1. 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: /j

2. Content Publication Empirical Science
Issue with publication - Empirical Science and Selection
Case Study: Paxil (Paroxetine) and GSK
Conclusion
This is the overview of the entire presentation

3. 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.
Publication - not a foreign term itself
The diagram Take us through the process of publication
Publication: Bringing ideas out to the scientific community to open discussion or debate
The whole idea about publication is that we bring new ideas or content that are based on evidence into the scientific community and public.
This we how we acquire new information or establish credible claims and cite the works of others to support your own
Source:

4. 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.
From publication,
The result of this entire process is that we have a system that sieves through the works and studies of many researchers
The content and credibility of the are that are published are reassured and checked by professionals
Contribution of publication to scientific progress: we do not get hold up on false claim and wrong information
Steers the community in the right direction/path for progress

5. What’s the issue then?

6. 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.

7. 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.

8. 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

9. Result of Selection “File Drawer Problem”
Investigators might be discouraged by negative results (e.g. failing to reject null hypothesis), terminating the studies in advance.
Current Incentive system: No merits for scientist to publish negative results.
Likewise they would only submit studies that are likely to be published.
“File Drawer Problem”

10. Authors submitting findings that are likely to be publish.
Publication Bias:
Authors submitting findings that are likely to be publish.
Publishers selecting studies that are worthy to be publish.

11. 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

12. Biases - Author publishing positive results, publishers approving study worth of publication… etc.
Studies Conducted
Published Studies : Those we can see.

13. Result of Publication Bias Published Studies
Negative and ‘Neutral’ Studies published
Result of Publication Bias
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
And this is, a problem as it can possibly alter the statistics associated with a drug or treatment. In this hypothetical scenario, the number of studies that reflect the effectiveness of the drug rose from 30 to 80% and this was not representative of what happened in the actual scenario, where the mild effects and negative results cancelled out to conclude that the drug is not as effective.

14. Result of Publication Bias
Original Distribution - Observed by all 100 studies. Result: Normally Distributed success rate - Drug is ineffective

15. Result of Publication Bias
Published Results - Strong evidence showing that the drug/treatment is effective
Original Distribution - Observed by all 100 studies. Result: Drug is ineffective
When physician review the published results randomly, it reflects only part of the truth.

16. Case Study -Paxil

17. 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).
Manufacturer and background of Paxil -

18. 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

19. 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.

20. 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.

21. 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

22. 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 efficacy in treating depression in patients under 18.”

23. 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.

25. References
Reading Article: Copas, J. (2005), The downside of publication. Significance, 2: 154–157. doi: /j 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): e doi: /journal.pone Investigation of Paxil: policy/documents/websiteresources/con pdf
Paxil Settlement: report

26. The End
Thank you! :)