Sorry, The FDA Information You Seek Is Classified
11 CommentsBy Ed Silverman // August 7th, 2008 // 12:44 pm
Have you noticed that when a drugmaker announces it has received a bad news letter from the FDA - a ‘non-approvable’ or ‘unapprovable’ letter - there is little in the way of specifics? And while a drugmaker generally tries desperately to play down the disappointment, the FDA says nothing.
That’s because, as a matter of law, the FDA must keep communications about unapproved drugs confidential. “Many of us at FDA would like to see greater transparency,” John Jenkins, who heads the FDA’s Office of New Drugs, tells Forbes. “But we’re restricted by the current statutory limitations.”
The issue is particularly confounding when such letters are issued after an FDA advisory panel recommends a drug be approved. This happened last week when the FDA unexpectedly rejected Bridion, an anesthesia drug from Schering-Plough, over concerns “primarily related to hypersensitivity/allergic reactions,” according to the drugmaker’s press release. Nothing else was said.
There was similar confusion last year when the agency ignored a recommendation from an advisory committee to approve Dendreon’s Provenge prostate-cancer vaccine. The decision has been cloaked in controversy, in part, because the refusal came after two committee members quietly wrote FDA officials urging them not to approve the med. Since then, patients and investors have been locked in a court battle to obtain FDA documents explaining the decision, which they want overturned (back story).
In general, Jenkins suggests putting more pressure on drugmakers to disclose information. “One thing I’ve said now for several years is, if a company is telling you about the letter, I would ask to see the letter, because that’s the only way to know what the FDA said,” Jenkins tells Forbes. Ironically, a recent FDA move to begin issuing ‘complete response’ letters, instead of a non-approvable or unapprovable missive, may only make it harder to discern just how much more distance must be traveled before a drug can be approved.
Jeffrey Clark, CEO of Beaker.com - The Online Community for Life Sciences Professionals
We are beginning to see the PR function in each company dominate the process of communication FDA outcomes. Schering Plough last week is only one example. Look at the latest example in the most recent posts from another industry blog:
“Eisai was not as forthcoming as Vanda Pharmaceuticals was earlier today regarding their receipt of a non-approval letter and did not state the reasons for the FDA’s non-approval of the drug. The only thing the company did say in the subtitle of the press release was that the FDA’s letter did outline a path to approval. Eisai decided not to share what that path might be”
Obviously that was an arbitrary decision by the Investor Relations or PR team at Eisai on how they thought they should communicate the outcome. Here you have two companies receiving the same notification from the FDA & sharing different levels of detail with the public.
I can imagine no better clue pointing toward the ambiguity we can now expect when there is a corporate filter on the information coming from the FDA.
Most of this is directly attributable to the agency’s new Complete Response letter. The devil will be in the details communicated to the company as to why the FDA acted as they did and suggesting a path forward. The big question moving forward is how available & transparent that information will be to the public.
Kerry Donahue, Esq.
As far as we know CR letters do not show, who, where, when and how a decision not to approve a license application was made. According to the FDA legal pleadings the FDA never even considered the Provenge application at a level high enough to approve it. I can almost guarantee it does not set forth the process the FDA followed when it denied approval to Provenge in the CR. More certainly it does not set forth the threats made by Dr. Pazdur to CBER and other methods he employed to assert his politcal agenda and deny real due process to the Provenge application. Not disclosing correspondence with the company and not disclosing anything about anything is different.
Where does it say that Richard Pazdur is not allowed to deny the accusations about him if they are not true. Point me to that statute.
If there is no transparency from the FDA they can hide how a decision was made, who influenced it, what votes or meetings occurred and the full depth of the sabotage by Dr. Pazdur or others. In this case they continue to ignore the apparent mistake they made in reviewing the Provenge matter despite a Citizen Petition filed in July 2007 that would give them carte blanch to respond to the public in a meaningful way, or at least try to demonstarte that they takes patients concerns seriously, and actually reconsider as requested in the petition.
The FDA is here to protect the public and see that innovative medicines are brought to the Patients in a timely manner! Somewhere the FDA has lost its way and forgotten that it is the patients it owes the duty to.
If Pazdur and CDER merely complied with the Freedom of Information Act submited by CareToLive we would have much more transparency and may with more particularity identify the short comings in the process afforded to Provenge. Where does it say that sticking stuff in a CR letter operates so as to prohibit it from being therafter discussed by the FDA with the patients and their families. Disclosing the correspondence sent Dendreon and responding to Citizen concerns are not entirely the same.
There is no prohibition against the FDA being more transparent. This is another FDA perpetuated falsehood. Do not buy into the FDA argument that it desires to be more transparent but is not allowed.
Show me the statutory sections that say the FDA cannot explain the reason for denying licensure to Provenge and explain how the decision was reached so as to insure public faith in the agency. Show me where it says they can’t timely respond to FOIA requests that might provide more transparency in a matter as important as this one.
The FDA conveniently blames it on the companies but it is they that hide in the dark shadows. A treatment for AIPC is an important matter and the FDA chooses to be unresponsive to patients. IF THEY REALLY WANTED TRANSPARENCY then respond to the FOIA made by CareToLive and properly respond to the Citizen Petition. Both those authorized (by statute) methods to seek responsiveness and review from the FDA demand transparency. When the FDA is consistently avoiding providing information and answering questions then who can really believe they desire transparency.
Where is the statute that says you cannot explain things in a response to a Citizens Petition and why is there such a petition mechanism (answer: to protect them from accountability) if it is not meaningful (Abigail Alliance has been waiting for a proper response since 2003 and CTL now since July 2007).
As demonstrated by Howard Streicher, the FDA decion to deny a licence to Provenge or refusal to grant conditional approval may have ben made by some mistaken evaluation of the data. Streicher went to Petrylak’s November 2006 study, reviewed it, seemingly misunderstood it (possibly referenced Petrylak as a liar) and then quickly tried to encourage the sabotage of Provenge by Dr. Pazdur’s recruited AC member Howard Scher, despite the fact he admittedly knew very little about it. If the FDA made its decision based on wrongful information such as opinions by those with then unknown conflicts of interests and other faulty reasons, then a review of the REAL PROCESS might reveal the mistake and allow for correction while patients cans still benefit. Without review (transparency) there can be no accountability.
The AC hearing is a chance to disucss all concerns in a public forum so that the public and the other AC members can address them and SEE and UNDERSTAND the process. Its a farce for a couple of AC members to convene afterwords, recruit help from friends at NCI then attack an immunotherapy…..for which you had fulll opportunity to discuss at the proper place and time…..THE PUBLIC AC.
If they do not have to be transparent or accountable they will continue to do whatever they want, however they want to do it, and the public will continue to lose faith in them.
Dan
I don’t get it…if the drug is “not approved”, then it won’t make it to the market. No one is harmed…the only people that want to know more are the stock arbitragers who want more info for stock trades.
The statute as it is protects the IP of the companies involved. Why would a company want the world to know how they can fix their drug to make it approvable? Whatever they did, it will be public eventually, WHEN IT’S APPROVED!!!
The public’s “right to know” doesn’t always supercede a company’s right to protect intellectual property, especially when the public will not be harmed as a result.
Typical, though, of the FDA to punt the responsibility to the companies. The statute regarding disclosure is on the books…if those who disagree don’t like it, convince Congress to change it.
Dan A.
Dan,
There are actually quite a few drugs that are not FDA approved, yet are marketed by some pharmaceutical companies. It’s about creating what is called a NDC number so the prescription medication is accessible to wholesalers, yet bypass the FDA with intent.
This does not include those drugs approved before the 1960s, which allows some pharma companies to market such drugs without FDA approval, which I believe are called DESI drugs.
Salmon
I can’t help but notice that this was announced the same day as Schering’s quarterly SEC Q-10 form was filed whereas Merck filed theirs the day before.
Does this mean that this information is in the Q-10 form or not? Did Schering got the Sugammadex non-approval letter that day or did they have it before? The news about the nonapproval letter was 10:45 AM, what time was the Q-10 form filed? When are the Schering executive’s programmed trades expected to occur?
As for not hurting anyone. I can guarentee that not releasing approvable letters until later can hide serious side effects that might effect either the same company’s or another drug company’s products. These letters can have implications either for drugs already on the market or on ongoing reviews within the FDA in other therapeutic areas. FDA reviewers keep an eye on these things because they know that they can learn stuff that FDA management isn’t telling them. In fact I can think of examples going back to the late 1980’s. Plus sometimes FDA management delay these things until after another review is finished. One of the reasons for nonapproval of a drug under the FD&CA is safety information gleaned from other information before the reviewer. So yes people do get hurt and die because the information isn’t released.
Salmon
Tony F
Ed, I am one of your biggest fans because of your honest and fair-handed approach to reporting.
Don’t know why the below comment made me prickly–perhaps, it’s the dog-days of summer.
>>There was similar confusion last year when the agency ignored a recommendation from an advisory committee to approve Dendreon’s Provenge prostate-cancer vaccine. The decision has been cloaked in controversy, in part, because the refusal came after two committee members QUIETLY WROTE [emphasis mine] FDA officials urging them not to approve the med. Since then, patients and investors have been locked in a court battle to obtain FDA documents explaining the decision, which they want overturned (back story).<<
First, we all know from the Provenge story that the two negative and conflicted committee members are Maha Hussain of University of Michigan and Howard Isadore Scher of Sloan Kettering in New York City.
Secondly, there was nothing “QUIETLY WRITTEN” about their “Confidential” letters written to the FDA AFTER the overwhelmingly positive AC vote (17-0 safe; 13-4 effective)opposing Provenge approval.
Events show that not only did these two conflicted AC members go outside the norm of writing negative letters to push the 4 minority votes against Provenge approval… a highly unusual and ethically-challenged maneuver… but also these very same letters were somehow “leaked” to a non-peer reviewed cancer “publication” run out of a home basement by 2 people in surburban Washington, DC.
How did this so-called publication acquire copies of “Confidential” FDA letters?
Wasn’t the major purpose of writing these letters was to get them leaked to prevent FDA approval of Provenge and to try to unduely–outside the the FDA approval process–influence in the hopes of preventing approval?
Wouldn’t Provenge approval deep-six or, at a minimum, adversely affect existing treatments–chemotherapy, radiation and surgery–and products in developmental clinical trials such as Asentar–Scher was the Lead Investigator of this Provenge competitor whose trial was halted 6 months later for killing patients? It would do so by setting a higher bar which these other treatments would then have to measure up to.
Lastly, as repeatedly posted here and elsewhere, it is a fact that Howard Isadore Scher certified, in writing, to the FDA that he had 3 Conflicts of Interest in order for him to qualify for an FDA waiver to sit in judgment of Provenge on the FDA AC for it.
Internet research shows not 3, but 17 Conflicts of Interest for Howard Isadore Scher.
1. NOVACEA: Grants & Research support; STUDY CHAIR of DN-101
… a DIRECT competitor to Provenge
… DN-101 failed its clinical trial
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 MYERSSQUIBB: 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. CONFOMA THERAPEUTICS: Scientific Advisory Board
14. DEPARTMENT of DEFENSE: Principal Investigator PC Clinical Trials-P1 and P2
15. AMBRILIABIOPHARMA INC: Principal Investigator PCK3145, Phase I/II
16. MEDIVATION, INC: Principal Investigator MDV3100
17. PROQUEST INVESTMENTS,
… Board of Directors
… Advisor
… INVESTED in Novacea.
So, why won’t the FDA investigate claims of a “Special Government Employee” violating the law?
No FDA transparency here either, Ed. None at all.
Tanin
I agree with Dan that in most cases it does not make sense for a company to reveal what is in a non-approval letter. However particularly in the case of Provenge, I do not think it is appropriate to second guess the FDA without being able to review the letter sent to Dendreon. I think there is a good chance they haven’t released it is because there are ‘real’ concerns about there drug (possibly efficacy) and if it became public knowledge they would lose the support of their fan base.
kyoto27
Ed, I have a question I hope you can answer regarding the FDA’s procedure in overruling its Advisory Committee panels/and the CRL.
Specifically:
If an FDA’s public Advisory Committee (AC) hearing recommends the approval of a new drug and the FDA later issues a Complete Response Letter is there public access or a public record kept at the FDA regarding the “non-public” closed door hearing (s) that resulted in the FDA overruling such a positive AC panel?
Witness the FDA’s Provenge decision:
We all know the FDA has never overruled an overwhelming AC recommendation for approval of a drug for an end-stage disease…making the FDA’s Provenge decision “unprecedented.? Which begs the question: Why this time? It was a decision that made a lot of waves and yet I find it ironic that the media failed to ask the FDA “Who made the decision to overrule the public panel?”
The FDA has been unwilling to answer the even simpler question of whether there is even a public record available (even if one is “unavailable” to the public now). And if there is no public record, is the FDA telling Americans that it does not keep transcripts of all the arguments, notes and votes of those who attend the “non-public” meetings? Are life and death decisions at the FDA made with “winks & nods” without serious discussion and debate? And who would that benefit? It would also be nice to know who calls the non-public meeting(s) to order, and who decides who attends the “non-public” meeting(s)? And finally, is there even a meeting?
Considering this is The United States of America, it appears that it is not meaningful if the public AC hearing is merely a sham and the “real meeting (s)” occurs behind closed doors.
The CRL is one issue; but the other issue is whether there is/are formal meetings at the FDA “prior” to the issuing of a CRL? And God forbid the FDA tells us who called the meeting (s), who attends and how they voted? Because no one outside of the FDA appears to be able to answer this question, it raises a bizzare thought: What if there is/are no meetings?
Thank you Ed for any help here.
Ed Silverman
Hi Kyoto,
I believe one has to file a Freedom of Information Act request, otherwise known as a FOIA. Of course, that doesn’t mean you’ll get anything, because material may be deemed confidential trade secrets concerning the drug manufacturer whose drug is being reviewed.
Hope this helps,
ed
Dan A.
Tony F:
Great illustration of the issue.
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