Time for a Drug Test Registry - Marcia Angell

[Guest guest]

> Sat, 14 Aug 2004 03:04:17 -0000

> Time for a Drug Test

> Registry/Marcia Angell/Why NIH is Not Up to the Task

>

> ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)

> Promoting openness and full disclosure

> http://www.ahrp.org

>

> FYI

>

> The uncovering of concealed, unpublished evidence

> showing that

> children suffered harm in antidepressant drug

> trials, has led to a

> rude public awakening. Selective reporting of

> clinical trial data has

> become " standard practice " and the scientific

> literature has been

> corrupted by biased medical reports.

>

> Caught in the cross-fire, the American Medical

> Association and the

> International Committee of Medical Journal Editors

> recommended

> establishing a clinical trial registry. Slapped with

> a lawsuit by NYS

> Attorney General, GlaxoSmithKline put some of its

> Paxil pediatric

> trial data on its website. Eli Lilly and other drug

> companies stated

> their intention to do even better. But voluntary

> disclosure is no

> longer an option.

>

> Dr. Marcia Angell, former editor of The New England

> Journal, doesn't

> just call for a clinical trial registry, she

> enumerates essential

> conditions for a meaningful clinical trial registry

> in a Washington

> Post Op Ed:

>

> 1. The registry should contain all trials, not just

> those that the

> companies want to include, and it should be

> administered by a

> publicly accountable agency, such as the National

> Institutes of

> Health.

>

> 2. Clinical trials should be registered at

> inception, not after they

> are completed.

>

> 3. The registry should identify the main researchers

> and disclose any

> financial ties they have to the companies whose

> drugs they are

> studying.

>

> The Alliance for Human Research Protection has but

> one disagreement

> with Dr. Angell's recommendations-entrusting

> oversight responsibility

> to the National Institutes of Health (NIH). We

> believe that in light

> of NIH's unseemly track record involving system wide

> conflicts of

> interest, NIH cannot possibly serve as a credible

> public agency to

> guard against industry's influence on overseeing

> clinical trial data.

>

> In addition to its failure to enforce federal

> conflicts of interest

> rules, NIH has failed to follow and enforce existing

> ethical

> standards in clinical trials conducted at NIH or

> funded by NIH--in

> accordance with 45 CFR 46.

>

> In the wake of an unending stream of revelations

> about hidden,

> ongoing conflicts of interest by top NIH scientists

> and directors,

> NIH's standing and credibility have been badly

> compromised. These

> conflicts first came to light in an investigative

> report by David

> Willman of The Los Angeles Times [1], then confirmed

> by an 8-month

> investigation by the House subcommittee on Oversight

> and

> Investigations. [2, 3, 4, 5]

>

> A recent report by the Office of Government Ethics

> (OGE) is yet

> another stinging indictment of the agency's

> " permissive attitude

> toward outside activities [which] played a major

> role " in encouraging

> industry's penetration and influence on NIH

> research. The OGE deemed

> Dr. Zerhouni's proposals for dealing with conflicts

> of interest

> ineffectual, calling his proposal to expand

> financial disclosure " not

> a substitute for appropriate substantive standards

> of ethical

> conduct. " [6]

>

> Instead, Marilyn Glynn, director of the OGE called

> for firm, across-

> the-board restrictions, necessary to restore public

> confidence in the

> nation's preeminent medical-research agency. [7, 8]

> The OGE report

> made 10 recommendations to rout out conflicts of

> interest both within

> the agency (restricting intramural scientists) and

> scientists funded

> by NIH who work off campus (extramural).

>

> In a show of fraternal solidarity, the Federation of

> American

> Societies for Experimental Biology (FASEB) sided

> with Dr. Zerhouni,

> objecting to the restrictions on intramural

> scientists, calling

> them " punitive. " [9] But this argues for selective

> legitimizing of

> impropriety.

>

> Glynn pointed out the fallacy of the NIH / FASEB

> partial approach to

> ethics, noting especially the safety of human

> subjects:

>

> " probably the most compelling argument that can be

> made for any

> absolute prohibition on consulting with drug

> companies is that some

> NIH officials actually are involved in making

> clinical decisions

> affecting the health and safety of patients and

> other intramural

> research subjects, and those subjects need to be

> confident that

> decisions about their care are free from any

> potential influence from

> extraneous business connections. "

>

> AHRP believes that there is a clear need for an

> independent agency to

> administer and oversee a public registry-and that

> agency should be

> accountable to Congress.

>

> AHRP agrees with Dr. Angell's call " to break the

> industry's hold over

> the testing of its own products so that we will know

> whether new

> drugs are as effective as their makers claim. Talk

> of " miracles "

> and " innovation " is no substitute for evidence. "

>

> However, given the record of egregious violations

> and abuse, there is

> a pressing need for sanctions to be imposed on

> researchers and

> institutions that fail to comply with the registry's

> requirements.

>

> Only when such a clinical trial registry is

> established will evidence-

> based medical practice become a reality.

>

>

> References:

>

> 1. Willman, D. " Stealth merger: Drug companies and

> government medical

> research, " Los Angeles Times, December 7, 2003. p.

> A-1.

> http://www.latimes.com/news/nationworld/

> nation/la-na-

> nih7dec07 .story

>

http://www.latimes.com/news/nationworld/nation/la-na-

> nih6aug06,1,2647063.sto

> ry?coll=la-headlines-nation

>

> 2. Willman,D. Lawmakers Assail NIH Conflict Rules.

> Los Angeles Times,

> May 13, 2004:

>

http://www.latimes.com/news/nationworld/nation/la-na-

> nih13may13,1,3459920.st

> ory?coll=la-headlines-nation

>

> 3. AHRP Infomail. Lawmakers Accused Leaders of the

> NIH of

> Encouraging " the option of corruption. " May 18,

> 2004:

> http://www.ahrp.org/infomail/04/05/18.html

>

> 4. Wysocki, B. National Institutes of Health Is

> Under Fire; Longtime

> Favorite of Congress Grapples With Slim Funding

> Increases, Conflicts

> Inquiry. Wall Street Journal Jun 22, 2004 p. A.4

>

> 5. Weiss, R. NIH Scientists Broke Rules, Panel Says

> Deals With

> Companies Went Unreported, Probe of Potential

> Conflicts of Interest

> Finds. Washington Post, June 23, 2004; Page A19

>

> 6. Report of the NIH Blue Ribbon Panel on Conflicts

> of Interest: A

> Working Group of the Advisory Committee to the

> Director NIH, Jun 22,

> 2004:

> http://www.nih.gov/about/ethics_COI_panelreport.pdf

>

> 7. Weiss, R. NIH to Set Stiff Restrictions on

> Outside Consulting,

> Washington Post, August 4, 2004, Page A-1

>

http://www.washingtonpost.com/ac2/wp-dyn/A37841-2004Aug3?

> language=printer

>

> 8. Willman, D. NIH Is Pressured to Bar Drug Industry

> Stipends. Los

> Angeles Times, August 6, 2004, Page A-1:

>

http://www.washingtonpost.com/ac2/wp-dyn/A37841-2004Aug3?

> language=printer

>

> 9. Agres, T. NIH ethics report draws critics. The

> Scientist. August

> 12, 2004. online at:

> http://www.biomedcentral.com/news/20040812/02

>

>

> Contact: Vera Hassner Sharav

> Tel: 212-595-8974

> e-mail: veracare

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

>

>

>

http://www.washingtonpost.com/wp-dyn/articles/A61488-2004Aug12.html

> THE WASHINGTON POST

> Time for a Drug Test Registry

> By Marcia Angell

>

> Reports that the drug giant GlaxoSmithKline

> buried evidence that

> its top-selling antidepressant, Paxil, is not

> effective in children

> have stimulated calls for a public registry of

> company-sponsored

> research. It's about time. You might imagine that

> this was an

> isolated case of corporate misbehavior, but in fact

> suppressing

> unfavorable research results is fairly standard

> practice in the

> pharmaceutical industry.

>

> Before drug companies are allowed to bring a new

> drug to market,

> they are required by the Food and Drug

> Administration to conduct

> clinical trials to show that the drug is safe and

> effective. They

> are supposed to provide the agency with the results

> of all the

> trials, not just some. But they don't have to

> publish or otherwise

> make the results available, and neither does the

> FDA. Moreover, the

> FDA may approve a drug on the basis of a few trials

> that make it look

> good, even though other trials may indicate it is

> not effective. The

> companies selectively publicize the most positive

> results, and

> legions of sales representatives then visit doctors

> to tout the

> positive findings.

>

> Just as troubling as the outright suppression of

> unfavorable

> research is the bias in the research that is

> published. Clinical

> trials can be set up to make drugs look good, and

> that, too, has

> become common. Companies can, for example, enroll

> only young people

> as human subjects, even if the drug is likely to be

> used by older

> patients -- thereby lessening the chance that side

> effects will show

> up. Or they can compare a new drug with an older

> drug administered at

> too low a dose, which means the new drug is bound to

> look better.

>

> Sometimes they sift through the results of a trial

> and select just

> the positive findings for publication -- a practice

> known as " data

> dredging. " For instance, a trial of the effect of a

> drug on heart

> attacks may be converted to a trial of the drug's

> effect on blood

> pressure, if it begins to look as if the drug isn't

> much good for

> heart attacks. Or a one-year trial may be converted

> to a six-month

> trial if the drug looks good only in the first half

> of the study.

>

> Researchers, even in our best universities, often

> go along with this

> sort of thing, because sponsors insist on it. A

> public registry of

> clinical trials would help eliminate many of these

> abuses, but only

> if it met the following three conditions:

>

> First, it should contain all trials, not just those

> that the

> companies want to include, and it should be

> administered by a

> publicly accountable agency, such as the National

> Institutes of

> Health. Registration should be a condition of

> enrolling human

> subjects in research, since volunteers expect their

> participation to

> contribute to scientific knowledge and the public

> has a right to

> accountability. The argument that listing trials

> might reveal

> important proprietary secrets is not persuasive,

> because by the time

> drugs enter clinical trials, they are already

> patented and largely

> developed.

>

> Second, it is crucial that trials be registered at

> inception, not

> after they are completed. The initial information

> should include a

> brief description of the design of the trial,

> including the kinds of

> patients to be enrolled, the drugs and doses to be

> tested, what the

> new drug will be compared with, the duration of the

> trial, the

> endpoints that will be measured, and the methods of

> measurement. That

> way any bias in the design of the study would be

> immediately

> apparent, and sponsors could not shift the endpoints

> as the trial

> progressed. At completion, the salient results

> should be reported.

> Not all trials are worth publishing in medical

> journals, but

> companies will still want their best studies to gain

> the added

> prestige and attention afforded by publication in a

> good peer-

> reviewed journal. That is fair only if information

> about all of the

> trials is available in the registry.

>

> Third, the registry should identify the main

> researchers and

> disclose any financial ties they have to the

> companies whose drugs

> they are studying. Since drug companies don't have

> direct access to

> patients, they depend on academic researchers and

> private doctors to

> supply human subjects and collect the data.

> Identifying them in the

> registry would hold them responsible for the quality

> of the research

> they perform.

>

> The evidence of bias in medical reports is

> undeniable. It's time to

> break the industry's hold over the testing of its

> own products so

> that we will know whether new drugs are as effective

> as their makers

> claim. Talk of " miracles " and " innovation " is no

> substitute for

> evidence. The establishment of a government registry

> of clinical

> trials is a good way to begin, but it must be done

> right.

>

> The writer is a former editor in chief of the New

> England Journal of

> Medicine and author of the forthcoming book, " The

> Truth About the

> Drug Companies. "

>

>

> C 2004 The Washington Post Company

>

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