Vocabulary > Health > Drugs
29 July 2010
clinical trial / drug trial
being on medication
antipsychotic drug /
medicinal uses of smoked marijuana
biotechnology drugs / biologics
drug giant / pharmaceutical company /
Johnson & Johnson
breast cancer drugs
sedatives > neuroleptics
antibiotic resistance / misuse of antibiotics / drug-resistant
NDM-1 (New Delhi metallo-beta-lactamase) 1 positive bacteria
research and development
medical guinea pigs
The Denver Post
3 August 2010
FDA: Food and Drug Administration
Food and Drug Administration
Federal drug regulators
Attention Deficit Hyperactivity
Disorder > medications > Adderall
give a placebo / sugar pill
cartoons > Cagle > Pills, pills, pills
Marijuana and Medical Marijuana
28 August 2009
Drugs and Profits
May 24, 2011
The New York Times
By FREDERICK C. TUCKER Jr.
LAST year the Food and Drug Administration rescinded approval of the drug
Avastin for treating breast cancer patients, prompting a firestorm of criticism.
The decision was denounced by some politicians as health care rationing, and by
breast cancer patients who feared that they would be deprived of a drug that
they felt had helped them immensely.
But these criticisms ignore the facts: Avastin was rejected simply because it
didn’t work as it was supposed to, and the F.D.A. should resist the aggressive
campaign by Genentech, the drug’s maker, to get that ruling reconsidered at a
hearing in late June.
Avastin has been on the market for seven years, and combined with other drugs it
is effective in treating, but not curing, some colon, lung, kidney and brain
cancers. It inhibits the development of new blood vessels and in so doing can
starve a growing tumor.
Treating a breast cancer patient with Avastin costs about $90,000 a year, and
Genentech could lose $500 million to $1 billion a year in revenue if the F.D.A.
upholds the ban.
A clinical trial published in 2007 demonstrated that Avastin, when paired with
the chemotherapy drug Taxol, halts the growth of metastatic breast cancer for
about six months longer than chemotherapy alone. Genentech then asked the F.D.A.
for approval of Avastin, combined with Taxol, for use against metastatic breast
This halt in tumor growth is known as progression-free survival. But delaying
the worsening of cancer does not necessarily prolong life, and Avastin was not
shown to lengthen patients’ overall survival time. So Genentech argued that the
drug led not to longer life, but to improved quality of life.
In 2007, an F.D.A. advisory committee rejected the application, deciding that
the toxic side effects of Avastin outweighed its ability to slow tumor growth.
The F.D.A., however, overrode the committee and granted what is called
accelerated approval, allowing Avastin to be used pending further study. The
criteria for full approval was that Avastin not worsen overall survival and that
the drug provide clinically meaningful progression-free survival.
To support its case Genentech submitted data from two additional clinical trials
in which Avastin was paired with chemotherapy drugs other than Taxol. Like the
first trial, neither showed a survival benefit. Both showed an improvement in
progression-free survival, though this outcome was much less impressive than in
the original study. In addition to seeking full approval for the Avastin-Taxol
combination, Genentech also asked the F.D.A. to approve the use of Avastin with
the drugs used in these follow-up studies.
Genentech presented progression-free survival as a surrogate for better quality
of life, but the quality-of-life data were incomplete, sketchy and, in some
cases, non-existent. The best that one Genentech spokesman could say was that
“health-related quality of life was not worsened when Avastin was added.”
Patients didn’t live longer, and they didn’t live better.
It was this lack of demonstrated clinical benefit, combined with the potentially
severe side effects of the drug, that led the F.D.A. last year to reject the use
of Avastin with Taxol or with the other chemotherapies for breast cancer.
In its appeal Genentech is changing its interpretation of its own data to pursue
the case. Last year Genentech argued that the decrease in progression-free
survival in its supplementary studies was not due to the pairing of Avastin with
drugs other than Taxol. This year, however, in its brief supporting the appeal,
Genentech argues that the degree of benefit may indeed vary with “the particular
chemotherapy used with Avastin.” In other words, different chemotherapies
suddenly do yield different results, with Taxol being superior. The same data
now generate the opposite conclusion.
Perhaps more troubling is the resort to anecdote in the brief to the F.D.A. and
in the news media. Oncologists recounted their successes, and patients who were
doing well on Avastin argued for its continued approval. But anecdote is not
science. Such testimonials may represent the human voices behind the statistics,
but the sad fact is that there are too many patients who have been treated with
Avastin but are not here to tell their stories.
Avastin will not disappear because of the F.D.A. decision. It remains available
for treating other cancers, and research to find its appropriate role in breast
cancer treatment continues. In the meantime, the F.D.A., which is expected to
make its decision in September, needs to resist Genentech’s attempt to have it
ignore scientific evidence.
Serious progress in the treatment of cancer will not be the result of polemics,
lobbying or marketing. Genentech’s money and efforts would be better spent on
research for more meaningful treatments for breast cancer.
Frederick C. Tucker Jr. is an oncologist.
Drugs and Profits, NYT, 24.6.2011,
F.D.A. to Restrict Avandia,
Citing Heart Risk
September 23, 2010
The New York Times
By GARDINER HARRIS
WASHINGTON — In a highly unusual coordinated announcement, drug regulators in
Europe and the United States said Thursday that Avandia, the controversial
diabetes medicine, would no longer be widely available.
The drug’s sales will be suspended entirely in Europe, while patients in the
United States will be allowed access to the medicine only if they and their
doctors attest that they have tried every other diabetes medicine and that
patients have been made aware of the drug’s substantial risks to the heart.
Patients now taking Avandia may continue to do so.
The Food and Drug Administration’s decision shows that the Obama administration
is taking a harder line on drug safety issues, even in the face of scientific
uncertainty. Along with its announcement, the agency for the first time
immediately posted on its Web site internal memorandums from top staff members
that in some cases offered entirely contradictory advice. Dr. Margaret Hamburg,
the agency’s commissioner, said that passions within the agency had run high on
the Avandia decision.
“As F.D.A. commissioner, my job would be infinitely easier if we had consensus
and full scientific clarity,” she said.
Dr. Steven Nissen, a Cleveland Clinic cardiologist whose studies highlighted
Avandia’s heart attack risks, said that the decision brought an end to “one of
the worst drug safety tragedies in our lifetime,” adding that it was “essential
to fully investigate what went wrong with the regulatory process to prevent this
type of tragedy from endangering patients in the future.”
One study estimated that from 1999 to 2009, more than 47,000 people taking
Avandia needlessly suffered a heart attack, stroke or heart failure, or died.
The decision on Avandia signals a new era in the treatment of diabetes, a
disease that is reaching epidemic proportions in much of the industrialized
world. Because of Avandia, the F.D.A. announced in 2008 that it would no longer
approve medicines simply because they help diabetics control blood sugar levels
— the standard for more than 80 years. Instead, the F.D.A. now insists that
drugmakers conduct trials lasting at least two years to show that their
medicines do not hurt the heart and that they improve the quality or length of
diabetics’ lives, far tougher tests.
The Avandia story also begins a new and unsettling period for pharmaceutical
companies because Avandia’s risks became known only after Dr. Nissen analyzed
data from clinical trials that GlaxoSmithKline, the maker of the drug, had been
forced to post on its Web site as a result of a legal settlement. Such public
postings are increasingly the norm, which means that drugmakers can no longer
easily hide or control scientific information about their medicines.
The agency’s decision to order restrictions on Avandia’s sales also demonstrates
that the F.D.A. — given new powers over drugmakers and drug distribution in a
2007 law — intends to use those powers. The agency has now ordered that dozens
of drugs be sold only with special restrictions.
In explaining why the F.D.A. decided against only adding more warnings to
Avandia’s label, Dr. Janet Woodcock, director of the F.D.A.’s drug center said,
“We know that labels are often not read.” It was an extraordinary acknowledgment
from a veteran of an agency that for decades relied almost exclusively on label
warnings to control drug use.
The suspension and restrictions all but ensure that Avandia’s sales — $1.19
billion last year and $3.2 billion as recently as 2006 — will plunge as
regulatory authorities around the world are bound to follow with similar
restrictions. Avandia was once the biggest-selling diabetes drug around the
world, but concerns about heart attack risks have already cut sales. There are
about 600,000 people currently taking Avandia in the United States, Dr. Hamburg
said at a press conference. “I think the numbers will go down very, very
significantly with these new requirements.”
GlaxoSmithKline responded that “the company continues to believe that Avandia is
an important treatment for patients with Type 2 diabetes” and is working with
the F.D.A. and European regulators “to implement the required actions.” The
company promised that it would end Avandia promotions around the world.
The restrictions will take months to put in place. Patients now taking Avandia
should continue to do so until they can consult their doctors, said Dr. Joshua
Sharfstein, the F.D.A.’s principal deputy commissioner. But he said that doctors
should now consider switching patients to other medicines.
European regulators began their own reassessment of Avandia in July after seeing
a study of the drug by F.D.A. medical officers and another by Dr. Nissen in
advance of a July F.D.A. advisory meeting. Once each agency learned of the
other’s impending and similar decision — both were reached independently, Dr.
Hamburg emphasized — they decided to coordinate their announcements.
Several consumer groups said that the F.D.A. should have removed Avandia from
the market just as the Europeans did.
The F.D.A. announced that it had ordered Glaxo to end a controversial study
comparing Avandia and Actos, made by Takeda. It also ordered Glaxo to conduct an
independent assessment of the Record trial, a landmark study of Avandia’s heart
effects that an F.D.A. medical officer found was riddled with what he said were
unpardonable errors that seriously biased the trial’s conclusions.
In 2007, after a study by Dr. Nissen found that Avandia increased the risk of
heart attacks, an advisory committee agreed but voted to keep it on the market.
More studies intensified the controversy, so the F.D.A. held another advisory
meeting in July. This time, a majority of experts — many of whom had supported
Avandia’s continued sales in 2007 — decided that the drug should either be
withdrawn or its sales should be severely restricted. With Thursday’s
announcements, the F.D.A. and the European Medicines Agency are following that
Dr. Clifford J. Rosen, a member of the advisory panel that met in July, said he
was gratified that the F.D.A. had followed the panel’s advice, and he said the
new guidelines “will protect patients while at the same time allowing those few
patients who have benefited from treatment to stay on the drug.”
Approved in 1999, Avandia helps control blood sugar levels in diabetics by
making patients more sensitive to their own insulin. It is one of a class of
three drugs, the first of which, Rezulin, was withdrawn because it caused liver
damage. Actos, the last remaining drug in the class, appears safe in part
because it seems to affect a different set of genes than either Rezulin or
Senate investigators found that GlaxoSmithKline spent years hiding from
regulatory authorities clear indications that Avandia increased heart risks. In
July, GlaxoSmithKline took a $2.3 billion liability charge related to legal
cases involving Avandia and another medicine, Paxil. At the time, investors
cheered the news as the company’s attempt to set a ceiling for its liability
surrounding the medicine.
But the twin announcements by European and American regulators, along with a
string of troubling findings about the company’s conduct by Senate
investigators, may increase the company’s legal exposure.
Senator Max Baucus, a Democrat from Montana who helped to spearhead an
investigation of Avandia, said he was pleased. “The FDA’s tough new restrictions
on the drug will help protect patients,” Mr. Baucus said.
F.D.A. to Restrict
Avandia, Citing Heart Risk, NYT, 23.9.2010,
Child’s Ordeal Shows
Risks of Psychosis Drugs for Young
September 1, 2010
The New York Times
By DUFF WILSON
OPELOUSAS, La. — At 18 months, Kyle Warren started taking a daily
antipsychotic drug on the orders of a pediatrician trying to quell the boy’s
severe temper tantrums.
Thus began a troubled toddler’s journey from one doctor to another, from one
diagnosis to another, involving even more drugs. Autism, bipolar disorder,
hyperactivity, insomnia, oppositional defiant disorder. The boy’s daily pill
regimen multiplied: the antipsychotic Risperdal, the antidepressant Prozac, two
sleeping medicines and one for attention-deficit disorder. All by the time he
He was sedated, drooling and overweight from the side effects of the
antipsychotic medicine. Although his mother, Brandy Warren, had been at her
“wit’s end” when she resorted to the drug treatment, she began to worry about
Kyle’s altered personality. “All I had was a medicated little boy,” Ms. Warren
said. “I didn’t have my son. It’s like, you’d look into his eyes and you would
just see just blankness.”
Today, 6-year-old Kyle is in his fourth week of first grade, scoring high marks
on his first tests. He is rambunctious and much thinner. Weaned off the drugs
through a program affiliated with Tulane University that is aimed at helping
low-income families whose children have mental health problems, Kyle now laughs
easily and teases his family.
Ms. Warren and Kyle’s new doctors point to his remarkable progress — and a more
common diagnosis for children of attention-deficit hyperactivity disorder — as
proof that he should have never been prescribed such powerful drugs in the first
Kyle now takes one drug, Vyvanse, for his attention deficit. His mother shared
his medical records to help document a public glimpse into a trend that some
psychiatric experts say they are finding increasingly worrisome: ready
prescription-writing by doctors of more potent drugs to treat extremely young
children, even infants, whose conditions rarely require such measures.
More than 500,000 children and adolescents in America are now taking
antipsychotic drugs, according to a September 2009 report by the Food and Drug
Administration. Their use is growing not only among older teenagers, when
schizophrenia is believed to emerge, but also among tens of thousands of
A Columbia University study recently found a doubling of the rate of prescribing
antipsychotic drugs for privately insured 2- to 5-year-olds from 2000 to 2007.
Only 40 percent of them had received a proper mental health assessment,
violating practice standards from the American Academy of Child and Adolescent
“There are too many children getting on too many of these drugs too soon,” Dr.
Mark Olfson, professor of clinical psychiatry and lead researcher in the
government-financed study, said.
Such radical treatments are indeed needed, some doctors and experts say, to help
young children with severe problems stay safe and in school or day care. In
2006, the F.D.A. did approve treating children as young as 5 with Risperdal if
they had autistic disorder and aggressive behavior, self-injury tendencies,
tantrums or severe mood swings. Two other drugs, Seroquel from AstraZeneca and
Abilify from Bristol-Myers Squibb, are permitted for youths 10 or older with
But many doctors say prescribing them for younger and younger children may pose
grave risks to development of both their fast-growing brains and their bodies.
Doctors can legally prescribe them for off-label use, including in preschoolers,
even though research has not shown them to be safe or effective for children.
Boys are far more likely to be medicated than girls.
Dr. Ben Vitiello, chief of child and adolescent treatment and preventive
research at the National Institute of Mental Health, says conditions in young
children are extremely difficult to diagnose properly because of their emotional
variability. “This is a recent phenomenon, in large part driven by the
misperception that these agents are safe and well tolerated,” he said.
Even the most reluctant prescribers encounter a marketing juggernaut that has
made antipsychotics the nation’s top-selling class of drugs by revenue, $14.6
billion last year, with prominent promotions aimed at treating children. In the
waiting room of Kyle’s original child psychiatrist, children played with Legos
stamped with the word Risperdal, made by Johnson & Johnson. It has since lost
its patent on the drug and stopped handing out the toys.
Greg Panico, a company spokesman, said the Legos were not intended for children
to play with — only as a promotional item.
Cheaper to Medicate
Dr. Lawrence L. Greenhill, president of the American Academy of Child and
Adolescent Psychiatry, concerned about the lack of research, has recommended a
national registry to track preschoolers on antipsychotic drugs for the next 10
years. “Psychotherapy is the key to the treatment of preschool children with
severe mental disorders, and antipsychotics are adjunctive therapy — not the
other way around,” he said.
But it is cheaper to medicate children than to pay for family counseling, a fact
highlighted by a Rutgers University study last year that found children from
low-income families, like Kyle, were four times as likely as the privately
insured to receive antipsychotic medicines.
Texas Medicaid data obtained by The New York Times showed a record $96 million
was spent last year on antipsychotic drugs for teenagers and children —
including three unidentified infants who were given the drugs before their first
In addition, foster care children seem to be medicated more often, prompting a
Senate panel in June to ask the Government Accountability Office to investigate
In the last few years, doctors’ concerns have led some states, like Florida and
California, to put in place restrictions on doctors who want to prescribe
antipsychotics for young children, requiring a second opinion or prior approval,
especially for those on Medicaid. Some states now report prescriptions are
declining as a result.
A study released in July by 16 state Medicaid medical directors, which once had
the working title “Too Many, Too Much, Too Young,” recommended that more states
require second opinions, outside consultation or other methods to assure proper
prescriptions. The F.D.A. has also strengthened warnings about using some of
these drugs in treating children.
No Medical Reason
Kyle was rescued from his medicated state through a therapy program called Early
Childhood Supports and Services, established in Louisiana through a confluence
of like-minded child psychiatrists at Tulane, Louisiana State University and the
state. It surrounds troubled children and their parents with social and mental
health support services.
Dr. Mary Margaret Gleason, a professor of pediatrics and child psychiatry at
Tulane who treated Kyle from ages 3 to 5 as he was weaned off the heavy
medications, said there was no valid medical reason to give antipsychotic drugs
to the boy, or virtually any other 2-year-old. “It’s disturbing,” she said.
Dr. Gleason says Kyle’s current status proves he probably never had bipolar
disorder, autism or psychosis. His doctors now say Kyle’s tantrums arose from
family turmoil and language delays, not any of the diagnoses used to justify
“I will never, ever let my children be put on these drugs again,” said Ms.
Warren, 28, choking back tears. “I didn’t realize what I was doing.”
Dr. Edgardo R. Concepcion, the first child psychiatrist to treat Kyle, said he
believed the drugs could help bipolar disorder in little children. “It’s not
easy to do this and prescribe this heavy medication,” he said in an interview.
“But when they come to me, I have no choice. I have to help this family, this
mother. I have no choice.”
Ms. Warren conceded that she resorted to medicating Kyle because she was
unprepared for parenthood at age 22, living in difficult circumstances,
sometimes distracted. “It was complicated,” she said. “Very tense.”
Kyle was a healthy baby physically, but he was afraid of some things. He spent
hours lining up toys. When upset, he screamed, threw objects, even hit his head
on the wall or floor — not uncommon for toddlers, but frightening.
“I’d bring him to the doctor and the doctor would say, ‘You just need to
discipline him,’ ” Ms. Warren said. “How can you discipline a 6-month-old?”
When Kyle’s behavior worsened after his brother was born, Ms. Warren turned to a
pediatrician, Dr. Martin J. deGravelle.
“Within five minutes of sitting with him, he looked at me and said, ‘He has
autism, there’s no doubt about it,’ ” Ms. Warren said.
Dr. deGravelle’s clinic notes say Kyle was hyperactive, prone to tantrums, spoke
only three words and “does not interact well with strangers.”
He prescribed Risperdal. At the time, Risperdal was approved by the F.D.A. only
for adults with schizophrenia or acute manic episodes. The following year it was
approved for certain children, 5 and older, with autism and extremely aggressive
behavior. It has never been approved by the F.D.A. for use in children younger
than 5, although doctors may legally prescribe it as an off-label use.
“Kyle at the time was very aggressive and easily agitated, so you try to find
medication that can make him more easily controlled, because you can’t reason
with an 18-month-old,” Dr. deGravelle said in a telephone interview. But Kyle
was not autistic — according to several later evaluations, including one that
Dr. deGravelle arranged with a neurologist. Kyle did not have the autistic
child’s core deficit of social interaction, Dr. Gleason said. Instead, he craved
more positive attention from his mother.
“He had trouble communicating,” Dr. Gleason said. “He didn’t have people to
listen to him.”
After the neurologist review, the diagnosis changed to “oppositional defiant
disorder” and the Risperdal continued.
“Yes, I did ask for it,” Ms. Warren said. “But I was at my wit’s end, and I
didn’t know what else to do.”
Dr. deGravelle referred her to Dr. Concepcion, who in turn diagnosed Kyle’s
condition as bipolar disorder.
“Some children, when they come to me, the parents are really so frustrated,” Dr.
Concepcion said in a phone interview. “Especially the mothers are so scared or
desperate in getting help. Their children are really acting psychotic.”
Dr. Concepcion also spoke with Dr. Charles H. Zeanah, a Tulane medical
professor, who disagreed with both the diagnosis and the treatment. “I have
never seen a preschool child with bipolar disorder in 30 years as a child
psychiatrist specializing in early childhood mental health,” Dr. Zeanah said.
“It’s a controversial diagnosis, I agree with that,” said Dr. Concepcion. “But
if you will commit yourself in giving these children these medicines, you have
to have a diagnosis that supports your treatment plan. You can’t just give a
nondiagnosis and give them the atypical antipsychotic.”
He also prescribed four more pills.
Kyle’s third birthday photo shows a pink-cheeked boy who had ballooned to 49
pounds. Obesity and diabetes are childhood risks of antipsychotics. Kyle smiles
at the camera. He is sedated.
“His shell was there, but he wasn’t there,” Ms. Warren said. “And I didn’t like
Dr. Concepcion referred Kyle to the early childhood support program, which has
helped about 3,000 preschoolers from low-income families at risk for mental
health problems since 2002.
His speech improved. He threw fewer tantrums. “They started working with us as a
family,” said Ms. Warren, who also received parenting advice. “That helps.”
Kyle’s treatment was directed by Dr. Gleason, a Columbia medical graduate who
had led a team that wrote 2007 practice guidelines for psychopharmacological
treatment of very young children.
“Families sometimes feel the need for a quick fix,” Dr. Gleason said. “That’s
often the prescription pad. But I’m concerned that when a child sees someone who
prescribes but doesn’t do therapy, they’re closing the door that can make
Off most drugs, Kyle started losing weight and his behavior improved. Ms.
Warren’s life also improved. She met a man and they moved into their own house
five miles out of Opalousas, a town of 25,000. They were married last Saturday.
At their home recently, Kyle and his brother, Jade, ran and played while their
baby sister watched from a playpen. Their clothes were neatly folded in a shared
bedroom. They often responded “Yes, ma’am” or “Yes, sir.”
“They’re respectful, but they’re hyper kids,” Ms. Warren said. “Once he came off
the medication, he’s Kyle. He’s an intelligent person. He’s loud. He’s funny.
He’s smart. He’s bouncy. I mean, there’s never a dull moment. He has a few
little behavior issues. But he’s like any other normal 6-year-old.”
Kyle paused to show a reading report card from the end of his kindergarten year,
with an A grade.
“Awesome job, Kyle!” his kindergarten teacher wrote.
Child’s Ordeal Shows
Risks of Psychosis Drugs for Young, NYT, 1.9.2010,
Diabetes Drug Maker
Hid Test Data on Risks,
July 12, 2010
The New York Times
By GARDINER HARRIS
In the fall of 1999, the drug giant SmithKline Beecham secretly began a study
to find out if its diabetes medicine, Avandia, was safer for the heart than a
competing pill, Actos, made by Takeda.
Avandia’s success was crucial to SmithKline, whose labs were otherwise all but
barren of new products. But the study’s results, completed that same year, were
disastrous. Not only was Avandia no better than Actos, but the study also
provided clear signs that it was riskier to the heart.
But instead of publishing the results, the company spent the next 11 years
trying to cover them up, according to documents recently obtained by The New
York Times. The company did not post the results on its Web site or submit them
to federal drug regulators, as is required in most cases by law.
“This was done for the U.S. business, way under the radar,” Dr. Martin I. Freed,
a SmithKline executive, wrote in an e-mail message dated March 29, 2001, about
the study results that was obtained by The Times. “Per Sr. Mgmt request, these
data should not see the light of day to anyone outside of GSK,” the corporate
successor to SmithKline.
The heart risks from Avandia first became public in May 2007, with a study from
a cardiologist at the Cleveland Clinic who used data the company was forced by a
lawsuit to post on its own Web site. In the ensuing months, GlaxoSmithKline
officials conceded that they had known of the drug’s potential heart attack
risks since at least 2005.
But the latest documents demonstrate that the company had data hinting at
Avandia’s extensive heart problems almost as soon as the drug was introduced in
1999, and sought intensively to keep those risks from becoming public. In one
document, the company sought to quantify the lost sales that would result if
Avandia’s cardiovascular safety risk “intensifies.” The cost: $600 million from
2002 to 2004 alone, the document stated.
Mary Anne Rhyne, a GlaxoSmithKline spokeswoman, said that the company had not
provided the results of its study because they “did not contribute any
significant new information.”
The company said that Avandia was safe and that Dr. Freed no longer worked for
A panel of experts will meet Tuesday and Wednesday to decide whether Avandia
should still be sold and whether it is ethical to test Avandia directly against
Whether to withdraw Avandia is a question that has split the F.D.A., with some
officials arguing that the drug is useful despite its risks and others insisting
that it must be withdrawn.
According to the documents, Dr. John Jenkins, director of the agency’s office of
new drugs, who has argued internally that Avandia should remain on the market,
briefed the company extensively on the agency’s internal debate.
“It is clear the office of new drugs is trying to find minimal language that
will satisfy the office of drug safety,” a top company official wrote in an
e-mail message after he spoke with Dr. Jenkins, according to a sealed deposition
obtained by The Times.
In the deposition, Dr. Rosemary Johann-Liang, a former supervisor in the drug
safety office who left the F.D.A. after she was disciplined for recommending
that Avandia’s heart warnings be strengthened, said of Dr. Jenkins’
conversations with GlaxoSmithKline, “This should not happen, and the fact that
these kind of things happen, I mean, I think people have to make a determination
about the leadership at the F.D.A.”
An F.D.A. spokeswoman said the agency would not comment on the contents of the
Members of Congress, where the Avandia case has led to legislative changes, said
they were outraged at GlaxoSmithKline’s behavior.
“When drug companies withhold data regarding safety concerns about their
medicines, they put patients at risk,” said Senator Max Baucus, Democrat of
Montana, who is chairman of the Senate Finance Committee. Mr. Baucus and Senator
Charles E. Grassley of Iowa, the committee’s ranking Republican, spent years
investigating GlaxoSmithKline’s development of Avandia.
Besides the trial comparing Avandia with Actos, the company also conducted
trials comparing Avandia with glyburide, a cheaper and older diabetes medicine.
When Rhona A. Berry, a company official, asked about publishing two of the
trials, Dr. Freed responded in an e-mail message dated July 20, 2001, that
referred to Avandia by the abbreviation of its generic name, rosiglitazone:
“Rhona — Not a chance. These put Avandia in quite a negative light when folks
look at the response of the RSG monotherapy arm,” the message said. “It is a
difficult story to tell and we would hope that these do not see the light of
Hiding the results of negative clinical trials was once widespread in the drug
But after GlaxoSmithKline was found in 2004 to have hidden data that showed that
its antidepressant, Paxil, led children and teenagers to have more suicidal
thoughts and behaviors, the company settled a lawsuit by agreeing to publicly
post data from all of its trials. In 2007, Congress mandated such disclosures.
But the postings are often little more than cryptic references, so the issue is
far from resolved.
With Avandia, GlaxoSmithKline has done more than hide trial data. An F.D.A.
reviewer who closely examined a landmark Avandia clinical trial called “Record,”
found at least a dozen instances in which patients taking Avandia suffered
serious heart problems that were not counted in the trial’s tally of adverse
events, mistakes that further obscured Avandia’s heart risks.
The company’s conduct of the Record trial has received sharp criticism from
medical leaders for other reasons as well. To compare Avandia and Actos in 1999,
researchers at SmithKline measured Actos’s effects in patients in the same way
that they had conducted earlier trials of Avandia so that the results for the
two drugs could be compared.
When the results of the study suggested that Avandia was more dangerous than
Actos, the company decided against further comparisons.
Diabetes Drug Maker Hid
Test Data on Risks, Files Indicate, NYT, 12.7.2010,
Pfizer Details Its Payments
to Doctors and Researchers
March 31, 2010
The New York Times
By DUFF WILSON
Pfizer, the world’s largest drug maker, said Thursday that it paid about $20
million to 4,500 doctors and other health care professionals in the United
States for consulting and speaking on its behalf in the last six months of 2009,
its first public accounting of payments to the people who decide which drugs to
Pfizer said it also paid $15.3 million to 250 academic medical centers and other
research groups for clinical trials in the final six months of last year.
While several other pharmaceutical companies have previously disclosed payments
to doctors, Pfizer is the first to disclose payments for the clinical trials
where drugs are tested. The disclosure does not include payments outside the
A spokeswoman for Pfizer, Kristen E. Neese, said the disclosures were required
by an integrity agreement that the company signed in August to settle a federal
investigation into the illegal promotion of drugs for off-label uses. Pfizer
paid a $2.3 billion fine in that case, the largest criminal fine of any type in
the nation’s history.
Company executives said they had long planned to be more transparent — an
assertion met with skepticism by some outside experts.
“We’re proud of the relationships that we have with researchers and clinicians,”
Dr. Freda C. Lewis-Hall, Pfizer’s chief medical officer, said Tuesday. She
characterized the disclosure and Web site as part of “a march to disclosure”
that Pfizer started in 2002.
Pfizer is the fourth major drug company to make such disclosures, following Eli
Lilly, Merck and GlaxoSmithKline. All four Web sites are searchable by the names
of doctors or organizations, but all are set up in ways that make it difficult
to download and analyze the entire database.
“All of them are welcome, but none of them is a replacement for a single
national database,” Allan Coukell, director of the Pew Prescription Project, a
Boston nonprofit that seeks to protect consumers, said in a telephone interview.
Beginning in 2012, drug and medical device companies will be required to
disclose payments to physicians of more than $10, with the first report
available in 2013. The federal Physician Payment Sunshine Act was passed as part
of health care reform and signed by President Obama last week. Some states also
have disclosure laws.
Pfizer’s disclosure met with skepticism from one leading expert on conflicts of
interest in medicine.
“I think it’s a good thing to do, but I put absolutely no trust in what drug
companies voluntarily disclose to the public when those things are unaudited,”
said Eric G. Campbell, lead author of a 2007 study of physician-industry
relationships published in The New England Journal of Medicine.
The survey of 3,167 physicians in six specialties found 94 percent had some
relationship with drug companies in 2003 and 2004, mostly receiving free meals,
with 28 percent being paid for consulting, speaking or enrolling patients in
Professor Campbell, who is director of research at the Institute for Health
Policy at Massachusetts General Hospital and an associate professor at Harvard
Medical School, said drug companies were trying to get ahead of a rising tide of
public opinion for disclosure.
“The drug companies are disclosing voluntarily now not necessarily because they
believe it’s the right thing to do,” he said, “but because they want to get
ahead of what is an inevitable thing in the United States.”
Pfizer executives reviewed the company’s disclosure system with the staff of
Senator Charles Grassley, Republican of Iowa, who is investigating the influence
of money in medicine. Senator Grassley said Wednesday in a statement: “It’s a
real milestone for the transparency campaign to have one of the biggest drug
makers in the world respond with an initiative like this.”
Pfizer’s clinical-trials disclosure identifies all such payments to academic
medical centers from July 1, 2009 to Dec. 31, 2009, the company said, and
payments for new clinical trials initiated in that time by non-academic research
organizations. “These payments represent a small portion of Pfizer’s total
investment in research and development,” the company said in a statement
The payments to doctors covered fees, travel and meals worth $25 or more and
totaling $500 or more during the six-month period, Pfizer said. In all, Pfizer
said, 1,500 licensed health care professionals were paid an average of $5,000
during the six-month period for consulting, and 2,800 were paid an average of
$3,400 for speaking.
The company plans to post its next report on March 31, 2011, with expanded data
on payments during 2010.
Pfizer Details Its
Payments to Doctors and Researchers, NYT, 31.3.2010,
Research Ties Diabetes Drug to Heart Woes
February 20, 2010
The New York Times
By GARDINER HARRIS
Hundreds of people taking Avandia, a controversial diabetes medicine,
needlessly suffer heart attacks and heart failure each month, according to
confidential government reports that recommend the drug be removed from the
The reports, obtained by The New York Times, say that if every diabetic now
taking Avandia were instead given a similar pill named Actos, about 500 heart
attacks and 300 cases of heart failure would be averted every month because
Avandia can hurt the heart. Avandia, intended to treat Type 2 diabetes, is known
as rosiglitazone and was linked to 304 deaths during the third quarter of 2009.
“Rosiglitazone should be removed from the market,” one report, by Dr. David
Graham and Dr. Kate Gelperin of the Food and Drug Administration, concludes.
Both authors recommended that Avandia be withdrawn.
The internal F.D.A. reports are part of a fierce debate within the agency over
what to do about Avandia, manufactured by GlaxoSmithKline. Some agency officials
want the drug withdrawn because they believe there is a safer alternative;
others insist that studies of the drug provide contradictory information and
that Avandia should continue to be an option for doctors and patients.
GlaxoSmithKline said that it had studied Avandia extensively and that
“scientific evidence simply does not establish that Avandia increases” the risk
of heart attacks.
The battle has been brewing for years but has been brought to a head by
disagreement over a new clinical trial and a Senate investigation that concluded
that GlaxoSmithKline should have warned patients earlier of the drug’s potential
Avandia was once one of the biggest-selling drugs in the world. Driven in part
by a multimillion-dollar advertising campaign, sales were $3.2 billion in 2006.
But a 2007 study by a Cleveland Clinic cardiologist suggesting that the drug
harmed the heart prompted the F.D.A. to issue a warning, and sales plunged. A
committee of independent experts found in 2007 that Avandia might increase the
risk of heart attack but recommended that it remain on the market, and an F.D.A.
oversight board voted 8 to 7 to accept that advice.
Hundreds of thousands still take the medicine, although some top
endocrinologists say they have sworn off the drug.
Since 2007, more studies have been done. In a December 2009 internal memorandum,
Dr. Janet Woodcock, director of the F.D.A.’s drug center, wrote that “there are
multiple conflicting opinions” about Avandia within the agency, and she ordered
officials to assemble another advisory committee, expected this summer, to
reconsider whether the drug should be sold.
“I await the recommendations of the advisory committee,” the agency’s
commissioner, Dr. Margaret Hamburg, said Friday night. “Meanwhile, I am
reviewing the inquiry made by Senators Baucus and Grassley and I am reaching out
to ensure that I have a complete understanding and awareness of all of the data
and issues involved.”
The bipartisan multiyear Senate investigation — whose results are expected to be
released publicly on Monday but which were also obtained by The Times — sharply
criticizes GlaxoSmithKline, saying it failed to warn patients years earlier that
Avandia was potentially deadly.
“Instead, G.S.K. executives attempted to intimidate independent physicians,
focused on strategies to minimize or misrepresent findings that Avandia may
increase cardiovascular risk, and sought ways to downplay findings that a
competing drug might reduce cardiovascular risk,” concludes the report, which
was overseen by Senator Max Baucus, a Montana Democrat, and Senator Charles E.
Grassley, an Iowa Republican.
Mr. Baucus said of the report, “Patients trust drug companies with their health
and their lives, and GlaxoSmithKline abused that trust.”
In response, GlaxoSmithKline said that it disagreed with the Senate
investigation’s conclusions. The company said that it could not comment on
internal F.D.A. documents but that “the official ruling from F.D.A. is that
Avandia remain on the market.”
In the wake of the controversy, agency officials ordered GlaxoSmithKline to
undertake a study comparing how many heart attacks, strokes and heart-related
deaths occur among patients given either Avandia, Actos or a placebo. Studies
suggest that Actos, made by Takeda, lowers blood sugar as well as Avandia but
without hurting the heart as much.
But Dr. Graham and Dr. Gelperin, working in the F.D.A.’s office of surveillance
and epidemiology, argued in two separate internal reports that the new
GlaxoSmithKline study, called TIDE, is “unethical and exploitative” because
patients given Avandia face far greater risks than those given Actos, with no
promise of any additional benefit. The trial may include patients who have had
heart attacks or chest pains even though some foreign drug authorities have
warned against Avandia’s use by precisely such patients, the reports note.
“Although the proposed TIDE trial is motivated by a desire for definitive
answers regarding the cardiovascular safety of the drug rosiglitazone, the
safety of the study itself cannot be assured and is not acceptable,” one of the
These concerns, in internal reports dated October 2008 but not made public until
now, were later overruled by other agency officials, and GlaxoSmithKline is
currently enrolling patients in the TIDE trial. The trial is not expected to be
completed until 2020, although the company is hoping to report some results to
the F.D.A. by 2014. The company’s patent on Avandia expires in 2012, and generic
versions will probably swallow most remaining profits.
In a letter sent Thursday to Dr. Hamburg, the Food and Drug Administration
commissioner, Mr. Baucus and Mr. Grassley asked “what steps the F.D.A. has taken
to protect patients in the TIDE trial” and said the trial’s patients had never
been told about the concerns raised by the agency’s own safety officers.
Mr. Grassley said the internal agency battle showed that the agency needed to be
restructured to give more power to safety officials like Dr. Graham and Dr.
Gelperin over their counterparts who approve medicines and deal more directly
with drug makers.
“It doesn’t make any sense to have these experts who study drugs after they have
been on the market for several years under the thumb of the officials who
approved the drug in the first place and have a natural interest in defending
that decision,” Mr. Grassley said. “The Avandia case may be the most alarming
example of the problem with this setup.”
The question of when and how to communicate possible drug risks has long
bedeviled drug makers and regulators. Hints are common that drugs may cause
injuries; thousands of drug injury reports pour into the Food and Drug
Administration every week. For example, Avandia ranked first among all
prescribed drugs in the number of serious, disabling and fatal problems —
including 304 deaths — reported to the agency in the third quarter of 2009,
according to an analysis done by the Institute for Safe Medication Practice, a
drug safety oversight group.
But companies say that such reports do not offer proof of a problem and that
highlighting them can scare patients away from needed treatment, so they often
argue that more certainty is needed before alarms are raised. GlaxoSmithKline
said a “vast majority” of the recent reports regarding Avandia was related to
The Senate investigation — the result of years of digging through more than
250,000 internal company documents — concludes that GlaxoSmithKline and by
extension the F.D.A. delayed far too long in this process.
In November 2003, for instance, the company completed a study in which diabetics
given Avandia had far more heart problems than those given placebos. Two months
later, the World Health Organization sent the company an alert linking Avandia
to heart ailments. In a June 2004 meeting, the company’s Global Safety Board
said a hard look should be taken at all Avandia clinical trials for more signs
of heart problems, documents show.
European regulators had earlier ordered GlaxoSmithKline to conduct a study —
called the Record trial — to examine Avandia’s heart risks because hints of
these problems appeared in the company’s earliest trials.. But the Senate report
shows that by at least 2004, company executives were aware that the Record trial
was going so poorly that it would never answer the heart question with any kind
So company executives gathered dozens of Avandia studies and sifted their
combined data. Called a meta-analysis, this combined look found first in 2005
and in an updated look in 2006 that Avandia increased the risks of serious heart
problems by nearly a third, the Senate investigation shows. Because two-thirds
of diabetics die of heart problems, this was hugely worrying.
In 2005, executives revealed the results of their meta-analysis to the F.D.A.,
and in 2006 they provided the agency with the underlying data.
Two large company-sponsored trials — called Dream and Adopt — were published
near the end of 2006, and each provided more hints that Avandia hurts the heart,
the documents show. In a March 2007 meeting of the company’s Diabetes Franchise
Cardiology Advisory Board, advisers called the safety worries found in these
many studies “disquieting.” Negotiations with agency officials about how and
whether to alert the public continued.
Meanwhile, the company continued to market and advertise Avandia aggressively.
The Senate inquiry concludes that the company threatened doctors who suggested
in public that Avandia might have serious risks.
In 1999, for instance, Dr. John Buse, a professor of medicine at the University
of North Carolina, gave presentations at scientific meetings suggesting that
Avandia had heart risks. GlaxoSmithKline executives complained to his supervisor
and hinted of legal action against him, according to the Senate inquiry. Dr.
Buse eventually signed a document provided by GlaxoSmithKline agreeing not to
discuss his worries about Avandia publicly. The report cites a separate episode
of intimidation of investigators at the University of Pennsylvania.
GlaxoSmithKline said that it “does not condone any effort to silence” scientific
debate, and that it disagrees with allegations that it tried to silence Dr.
Buse. Still, it said the situation “could have been handled differently.”
Research Ties Diabetes Drug to Heart Woes,
May Help Only Severe Depression
January 6, 2010
The New York Times
By BENEDICT CAREY
Some widely prescribed drugs for depression provide relief in extreme cases
but are no more effective than placebo pills for most patients, according to a
new analysis released Tuesday.
The findings could help settle a longstanding debate about antidepressants.
While the study does not imply that the drugs are worthless for anyone with
moderate to serious depression — many such people do seem to benefit — it does
provide one likely explanation for the sharp disagreement among experts about
the drugs’ overall effectiveness.
Taken together, previous studies have painted a confusing picture. On one hand,
industry-supported trials have generally found that the drugs sharply reduce
symptoms. On the other, many studies that were not initially published, or were
buried, showed no significant benefits compared with placebos.
The new report, appearing in The Journal of the American Medical Association,
reviews data from previous trials on two types of drugs and finds that their
effectiveness varies according to the severity of the depression being treated.
Previous analyses had found a similar pattern. But the new study is the first to
analyze responses from hundreds of people being treated for more moderate
symptoms, as are most people who seek care.
“I think the study could dampen enthusiasm for antidepressant medications a bit,
and that may be a good thing,” said Dr. Erick H. Turner, a psychiatrist at
Oregon Health and Science University. “People’s expectations for the drugs won’t
be so high, and doctors won’t be surprised if they’re not curing every patient
they see with medications.”
But Dr. Turner added, “The findings shouldn’t dampen expectations so much that
people refuse to even try medication.”
A team of researchers, including psychologists who favor talk therapy and
doctors who consult widely with drug makers, performed the new analysis, using
government grants. The group evaluated six large drug trials, including 728 men
and women, about half of them with severe depression and half with more moderate
Three of the trials were of Paxil, from GlaxoSmithKline, a so-called S.S.R.I.,
and the other three were of imipramine, an older generic drug from the class
known as tricyclics. The team, led by Jay C. Fournier and Robert J. DeRubeis of
the University of Pennsylvania, found that compared with placebos, the drugs
caused a much steeper reduction in symptoms of severe depression (cases scoring
25 or higher on a standard scale of severity, putting them in the top quarter of
the sample). Patients with scores of less than 25 got little or no added benefit
from the medications.
“We were able to give an overall estimate of effectiveness for the first time in
this more moderate severity range, from 14 to 20 on the scale, in which there’s
no question that doctors would likely consider prescribing medication,” Dr.
His co-authors included Steven D. Hollon and Dr. Richard C. Shelton of
Vanderbilt University, Sona Dimidjian of the University of Colorado, Dr. Jan
Fawcett of the University of New Mexico and Dr. Jay D. Amsterdam of Penn.
The effects of other popular S.S.R.I.’s like Lexapro and Prozac are not likely
to be much different than those of Paxil, experts said.
Dr. DeRubeis and others said antidepressants’ inability to outperform placebos
against moderate symptoms stemmed partly from the sustained attention that
patients in drug trials received from top doctors — which itself can help
relieve symptoms, drug or no drug. For some people, too, the drugs’ side effects
may cancel any benefit.
“The message for patients with mild to moderate depression,” Dr. DeRubeis said,
“is, ‘Look, medications are always an option, but there’s little evidence that
they add to other efforts to shake the depression — whether it’s exercise,
seeing the doctor, reading about the disorder or going for psychotherapy.’ ”
Popular Drugs May Help
Only Severe Depression, NYT, 6.1.2010,
Rising Prices of Drugs
Lead to Call for Inquiry
November 19, 2009
The New York Times
By DUFF WILSON
Democrats in Congress asked for two separate investigations of drug industry
pricing Wednesday as they continue working on legislation to overhaul the
nation’s health care system.
Responding to news reports of unusually high wholesale price increases in
brand-name prescription drugs, four House leaders and one senator asked for
government reviews of the pricing practices.
Although drug makers challenge the theory, some experts say the run-up in
wholesale prices may be partly related to the industry’s concerns about future
cost containment under any health care legislation.
“Recent studies have indicated that the industry may be artificially raising
prices for certain pharmaceutical products in expectation of new reforms,” the
House Democrats wrote in a letter to the Government Accountability Office, a
nonpartisan investigative arm of Congress. “Any price gouging is unacceptable,
but anticipatory price gouging is especially offensive,” the letter added,
asking the G.A.O. to conduct an expedited review of the price increases.
The House letter was signed by four representatives who have been active in the
health care legislation: Charles B. Rangel of New York, chairman of the Ways and
Means Committee; Henry A. Waxman of California, chairman of the Energy and
Commerce Committee; and Pete Stark of California, and John Lewis of Georgia,
chairmen of two Ways and Means subcommittees.
Separately, Senator Bill Nelson of Florida, a Democrat who has led efforts in
the Senate to seek more concessions from drug makers, wrote to the inspector
general of the Department of Health and Human Services asking for “an immediate
and thorough investigation into drug industry pricing and recent increases, and
the extent to which these increases may affect the Medicare and Medicaid
Both letters cited a New York Times article on Monday reporting that wholesale
prices of brand-name drugs rose about 9 percent in the 12 months that ended
Sept. 30, the highest increase in years — even as the Consumer Price Index was
declining during the same 12-month period.
The Times article cited a Wall Street analyst’s calculations; a study sponsored
by the AARP, the advocacy group for older Americans; and a report by IMS Health,
a consulting firm to the drug industry.
The price increases could add more than $10 billion to the nation’s drug bill,
which is on track to exceed $300 billion this year.
At that rate, the increases would more than offset at least the first year of
savings that the drug industry has agreed to make under a provision of the
health care bill that was approved by the Senate Finance Committee and has been
incorporated into the full Senate bill introduced on Wednesday. That measure
calls for the industry to come up with discounts and rebates that would save
Medicare recipients and the government $8 billion a year for 10 years.
“I want to know if there’s a back-door move under way by the drug makers to
recover some of the concessions they’ve promised for health care reform,”
Senator Nelson said in a statement Wednesday.
Drug companies do not deny having raised wholesale prices at the highest rate in
years. But they say it has nothing to do with the impending health care
legislation. They say the price increases are necessary to maintain profits for
research and employment in the face of a difficult business environment, which
includes a slowdown in sales of many brand-name products, expiring patents and
increasing competition from generic drugs.
The wholesale prices of brand-name drugs most commonly used by Medicare
recipients rose in the latest 12-month period at the fastest rate since at least
1992, according to Stephen W. Schondelmeyer, a pricing expert working with AARP.
Separately, a study by the investment bank Credit Suisse found that prices for
all drugs from the eight largest United States pharmaceutical companies had
risen, on average, at the highest rate in at least five years.
And IMS Health said there were higher-than-expected price increases this year.
Mr. Schondelmeyer, professor of pharmaceutical economics at the University of
Minnesota, and Catherine J. Arnold, a senior drug industry analyst for Credit
Suisse, have said they believe that part of the reason for the price increases
was to get ahead of possible cost containment measures in health care reform.
Professor Schondelmeyer and Joseph P. Newhouse, a Harvard health economist, said
there were precedents for drug price increases before government actions
affecting the industry.
The House Democrats also said the G.A.O. had previously found unusual price
increases in some prescription drugs in the year before Congress added drug
benefits to Medicare.
The House letter on Wednesday said that the G.A.O. could build on that work.
The House members are also asking the G.A.O. to submit a proposal to
continuously monitor prescription drug prices. The House health care bill
already includes a provision authorizing Medicare to negotiate directly with
manufacturers — a proposal hotly opposed by the industry.
Ken Johnson, an official with the drug industry’s trade association, said in a
statement that calls for an investigation were “based on misleading use of
statistics and sensationalized media reports.”
Mr. Johnson, senior vice president for the Pharmaceutical Manufacturers and
Research Association, did not deny any of the specific findings of AARP, Credit
Suisse and IMS Health reports, which were based on data supplied by
manufacturers and wholesalers. But he said other measurements of drug price
increases show they have risen substantially less than 9 percent.
Mr. Johnson accused AARP of “trying to muddy the waters for its own political
gain as we enter the homestretch of the health care reform debate.”
An AARP executive vice president, John Rother, said in a statement: “This isn’t
about politics. It’s about affordable health care.”
Rising Prices of Drugs
Lead to Call for Inquiry, NYT, 19.11.2009,
Costly Drugs Known as Biologics
Prompt Exclusivity Debate
July 22, 2009
The New York Times
By ANDREW POLLACK
A bitter Congressional fight over the cost of superexpensive biotechnology
drugs has come down to a single, hotly debated number: How many years should
makers of those drugs be exempt from generic competition?
But what few people in Washington seem to recognize — or publicly acknowledge,
anyway — is that this magic number may ultimately not matter as much as the most
vitriolic debaters insist.
At issue are such drugs as Biogen Idec’s Avonex, for multiple sclerosis, which
can cost more than $20,000 a year; Genentech’s Avastin for cancer, which can
cost more than $50,000; and several Genzyme drugs for rare diseases that can
cost $200,000 a year or more. Typically, such drugs are given by injection or
These drugs, known as biologics, are complex proteins made in vats of living
cells. Because they are hard to copy exactly, they have not been subject to the
generic competition that eventually knocks down the price of drugs like Lipitor
and Prozac. Pills like Lipitor, known in the industry as small-molecule drugs,
are made from simple chemicals whose recipes are easy to reproduce.
But now Congress, as a cost-cutting piece of the overall health care effort, is
preparing legislation to enable the Food and Drug Administration to approve
copycat versions of biologic drugs. That could save consumers, insurers and the
government billions of dollars in the coming years.
The trick is to allow competition without undermining the financial incentives
the pharmaceutical industry needs to undertake the risky job of developing the
next drugs for cancer and other diseases. That is where the magic year number
comes in. Trade groups for the big pharmaceutical and biotechnology companies
say that to recoup their investments, they need an exclusivity period free of
generic competition that would last 12 to 14 years from the time the F.D.A.
approves a drug for sale.
But consumer groups, insurers, employers and generic drug companies say anything
more than five years — the exclusivity period now given to small-molecule drugs
like Lipitor — would eviscerate any potential savings from the new competition.
So far, the biotechnology industry appears to be winning. The Senate’s health
committee, for example, has agreed to 12 years of exclusivity. In the House, a
bill that provides at least 12 years of exclusivity has many more co-sponsors
than one that would provide five years. The Obama administration has said that
seven years would be a “generous compromise.”
But in reality, neither the threats to innovation nor the potential savings from
generic competition are as great as claimed.
For starters, whatever the exclusivity period, biologic drugs would also
continue to be protected from copycats by patents. And in many cases, the patent
protection would last longer than the exclusivity period, making the
Congressionally mandated exclusivity a moot point.
Genentech’s Avastin, for instance, has patent protection until 2019 — 15 years
after the drug’s 2004 approval by the F.D.A. The company’s breast cancer drug,
Herceptin, has patents that extend 21 years from its 1998 approval.
Where the exclusivity period might matter most would be in the cases of drugs
whose patents were nearing expiration by the time the developer succeeded in
winning F.D.A. approval. But that seldom happens.
“I can’t think of a biotech drug that’s been on the market that doesn’t have
more than 7 to 14 years of patent protection,” said Eric Schmidt, biotechnology
analyst at Cowen & Company.
Still, it is probably not true, as the other side claims, that the legislation
would be virtually worthless if it granted a long exclusivity period. There are
plenty of blockbuster biologics, like Epogen and Neupogen from Amgen, that have
been on the market more than 12 or 14 years and thus would get no extra
protection from even an exclusivity period at the long end of the ranges now
As for cost savings, the Congressional Budget Office has estimated that generic
biologics might save the government only about $10 billion in the next 10 years.
That is a relative drop in the bucket when it comes to paying for health care
reform, which is expected to cost about $1 trillion over 10 years.
One reason for limited savings in the first decade is that it would probably
take a few years for copycat biologics to reach the market after the law was
enacted. Another factor is that biologics accounted for only 16 percent — about
$46 billion — of total prescription drug spending last year, according to the
market researchers IMS Health. And pharmaceuticals represent only about 10
percent of the nation’s overall health care spending.
The real savings might come more than 10 years out, as new biologic drugs
appeared and as biologics represented an increasingly greater part of overall
spending on drugs. That ramp-up is already evident: Express Scripts, a pharmacy
benefits manager, says its spending on biologics grew 10 percent last year,
compared with 2.5 percent for other drugs.
But anyone expecting the price wars that ensue when generic pills come on the
market — when prices often drop by more than 60 percent — might be disappointed
by the way competition plays out in biologic drugs.
Because it is harder and costlier to make biologic drugs than it is to copy
pills, fewer generic competitors are likely to enter the fray. Many experts,
including the Federal Trade Commission, expect price declines of more like 10 to
40 percent in biologics.
Even that would be a substantial savings for the overall health care system. But
for many individuals, a $35,000 copycat version of a $50,000 cancer drug would
still be unaffordable.
Another factor is that generic biologics are likely to undergo greater
regulatory scrutiny than generic pills require.
It is difficult or impossible to verify that a copy of a biologic is exactly the
same as the original — which is why the drugs are often called “biosimilars”
rather than generic biologics. Because even small changes might affect the
drug’s safety or activity, it is likely that makers of biosimilars will have to
conduct at least some clinical trials to win F.D.A. approval of their drugs,
which makers of generic small-molecule pills are not required to do. Such trials
can cost a lot of money.
Since biosimilars will not be exact replicas, generic makers will probably need
sales forces to persuade doctors to prescribe their drugs and pharmacists to
dispense them. All of that costs money, too.
In Europe, which has approved biosimilar versions of three biologic drugs,
companies generally price their biosimilar drugs about 20 to 30 percent lower
than the originals. The impact in Europe has been limited so far, but in Germany
the biosimilars have captured about 30 percent of the market for anemia drugs
and forced the brand-name manufacturers to lower their prices.
The likelihood that biosimilar competition might be somewhat muted means that
sales and profits of the originals may not necessarily dry up.
Kevin W. Sharer, Amgen’s chief executive, told investors in May that he hoped
biotechnology companies would retain 30 to 50 percent of the cash flow from
their drugs even after biosimilars reached the market. That, he said, “is a
dramatically different outcome than we see in the small-molecule companies.”
That is also one reason the Federal Trade Commission, in a report last month,
said that no exclusivity period at all was needed. At the very least, because
biologic drugs do not require appreciably more time or money to bring to market
than small-molecule drugs, it is reasonable to ask why they should deserve
longer protection from competition than the five years that small-molecule drugs
The reason, biotechnology executives say, is that patents may offer less
protection for biologics than for small-molecule drugs. Because a biosimilar is
not an exact knock-off of the original, a competitor might persuasively claim
that it is not infringing the patents on the original drug.
So far biologic patents have held up well in court cases. Amgen, for example,
has won legal victories preventing competitors from introducing anemia drugs
that are slightly different from its own Epogen.
But generic makers and their supporters, sensing that many of the biologic
patents may not withstand court challenges, are lobbying for the shortest
possible exclusivity period.
“If your patents are strong, let your patents stand for themselves,” said Katie
Huffard, executive director of the Coalition for a Competitive Pharmaceutical
Market, a group of employers, insurers, pharmacies and generic makers lobbying
for easier access to biosimilars. “That’s what every other industry has to do.”
Costly Drugs Known as
Biologics Prompt Exclusivity Debate, NYT, 22.7.2009,
Drug Costs Soar Beyond Reach
The New York Times
take a health policy expert to recognize that something has gone terribly wrong
when patients have to pay thousands of dollars a month for drugs that they need
to maintain their health — and possibly save their lives. Congress needs to
determine why this is happening and what can be done about it.
The plight of patients who have recently been hit with a huge increase in their
insurance co-payments for high-priced prescription drugs was laid out in The
Times on Monday by Gina Kolata. Instead of paying a modest $10 to $30
co-payment, as is usually the case for cheaper drugs, patients who need
especially costly medicines are being forced to pay 20 percent to 33 percent of
the bill (up to an annual maximum) for drugs that can cost tens of thousands of
dollars, or even hundreds of thousands of dollars, a year.
These drugs — what insurers call Tier 4 medicines — are used to treat such
serious illnesses as multiple sclerosis, hemophilia, certain cancers and
rheumatoid arthritis. And since there are usually no cheaper alternatives,
patients must either pay or do without, unless they can get their medicines
through some charitable plan.
There is little doubt that the so-called tiered formularies, in which
co-payments rise along with the cost of the drugs, are a sensible approach for
encouraging consumers to use the cheapest drug suitable for their condition. But
the system seems to break down when it moves to Tier 4 drugs where co-payments
can be huge and suitable alternatives don’t exist.
The insurers say that forcing patients to pay more for unusually high-priced
drugs allows them to keep down the premiums charged to everyone else. That turns
the ordinary notion of insurance on its head. Instead of spreading the risks and
costs across a wide pool of people to protect a smaller number of very sick
patients from financial ruin, insurers are gouging the sickest patients to keep
premiums down for healthier people.
The health insurance system is so complex that it is hard to parse the blame for
this injustice. The drug companies, especially the biotechnology companies, are
at the root of the problem; they often charge exorbitant prices for monopoly
drugs that were developed with heavy government assistance. Washington needs to
rein them in by encouraging generic competition for biological drugs and
allowing government programs to negotiate lower prices.
Employers, including the federal government, also bear responsibility. They have
been pressing to reduce their prescription drug expenditures, and all health
care expenditures, by shifting more of the burden to patients. One patient who
had been paying only $20 for a month’s supply of a multiple sclerosis drug was
shocked when the charge rose to $325 per month. (It has since been suspended.)
Another patient found that his co-payment for a newly prescribed leukemia drug
would exceed $4,000 for a 90-day supply, so he has deferred buying it.
If patients do without medicines or put off taking them, the likely result will
be sicker patients, and higher costs, down the road.
What is not clear is whether insurers are primarily reacting to pressure from
employers or are exploiting the situation to increase their profits. Congress
needs to probe hard to find out how many patients are facing enormous drug bills
and how best to protect them from medical and financial disaster.
When Drug Costs Soar Beyond Reach, NYT, 15.4.2008,
27 January 1926
New vaccines for tetanus and
From The Guardian Archive
[ Diptheria, nicknamed "the
was until the mid-1920s
the prime cause of death among children
to their mid-teens.
Immunity Claimed for Infants. "Vaccines" against diphtheria and tetanus,
comparable as prophylactics with Jenner's vaccine against smallpox, have been
discovered at the Pasteur Institute here by a French chemist, M. G. Ramon. They
are harmless, do not cause the slightest reaction, and confer an immunity even
more lasting than that of calf-lymph against small-pox. It is suggested that all
infants over twelve months' old should henceforth go through a second
vaccination for diphtheria, and that all soldiers on active service should be
vaccinated against tetanus, as they are now against typhus.
A generation ago Dr. Roux, the friend and successor of Pasteur, discovered
specific serums against diphtheria and tetanus, but the immunising effect of
injections in both cases has been extremely ephemeral, lasting only a few days.
M. Ramon set himself to find something that would be as good, if not better,
than Jenner's vaccine.
It is, of course, known that the microbes of diphtheria and of tetanus develop
in the blood, or in a serum, extremely harmless specific poisons, the diphtheria
toxin and the tetanus toxin. By subjecting these toxins to about blood
temperature, 38 degrees centigrade, for about a month and utilising certain
chemicals, as, for example, formol, M. Ramon has succeeded in obtaining new
products that he calls anatoxins, an anti-diphtheria anatoxin and an
Two years ago experiments began with anatoxins upon human beings at the Pasteur
hospital and the military hospital in Paris. Some scores of thousands of
patients, chiefly babies, have been innoculated against diphtheria, and the
results are such that it is claimed that if infants are vaccinated against it,
this dread disease of early life would disappear.
At the Pasteur Institute it has been equally shown that human beings – and
domestic animals too – can be immunised against tetanus. Over a hundred human
subjects have been treated, with a consequent immunity that is remarkably high.
Soldiers on campaign are a class especially exposed to tetanus infections. They
are already subjected to anti-typhoid inoculation. M. Ramon has formed a mixture
of "vaccines" which dispenses with a second injection and enables young soldiers
to be immunised simultaneously against typhoid fever and tetanus, the twin
scourges of armies in the field.
New vaccines for tetanus and
diptheria, G, 27 January 1926, republished 27.1.2009, p. 32,
March 6, 1844
Cure your worms, teeth and
From The Guardian Archive
Wednesday March 6, 1844
Medicine never witnessed a
more important discovery than in Pritchett's Vegetable Vermifuge, a remedy that
neither purges, vomits, nor otherwise affects the constitution; requires no
confinement, has neither taste nor smell, and is so harmless that it may be
taken by an infant of an hour old; yet never, in one instance, failed destroying
every worm in the body.
It contains not a particle of calomel, scammony, gamboge, or other drastic
article. Large packets 2s.9d.
Determination of blood to the head effectually prevented by the occasional use
of Frampton's Pill of Health, which, by strengthening the action of the stomach,
prevents alarming giddiness, oppression of the brain, singing noise in the ears,
headache. They are an excellent aperient, without griping or prostration of
strength. Price 1 1/2d. and 2s.9d. a box.
For stopping decayed teeth
Patronised by her Majesty the Queen, his Royal Higness Prince Albert, her Royal
Highness the Duchess of Kent, his Majesty the King of the Belgians, his Majesty
the King of Prussia, his Grace the Archbishop of Canterbury, and nearly all the
nobility, the bishops, and the clergy. Mr Thomas's Succedaneum, for filling
decayed teeth, however large the cavity.
It is superior to anything ever before used, as it is placed in the tooth in a
soft state, without any pressure or pain, and in a short time becomes as hard as
the enamel, and will remain firm in the tooth for many years, rendering
It arrests all further progress of decay, and renders them again useful in
mastication. All persons can use Mr Thomas's Succedaneum themselves with else,
without the aid of a dentist. Prepared only by Mr. Thomas, surgeon-dentist, 8,
Berners-street, Oxford-street, London ; price 4s. 6d. Mr Thomas will send it
free by post.
To these who are suffering from nervous complaints, rheumatism, scurvy, sorbutic
eruptions and all diseases arising from impurity of the blood. The Cordial Balm
of Syriacum is a gentle stimulant and enovator of the impaired functions of
life, and is, therefore, calculated to afford decided relief to those who have
fallen into a state of most chronic debility. It possesses wonderful efficacy in
fits, headache, weakness, heaviness, dimness of sight, confused thoughts,
wandering of the mind, and all kinds of hysteric complaints. Price 11s.
From The Guardian Archive > Cure
your worms, teeth and giddiness, 6.3.1844,
G, Republished 6.3.2006,