Concealed Drug Trial Results Mislead Doctors & Put Children's Lives at Risk-NYT

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> Fri, 23 Jul 2004 01:47:31 -0000

> [sSRI-Research] Concealed Drug Trial

> Results Mislead Doctors & Put Children's Lives at

> Risk-NYT

>

> ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)

> Promoting openness and full disclosure

> http://www.ahrp.org

>

> Contact: Vera Hassner Sharav

> Tel: 212-595-8974

> e-mail: veracare

>

> FYI

>

> The inordinate influence that drug companies wield

> on government

> healthcare regulatory policies--through campaign

> contributions to

> elected officials and lucrative job offers to public

> officials--has

> seriously compromised children's safety in numerous

> ways.

>

> An illuminating article in The New York Times

> describes how loopholes

> in drug legislation and public officials who have

> turned a blind eye

> and a deaf ear to drug safety issues, are putting

> children's health

> and safety at risk of serious harm.

>

> Public policymakers and oversight agency officials

> have become

> government protectors of the drug industry-even as

> they know about

> severe adverse drug effects that put children's

> health at risk--they

> put industry's financial interests first.

>

> The Times reports how drug companies are exploiting

> loopholes in the

> 1997 FDA Modernization Act (FDAMA) to conceal vital

> information about

> severe adverse drug effects in children. FDAMA was

> enacted to

> encourage the testing of drugs in

> children-presumably the tests were

> needed to provide safety and dosing information to

> physicians who

> prescribe the drugs for children off-label. But as

> we had predicted,

> the law's beneficiaries are not children.

> See:

> http://www.ahrp.org/infomail/0402/april192002.htm

>

> FDAMA offers drug companies six month patent

> extension to protect

> their freedom from competition if they test their

> drugs in children.

> Drug companies have been cashing in on the financial

> incentive at a

> brisk pace. But, when the test findings are

> negative-either

> demonstrating no benefit for children-such as

> antidepressants and

> drugs to treat headaches--or when drugs are linked

> to severe adverse

> effects-antidepressants, anti-fungal drugs, such as

> Diflucan--the

> companies conceal the findings, and conceal the fact

> that the drug

> was ever tested in children.

>

> The Times reports: " Reviewing test data provided by

> the maker,

> Pfizer, the F.D.A. concluded that Diflucan was not

> very effective for

> ringworm - and that a child could risk liver damage

> if given high

> doses of the drug. "

>

> That information never made it to the drug's label.

> When asked about

> the need to protect children's lives by disclosing

> adverse drug

> effects, FDA officials point to loopholes in the law

> and shrug their

> shoulders. The Times calls it " a quirk " that " labels

> are often

> allowed to remain silent about a test when the

> F.D.A. turns down a

> company's application for approval of a new use or a

> new patient

> group - as in the case of Diflucan and ringworm. " We

> call it

> deception.

>

> The priority of FDA's mission is: " protecting the

> public health by

> assuring the safety, efficacy, and security

> of...drugs...biological

> products, medical devices... " and " helping the

> public get accurate,

> science-based information they need to use medicines

> and foods to

> improve their health. " FDA officials who are more

> concerned about

> protecting corporate secrecy than protecting

> children's lives, they

> are perverting FDA's mission:

> See:

> http://www.fda.gov/opacom/morechoices/mission.html

>

> We believe that FDA officials who have turned their

> back safety

> issues that threaten the health of children, by

> helping drug

> manufacturers conceal vital health safety

> information, should be

> prosecuted as partners in crime against children.

>

> For those who may be interested in a critical

> analysis of the impact

> of FDAMA and its successor, the 2002 Best

> Pharmaceuticals for

> Children Act, on children's safety, see: ETHICAL

> HUMAN SCIENCES &

> SERVICES Summer 2003, vol. 5 pp. 83-108

>

http://www.ahrp.org/testimonypresentations/FDAmodernization03.html

>

>

> ~~~~~~~~~~~~~~~

>

http://www.nytimes.com/2004/07/21/business/21drug.html?

> ex=1091411575 & ei=1 & en

> =e4be748b760982ea

>

> July 21, 2004

> MEDICINE'S DATA GAP

> Results of Drug Trials Can Mystify Doctors Through

> Omission

> By BARRY MEIER

>

> A pediatrician who has read medical journals lately

> might have seen

> articles advocating the use of the antifungal drug

> Diflucan for the

> treatment of ringworm, a childhood skin infection.

> But reading the

> extensive medical information enclosed in the drug's

> package, the

> same doctor would not learn that federal drug

> regulators had rejected

> Diflucan for ringworm use. Reviewing test data

> provided by the maker,

> Pfizer, the F.D.A. concluded that Diflucan was not

> very effective for

> ringworm - and that a child could risk liver damage

> if given high

> doses of the drug.

>

> It is a quirk of the F.D.A.'s labeling rules. For a

> drug's government-

> approved uses, the label gives doctors important

> data from clinical

> tests involving those treatments while spelling out

> the drug's risks

> and providing directions for administering it to

> patients.

>

> But labels are often allowed to remain silent about

> a test when the

> F.D.A. turns down a company's application for

> approval of a new use

> or a new patient group - as in the case of Diflucan

> and ringworm.

>

> Pfizer and the F.D.A. both say that the Diflucan

> label conforms to

> the agency's rules and accurately reflects the

> drug's approved uses

> for adults and children, as well as its risks.

> The labeling issue is another facet of an expanding

> debate over the

> incomplete disclosure and publication of the results

> of clinical drug

> trials. And it is one of growing importance to a

> number of

> physicians.

>

> The doctors worry that ambiguous or incomplete drug

> labels may lead

> them to prescribe drugs for treatments that

> F.D.A.-reviewed tests

> have shown to be ineffective or potentially risky.

> Printed material

> accompanying many drugs says the drug's safety and

> effectiveness " has

> not been established'' in children - when some have

> been tested for

> pediatric use, with equivocal results.

>

> Until recently, several popular antidepressants

> carried the " has not

> been established'' language despite tests in

> children and adolescents

> that raised questions about their efficacy.

> Regulators and

> manufacturers have since issued safety warnings

> about those drugs

> amid concerns that, in a sharply limited number of

> cases, they may

> cause depressed youngsters to consider suicide.

> " If it has been tested, we want that to be

> reflected " on the label,

> said Dr. Richard Gorman, a pediatrician who is

> chairman of the

> committee on drugs of the American Academy of

> Pediatrics.

>

> In recent weeks, the academy and other medical

> groups have met with

> lawmakers to discuss possible legislation requiring

> companies to list

> tests of drugs and medical devices in a public

> database. And

> yesterday, Representative Henry A. Waxman, Democrat

> of California,

> sent a letter to Health and Human Services Secretary

> Tommy G.

> Thompson, urging him to release data from all

> pediatric drug trials

> that have been conducted under federal laws that

> encourage such tests.

>

> Dr. Shirley Murphy, director of the F.D.A.'s

> division of pediatric

> drug development, said that several members of an

> agency advisory

> committee that met in May had expressed concern that

> some drug labels

> omitted any reference to clinical drug trials that

> were negative or

> equivocal. The group included Dr. Gorman. " They

> noticed that some

> labels have lots of information and other labels

> didn't have

> information, " Dr. Murphy said.

>

> The issue of test disclosure on labels is not

> limited to pediatric

> trials. With few exceptions, federal law bars the

> F.D.A. from

> acknowledging that clinical tests were conducted, if

> the agency

> receives the test data as part of a drug maker's

> effort to have an

> existing product approved for a new use or category

> of patients and

> the F.D.A. turns down the request. Drug companies

> may publicly

> disclose such failures through a press release or a

> filing with the

> Securities and Exchange Commission, though such

> information would not

> necessarily find its way onto a label. And if a

> company chooses not

> to publicize a test failure, a doctor typically

> would not learn from

> a drug's label that such trials ever took place, a

> high-ranking

> F.D.A. official, Dr. Robert Temple, said.

>

> " If we don't agree " with the company, said Dr.

> Temple, the F.D.A.'s

> associate director for medical policy, " the doctor

> would not know

> about that. "

>

> Dr. Temple said there were exceptions, like a case

> when the trial of

> a drug shows a new or increased safety risk beyond

> those previously

> indicated on the label. Other exceptions include

> pediatric drug

> trials conducted under a federal law passed in 2002,

> the Best

> Pharmaceuticals for Children Act.

>

> As with an earlier law in 1997, the 2002 measure was

> passed to

> promote the testing of drugs in children because

> pharmaceutical

> companies had customarily not performed such trials.

> Instead, the

> practice was to seek approval for uses in adults,

> then leave it to

> pediatricians to prescribe the drugs on an off-label

> basis - as

> doctors are allowed to do, although drug makers

> cannot actively

> market drugs for such nonapproved uses.

>

> To encourage tests in children and adolescents, who

> may react

> differently than adults do to some drugs, the laws

> gave drug makers a

> powerful financial incentive - an additional six

> months of patent

> protection from generic competition when the

> medications were tested

> for pediatric use, even if the trials showed the

> drugs to be of

> dubious value.

>

> Dr. Gorman said he and others who helped draft the

> 1997 legislation

> quickly realized that they had failed to include a

> way to force a

> company to disclose all results from medications

> tested under the

> law. And so the 2002 law required that the F.D.A.

> release summary

> reports of such drug tests.

>

> Currently, reports on about 30 drugs received by the

> agency since mid-

> 2002 are on the Web at www.fda.gov/cder/pediatric.

> There, for

> example, a browser would find the summary report on

> Pfizer's

> pediatric tests of Diflucan. But Dr. Gorman says he

> now believes, as

> a result of the antidepressant controversy, that the

> 2002 bill was

> not explicit enough. " We didn't go the next step -

> about what would

> go on the label, " he said.

>

> All involved agree that the laws have increased the

> amount of

> labeling information about the use of many drugs in

> children, like

> the age groups where they are effective or how the

> drugs should be

> administered. And in some cases, new warning

> information reflects

> safety issues that arose in tests, like those on

> packaging of some

> cortisone-based treatments for skin infections.

> Of the 98 drugs that qualified for testing under the

> 1997 and 2002

> laws, the labels on 76 have been changed, F.D.A.

> officials said,

> while to date the labels on 22 drugs have not.

>

> The information gap between test findings and label

> information can

> occur even when F.D.A. officials are aware that

> doctors are

> increasingly using a medication off label for a

> particular problem.

>

> In the case of Diflucan, according to a test

> summary, it was the

> agency that asked Pfizer to run the ringworm trials.

> Regulators were

> concerned, according to that report, that

> pediatricians were turning

> to Diflucan because of dissatisfaction with an older

> medication and

> because published studies, some sponsored by Pfizer,

> reported that

> Diflucan was superior.

>

> After reviewing two Pfizer-run pediatric studies,

> the F.D.A.

> concluded earlier this year that Diflucan did not

> work any better

> than the older, generic drug, griseofluvin, which

> also poses toxicity

> risks. In the agency's report, regulators also

> raised concerns that

> children could face liver problems and other risks

> if doctors,

> seeking to treat ringworm more effectively, started

> using higher

> doses of Diflucan, which is known generically as

> fluconazole.

>

> " As some adverse events may be dose-dependent, " the

> F.D.A. document

> said, " it is expected that higher doses of

> fluconazole may approach

> dosages where the safety of pediatric patients may

> be at greater

> risk. " Dr. Murphy, at the F.D.A., said that the

> ringworm tests had

> not been noted on Diflucan's label because it did

> not win approval as

> a ringworm treatment.

>

> A Pfizer spokeswoman, Mariann Caprino, said the

> company was

> discussing the drug's labeling language with F.D.A.

> officials. She

> also said the tests did not raise any safety

> concerns beyond those

> already mentioned in the label. The F.D.A. also

> turned down an effort

> last year by another drug maker, Allergan, to get

> its antibacterial

> eye ointment, Ocuflox, approved for use in infants

> because trial data

> suggested the drug was not particularly effective in

> newborns. But

> the label continues to say that the drug's " safety

> and effectiveness

> in infants below the age of one has not been

> established. "

>

> There is little question that some drugs fail in

> pediatric trials

> because the tests are poorly run or not properly

> designed for

> children. F.D.A. reviewers raised the possibility of

> a design flaw in

> their report about Ocuflox.

>

> And while the F.D.A. review of pediatric test

> results for the popular

> migraine treatments Imitrex and Zomig found that the

> drugs worked no

> better than placebos in children, pediatric headache

> experts involved

> in those trials cited flaws in the test design. Dr.

> Gorman said it

> was important for all doctors, not just those who

> treat children, to

> know that trials with negative or equivocal outcomes

> have been

> conducted when considering the benefits and risks of

> a medication

> before prescribing it.

>

> Dr. Temple said that, speaking personally, he also

> believed that drug

> companies and medical device producers should

> voluntarily disclose

> test results - regardless of what F.D.A. rules may

> require.

> Otherwise, they face the risk of seeming to bury

> information.

> " If I was consulting companies, I would say 'Let it

> out,' " Dr.

> Temple said. " Now, it looks like something secret

> has been uncovered. "

>

> Copyright 2004 The New York Times Company

>

>