Session IISafe PCI For Women

David R Rutledge, Pharm.D., FCCP, FAHADirector, Worldwide Clinical Research

Device Industry View

Which Ultimately Determines a Which Ultimately Determines a Medical Device Company’s Success?Medical Device Company’s Success?

a) Protocol and ICF Sign-Offs

b) SAP and mock table Sign-Offs

c) EDC Build with Edit Checks

d) Achieving FPI goal

e) LPI/LPV goals ahead of timeline

f) Database Lock ahead of timeline

g) IFU Updates

h) Timely, Valid and Positive Data

i) NEJM, JAMA, and LANCET Articles

j) Final Report

k) Large data sets with tens of thousands of patients

2TREAT IVTransradial WorkshopFourth Thinktank at FDA Headquarters

2013 Abbott Vascular29JUL13

TREATExperience with a Large Public Databases

• Tiptoe into a public database

–Anonymized patient data back to the patient’s source documents

• New way of thinking shifting our thinking about a Sponsor’s commitment to “Innovation”

–Designing trial then building the database

–Accessing the database then designing the trial

TREAT IVTransradial WorkshopFourth Thinktank at FDA Headquarters

32013 Abbott Vascular29JUL13

Medical Device CompaniesMedical Device Companies

42013 Abbott Vascular29JUL13

TREAT IVTransradial WorkshopFourth Thinktank at FDA Headquarters

Issues For Further Issues For Further Discussion TodayDiscussion Today

Tipping Point For InvestmentTipping Point For Investment

Venture Capitalist “You bet on the Jockey not the Horse”

Determine the “Tipping Point” between what Device companies can get from a public database and a Sponsor’s willingness to invest

TREAT IVTransradial WorkshopFourth Thinktank at FDA Headquarters

52013 Abbott Vascular29JUL13

OverlapOverlap ImportantImportantOurs not TheirsOurs not Theirs

Not ImportantNot ImportantTheirs not OursTheirs not Ours

SurveillanceSurveillance 60% ??% ??%

Label Label ExpansionExpansion

30% ??% ??%

ApprovalApproval 10% ??% ??%

What’s our value proposition?

6

Ability to Tweak a Public DatabaseAbility to Tweak a Public Database

• On Demand (Response from Regulator or IRB/EC)

– Product specific entry, e.g., expiration date, times

– Clarify a safety field

– Change in a clinical definition

– Concomitant drug therapies

• Early On During Enrollment

– Inclusion/Exclusion criteria

– Device line extensions/updates become available

– Newer accessories become available

– Scientific data become available during the trial, e.g., company or competitor, safety or efficacy

TREAT IVTransradial WorkshopFourth Thinktank at FDA Headquarters

2013 Abbott Vascular29JUL13

Initial EDC Build versus Amendment Releases*** Simulation = Set Targets and Negotiate ***

7

  

Activity

Fully Executed (10

wks.)Amendments

Executed (3 wks.)Requirements = Determine the requirements from the protocols $ 5,000 $2,000Specifications = Data Management (translate from protocol to eCRF spec) $ 50,000 $ 30,000 EDC Programming(Implementation of change into database) $ 50,000 $ 20,000 Validation (Outsourced) $ 50,000 $ 30,000 UAT (User Acceptance Testing) $ 15,000 $ 5,000Integration Programming* Safety Database (EDC-Commercial)* IVRS* Inventory* Payments $ 50,000 $ 15,000 Release $ 15,000 $ 5,000

TOTAL $230,000 $107,000TREAT IVTransradial WorkshopFourth Thinktank at FDA Headquarters

2013 Abbott Vascular29JUL13

Is There an Appetite to Waive Portions of GCP ICH-E6 5.5.3a-g?

5.5.3 When using electronic trial data handling and/or remote electronic trial data systems, the sponsor should:

(a) Ensure and document that the electronic data processing system(s) conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistent intended performance (i.e. validation).

(b) Maintains SOPs for using these systems.

(c) Ensure that the systems are designed to permit data changes in such a way that the data changes are documented and that there is no deletion of entered data (i.e. maintain an audit trail, data trail, edit trail).

(d) Maintain a security system that prevents unauthorized access.

(e) Maintain a list of the individuals who are authorized to make data changes (see 4.1.5 and 4.9.3).

(f) Maintain adequate backup of the data.

(g) Safeguard the blinding, if any (e.g. maintain the blinding during data entry and processing).

82013 Abbott Vascular29JUL13

TREAT IVTransradial WorkshopFourth Thinktank at FDA Headquarters

Medical Device Approval TrialsMedical Device Approval Trials

Medical Device companies prefer to focus on“Out of Control Group”

TREAT IVTransradial WorkshopFourth Thinktank at FDA Headquarters

92013 Abbott Vascular29JUL13

Value of Large Public Databases

Construct PerformanceGoals or ObjectivePerformance Criteriafor smaller, single-arm studies

Issues For Further DiscussionIssues For Further Discussion• Standard Definitions

Once you go beyond one database, there are no standard definitions for data elements, e.g., sex/gender/gender at birth, MI, Race/Cultural Origin, Renal Failure/SrCr, Date of Birth/Day of Birth

• Research CommunityBy the time the DB gets large and robust, the research community has gone forward, e.g., “Practice lags behind research.”

• PARTNERSHIPWhat does “partnership” mean? Strategic Partnerships? What is the legal framework?

TREAT IVTransradial WorkshopFourth Thinktank at FDA Headquarters

102013 Abbott Vascular29JUL13

Audit Readiness?Audit Readiness?

TREAT IVTransradial WorkshopFourth Thinktank at FDA Headquarters

112013 Abbott Vascular29JUL13

No clear ownership and accountability of databaseNo clear ownership and accountability of database

Issues For Further DiscussionIssues For Further Discussion(cont.)(cont.)

• How do we improve site relationships/management?

–Sites get upset too

–They are busy

• Are screening failures more easily accessible?

• Is this a real aid to site selection?

–Experience and expertise of the interventionalist

–PI resources to conduct study

–Cross discipline expertise for the interventionalist

• Is this a real aid to patient selection?

122013 Abbott Vascular29JUL13

TREAT IVTransradial WorkshopFourth Thinktank at FDA Headquarters

13

Benefits vs. Risks: Public DatabaseBenefits vs. Risks: Public Database

Risks to Medical Device Companies

Ben

efit

s to

Co

mp

anie

s

High

Moderate

Low

Low

HighModerate

+++

++++ +++

-------

---++/--

++/-

+/--

Can FDA, public databases, and medical device companiesCan FDA, public databases, and medical device companiesmitigate factors for cost-effective IDE approvals?mitigate factors for cost-effective IDE approvals?

TREAT IVTransradial WorkshopFourth Thinktank at FDA Headquarters

2013 Abbott Vascular29JUL13