November 11, 2009
ABC News
by Julie Steenhuysen
A study of internal company documents suggests Pfizer Inc altered or omitted unfavorable study findings to expand its epilepsy drug Neurontin’s market, U.S. researchers said on Wednesday, offering a look at how drugmakers influence scientific research.
Clinical trials are supposed to answer a specific, predetermined scientific question, but a comparison of Pfizer documents and published studies on Neurontin for conditions other than epilepsy found that eight out of 20 study reports never made it into medical journals.
And in eight of the 12 published studies, the primary outcome — the answer to the main scientific question — was changed by Pfizer, the world’s biggest drugmaker, from the original study design.
“There were a lot of primary outcomes that were shifted around between the planning of the protocol and the reporting of the study,” said Kay Dickersin of Johns Hopkins University in Baltimore, whose study appears in the New England Journal of Medicine.
“Some primary outcomes were lost altogether. Some were brand new. Some were secondary outcomes that were upgraded to primary,” she said in a telephone interview.
The studies, all funded by Pfizer, showed how the drug worked in people with problems like migraines or pain, which are off-label uses of the drug.
Once a drug is approved, doctors are free to prescribe it as they see fit, and while companies are not permitted to market a drug for anything but the approved use, they can hand out reprints of studies published in medical journals showing how the drugs work in patients with different problems.
Dickersin got the documents while serving as an expert witness against Pfizer, which in 2004 paid $430 million to settle a lawsuit over illegal promotion of Neurontin.
Pfizer was sued again last year by lawyer Thomas Greene, who brought the original case against the company for off-label marketing practices, for holding back negative study results and changing the design of its trials to produce more favorable results.
That case was the latest in a string of allegations against the pharmaceutical industry suggesting it has controlled the flow of clinical trial research to boost its marketing position.
Pfizer spokesman Chris Loder said in a statement the suggestion that the company attempted to mislead the medical community is untrue and was “derived from a report created for litigation and coauthored by plaintiffs’ expert witness.”
Dickersin said the studies she reviewed are still not publicly available.
She said while there can be legitimate reasons to change a study’s primary goal or endpoint, that change needs to be included in a formal amendment and published in a journal.
Not taking that step leaves a false impression, and in the case of companies, reveals the competing interests of scientists and marketing departments, she said.
To improve transparency, Dickersin said study protocols and primary endpoints should be required when companies register their clinical trials on the public database clinicaltrials.gov.
“It’s important for us not to give up on trying to understand this because if we don’t, the truth of science will not be upheld,” she said.
Click here for full report
September 24, 2009
Reuters
By Stephanie Nebehay
Drug makers can only produce enough H1N1 vaccine each year for half the planet because they lack factory capacity, the World Health Organization said on Thursday.
The H1N1 vaccine looks to be as safe as the regular flu shot, the WHO said in a statement, adding that drug makers worldwide can produce an estimated 3 billion doses per year and a single dose should be enough to give immunity to healthy adults and older children.
But it said companies had “limited, inadequate and not readily augmented” capacity to increase output to cover the planet’s 6.8 billion population.
The WHO’s previous projection last May was that global production capacity would be close to 5 billion doses, but its new estimate was made on the basis of results from clinical trials and confidential data provided to the U.N. agency.
“There is not enough production capacity worldwide to vaccinate everyone,” WHO spokesman Gregory Hartl told Reuters.
“New production capacity takes a long time to come on line. Any new single plant for vaccine production takes about five years to build, test and get approval,” he added.
It was not immediately clear whether the WHO’s new estimate of 3 billion doses per year implied switching all production from seasonal flu vaccine to H1N1 pandemic vaccine.
Marie-Paule Kieny, director of WHO’s initiative for vaccine research, is due to give a teleconference at 1500 GMT on Thursday.
“Outcomes of trials completed to date suggest that pandemic vaccines are as safe as seasonal influenza vaccines,” WHO said.
“However, even very large clinical trials will not be able to identify possible rare events that can occur when pandemic vaccines are administered to many millions of people,” it said.
Pandemic vaccines are most effective as a preventive strategy when given before or near the peak incidence of cases in an outbreak, it said.
The WHO advised countries to closely monitor the vaccine’s safety and report “adverse events.” This was vital to determine whether changes in vaccination policies were needed.
Side effects are expected to be similar to those with seasonal flu vaccines, including soreness or swelling at the point of injection and possible fever, headache, muscle or joint aches, according to the United Nations agency.
In almost all people, these symptoms should be mild and last 1-2 days, it said.
Most rich nations have contracts with drug makers to obtain enough vaccine to cover their entire populations, it said.
But most low- and middle-income countries lack the financial resources to compete for an early share of limited supplies, which in such countries would depend mainly on donations.
The WHO said it would begin an initial distribution of some 300 million doses of vaccine donated by rich nations to more than 90 developing countries from November.
Leading flu vaccine makers include Sanofi-Aventis, Novartis, Baxter, GlaxoSmithKline and Solvay.
Regulatory authorities have licensed pandemic vaccines in Australia, China, Hungary and the United States, soon to be followed by Japan and several countries in Europe, the WHO said.
Click here for the full report from Reuters
Tags: 3 billion doses, Baxter, clinical trials, drug makers, flu shot, GlaxoSmithKline, H1N1, immunity, influenza, Novartis, pandemic, production, Solvay, symptoms, vaccine, WHO
July 12, 2009
Reuters
The United States will spend another $1 billion on ingredients for an H1N1 vaccine, U.S. Health and Human Services Secretary Kathleen Sebelius said on Sunday.
“There’ll be another $1 billion worth of orders placed to get the bulk ingredients for an H1N1 vaccination. Congress has agreed with the president that this is the number one priority, keeping Americans safe and secure,” Sebelius said on CNN.
Sebelius has said plans were on track for a mid-October vaccination program, although it was not certain Americans would be offered the vaccine for the so-called swine flu.
“We are aggressively working on, first of all, testing the virus strains to get a vaccination ready. It needs to be safe so testing and clinical trials will start this month. We’ll know a lot more by the end of the summer and it needs to be effective,” she said.
The World Health Organization may issue guidance as soon as Monday on whether an H1N1 swine flu vaccine will be offered alongside the seasonal flu vaccine.
Vaccine makers Sanofi-Aventis, Novartis, Baxter, GlaxoSmithKline, Solvay and AstraZeneca’s MedImmune subsidiary have finished making seasonal flu vaccines for this year.
The U.S. Food and Drug Administration has scheduled a July 23 advisory panel meeting to discuss clinical trials of the vaccines against the H1N1 influenza virus and the U.S. Advisory Committee on Immunization Practice wills meet July 29.
“FDA is working with the scientists at NIH (National Institutes of Health) to make sure that we have a safe and effective strain and then we’re getting ready to make sure that we have a vaccination program,” Sebelius said.
Health experts estimate at least 1 million people have been infected with H1N1 in the United States, and the U.S. Centers for Disease Control and Prevention has confirmed 211 deaths. It often takes weeks or months to collect data on flu deaths.
About 36,000 people die each year from the seasonal flu in the United States alone, and 250,000 to 500,000 die globally.
Click here for the full report from Reuters.
Tags: another $1 billion, AstraZeneca, Baxter, clinical trials, confirmed 211 deaths, congress, FDA, Food and Drug Administration, GlaxoSmithKline, H1N1 vaccine, ingredients, Kathleen Sebelius, MedImmune, Novartis, number one priority, safe and secure, Sanofi-Aventis, seasonal flu, Solvay, swine flu, U.S. Advisory Committee on Immunization Practice, U.S. Centers for Disease Control and Prevention, U.S. Health and Human Services, World Health Organization
July 2, 2009
New York Times
by Gardiner Harris & Duff Wilson
WASHINGTON — Federal drug regulators warned Wednesday that patients taking two popular drugs to stop smoking should be watched closely for signs of serious mental illness, as reports mount of suicides among the drugs’ users.
But officials emphasized that fear should not stop patients from taking the smoking-cessation medicines, Chantix, made by Pfizer, and Zyban, made by GlaxoSmithKline, which also sells it under the brand name Wellbutrin, for depression.
“Stopping smoking is a goal we should all be working towards,” said Dr. Curtis J. Rosebraugh, director of a drug evaluation office at the Food and Drug Administration. “We don’t want to scare people off from trying a medication that could help them achieve this goal. You should just be careful.”
Pfizer will add a so-called black box warning — the F.D.A.’s most serious caution — to the packaging information for Chantix.
The Pfizer drug, introduced in 2006, has about 90 percent of the market for prescription smoking-cessation drugs, according to IMS Health, a health care information company. Even so, Chantix sales — $846 million in 2008 — had been less than Pfizer had hoped because of previous warnings of its side effects.
Glaxo will expand its existing black box warning on Wellbutrin, citing suicidal thoughts by patients who use it for depression, to include Zyban, which has had only modest sales in the smoking cessation market.
Both companies will also be required to conduct clinical trials to assess the mental health risks associated with the drugs’ uses. Pfizer is already enrolling schizophrenia patients in a trial.
Because smokers and people trying to quit are statistically more likely to be depressed and suicidal, officials for both companies said it was difficult to identify the specific impact of the drugs on those risks. “Nicotine withdrawal itself can be very difficult for people to endure,” Dr. Steve Romano, a Pfizer vice president, said Wednesday.
Analysts said the F.D.A. action would have little effect on sales because of previous indications of the drugs’ psychiatric risks.
“I think the market and physicians have already been sensitized to this,” said Catherine J. Arnold, an analyst for Credit Suisse.
“I’m not panicking,” said Jami Rubin, an analyst for Goldman Sachs, “Sales are already down a lot. It is and will remain a small niche product.”
Chantix had already experienced a slight sales decline last year from the $883 million achieved in 2007. And this year’s first-quarter sales of $177 million were 36 percent below the corresponding period last year.
Ms. Arnold predicted that sales would probably continue falling to around $740 million for all of 2009, but that demand for smoking-cessation treatments would enable it to grow modestly after that — to perhaps half of the $2 billion in annual sales Pfizer had originally hoped for the drug.
European officials first alerted the F.D.A. in 2007 to problems associated with Chantix. In September of that year, Jeffrey Carter Albrecht, a keyboard player from the pop-music group Edie Brickell and New Bohemians, was killed by a neighbor who had complained that Mr. Albrecht was banging on his door, ranting. Mr. Albrecht’s girlfriend blamed Chantix, which she said had made him hostile.
The widely publicized event led to a cascade of similar reports and scrutiny by F.D.A. safety officials, who have now received 98 reports of suicides and 188 reports of suicide attempts among those taking Chantix.
As officials looked more closely, they found to their surprise that Zyban has similar associated risks. The agency received 14 reports of suicides and 17 reports of suicide attempts among those taking Zyban.
No one knows why the drugs are associated with mental problems. In some cases, patients could be experiencing nicotine withdrawal, but some of the reports involved patients who had yet to stop smoking. And many of the events happened just as patients began or stopped therapy, officials said.
“If this is nicotine withdrawal, it really doesn’t matter,” said Dr. Robert Temple, an F.D.A. official. “You need to pay attention to them.”
The agency’s action requires the drugs’ makers to mention the risk of suicide in advertising, and it prevents the companies from using “reminder” ads, during which consumers are encouraged to talk to their doctors about a health issue but the product’s name is not mentioned.
Click here for the full report from the New York Times.
Tags: black box warning, Chantix, clinical trials, Credit Suisse, depression, FDA, Food and Drug Administration, GlaxoSmithKline, Goldman Sachs, IMS Health, mental health, mental illness, Nicotine withdrawal, patients, Pfizer, psychiatric risks, schizophrenia, smoking, smoking cessation, suicidal thoughts, Wellbutrin, Zyban
