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

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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.

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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

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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)

Why publishing/disclosing

more Clinical Trials.

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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

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Pharmacovigilance During Clinical Trial Phases

Pharmacovigilance: Ensuring the Safe Use of Medicines - WHO Policy Perspectives on Medicines, No. 009, October 2004

(2004; 6 pages)

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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

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Number of registered studies with posted results over time

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Number of published articles indexed in Medline

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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.

What did it bring,

pros and cons

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BMJ 2011;342:d1250

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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

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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.

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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.

What is being done about it.

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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

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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.

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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.

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Making All Research Data Available

Publishing Open Access Journal publishing less impactful and negative

results

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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/

Conclusion and perspectives.

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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.

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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.

Thank you! Any questions?