Transparency in Clinical Trials and its Impact on the Intelligence Community

1
Transparency in Clinical Trialsand its Impact on
the Intelligence Community
Mark R Little, PhD Vice President, Business
Intelligence Covance, Inc

• SLA, Boston
• March 20, 2007

2
Whats 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?

3
Whats 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

4
A Brief History of the Clinical Trial
1747 James Lind On Board the Salisbury
1980 First Issue of Controlled Clinical Trials
1962 Kefauver/ Harris Amendment
The Present-Day Controlled Clinical Trial is a
relatively new Tool for Drug Development
5
Pharma Companies Reveal Clinical Trial Studies in
various formats
DRUG LABEL
PUBLISHED CLINICAL STUDIES
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 Nov49(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
292632-2637. 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 2006292638-2643. PMID 17130197
Clinical Trials predict the dose, patient
population, efficacy endpoints and safety of
future drug indications
6
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
7
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
8
Clinical Trial Intelligence in Action

• Clinical trial intelligence needs to be
  actionable
• Likely impact
• Direct licensing activities
• Stir / accelerate fast-follower activities
• Influence design of clinical trials
• Build counter marketing strategies

Clinical trial intelligence can make an important
contribution to Pharma CI
9
CASE REPORT

• 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

Pursuit of clinical trial intelligence extremely
important in this case to licensing
10
Market Exclusivity for First-in-Class has
Declined Mean Time to First Follow-on Approval
Source DiMasi and Paquette, PharmacoEconomics
200422(Suppl 2)1-14
Can adoption of Competitive Intelligence units be
partly to blame for diminishing exclusivity?
11
Market Exclusivity Vs Average SCIP membership
An interesting observation
Inverse relationship between Time of Market
Exclusivity and Average SCIP Membership
12
The Push Toward Clinical Trial Transparency

• Safety 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

However, Data without perspective is still data,
and not information Felix Gyi, Pharm D
13
Effects of a Post- Vioxx Era
BEFORE

• 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.

AFTER

• 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
  AstraZenecas clinical trials.  We will provide
  details of new and ongoing clinical trials
  sponsored by AstraZeneca.  

Source Surfing the Pipeline Comparing the
coverage and content of drugs in development
databases, June, 2003
Initiatives in clinical trial transparency have
made competitor pipelines more accessible, but to
what end?
14
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
15
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

16
RD spend and trial listing of a select Pharma
cohort
311 350 246 355 160 143 194 209 174 193
90 62 69 22 24 37 67 23
Source ClinicalTrials.gov
17
Ranking Companies by Trials per RD Spent
Novartis Bristol-Myers Squibb Co. Eli Lilly
and Co. Wyeth GlaxoSmithKline Plc. Abbott
Laboratories AstraZeneca Plc. Sanofi-Aventis Bo
ehringer Ingelheim GmbH Pfizer
Inc. Roche Amgen Inc. Merck
Co. Schering-Plough Corp. Astellas Schering
AG Daiichi-Sankyo Takeda Chemical Industries
Ltd.
18
A SURVEY OF CI PROFESSIONALS

• CBIs 3rd Annual
• Predictive Intelligence
• For Pharmaceutical and Biotech Companies
• January 22-23, 2007

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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
20
How important is CT Intelligence to your work?
Extremely Important
10
Important
3
Extremely Unimportant
2
Unimportant
0
13/15 Respondents described CT Intelligence as
Important or Extremely Important
21
Respondent breakdown according to company revenue

gt 10Billion
6
lt 1Billion
4
4
gt 1B, but lt5B
gt5B, but lt10B
1
Large, medium and small biopharma companies
represented
22
How often is CT Intelligence incorporated into
your output?
As might be expected, clinical trial intelligence
is frequently used in reporting
23
How is the CT Intelligence used?
Product Positioning and Trial Design were most
often selected uses
24
Who is the internal customer?
Other New Product Planning, Corporate
Strategy, Various
The Internal Customer tended to Map to Medical/
Marketing Departments
25
Has Clinical transparency helped you in your job?
Agree
11
Disagree
3
Stongly Agree
1
Stongly Disagree
0
The Transparency push has helped the CI
community.
26
What improvements are needed?
More comprehensive
10
Up-to-date
6
Structure/Searchable
5
Other
0
..but more postings are needed to significantly
improve the registries.
27
What is the level of satisfaction with external
sources?
Somewhat satisfied
13
Somewhat dissatisfied
2
Very satisfied
0
Very dissatisfied
0
In general, External Sources only partially
satisfy demand
28
How effective are some common sources?
For Trialtrove, N13 all others N15.
29
Sources Force Ranked ..
For Trialtrove, N13 all others N15.
Effectiveness is most effectively linked to
contracted primary research
30
Categorization of the forced rank.
Human Intelligence
Secondary Sources
For Trialtrove, N13 all others N15.
Interestingly, Effectiveness is linked to Humint
activities using internal networks, contracted
vendors, and conference coverage
31
.Or are we simply viewing the Intelligence
Pyramid in action.
For Trialtrove, N13 all others N15.
32
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)

33
CONCLUSIONS Final Thoughts

• Intellectual Property
• Product Profile
• Clinical design
• Competitive Advantage

• Legal / Regulatory
• Public Safety Trust
• Business Ethics

Protect
Provide
April 2nd Annual Premier Forum on Clinical
Trial Registries and Results Databases http//www.
cbinet.com/show_conference.cfm?confCodeHB735
34
ACKNOWLEDGEMENTS
Jamie Denison-Pender, CIS Scott Taylor, BMS Debra
Weintraub, MedImmune Tracy Degregorio, Citeline,
Inc Jan Herring, Herring Associates Joe
Bedford, Covance N 15