[e-drug] Double standards in information should go

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E-drug: Double standards in information should go
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BMJ 326:1156-1157 (31 May 2003)

Information from drug companies and opinion leaders 
Double standards in information for medical journals and
practitioners should go 

Medicines can offer enormous health benefits if choices for
treatment are made appropriately, and availability of valid
information is a necessary condition. The asymmetry in the
information available to health professionals and consumers is a
fundamental barrier to rational and informed choice. Good quality
information, however, is a rationed commodity for health
professionals also, and the use of different standards in its
dissemination represents a major determinant of the failure of the
therapeutic chain.1 Healthcare systems make limited investments
to provide independent information, and pharmaceutical
companies who fund most clinical research therefore become
major players in the dissemination of information to health
professionals and the public. Do pharmaceutical companies and
the researchers acting as opinion leaders for them behave fairly
and consistently or do they adopt double standards when they write
in peer reviewed journals and talk to practitioners? We know that
this form of information asymmetry exists.2 Two recent
examples a document from the European Federation of
Pharmaceutical Companies3 and the debate generated by the
ALLHAT study, a landmark trial in the treatment of
hypertension illustrate this danger.4 8 

The document from the European Federation of Pharmaceutical
Companies identifies 20 diseases and conditions, such as
dementia, asthma, hepatitis C, rheumatoid arthritis, some cancers,
and osteoporosis, for which "potentially achievable benefits are not
achieved."4 According to the document, this happens because
patients are denied access to important therapeutic interventions
due to poor diagnosis, limited awareness of patients of effective
drugs, and strict cost containment by healthcare systems. 

The document is worth reading for the way it is written it overlooks
basic principles of synthesis of scientific information. In 98 pages
and 184 citations readers are warned against an alleged underuse
of effective drugs. None of the 20 conditions is discussed with
reference to systematic reviews. In Clinical Evidence and the
Cochrane Library one can find 5-15 systematic reviews for each of
the conditions discussed.9 10 For each disease the document
quotes only some of the positive studies negative ones are
ignored. This selectivity is not limited to studies of effectiveness
and extends to those on appropriateness. Not a single study on
overuse the dimension of quality of care predominantly
addressed by the literature is quoted, and only research looking
at underuse is mentioned. In the section on Alzheimer's disease,
for example, the document from the European Federation of
Pharmaceutical Companies says that with second generation
acetylcholinesterase agents patients can enjoy an increase in their
quality of life, with massive economic benefits for the society. Only
one reference (in German) supports the statement. Available
systematic reviews, however, do not support this view, given the
inadequate follow up, questionable end points, and lack of data
about quality of life in the studies, and conclude that the practical
importance of changes to patients and carers is unclear.10 

The ALLHAT study

The second example is the different approach chosen by
pharmaceutical companies and some opinion leaders in the
scientific discussion in peer reviewed journals5 6 and in the
rejection of the ALLHAT study's results published in national
journals targeted at prescribers and cardiologists.7 8 This double
standard represents a predefined strategy aimed at challenging
unwelcome results.11 ALLHAT had immediate responses in the
Journal of Hypertension, whose editors asked specialists to discuss
its methodological strengths and weaknesses.5 The invited
commentaries substantially praised the strengths, identifying only
minor weaknesses.11 14 

Full scale attacks directed at the design, analysis, and
interpretation of ALLHAT appeared instead in the journal of the
Italian Society of Hypertension (Ipertensione & Prevenzione
Cardiovascolare)7 and in a weekly medical magazine.8 According
to the Italian editorial, the drawbacks of ALLHAT were a lack of
previous experience in research trials in most centres, the short
duration of the study, the lack of a washout period before
randomisation, and the unusual combination of drugs associated
with the experimental ones. The editorial also implied that the
ALLHAT investigators had their own competing interests since a
priority for the public institutions that funded ALLHAT (National
Institutes of Health in the United States) is keeping the costs of
care low.7 

In the other article the major flaws in ALLHAT were listed as the
ineffectiveness of monotherapy (actually 55% of patients were well
controlled with monotherapy; the need to add a second drug, which
could have favoured chlortalidone; the fact that 90% of the
population was already treated with antihypertensive drugs (doesn't
this happen in almost all hypertension trials?); that heart failure was
not a prespecified end point (it was, and a totally validated one too);
and that follow up was too short to show differences that could
become important with long term treatments (ALLHAT has one of
the longest follow ups among hypertension trials). In its conclusion
the article says that ALLHAT's results should not be applied to
Italian or European clinical practice, given the countries' low
percentage of black patients (who benefit most from a thiazide
diuretic treatment).8 Interestingly, in ALLHAT's main report, a
subgroup analysis indicated that results did not change according
to race.4 However, none of these arguments was present in the
letters to the editors published by JAMA a few months after the
ALLHAT report.6 

These two cases underscore the need for a common set of rules if
pharmaceutical companies and opinion leaders want to save their
credibility. Firstly, pharmaceutical companies need to agree to
collaborate on an explicitly prioritised research agenda where
questions related to care are more relevant than drug specific
issues. Secondly, a transparent code of conduct against
publication bias or selective suppression of information should be
developed. Since only a minority of randomised controlled trials
gets published, a registry of ongoing studies following the example
of the US National Cancer Institute's physician data query
database (www.nci.nih.gov/cancer_information/pdq/) is warranted,
together with disclosure of investigators' competing interests and
their roles in the design, conduct, analysis, and interpretation of the
study. Finally, both pharmaceutical companies and opinion leaders
should recognise their ethical duty to avoid speaking two different
languages the scientific one in peer reviewed journals and the
language stuffed with personal opinions when they speak directly to
practitioners or policy makers. 

Alessandro Liberati, associate professor 
University of Modena and Reggio Emilia, Via Campi 287, 44100
Modena, Italy (alesslib@tin.it) 

Nicola Magrini, director 
Centre for Evaluation of the Effectiveness of Health Care
(CeVEAS), Via Le Huratori, 44100 Modena, Italy 



References

Figueras A, Laporte JR. Failures of the therapeutic chain as a
cause of drug ineffectiveness: promotion, misinformation, and
economics work better than needs. BMJ 2003;326: 895-6.
Collier J, Iheanacho I. The pharmaceutical industry as an
informant. Lancet 2002:360: 1405-9.
Sch?ffski O, on behalf of the European Federation of
Pharmaceutical Industries and Associations. Diffusion of medicines
in Europe. EFPIA, September 2002. www.gm.wiso.uni-erlangen.de/ 
ALLHAT Officers and Coordinators for the ALLHAT Collaborative
Research Group. Major outcomes in high risk hypertensive patients
randomised to angiotensin-converting enzyme inhibitor or calcium
channel blocker vs diuretic: the antihypertensive and lipid lowering
treatment to prevent heart attack trial (ALLHAT). JAMA 2002;288:
2981-97.
Zanchetti A, Mancia G. The ALLHAT trial: a verdict or a challenge?
J Hypertens 2003;21: 223.
Wright JT, Davis BR, Cutler JA for the ALLHAT Collaborative
Research Group. JAMA 2003;289: 2069. (Reply to
correspondence on page 2066-8.)
Agabiti Rosei P. Quali nuovi insegnamenti dallo studio ALLHAT per
il trattamento dell'ipertensione arteriosa. Ipertensione &
Prevenzione Cardiovascolare 2002; Dicembre: 133-5. 
Ambrosioni E. Valutare l'effectiveness pesando tutti gli effetti. Sole
24 Ore Sanit?, 2003 March 4-10: 21. 
Clinical Evidence. London: BMJ Publishing, 2002. (Issue 8.) 
Cochrane Library. Issue 4. Oxford: Update software. 2002. 
Lenzer J. Spin doctors soft pedal data on antihypertensives. BMJ
2003;326: 170.[Free Full Text] 
Chalmers J. All hats off to ALLHAT: a massive study with clear
message. J Hypertens 2003;21: 225-8.
Fagard RH. The ALLHAT trial: strengths and limitations. J
Hypertens 2003;21: 229-32.
Kaplan NM. The meaning of ALLHAT. J Hypertens 2003;21: 233-4.
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