The standard biomedical paradigm
for drug treatment of
disease follows a straightforward
algorithm. A disease is identified and
diagnostic criteria are developed.
Promising medications are tested using
the scientific method, especially
randomized controlled trials (RCTs),
to determine safety and efficacy. The
results of these studies are presented
to the scientific community in peerreviewed
journals and scientific debate
If a drug is approved by the FDA,
the results of the trials and the conflicting
scientific opinions are presented to
physicians. Practicing psychiatrists must
evaluate the results for their own patients
and decide whether the benefits of a
medication outweigh its shortcomings.
In this article, we discuss evidence
that the pharmaceutical industry influences
this paradigm in ways that
encourage sales of their products and
that are not always in the best interests
of the patient.
Expanding the indications:
An investigative article in the British
Medical Journal by Moynihan and
associates1 describes how drug companies
developed an explicit campaign to
promote shyness as an important and
treatable disorder, successfully shaping
medical and public opinion about
social phobia. A senior pharmaceutical
industry executive involved in the
promotion of social phobia in Australia
acknowledged that marketing efforts
exaggerated the prevalence of disease,
and recognized the inherent conflict of
interest when a drug company sponsors
publicity about a disease for which
it markets a treatment, as his company
did with social phobia.2
An article in the Pharmaceutical
Executive (a trade journal) discusses
generally the making of a new disease,
and how new markets can be created
by defining a new disease (such as the
metabolic syndrome).3 Another way to
expand indications for a drug (and thus
the market) is to lower the threshold of
normal, rendering more people ill
and in need of medication. Some critics
think that pharmaceutical companies
have succeeded in medicalizing
risk factors or normal experiences, thus
making otherwise healthy people think
they need certain drugs.4
Pharmaceutical companies have
successfully expanded the FDAapproved
uses of various selective serotonin
reuptake inhibitors (SSRIs) to
include a variety of psychiatric
diseases, such as generalized anxiety
disorder, obsessive-compulsive disorder,
premenstrual dysphoric disorder,
posttraumatic stress disorder, and
bulimia nervosa.5 Trials for many offlabel uses such as premature ejaculation,
migraine headache prophylaxis,
and neurocardiogenic syncope are
conducted and offlabel uses are often
suggested.6 Drug company efforts to
get patients on treatment have been
motivated by a variety of reasons.
Although there is no doubt that some
patients have benefited from the
promotion of treatment for these
syndromes, drug company sales have
In Australia, where direct-toconsumer
advertising (DTCA) is not
permitted, the value of campaigns
promoting diseases can be clearly
seen. At the same time that Merck's
hair growth drug finasteride was
approved in Australia, a public relations
firm hired by the manufacturer
launched a vigorous campaign about
the dangers and tragedy of baldness.
Eventually, newspapers published articles
about the emotional trauma associated
with hair loss, including expert
opinions that losing hair could lead to
emotional problems, harm to mental
well-being, and loss of job prospects.
These articles did not reveal that the
studies they cited were funded by
Merck, and that the experts quoted had
been supplied by the company's public
Industry funding in the peerreviewed
For many practicing psychiatrists, the
results of peerreviewed, published
RCTs are an essential element in
making treatment decisions about drug
therapy. A systematic review of all clinical
trials published in 4 leading, peerreviewed
psychiatry journals from
2001 to 2003 found that pharmaceutical
sponsorship was common and
was statistically associated with
outcomes that favored the sponsor.7 Of
the 162 RCTs published during this
time, 70% were funded by pharmaceutical
companies and 46% had at
least 1 author who had a financial
conflict of interest either through
employment or by having received
direct financial support from a pharmaceutical
company. Studies with at
least 1 author with a conflict of interest
were about 5 times more likely to
report positive results than were nonindustry
This article can only point to a
strong correlation between industrysponsored
studies and the reporting of
positive results but cannot establish
causation. A summary of the types of
design and reporting modifications that
have been used in industrysponsored
psychopharmacology trials is presented
in the Table.8
Clinical trials research on atypical
or secondgeneration antipsychotics
(SGAs) provides an example of this
association between a trial's sponsorship
and its outcome.9 Of 59 RCTs
studying SGAs, those sponsored by the
vendors of SGAs were significantly
more likely to find them superior to firstgeneration
antipsychotics than were
nonindustry-funded RCTs (P = .02).
Furthermore, studies with first authors
employed by the industry showed a
strong trend (P = .05) toward favoring SGAs over conventional antipsychotics,
compared with articles whose first
authors were independent of industry.
Could the industry-sponsored trials
simply have been bigger, better, and
more able to identify a true superiority
of the sponsored drug? Two lines of
evidence argue against this possibility.
First, the researchers who reported this
difference in outcome found a trend (P
= .07) toward higher overall RCT quality
score in the studies that were not
industry funded. The second line of
evidence is indirect. A review by Hogan
and associates10 of studies comparing
one cholinesterase inhibitor with
another for Alzheimer disease (AD)
concluded that, All studies were funded
by pharmaceutical companies, coauthored
by their employees, and reported
results that favoured the sponsor's product.
Similarly, industry-funded studies
that compared 2 long-acting inhaled
corticosteroids and found a difference
between them, found evidence in favor
of the sponsor's product in 37 of 38 of
the peer-reviewed published RCTs.11
Summary of examples of design and reporting modifications in industry-sponsored trials8
|Technique used||Examples from the literature|
|Using doses outside the usual range||Haloperidol at a dose of 20 mg was the comparator in studies of EPS
with second-generation antipsychotics30
|Altering the dosing schedule||Twice daily amitriptyline was the comparator in evaluation of daytime
sleepiness (vs paroxetine)31
|Using self-serving measurement scales||“Worst EPS score” rather than total or last observed EPS score was used to show risperidone causes the same amount of EPS as placebo30|
|Selecting major findings and end points post hoc (secondary analyses or "data dredging")||Although not the initial hypothesis of the trial, side-effect differences at 1 week were used to compare venlafaxine and fluoxetine32|
|Masking unfavorable side effects||Specific questions about sexual side effects of SSRIs elicit a 73% positive
response; change to unstructured open-ended questions drops the rate to 2%33,34
|Repeatedly publishing the same or similar positive studies||Multiple publication of the same study (stand-alone or as pooled data) is discussed in the text and in an editorial35|
|Selectively highlighting findings||Ignoring placebo as being as efficacious as the drugs (and having fewer side effects) in the comparisons of 2 antidepressants for anxiety symptoms36|
|Editorializing for the sponsor in abstracts and conclusions||The study drug heralded as the “new first-line treatment” when data do not support this conclusion37|
|Publishing the obvious to emphasize a point for marketing||Publications of the risks of nortriptyline in older adults with heart disease in comparative trials versus various SSRIs38,39; these publications add little to medical knowledge but are of great use for marketing|
|Touting nonsignificant but favorable differences and negating dropout differences statistically||A conclusion that paroxetine was better tolerated than clomipramine was based on insignificant differences40|
|Selection of participants and trial duration||Short trial duration of 8 weeks was used to compare olanzapine
or risperidone versus chlorpromazine in treatment-resistant patients; chlorpromazine typically shows effects over a longer time frame41
|Withholding unfavorable results||Withholding unfavorable results|
|Masking sponsorship||Ghostwriting is discussed in the text; disclosure of conflict of interest
is now more commonly required
EPS, extrapyramidal symptoms; SSRIs, selective serotonin reuptake inhibitors.
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