Re: Rofecoxib withdrawal sparks criticism of FDA and overaggressivemarketing of coxibs

October 4, 2004

This is a very good article, a, and I hope all members take the time

to read it.

The approval process is flawed, and it's hard to take a drug off the

market once it's out there.

The pharmaceutical companies should be distanced from the FDA. How can

the FDA be impartial if it receives funding from the drug manufacturers?

Why is so much data from trials suppressed?

Even if patients are foolish enough to believe that slick advertising,

why do doctors fall for it, too? Or why do they cave in so easily to

patient pressure? I know of so many people (outside of this group) who

have been inappropriately prescribed one of the COX-2s. In the end, we

all pay for that, one way or another.

I know I must sound like a broken record, but the FDA and their adverse

drug reaction reporting system needs to be revamped pronto!

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org

[ ] Rofecoxib withdrawal sparks criticism of FDA and

overaggressivemarketing of coxibs

>

> Rofecoxib withdrawal sparks criticism of FDA and overaggressive

marketing of

> coxibs

>

> Oct 4, 2004 Zosia Chustecka

>

> The withdrawal of rofecoxib (Vioxx, Merck & Co) has sparked questions

about

> the way that the FDA handled the issue as well as the way this group

of

> drugs was marketed.

>

> Some of the sharpest criticism comes from cardiologist Dr Topol

> (Cleveland Clinic, OH), who was one of the first to raise concerns

over the

> cardiovascular risk with rofecoxib. " Good riddance to a bad drug, " he

snipes

> in an editorial in the New York Times [1]. " After 3 years of denying

that

> the arthritis drug Vioxx could induce heart attacks and strokes, this

week

> Merck bowed to reality. "

>

> Our 2 most common deadly diseases should not be caused by a drug.

>

> Topol hits out at both the company and the FDA, accusing both of

passivity

> in the face of mounting evidence. " Despite studies showing the

magnitude of

> the public-health problem, for several years Merck did nothing to

> investigate, " he charges, pointing out that at the same time the

company was

> spending vast amounts on direct-to-consumer advertising for the

product.

> " The FDA could have forced Merck to do the appropriate research

studies, but

> instead it was a bystander, " he adds.

>

> " As the Vioxx debacle shows, we have a long way to go in this country

to get

> on track with prescription medications, " Topol thunders in the

editorial.

> " Most important, we need a strong regulatory agency to compel

pharmaceutical

> companies to do the proper studies and force these companies to stop

> direct-to-consumer advertising unless a drug has major benefits for

patients

> and negligible increased risk of heart attacks and strokes. Our 2 most

> common deadly diseases should not be caused by a drug. "

> Could the FDA have acted sooner, done more?

>

> Others have also lashed out at the FDA, pointing out that there have

been a

> number of signals suggesting an increased cardiovascular risk with the

drug

> over the past few years. The Newark Star-Ledger found several critics

[2].

>

> " The FDA was being inappropriately passive, " says Dr Jerry Avron

(Harvard

> Medical School, Boston, MA), author of the recently published book

Powerful

> Medicines: The Benefits, Risks, and Costs Of Prescription Drugs. He

suggests

> that the US Congress should consider " a separate government agency

> responsible for looking at safety problems of drugs that have been

> approved. "

>

> " The FDA has had a pattern of not being able to act quickly when

products

> are already on the market, " says Dr Wayne Ray (Vanderbilt University,

> Nashville, TN). " Everyone thinks that the FDA is minding the store,

but in

> fact, they are not. " Ray led one of the studies that found an

increased

> cardiovascular risk, which was published in 2002.

>

> But the first inkling of risk came from the company-sponsored VIGOR

trial,

> published in 2000, shortly after the product was launched. These and

other

> data were considered by an FDA advisory meeting in 2001, and a warning

about

> cardiovascular risks was added to rofecoxib's label in 2002. In

Europe,

> warnings were added in 2003.

>

> Everyone thinks that the FDA is minding the store, but in fact,

they are

> not.

>

> Back in 2000, there were enough data to suggest that the FDA could

have

> ordered Merck to conduct an extensive clinical trial to look

specifically at

> safety issues, says Dr Alistair Wood (Vanderbilt University). He told

the

> Star-Ledger he was " confused " as to why there had only been a warning

and

> says there should be an investigation into the agency's handling of

this

> product. " We are dealing with powerful companies and powerful

interests, and

> we need to know what happened, " Wood says. " The public deserves to

have an

> open and proper discussion and an inquiry that involves people other

than

> the interested parties. "

>

> The FDA argues thatuntil last weekthe data were inconclusive. " No drug

is

> fully safe, " says FDA spokesperson Crystal Rice. " Our job is to

> appropriately balance our decisions based on the risk/benefit profile

for a

> drug and the societal need and desire for new drugs and a range of

options

> to treat diseases. "

>

> Even one of the cardiologists who highlighted the CV concerns, Dr

> Nissen (Cleveland Clinic), comes to the agency's defense. " The FDA did

the

> best it could. I would be cautious laying the blame at the feet of the

FDA, "

> he tells the Star-Ledger. " We have a system of adverse-event

surveillance

> that is weak. I don't know if the FDA can force companies to do

clinical

> trials. There is a limited amount that the FDA can do under current

law. "

>

> Rice reiterates this point. " The agency can only asknot ordercompanies

to do

> further studies on drugs already approved, " she says in an Associated

Press

> article that was syndicated to several newspapers, including the

Houston

> Chronicle [3]. But this article also quotes Wood as saying that " a

very

> quick, very cheap study would have determined the risk had the FDA

taken a

> tougher stance at the first sign of trouble. "

>

> In an interview with Business Week, Nissen recalls how he was asked to

> evaluate rofecoxib when it came up for approval 5 years ago [4].

Although he

> was concerned then about cardiovascular risks, he says there was no

reason

> for the FDA to reject it at that time. " This was an unusual and subtle

> enough signal that it would have been premature to act on it when we

first

> noticed it. Even in August 2001, when we published our first report on

the

> risks, it was highly speculative. We didn't have hard data. We had

some soft

> data and suspicions about the mechanism of action. We could have just

as

> easily been wrong. "

>

> Even now, he says, " we don't know exactly why " rofecoxib poses a

> cardiovascular risk. One theory is that it affects the balance between

> thromboxane and prostacyclin. Aspirin reduces the levels of

thromboxane

> without affecting prostacyclin, while rofecoxib may be raising the

levels of

> thromboxane and not affecting prostacyclin, he explains. " Celecoxib

> [Celebrex, Pfizer] may work slightly differently. We haven't seen the

heart

> risks with Celebrex, and it has been on the market for about as long

as

> Vioxx. " He doesn't think that celecoxib will now receive a lot of

additional

> scrutinybut any new selective COX-2 inhibitor should.

>

> " We also need a more robust postapproval surveillance system to keep

track

> of adverse events with new drugs, " Nissen says. " Studies have found

that

> only 1% to 10% of serious adverse events with drugs on the market are

> actually reported. So the FDA is making decisions on inadequate data

now. "

> Overaggressive marketing and misleading adverts

>

> Sharp criticism has also been leveled at the way in which rofecoxib

and

> other similar drugs have been marketed. Direct-to-consumer advertising

> included sophisticated mass-media campaigns and television

advertisements,

> often featuring celebrity endorsements.

>

> Some patients came and asked for it after seeing Dorothy Hamill

skating

> on TV.

>

> " These agents have been the subject of absolutely intensive,

unrelenting

> marketing, " says Dr Wofsy (University of California, San

Francisco),

> current president of the American College of Rheumatology, in Time

[5].

> " Even if you don't have arthritis, you can probably hum the Celebrex

jingle

> or Vioxx's 'It's a beautiful morning,' " the magazine adds.

>

> " I believe they have been overaggressively marketed, " Dr

Greenwald,

> chief of rheumatology at Long Island Jewish Medical Center in New Hyde

Park,

> NY, tells Newsday [6]. Referring to a rofecoxib advertisement

featuring a

> former Olympic ice skater, he says: " Some patients came and asked for

it

> after seeing Dorothy Hamill skating on TV. " Referring to the

nonselective

> nonsteroidal anti-inflammatory drugs (NSAIDs), he adds: " I believe

that

> manynot allcould be treated with the old drugs. "

>

> Misleading advertisements are one of the problems, says a Los Angeles

Times

> editorial about the withdrawal [7]. Vioxx and its rival celecoxib have

been

> " touted as 'super aspirins' in numerous TV commercials that have

downplayed

> their known cardiovascular risks. Such commercials show how far the

FDA has

> slipped in enforcing its own rules. "

>

> The editorial also maintains that rofecoxib's increased risk of a

heart

> attack compared with older, equally effective, arthritis treatments

such as

> ibuprofen and naproxen has been known since 2000. " So why is Merck is

> recalling the drug now? One can only speculate, but it may have less

to do

> with side effects outweighing benefits than with legal liabilities

> outweighing profits. "

>

> One of the lawsuits that were filed the day after the withdrawal

involves a

> young woman who died of a heart attack after taking rofecoxib for 2

years,

> the Associated Press reports [8]. Filed by her mother through Missouri

> lawyer McClain, the lawsuit claims that Merck knew of the

risks long

> before its announcement last week. It also claims the doctor who

prescribed

> the drug failed to diagnose the severity of her daughter's heart

condition

> and prescribed rofecoxib despite her medical history.

>

> There is this newer-is-better mentality, and this is why we can't

afford

> healthcare.

>

> The Washing Post highlights the intense promotional efforts directed

at

> physicians, reporting that an IMS Health survey estimated that Merck

spent

> $500 million in 2003 promoting rofecoxib through advertisements in

medical

> journals, free samples, and salespeople's visits to doctors' offices

[9]. It

> also cites another IMS survey, which found that 52% of physicians were

> willing to write a prescription for a COX-2 inhibitor if patients

requested

> them and needed painkillers.

>

> " When a patient comes in and wants something, there is a desire to

serve

> them, " comments Wofsy. " There is a desire on the part of physicians,

as

> there is on anyone else who provides a service, to keep the customer

happy. "

>

> " One of the things that drove their overuse was the widespread

perception,

> even among doctors, that they were somehow better pain relievers, and

they

> never really were, " Avron tells the Washington Post. The newspaper

says the

> coxibs may have worked better in some patients, as individuals vary in

their

> individual response to painkiller, but it also suggests that the

novelty

> coxibs may have produced " something analogous to a placebo effect that

> enhanced their real effect. "

>

> The fact that they were new " alone holds great sway with American

consumers

> and physicians, " it asserts. " They were supposed to be safer, another

> natural appeal. Perhaps most important, they had the cachet of being

an

> expensive prescription medicine in a world of mundane over-the-counter

> generics. "

>

> One of the consequences of the " Vioxx debacle " is that American

society may

> wonder whether expensive new drugspart pharmaceutical, part fetish

objectare

> worth the money, the Washington Post comments. Avron says the answer

is

> generally no. The use of Vioxx by people who did not need the modest

amount

> of stomach protection it offered " has cost billions of dollars that

could

> have been better used for other purposes in our healthcare system, " he

says.

> " There is this newer-is-better mentality, and this is why we can't

afford

> healthcare. "

>

> Forum

>

> For further discussions of this topic, please go to Topic: Reactions

to

> rofecoxib withdrawal in the Forum.

>

> Sources

>

> 1. Topol EJ. Good riddance to a bad drug. New York Times, October

2,

> 2004; Available at:

> 2. http://www.nytimes.comCohen R and Silverman E. What's next for

drug

> regulation. Star-Ledger, October 3, 2004; Available at:

> 3.

>

http://www.nj.com/search/index.ssf?/base/business-0/1096777910132280.xml?sta

> rledger?bpha LA. Removal of Vioxx prompts questions about drug

tests.

> Houston Chronicle October 2, 2004; Available at:

> 4. http://www.chron.comO'Connell, P, ed. Early twinges over Vioxx.

> Business Week October 1, 2004; Available at:

> 5. http://www.businessweek.comGorman C. A painful mistake. Time

October

> 4, 2004; Available at:

> 6. http://www.time.comRabin R. Many choices beyond Vioxx. Newsday

> October 2, 2004; Available at:

> 7. http://www.newsday.comLos Angeles Times editorial. A Symptom of

FDA

> laxity. Los Angeles Times October 1, 2004; Available at:

> 8. http://www.latimes.comAssociated Press. Vioxx maker sued over

woman's

> death. New York Times October 3, 2004; Available at:

> 9. http://www.nytimes.comBrown D. Promise and peril of Vioxx cast

harsher

> light on new drugs. Washington Post October 3, 2004; Available at:

> http://washingtonpost.com

October 4, 2004

This is a very good article, a, and I hope all members take the time

to read it.

The approval process is flawed, and it's hard to take a drug off the

market once it's out there.

The pharmaceutical companies should be distanced from the FDA. How can

the FDA be impartial if it receives funding from the drug manufacturers?

Why is so much data from trials suppressed?

Even if patients are foolish enough to believe that slick advertising,

why do doctors fall for it, too? Or why do they cave in so easily to

patient pressure? I know of so many people (outside of this group) who

have been inappropriately prescribed one of the COX-2s. In the end, we

all pay for that, one way or another.

I know I must sound like a broken record, but the FDA and their adverse

drug reaction reporting system needs to be revamped pronto!

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org

[ ] Rofecoxib withdrawal sparks criticism of FDA and

overaggressivemarketing of coxibs

>

> Rofecoxib withdrawal sparks criticism of FDA and overaggressive

marketing of

> coxibs

>

> Oct 4, 2004 Zosia Chustecka

>

> The withdrawal of rofecoxib (Vioxx, Merck & Co) has sparked questions

about

> the way that the FDA handled the issue as well as the way this group

of

> drugs was marketed.

>

> Some of the sharpest criticism comes from cardiologist Dr Topol

> (Cleveland Clinic, OH), who was one of the first to raise concerns

over the

> cardiovascular risk with rofecoxib. " Good riddance to a bad drug, " he

snipes

> in an editorial in the New York Times [1]. " After 3 years of denying

that

> the arthritis drug Vioxx could induce heart attacks and strokes, this

week

> Merck bowed to reality. "

>

> Our 2 most common deadly diseases should not be caused by a drug.

>

> Topol hits out at both the company and the FDA, accusing both of

passivity

> in the face of mounting evidence. " Despite studies showing the

magnitude of

> the public-health problem, for several years Merck did nothing to

> investigate, " he charges, pointing out that at the same time the

company was

> spending vast amounts on direct-to-consumer advertising for the

product.

> " The FDA could have forced Merck to do the appropriate research

studies, but

> instead it was a bystander, " he adds.

>

> " As the Vioxx debacle shows, we have a long way to go in this country

to get

> on track with prescription medications, " Topol thunders in the

editorial.

> " Most important, we need a strong regulatory agency to compel

pharmaceutical

> companies to do the proper studies and force these companies to stop

> direct-to-consumer advertising unless a drug has major benefits for

patients

> and negligible increased risk of heart attacks and strokes. Our 2 most

> common deadly diseases should not be caused by a drug. "

> Could the FDA have acted sooner, done more?

>

> Others have also lashed out at the FDA, pointing out that there have

been a

> number of signals suggesting an increased cardiovascular risk with the

drug

> over the past few years. The Newark Star-Ledger found several critics

[2].

>

> " The FDA was being inappropriately passive, " says Dr Jerry Avron

(Harvard

> Medical School, Boston, MA), author of the recently published book

Powerful

> Medicines: The Benefits, Risks, and Costs Of Prescription Drugs. He

suggests

> that the US Congress should consider " a separate government agency

> responsible for looking at safety problems of drugs that have been

> approved. "

>

> " The FDA has had a pattern of not being able to act quickly when

products

> are already on the market, " says Dr Wayne Ray (Vanderbilt University,

> Nashville, TN). " Everyone thinks that the FDA is minding the store,

but in

> fact, they are not. " Ray led one of the studies that found an

increased

> cardiovascular risk, which was published in 2002.

>

> But the first inkling of risk came from the company-sponsored VIGOR

trial,

> published in 2000, shortly after the product was launched. These and

other

> data were considered by an FDA advisory meeting in 2001, and a warning

about

> cardiovascular risks was added to rofecoxib's label in 2002. In

Europe,

> warnings were added in 2003.

>

> Everyone thinks that the FDA is minding the store, but in fact,

they are

> not.

>

> Back in 2000, there were enough data to suggest that the FDA could

have

> ordered Merck to conduct an extensive clinical trial to look

specifically at

> safety issues, says Dr Alistair Wood (Vanderbilt University). He told

the

> Star-Ledger he was " confused " as to why there had only been a warning

and

> says there should be an investigation into the agency's handling of

this

> product. " We are dealing with powerful companies and powerful

interests, and

> we need to know what happened, " Wood says. " The public deserves to

have an

> open and proper discussion and an inquiry that involves people other

than

> the interested parties. "

>

> The FDA argues thatuntil last weekthe data were inconclusive. " No drug

is

> fully safe, " says FDA spokesperson Crystal Rice. " Our job is to

> appropriately balance our decisions based on the risk/benefit profile

for a

> drug and the societal need and desire for new drugs and a range of

options

> to treat diseases. "

>

> Even one of the cardiologists who highlighted the CV concerns, Dr

> Nissen (Cleveland Clinic), comes to the agency's defense. " The FDA did

the

> best it could. I would be cautious laying the blame at the feet of the

FDA, "

> he tells the Star-Ledger. " We have a system of adverse-event

surveillance

> that is weak. I don't know if the FDA can force companies to do

clinical

> trials. There is a limited amount that the FDA can do under current

law. "

>

> Rice reiterates this point. " The agency can only asknot ordercompanies

to do

> further studies on drugs already approved, " she says in an Associated

Press

> article that was syndicated to several newspapers, including the

Houston

> Chronicle [3]. But this article also quotes Wood as saying that " a

very

> quick, very cheap study would have determined the risk had the FDA

taken a

> tougher stance at the first sign of trouble. "

>

> In an interview with Business Week, Nissen recalls how he was asked to

> evaluate rofecoxib when it came up for approval 5 years ago [4].

Although he

> was concerned then about cardiovascular risks, he says there was no

reason

> for the FDA to reject it at that time. " This was an unusual and subtle

> enough signal that it would have been premature to act on it when we

first

> noticed it. Even in August 2001, when we published our first report on

the

> risks, it was highly speculative. We didn't have hard data. We had

some soft

> data and suspicions about the mechanism of action. We could have just

as

> easily been wrong. "

>

> Even now, he says, " we don't know exactly why " rofecoxib poses a

> cardiovascular risk. One theory is that it affects the balance between

> thromboxane and prostacyclin. Aspirin reduces the levels of

thromboxane

> without affecting prostacyclin, while rofecoxib may be raising the

levels of

> thromboxane and not affecting prostacyclin, he explains. " Celecoxib

> [Celebrex, Pfizer] may work slightly differently. We haven't seen the

heart

> risks with Celebrex, and it has been on the market for about as long

as

> Vioxx. " He doesn't think that celecoxib will now receive a lot of

additional

> scrutinybut any new selective COX-2 inhibitor should.

>

> " We also need a more robust postapproval surveillance system to keep

track

> of adverse events with new drugs, " Nissen says. " Studies have found

that

> only 1% to 10% of serious adverse events with drugs on the market are

> actually reported. So the FDA is making decisions on inadequate data

now. "

> Overaggressive marketing and misleading adverts

>

> Sharp criticism has also been leveled at the way in which rofecoxib

and

> other similar drugs have been marketed. Direct-to-consumer advertising

> included sophisticated mass-media campaigns and television

advertisements,

> often featuring celebrity endorsements.

>

> Some patients came and asked for it after seeing Dorothy Hamill

skating

> on TV.

>

> " These agents have been the subject of absolutely intensive,

unrelenting

> marketing, " says Dr Wofsy (University of California, San

Francisco),

> current president of the American College of Rheumatology, in Time

[5].

> " Even if you don't have arthritis, you can probably hum the Celebrex

jingle

> or Vioxx's 'It's a beautiful morning,' " the magazine adds.

>

> " I believe they have been overaggressively marketed, " Dr

Greenwald,

> chief of rheumatology at Long Island Jewish Medical Center in New Hyde

Park,

> NY, tells Newsday [6]. Referring to a rofecoxib advertisement

featuring a

> former Olympic ice skater, he says: " Some patients came and asked for

it

> after seeing Dorothy Hamill skating on TV. " Referring to the

nonselective

> nonsteroidal anti-inflammatory drugs (NSAIDs), he adds: " I believe

that

> manynot allcould be treated with the old drugs. "

>

> Misleading advertisements are one of the problems, says a Los Angeles

Times

> editorial about the withdrawal [7]. Vioxx and its rival celecoxib have

been

> " touted as 'super aspirins' in numerous TV commercials that have

downplayed

> their known cardiovascular risks. Such commercials show how far the

FDA has

> slipped in enforcing its own rules. "

>

> The editorial also maintains that rofecoxib's increased risk of a

heart

> attack compared with older, equally effective, arthritis treatments

such as

> ibuprofen and naproxen has been known since 2000. " So why is Merck is

> recalling the drug now? One can only speculate, but it may have less

to do

> with side effects outweighing benefits than with legal liabilities

> outweighing profits. "

>

> One of the lawsuits that were filed the day after the withdrawal

involves a

> young woman who died of a heart attack after taking rofecoxib for 2

years,

> the Associated Press reports [8]. Filed by her mother through Missouri

> lawyer McClain, the lawsuit claims that Merck knew of the

risks long

> before its announcement last week. It also claims the doctor who

prescribed

> the drug failed to diagnose the severity of her daughter's heart

condition

> and prescribed rofecoxib despite her medical history.

>

> There is this newer-is-better mentality, and this is why we can't

afford

> healthcare.

>

> The Washing Post highlights the intense promotional efforts directed

at

> physicians, reporting that an IMS Health survey estimated that Merck

spent

> $500 million in 2003 promoting rofecoxib through advertisements in

medical

> journals, free samples, and salespeople's visits to doctors' offices

[9]. It

> also cites another IMS survey, which found that 52% of physicians were

> willing to write a prescription for a COX-2 inhibitor if patients

requested

> them and needed painkillers.

>

> " When a patient comes in and wants something, there is a desire to

serve

> them, " comments Wofsy. " There is a desire on the part of physicians,

as

> there is on anyone else who provides a service, to keep the customer

happy. "

>

> " One of the things that drove their overuse was the widespread

perception,

> even among doctors, that they were somehow better pain relievers, and

they

> never really were, " Avron tells the Washington Post. The newspaper

says the

> coxibs may have worked better in some patients, as individuals vary in

their

> individual response to painkiller, but it also suggests that the

novelty

> coxibs may have produced " something analogous to a placebo effect that

> enhanced their real effect. "

>

> The fact that they were new " alone holds great sway with American

consumers

> and physicians, " it asserts. " They were supposed to be safer, another

> natural appeal. Perhaps most important, they had the cachet of being

an

> expensive prescription medicine in a world of mundane over-the-counter

> generics. "

>

> One of the consequences of the " Vioxx debacle " is that American

society may

> wonder whether expensive new drugspart pharmaceutical, part fetish

objectare

> worth the money, the Washington Post comments. Avron says the answer

is

> generally no. The use of Vioxx by people who did not need the modest

amount

> of stomach protection it offered " has cost billions of dollars that

could

> have been better used for other purposes in our healthcare system, " he

says.

> " There is this newer-is-better mentality, and this is why we can't

afford

> healthcare. "

>

> Forum

>

> For further discussions of this topic, please go to Topic: Reactions

to

> rofecoxib withdrawal in the Forum.

>

> Sources

>

> 1. Topol EJ. Good riddance to a bad drug. New York Times, October

2,

> 2004; Available at:

> 2. http://www.nytimes.comCohen R and Silverman E. What's next for

drug

> regulation. Star-Ledger, October 3, 2004; Available at:

> 3.

>

http://www.nj.com/search/index.ssf?/base/business-0/1096777910132280.xml?sta

> rledger?bpha LA. Removal of Vioxx prompts questions about drug

tests.

> Houston Chronicle October 2, 2004; Available at:

> 4. http://www.chron.comO'Connell, P, ed. Early twinges over Vioxx.

> Business Week October 1, 2004; Available at:

> 5. http://www.businessweek.comGorman C. A painful mistake. Time

October

> 4, 2004; Available at:

> 6. http://www.time.comRabin R. Many choices beyond Vioxx. Newsday

> October 2, 2004; Available at:

> 7. http://www.newsday.comLos Angeles Times editorial. A Symptom of

FDA

> laxity. Los Angeles Times October 1, 2004; Available at:

> 8. http://www.latimes.comAssociated Press. Vioxx maker sued over

woman's

> death. New York Times October 3, 2004; Available at:

> 9. http://www.nytimes.comBrown D. Promise and peril of Vioxx cast

harsher

> light on new drugs. Washington Post October 3, 2004; Available at:

> http://washingtonpost.com

October 5, 2004

Personally , I think direct drug marketing to the consumer should once

again be illegal. The billions spent on marketing drives the costs up as

well as creates a burden on doctors faced with patient demanding new drugs.

We're both broken records when it comes to this topic. Our doctors train at

medical schools funded by pharmaceuticals so it's not surprising that they

fall for their slick advertising. I've lost so much faith in the FDA's

ability to protect us from poorly run drug trials. Until they are required

to reveal ALL data from trials, we will continue to have people suffering

serious adverse side effects. How can we even make an educated decision to

take medications when we don't have all the data?

a

>

> This is a very good article, a, and I hope all members take the time

> to read it.

>

> The approval process is flawed, and it's hard to take a drug off the

> market once it's out there.

>

> The pharmaceutical companies should be distanced from the FDA. How can

> the FDA be impartial if it receives funding from the drug manufacturers?

> Why is so much data from trials suppressed?

>

> Even if patients are foolish enough to believe that slick advertising,

> why do doctors fall for it, too? Or why do they cave in so easily to

> patient pressure? I know of so many people (outside of this group) who

> have been inappropriately prescribed one of the COX-2s. In the end, we

> all pay for that, one way or another.

>

> I know I must sound like a broken record, but the FDA and their adverse

> drug reaction reporting system needs to be revamped pronto!

>

> I'll tell you where to go!

>

> Mayo Clinic in Rochester

> http://www.mayoclinic.org/rochester

>

> s Hopkins Medicine

> http://www.hopkinsmedicine.org

>

> [ ] Rofecoxib withdrawal sparks criticism of FDA and

> overaggressivemarketing of coxibs

>

>>

>> Rofecoxib withdrawal sparks criticism of FDA and overaggressive

> marketing of

>> coxibs

>>

>> Oct 4, 2004 Zosia Chustecka

>>

>> The withdrawal of rofecoxib (Vioxx, Merck & Co) has sparked questions

> about

>> the way that the FDA handled the issue as well as the way this group

> of

>> drugs was marketed.

>>

>> Some of the sharpest criticism comes from cardiologist Dr Topol

>> (Cleveland Clinic, OH), who was one of the first to raise concerns

> over the

>> cardiovascular risk with rofecoxib. " Good riddance to a bad drug, " he

> snipes

>> in an editorial in the New York Times [1]. " After 3 years of denying

> that

>> the arthritis drug Vioxx could induce heart attacks and strokes, this

> week

>> Merck bowed to reality. "

>>

>> Our 2 most common deadly diseases should not be caused by a drug.

>>

>> Topol hits out at both the company and the FDA, accusing both of

> passivity

>> in the face of mounting evidence. " Despite studies showing the

> magnitude of

>> the public-health problem, for several years Merck did nothing to

>> investigate, " he charges, pointing out that at the same time the

> company was

>> spending vast amounts on direct-to-consumer advertising for the

> product.

>> " The FDA could have forced Merck to do the appropriate research

> studies, but

>> instead it was a bystander, " he adds.

>>

>> " As the Vioxx debacle shows, we have a long way to go in this country

> to get

>> on track with prescription medications, " Topol thunders in the

> editorial.

>> " Most important, we need a strong regulatory agency to compel

> pharmaceutical

>> companies to do the proper studies and force these companies to stop

>> direct-to-consumer advertising unless a drug has major benefits for

> patients

>> and negligible increased risk of heart attacks and strokes. Our 2 most

>> common deadly diseases should not be caused by a drug. "

>> Could the FDA have acted sooner, done more?

>>

>> Others have also lashed out at the FDA, pointing out that there have

> been a

>> number of signals suggesting an increased cardiovascular risk with the

> drug

>> over the past few years. The Newark Star-Ledger found several critics

> [2].

>>

>> " The FDA was being inappropriately passive, " says Dr Jerry Avron

> (Harvard

>> Medical School, Boston, MA), author of the recently published book

> Powerful

>> Medicines: The Benefits, Risks, and Costs Of Prescription Drugs. He

> suggests

>> that the US Congress should consider " a separate government agency

>> responsible for looking at safety problems of drugs that have been

>> approved. "

>>

>> " The FDA has had a pattern of not being able to act quickly when

> products

>> are already on the market, " says Dr Wayne Ray (Vanderbilt University,

>> Nashville, TN). " Everyone thinks that the FDA is minding the store,

> but in

>> fact, they are not. " Ray led one of the studies that found an

> increased

>> cardiovascular risk, which was published in 2002.

>>

>> But the first inkling of risk came from the company-sponsored VIGOR

> trial,

>> published in 2000, shortly after the product was launched. These and

> other

>> data were considered by an FDA advisory meeting in 2001, and a warning

> about

>> cardiovascular risks was added to rofecoxib's label in 2002. In

> Europe,

>> warnings were added in 2003.

>>

>> Everyone thinks that the FDA is minding the store, but in fact,

> they are

>> not.

>>

>> Back in 2000, there were enough data to suggest that the FDA could

> have

>> ordered Merck to conduct an extensive clinical trial to look

> specifically at

>> safety issues, says Dr Alistair Wood (Vanderbilt University). He told

> the

>> Star-Ledger he was " confused " as to why there had only been a warning

> and

>> says there should be an investigation into the agency's handling of

> this

>> product. " We are dealing with powerful companies and powerful

> interests, and

>> we need to know what happened, " Wood says. " The public deserves to

> have an

>> open and proper discussion and an inquiry that involves people other

> than

>> the interested parties. "

>>

>> The FDA argues thatuntil last weekthe data were inconclusive. " No drug

> is

>> fully safe, " says FDA spokesperson Crystal Rice. " Our job is to

>> appropriately balance our decisions based on the risk/benefit profile

> for a

>> drug and the societal need and desire for new drugs and a range of

> options

>> to treat diseases. "

>>

>> Even one of the cardiologists who highlighted the CV concerns, Dr

>

>> Nissen (Cleveland Clinic), comes to the agency's defense. " The FDA did

> the

>> best it could. I would be cautious laying the blame at the feet of the

> FDA, "

>> he tells the Star-Ledger. " We have a system of adverse-event

> surveillance

>> that is weak. I don't know if the FDA can force companies to do

> clinical

>> trials. There is a limited amount that the FDA can do under current

> law. "

>>

>> Rice reiterates this point. " The agency can only asknot ordercompanies

> to do

>> further studies on drugs already approved, " she says in an Associated

> Press

>> article that was syndicated to several newspapers, including the

> Houston

>> Chronicle [3]. But this article also quotes Wood as saying that " a

> very

>> quick, very cheap study would have determined the risk had the FDA

> taken a

>> tougher stance at the first sign of trouble. "

>>

>> In an interview with Business Week, Nissen recalls how he was asked to

>> evaluate rofecoxib when it came up for approval 5 years ago [4].

> Although he

>> was concerned then about cardiovascular risks, he says there was no

> reason

>> for the FDA to reject it at that time. " This was an unusual and subtle

>> enough signal that it would have been premature to act on it when we

> first

>> noticed it. Even in August 2001, when we published our first report on

> the

>> risks, it was highly speculative. We didn't have hard data. We had

> some soft

>> data and suspicions about the mechanism of action. We could have just

> as

>> easily been wrong. "

>>

>> Even now, he says, " we don't know exactly why " rofecoxib poses a

>> cardiovascular risk. One theory is that it affects the balance between

>> thromboxane and prostacyclin. Aspirin reduces the levels of

> thromboxane

>> without affecting prostacyclin, while rofecoxib may be raising the

> levels of

>> thromboxane and not affecting prostacyclin, he explains. " Celecoxib

>> [Celebrex, Pfizer] may work slightly differently. We haven't seen the

> heart

>> risks with Celebrex, and it has been on the market for about as long

> as

>> Vioxx. " He doesn't think that celecoxib will now receive a lot of

> additional

>> scrutinybut any new selective COX-2 inhibitor should.

>>

>> " We also need a more robust postapproval surveillance system to keep

> track

>> of adverse events with new drugs, " Nissen says. " Studies have found

> that

>> only 1% to 10% of serious adverse events with drugs on the market are

>> actually reported. So the FDA is making decisions on inadequate data

> now. "

>> Overaggressive marketing and misleading adverts

>>

>> Sharp criticism has also been leveled at the way in which rofecoxib

> and

>> other similar drugs have been marketed. Direct-to-consumer advertising

>> included sophisticated mass-media campaigns and television

> advertisements,

>> often featuring celebrity endorsements.

>>

>> Some patients came and asked for it after seeing Dorothy Hamill

> skating

>> on TV.

>>

>> " These agents have been the subject of absolutely intensive,

> unrelenting

>> marketing, " says Dr Wofsy (University of California, San

> Francisco),

>> current president of the American College of Rheumatology, in Time

> [5].

>> " Even if you don't have arthritis, you can probably hum the Celebrex

> jingle

>> or Vioxx's 'It's a beautiful morning,' " the magazine adds.

>>

>> " I believe they have been overaggressively marketed, " Dr

> Greenwald,

>> chief of rheumatology at Long Island Jewish Medical Center in New Hyde

> Park,

>> NY, tells Newsday [6]. Referring to a rofecoxib advertisement

> featuring a

>> former Olympic ice skater, he says: " Some patients came and asked for

> it

>> after seeing Dorothy Hamill skating on TV. " Referring to the

> nonselective

>> nonsteroidal anti-inflammatory drugs (NSAIDs), he adds: " I believe

> that

>> manynot allcould be treated with the old drugs. "

>>

>> Misleading advertisements are one of the problems, says a Los Angeles

> Times

>> editorial about the withdrawal [7]. Vioxx and its rival celecoxib have

> been

>> " touted as 'super aspirins' in numerous TV commercials that have

> downplayed

>> their known cardiovascular risks. Such commercials show how far the

> FDA has

>> slipped in enforcing its own rules. "

>>

>> The editorial also maintains that rofecoxib's increased risk of a

> heart

>> attack compared with older, equally effective, arthritis treatments

> such as

>> ibuprofen and naproxen has been known since 2000. " So why is Merck is

>> recalling the drug now? One can only speculate, but it may have less

> to do

>> with side effects outweighing benefits than with legal liabilities

>> outweighing profits. "

>>

>> One of the lawsuits that were filed the day after the withdrawal

> involves a

>> young woman who died of a heart attack after taking rofecoxib for 2

> years,

>> the Associated Press reports [8]. Filed by her mother through Missouri

>> lawyer McClain, the lawsuit claims that Merck knew of the

> risks long

>> before its announcement last week. It also claims the doctor who

> prescribed

>> the drug failed to diagnose the severity of her daughter's heart

> condition

>> and prescribed rofecoxib despite her medical history.

>>

>> There is this newer-is-better mentality, and this is why we can't

> afford

>> healthcare.

>>

>> The Washing Post highlights the intense promotional efforts directed

> at

>> physicians, reporting that an IMS Health survey estimated that Merck

> spent

>> $500 million in 2003 promoting rofecoxib through advertisements in

> medical

>> journals, free samples, and salespeople's visits to doctors' offices

> [9]. It

>> also cites another IMS survey, which found that 52% of physicians were

>> willing to write a prescription for a COX-2 inhibitor if patients

> requested

>> them and needed painkillers.

>>

>> " When a patient comes in and wants something, there is a desire to

> serve

>> them, " comments Wofsy. " There is a desire on the part of physicians,

> as

>> there is on anyone else who provides a service, to keep the customer

> happy. "

>>

>> " One of the things that drove their overuse was the widespread

> perception,

>> even among doctors, that they were somehow better pain relievers, and

> they

>> never really were, " Avron tells the Washington Post. The newspaper

> says the

>> coxibs may have worked better in some patients, as individuals vary in

> their

>> individual response to painkiller, but it also suggests that the

> novelty

>> coxibs may have produced " something analogous to a placebo effect that

>> enhanced their real effect. "

>>

>> The fact that they were new " alone holds great sway with American

> consumers

>> and physicians, " it asserts. " They were supposed to be safer, another

>> natural appeal. Perhaps most important, they had the cachet of being

> an

>> expensive prescription medicine in a world of mundane over-the-counter

>> generics. "

>>

>> One of the consequences of the " Vioxx debacle " is that American

> society may

>> wonder whether expensive new drugspart pharmaceutical, part fetish

> objectare

>> worth the money, the Washington Post comments. Avron says the answer

> is

>> generally no. The use of Vioxx by people who did not need the modest

> amount

>> of stomach protection it offered " has cost billions of dollars that

> could

>> have been better used for other purposes in our healthcare system, " he

> says.

>> " There is this newer-is-better mentality, and this is why we can't

> afford

>> healthcare. "

>>

>> Forum

>>

>> For further discussions of this topic, please go to Topic: Reactions

> to

>> rofecoxib withdrawal in the Forum.

>>

>> Sources

>>

>> 1. Topol EJ. Good riddance to a bad drug. New York Times, October

> 2,

>> 2004; Available at:

>> 2. http://www.nytimes.comCohen R and Silverman E. What's next for

> drug

>> regulation. Star-Ledger, October 3, 2004; Available at:

>> 3.

>>

> http://www.nj.com/search/index.ssf?/base/business-0/1096777910132280.xml?sta

>> rledger?bpha LA. Removal of Vioxx prompts questions about drug

> tests.

>> Houston Chronicle October 2, 2004; Available at:

>> 4. http://www.chron.comO'Connell, P, ed. Early twinges over Vioxx.

>> Business Week October 1, 2004; Available at:

>> 5. http://www.businessweek.comGorman C. A painful mistake. Time

> October

>> 4, 2004; Available at:

>> 6. http://www.time.comRabin R. Many choices beyond Vioxx. Newsday

>> October 2, 2004; Available at:

>> 7. http://www.newsday.comLos Angeles Times editorial. A Symptom of

> FDA

>> laxity. Los Angeles Times October 1, 2004; Available at:

>> 8. http://www.latimes.comAssociated Press. Vioxx maker sued over

> woman's

>> death. New York Times October 3, 2004; Available at:

>> 9. http://www.nytimes.comBrown D. Promise and peril of Vioxx cast

> harsher

>> light on new drugs. Washington Post October 3, 2004; Available at:

>> http://washingtonpost.com

>

October 5, 2004