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CT:
Progress and Plans
Andrew J. Buckler, MS
Principal, Buckler Biomedical
LLC
Background: Anecdotal
Evidence
-30% Δ
from BL =
RECIST
threshold
for PR
Progressive
Disease
RECIST: Sum of LD
Disease
4cm lesion Unaided 1D
Stable
Interpretation
Response
Partial
∆ t
Response
Time Complete
Progressive
Disease
RECIST: Sum of LD
Disease
4cm lesion
Stable
Aided 3D
Interpretation
Response
Partial
Shorter ∆ t
Response
Time Complete
Early Detection
& Nodule Sizing ?
May 2010 Buckler Biomedical LLC 4
Key Questions that Need
Answers
What is the potential to
decrease time needed on
trial (or enable more
adaptive designs)?
Description o f Issu e
Des crib e the nature of the iss ue(s )
Sig nificance
Is this Challenge really an iss ue?
Ra te (and explain if you lik e) How m uch
im pact this is s ue will have on prac tic al
Sourceof Processing& V a ria tio n in dos e, injection effectivenes s, tim ing… infus ion protoc ols ) HIG H
SENSOR Decision P ha rm a ce u tica l / s td volum e vs volum e per unit body m as s for lesions near c ertain structures ,
V a ria tio n in P a tie nt /(e.g., biology , tem perature, wak efulnes s, m otion, res piration… ) LO W -M E D
Bio ch e m istry infrequent fac tor and m os tly affects
Large patient weight chan ge could affect atten uation/s catter noise?
Transmission Cardiac output will affect c ontras t c irculation
Medium V a ria tio n in P a tie nt Different staff, different s ites prepare and pos ition the patient diffe rently
Ha n dling P roto col Lung tum or volum e m ight vary with res piration
M E. D-HIG H
im portant but reas ona bly eas y to c ontrol
(patien t positioning)
Anatomical Les ion loc ation in FO V m ay vary
Region Data Joint V a ria tio n d ue to (e.g., atte nuation, phys ic al im aging proc es s… P E T colinearity reduces
LO W
Specific M od a lity P h ysics res olution but not s pa tial integrity)
V a ria tio n in S ca nn e rS patial S am pling (e.g., finite s ys tem P S F , detector c hara cteristic s, table
HIG H
De sign s des ign … ) # detector rows are a big is sue relating to
Different # of rows c an affect s peed of volum e c overage single breathhold span
Les s than 4 s lic e results in breathing artifac ts 10-20% varianc es
S c atter, differenc es in energy
Different vendo rs use different s ys
V a ria tio n in Ind ividu aMl anufac turing variation, aging, P M , etc LO W
Inconsistency of measurements
S ca n ne rs Pretty stab le/c onsis tent and ea sily
calibrated for
Sourceof Processing& V a ria tio n in CT Low k V c an inc reas e noise to the point that nodule boundaries becom HIGeH
SENSOR Decision
Acqu isition P ro toco l unc lea r… (m ay relate to whether quant is vis ual/m anual or autom aticm) any attributes im pac t the results
Collim ation used during ac quis ition affec ts the fund amental res olution
REVIEW PROCESS
reviews to all Offices
13) BQ Project Manager schedules the BQ review for
presentation at a CDER Regulatory Briefing.
14) CDER Regulatory Briefing presentation and
discussion is held.
15) CDER Office Directors make decisions to accept or
reject the BQRT recommendations.
H) Promote use of the imaging biomarker Signoff 16) BQC drafts letter for sign-off by the Director of
through education. Letter CDER communicating to the sponsor the results of the
biomarker qualification.
Thanks Andy, we (Pfizer) agree with the position from Dave Mozely and would
support the letter. -Tim.
Dear Andy, I am totally in support of sending this Request Letter to the Agency.
Also I see no reason why there would be any objection to the Request Letter
from Novartis. As I mentioned before, I am working on getting a firmer
commitment from Senior Management. Best regards, Haren
Hi Andy, Definiens is very eager to support, both the request letter but
especially some of the tasks of the project plan. More concrete, we feel
in the postion to support the following tasks: 11, 12, 13, 14, 15, 24, 25,
26, 27, 36
Dr. Maria Athelogou will be the principal representative of Definiens in
this regard.
Best, Frank
May 2010 Buckler Biomedical LLC 17
Short Term Action Plan
Complete Consultative Phase leading to Scope Confiden Other group Overlap Ower/ Target Action/Comm
Qualification of VIA with chest CT for Lung of Work ce of alredy doing of worh Driver date/Stat ents
Cancer Clinical Trials Achiving it other us
group
Compose letter and review Low High 0% Paul Q2-10
Send letter
Follow-up through BQRT meeting Medium High 40% Paul
A Assemble Declaratory information High Low UPICT, CTN 30% Andy Q4-10
Write Clinical Context section in Briefing Document
Write literature review sections in Briefing Document
Write QIBA process section in Briefing Document
B <phantom task 1> Low High 0% Paul Q2-10
…
<phantom task n, e.g., write section in Briefing Medium High 40% Paul
Document>
C <Profile task 1, e.g., UPICT consensus protocol> Low
… (e.g., create non-protocol portions of Profile) Low
… (e.g., add QIBA subcommittee findings)
<Profile task n, e.g., write section in Briefing High High 100%
Document>
D <process map task 1, e.g., determine what steps are Medium Low 60%
needed>
…
<process map task n, e.g., write section in Briefing Low Med 40%
Document>
E <clinical performance task 1, e.g., summary of what's Medium Low 60%
ongoing>
… (e.g., compile performance evaluation figures of
merit)
<clinical performance task n> Low Med 40%
Write Results section of Briefing Document Medium Low 60%
Write Completing the Full Data Package section
Review Briefing Document
Send to agency
Participate in BQRT
Iterate with BQRT Low Med 40%