A former Pfizer oncology director has been given a green light by a federal judge to pursue a whistleblower lawsuit against the drugmaker over claims that allegedly 'dirty data' was being hidden from the FDA. And the judge struck down a Pfizer argument that the former employee, who claimed she lost her job over the disclosures, was not protected by a state labor law governing retaliation.
Here is the background: For two years, Delina Ferretti was director of oncology at Pfizer, where she was responsible for handling clinical operations for various compounds and overseeing data reviews. But five months into the job, she noticed a problem with one drug that was in Phase I testing - study participants were using prohibited medications and adverse events were not reported to the FDA.
In effect, the data was dirty. And Ferretti asked two clinical project managers, who concurred, according to her lawsuit. So in November 2008, she told her supervisor that the study needed to be redone and that Phase III testing should not be undertaken. As the lead clinical protocol manager, Ferretti was responsible for overseeing Phase II studies and establishing Phase III studies.
Her entreaties went nowhere, so she later informed Louis Denis, who was director of clinical research for Pfizer Oncology at the time, according to the lawsuit. He allegedly refused to distribute the information to study sites or clinical investigators, and ordered Ferretti to rescind her communications about the data on the drug, which was called PF-0299804 and was part of the PanHER program.
She claims she was subsequently ostracized and later transferred to another program, but ultimately, was given poor performance reviews and was fired in August 2010, but not before reporting the episode to the internal Pfizer compliance hotline. She filed her lawsuit, which you can read here, one month later.
In response, Pfizer argued that California's labor code, which says that an employer may not retaliate against an employee for refusing to participate in activities that violate state or federal law, did not apply. The drugmaker maintained that Ferretti's refusal to proceed with the clinical trial work for the drug was not considered protected activity (read here). But US District Court Judge Lucy Koh disagreed. "Thus, taking all the facts in the light most favorable to plaintiff, as the court must on a motion to dismiss, it is reasonable to infer that plaintiff refused to participate in defendant's PanHER program because defendant's PanHER program violated and would continue to violate several federal IND regulations," Koh wrote in her ruling last week (here is the ruling).
By the way, Ferretti also maintained that Pfizer, at the time her lawsuit was filed, had still not provided a clinical study report to the FDA, allegedly because the drugmaker was concerned about the 200 instances in which study participants had taken other medications and the lack of adverse events reported to the agency or the annual update of an investigator's brochure.
pic thx to katerha on flickr
37 Comments
Seems like the typical way Pfizer handles everything and for God's sake don't call the corporate compliance hotline unless you want to be fired. They should rename the hotline the automatic termination number instead. Their written compliance rules mean nothing because that is not how the company does business. Fines have had very little influence on Pfizer since those guilty never pay for their crimes, just the stock holders.
What were the names of the drugs and how was the data corrupted by the drugs?
Company,
I have seen a lot of this 'stuff' going on, as long as I can recall. It's very scary to see what meds are going into your body that may not do what they are advertised to.
For instance, the average cancer drug shouts from the rooftops, that they have been able to extend the lives or prevent remission for a whopping three or four months. Is it really that meaningful to spend literally billions of dollars for medicine that gives no quality, just quantity? Just enough time to get your will together.
Was this 200 different meds, or was this, like onen baby aspirin for headache 200 times?
In the lab the mantra is "don't waste clean thoughts on dirty data". However, real life ain't like the lab. In fact, show me a "clean" Phase I study and I'll show you the way to the land of Oz. Given the fact that P-I studies require exact timed dosings, exact meal times, exact blood draw times, etc., every P-I study could conceivably contain hundreds of protocol violations due to timing errors alone, since humans can't be controlled like lab rats.
Also what do you do if you catch a participant sneaking a cigarette out the back door after curfew on the final study day, since tobacco is a non-no. Do you trash all of that subjects' data, go back to square one and spend $20K in a new subject.
The reality is that 99.9% of such deviations don't influence the data, and even a con. med is not likely to either unless it is a metabolic enhancer or inhibitor.
Hi Question,
The name of the drug - or in this case, the number - is listed as PF-0299804.
Hope this helps, ed
The world needs more people like Ms. Ferretti. Kudos to her for putting public interest ahead of profits and to Judge Koh for cutting through the corporate BS. Remember that Pfizer is the company that left the "50 something" female employee stranded in the parking lot when they terminated her and took the company car back. I believe she lost her discrimination case. As a 12 year veteran of "big pharma" there is far too much of this nonsense going on and virtually no accountability. I hope she wins big in this suit, but unfortunately I'll take a guess that the bad behavior will continue because, after all, profits come before people. What a disgrace!!
Karen Kirkpatrick was left in a storage unit parking lot two miles from home. Anybody who can't figure out how to get two miles to their house is someone I would wonder about. If all else failed she caould have walked home since all her gear had been taken away.
Geoff Holt has nothing on our old boss, Don Rumsfeld, the "silver shark" CEO at Searle. Rummy's favorite move was to wait until you were on a business trip. He wouls call your hotel and leave a message to call his secretary. When you called back you were told not to return to the office, and that your desk contents were being packed up in a box and shipped to your house.
Nice welcome home present.
Unprofessional behavior, and inexcusable. Glad to see people are finally standing up to these idiots.
Some, or most of you make the industry look rift with crooks. I wonder how drugs that work, get to the marketplace.
FYI -
Generic Name: dacomitinib Synonym: PF-299 PF 00299804
www.pfizer.com/files/news/esmo/dacomitinib_pf_00299804_fact_sheet.pdf
Go Ms. Ferretti! Sue the living hell out of those frauds!
Gay
One problem here is that adverse events were not being reported to the FDA. This is a phase I study for a drug that is still under development. That means that SERIOUS adverse events were not being reported to the FDA.
SAEs have to be reported to the FDA within 15 days.
Not reporting is a misdemeanor (first time) or felony (second time).
Here's what SAEs are from the FDA's website:
Death
Life-threatening (substantial risk of dying)
Hospitalization (initial or prolonged
Disability or Permanent Damage
Congenital Anomaly/Birth Defect
Required Intervention to Prevent Permanent Impairment or Damage
Other Serious (Important Medical Events) (When the event does not fit the other outcomes, but the event may jeopardize the patient and may require medical or surgical intervention (treatment) to prevent one of the other outcomes.)
Anyone with any experience with clinical drug trials is required to be trained regarding this, and not knowing it (much less not doing it) is inexcusable.
As for allowing other drugs.
Since this was a Phase I study (assuming it was an early study in humans), even basic information to predict interactions was almost certainly not done at this point. For a cancer drug administration with other cancer drugs or the an inducer or inhibitor can result in death and is also inexcusable. (I've seen this actually happen in academic centers with experimental anticancer agents.)
Salmon
Salmon, as you know many ex US Phase I studies are carried out pre-IND, requiring only Ethics Committee Review and approval. The IND is filed later in the US FDA. Under such circumstances only the IRB needs to be informed when an SAE occurs, and the SAE's are later included when the IND is ultimately filed in the US.
To the best of my knowledge this has not been superseeded by ICH Guidelines. Given the popularity of P-I studies in Third World countries I doubt that some of these SAE's would ever see the light of day if an IND is never filed.
I hope she prevails and wins millions of dollars.
Steve, do you really? Seriously, do you?
I either have to pay $190 out of pocket for nine doses of migraine medication, or use "CVS Extra Strength Headache Relief" which does SQUAT. I could at least be using "Excedrin Migraine" but the GD angels that you're referring to were SPIKING THE OCD DRUG WITH OPIATES.
You wonder how drugs that work get to the market? Here's how: there is insufficient oversight and enforcement to catch all the bastards. And insiders on both ends with greasy palms accepting "gifts" for "plausible deniability."
Gay
While SAEs not under an IND (such as early studies not conducted in the US) do not have to be reported to the FDA within the 15 day deadline the article clearly states "adverse events were not reported to the FDA." It also states that the drug was in Phase II and was heading into Phase III.
Typically initial phase I studies have been conducted in the UK because the drug laws only regulate studies in patients (not healthy volunteers) or Belgium because you only have to notify the government that you are doing a study. It's after these early (and almost definitely for phase II studies) that an IND is submitted for US studies and that's frequently for a US conducted phase II study.
Even if the SAEs occurred ex-US, when the IND was submitted for US studies they would have to be reported to the FDA to get approval to do US studies. In this case it may not violate the FD&CA (law not a regulation) as to the 15 day SAE reporting deadline but it would probably be fraud on the FDA and probably violate Federal Criminal Laws:
18 USC § 1001 - Statements or entries generally
(a) Except as otherwise provided in this section, whoever, in any matter within the jurisdiction of the executive, legislative, or judicial branch of the Government of the United States, knowingly and willfully—
(1) falsifies, conceals, or covers up by any trick, scheme, or device a material fact;
(2) makes any materially false, fictitious, or fraudulent statement or representation; or
(3) makes or uses any false writing or document knowing the same to contain any materially false, fictitious, or fraudulent statement or entry;
shall be fined under this title, imprisoned not more than 5 years hen the IND (In Europe any deaths have to be reported to the regulatory bodies.)
Salmon
Big Pharma=Big Corruption, its the way they do business like payoffs, bribes promotions for increasing profits, yup, just like the mob, and no one can touch them!
I agree with original industry insider, and in my opinion the woman suing is a prime example of the greed of disgruntled ex-Pfizer employees who in this case is placing the approval of a promising oncology drug in jeopardy for their own personal gain, at the risk of depriving cancer patients of new and alternative therapies. I was let go by Pfizer myself, and I agree with original industry insider that 100% patient compliance is unrealistic. I have sat in and participated in clinical operations meetings every day as part of my job, and not just at Pfizer. If the company did not have convincing data that this drug was giving positive responses in its indication (lung cancer in this case) it would not be in Phase 3.
Hey Fat Old Man - you are an idiot. I too am an ex-Pfizer survivor. If you actually read beyond the fact the Ms. Ferretti identified SAFETY data that was not being reported and Pfizer, in their typical fashion decided to not only sweep it under the rug but also sideline and eventually do away with "the problem", aka Delina Ferretti, and then attempt to strip her of all her due benefits and protections as an employee, you might think differently. How can you possibly say she is "depriving cancer patients of new and alternative therapies" when Pfizer, by refusing to be forthcoming and being outright deceitful is "doing right" by the cancer patients? Would YOU want to take a drug that has not been properly vetted for safety and efficacy? She wasn't trying to take down a drug program - she was trying to make it better by pointing out errors in the data so Pfizer could CORRECT themselves and move forward with the program. Have you ever run a Phase I oncology trial? Do you even understand the FDA/ICH Regulations? If you did - you would not have made such a ridiculous comment! Shame on you for blaming the messenger!
Hey, fat old man, you've ben Pfizerized by OncMed, although I'm sure you've heard that term before. Stick with me and I promise you that we will both have expletives hurled at us like errant javelins from the Land of Pharmalot, yielding language unfit for the human ear.
Fear not. If you like verbal punishment stay close behind.
Seriously, anybodu that has ever set foot inside a Phase I Unit would know what we're talking about. If logic were to apply you would have to take every one of Lilly's drugs off the market. Because Lilly did many P-I studies on homeless alcoholics they scooped off the streets of Indianapolis by waving a wad of cash in front of them. Give them a tuneup, warm bed, a bath, three squaresa, a haircut, pool table and a big screen TV and they're ready for dosing. Maybe a tad high on the liver enzyme side, but who's quibbling. Certainly not the subjects.
How many decades behind the times are you?
Synthroid.
The Kennedy Hearings in the early 1970s.
I have not been Pfizerized; I have worked in other companies, and I do understand the agency guidances. I have not seen described what employee protections the lady was denied. I do know the group in San Diego and have a lot of respect for them. What I do have is a wife who is living today because of the new targeted therapies like PF-804 that are still being developed, so that is my motivation in hoping to see new drugs get launched. If you think that woman's motivation is anything other than personal enrichment at any cost you have a lot to learn.
FOM, personal enrichment is the new mantra for ex pharma folks. You nailed it. Go to any professional pharma website. Who do you you see as sponsors? You see wall to wall ads by whistleblower lawyers and qui tam lawyers, the ultimate detritus at the bottom of the ocean, scrounging for business. Take a glance at Cafe Pharma and what you WON'T see are discussions about pharmaceuticals. All you see is talk of overtime lawsuits, gender discrimination lawsuits, and lawsuits of just about every kind, just to get back at the corporation that provided them with a standard of living better than just about every other profession.
Clinical Pharmacologist, the FDA call for NDA's for levothyroxine products was published in the August 14, 1997 issue of the Federal Register. A day that will live in infamy.
That was 1.5 decades ago. Not that long. However, last I checked, the bank is still cashing the bonus checks I made while Synthroid was riding high in the saddle. Could have been 10.5 decades ago as long as Uncle Sam is still recognizing those greenbacks the Synthroid Franchise worked so hard to earn.
I doubt that the pointy heads at the FDA who yanked our chains and made me give up a Hilton Head vacation to write the Synthroid NDA have done as well over the past 175 months.
ps what we're the Kennedy Hearings? Did someone nail JFK for nailing all those secretaries in the White House pool?
Yep, and one more thing, a director is not an executive, she was a middle manager. My guess is she was paid for her work there just as I was, so I don't know what terrible things Pfizer did to her other than let her go, which has happened to so many other Pfizer employees that I can guarantee you they are very good at it.
Making it to Phase 3 is not an indication that the drug was giving positive responses - it sounds like it may very well may be based upon false data. Interesting spin from several Pharma people. Apparently fat old man thinks its okay to shove through non-compliant patients and false data? And why are consumers not demanding clean compliant data? Kudos to the Plaintiff. Does fat old man work for Pfizer? Certainly sounds like it.
In the Know, here's a typical Phase I subject recruited off the Mean Streets. Just needs a 200,000 mile oil change and he's good for dosing. You tell me how much "clean" data to expect.
http://www.fotosearch.com/CSP009/k0092219/
For your information, these studies Ms. Ferretti is referring to were not done in a "Phase I" unit. Phase I oncology studies are conducted on actual oncology patients with advanced/metastatic disease. It is imperative that data collected from these patients on studies is as accurate and accurately REPORTED to the FDA and in all sponsor documents, such as a CSR. To whitewash, suppress or omit safety data on these patients is completely unacceptable - by any company. Again, shame on all of you critics for defending such reprehensible behavior. Maybe if your employer did this to you and tried to deny you all your due benefits, you too might decide to push this matter. It is patently obvious what is going on here when a company doesn't deny the screwed up but tries to defend themselves by claiming the accuser does not have the right to defend themselves. I wish Ms. Ferretti all the best and hope this sends a chilling message to the industry that they had better conduct themselves in accordance to the FDA/ICH/GCP regulations, State and Federal laws. Remember, Honor Thy Patient - for without them, none of us would have jobs. Once they sign the consent, we MUST do right by THEM no matter the "cost"...
"Phase I oncology studies are conducted on actual oncology patients with advanced/metastatic disease."
I can tell you from professional and personal excperience that such patients are usually on at least one dozen other medications, many of them powerful metabolic inhitors or inducers. They also have gossly altered metabolism because of their disease, mostly a wasting, cachectic hypermetabolic state because their tumor is eating up their nutients faster than they can.
And you're worried about a few contraindicated concomitant meds? Now that you have given this additional information about the setting for Phase I Oncology studies, I'm convinced that Ms. Ferretti's charges are more baseless than before.
If you've done these studies you know that we call these patients "PPP"- p**s poor protoplasm. The last thing I'd worry about is conmeds, and if there were ONLY 200 such protocol violations in a mets oncmed study i'd say that wasn't half darn bad.
BTW you guys shouldn't even be doing Phase I trials in such sick patients. Get with modern times and switch to Phase 0 studies in this patient population. Lower doses, fewer patients, lower toxicity, and then we won't have people like Ferretti to complain about the "ethics" of a study that ethically speaking should never have been done in the first place. Then again Pfizer was never on the cutting edge of much of anything R&D.
http://www.cancer.gov/newscenter/qa/2007/phasezeronextqa
Let's go to the study, for which I have found the protocol outline for Phase I study. Here is the actual, VERY extensive list of prohibited concomitant medications, so extensive, IMO, as to render it almost impossible to to the study without encountering numerous con med protocol violations. Whoever approved this protocol in house should be shot on site:
"Use of drugs or foods that are known potent CYP3A4 inhibitors within 7 days prior to the first dose of study medication, including but not limited to itraconazole, ketoconazole, miconazole, clarithromycin, erythromycin, indinavir, nefazodone, amprenavir, delavirdine, nelfinavir, ritonavir, saquinavir, diltiazem, verapamil and grapefruit juice. - Use of drugs that are known potent CYP3A4 inducers within 12 days prior to the first dose of study medication, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifabutin, rifampin, tipranavir, ritonavir, and St. John's wort. - Concurrent use of drugs that are CYP3A4 substrates with narrow therapeutic indices, including but not limited to pimozide, aripiprazole, triazolam, ergotamine and halofantrine. - Concurrent use of drug that are highly dependent on CYP2D6 metabolism including S-metoprolol, propafenone, timolol, amitriptyline, clomipramine, desipramine, imipramine, paroxetine, haloperidol, risperidone, thioridazine, codeine, flecainide, mexilletine, tamoxifen, venlafaxine.
Dextromethorphan, a CYP2D6, substrate is allowed if medically indicated and no suitable alternative anti-tussive medication is available. However, the dose of dextromethorphan may need to be modified. In a clinical study in healthy volunteers who were extensive metabolizers (A7471039) PF-00299804 increased mean total exposure (AUC(last) and C(max)) of dextromethorphan 855% and 874%, respectively, following concomitant administration with PF-00299804 45 mg compared to exposure of administration of dextromethorphan alone. Extensive metabolizers comprise approximately 80% of the population, with ultra-, intermediate-, and poor-metabolizers accounting for the remaining portion of the general population. Therefore, if no alternative is available dextromethorphan dosing should be initiated at a lower dose (approx 25%) with close monitoring of patient clinical status. Dose increases or decreases of dextromethorphan may be considered based upon individual patient tolerability. Lidocaine may be used systemically with clinical monitoring (including telemetry).Opiates such as morphine, oxycodone, dihydrocodeine, hydrocodone, and tramadol can be used as substitutes to replace codeine. Use of these opiates should be monitored for altered analgesic effect during treatment as they may be partly metabolized by CYP2D6."
That's 52 prohibited con meds for starters, probably several hundred if you include all the meds that are listed only by class. This study was a protocol vioation waiting to happen.
http://clinicalstudies.info.nih.gov/detail/A_2011-C-0250.html
Original Insider must be jailed! The debate here is not about how sick the phase 1 oncology patients are. the issue is did Pfizer obey the regulations? If you are showing off how much you know about oncology please dispaly that somehwhere else. Bottomline, whether or not the trial was conducted ethically and the side effects were reported on time per the regulations or reported at all, are the questions in this law suit. For example his advsisory "BTW you guys shouldn’t even be doing Phase I trials in such sick patients" yoh, go tell this to Pfizer! Again, this is not the issue here or the subject of this law suit!! kapish??
reg expert, I hope you will petition me for early release so that I can get you out of the office and instruct you on how to properly write a clinical trial protocol that would have avoided these problems in the first place.
Have you ever actually written a 150 page protocol in less than two weeks?. Yes these types of protocols can be that long, as you know. Or, have you just sat back in your La-Z-Boy, with red pen in one hand and a nice cold Snapple in the other hand, taking your sweet time to nitpick every other work the medical honchos like me wrote?
Regulatory folks are experts at wielding the retrospectoscope since the've never really been in the trenches of actually doing clinical trials.
I refer for your reading the book "Analysis of Messy Data". Read it, all three volumes, that is if you know anything about statistics. That's because these messy data need to be analyzed, maybe reanalyzed 5X without the outliers, and NOT second guessed or subject to crimimal prosecution, as you guys are so eager to pull the trigger on.
http://www.amazon.com/Analysis-Messy-Data-Nonreplicated-Experiments/dp/0412063719
http://www.amazon.com/Analysis-Messy-Data-III-Covariance/dp/158488083X#_
http://www.amazon.com/Analysis-Messy-Data-Designed-Experiments/dp/0412990814
Orig Insider:
You are a medical honcho??? no wonder you are an incompetent! do you write clinical protocols for ghost studies??? You heard about ghost articles, written by corrupt so called medical spin doctors or medical honchos like you!
then you probably know nothing about clinical development/science.......let alone oncology drug development. I'll take a guess, either you are from Abbott, Pfizer or JNJ, the marketing and medical spin based corrupt companies..... Big Pharma minus the true very few innovative drug development companies, are total FRAUD!!! they are playing with the sick patients lives and taking advantage with their pseudoscience and corrupt science....
Reg expert, when I worked on expanding the clinical program for Synthroid, we were know as "The Measure of Excellence" and "The Trusted Brand". It's still a pretty good drug, though probably not innovative by your standards. I also worked on the clinical NDA for zolpidem, the most successful sedative hypnotic in history. I also worked on competitive products to Premarin to try to break up their monoploy on the women's health market. That;s just a brief sampling of my many accomplishments.
I don't know what a ghost protocol is, but I do confess to ghost writing several NIH grants as a National Institutes of Health Post Doctoral Fellow. I wrote these grants for Medical School faculty members who were expected to do research but who were too busy taking care of critically ill patients, a humanistic endeavor I trust you have little experience from the cozy confines of the reg affairs chair.
Thus I've been in the trenches my whole career. Where have you been for the past thirty years? I'm sure we are all waiting with eager anticipation as to exactly where ny above experience places me on your most wanted list of pharma fraudsters. Perhaps you can put down that Snapple to grace us with a few keystrokes.
Actually, regexpert, I do know what a ghost protocol is. It's the subtitle in the latest sequel to the "Mission Impossible" series. It is a total work of fiction, but then again most critics of my industry lack the intellectual sophistication to tell the difference between fiction and reality. No problem. I enjoy humoring you guys anyway.