Charles Grassley

U.S. Paxil probe broadens

Tracy Staton — Fri, 20 Jun 2008 09:20:10 -0400

More government watchdogs appear to be boarding the Paxil investigation train. The Justice Department is coordinating a probe that includes Colorado's Justice folks and the Boston U.S. attorney's office. GlaxoSmithKline had already disclosed the Colorado investigation and confirmed the rest in today's Wall Street Journal. Investigators are gathering documents and depositions about Paxil's potential link to suicidal behavior, at least in part from plaintiff's lawyers representing families suing the drugmaker, and about GSK's portrayal of those risks to doctors and the FDA, the WSJ says.

Glaxo says it's cooperating with the investigation and that it can't comment further. In the past, the company has said that it "acted properly and responsibly" in testing Paxil and passing on trial data to regulators.

According to the WSJ, the probe is particularly focused on Glaxo's submissions to the FDA about Paxil and suicidality when the drug's approval was pending. Investigators also were anxious to get their hands on some documents, under court seal, that disputed GSK's research conclusions on suicidality risks. GSK gave the Justice Department those documents, stipulating that they not be passed along to the FDA.

You'll recall that last week, Sen. Charles Grassley demanded an FDA investigation of Paxil's 1992 approval. That followed a years-long U.K. investigation that recently ended with no charges against GSK because British laws on data-sharing are unclear.

- read the Wall Street Journal story

Grassley asks FDA for Paxil review

Tracy Staton — Fri, 13 Jun 2008 10:25:02 -0400

Seemingly tireless FDA critique-man Sen. Charles Grassley now has his eye on GlaxoSmithKline. He's asking the FDA to review GSK's antidepressant Paxil, which just emerged from a years-long probe in the U.K. Namely, Grassley wants the agency to determine whether the company knew about Paxil's links to suicidality when it asked for U.S. approval, and whether GSK concealed knowledge of those risks as time went on. Grassley is also questioning a particular trial in which, he says, GSK may have assigned patients with previous suicide attempts to the placebo group to inflate suicidal behavior in that group so that the Paxil-taking group would look better. "Essentially, it looks like GlaxoSmithKline bamboozled the FDA," he said during a statement on the Senate floor.

You'll recall that the U.K. investigation--into whether GSK withheld unflattering Paxil data from drug watchdogs--yielded no criminal charges. It did lead to a public chiding from officials, who said the only reason they weren't pressing charges was because U.K. law was inadequate. Immediately MPs pledged to change the law to require drugmakers to fork over all the data they have on drugs they're submitting for approval. Grassley wonders whether U.S. law is also inadequate. "I am asking the FDA to take a look at the same information that was examined in the U.K.," he said in his letter. "And I am asking the FDA if we need to change any laws here in the United States."

- check out Grassley's release and letter
- see the WSJ Health Blog item

Pfizer strikes back with Chantix ads

Tracy Staton — Thu, 29 May 2008 10:01:45 -0400

Hit by new concerns about the safety of its stop-smoking drug Chantix, Pfizer is hitting back with an advertising and PR campaign. And no wonder: The drugmaker has been counting on that drug, with $883 million in sales last year, to help make up some of the $13 billion it could lose off its top line once Lipitor faces generic competition. Major newspaper ads today are designed to explain Chantix's risk-vs.-benefits calculus, and next week, Pfizer will host roundtable discussions with reporters.

Meanwhile, Sen. Charles Grassley is asking the FDA about the study released last week linking Chantix to a litany of adverse events, including 988 serious reports during the fourth quarter of last year, more reports than with any other drug, Grassley noted in a letter to the agency. One issue: whether Chantix is safe at the recommended dosage. Even before the drug was approved, FDA questioned whether the dosing should be lowered. But Pfizer reminds us that FDA did end up approving the current dosing levels, and that the newly reported side effects are in fact listed on the product label. We'll see how the brouhaha shakes out.

- see the story in the Wall Street Journal

JAMA: Merck paid docs for bylines

Wed, 16 Apr 2008 06:59:58 -0400

Merck wrote its own articles on Vioxx research and then paid prestigious doctors to append their bylines, according to a new story in the Journal of the American Medical Association. Of course, Merck isn't alone: the JAMA article notes that ghostwriting appears to be widespread in the pharma industry. "It almost calls into question all legitimate research that's been conducted by the pharmaceutical industry with the academic physician," said the study's lead author, Dr. Joseph S. Ross of the Mount Sinai School of Medicine.

But the ghostwritten Vioxx research is noteworthy because the drug went on to become a best-seller--and then a fiasco, as Merck withdrew it because of links to heart attacks and, most recently, agreed to pay $4.85 billion to settle related lawsuits. It's also interesting because those very lawsuits unearthed documents that shine a bright light on the way Merck promoted Vioxx data. Usually, those documents are kept in drug company filing cabinets and never meet the public eye. Also, the JAMA reports allege that Merck dragged its feet when reporting data on safety risks that arose during two studies of Vioxx in dementia patients.

Now, these JAMA articles relied only on the legal documents and published studies; none of the authors were contacted. Since the reports were published, some expert authors have defended their roles in the Vioxx articles, saying that they didn't simply come in after the fact and add their names, but participated in the research itself. "It's simply false that we didn't contribute to the final publication," one said. But that same professor told USA Today that he never had all the statistical analyses for that study; his role in it was to judge the accuracy of participants' Alzheimer's diagnosis, not the effect of the drug, he said.

We may get some more public documents to pore over soon, however: Sen. Chuck Grassley has put one of the ghostwriting companies--Scientific Therapeutics Information--on the hot seat, asking the company about its dealings with Merck.

Plus, expect to see debate over JAMA's proposals for reform. They include a half-dozen bids for increased transparency in clinical trials and study publication.

- check out Merck's response to the JAMA articles
- find the JAMA abstract
- see Grassley's letters
- read the Boston Globe story
- see one researcher's conflicting accounts of a Vioxx study at Pharmalot
- check out JAMA's recommendations

Related Articles:
Could full data disclosure avert scandal? Report
Vioxx plaintiffs sign on, deal proceeds. Vioxx report
Positive data more likely to find its way to public. Report

Arms twisted, pharma promises disclosure

Fri, 11 Apr 2008 06:59:55 -0400

Pharma knows that self-regulation is the best kind. That's why 12 drug and device makers have promised Sen. Chuck Grassley that they are working on plans to disclose CME grants. You know, the money companies spend to sponsor educational conferences for doctors--conferences where sponsors sometimes influence not only who speaks, but what those speakers say. Some companies are even pledging to disclose their support of patient groups such as the American Heart Association or the American Diabetes Association.

Eli Lilly already discloses its CME funding. In response to Grassley's prodding, Medtronic and AstraZeneca said they'd post payments for professional meetings and patient-advocacy groups on their company websites, beginning May 1 and August 1, respectively. Merck said it's "developing an action plan." Amgen and Abbott Labs have formed working groups to study the subject.

Only Schering-Plough balked. "We do not publish or have plans at the moment to publish a list of charitable contributions or educational grants that medical organizations have received from us," the company wrote Grassley. We'll see if that refusal stands.

- see the Los Angeles Times story
- check out the item in the WSJ Health Blog

ALSO: According to California's Public Interest Research Group, disclosure of doctor payments isn't working to enforce limits on those gifts. A new report on these payment limits concluded that drugmakers don't always count meals as "gifts," that some companies reserve the right to exceed the limits if they choose to, and others say they're following limits, but don't say what their limits are. Some don't even post their policies. Study

Related Articles:
Pharma racks up multibillion-dollar marketing bill. Pharma report
Senate investigates pharma influence on CME. Senate report
Australia eyes CME's ties to pharma. CME report

Seroquel researcher got cash from AZ

Tue, 08 Apr 2008 06:59:56 -0400

Sen. Charles Grassley's hall of shame: The chairman of the Senate Finance Committee, who's been trying to rally support for a bill requiring drug and device makers to disclose anything of value given to doctors, raised the case of Dr. Melissa DelBello, a psychiatrist who got hundreds of thousands of dollars in travel expenses, consulting fees, and lecture payments from AstraZeneca. DelBello also happened to be lead author of a study that concluded kids did well on AstraZeneca's antipsychotic med Seroquel.

Here's the timeline: DelBello authored the study, published in 2002. In 2003, she got $100,000 from the drugmaker, or so she told the University of Cincinnati. In 2004, she reported $80,000. AstraZeneca's figures total $238,000.

Grassley was pretty peeved not only about the apparent conflict of interest--which AstraZeneca denied; DelBello wasn't available for comment--but also by the fact that DelBello also got NIH funding during the same period. University of Cincinnati said it applauds Grassley's "looking into this very important issue."

- read the WSJ Health Blog item
- see Grassley's Physician Payment Sunshine bill

Related Articles:
AZ takes steps to shore up Seroquel. Report
AZ's Seroquel receives additional approval. Report

Congress: M/S-P sat on bad news

Tue, 01 Apr 2008 07:59:58 -0400

The Vytorin onslaught continues, with Congressional committees circling and secret emails surfacing. And Merck and Schering-Plough, looking to minimize the damage, are criticizing the American College of Cardiology panel convened to discuss the controversial Enhance study and readying a sales-and-marketing push to counteract the negative publicity.

First, Congress. The Senate Finance Committee and House Energy and Commerce Committee have been on the Vytorin/Zetia case for months, probing everything from the reasons behind the delay in presenting study results to the DTC marketing that went on while the Enhance data was under review. Now, the Senate is asking for more information on the study's delay. And Sen. Charles Grassley has released evidence that the companies might have known long ago that Vytorin wasn't any more effective than Zocor alone, but kept mum to avoid deflating sales. Among that evidence: Emails from the study's lead investigator John Kastelein, who was left out of the loop when Merck and Schering Plough considered changing the study's primary endpoint. "[T]his starts smelling like extending the publication for no other (than) political reasons," one message read. Another said, "You will be seen as a company that tries to hide something and I will be perceived as being in bed with you!"

Schering says those emails were taken out of context and that Kastelein's complaints were resolved long ago. Merck says the study was delayed because of difficulties interpreting complex data. But the House committee has cited evidence from an Internet site where sales reps posted back in March 2007 that "the study is a bust."

Meanwhile, Merck and Schering-Plough are doing damage control as they watch their stocks drop, 15 percent in Merck's case and 26 percent in Schering's. Among their strategies: a letter for doctors that presents the companies' view of Enhance, covering a copy of the entire study. "Our sales force and medical-affairs group have been well prepared about what this study is and how to talk about it." The companies also plan to aggressively defend Vytorin and Zetia to managed care plans and pharmacy benefits managers--and are considering when and whether to resume DTC ads.

- see Senate Finance's press release, including Grassley's letters (.pdf)
- read the Washington Post story
- check out the NYT's coverage of Congressional accusations
- get more on the emails from the WSJ Health Blog
- see Merck and Schering's defensive plans in the WSJ
- find more on Grassley's letters, also in the WSJ

ALSO: Silver lining in the Enhance cloud? Maybe, for Merck's awaiting-approval cholesterol med Cordaptive and Abbott Laboratories' niacin-based meds Niaspan and SimCor and fibrate TriCor. Niacins and fibrates were both recommended by the New England Journal of Medicine as backups for when first-line statins have failed. The NEJM said Vytorin and Zetia should be last resorts. Report | Report

Related Articles:
ACC panel unleashes Vytorin whirlwind. Report
Companies saw Vytorin threat in 2005. Report
Congress: Were Enhance results secret? Report
Congress promises Vytorin hearings. Report
Merck, Schering defend embattled Vytorin. Report
Merck, Schering's Vytorin fails trial. Report

GAO to probe FDA's post-market follow-up

Wed, 05 Mar 2008 06:59:58 -0500

The government's own watchdog will soon be sniffing around FDA drug approvals and FDA-ordered post-marketing studies. Prompted by Sen. Charles Grassley, the Government Accountability Office plans to investigate the practice of using biomarkers such as blood sugar in diabetics and cholesterol levels among those at risk of heart disease, in evaluating efficacy. These measures are used in drug trials in part because assessing actual outcomes like heart attacks and strokes requires years-long studies that cost megabucks. If the FDA required pre-approval outcomes studies, new drugs would come to market even more slowly than they do now. And development costs would skyrocket.

Lately, though, biomarkers have become controversial as safety and effectiveness questions arose about meds such as GlaxoSmithKline's Avandia. That drug was approved because it lowered blood sugar, which docs believe will in turn cut the risk of heart attack. But a study last year showed that Avandia might actually increase heart-attack risk. Then, early this year, a major trial of Merck and Schering-Plough's cholesterol med Vytorin showed that it did a better job of lowering bad cholesterol than a generic statin did--but it did no better at preventing plaque buildup in patients' arteries. So in these cases, long-trusted biomarkers were called into question, and some experts contended that the FDA shouldn't OK a product without real outcomes studies.

Now, the GAO has agreed to weigh in on the subject. Sen. Charles Grassley (R-IA) asked the watchdog to investigate. His point: If the FDA uses biomarkers to approve a drug, then it needs to enforce its own calls for post-marketing outcomes studies, so-called Phase IV trials. Is the FDA doing so? According to a 2006 Health and Human Services investigation, no; at the time, the FDA couldn't even readily identify which companies had made progress on those studies and if so, how much. Recently, the FDA said that of 1,200 of the studies it had required 900 hadn't even begun.

Under a new law, FDA can fine companies up to $1 million for failing to perform those studies. But is $1 million an adequate punishment? Grassley has argued for higher fines, and in his request to the GAO, asked whether FDA needs more authority to compel the studies. All we can say is, if the FDA got all the power and money its critics say it needs these days, it would be formidable indeed.

- check out Grassley's release and letter to the GAO
- read the AP report

Related Articles:
FDA, drug industry re-negotiate user fees. Report
Report faults FDA's post-marketing vigilance. Report
Analysis shows post-marketing studies ignored. Report
Sponsors say post-marketing drug studies are a bust. Report

Grassley takes aim at Prodisc

Thu, 28 Feb 2008 06:59:54 -0500

Yet another medical device maker has been called on the Congressional carpet. Sen. Charles Grassley is asking Synthes, which makes an artificial spinal disk known as Prodisc, whether doctors whose research led to its FDA approval also had a financial interest in its success.

Last month, The New York Times reported on financial relationships between Prodisc's developer, Spine Solutions, and the doctors who helped test it. A New York investment firm financed R&D on the device via investment funds in which many of the clinical investigators owned an interest. Spine Solutions later was sold to Switzerland-based Synthes.

Grassley asked Synthes for information on the company's financial disclosures to the FDA and for details about the clinical researchers' interests in Prodisc. The senator also wrote to the FDA, asking whether the agency knew about the financial relationships between those doctors and the device's developer. "If FDA found out the investment interests did not raise serious questions about the study's integrity," Grassley wrote, "why not?"

- read the article from the New York Times

Related Articles:
Congress probes med device payments. Report
Feds probe Medtronic payments to docs. Report
Medtronic's doc payments draw new fire. Report
Medtronic will settle accusations on kickbacks. Report

Congress: Were Enhance results secret?

Tue, 12 Feb 2008 06:59:57 -0500

Finally, someone asked the question we've been wanting to ask ourselves: Even if the Enhance study data remained blinded, could Merck or Schering-Plough have divined its overall sway? Sen. Charles Grassley, who's been shooting out letters to the two companies at the rate of at least two a week, made the query in another round of correspondence yesterday.

The question of who knew what exactly when has been central to the whole Vytorin controversy. As the world waited for the Enhance results, did Merck and Schering execs know Vytorin didn't slow the progression of heart disease any better than simvastatin alone? Did Schering execs know anything, for instance, when they sold millions worth of stock last May? Did the companies know anything while they were pushing Vytorin via a big-time TV ad blitz?

Grassley's counterparts in the House also posted new letters this week, asking about some posts on a website for drug reps, Café Pharma. One post last March said, "have a buddy at [Schering-Plough Research Institute]. He says that the study is a bust." Who else, Congress wants to know, might this "buddy" have told?

- find links to the House letters at Energy and Commerce's website
- read the Grassley piece at the Wall Street Journal Health Blog
- check out the Café Pharma item

Related Articles:
FDA to review Enhance study. Report
Congress promises Vytorin hearings. Report
Merck, Schering's Vytorin fails trial. Report