How a New Policy Led to Seven Deadly Drugs

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How a New Policy Led to Seven Deadly Drugs

_http://www.latimes.com/news/nation/reports/fda/lat_fda001220.htm_

(http://www.latimes.com/news/nation/reports/fda/lat_fda001220.htm)

_http://www.drugawareness.org/Archives/Miscellaneous/122002Howanew.html_

(http://www.drugawareness.org/Archives/Miscellaneous/122002Howanew.html)

By DAVID WILLMAN

 

 

WASHINGTON--For most of its history, the United States Food and Drug

Administration approved new prescription medicines at a grudging pace, paying

daily homage to the physician's creed, **First, do no harm.**

 

Then in the early 1990s, the demand for AIDS drugs changed the political

climate. Congress told the FDA to work closely with pharmaceutical firms in

getting new medicines to market more swiftly. President Clinton urged FDA

leaders to trust industry as **partners, not adversaries.**

 

The FDA achieved its new goals, but now the human cost is becoming clear.

 

Seven drugs approved since 1993 have been withdrawn after reports of

deaths and severe side effects. A two-year Los Angeles Times investigation has

found that the FDA approved each of those drugs while disregarding danger

signs or blunt warnings from its own specialists. Then, after receiving

reports of significant harm to patients, the agency was slow to seek

withdrawals.

 

According to **adverse-event** reports filed with the FDA, the seven drugs

were cited as suspects in 1,002 deaths. Because the deaths are reported by

doctors, hospitals and others on a voluntary basis, the true number of

fatalities could be far higher, according to epidemiologists.

 

An adverse-event report does not prove that a drug caused a death; other

factors, such as preexisting disease, could play a role. But the reports are

regarded by public health officials as the most reliable early warnings of

danger.

 

The FDA*s performance was tracked through an examination of thousands of

pages of government documents, other data obtained under the Freedom of

Information Act and interviews with more than 60 present and former agency

officials.

 

The seven drugs were not needed to save lives. One was for heartburn.

Another was a diet pill. A third was a painkiller. All told, six of the

medicines were never proved to offer lifesaving benefits, and the seventh, an

antibiotic, was ultimately judged unnecessary because other, safer antibiotics

were available.

 

The seven are among hundreds of new drugs approved since 1993, a period

during which the FDA has become known more for its speed than its caution. In

1988, only 4% of new drugs introduced into the world market were approved

first by the FDA. In 1998, the FDA's first-in-the-world approvals spiked to

66%.

 

The drug companies* batting average in getting new drugs approved also

climbed. By the end of the 1990s, the FDA was approving more than 80% of the

industry*s applications for new products, compared with about 60% at the

beginning of the decade.

 

And the companies have prospered: The seven unsuccessful drugs alone

generated U.S. sales exceeding $5 billion before they were withdrawn.

 

Once the world*s unrivaled safety leader, the FDA was the last to withdraw

several new drugs in the late 1990s that were banned by health authorities

in Europe.

 

**This track record is totally unacceptable,** said Dr. Curt D. Furberg, a

professor of public health sciences at Wake Forest University. **The

patients are the ones paying the price. They*re the ones developing all the

side

effects, fatal and non-fatal. Someone has to speak up for them.**

 

The FDA*s faster and more lenient approach helped supply pharmacy shelves

with scores of new remedies. But it has also yielded these fatal missteps,

according to the documents and interviews:

 

 

1. Only 10 months ago, FDA administrators dismissed one of its medical

officer*s emphatic warnings and approved Lotronex, a drug for treating

irritable bowel syndrome. Lotronex has been linked to five deaths, the removal

of

a patient*s colon and other bowel surgeries. It was pulled off the market

on Nov. 28.

 

 

2. The diet pill Redux, approved in April 1996 despite an advisory

committee's vote against it, was withdrawn in September 1997 after heart-valve

damage was detected in patients put on the drug. The FDA later received

reports identifying Redux as a suspect in 123 deaths.

 

 

3. The antibiotic Raxar was approved in November 1997 in the face of

evidence that it may have caused several fatal heart-rhythm disruptions in

clinical studies. FDA officials chose to exclude any mention of the deaths from

the drug's label. The maker of the pill withdrew it in October 1999. Raxar

was cited as a suspect in the deaths of 13 patients.

 

 

4. The blood pressure medication Posicor was approved in June 1997 despite

findings by FDA specialists that it might fatally disrupt heart rhythm and

interact with certain other drugs, posing potentially severe risk. Posicor

was withdrawn one year later; reports cited it as a suspect in 100 deaths.

 

 

5. The painkiller Duract was approved in July 1997 after FDA medical

officers warned repeatedly of the drug's liver toxicity. Senior officials sided

with the manufacturer in softening the label's warning of the liver threat.

The drug was withdrawn 11 months later. By late 1998, the FDA had received

voluntary reports citing Duract as a suspect in 68 deaths, including 17

that involved liver failure.

 

 

6. The diabetes drug Rezulin was approved in January 1997 over a medical

officer's detailed opposition and was withdrawn this March after the agency

had linked 91 liver failures to the pill. Reports cite Rezulin as a suspect

in 391 deaths.

 

 

7. The nighttime heartburn drug Propulsid was approved in 1993 despite

evidence that it caused heart-rhythm disorders. The officials who approved the

drug failed to consult the agency's own cardiac specialists about the

signs of danger. The drug was taken out of pharmacies in July after scores of

confirmed heart-rhythm deaths. Overall, Propulsid has been cited as a suspect

in 302 deaths.

 

The FDA*s handling of Propulsid put children at risk.

 

The agency never warned doctors not to administer the drug to infants or

other children even though eight youngsters given Propulsid in clinical

studies had died. Pediatricians prescribed it widely for infants afflicted with

gastric reflux, a common digestive disorder.

 

Parents and their doctors had no way of knowing that the FDA, in August

1996, had found Propulsid to be **not approvable** for children.

 

**We never knew that,** said Jeffrey A. Englebrick, a heavy-equipment

welder in Shawnee, Kan., whose 3-month-old son, Scott, died on Oct. 28, 1997,

after taking Propulsid. **To me, that means they took my kid as a guinea pig

to see if it would work.**

 

By the time the drug was pulled, the FDA had received reports of 24 deaths

of children under age 6 who were given Propulsid. By then the drug had

generated U.S. sales of $2.5 billion for Johnson & Johnson Co.

 

Questions also surround the recent approvals of other compounds that

remain on the market, including a new flu drug called Relenza. In February of

1999, an FDA advisory committee concluded that Relenza had not been proved

safe and effective. The agency nevertheless approved it. Following the deaths

of seven patients, the FDA in January issued a **public health advisory**

to doctors.

 

A *Lost Compass*

 

A total of 10 drugs have been pulled from the market in just the past

three years for safety reasons, including three pills that were approved before

the shift that took hold in 1993. Never before has the FDA overseen the

withdrawals of so many drugs in such a short time. More than 22 million

Americans--about 10% of the nation*s adult population--took those drugs.

 

With many of the drugs, the FDA used tiny-print warnings or

recommendations in package labeling as a way to justify approvals or stave off

withdrawals. In other instances, the agency has withheld safety information from

labels that physicians say would call into question the use of the product.

 

Present and former FDA specialists said the regulatory decisions of senior

officials have clashed with the agency*s central obligation, under law, to

**protect the public health by ensuring . . . that drugs are safe and

effective.**

 

**They*ve lost their compass and they forget who it is that they are

ultimately serving,** said Dr. Lemuel A. Moye, a University of Texas School of

Public Health physician who served from 1995 to 1999 on an FDA advisory

committee. **Unfortunately the public pays for this, because the public

believes that the FDA is watching the door, that they are the sentry.**

 

The FDA*s shift is felt directly in the private practice of medicine, said

Dr. William L. Isley, a Kansas City, Mo., diabetes specialist. He implored

the agency to reassess Rezulin three years ago after a patient he treated

suffered liver failure taking the pill.

 

**FDA used to serve a purpose,** Isley said. **A doctor could feel sure

that a drug he was prescribing was as safe as possible. Now you wonder what

kind of evaluation has been done, and what's been swept under the rug.**

 

FDA officials said that they have tried conscientiously to weigh benefits

versus risks in deciding whether to approve new drugs. They noted that many

doctors and patients complain when a drug is withdrawn. **All drugs have

risks; most of them have serious risks,** said Dr. Janet Woodcock, director

of the FDA*s drug review center. She added that some of the withdrawn drugs

were **very valuable, even if not lifesaving, and their removal from the

market represents a loss, even if a necessary one.** Once a drug is proved

effective and safe, Woodcock said, the FDA depends on doctors **to take into

account the risks, to read the label. . . . We have to rely on the

practitioner community to be the learned intermediary. That*s why drugs are

prescription drugs.**

 

In a May 12, 1999, article co-authored with FDA colleagues and published

by the Journal of the American Medical Assn., Woodcock said, **The FDA and

the community are willing to take greater safety risks due to the serious

nature of the [illnesses] being treated.**

 

Compared to the volume of new drugs approved, they wrote, the number of

recent withdrawals **is particularly reassuring.**

 

However, agency specialists point out that both approvals and withdrawals

are controlled by Woodcock and her administrators. When they consider a

withdrawal, they face the unpleasant prospect of repudiating their original

decision to approve.

 

Woodcock, 52, received her medical degree at Northwestern University and

is a board-certified internist. She alluded in a recent interview to the

difficulty she feels in rejecting a proposed drug that might cost a company

$150 million or more to develop. She also acknowledged the commercial

pressures in a March 1997 article.

 

**Consumer protection advocates want to have drugs worked up well and

thoroughly evaluated for safety and efficacy before getting on the market,**

Woodcock wrote in the Food and Drug Law Journal. **On the other hand, there

are economic pressures to get drugs on the market as soon as possible, and

these are highly valid.**

 

But this summer--following the eighth and ninth drug withdrawals--Woodcock

said the FDA cannot rely on labeling precautions, alone, to resolve safety

concerns.

 

**As medical practice has changed . . . it*s just much more difficult for

[doctors] to manage the expanded drug supply**, Woodcock said in an

interview. **They rely upon us much more to make sure the drugs are safe.**

 

Another FDA administrator, Dr. Florence Houn, voiced similar concern in

remarks six months ago to industry officials: **I think the lessons learned

from the drug withdrawals make us leery.**

 

Yet the imperative to move swiftly, cooperatively, remains.

 

**We are now making decisions more quickly and more predictably while

maintaining the same high standards for product safety and efficacy,** FDA

Commissioner Jane E. Henney said in a National Press Club speech on Dec. 12.

 

Motivated by AIDS

 

The impetus for change at the FDA emerged in 1988, when AIDS activists

paralyzed operations for a day at the agency*s 18-story headquarters in

Rockville, Md. They demanded immediate approval of experimental drugs that

offered at least a ray of hope to those otherwise facing death.

 

The FDA often was taking more than two years to review new drug

applications. The pharmaceutical industry saw a chance to loosen the regulatory

brakes and expedite an array of new products to market. The companies and their

Capitol Hill lobbyists pressed for advantage: If unshackled, they said, the

companies could invent and develop more remedies faster.

 

The political pressure mounted, and the FDA began to bow. By 1991, agency

officials told Congress they were making significant progress in speeding

the approval process.

 

The emboldened companies pushed for more. They proposed that drugs

intended for either life-threatening or **serious** disorders receive a quicker

review.

 

**The pharmaceutical companies came back and lobbied the agency and the

Hill for that word, *serious*, ** recalled Jeffrey A. Nesbit, who in 1991 was

chief of staff to FDA Commissioner David A. Kessler. **Their argument was,

*Well, OK, there*s AIDS and cancer. But there are drugs [being developed]

for Alzheimer*s. And that*s a serious illness.* They started naming other

diseases. They began to push that envelope.**

 

The wielding of this single, flexible adjective--*serious*--swung wide the

regulatory door knocked ajar by the AIDS crisis.

 

New Order Takes Hold

 

In 1992, Kessler issued regulations giving the FDA discretion to

**accelerate approval of certain new drugs** for serious or life-threatening

conditions. That same year a Democrat-controlled Congress approved and President

Bush signed the Prescription Drug User Fee Act. It established goals that

call for the FDA to review drugs within six months or a year; the

pharmaceutical companies pay a user fee to the FDA, now $309,647, with the

filing of

each new drug application.

 

The newly elected Clinton administration climbed aboard with its

**reinventing government** project. Headed by Vice President Al Gore, the

project

called for the FDA, by January 2000, to reduce **by an average of one year

the time required to bring important new drugs to the American public.** As

Clinton put it in a speech on March 16, 1995, the objective was to **get rid

of yesterday's government.**

 

For the FDA*s medical reviewers--the physicians, pharmacologists, chemists

and biostatisticians who scrutinize the safety and effectiveness of

emerging drugs--a new order had taken hold.

 

The reviewers work out of public view in secure office buildings clustered

along Maryland*s Route 355. At the jet-black headquarters building, the

decor is institutional, the corridors and third-floor cafeteria without

windows. The reviewers examine truckloads of scientific documents. They are

well-educated; some are highly motivated to do their best for a nation of

patients who unknowingly count on their expertise.

 

One of these reviewers was Michael Elashoff, a biostatistician who arrived

at the FDA in 1995 after earning degrees from UC Berkeley and the Harvard

School of Public Health. **From the first drug I reviewed, I really got the

sense that I was doing something worthwhile. I saw what a difference a

single reviewer can make,** said Elashoff, the son and grandson of

statisticians.

 

Last year he was assigned to review Relenza, the new flu drug developed by

Glaxo Wellcome. He recommended against approval.

 

**The drug has no proven efficacy for the treatment of influenza in the

U.S. population, no proven effect on reducing person-to-person

transmissibility, and no proven impact on preventing influenza,** Elashoff

wrote, adding

that many patients would be exposed to risks **while deriving no benefit.**

 

An agency advisory committee agreed and on Feb. 24 voted 13 to 4 against

approving Relenza. After the vote, senior FDA officials upbraided Elashoff.

They stripped him of his review of another flu drug. They told him he would

no longer make presentations to the advisory committee. And they approved

Relenza as a safe and effective flu drug.

 

Lost Faith in the System

 

Elashoff and other FDA reviewers discern a powerful message. **People are

aware that turning something down is going to cause problems with

[officials] higher up in FDA, maybe more problems than it*s worth,** he said.

**Before I came to the FDA I guess I always assumed things were done properly.

I've lost a lot of faith in taking a prescription medicine.**

 

Elashoff left the FDA four months ago.

 

**Either you play games or you*re going to be put off limits . . . a

pariah,** said Dr. John L. Gueriguian, a 19-year FDA medical officer who

opposed

the approval of Rezulin, the ill-fated diabetes drug. **The people in

charge don*t say, *Should we approve this drug?* They say, *Hey, how can we get

this drug approved?* **

 

Said Dr. Rudolph M. Widmark, who retired in 1997 after 11 years as a

medical officer: **If you raise concern about a drug, it triggers a whole

internal process that is difficult and painful. You have to defend why you are

holding up the drug to your bosses. . . . You cannot imagine how much

pressure is put on the reviewers.**

 

The pressure is such that when a union representative negotiated a new

employment contract for the reviewers last year, one of his top priorities was

to defend what he called the *scientific integrity* of their work.

 

**People feel swamped. People are pressured to go along with what the

agency wants,** said Dr. Robert S.K. Young, an FDA medical officer who in 1998

formed a union chapter to represent the reviewers. **You*re paying for

these highly educated, trained people, and they*re not being allowed to do their

job.**

 

Each new drug application is accompanied by voluminous medical data,

enough at times to fill 1,000 or more phone books. The reviewers must master

this material in less than six months or a year, while juggling other tasks.

 

**The devil is in the details, and detail is something we no longer have

the time to go into,** said Gurston D. Turner, a veteran pharmacologist with

the FDA*s scientific investigations division who retired this year. **If

you know you must have your report done by a certain date, you get something

done. That*s what they [top FDA officials] count, that*s all they count.

And that is really, to me, a worrisome thing.** The FDA did spur reviewers

to move at record speed.

 

In 1994, the FDA*s goal was to finish 55% of its new drug reviews on time;

the agency achieved 95%. In 1995, the goal was 70%; the FDA achieved 98%.

In 1996, the goal was 80%; the FDA achieved 100%. In both 1997 and 1998,

the goal was 90% and the FDA achieved 100%.

 

From 1993 to 1999 the agency approved 232 drugs regarded as **new

molecular entities,** compared with 163 during the previous seven years, a 42%

increase.

 

The time-limit goals quickly were treated as deadlines within the

FDA--imposing relentless pressure on reviewers and their bosses to quickly

conclude

their work and approve the drugs.

 

**The goals were to be taken seriously. I don*t think anybody expected the

agency to make them all,** said William B. Schultz, a deputy FDA

commissioner from 1995 to 1999.

 

Schultz, who helped craft the 1992 user-fee act as a congressional staff

lawyer, added: **You can meet the goal by either approving the drug or

denying the approval. But there are some who argue that what Congress really

wanted was not just decisions, but approvals. That is what really gets

dangerous.**

 

Indeed, the FDA drug center*s 1999 annual report referred to the review

goals as **the law*s deadlines.** And, Dr. Woodcock, the center director,

elaborated in a subsequent agency newsletter:

 

**In exchange [for the user fees], FDA makes a commitment to meet certain

goals for review times. [The agency] has exceeded almost all of the goals,

and it expects to continue to exceed them. Basically, the number of new

approved drugs has doubled, and the review times have been cut in half.**

 

The user fees have enabled the FDA to hire more medical reviewers. Last

year, 236 medical officers examined new drugs compared with 162 officers on

duty in 1992, the year before the user fees took effect.

 

Even so, Woodcock acknowledged in an FDA publication this fall that the

workloads and tight performance goals **create a sweatshop environment that*s

causing high staffing turnover.**

 

An FDA progress report in 1998, describing the work of agency chemists,

said that **too many reviews are coming *down to the wire* against the goal

date. . . . This suggests a system in stress.**

 

Said Nesbit, the former aide to Commissioner Kessler: **The clock is

always running, whereas before the clock was never running. And that changes

people*s behavior.**

 

Dozens of officials interviewed by The Times made similar observations.

 

**The pressure to meet deadlines is enormous,** said Dr. Solomon Sobel,

65, director of the FDA*s metabolic and endocrine drugs division throughout

the 1990s. And the pressure is not merely to complete the reviews, he said.

**The basic message is to approve.**

 

Over the last seven years, **there has been a huge shift,** said Kathleen

Holcombe, a former FDA legislative affairs staffer and congressional aide

who now is a drug industry consultant. **FDA, historically, had an approach

of, *Regulate, be tough, enforce the law [and] don*t let one thing go

wrong,* ** Holcombe said, adding that now, **the FDA sees itself much more in

a

cooperative role.**

 

How Deaths Were Calculated

 

Reports of adverse drug reactions to the Food and Drug Administration are

considered by public health officials to be the most reliable early

warnings of a product*s danger. The reports are filed to the FDA by health

professionals, consumers and drug manufacturers. The Los Angeles Times inspected

all reports filed in connection with seven drugs that were approved and

withdrawn since 1993. By hand and by computer, The Times counted 1,002 deaths in

which the filer identified the drug as the leading suspect. Since fall

1997, this top category has been termed *primary suspect.* The Times did not

count any death in which the drug was identified as the *secondary suspect*

or less. The methodology and results were reviewed by Sheila R. Weiss, a

former FDA epidemiologist who is an assistant professor at the University of

Maryland*s department of pharmacy practice and sciences.

 

The perception of coziness with drug makers is perpetuated by potential

conflicts of interest within the FDA*s 18 advisory committees, the

influential panels that recommend which drugs deserve approval or should remain

on

the market. The FDA allows some appointees to double as consultants or

researchers for the same companies whose products they are evaluating on the

public*s behalf. Such was the case during committee appraisals of several of the

recently withdrawn drugs, including Lotronex and Posicor, The Times found.

 

Few doubt the $100-billion pharmaceutical industry*s clout. Over the last

decade, the drug companies have steered $44 million in contributions to the

major political parties and to candidates for the White House and both

houses of Congress.

 

The FDA reviewers said they and their bosses fear that unless the new

drugs are approved, companies will erupt and Congress will retaliate by

refusing to renew the user fees. This would cripple FDA operations--and

jeopardize

jobs.

 

The companies* money now covers about 50% of the FDA*s costs for reviewing

proposed drugs--and agency officials say that persuading Congress to renew

the user fees into 2007 is now a top priority.

 

Yet even if the user fees remain, the FDA is prohibited from spending the

revenue for anything other than reviewing new drugs. So while the budget

for pre-approval reviews has soared, the agency has gotten no similar

increase of resources to evaluate the safety of the drugs after they are

prescribed.

 

**It*s shocking,** said Dr. Brian L. Strom, chairman of epidemiology at

the University of Pennsylvania. **How can you say, *Release drugs to the

market sooner,* and not know if they*re killing people? . . . It really is a

dramatic statement of public priorities.**

 

More than 250,000 side effects linked to prescription drugs, including

injuries and deaths, are reported each year. And those **adverse-event**

reports by doctors and others are only filed voluntarily. Experts, including

Strom, believe the reports represent as few as 1% to 10% of all such events.

**There's no incentive at all for a physician to report [an adverse drug

reaction],** said Strom, who has documented the phenomenon. **The

underreporting is vast.**

 

Even when deaths are reported, records and interviews show that companies

consistently dispute that their product has caused a given death by

pointing to other factors, including preexisting disease or use of another

medicine.

 

To be sure, a chain of events affects the safe use of a prescription drug:

The companies* conduct of clinical studies; the FDA*s regulatory actions;

the doctor*s decision to prescribe; the pharmacist*s filling of a

handwritten prescription; the patient*s ability to take the drug as directed. A

lapse at any link could prove fatal.

 

And once a pill is approved by the FDA, the manufacturer often spends

heavily on promotion to seize the largest possible market share. This can

exacerbate the risk to public health, according to experts.

 

**Aggressive promotion increases exposure--and doesn*t give you the time

to find the problem before patients get hurt,** said Dr. Raymond L.

Woosley, pharmacology department chairman at Georgetown University and a former

FDA advisory committee member.

 

When serious side effects emerge, the FDA officials have championed using

package labeling as a way to, in their words, **manage** risks. Yet the

agency typically has no way to know if the labeling precautions--dense,

lengthy and in tiny print--are read or followed by doctors and their patients.

 

The FDA often addresses unresolved safety questions by asking companies to

conduct studies after the product is approved. But the research frequently

is not performed--prompting the inspector general of the Department of

Health and Human Services to say in 1996 that **FDA can move to withdraw drugs

from the market if the post-marketing studies are not completed with due

diligence.**

 

Since that report was issued, the FDA has not withdrawn any drug due to a

company*s failure to complete a post-approval safety study. Officials

conceded this week that they still do not know how often the studies are

performed.

 

One consequence is that greater risk is shifted to doctors and patients.

 

For example, Woodcock and her senior aides allowed Rezulin to remain on

the U.S. market nearly 2 years after it was withdrawn in Britain in December

1997. The FDA recommended frequent laboratory testing of patients using the

drug but had no scientific assurance that the tests would prevent

Rezulin-induced liver failure.

 

**They kept increasing the number of liver-function tests you should

have,** noted Dr. Alastair J.J. Wood, a former FDA advisory committee member

who

is a professor of medicine at Vanderbilt University. **That was clearly

designed to protect the FDA, to protect the manufacturer, and to dump the

responsibility on the patient and the physician. If the patient developed

liver disease and he hadn*t had his [tests] done, somebody was to blame and it

wasn*t the manufacturer and it wasn*t the FDA.**

 

Industry Assurances

 

Leading industry officials say Americans have nothing to fear from the

wave of drug approvals.

 

**Do unsafe drugs enter and remain in the marketplace? Absolutely not,**

said Dr. Bert A. Spilker, senior vice president for scientific and

regulatory affairs for the Pharmaceutical Research and Manufacturers of

America, in

remarks last year to industry and FDA scientists.

 

But during interviews over the last two years, current and former FDA

specialists cited repeated instances when drugs were approved with less than

compelling evidence of safety or effectiveness. They also said that important

information has been excluded from the labels on some medications.

 

Elashoff, for instance, was surprised at the labeling for a drug called

Prograf, approved in 1997 to prevent rejection of transplanted kidneys. The

drug first had been approved in 1994 for use among liver-transplant

patients.

 

The new label notes that Prograf was proved effective in a study of 412

U.S. kidney transplant patients. But no mention is made of the company*s

448-patient European study, in which 7% of the patients who took Prograf

died--double the 3.5% death rate among those who received a different

anti-rejection drug, documents show.

 

 

An auditor from the FDA*s scientific investigations unit, Antoine El-Hage,

examined the European study results and concluded the **data are

reliable.** Elashoff agreed in his review. Yet the only way for doctors or

patients

to find that data is to search the medical literature or seek the FDA's

review documents.

 

 

Excluding the European study from the Prograf label, Elashoff said, **was

just a total whitewash. . . . I think any rational person would reconsider

taking this drug if they knew what happened in Europe.**

 

 

A spokesman for the manufacturer of Prograf said the company had no

objection to including the European study results in the labeling. William E.

Fitzsimmons, a vice president of drug development for Fujisawa Healthcare

Inc., said the decision to exclude the results was entirely the FDA*s.

 

 

**We submitted that data,** he said. **It came down to what the FDA was

comfortable putting in the label. We certainly have no interest in trying to

hide that information. We presented it at major meetings on

transplantation. . . . We*re comfortable with that information being out in the

public

domain.**

 

 

But if the FDA had included the European results in the label, it would

have impugned the agency*s basis for approving the new, expanded use for

Prograf, according to Elashoff and others.

 

 

Asked why the agency excluded the information, Woodcock said the European

results were **unreliable and could be potentially misleading to doctors

and patients in the U.S. if these were included in the label.**

 

Contributors to this Report

Design director: Joe Hutchinson

Photographer: Brian Walski

Photo editor: Steve Stroud

Graphics: Rebecca Perry

Graphics editor: Chris Erskine

Researchers: Janet Lundblad, Sunny Kaplan

Editors: Roger Smith, Nan Williams, Steve Devol, Bobbi Olson, Kathie

Bozanich

Web site Editors: Sarah D. Wright, Clare Sup

 

 

Copyright 2000 Los Angeles Times

 

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