Download The Downside of Publication

The Downside of Publication
Group 2: Jing Kai, Nabilah and Soon Guan
Presenter: Soon Guan
Reading:
Copas, J. (2005), The downside of publication.
Significance, 2: 154–157. doi:10.1111/j.17409713.2005.00127.
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Content
● Publication
● Empirical Science
● Issue with publication - Empirical Science and Selection
● Case Study: Paxil (Paroxetine) and GSK
● Conclusion
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Publication
- Publication: Bringing new
ideas and knowledge out into
the scientific community and
the public.
- Articles and studies are put
through rigorous rounds of
checks and review.
Source:http://www.iosrphr.org/images/publication%20process.jpg
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Publication - The Result
-
The system sieves through the works and studies of many
researchers.
-
The content and credibility of the articles that are published are
reassured and checked by
editors and peer reviewed.
-
Only those that made the cut are selected.
http://orig03.deviantart.net/0469/f/2010/225
/1/0/joey__s_rattata_by_spiffee.png
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What’s the issue then?
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Problem - Selection in
Empirical Science
- Empirical Sciences: Evidence based
science.
- Examples: Medicine, Clinical Trials
and experimental studies.
- Often involve hypothesis testing to
test for statistical significance of
the results.
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Cause of Selection
- The complication does not stem from the quality of the
author’s work, but the process that it is going to be
subjected to.
- Not all studies that can be/ supposed to be published
are published.
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Need to publish
articles that warrant
sufficient interest
Feedback:
Unlikely to
publish negative
results
Selectively send
studies that are
likely to be
approved
Terminate
studies that
show negative
results
Considerations:
Journal’s
Reputation whether it will
bring merit in
publishing a
certain article
Considerations:
Unlikely to
publish negative
results that have
little impact
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Result of Selection
- Investigators might be discouraged by negative
results (e.g. failing to reject null hypothesis),
terminating the studies in advance.
“File Drawer Problem”
- Current Incentive system: No merits for scientist
to publish negative results.
- Likewise they would only submit studies that are
likely to be published.
https://oikosjournal.files.wordpress.com/2014/05/data_
01.jpg
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Publication Bias:
Authors submitting findings that are likely to be
publish.
Publishers selecting studies that are worthy to be
publish.
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Hypothetical Example - In Clinical Trial
- Suppose I want to find whether Drug X
works in treating depression.
- I conduct the same study with the same
experiment design for 100 times.
- Result:
30% Negative Results,
40% No effect (or difference),
30% Positive Results
Conclusion: Drug is ineffective
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Biases - Author publishing positive results,
publishers approving study worth of
publication… etc.
Studies Conducted
Published Studies : Those
we can see.
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Result of Publication Bias
Negative and ‘Neutral’
Studies published
- As a result, the proportion of
positive effects was inflated: from
30% to 80%.
- What is presented is not
representative of the actual
scenario.
- Because of biases, the
effectiveness of a treatment
can be significantly altered.
Published Studies
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Result of Publication Bias
Original Distribution Observed by all 100
studies.
Result: Normally
Distributed success rate Drug is ineffective
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Result of Publication Bias
Original Distribution Observed by all 100
studies.
Result:
Drug is ineffective
Published Results Strong evidence
showing that the
drug/treatment is
effective
When physician
review the
published results
randomly, it
reflects only part
of the truth.
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Case Study -Paxil
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Case Study - Paxil (Paroxetine)
- Paxil (Paroxetine) – Marketed in 1990s
- Treatment of depression and anxiety problem.
- Antidepressant that works by selectively
inhibiting reuptake of serotonin (SSRI).
- Manufactured by GlaxoSmithKline (GSK).
http://www.depressionhealth.net/wpcontent/uploads/2014/06/paxil-paroxetine10mg-20mg-30mg-40mg.jpg
http://emit.medschl.cam.a
c.uk/wpcontent/uploads/2014/07/
GSK_LOS_RGB.jpg
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Case Study - Paxil (Paroxetine)
- The efficacy and safety of the drug was unknown in Adolescent.
- The Product Leaflet states that it is not recommended in children.
- Paxil is known as Seroxat in the UK
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Case Study - Paxil (Paroxetine)
- GSK conducted two trials, Study 329 and Study 377, both failed to show
Paxil was effective in treating depressive disorder in children.
- No amendments were made to the product summary despite these
findings.
- “It would be commercially unacceptable to include a statement that efficacy
had not been demonstrated, as it will undermine the profile of paroxetine” GSK Internal Management.
- 32,000 Paxil prescriptions were already issued to children in UK alone.
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Case Study - Paxil (Paroxetine)
- Negative effect of the trial was downplayed and not included in the
conclusion when published.
- Further analysis showed children taking Paxil are 1.5 to 3.2 times more
likely to exhibit suicidal behaviour than those that are taking placebo.
- This finding was not published as well.
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Findings published on BMJ on Paxil
"The published manuscript was biased in its conclusions, made
unsubstantiated efficacy claims and downplayed the adverse-event profile of
Paxil," – The British Medical Journal
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Case Study - Paxil (Paroxetine)
“ The United States alleges that, among other things, GSK participated in preparing, publishing and
distributing a misleading medical journal article that misreported that a clinical trial of Paxil
demonstrated efficacy in the treatment of depression in patients under age 18, when the study
failed to demonstrate efficacy.”
“GSK did not make available data from two other studies in which Paxil also failed to demonstrate
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efficacy in treating depression in patients under 18.”
Message
- Publications are put through rigorous checks and review to ensure its
quality.
- The flaw of the system stems from the nature of how it works and biases
are introduced which distorts the actual statistical results.
- Case Study: GSK and Paxil.
- Important for us to be aware of the truth.
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http://cdn.quotationof.com/images/tip-of-the-iceberg-quotes-1.jpg
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References
Reading Article:
Copas, J. (2005), The downside of publication. Significance, 2: 154–157. doi:10.1111/j.1740-9713.2005.00127.x
Paxil: Article Source:
The Efficacy of Paroxetine and Placebo in Treating Anxiety and Depression: A Meta-Analysis of Change on the
Hamilton Rating Scales
Sugarman MA, Loree AM, Baltes BB, Grekin ER, Kirsch I (2014) The Efficacy of Paroxetine and Placebo in Treating
Anxiety and Depression: A Meta-Analysis of Change on the Hamilton Rating Scales. PLOS ONE 9(8): e106337. doi:
10.1371/journal.pone.0106337
Investigation of Paxil:
http://webarchive.nationalarchives.gov.uk/20141205150130/http://www.mhra.gov.uk/home/groups/espolicy/documents/websiteresources/con014155.pdf
Paxil Settlement:
https://www.justice.gov/opa/pr/glaxosmithkline-plead-guilty-and-pay-3-billion-resolve-fraud-allegations-and-failurereport
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The End
Thank you! :)
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