Clinical data sharing: why publishing negative and less impactful results is important for patient safety Clinical trials are essential in drug development and are the cornerstone for getting a medicinal product authorized for marketing, because clinical trials investigate efficacy and drug safety. When the results of clinical trials are published, they can be informative to health care professionals, policy makers, media and the general public. But not all trial results are conclusive or significant, and many trials show that drugs are ineffective. These results often do not get published, either because these results are not suitable for a journal or because the researcher does not think these results are worth publishing. Due to the fact that inconclusive and insignificant results are not published, we are facing a publication bias towards positive results. During this webinar the speaker will demonstrate why publishing negative and less impactful results of clinical trials, as in Elsevier’s newly launched Open Access Journal ‘Contemporary Clinical Trials Communications’ reduces publication bias and is important for patient safety.

1. Sharing Clinical Data: Why
publishing studies with negative
or non-conclusive results is
important for patient’s safety.
Presented by: Pascal Hua Customer Consultant
Date: 09 February 2016

2. 2
Goals of pharmacovigilance
• To improve patient care and safety in relation to the use of
medicines, and all medical and paramedical interventions
• to improve public health and safety in relation to the use of
medicines;
• To contribute to the assessment of benefit, harm, effectiveness and
risk of medicines, encouraging their safe, rational and more effective
(including cost-effective) use;
• To promote understanding, education and clinical training in
pharmacovigilance and its effective communication to health
professionals and the public.

3. 3
Impact of Adverse events
New EU
Pharmacovigilance
Legislation
Adverse events are important risk for public health and have major economic
impact
- 5% of all EU hospital admissions are due to adverse drug reactions
- ADRs the fifth most common cause of hospital deaths (197,000 deaths per year)
~197k
Deaths annually
~5k
Lives saved
annually
Highlights form the World Drug Safety Congress Europe Held in London, UK, 10-11 September 2014.
http://www.fishawack-archimed.com/Newsletters/Fishawack_Archimed_Safety_Reports_Issue1.pdf

4. 4
New PV legislation since 2012
• Adverse drug reactions are preventable in majority of cases
• Small improvements will have major impact, meaning small
improvements saves lot of patients lives
• Relatively “easy” to save money in area of healthcare
>> New PV legislation in EU implemented since 2012 (still ongoing)

5. Why publishing/disclosing
more Clinical Trials.

6. 6
Clinical Studies are the 5th largest source of AE reporting
Often overlaps with reports from health professionals
FDA Adverse Event Reporting System (FAERS) Quarterly Data Files, Q2 and Q3 2013
Reported adverse events by report source,
Q2 & Q3 2013
N = 34,469 unique events
Overlap of adverse events sourced from
literature by reporting sources, Q2 & Q3 2013
N = 4,691 unique events

7. 7
Pharmacovigilance During Clinical Trial Phases
Pharmacovigilance: Ensuring the Safe Use of Medicines - WHO Policy Perspectives on Medicines, No. 009, October 2004
(2004; 6 pages)

8. 8
History, Policies and Laws about Clinical Trials
• 1997: Congress Passes Law (FDAMA) Requiring Trial Registration
• 2000: NIH National Library of Medicine releases ClinicalTrials.gov website
• 2005: International Committee of Medical Journal Editors Requires Trial
Registration
• 2006: World Health Organization Establishes Trial Registration Policy
• 2008: Clinical Trials.gov Releases Results Database
• 2008: Declaration of Helsinki Revision Promotes Trial Registration and
Results Dissemination
• 2013: EMA Expands Clinical Trial Database to include Summary Results
• 2014: Notice of proposed Rulemaking (NPRM) for FDAAA 801 Issued for
Public Comment
• 2014: NIH Draft Policy on Registration and Results Submission of NIH-
Funded Clinical Trials Issued for Public Comment
• 2015: National Cancer Institute Issues Clinical Trial Access Policy

9. 10

10. 11
Number of registered studies with posted results over time

11. 12
Number of published articles indexed in Medline

12. 13

13. 14
Bias in the non publication of clinical trials.
David K. Vawdrey, George Hripcsak, Publication bias in clinical trials of electronic health records,
Journal of Biomedical Informatics, Volume 46, Issue 1, February 2013, Pages 139-141.

14. What did it bring,
pros and cons

15. 16
BMJ 2011;342:d1250

16. 17
Challenges of Detecting Adverse drug reactions in Clinical trials
Eichler, H.-G., Pignatti, F., Flamion, B., Leufkens, H., Breckenridge, A. Balancing early market access to new drugs with the
need for benefit/ risk data: A mounting dilemma (2008) Nature Reviews Drug Discovery, 7 (10), pp. 818-826
Myocardial Infarction

17. 18
To Share or Not to Share.
Pros Cons
Suppressing null results can
put patients at risk.
Issue of patient consent and
confidentiality.
Increased rigor and
transparency of data
management and analysis.
Dissemination of incorrect
or misleading analyses.
More secondary analyses
available for authorship.
Persons bent on
discrediting publishing work
may perform rogue
analyses.
Junior investigators have
more opportunities for trial-
based analyses.
Losing first authorship
opportunity for junior
investigators
Academic credit assigned to
data sets.
Loss of publishing potential
by academic clinical
trialists.

18. 19
To Share (or Not to Share).
• Better examples to educate and
motivate young scientist.
• Increased proportion of trials that are
published.
• Accelerate the publication speed of
clinical trial research.
• Fulfilling promise to participants of
benefiting others.

19. What is being done about it.

20. 21
From Publishing:
• Public Library of Science (PLOS)
• Requires authors to make all data underlying the findings described in
their manuscript fully available without restriction. For studies involving
human participants, data must be handled so as not to compromise
participant’s privacy. http://journals.plos.org/plosone/s/data-availability
• British Medical Journal:
• Requires all authors of drug or device clinical trials to provide detailed
scientific study data to anyone with a reasonable request, whether or not
the work is funded by the pharmaceutical industry.
http://www.bmj.com/content/350/bmj.h2373

21. 22
From Publishing, Elsevier
• Many or our medical journals already require registration of clinical
trials in a public trials registry at or before the time of first patient
enrollment as a condition for publication.
• Leading the field in data sharing:
• One of the first publisher to endorse the Joint Declaration of Data Citation
Principle. https://www.force11.org/group/joint-declaration-data-citation-
principles-final
• Encouraging authors to include data DOI when relevant.
• Linking to datasets within articles.

22. 23
From Publishing, Elsevier
• Disclosure of results before publication
• Presentation of data at a scientific meeting, as a poster, abstract, orally, on
a CD, or as an abstract on the web does not conflict with submission to The
Lancet
• As a member journal of the International Committee for Medical Journal
Editors, The Lancet does not regard results that are posted in the same
clinical trials registry in which primary registration resides as prior
publication, if the results are presented in the form of a brief structured
abstract or table (<500 words; see Lancet 2007; 369: 1909-11). However,
presentation of results in other circumstances (eg, investors’ meetings) is
discouraged and could jeopardise consideration of the manuscript
• http://www.thelancet.com/lancet/information-for-authors/disclosure-
of-results.

23. 24
Making All Research Data Available
Publishing Open Access Journal publishing less impactful and negative
results

24. 25
From Pharmaceutical companies:
• GlaxoSmithKline
• Provides access to de-identified patient-level data from its sponsored
clinical trials subject to review and oversight by an independent review
panel. http://www.gsk.com/en-gb/research/sharing-our-research/patient-
level-data/
• Now joined by Astellas, Bayer, Boehringer Ingelheim, Eisai,
Lilly, Novartis, Roche, Sanofi, Takeda, UCB and
ViiV Healthcare. https://www.clinicalstudydatarequest.com/

25. Conclusion and perspectives.

26. 27
In summary
Clinical studies contain significant amount of information on
safety and efficacy of medicine
A significant number of clinical trial stay unpublished
Effort from all sides are happening to fill this gap.

27. 28
Conclusion and Questions to Consider
• Is more data always better ?
– Multiplicity of repository/sources to consult.
– Data/information mining... (Indexing
structure, text mining).
• Issues in normalization of the conditions and the
reporting for data interpretation.

28. Thank you!
Any questions?