any other group.
Think about the drug company lobby, it’s larger than defense, heavy industry, and even the financial banking lobby pales in comparison. Too assume that all doctors in the FDA and those peripherally associated with the FDA in some capacity have not been tainted by the “drug money” is extremely naive on your part! That trillion dollar plus combined market cap is linked directly to Wall Street. If you take the time to understand the manipulative trading of Dendreon stock, the makers of Provenge, that occurred after the FDA advisory committee’s green light on April 30th and the FDA’s approvability letter of May 9th you will see that which again is “intuitively obvious” to the most casual stock trader/investor. Somebody on the inside of the FDA leaked pertinent info about Provenge, resulting in a massive short interest in Dendreon stock, in other words “The Street” knew that Provenge wasn’t going to be approved for immediate marketing. And guess what Doc? That’s against the law! It was a clear violation of the Security and Exchange Commissions laws concerning insider trading and Fair Disclosure, commonly know as Reg FD. Somebody “leaked” that information and I don’t think it was “Betty the secretary”.
The powerful Pharma companies, those which manufacture the chemo-therapy drugs will lose billions of dollars when those drugs are replaced with cancer immuno-therapy treatments that are seemly being developed by the biotech drug industry. The “old guard” will try every trick in the book to hold on to their piece of the cancer treatment pie at the expense of the cancer patients. The present day cancer treatment methodology seems to have been institutionalized by Big Pharma; as well the FDA and any change to this antiquated treatment philosophy will be met with great resistance until all parties have laid their own self serving financial groundwork as the cancer treatment paradigm shift occurs. After all, that’s the way this country and the capital markets work; you just simply “follow the money” and everything else including the Hippocratic Oath and general ethics and will always take a back seat!
August 13th, 2007 at 12:30 pm
Dr West, like you, I too have been “shaken of many of my presumptions that there is little reason to question the inner workings of the process.”
Certainly the FDA has approved drugs against the recommendations of its advisory panel, but I am not aware of a decision to overrule a strong positive panel vote for a terminal illness that has no really acceptable treatment options. This decision would appear to be unprecedented, and calls for a full and open public statement of why the FDA disagrees with this panel and cannot make this drug available to terminal patients.
We know of course it was not due to safety concerns. Also, if FDA found the clinical trial data submitted by Dendreon to be insufficient, why did they even submit the data to a panel of experts for their opinions?
Also troubling is an explanation by Dr Mark Thornton, formerly the medical officer in the FDA Office of Oncology Products, and now President of the Sarcoma Foundation of America, on why he believes the FDA did not listen to the majority opinion of its medical panel. Dr Thornton wrote on May 9th, 2007 (Black Wednesday, WSJ On Line) quote:
“Those voting in the minority, very powerful members of the oncology community, (and I would add who had strong financial interests in seeing Provenge disapproved) launched an unprecedented PR campaign accusing those in the majority of incompetence and naiveté in matters relating to cancer products. The arrogance of this campaign overlooked the notion that survival data from immune-based products may be qualitatively different from, and may need to be judged by different criteria than, survival data from chemotherapy drugs.”
Meanwhile, the FDA decision with regard to Provenge is also troubling because it appears that 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?’
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, and were reminded again recently by the NCI’s Dr Jeffrey Schlom:
“Clinical data are providing evidence that patients are living longer following vaccination, de-spite the fact that trials do not show the vaccines can induce the immune system into shrinking tumors,” said Jeffrey Schlom, Ph.D., chief of the Laboratory of Tumor Immunology and Biology at the National Cancer Institute. “The data suggests that the scientific community and regulatory committees ought to rethink the design of clinical vaccine trials and our current approach to measuring the effectiveness of a cancer vaccine.”
And yet the FDA went blindly ahead overuling the conclusions of its own workshop and its own Provenge Advisory Committee where every single member of the AC who had recognized expertise in immunotherapy (and they were from Moffit, MD Anderson, NIH, Harvard, Stanford, UCLA, Duke, U WA) voted 13-4 that there was “substantial evidence” of effectiveness and unanimously (17-0) that there were no safety issues. Not one of the “no” voters on the panel had recognized expertise in immunotherapy. The drug in question was an immunotherapeutic agent.
So if all the FDA wants to continue to study is why the round ball will not fit into the square hole, the inner workings of the FDA process appear to be not science based and seriously flawed.
It also begs the question whether America’s cancer patients, and citizens are not being held hostage at the FDA because of academic turf wars, financial interests or the chemotherapy industry.
Like you, will be following this story closely!
August 13th, 2007 at 1:59 pm
Dr. West,
How refreshing it is to see an expert and active clinician in his field also have an open mind and be receptive to ideas which might have previously been counter to those held. Additionally, kudos for allowing and having a cordial discourse. The Provenge sage is genuinely an almost UNbelieveable story and I’m anxiously awaiting the end, myself.
My true 3 disappointments are:
1. the 82 men who died EACH DAY from prostate cancer who do not currently have Provenge available if they and their Doctors believe it can help them;
2. for the victim’s of other cancers such as lung, colon, ovarian, breast, etc for which Dendreon has treatments in its deep pipeline of products under development who will be delayed in receiving possible help for their diseases;
3. that this tragedy has not yet caught the attention of someone in the investigative media who can check out the allegations being made and verify the truth or not about them. It appears, from the allegations made, that such an investigative report could well-be an award winning one exposing the worst of the unknown and the worse of human nature of those dealing with other people’s lives.
Frankly, there appears to be substantial evidence of the truthfulness of many of the allegations–especially regarding Scher of Sloan-Kettering–who has at least 16 potential Conflict of Interests of which he only disclosed 3 to the FDA in his Waiver Application to sit in judgment on Provenge. Hussain, at Michigan and her husband are also deeply involved in prostate cancer research/treatment and likewise appear to have COIs that may possibly be undisclosed.
For those able to attend, there is to be a Rally at the FDA on Sept 18th - 10 a.m. Details are at www.caretolive.com Can’t attend, then become a member, email Congress in support of cancer victims, volunteer within your local area (such as driving a patient to treatments, visiting with them, advocating for them, etc) or otherwise support cancer victims. If we do not support and advocate for them, who will? And, don’t forget, we–and our family/loved ones/friends–can also become victims of this terrible disease ourselves.
Thank You! for your candidness and your continuing public presentation on this topic…
You should know that in Dendreon’s “pipeline” of cancer treatments which have been delayed due to the “approvable” status of Provenge that is requiring the focus of the company now, there are Active Immunotherapy treatments being investigated for:
Provenge - AIPC and ADPC
Neuvenge - Breast, ovarian and colon cancer
TRP-P8 - Lung, breast, colon and prostate cancer
CEA - Lung, breast and colon cancer
CA9 - Colon, kidney and cervical cancer
Monoclonal Antibody
Anti-Serine Protease - Multiple cancers
Small Molecule
TRP-P8 - Lung, breast, colon and prostate cancer
Clearly, this company and its pipeline represents investigation into treating multiple cancers… including lung which appears to be the primary focus of your endeavors.
August 14th, 2007 at 9:59 am
Wonderful article and postings here. I’m in total awe of this community! Thanks always for the education.
August 14th, 2007 at 8:48 pm
I thank everyone for their contributions here. As Yirol said, I’ll just reiterate, “thanks always for the education”. I may be doing a lot of these posts, but I learn a lot from the members here.
August 21st, 2007 at 1:28 pm
Hey Doc take some time and watch the link below and it may help you understand what happened to Dendreon stock around the time of the FDA’s decision about Provenge!
http://www.businessjive.com/