SAE data entry: Clinical versus Pharmacovigilance standards

Daniel BeckerSolvay Pharmaceuticals

Hannover, GermanyDaniel.Becker@solvay.com

T: +49 511 857 3708

© Daniel Becker PSDM, Weesp, 22 May 2008

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Who am I?

Global Safety Physician in Solvay Global Clinical Safety (part of Global Clinical Development)

Chair of Solvay-Quintiles Joint Clinical Safety and Coding Team

Solvay SAE reporting coordinator

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Disclaimer

These are my current views and not necessarily those of every concerned

Solvay colleague

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SAE data discrepancies between Pharmacovigilance and Clinical

databases: Origins

I. Different philosophies

II. Different industry standards

III. Multiple datasets

IV. Technical aspects

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I. Philosophies

Pharmacovigilance

Safety first!

Clinical

CRF data authenticity first!

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Consequences (1)

Pharmacovigilance data entry

1. interpretation of supplied data is entered

2. if inconsistent data is supplied (e.g. SAE report vs. discharge summary) the medically worse data is entered

3. selected non-serious AEs are updated to medically serious

Clinical data entry

1. data is entered/accepted (in case of eCRF) as is

2. only data reported in the CRF/as query response is accepted

3. no change in seriousness

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Consequences (2)

Pharmacovigilance data entry

potential AEs mentioned e.g. in the narrative which are not reported as AEs are extracted and entered

worst-case assumption is entered, and confirmation is requested thereafter

Pharmacovigilance controls entries

Clinical data entry

no data transfer to other variable

questionable entry is kept and query is issued

Reporter controls entries

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II. Industry Standards

Pharmacovigilance

ICH-E2B

Clinical

SDTM, HL7, ...

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Consequences

different variables and formats not all related variables may match in

definition, formats and/or rules

particularly, if non-current versions of the industry standards are used or when not defined in them

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III. Multiple datasets

Pharmacovigilance1. SAE form entry, as

well as formless submissions (e.g., hospital discharge summary, query replies)

2. Pharmacovigilance database

Clinical3. CRF entries in

several modules (demographics, concomitant medication, adverse event)

4. Clinical database

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Consequences

investigators regularly report inconsistently to the clinical versus the pharmacovigilance databases or provide corrections / relevant follow-up information like a final hospital discharge diagnosis only to one database

unless the same person codes for both databases, codes will not always match

if a standard or its guide is modified the other three may have to be updated, too

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IV. Technical aspects (1)

Pharmacovigilance database never locks

medical history occurs before the SAE

SAE start date is date of first sign / symptom / diagnosis.

Clinical database locks at

study end medical history

occurs before the study. Medical events between study start and SAE are AEs.

SAE start date is date AE became serious.

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IV. Technical aspects (2)

Pharmacovigilance If an SAE started during

core study but extended into extension study it is recorded under the core study only.

Concomitant medication is only that administed at the time of the SAE and which is non-suspect to have caused the SAE.

Clinical If an SAE started during

core study but extended into extension study it is recorded under both studies.

Concomitant medication is any medication administered during the study, whether suspect to have caused the SAE or not.

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IV. Technical aspects (3)

unless data entry in both databases is done by the same person, discrepancies are inevitable, e.g. inconsistent➤ splitting of verbatims (e.g., „pneumonia,

malaise“ in „pneumonia“ and „malaise“)➤ combination of related, concomitant events

to code to inclusive term (e.g., „shortness of breath“ and „asthma“ to „asthma“)

➤ duplication of verbatims to code to two terms (e.g., „toxic psychosis“ duplicated and coded to „toxic reaction“ respectively „psychosis“)

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My thoughts

I don‘t see how you can get around two databases reconcile only medically most relevant items, e.g.:

1. Study Number2. Subject Number3. Randomization Number (if available)4. Gender5. Date of Birth6. SAE verbatim7. Stop Date8. Ongoing9. Outcome10. Study Drug-Event relationship as judged by the investigator11. Action taken with study drug

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Questions?

Comments?