Drug safety Hearings-Sept-Congress/ FDA-Lilly Plans to Disclose Data

[Guest guest]

> JustSayNo

> Wed, 04 Aug 2004 03:05:19 -0000

> [sSRI-Research] Drug safety

> Hearings-Sept-Congress/ FDA-Lilly Plans to Disclose

> Data

>

>

> ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)

> Promoting openness and full disclosure

> http://www.ahrp.org <http://www.ahrp.org/>

>

> FYI

>

> A hearing about the possible connection between

> suicide and

> antidepressant drugs will be held on Aug 4, by the

> California Senate

> by Sen. Tom Torkalson, chairman of the Senate Task

> Force on Youth and

> Workplace Wellness and Sen. Deborah Ortiz, Chair of

> the Senate Health

> and Human Services Committee. A noon press

> conference will precede

> the hearing which is scheduled for 1:30 p.m. in Room

> 112, State

> Capitol. Federal hearings are scheduled for

> September.

>

> FDA's response to public criticism and Congressional

> investigations

> of the agency's failure to take action to protect

> children's lives is

> to convene advisory committee meetings. The meetings

> were announced

> even before committee members have been appointed to

> a newly formed

> Pediatric Advisory Committee and Pediatric Ethics

> Sub-Committee.

>

> Sept. 10: FDA Pediatric Ethics Committee (inaugural

> meeting) will

> consider whether the scientific merit of a proposed

> NIH study

> outweighs the risk of administering

> dextroamphetamine to healthy

> children. Dexamphetamine is an addictive drug of

> abuse: it is linked

> to cardiovascular and central nervous system adverse

> effects. See:

>

http://www.healthyplace.com/medications/dextroamphetamine.htm#adverse

>

>

>

> This proposed trial is the latest example of medical

> abuse. It is a

> barometer of the prevailing culture in psychiatry

> and at the National

> Institute of Mental Health. It is immoral to

> entertain conducting an

> experiment that exposes healthy, but helpless

> children to the hazards

> of amphetamines. Those who propose it, have no

> regard for children's

> rights and welfare. Such experiments are

> proliferating since the

> enactment of federal laws that encourage the testing

> of drugs in

> children. The FDA Modernization Act (1997) and Best

> Pharmaceuticals

> for Children Act (2002) provide lucrative 6 month

> patent extension

> rights to companies that test their drugs in

> children-whether the

> drugs are beneficial or harmful for children.

>

> Sept. 13-14: a follow-up to the Feb 2 meeting will

> review FDA

> Analysis Of Antidepressant Pediatric Suicidality

> Data. Of concern is

> the process by which the FDA is selecting a new

> panel of experts to

> replace the Feb 2 panel-a panel that had urged the

> FDA to issue

> immediate stronger warnings to

> the public.

>

> Eli Lilly is the latest drug company to announce

> plans to disclose

> trial data on the website. As the Wall Street

> Journal correctly

> observes, recent drug company " pledges " for " broader

> disclosure " of

> clinical trial data are meant " to quell the furor "

> about concealed

> evidence of drug-related harm. But public furor is

> unlikely to recede

> in the absence of enforced, mandatory, full and

> explicit disclosure.

>

> As long as the drug industry controls the trial data

> and voluntarily

> reports--or conceals--the post-marketing adverse

> event data, the

> reports are not trustworthy. If public officials,

> who have been

> entrusted with oversight authority over the drug

> industry, betray

> their public trust and serve that industry's

> interests, public furor

> is unlikely to be quelled. FDA's failure to disclose

> severe adverse

> drug effects to physicians and patients, its

> delaying tactics and

> continued suppression of the agency's own expert

> medical officer's

> report and recommendations are a demonstration of

> bad faith. The

> suppressed report is posted on the AHRP website as a

> public service

> at:

> http://www.ahrp.org/risks/SSRImosholder/index.html

>

> FDA's record leads to suspicions that FDA officials

> cannot be trusted

> to select objective experts for the new Pediatric

> Advisory Committee.

> What safeguards are there to prevent the FDA from

> appointing

> panelists with financial ties to drug manufacturers?

>

> Congressional committees have also fallen prey to

> drug industry

> influence. A July 20 hearing of the House Oversight

> and

> Investigations subcommittee-- " Publication and

> Disclosure Issues in

> Anti-Depressant Pediatric Clinical Trials " --was

> scuttled when Cong.

> James Greenwood, the committee chairman, accepted a

> job offer by a

> pharmaceutical /biotech trade association.

> The hearing has scheduled a hearing Sept. 9, at

> 11:00 AM.

>

> The original (July 20) hearing had all the makings

> of breaking the

> silence about undisclosed hazardous side-effects

> linked to

> antidepressant drugs. Seven representatives of the

> major

> pharmaceutical companies, and a representative of

> the drug trade

> organization, PhRMA, were scheduled to testify under

> oath about their

> concealment of safety and efficacy data. Also

> scheduled to testify on

> July 20, was Dr. Robert Temple, Associate Director

> for Medical

> Policy, Food and Drug Administration.

>

> * The FDA Hearing will be held at the Holiday Inn in

> Bethesda,

> Maryland. For those wishing to speak, call Anuja

> Patel to register:

> 301-827-6790. To submit a written report, call

> 800-741-8138 ex. 301-

> 451-2544 or go to www.fda.gov, scroll down the page

> about half way

> and click References, then go to Dockets.

>

> Contact: Vera Hassner Sharav

> Tel: 212-595-8974

> e-mail: veracare

>

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

> FDA Analysis Of Antidepressant Pediatric Suicidality

> Data To Be

> Reviewed Sept. 13-14

>

> FDA's analysis of independently reviewed pediatric

> suicidality data

> for antidepressants will be discussed Sept. 13 & 14

> during a joint

> meeting of the Psychopharmacologic Drugs Advisory

> Committee and the

> newly formed Pediatric Advisory Committee.

>

> The meeting is being held as a follow-up to a Feb. 2

> meeting where

> advisory committee members expressed concern about

> the high degree of

> variability and lack of categorization of events

> believed to be

> suicide related.

>

> FDA's preliminary review of over 4,000 pediatric

> patients from

> clinical trials of several antidepressants

> identified 109 cases

> as " possibly suicide related. "

>

> Since the Feb. 2 meeting, " experts in pediatric

> suicidality,

> assembled by Columbia University, have independently

> classified these

> reported events, and FDA has conducted an analysis

> of these data, " a

> Federal Register notice slated for publication Aug.

> 4 states.

>

> The Columbia group employed a standardized

> methodology to categorize

> events into " suicidal, " " non-suicidal, " and

> " indeterminate. " The

> suicidal category has three subdivisions: " suicide

> attempt, " " suicidal ideation, " and " suicidal

> behavior without injury. "

>

> " The committees will consider the results of FDA's

> analysis of these

> independently classified events and will consider

> what further

> regulatory action may be needed with regard to the

> clinical use of

> these products in pediatric patients, " the Federal

> Register notice

> reports.

>

> Also on the agenda for the two-day meeting is

> discussion of further

> research needed to address questions of pediatric

> suicidality with

> antidepressant use. FDA's conduct with regard to the

> pediatric data

> remains under investigation by the Senate Finance

> Committee. The

> investigation was recently expanded with an inquiry

> regarding the

> relationship between CDER's Office of New Drugs and

> Office of Drug

> Safety.

>

> In the wake of the investigation, eight out of 10 of

> the selective

> serotonin reuptake inhibitors have added class

> warnings on

> suicidality to labeling. Pfizer is negotiating

> language for Zoloft;

> Solvay's Luvox was withdrawn in 2002.

>

> The Sept. 13-14 meeting will be the first meeting of

> the full

> Pediatric Advisory Committee. The Pediatric Ethics

> Subcommittee will

> meet Sept. 10 to discuss a study protocol for

> dextroamphetamine; a

> full committee review will follow Sept. 15.

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

>

>

> Dextroamphetamine Study Including Healthy Children

> Will Be First Test

> For Pediatric Ethics Subcmte.

>

> FDA's Pediatric Ethics Subcommittee will consider

> whether the

> scientific merit of a proposed NIH study outweighs

> the risk of

> administration of dextroamphetamine to healthy

> children during its

> inaugural meeting on Sept. 10.

>

> The " Effects of a Single Dose of Dextroamphetamine

> in Attention

> Deficit Hyperactivity Disorder; A Functional

> Magnetic Resonance

> Study " protocol covers the administration of a

> single 10 mg dose of

> dextroamphetamine to both children with ADHD and

> healthy volunteer

> children. The study would be conducted by the

> National Institute of

> Mental Health.

>

> " The central question raised by this protocol is

> whether the

> administration of dextroamphetamine in healthy

> children is

> permissible under the federal regulations as a

> minimal risk

> procedure, " NIMH IRB Chair Donald Rosenstein, MD,

> explained in a

> March 5 letter to HHS.

> NIH's Institutional Review Board requested a special

> panel review by

> HHS after two split votes on the level of risk: on

> Oct. 28, 2003 four

> members voted there was minimal risk versus six

> votes for more than

> minimal risk; on Nov. 4, 2003 the committee was

> divided with five

> votes for minimal risk and seven votes for greater.

>

> " Although the official vote of the NIMH IRB was

> divided, " Rosenstein

> stated, " the final decision of the Board was that

> this is a study

> which offers no direct medical benefit to

> participants but has

> scientific merit. " IRB members were concerned about

> " possible risks

> to a healthy child from exposure to a psychoactive

> controlled

> substance (albeit a single dose), " he noted. Some

> members suggested

> that patients " might subsequently conclude that

> experimentation with

> stimulants or related substances of abuse (e.g.

> cocaine) was not a hazardous activity. "

>

> " In contrast, several Board members considered a

> single dose of

> dextroamphetamine to pose only minimal risks since

> the likely acute

> physiological and psychological effects of this

> medication were

> commensurate with risks ordinarily encountered in

> the daily lives of

> children, " Rosenstein added.

> Another concern was that the proposed compensation

> of up to $570 " may

> constitute an undue inducement for potential study

> subjects and/or

> their parents. "

>

> The newly-formed Pediatric Advisory Committee will

> consider the

> subcommittee's recommendation during its Sept. 15

> meeting, in

> addition to hearing adverse event reporting for

> Pulmicort/Rhinocort

> (budesonide), Clarinex (desloratadine),

> Flonase/Flovent/Cutivate

> (fluticasone), Ocuflox (ofloxacin), Fludara

> (fludarabine) and Fosamax

> (alendronate) as mandated in the Best

> Pharmaceuticals For Children

> Act.

>

> On Sept. 13 and 14 the committee will meet in a

> joint session with

> the Psychopharmacologic Drugs Advisory Committee to

> review the issue

> of pediatric suicidality associated with

> antidepressants.

>

>

>

http://online.wsj.com/article/0,,SB109147750665480746,00.html

>

> THE WALL STREET JOURNAL

> Lilly Plans Broad Access

> To Results of Drug Trials

> By LEILA ABBOUD

> August 3, 2004; Page B1

>

> Seeking to defuse criticism that pharmaceutical

> companies hush up

> negative results in clinical trials, U.S. drug maker

> Eli Lilly & Co.

> plans to disclose extensive data on almost all

> clinical trials, past

> and present, for the drugs it sells.

>

> Under the new policy, once a drug is on the market,

> Indianapolis-

> based Lilly will publish data from all early to

> late-stage clinical

> trials, including safety information and outcomes.

> Test results that

> did not support the hypothesis or that were contrary

> to the expected

> outcome also will be disclosed, the company says.

> Results of trials

> on unapproved uses of medicines -- known as

> off-label use -- also

> will be available.

>

> Lilly's plan, expected to be in place by the end of

> the year, goes

> beyond the more limited and less detailed policies

> announced by other

> drug companies. Lilly plans to offer access to data

> from all phases

> of its clinical trials while other drug companies

> haven't decided if

> they'll publish the same amount of information or

> just the later-

> phase trials. Lilly's policy could spur other drug

> makers to follow

> suit.

>

> Drug companies have long been criticized for

> selectively releasing

> data from clinical trials. Companies typically

> trumpeted studies that

> were favorable for a given drug and quietly shelved

> those that showed

> side effects, safety problems or raised questions

> about the drug's

> effectiveness.

>

> Alan Breier, Lilly's chief medical officer, says the

> company decided

> to publish such trial details because the " the

> public is demanding

> greater openness. " Dr. Breier also says that Lilly

> wanted to be

> certain that its medicines were being used properly.

> " Patient care is

> served best by open disclosure, " he says.

>

> GETTING RESULTS

> Outcomes from some clinical trials for

> antidepressant use in children

> have not been published to date.

>

> DRUG TOTAL # TRIALS UNPUBLISHED

> Prozac/Eli Lilly 6 2

> Paxil/GlaxoSmithKline 7 2

> Zoloft/Pfizer 5 1

> Celexa/Forest 3 3

> Effexor/Wyeth 2 2

> Source: The Lancet, April 2004

>

> Lilly's trials will be published on a company Web

> site open to the

> public.

>

> In June, the American Medical Association called for

> all drug

> companies' trials to be registered with the federal

> government (they

> aren't currently). While the AMA didn't offer a

> specific outline, it

> said a government-run system that tracks data from

> all clinical

> trials would help make the research more open to the

> public.

>

> The AMA also wants trials of experimental drugs to

> be disclosed --

> something the drug industry opposes because of

> concerns that

> competitors would learn their research and

> development secrets. Lilly

> won't publish results of trials on drugs that aren't

> yet approved,

> but it will list on its Web site when late-stage

> trials are to begin.

>

> Questions about the safety of antidepressants in

> children have

> brought the issue of medical disclosure to a head.

> Doctors and

> regulators were stymied by incomplete public data as

> they weighed

> whether children taking antidepressants were

> initially at greater

> risk of suicide. Doctors couldn't see the results of

> tests that drug

> companies had done with children, even as

> prescriptions for the young

> ballooned. In June, New York State Attorney General

> Eliot Spitzer

> sued GlaxoSmithKline PLC, alleging that the company

> concealed

> efficacy and safety in tests done with children and

> the company's

> blockbuster drug Paxil for treating depression. The

> lawsuit is

> continuing.

>

> To quell the furor, several drug makers have pledged

> broader

> disclosure. Glaxo released all its Paxil data on its

> Web site (the

> company says the move was not in connection with the

> lawsuit) and

> said it would disclose data from trials of all its

> marketed products.

> Glaxo is still hashing out what kind of information

> will be disclosed

> and declined to comment on its plan. Merck & Co. has

> indicated that

> it would support a government-run listing system,

> and pledged more

> openness -- but only about late-stage clinical

> trials or postapproval

> tests. Johnson & Johnson also said it supported the

> idea of a

> clinical trials registry.

>

> Federal law requires drug companies to list all

> studies done in

> serious or life-threatening illnesses on the public

> Web site

> ClinicalTrials.gov. The site does not provide any

> results of trials

> because it is geared to people looking to enlist in

> studies.

>

> Lilly says it will release historical information

> for all of the

> drugs it now sells going back 10 years. Dr. Breier

> says that such

> retrospective data on drugs already on the market

> immediately help

> doctors in prescribing medication for patients.

> Despite ongoing

> litigation, Lilly plans to release historical data

> on Zyprexa, the

> blockbuster antipsychotic that brings in a third of

> the company's

> revenues. Zyprexa was at the center of a debate last

> year over

> whether antipsychotic drugs cause weight gain and

> increase the risk

> of diabetes. Lawsuits involving Zyprexa are getting

> under way in

> federal and state courts. Lilly's Dr. Breier says

> the company isn't

> concerned that it's giving plaintiffs' lawyers an

> edge in the

> litigation because much of the data already has been

> published.

>

> In another new approach, Lilly says it will rely on

> a third-party

> auditor to monitor its adherence to the policies,

> something no other

> company has said it would do. Lilly also pledged to

> notify the public

> when it begins a trial that will later be included

> in the application

> submitted to the Food and Drug Administration for

> approval or when it

> will conduct a postmarketing study that explores

> using the drug for

> another disorder -- both moves aren't common

> practice in the industry.

>

> That move would make it easier for patients to

> locate clinical trials

> to join, and as act an " accountability check " to

> ensure that Lilly

> actually publicized all results when the trial

> ended. Some lawmakers

> and associations of medical journal editors and

> doctors have called

> for all companies to disclose such information.

> After a drug comes to

> market, companies aren't required to publish or give

> the FDA further

> test results on a drug's effectiveness for other

> conditions or if it

> was studied on special populations, such as

> children. Lilly will

> publish its clinical trial results for unapproved

> uses. Lilly's

> antidepressant Prozac was the only one that received

> FDA approval for

> use in children with depression. Dr. Breier says

> Lilly will release

> its tests of Prozac in kids on its Web site.

>

> Since doctors frequently prescribe drugs for

> unapproved uses, more

> information would help them in treating patients.

> For example,

> Lilly's antipsychotic drug, Zyprexa, is widely

> prescribed for hard-to-

> treat cases of depression and dementia in the

> elderly. Yet there

> haven't been any large-scale studies to determine

> whether Zyprexa

> works in those disorders. A clinical trial registry

> along the lines

> of Lilly's plan would let doctors know if the

> company had ever done

> tests of Zyprexa for unapproved uses -- and what the

> results were.

>

> Write to Leila Abboud at leila.abboud

>