# Presentation: 916366

## CIOMS V:Pragmatic Approaches to Some Current Challenges in Pharmacovigilance

**Session Chair:**
**	****Murray M. Lumpkin, M.D.**
**	****FDA        USA**
**DIA EuroMEETING 2000**
**Nice, France**
**09 March 2000**

## COPIES OF OVERHEADS

**www.fda.gov**
**go to CDER section of website**

- Murray M. Lumpkin, M.D.

- 3/9/00

## CIOMS - Background

**WHO organisation - 1949**
**Drug Safety Working Group: industry, regulators, academia**
**Four publications over past decade**
**No regulatory status - ****DISCLAIMER**** **
**Really a “think tank” on issues of importance to international pharmacovigilance community**
**Identify significant issues and offer pragmatic solutions**

- Murray M. Lumpkin, M.D.

- 3/9/00

## CIOMS V

**Single set of “best practices”**
**Simplify, Clarify, and Harmonise some of the areas of continued concerns in international PV**
**Report now in final editing**
**Due for WHO publication later this year **

- Murray M. Lumpkin, M.D.

- 3/9/00

## CIOMS V:  4 MAJOR TOPIC AREAS

**Sources of individual cases**
**Consumer reports**
**Defining “literature”**
**Internet reports/chat rooms**
**Solicited/stimulated reports**
**Observational studies**
**Registries**
**Licensor-Licensee Interactions**

- Murray M. Lumpkin, M.D.

- 3/9/00

## CIOMS V:  4 MAJOR TOPIC AREAS

**Good Case Management Practices**
**Assessing Patient and Reporter Identifiability**
**Criteria for “Seriousness”**
**Criteria for “Expectedness”**
**Not new definitions; rather ambiguous cases and how one might approach**
**Case Follow-Up Approaches**
**Role of Narratives - uses of computers to aid in preparation**

- Murray M. Lumpkin, M.D.

- 3/9/00

## CIOMS V:  4 MAJOR TOPIC AREAS

**Good Summary Reporting Practices:  Beyond PSURs**
**How to best integrate international core PSURs into present safety reporting and product re-licensing requirements**
**Summary Bridging Reports**
**Summary Comprehensive Reports**
**Simplified Reports**

- Murray M. Lumpkin, M.D.

- 3/9/00

## CIOMS V:  4 MAJOR TOPIC AREAS

**Determination and Use of Population Exposure Data**
**Covariates defining a treated population**
**Units of measurement**
**Sources of data**
**Uses of data: calculations and caveats**
**Spontaneous reporting and population exposure**
**Special applications for estimating risk**

- Murray M. Lumpkin, M.D.

- 3/9/00

## AGENDA

**Clinical Evaluation and Follow Up**
**Murray M. Lumpkin     FDA, USA**
**Beyond PSURs**
**Sue Roden       GlaxoWellcome,  UK**
**Measuring Population Exposures**
**Bengt-Erik Wiholm,   MPA, Sweden**
**Questions / Discussion****       **

- Murray M. Lumpkin, M.D.

- 3/9/00

## Clinical Evaluation of Cases

**Information:**** documented, assessed, understood, and placed in proper perspective relative to the already established benefit: risk profile of the marketed product**
**Part of a comprehensive signal detection and evaluation programme**

- Murray M. Lumpkin, M.D.

- 3/9/00

## Clinical Evaluation of Cases

**Are we learning something new or is this reinforcing something already known about our product?**
**Is it important to the patients and practitioners who use our product?**

- Murray M. Lumpkin, M.D.

- 3/9/00

## Clinical Evaluation of Cases

**Receipt and processing of sADRs ****should not be a passive activity****, but must be part of a systematic process --> open exchange of medical information with the reporter**
**Goal: ****Improve case documentation and understanding**
**Often requires follow up with reporter**

- Murray M. Lumpkin, M.D.

- 3/9/00

## Follow Up

**Information in reports generally incomplete when first received**
**Extent and nature of follow up should be driven by nature of the case and consideration of the value of learning more detail, tempered by insight into the likelihood of success at such attempts**
**Easy in theory; difficult in reality**

- Murray M. Lumpkin, M.D.

- 3/9/00

## Follow Up

**Resources (human, financial, and temporal) not unlimited**
**Need to focus responsibly on most important cases**
**Need to focus responsibly on most relevant data elements**
**Need to assure that reporter is not burdened with redundant or clearly unnecessary queries**

- Murray M. Lumpkin, M.D.

- 3/9/00

## Follow Up

**Other factors influencing f/u:**
**Source of the report**
**Most effective method of follow up (site visit, post, fax, email, telephone)**
**Medical confirmation of consumer reports**
**Local culture**
**“****Age” of the drug (beware serious, unexpected cases and new drug interactions)**

- Murray M. Lumpkin, M.D.

- 3/9/00

## Follow Up

**Fundamental Questions:**
**How to prioritise?**
**What data elements really needed and are they the same for all reports?**
**Do I need a narrative? **
**Do I need to assure something more serious not occurring?**
**When I don’t get information I need, when can I stop trying?**

- Murray M. Lumpkin, M.D.

- 3/9/00

## Follow Up: Proposal

**Criteria for Prioritisation**
**First: Serious/unexpected**
**Second: Serious/expected and non-serious/unexpected**
**Third: Non-serious/expected**
**Remember cases of “special interest” and cases that might lead to significant labeling changes (handled like First Priority)**

- Murray M. Lumpkin, M.D.

- 3/9/00

## Follow Up: Proposal

**Cases received from regulators**
**Need to establish who is going to do follow up**
**Usually company unless agreed otherwise**
**Special cases when reporter’s identity is not available**

- Murray M. Lumpkin, M.D.

- 3/9/00

## Follow Up: Proposal

**What specific information should be sought for the various types of cases?**
**Extent of detail driven by seriousness and expectedness**
**ICH-E2B extensive list of data elements that ideally would be obtained and archived for complete case documentation**
**Suggestion on sets of data elements**

- Murray M. Lumpkin, M.D.

- 3/9/00

## TRIAGE of sADRs: FOLLOW UP

- VALID
- CASE

- SEEK
- CLARIFICATION

- Non-Serious
- Expected

- Serious/Exp
- NS/Unexp

- Serious/Unexp
- Spec Interest

- NO

- YES

- LIST A

- LIST B

- LIST C

- Murray M. Lumpkin, M.D.

- 3/9/00

## Follow Up: Proposal

**LIST A  (report all E2B info you have but only follow up to get the following:) ****(Non-serious/expected****)**
**Country of occurrence (A.1.2)**
**Identifiable reporter  (A.2.1.1)**
**Source of report (A.2)**
**Identifiable patient (B.1.1 or B.1.2.) **
**Suspect drug/s (B.4.k.1 & B.4.k.2)**
**One or more sADR (B.2.i.2)**

- Murray M. Lumpkin, M.D.

- 3/9/00

## Follow Up: Proposal

**LIST B ****(report all E2B info you have but only follow up to get the following:)**** ****(Serious/expected & NS/unexpected)**
**List A Plus:**
**Daily dose of suspected drug and regimen**
**Route of administration**
**Indication(s) for which prescribed/used**
**Starting date/time of day of trtmnt**
**Full description of sADR incl body site and severity**
**Time of onset of sADR**

- Murray M. Lumpkin, M.D.

- 3/9/00

**LIST B (continued)**
**If not available, time interval between drug administration and start of sADR**
**If not available, treatment duration**
**Time lag if sADR occurred after cessation of treatment**
**Patient outcome  (at case level)**
**Information on recovery and any sequelae**
**Dechallenge information**
**Rechallenge information**
**Causal relationship assessment**
**Criterion/a for regarding case as serious,if so regarded**
**Other relevant etiologic factors**

- Murray M. Lumpkin, M.D.

- 3/9/00

## Follow Up: Proposal

**LIST C ****(report all E2B info you have but only follow up to get the following:)**** ****(Serious/Unexpected)                    (Drugs of “special interest”)**
**Lists A&B PLUS:**
**Stopping date and time or duration of treatment**
**For concomitant medications:**
**daily dose and regimen**
**Stopping date and time or duration of treatment**
**Special tests or treatment required and their results**

- Murray M. Lumpkin, M.D.

- 3/9/00

**LIST C (continued)**
**Setting**
**For a fatal outcome, cause of death and a comment of its possible relationship to the sADR**
**Any autopsy or other post-mortem findings**
**Whether or not the hospital discharge summary is available if patient hospitalised**
**Anything relevant to facilitate assessment of the case such as medical history, drug history, drug/ETOH abuse**
**Medical confirmation (if appropriate)**

- Murray M. Lumpkin, M.D.

- 3/9/00

## Follow Up: Proposal

**Good Follow Up Practices:**
**Follow up information should be obtained in writing (email OK)**
**Written confirmation of details supplied verbally should be obtained**
**Every effort should be made to follow up unexpected deaths or life-threatening sADRs within 24 hours of first knowledge of the event**

- Murray M. Lumpkin, M.D.

- 3/9/00

## Good Follow Up Practices(Contd.)- Proposal

**All attempts to obtain follow up information (whether or not successful) should be documented as part of the case file**
**Acknowledgement letters should be sent to suppliers of follow up information with relevant feed back**
**Follow up encounters should optimally occur just once- ****PLAN!**

- Murray M. Lumpkin, M.D.

- 3/9/00

## Good Follow Up Practices(Contd.)- Proposal

**When have I done enough if I get no response?**
**List A sADRs - ****one letter**
**List B sADRs - ****two letters after phone call**
**List C sADRs ****- two letters after site visit**
**Second letter should be sent no later than 4 weeks after first attempt fails to generate a satisfactory response**

- Murray M. Lumpkin, M.D.

- 3/9/00

## Good Follow Up Practices (Contd.) - Proposal

**How long should case be followed?**
**When case is serious or outcome still unknown (whether sADR is expected or unexpected) and the sADR has not resolved at the time of the initial report, it is important to continue to follow up until the outcome has been established or the condition is stabilised**

- Murray M. Lumpkin, M.D.

- 3/9/00

## CONCLUSIONS

**Can’t realistically get full follow up information on all reported cases**
**Prioritise into three “Lists” of data elements that one will attempt to get in follow up based on S/E**
**Need to know when to call it quits**
**Recommends timing and amount of effort usually adequate to deem a good faith effort at follow up**

- Murray M. Lumpkin, M.D.

- 3/9/00