Drugs being developed for the treatment of diseases of the central nervous system (CNS take 35% longer to complete clinical trials and receive regulatory approval than other new prescription medicines, according to a new analysis.
Between 1996 and 2010, the mean clinical-plus-approval-phase time for CNS drug treatments approved in the US was 32 months, 35% longer than the mean for non-CNS drugs approved during the same period, according to the analysis, which is published by the Tufts Center for the Study of Drug Development (CSDD .
But despite the longer and more costly development associated with CNS drugs, "the CNS new product pipeline is among the richest in the R&D-based drug industry," comments Joseph DiMasi, who conducted the study and is director of economic analysis at the Tufts Center.
The industry's CNS drug pipeline includes products to treat neurological diseases such as Alzheimer's disease, epilepsy, migraine headaches and stroke, and mental health conditions such as addictions, autism, depression, panic and schizophrenia.
The pipeline has grown by an annual average of 6% over the last decade and currently accounts for 11% of all drug development projects worldwide, the study notes. Nevertheless, development of these treatments poses a challenge for drugmakers, with the clinical approval success rate for "self-originated" CNS drugs entering clinical trials between 1993 and 2004 estimated at about one in 10. That compares to around one in six for all self-originated drugs, according to the study, which goes on to explain that "self-originated" drugs are those developed entirely by one manufacturer, in contrast to compounds which a company may obtain through licensing, purchase or other means.
Also, the "clinical approval success rate" refers to the share of New Chemical Entities (NCEs in clinical development that eventually obtain marketing approval from the US Food and Drug Administration (FDA .
The analysis is reported in the March/April issue of the Tufts CSDD Impact Report. It also reveals that the clinical approval success rate for self-originated CNS drugs varied from a low of 7.1% for products entering clinical testing during the period from 1995 to 2000 to 14.8% - or more than double - for drugs which entered clinical testing during 1998-2003.
It also notes that the mean clinical time for CNS drugs during 1996-2010 was 102.1 months, which is 40% longer than for non-CNS drugs, while the mean approval time for these products was 20.3 months, or 13% longer than for non-CNS treatments.
"That's not even a quarter of their profits," said Copeland, a law professor at
Pennsylvania State University. "I was up in arms."
Government officials say they are, too, and they've talked about incorporating some of Copeland's ideas.
"That's a question we've been struggling with for the last couple of years," said Gregory Demske, assistant inspector general for legal affairs at Health and Human Services. "We recognize there's a problem."
If a company is excluded from doing business with the government, then medications that only those companies produce will not be available to beneficiaries. But, Copeland said, the fees associated with corporate integrity agreements haven't been enough to keep companies from bilking the government again.
"It's still in the company's interest to promote off-label marketing because they're still going to make more in profits than they lose in fines," she said.
HHS officials are talking with those at the
Justice Department and Food and Drug Administration to fix the problem, Demske said.
Most of the cases come from off-label marketing of prescription medications. For example, Pfizer was accused of marketing Bextra, a painkiller, for uses other than what the
FDA had approved. Such uses constitute fraud because they take government money for purposes the FDA has not approved.
Instead of excluding an entire company from doing business with the government, Copeland said, the drug being marketed off-label could be excluded.
HHS officials considered that, Demske said, but they needed to ensure that beneficiaries could get their medications. The agency is considering taking away a company's patent rights as part of a settlement with the government.
That, he said, would allow other companies to make and sell the drugs to the government. Such a deal could be negotiated with companies as part of a fraud settlement and would not require congressional approval.
"We could require other things if the defendant will agree to it," he said. "If not, there might not be a settlement."
And if there's no settlement, there may be an exclusion.
Copeland suggested requiring companies to conduct clinical trials for the off-label uses they were accused of, requiring that they license a product to other manufacturers and holding high-level individuals criminally liable. Demske said that investigators began going after individuals in companies in 2010 and that they have focused resources on that idea.
Pfizer,
Bristol-Myers Squibb and
Abbott Laboratories did not respond to questions from USA TODAY.
"Imposing such a severe penatly on a person who had no knowledge of the wrongdoing at issue is manifestly unfair and unjust," said
Matthew Bennett, senior vice president of the Pharmaceutical Research and Manufacturers of America.
The Supreme Court ruled in the 1970s that the government may go after officials who should have knowledge that fraudulent behavior is happening under their management. However, the law applies only to individuals holding a position at a company.
"If they leave, we can't reach them," Demske said. "The law is written in present tense."
The government has to send a note notifying the person that it is considering excluding them, which leaves the person plenty of time to leave the company.
"They would be free to work elsewhere," Demske said.
A bill to address the problem passed the House last year but hit the Senate too late in the session to make it to a vote. A new bill, HR 675, has been introduced.
Officials with the Centers for Medicare and Medicaid Services are looking for answers, said Ted Doolittle, deputy director of CMS' Center for Program Integrity. Instead of excluding a company, the CMS can revoke payment, which the government plans to do more aggressively, he said.
Last month, 78 home health care agencies in Texas were suspended in connection with a fraud case, and Doolittle said the CMS will not pay them for services until they are cleared of wrongdoing. First, he said, the CMS had to make sure beneficiaries would be able to get the services they need if those centers were out of business.
Congress members have suggested mandatory exclusions for crimes, but Copeland said the cases often don't reach that point because the parties settle before a proclamation and because the government has to worry about patient access.
If the government targeted individuals more aggressively, that could send a powerful message to drug companies, said Stan Twardy, leader of law firm Day Pitney's health care compliance group.
"Something called a jail is going to send a lot stronger signal than a fine," he said. "The regulations can change, but individuals and companies will take advantage of any loopholes they may find. It's part of that game of maximizing profits."
Under a system of agreements and fines, he said, the corporate culture will remain the same.
Copeland said she doesn't think that's enough.
"If you go after the sales manager because the sales manager could have prevented the fraud, it doesn't change the corporate culture," she said. "The more prescriptions, the more money you make, so the incentive remains."
Patrick Burns, spokesman for the non-profit Taxpayers Against Fraud, said although there may be differences of opinion, there is a greater sense or urgency about fighting the problem.
"We're all thinking the same thing," Burns said of investigators and Congress members. "The good news is they're pushing to actually do it."
Piramal Healthcare is one of India’s largest healthcare companies, with a growth track record of above 27% CAGR since 1988. Piramal Healthcare had consolidated revenues of Rs. 2,990 crores in FY2011. With assets across North America, Europe and Asia, Piramal Healthcare is also one of the largest custom manufacturing companies across the world. It has significant presence in the critical care space with sales of anesthesia products to over 100 countries. In FY2011, Piramal Healthcare sold its domestic formulation business to Abbott USA for a consideration of Rs. 17,200 crores and Diagnostic Services business to Super Religare Limited for Rs. 600 crores
Post : Drosophila Scientist & Drosophila - Post Doctorate Fellow
No of Opening : Two
Experience : 1 to 3 yrs
Overall purpose :
a.The
molecular biology
department of pharmacology R&D is, located at the Piramal healthcare research centre is an internationally renowned institution delivering field-changing mechanistic insights into drug discovery focusing on the identification of new drugs/small molecule for cancer metabolic disorder, and inflammatory diseases.
b.The
molecular biology
department is concerned with development of in- vitro and cell based assay by cloning and expressions of various drugs targets for drugs screening in the context of cancer and diabetes. Department is also involved in the development of cancer and diabetic models of Drosophila
Main duties / key responsibilities :
1. Within the overall direction of the Drosophila programme of the group, the post-holder will make a significant input in the development of Drosophila Models including transgenic models
2. To develop and apply a broad range of techniques in order to pursue the research objectives of the group.
3. To participate in collaborative research, both within and external.
4. To be actively engaged in the dissemination of new research results in the form of scientific papers.
5. To present scientific work at seminars within the Unit and at external meetings where appropriate.
6. To communicate and collaborate with others to develop the most appropriate methodologies, and to receive training in the use of relevant experimental techniques.
Working relationships :
The post holder will report directly to the Sr. group leader but is expected to work closely with other members of the group. The post-holder will commit to develop and follow a personal development plan, attend relevant training courses and identify additional training which will support their career.
Salary : INR 4,00,000 - 7,00,000 P.A
Education :
M.Tech
- Bio-Chemistry/Bio-Technology,
M.Sc
- Biology, Bio-Chemistry,
Microbiology
,
Zoology
Desirable :
1. Experience with the following techniques: Drosophila development of transgenic Model
2.
molecular biology
: Cloning and expressions of genes of various pathways of Drosophila, protein Immunoprecipitation, confocal microscopy, cell transfections, SDS-PAGE, western blotting.
Location : Mumbai
Interested candidate can mail their resume : r
esearch.recruitment@piramal.com
Deadline : 02.04.12
Warnings that some prescription drugs cause violent thoughts
Tuesday, March 06, 2012
When it comes to cocaine, crystal meth or LSD, there is no difficulty believing a drug could drive a person to commit a crime.
However, in the case of prescription drugs, the drug is always innocent and the person guilty, a psychiatrist has said.
David Healy, an Irish-born professor based in the UK, has been an expert witness in homicide and suicide trials involving psychotropic drugs. He believes selectove serotonin re-uptake inhibitor (SSRIs anti-depressants can cause a delirium that leads to violent behaviour.
"They can also cause entirely normal people to start thinking aggressively and have violent thoughts they had never had before, as they did to some drug trial volunteers in Leeds in the 1980s.
"And they can switch off anxiety so that someone coldly starts to plan something they would be too scared to do ordinarily — so there can be pre-meditation. The problems can happen within 48 hours, or build up over two to three weeks, as in Shane Clancy’s case."
Prof Healy gave expert evidence at the inquest of Mr Clancy, who killed a man before taking his own life.
This view is strongly disputed by the College of Psychiatry of Ireland, which maintains there is no evidence anti-depressants can cause harm.
Researchers are looking for women who took part in a Leeds-based trial of antidepressant drugs in 1983.
The study had to be stopped after the participants suffered extreme side effects - and now experts want to know whether they had long-term problems.
Psychiatrist Prof David Healy is leading the search for the 12 women who tested the drug sertraline.
He said: “If alive, the women would be between 56 and 72. They may be living near Leeds still.”
The study was carried out by the-then Human Psychopharmacology Research Unit at the University of Leeds in 1983 on 12 healthy women then aged between 27 and 43. It was testing sertraline, a type of anti-depressant which was later launched under the brand name Zoloft.
Half of the women on the trial were given the drug and the other half had a placebo.
However the planned two-week study had to be stopped on the fourth day because of severe side effects. The results were never published.
Now Prof Healy, director of the North Wales Department of Psychological Medicine of Cardiff University, wants to find the women involved.
He said he had seen a medical report from the trial in the archive of drug company Pfizer in New York.
“The side effects that seemed most clearly linked to sertraline were apprehension, insomnia, movement disorders, and tremors,” he said.
In 2003 drugs watchdog the Medicines and Regulatory Authority issued a warning about certain types of anti-depressants, including sertraline, saying they should not be prescribed to children and young people because of an increased risk of suicidal behaviour in these age groups.
Research psychologist Dr Joanna Le Noury, who is working with Prof Healy, said they now wanted to track down the Leeds participants.
Dr Le Noury said: “The idea is to get some interviews about what went on with the study and their experiences.
“It’s also to find out how things have panned out since. Because they had a strange reaction to the drug at the time, whether they have had similar drug reactions since.”
Contact:
jo.lenoury@btopenworld.com, call 01248 384452 or via:
http://davidhealy.org.
On February 29, a federal district court judge issued an
Order requiring that Cardinal Health, Inc. comply with an Immediate Suspension Order ("ISO" issued by the Drug Enforcement Administration ("DEA" . The court previously granted a temporary restraining order delaying Cardinal's compliance with the ISO, pending a decision on a preliminary injunction requested by Cardinal. However, the Court denied this preliminary injunction in its Order. Cardinal
appealed this decision on the same day as the court's Order.
Partially at issue in this dispute is the question of who is responsible for stopping diversion, a form of illegal sales of controlled drug substances. Diversion is distributing controlled drug substances to an entity without a valid DEA registration. In this case, diversion of the prescription pain killer oxycodone allegedly took place at pharmacies supplied by Cardinal's Lakeland, Florida distribution facility. Cardinal states that it has a system in place to stop diversion and that it is ready and willing to suspend shipments to any pharmacy that the DEA identifies as likely to be engaged in diversion. The DEA, however, states that the Lakeland facility has a continuing, affirmative obligation to police its retail customers to ensure that the controlled drug substances it provides are not being unlawfully diverted--and the Lakeland facility fell short of its legal and contractual obligations.
According to a
Complaint filed by Cardinal, the ISO requires the Lakeland facility to immediately halt shipments of all controlled drug substances to about 2,700 pharmacies, hospitals, and other customers to prevent alleged imminent danger to the public health or safety. Notably, only Cardinal's Lakeland facility is subject to the ISO. The DEA, however, does not allege that Cardinal itself distributed controlled drug substances to any entity not permitted to purchase them. Instead, the ISO was issued because four pharmacies that were supplied by the Lakeland facility have allegedly distributed oxycodone for illegitimate uses.
Pfizer director defends virtual trial after recruitment struggle
By Nick Taylor+
06-Mar-2012
Related topics: Clinical evolution, Clinical Development, Phase III-IV
The head of Pfizer's virtual clinical trial has defended the project after its initial failure to recruit patients raised questions about its viability.
Approval of the trial, which allows patients to take part remotely, was hailed as a big step in the evolution of clinical research. However, since gaining approval the study has met problems.
“It didn't recruit”, Miguel Orri, senior director of clinical sciences at Pfizer, said at Partnerships in Clinical Trials in Orlando, Florida. After working towards approval for two years the setback was dispiriting for the Pfizer team.
Orri said problems stemmed from a failure, possibly caused by the team's regulatory focus, to appreciate what patients need. Aspects of the process were “quite complicated and tedious”, Orri said, and Pfizer has learned that patients are still wary putting lots of their health information online.
In response to these realisations Pfizer has revamped the model. A call centre now helps patients through the initial steps and Pfizer is receiving feedback from participants to help shape its plans for the virtual trial model.
Since making the changes Pfizer has seen an “immense inflow of subjects”, Orri said, but the delay means it is behind on its goal of recruiting 600 patients in the US. Despite the setback Pfizer is implementing plans to expand the trial into Europe.
The European trial, REMOTE 2.0, will learn from the mistakes of the US study. Pfizer wants to contract a recruitment vendor to help patients through the initial setup process to end the obstacles experienced in the US.
In a sign that Pfizer is considering the specific needs of the patient population, all participants in the European trial will receive a communication device. The device is like a simplified iPad and the idea is to help patients, particularly older woman from Southern Europe, who spend little time online.
“I don't think we've failed”
In the two years the Pfizer team spent working towards approval it faced internal skepticism, with Orri often being told the project was unfeasible. The struggle to recruit patients could give credence to these views but Orri was quick to defend the trial.
“I don't think we've failed. We have created a new online informed consent process I think we can use in many studies in the future”, Orri said. By taking a modular approach to the methods and tools used in REMOTE trial Pfizer can add effective virtual elements to its other clinical research projects.
The US Food and Drug Administration (FDA encouraged this approach by telling Pfizer to validate all tools used in the trial, Orri said. After talking about the trial FDA officials told Pfizer to “milk the study”, Orri said, and validate techniques for future use.
TRENTON, N.J. — Eight drugmakers are being sued by a consumer advocacy group that alleges their programs offering coupons that lower the cost of copayments for brand-name medicines are illegal.
Community Catalyst alleges that the couponing programs violate federal bribery laws because they’re meant to conceal information about the payments from health insurance plans.
Such coupons generally reduce patient copayments for brand-name drugs to what they would pay for a generic drug. The group says that drives up health insurance premiums and can cause patients to reach benefit caps quicker.
The companies sued are Abbott Laboratories, Amgen Inc., AstraZeneca PLC, Bristol-Myers Squibb Co., GlaxoSmithKline PLC, Merck & Co. Inc., Novartis AG and Pfizer Inc. They did not immediately respond to a request for comment.
Identical lawsuits, but with different defendants, were being filed Wednesday in federal courts in New York, Chicago, Philadelphia and Newark, N.J.
A U.S. unit of
Takeda Pharmaceutical Co. (4502 failed to give accurate reports to regulators about hundreds of congestive heart failure cases associated with its diabetes drug Actos, a whistle-blower claimed in a lawsuit.
The company failed to classify “non-hospitalized or non- fatal” congestive heart failure cases as serious from late 2007 to January 2010, former Takeda medical reviewer Helen Ge said in the complaint in federal court in
Boston. Takeda, like other drugmakers, is required to update the U.S.
Food and Drug Administration’s Adverse Event Reporting System.
“These events were not properly identified or reported in the FDA’s safety database,” Ge claimed in the complaint, filed in June 2010 and recently unsealed. “Takeda’s motivation to fraudulently report and under-report the serious adverse events was driven by an economic desire to falsely enhance Actos’s safety profile and to increase sales.”
The case against Takeda Pharmaceuticals North America Inc., filed by Ge on the government’s behalf, became public after the U.S. Justice Department declined to join it on Feb. 22. Twenty- four U.S. states also declined to join Ge’s complaint, said one of her attorneys, Michael L. Baum.
Generic Copies
Takeda, based in
Osaka,
Japan, said Feb. 1 that annual profit will fall 48 percent to 130 billion yen ($1.6 billion in the year ending March 31. Sales of Actos, which generated 27 percent of revenue last fiscal year, declined 19 percent in the previous nine-month period and will slump more when it faces competition from generic copies in August, Takeda said.
Jocelyn Gerst, a spokeswoman for Takeda, didn’t immediately return a call or e-mail seeking comment on the complaint.
Ge’s complaint claims that on “multiple occasions,” Takeda “improperly instructed” its medical reviewers to “change their professional opinion regarding adverse event classifications and assessments.” When she protested, “her contract was summarily terminated,” according to the complaint.
Takeda wanted to make it appear that Actos was safer than GlaxoSmithKline Plc’s Avandia diabetes drug, according to the complaint.
‘Systematic Fraud’
Ge sued under the federal
False Claims Act and similar state statutes, and seeks to recover damages on behalf of governments. She would be entitled to between 15 and 30 percent of any recovery.
“Takeda’s fraud has caused tens of thousands of false claims to be made on federal and state health care programs,” causing “hundreds of millions of dollars” in damages, according to the complaint.
In 2007, the FDA ordered Takeda and Glaxo to place its strongest warning on the labeling of their drugs about the risk of congestive heart failure, a condition that occurs when the heart doesn’t adequately pump blood.
Ge claimed that Takeda’s culture is “riddled with systematic fraud and deceit,” and that the company downplayed data suggesting a link between Actos and bladder cancer.
Baum, of Baum, Hedlund, Aristei & Goldman, said he is undeterred by the
Justice Department’s decision to not join the lawsuit after investigating. The U.S. declines to join four out of five cases filed under the False Claims Act. Companies settle the vast majority of cases when the U.S. intervenes.
“I believe that the documents we obtain in discovery will induce the government to come back in,” Baum said. “But whether they come back in or not, I believe the documents will show that the company violated the False Claims Act.”
One of Ge’s lawyers is
Michael Sullivan of The Ashcroft Group LLC. He is the former U.S. attorney in Boston.
The case is U.S. ex rel. Helen Ge v. Takeda Pharmaceutical Co., 10-cv-11043, U.S. District Court, District of
Massachusetts(Boston .
To contact the reporter on this story: David Voreacos in Newark at
dvoreacos@bloomberg.net
To contact the editor responsible for this story: Michael Hytha at
mhytha@bloomberg.net.
WASHINGTON – The nation's largest drugmakers have paid at least $8 billion in fines for repeatedly defrauding Medicare and Medicaid over the past decade, but they remain in business with the federal government because they are often the sole suppliers of critical products, records show.
"We're seeing some of the big companies a second and third time," said Gregory Demske, assistant inspector general for legal affairs for Health and Human Services. "The corporate integrity agreement is not sufficient to deter further misconduct."
In addition, the cases are labor- and cost-intensive as the companies fight often for years to avoid an exclusion, Demske said.
To try to change that trend, the government announced in 2010 that, rather than exclude an entire company, investigators would go after individuals within a company. Demske said his organization, the Justice Department and the Food and Drug Administration have come up with some ideas to use within the scope of the rules — such as taking away a company's patent rights as a condition of a settlement. That could begin with cases being investigated now, he said.
New York Times, Attorney General Lanny A. Breuer said “Taking advantage of his special access as a chemist at the F.D.A., Mr. Liang used sensitive inside information to reap illegal profits in the pharmaceutical securities market. “For years, he exploited his position in the agency to make easy money on the stock market. But today’s sentence shows that easy money has consequences. Investors engage in insider trading at their peril.” According to court documents, Mr. Liang told the judge, "I'm terribly sorry for what I've done.” --- On the Net:
On March 2, the United States Court of Appeals for the District of Columbia ordered an administrative
stay on the Immediate Suspension Order ("ISO" issued by the Drug Enforcement Administration ("DEA" against Cardinal Health, Inc.'s ("Cardinal" distribution facility in Lakeland, Florida. This stay postpones the ISO while the court considers Cardinal's emergency injunction
motion, which would halt the ISO pending Cardinal's separate appeal of the ISO. When granting the stay, the court stated that it had not yet considered the injunction motion on its merits. A decision on the merits will likely come soon, however, because the court ordered an
expedited briefing schedule, requiring the DEA's response to the motion by Friday, March 9, followed by Cardinal's reply on Monday, March 12.
The ISO, previously reported
here, suspended Cardinal's registration to distribute controlled substances (such as the pain medication oxycodone from its Lakeland facility to approximately 2,700 customers, including hospitals and pharmacies. Typically, the DEA revokes a registration after providing the registrant notice of the intent to revoke and a hearing. The DEA may issue an ISO without a hearing, however, when there is an "imminent danger to the public health or safety." Here, according to Cardinal, the DEA alleged imminent danger and issued the ISO without notice and a hearing.
Cardinal argues that there was no imminent danger to justify the DEA's action. The ISO did not allege that Cardinal distributed controlled substances to anyone that the DEA had not authorized to receive them. Instead, the ISO alleged that Cardinal sold high aggregate volumes of oxycodone to four pharmacies between 2008 and 2011. But by the time the ISO was issued, Cardinal had already suspended shipments to two of the pharmacies. Cardinal also noted that its shipments to the other two pharmacies had decreased by 80% prior to the ISO, which Cardinal then suspended after receiving the ISO. Consequently, Cardinal argues that its own remedial measures already negated any danger to the public and the ISO is unnecessary pending Cardinal's appeal.
A national shortage of injectable drugs has led the Alberta government to ask chemotherapy patients to buy their own anti-nausea medication from pharmacists starting Wednesday.
No comments:
Post a Comment