Published Clinical Trials Contradict Claimed Benefits - Front Page Pill Pushers

[Guest guest]

SSRI-Research@

Sat, 26 Nov 2005 19:01:38 -0500

[sSRI-Research] Published Clinical Trials Contradict Claimed

Benefits - Front Page Pill Pushers

 

 

 

 

Published Clinical Trials Contradict Claimed Benefits - Front Page

Pill Pushers

 

Tue Aug 16, 2005

 

http://www.ahrp.org/infomail/05/08/16.php

 

Two items from the BMJ

 

A systemic review of 22 randomized clinical trials of Alzheimer's

disease treatments in the BMJ found the studies to have suffered from

flawed methodology and to have revealed that commonly prescribed

treatments had neglible clinical use. [1] The study adds evidence in

yet another area of medicine whose clinical practice is misguided by

fraudulent clinical trial reports.

 

A commentary by Stefan Kruszeuski, M.D. and Jeffrey Brown, MD, JD,

MPH, below, cites the dubious " off-label " use of gabapentin

(Neurontin), a drug approved for adjunctive use in partial seizure

disorders and post-herpetic neuralgia, which is widely prescribed for

a variety of chronic pain and psychiatric syndromes. Pfizer had

pleaded guilty to criminal marketing practices and fined $430 million.

But clearly fines don't have much of an impact on companies that make

billions through fraud and deception.

 

Those flawed trials--i.e., designed to mislead--were conducted and

reported in the literature by physicians. Those physicians are

collaborators of drug manufacturers. Therefore, they bear no less

responsibility for misrepresenting the drugs' benefits and concealing

the hazardous effects. Doctors who pitch drugs for manufacturers are

largely responsible for those unsupportable " off label " prescriptions

for drugs such as Neurontin, whose adverse effects--including the

highest drug-related suicide rate--more than outweigh the undocumented

benefits.

 

A commentary by Naomi Marks about an excellent appraisal of the

media's role in hyping drugs in the Columbia Journalism Review by

Trudi Lieberman (See: http://cjr.org/issues/2005/4/lieberman.asp or

http://www.ahrp.org/infomail/05/07/27.php ).

 

When will the science reporters show demonstrate healthy skepticism

and stop disseminating false and misleading information about drugs

and medicine provided by those with substantial financial stakes in

the products they praise?

 

The drug industry has secured powerful friends who help pitch

misleading information about drugs. The drug industry's influence is

boght and paid for: the media which has come to depend upon income

from drug advertisements colors much of the reporting about medicine.

And public officials whose campaigns this industry finances turn a

blind eye and deaf ear to the death toll from harmful drugs.

 

1. Hanna Kaduszkiewicz, Thomas Zimmermann, Hans-Peter Beck-Bornholdt,

and Hendrik van den Bussche

Cholinesterase inhibitors for patients with Alzheimer's disease:

systematic review of randomised clinical trials

BMJ 2005; 331: 321-327

 

Contact: Vera Hassner Sharav

212-595-8974

 

 

BMJ 16 August 2005 Rapid Responses published:

http://bmj.bmjjournals.com/cgi/eletters/331/7512/321 The Timing of

Published Non-Confirmatory Data Re-Analysis Deserves Attention Stefan

P Kruszewski , M.D., & Jeffrey A Brown, M.D., J.D., M.P.H., Clinical

Associate Professor of Psychiatry, University of Medicine and

Dentistry of New Jersey (16 August 2005)

 

BMJ published an important paper by Kaduszkiewicz, Zimmermann, Beck-

Bornholdt and van den Bussche in their 06 August edition. (1) The

paper, " Cholinesterase inhibitors for patients with Alzheimer's

disease: Systematic review of randomised clinical trials " , is a

meta-analysis of 22 trials. It demonstrated that flawed methodology

and negligible clinical benefits undermine previously asserted

recommendations for some of the commonly prescribed anticholinesterase

inhibitors for Alzheimer's disease.

 

Separately, an important 2002 study by Ann Hamer and her associates

published in the Journal of Managed Care Pharmacy (JMCP) revealed

similar findings of flawed methodology and limited clinical benefits.

The subject of that investigation was the " off-label " use of

gabapentin, a drug approved for adjunctive use in partial seizure

disorders and post-herpetic neuralgia but not for the wider variety of

chronic pain and psychiatric syndromes which accounted for much of its

off-label prescribing.

 

In that study, the authors retrospectively reviewed medical records

from 105 patients who were treated with gabapentin, prescriptions

reimbursed by Oregon Medicaid. (2) 95% of the gabapentin prescriptions

were off-label. More significantly, 88% of patients receiving

gabapentin did not demonstrate a positive response.

 

Unfortunately for those who paid the bills for gabapentin therapy and

for those consumers who reported no benefit and/or unpleasant side-

effects, these published negative results came almost 9 years after

the successful release and marketing of gabapentin. [Gabapentin

(Neurontin- Parke-Davis) was approved by the US FDA on 30 December

1993. In 2001, according to Hamer et al, gabapentin was in the top-10

drug products by total costs paid by Oregon Medicaid fee-for-service. ]

 

One of the likely sources of over-enthusiastic off-label prescribing

and lack of documented off-label benefits has been the uncritical

adoption of claims of benefits based upon open-label trials or

inadequately populated cohorts. Another occurs when research

scientists are not expected to compare their original findings with

those of longer term studies which contradict their original conclusions.

 

Some of these problems were recently described in an investigative

report by John Ioannidis that appeared in the 13 July 2005 edition of

the Journal of the American Medical Association (JAMA.) (3) He

reviewed 49 highly cited original clinical research studies to

determine whether subsequent analysis could reiterate or replicate

original positive findings. Although some studies (24%) went

unchallenged, about 32% of studies----or nearly one-third of

preliminary highly touted research findings involving various

medicines and therapeutics---did not have the reliability and validity

of their findings confirmed by follow-up research, with some outcomes

specifically contradicted by subsequent studies.

 

Kudos to BMJ, JAMA, and JMCP (and other comparably reputable peer-

reviewed journals) for identifying research whose original findings

have subsequently been seriously qualified or invalidated. We believe

ethical journals have an obligation to expose research making claims

of efficacy-- -especially for off-label use of medications---when

these claims do not withstand subsequent prospective scrutiny.

Pharmaceutical journals have a particularly strong obligation to do

this since they hold a special trust in the provider community, often

being the first place where new drugs are introduced and off-label use

is promoted. Furthermore, we maintain that, in order to repair public

and provider trust in academic and pharmaceutically-sponsored

research, journals must expand their exposure of data analyses that

are later found to have been biased and/or predicated upon

misstatements regarding the reliability and validity of prior

published results.

 

Even more carefully considered research and publishing criteria still

fall short of protecting the patient and provider communities when

publication is too-long delayed. Timing is keenly important.

 

Indeed, even after the publication of spurious data collection or

misrepresented results, multi-year lapses routinely occur between non-

confirmatory re-analysis and bogus preliminary findings. Therefore, if

journal and media scrutiny are effectively to minimize the

ramifications (morbidity, mortality and added healthcare costs) of

questionable data, published re-analysis must occur, if at all

possible, in close temporal relationship to the original publications.

 

Stefan P. Kruszewski, M.D.

Jeffrey A. Brown, M.D., J.D., M.P.H.

Clinical Associate Professor of Psychiatry

University of Medicine and Dentistry of New Jersey

 

1 Kaduszkiewicz H, Zimmermann T, Beck-Bornholdt HP, van den Bussche H.

Cholinesterase inhibitors for patients with Alzheimer's disease:

systematic review of randomised clinical trials BMJ. 2005 Aug 6;

331(7512): 321-327

 

2 Hamer, AN M, Haxby, DG, McFarland, BH and Ketchum, K. Gabapentin Use

in a Managed Medicaid Population. JMCP 2002; 8(4): 266-271

 

3 Ioannidis, JP. Contradicted and Initially Stronger Effects in Highly

Cited Clinical Research. JAMA. 2005; 294 (2): 218-228

 

Competing interests: None declared

 

http://bmj.bmjjournals.com/cgi/content/full/331/7513/410

 

British Medical Journal

August 13, 2005

BMJ 2005;331:410 (13 August), doi:10.1136/bmj.331.7513.410

Front page pill pushers

How the media are complicit in drug marketing

 

The lay media have long come under attack for not adequately

scrutinising the information emerging from Big Pharma about new

prescription drugs, but now they stand accused of helping to publicise

and promote drug company products. In a hardhitting article in the

current issue of the prestigious US periodical the Columbia Journalism

Review, the press is criticised, in its coverage of drug industry

matters, for failing as a public watchdog.

 

" Americans have always been obsessed with all things health-related, "

says the article, " but today a drug can move almost instantaneously

from medical research to miracle cure through news media that too

often seem more interested in hype and hope than in critically

appraising new drugs on behalf of the public "

(www.cjr.org/issues/2005/4/lieberman.asp).

 

The article's author, Trudy Lieberman, who is health policy editor of

US watchdog organisation Consumers Union, blames various factors. In

short, she says, journalists all too often fail to:

 

* find information sources and case studies other than those offered

by drug companies and their public relations people

 

* disclose the financial or other interests of those they quote

 

* seek out and evaluate research data.

 

Other factors exacerbate the situation, she says: there is the

increasingly sophisticated way that drug companies hide aggressive

marketing activities; there is the growth in direct to consumer

advertising leading to conflict between advertising and editorial in

media organisations; and there is the hard to break culture of

newsrooms in which simplistic black and white stories are seen as so

much sexier than reports painted in more realistic shades of grey. Ms

Lieberman also points a finger at the US Food and Drug Administration

and its " somewhat cozy relationship with the companies it regulates, "

which sees those reporters asking tough questions being " frozen out. "

 

Overall, she says, such a mix finds the press caught up in a drug

industry marketing web that leaves the public without a reliable watchdog.

 

Ms Lieberman-whose article analyses coverage of various drugs that

have since been withdrawn, such as rofecoxib (Vioxx)-is writing about

the United States, but the scenario she outlines is recognised all too

clearly by Dr Ike Iheanacho, editor of the UK based Drug and

Therapeutics Bulletin. " These themes of how the drug industry

interacts with the public involving the media are universal and

perennial, " he says.

 

Dr Iheanacho points to the standard health reporting formula: " There's

a `break-through,' an interview or quotes from somebody who has

benefited, and maybe a quote from the manufacturer. You don't get a

sense of balance, that there might be side effects, or that the drug

might not even be available for a few years. " He adds: " It takes time

to be truly critical. Either you have to look at the studies yourself

or talk to someone or several people in detail. Having done all that

you may end up with a very confused picture and that doesn't make easy

journalism. "

 

Indeed, for journalists not content to settle for " easy journalism, "

reporting can be more than just time consuming. Jo Revill, health

editor of the UK Sunday broadsheet the Observer, believes that UK

journalists do at least display a greater scepticism toward the drug

industry than their US counterparts-but you need more than scepticism

to cover the health beat critically and effectively. The big drug

companies, she says, are reluctant to talk to journalists outside of

the trade press, and while invitations to press conferences about drug

launches are forthcoming, " when you want to ask more detailed

questions about a drug it can be really difficult getting information.

The PRs won't deal with these questions and people in-house don't want

to deal with you either. "

 

On the other hand, when drug companies are keen to speak to

journalists, they can be incredibly forthcoming-from offering trips

abroad to attend launches to paying " honorariums " to attend evening

" think tanks. "

 

According to Dr Iheanacho, however, there are glimmers of hope for a

better informed public. There are growing demands for clinical trial

information to be made public and patients are exhibiting a new

enthusiasm for asking questions about their health care. In addition,

uncritical reporting often has a fixed lifespan: as in the case of

Vioxx, today's miracle cure can turn out to be tomorrow's disaster.

" The public will become more sceptical, " he says.

 

Naomi Marks, freelance journalist

 

FAIR USE NOTICE: This may contain copyrighted (© ) material the use of

which has not always been specifically authorized by the copyright

owner. Such material is made available for educational purposes, to

advance understanding of human rights, democracy, scientific, moral,

ethical, and social justice issues, etc. It is believed that this

constitutes a 'fair use' of any such copyrighted material as provided

for in Title 17 U.S.C. section 107 of the US Copyright Law. This

material is distributed without profit.