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
2.8
5.1
5.9
8.2
0 9Years
1995-98
1990-94
1985-89
1980-84
1970s
Per
iod
of
Fir
st-i
n-C
lass
Ap
pro
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
Top Related