The Seroquel documents

• Seroquel (quetiapine): AstraZeneca’s atypical antipsychotic

• Many issues raised in documents released through litigation process (Federal court in Florida)– Particularly relevant: Selective publication of

clinical trial data and perhaps misleading analyses appearing in journals/presentations

• Available at blog: http://industry.bnet.com/pharma/10001228/e-mail-astrazeneca-knew-in-1997-that-seroquel-caused-weight-gain/

Seroquel documents

• These slides are excerpts from the files, and illustrate issues suggestive of buried trials, data manipulation and possible obscuring of adverse drug event information.

• Thus they are selective excerpts.• To read in full context go to the relevant file

according to the code number.

Omnibus MSJ Exhbit 43 – declaration by expert witness, psychiatrist Dr WirshingAZ obscured weight gain & diabetes issues re Seroquel for years

Omnibus MSJ Exhibit 44 testimony of expert witness, pharmacologist Dr PlunkettAZ ‘s buried study 15: weight gain “rapid”, “consistent”, “significant”, “dose related”, “doesn’t stop”

Omnibus MSJ Exhibit 44 testimony of expert witness, pharmacologist Dr Plunkett“the sales messages contradicted what AstraZeneca knew to be true about...weight gain”

Omnibus MSJ Exhibit 44 testimony of expert witness, pharmacologist Dr Plunkett

AZ aware of Seroquel association with diabetes/hyperglycemia 1999

Omnibus MSJ Exhibit 44 testimony of expert witness, pharmacologist Dr PlunkettSeroquel package insert distorts risk of diabetes/hyperglycemia

Omnibus MSJ Exhibit 44 testimony of expert witness, pharmacologist Dr PlunkettDiscredited AZ sponsored study claimed Seroquel cured diabetes

Omnibus MSJ Exhibit 44 testimony of expert witness, pharmacologist Dr PlunkettAs late as 2007 Seroquel label understates risk of diabetes/hyperglycemia

Omnibus MSJ Exhibit 44 testimony of expert witness, pharmacologist Dr PlunkettFDA admonish AZ in 2006 but in Oct 2007 label still inadequate

Omnibus MSJ Exhibit 44 testimony of expert witness, pharmacologist Dr Plunkett“Diabetes” level blood sugar changes downplayed as “hyperglycemia”

04_exhibit_27 from email Aug 1997

04_exhibit_27 from email Aug 1997

Omnibus MSJ Exhibit 13 “positive spin” on “cursed” study 15

Omnibus MSJ Exhibit 14 emails re buried trials, managing data1st email 2 Dec 99 – EPS data (presumably favourable) for symposium

Omnibus MSJ Exhibit 14 emails re buried trials, managing data2nd email 6 Dec 99 - “can we present the EPS data in isolation given nature of other results”

Omnibus MSJ Exhibit 14 emails re buried trials, managing data3rd email 6 Dec 99 “we can be accused of ‘cherry picking’...may fuel demands to see entire study”

Omnibus MSJ Exhibit 14 emails re buried trials, managing data4th email 6 Dec 99 “a short-term solution (given impending APA deadline) is

avoid reference to COSTAR in proposed APA abstract”

Omnibus MSJ Exhibit 14 emails re buried trials, managing data5th email 6 Dec 99 – “thus far we have buried Trials 15, 31, 56 and now considering

COSTAR”“how do we face the world when they begin to criticize us for suppressing data”

Omnibus MSJ Exhibit 14 emails re buried trials, managing dataother emails in chain 7 Dec 99

Omnibus MSJ Exhibit 14 emails re buried trials, managing dataother emails in chain 7 Dec 99

Omnibus MSJExhibit 2 AstraZeneca’s Internal Efficacy Analysis March 2000

*Based on same four studies presented in prior slide*Finds advantages for Haldol, not Seroquel*no better than CPZ, worse efficacy than Risp and “other (un-named typicals”

Omnibus MSJ Exhibit 2

Omnibus MSJ Exhibit 14 emails re buried trials, managing data5th full email 8 Dec 99 “if (JAMA) thought we were publishing positive data...whilst results from a

second trial were being buried, they’d be onto it in a flash.”

Omnibus MSJ Exhibit 6 slides for KOL speaker,email says have been “tweaked”

Omnibus MSJ Exhibit 5 AZ marketing director deposition Apr 2008

Omnibus MSJ Exhibit 5 AZ marketing director deposition Apr 2008

Omnibus MSJ Exhibit 5 AZ marketing director deposition Apr 2008

Omnibus MSJ Exhibit 5

AZ marketing director

deposition Apr 2008

Omnibus MSJ Exhibit 5 AZ marketing director deposition Apr 2008

Omnibus MSJ Exhibit 9 statement of expert witness, epidemiologist Dr Arnott

Omnibus MSJ exhibit 9 statement of expert witness, epidemiologist Dr Arnott

43_exhibit_12 study 15 may have been buried but another study published in Int J Psychiatry in Clin Prac 2000

43_exhibit_12 study published in Int J Psychiatry in Clin Prac 2000

43_exhibit_15

“may be rationale...return to normal eating”

43_exhibit_15Despite the argument in these emails, Haldol and Risperidone comparison groups had more efficacious response in the studies but didn’t get the “normal eating”

weight gain to same extent as Seroquel group.

Omnibus MSJ Exhibit 32 weight & diabetes sell sheet Aug 2005

Omnibus MSJ Exhibit 32 weight & diabetes sell sheet Aug 2005the truth is in there but appears underemphasised in the overall wording

Omnibus MSJ Exhibit 34 FDA to AZ re false or misleading promotional material

Omnibus MSJ Exhibit 34 FDA to AZ re false or misleading promotional material

Seroquel docs 43_exhibit_10Int memo Dec 2007