Transparency in Clinical Trialsand its Impact on the

Intelligence Community

SLA, Boston

March 20, 2007

Mark R Little, PhDVice President, Business Intelligence

Covance, Inc

What’s Ahead Objective: to explore the impact of clinical trial

transparency initiatives on pharma competitive intelligence units Has it been useful for CI activities? If so, useful for what? How do new sources rate

– Amongst themselves?– Vs more traditional sources?– Vs primary sources?

What’s Ahead Introduction

A History Clinical Trials What is clinical trial intelligence What makes clinical trial intelligence predictive What impact might clinical trial intelligence have Case study Impact on First in class exclusivity

The Push toward Clinical Trial transparency Survey of Pharma CI units Conclusions

A Brief History of the Clinical Trial

The Present-Day Controlled Clinical Trial is a relatively new Tool for Drug Development

1747: James Lind – On Board the Salisbury

1962: Kefauver/ Harris Amendment

1980: First Issue of Controlled Clinical Trials

Pharma Companies Reveal Clinical Trial Studies in various formats

Clinical Trials predict the dose, patient population, efficacy endpoints and safety of future drug indications

Raz I, Hanefeld M, Xu L, Caria C, Williams-Herman D, Khatami H, for the Sitagliptin Study 023 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia 2006 Nov;49(11):2564-71. PMID: 17001471

Aschner P, Kipnes M, Lunceford J, Sanchez M, Mickel C, Williams-Herman D. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care 2006; 29:2632-2637. PMID: 17130196

A Multicenter, Double-Blind, Randomized, Placebo-Controlled Dose-Range Finding Study of Once-Daily Dosing of MK-0431 in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control

Charbonnel B, Karasik A, Liu J, Wu M, Meininger G. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled on metformin alone. Diabetes Care 2006;29:2638-2643. PMID: 17130197

PUBLISHED CLINICAL STUDIES DRUG LABEL

Clinical Trial Intelligence – Defined

Clinical Trial Intelligence: Actionable information and/or insights about the Design: patient population, study arms, # sites, endpoints Status: enrollment, efficacy trends, side effect (AE) trends Results of a clinical trial: statistical significance, AEs, clinical

profile

Clinical Trial Intelligence is a subset of Competitive Technical Intelligence (CTI)

Like all intelligence, clinical trial intelligence needs to be actionable

Clinical Trial Intelligence – in Context

Pharma CI Units have traditionally focused on competitor pipelines & near-market assets

CI units have leveraged a variety of sources to gain insights into competitor pipeline activities

One-stop shopping does not exist Different internal customers require different

analytical outputs and perpectives

Clinical Trial intelligence adds a layer of granularity to Pipeline Intelligence

Clinical Trial Intelligence – in Action

Clinical trial intelligence can make an important contribution to Pharma CI

Clinical trial intelligence needs to be actionable

Likely impactDirect licensing activitiesStir / accelerate fast-follower activitiesInfluence design of clinical trialsBuild counter marketing strategies

CASE REPORT

Pursuit of clinical trial intelligence extremely important – in this case – to licensing

Company A desires to fill void in key therapeutic area Using typical pipeline databases and industry trade press, Company A targets a

specific drug in Phase II testing at a smaller company Business Case for in-licensing established, and the compound target is of the

highest priority. CI unit charged with gathering clinical trial intelligence CI unit hires third party to attend upcoming conference, where target company is

presenting Clinical abstract is reassuring: compound has met efficacy / safety profile & POC However, in after-hour discussions, company reveals that due to issues in non-clinical

testing, compound is to be discontinued in favor of back-up

RESULTS: Licensing jets cooled

Post-script: neither target compound nor backup reached the market

1.8

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1995-98

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lass

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val

Source: DiMasi and Paquette, PharmacoEconomics 2004;22(Suppl 2):1-14

Market Exclusivity for First-in-Class has Declined: Mean Time to First Follow-on Approval

Can adoption of Competitive Intelligence units be partly to blame for diminishing exclusivity?

Market Exclusivity Vs Average SCIP membership: An interesting observation

0

1

2

3

4

5

6

7

8

9

1970s 1980-84 1985-89 1990-94 1995-98

Yea

rs

0

1000

2000

3000

4000

5000

6000

Avg

Mem

ber

s

Years SCIP, avg m'ship

Inverse relationship between Time of Market Exclusivity and Average SCIP Membership

However, “Data without perspective is still data, and not information” – Felix Gyi, Pharm D

The Push Toward Clinical Trial TransparencySafety concerns in two widely prescribed drug classes have fueled the drive to Transparency:

Safety issues involving the use of SSRI antidepressants in children (Jun04) Safety issues involving COX-II inhibitors (VIOXX withdrawal, Sep04)…and the Post-Vioxx Era begins

GSK announces clinical trial database Merck, Lilly follow and PhRMA launches voluntary clinical trial results database in Sep04

Initiatives in clinical trial transparency have made competitor pipelines more accessible, but to what end?

Effects of a Post- Vioxx Era

2006: Welcome to the AstraZeneca Clinical Trials web site: This web site provides clinical trial data, results and other information from or regarding AstraZeneca-sponsored clinical trials….In line with our Group Corporate Responsibility Policy on transparency, we are committed to open communication of information on AstraZeneca’s clinical trials.  We will provide details of new and ongoing clinical trials sponsored by AstraZeneca.  

June 2003: “As a disclosure of compound information is balanced by the business need to maintain competitive advantage, some compound information has not been disclosed at this time.”*

BEFORE

AFTER

*Source: Surfing the Pipeline: Comparing the coverage and content of drugs in development databases, June, 2003

Effects of a Post-Vioxx Era: All Aboard All of top 15 Biopharm Co's are posting active clinical trials online

93% on clinicaltrials.gov 60% centerwatch.com 33% on their own website

Trial results are being published by most on the PhRMA site, clinicalstudyresults.org

15 companies have posted 1300 trials GSK has dedicated 40 FTEs for summaries and its registry. On average 40 FTE's / per company are dedicated to clinical trial

transparency efforts; once backlog has been processed, 5-10 FTE's will be needed.

*Source: "State of the Clinical Trials Industry" Report, 2006

ClinicalTrials.gov appears to be the most widely used registry for industry posting

A Word about Clinicaltrials.gov

The Debut of ClinicalTrials.gov The debut of ClinicalTrials.gov (http://clinicaltrials.gov) took place on February

29, 2000. This service provides patients, family members, health care professionals, and members of the public easy access to information on clinical trials for a wide range of diseases and conditions.

ClinicalTrials.gov contained over 4,000 clinical studies sponsored primarily by the National Institutes of Health.

ClinicalTrials.gov grew out of 1997 legislation that required the Department of Health and Human Services, through the NIH, to broaden the public's access to information about clinical trials on a wide range of diseases by establishing a registry for both federally and privately funded trials "on drugs for serious or life-threatening diseases and conditions.“

Appears to be the registry of choice for clinical trial listing

R&D spend and trial listing* of a select Pharma cohort

Company R&D Spend (2005 $milliions)Recruiting

trialsPfizer Inc. $7,256GlaxoSmithKline Plc. $5,495Sanofi- Aventis $4,949Novartis $4,372Roche $4,001Merck & Co. $3,848AstraZeneca Plc. $3,314Eli Lilly and Co. $2,940Wyeth $2,722Bristol- Myers Squibb Co. $2,513Amgen Inc. $2,302Schering- Plough Corp. $1,762Boehringer Ingelheim GmbH $1,544Takeda Chemical Industries Ltd. $1,507Daiichi- Sankyo $1,340Astellas $1,291Abbott Laboratories $1,140Schering AG $1,019

Selected companies ranked by health-care R&D expenditure

*Source: ClinicalTrials.gov

3113502463551601431942091741939062692224376723

Ranking Companies by Trials per R&D $ Spent

Company R&D Spend (2005 $milliions)Recruiting

trialsTrialsX100

/ $$4,372 355 8.12$2,513 193 7.68$2,940 209 7.11$2,722 174 6.39$5,495 350 6.37$1,140 67 5.88$3,314 194 5.85$4,949 246 4.97$1,544 69 4.47$7,256 311 4.29$4,001 160 4.00$2,302 90 3.91$3,848 143 3.72$1,762 62 3.52$1,291 37 2.87$1,019 23 2.26$1,340 24 1.79$1,507 22 1.46

Selected companies ranked by trials / $ index

Novartis Bristol-Myers Squibb Co.Eli Lilly and Co.WyethGlaxoSmithKline Plc.Abbott LaboratoriesAstraZeneca Plc.Sanofi-AventisBoehringer Ingelheim GmbHPfizer Inc.RocheAmgen Inc.Merck & Co.Schering-Plough Corp.AstellasSchering AGDaiichi-Sankyo Takeda Chemical Industries Ltd.

CBI’s 3rd Annual

Predictive Intelligence

For Pharmaceutical and Biotech Companies

January 22-23, 2007

A SURVEY OF CI PROFESSIONALS

Survey Method

Survey Tool: Zoomerang Participants: CI network across Biopharma companies

Invited: ~35 Completed Responses: N= 15

Objective: Assess the value of clinical trial transparency as a bolt-on tool for the competitive intelligence professional

Survey to assess value of CT Transparency as a tool for the CI Professonal

How important is CT Intelligence to your work?

13/15 Respondents described CT Intelligence as Important or Extremely Important

Extremely Unimportant 2Unimportant 0Important 3Extremely Important 10

15

How important is Clinical Trial Intelligence to your current work?

Total

Extremely Important

Important

Unimportant 1 5 10

10

3

2

0

Extremely Unimportant

Respondent breakdown according to company revenue

Large, medium and small biopharma companies represented

<$1B 4>$1B, but <$5B 4>$5B, but < $10B 1>$10B 6

15

Please place your company into one of the four revenue segments listed below.

Total

> $10Billion

< $1Billion

>$5B, but <$10B 1 5 10

6

4

4

1

> $1B, but <$5B

How often is CT Intelligence incorporated into your output?

As might be expected, clinical trial intelligence is frequently used in reporting

Once per week or more often 9Two or three times per month 2Once a month 3Once every few months 0Annually 1Less than once per year 0Never 0

15

2. How often do you or your associates research and incorporate clinical trial intelligence into your CI or BI reports?

Total

How is the CT Intelligence used?

Product Positioning and Trial Design were most often selected uses

Identifying licensing opportunities 3Influencing clinical trial design 7Setting clinical trial expectations (time to recruit,etc) 4Competitor product positioning 8Identifying low-cost geographies 0General competitor benchmarking 4Product life-cycle management 6Other, please specify 1

What are the best uses of clinical trial intelligence? Pick two.

Who is the internal customer?

The Internal Customer tended to Map to Medical/ Marketing Departments

“Other”: New Product Planning, Corporate Strategy, Various

Marketing / Medical Affairs 7Clinical Development 4Regulatory Affairs 0Regional Offices 0Licensing 1Other, please specify 3

15

6. Which internal customer has the highest demand for clinical trial intelligence?

Total

Has Clinical transparency helped you in your job?

Strongly disagree 0Disagree 3Agree 11Strongly agree 1

15Total

Please indicate your agreement level with the following statement: The push toward clinical trial transparency has significantly impacted my ability to do competitor intelligence.

The ‘Transparency’ push has helped the CI community…….

Agree

Disagree

Stongly Agree

Stongly Disagree1 5 10

11

3

1

0

What improvements are needed?

Better structured and searchable 5Known to be kept up-to-date 6More comprehensive, all active clinical trials 10Other, please specify 0

The data emerging from the push to clinical trial transparency would be significantly improved if it were....

…..but more postings are needed to significantly improve the registries.

More comprehensive

Up-to-date

Structure/Searchable

Other 1 5 10

10

6

5

0

What is the level of satisfaction with external sources?

In general, External Sources only partially satisfy demand

Very satisfied 0Somewhat satisfied 13Somewhat dissatisfied 2Very dissatisfied 0

15

How satisfied are you with the external sources used to track industry clinical trials?

Total

Somewhat satisfied

Somewhat dissatisfied

Very satisfied

Very dissatisfied 1 5 10

13

2

0

0

How effective are some common sources?

Top number is the count of respondents selecting the option. Bottom % is percent of the total

Not effective at all 2 3 4 Neutral 6 7 8 9 Highly effective

0 0 1 0 2 2 3 3 3 1

1 1 1 1 4 2 4 1 0 0

0 0 0 0 0 1 2 4 3 3

1 0 1 3 2 4 3 0 1 0

0 0 0 1 2 1 4 5 2 0

0 0 1 0 0 0 1 9 3 1

0 0 0 1 1 0 2 6 4 1

0 1 2 1 1 2 5 2 1 0

0 0 0 1 1 1 0 5 4 3

Conferences

Trade Press

Primary research (contracted CI firm)

Trialtrove (Citeline)*

Centerwatch.com

Commerical pipeline databases (IDdb, R&D Focus, etc)

Internal Networks

How effective are the following tools / sources for accessing clinical trial intelligence

Clinicaltrials.gov

PhRMA site (clinicalstudyresults.org)

*For Trialtrove, N=13; all others N=15.

Sources: Force Ranked …..

Effectiveness is most effectively linked to contracted primary research

TOTAL

Primary research (contracted CI firm ) 0 0 0 1 1 1 0 5 4 3 121

Internal Networks 0 0 1 0 0 0 1 9 3 1 119

Conferences 0 0 0 1 1 0 2 6 4 1 117

Trialtrove (Citeline)* 0 0 0 0 0 1 2 4 3 3 109

Clinicaltrials.gov 0 0 1 0 2 2 3 3 3 1 107

Commerical pipeline databases (IDdb, R&D Focus, etc)

0 0 0 1 2 1 4 5 2 0106

Trade Press 0 1 2 1 1 2 5 2 1 0 89

Centerwatch.com 1 0 1 3 2 4 3 0 1 0 80

PhRMA site (clinicals tudyresults .org) 1 1 1 1 4 2 4 1 0 0 78

SOURCE

*For Trialtrove, N=13; all others N=15.

Categorization of the forced rank….

Interestingly, Effectiveness is linked to Humint activities using internal networks, contracted vendors, and conference coverage

TOTAL

Primary research (contracted CI firm ) 0 0 0 1 1 1 0 5 4 3 121

Internal Networks 0 0 1 0 0 0 1 9 3 1 119

Conferences 0 0 0 1 1 0 2 6 4 1 117

Trialtrove (Citeline)* 0 0 0 0 0 1 2 4 3 3 109

Clinicaltrials.gov 0 0 1 0 2 2 3 3 3 1 107

Commerical pipeline databases (IDdb, R&D Focus, etc)

0 0 0 1 2 1 4 5 2 0106

Trade Press 0 1 2 1 1 2 5 2 1 0 89

Centerwatch.com 1 0 1 3 2 4 3 0 1 0 80

PhRMA site (clinicals tudyresults .org) 1 1 1 1 4 2 4 1 0 0 78

SOURCE

Human Intelligence

Secondary Sources

*For Trialtrove, N=13; all others N=15.

….Or are we simply viewing the Intelligence Pyramid in action….

TOTAL

Primary research (contracted CI firm ) 0 0 0 1 1 1 0 5 4 3 121

Internal Networks 0 0 1 0 0 0 1 9 3 1 119

Conferences 0 0 0 1 1 0 2 6 4 1 117

Trialtrove (Citeline)* 0 0 0 0 0 1 2 4 3 3 109

Clinicaltrials.gov 0 0 1 0 2 2 3 3 3 1 107

Commerical pipeline databases (IDdb, R&D Focus, etc)

0 0 0 1 2 1 4 5 2 0106

Trade Press 0 1 2 1 1 2 5 2 1 0 89

Centerwatch.com 1 0 1 3 2 4 3 0 1 0 80

PhRMA site (clinicals tudyresults .org) 1 1 1 1 4 2 4 1 0 0 78

SOURCE

*For Trialtrove, N=13; all others N=15.

DATA

Information

Intelligence

CONCLUSIONS Key Findings following 30 months of transparency

initiatives 12 of 15 respondents agree that transparency has had a

significant impact on their CI activities– 12/13 who consider clinical trial intelligence important to their work,

agree to the above 13/15 respondents are somewhat satisfied with all external

sources 8/15 and 7/15 respondents selected “competitor product

positioning” and “influencing clinical trial design”, resp, as a key action taken from clinical trial intelligence

Human intelligence sources rate slightly more effective than secondary sources – indicative of analysis and action (moving up the pyramid)

CONCLUSIONS: Final Thoughts•Intellectual Property

•Product Profile

•Clinical design

•Competitive Advantage

•Legal / Regulatory

•Public Safety & Trust

•Business Ethics

April – 2nd Annual Premier Forum on Clinical Trial Registries and Results Databaseshttp://www.cbinet.com/show_conference.cfm?confCode=HB735

Protect Provide

ACKNOWLEDGEMENTS

Jamie Denison-Pender, CIS

Scott Taylor, BMS

Debra Weintraub, MedImmune

Tracy Degregorio, Citeline, Inc

Jan Herring, Herring & Associates

Joe Bedford, Covance

N= 15