ACRIN Accelerated Accrual Demonstration Project:
Univ. of Southern California and MD Anderson Collaboration
Proposal for facilitating protocol development
and site pre-activation
Suzanne L. Palmer, M.D.
Tammie Possemato
2011 ACRIN Annual Meeting
Chaan Ng, M.D.
Sujaya Rao
Michelle Haynes
#2
pre-activation
phase
#1 Site
Protocol
development
phase
2011 ACRIN Annual Meeting
#1 Protocol development phase
STUDY SUMMARY FOR SITE ASSESSMENT SURVEY
•
Brief Study Summary
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–
–
–
Schema
Study objectives and end points
Patient eligibility and enrollment
Associated therapy or tissue biomarker
studies
– Imaging and equipment requirements
– Minimum imaging requirements
– Timeline for required imaging
– Information needed for the sites to evaluate
recruitment potential
– Clinical services involved
– Study schedule
– Reimbursement
ACRIN Study #:
ACRIN Study Name:


Study Contact Information
ACRIN Principal Investigator:
ACRIN Project Manager:

ACRIN schema:

Study objectives and end points:

Patient eligibility:

Basic protocol:

Enrollment:

Is this study being conducted in conjunction with a with a therapy or tissue biomarker study?
SELECT
If yes, enter name and number of the study:

Minimum imaging requirements: hardware, software and required inclusion studies
Pick a Modality

Pick a Modality

Timeline of required imaging:
INFORMATION FOR SITE RECRUITMENT ANALYSIS
Clinical services involved:
Choose service:
If other:
Basic Responsibilities:

Choose service:
If other:
Basic Responsibilities:
Ancillary services required
Laboratory/pathology component:
Study procedures/requirements:
Other requirements:
Reimbursement:
Will the cost of the studies required in the protocol be reimbursed by ACRIN?
2011 ACRIN Annual Meeting



SELECT

#2 Site pre-activation phase
STUDY SUMMARY AND SITE ASSESSMENT SURVEY
ACRIN Study #: 6690
ACRIN Study Name: Comparison of multiphase contrast-enhanced CT and MRI for diagnosis of HCC and
liver transplant allocation
Study Contact Information
ACRIN Principal Investigator: Christoph Wald, MD, Ph.D, 781-744-8170, christoph.wald@lahey
ACRIN Project Manager: Donna Hartfeil, 215 717-2765, dhartfeil@acr.org
Individual site assessment
•
•



Site Number:
Site Principal Investigator:
Site Research Associate (RA):
–
–
ACRIN Schema:
HCC diagnosis by baseline CT or
MRI
(SOC imaging at participating center)
–
Listing for liver transplantation with HCC-exception points and
enrolled in study
Local ablative
therapy
Complement imaging within 30 days of initial imaging
(SOC and complement CT and MRI imaging to be
performed)
Repeat serial imaging every 90 days
(CT and MRI)
Performed by RA and/or PI
Step-by-step
Imaging
(SOC + complement imaging,
no less than 28 days and no
more than 60 days after
completion of ablation)
Transplant
surgery
Explant pathology
analysis
Study objectives and end points:
The main objective of the ACRIN 6690 trial is to compare modern multiphase contrast-enhanced
CT and MRI with pathologic liver findings to establish the performance characteristics of these
imaging modalities to accurately detect, diagnose, and stage HCC in patients with chronic liver
disease. The CT and MRI examinations acquired within 90 days of transplantation will be
compared with the explant pathology findings.
The primary analysis will compare CT to MRI results at the lesion level using core laboratory
interpretations of the imaging studies; secondary analysis will be performed at the patient level.
Patient eligibility:
Patients diagnosed with HCC and listed for liver transplant surgery with priority MELD (Model for
End-Stage Liver Disease) points based on their cancer diagnosis will participate.
Eligible patients include those who may be waiting for a liver to become available from a deceased
donor or be scheduled to undergo a living donor adult liver transplant.
2011 ACRIN Annual Meeting
•
Review of the brief study summary
Assess study requirements and match to
site’s resources
Estimate patient recruitments
The Mock Screen
– Identify radiology department personnel
and conferences
– Identify referring clinicians and
coordinators
– Identify tumor boards and other sources of
patient recruitment
• If the site assessment is successful, the
activation and recruitment phases should
go more rapidly.
#2 Site pre-activation phase
Patient eligibility:
Patients diagnosed with HCC and listed for liver transplant surgery with priority MELD (Model for
End-Stage Liver Disease) points based on their cancer diagnosis will participate.
Eligible patients include those who may be waiting for a liver to become available from a deceased
donor or be scheduled to undergo a living donor adult liver transplant.
Patients must enroll in the trial within 30 days after initial listing with HCC-exception points to the
United Network for Organ Sharing (UNOS) waitlist.
Are the eligibility criteria realistic? Select
If no, please explain:
Individual site assessment
•
•

–
–
Basic protocol:
Each site will image a participant with CT or MRI approximately every 90 days (or earlier) per the
OPTN/UNOS HCC-exception point update requirements for their region. This imaging to evaluate
disease is considered standard of care.
This research trial requires that complement imaging (CT or MRI, whichever imaging was not done
as the standard of care) be completed at each 90-day interval. This imaging must be completed
within 7 days of the standard-of-care imaging for that time interval.
The goal is to compare the CT and MRI examinations acquired within 90 days of transplantation
with explant pathology findings.
Should a participant undergo local ablative therapy, CT and MRI should be completed no less than
28 days and no more than 60 days after each completed ablative therapy scheme.
Enrollment:
A total of 440 participants will be accrued to the ACRIN 6690 trial. Number per site was not
included in available protocol
Is this study being conducted in conjunction with a with a therapy or tissue biomarker study? No
Are there any current or pending competing clinical trials at your institution that target the same
patient population? SELECT

If yes, enter name and number of the competing clinical trial(s):
Is the patient population adequate to support this study AND the competing trial(s)? SELECT 
If No, please explain
2011 ACRIN Annual Meeting
Performed by RA and/or PI
Step-by-step
–
•
Review of the brief study summary
Assess study requirements and match to
site’s resources
Estimate patient recruitments
The Mock Screen
– Identify radiology department personnel
and conferences
– Identify referring clinicians and
coordinators
– Identify tumor boards and other sources of
patient recruitment
• If the site assessment is successful, the
activation and recruitment phases should
go more rapidly.
#2 Site pre-activation phase
Individual site assessment
IMAGING AND EQUIPMENT REQUIREMENTS
Minimum imaging requirements: hardware, software and required inclusion studies:
Computed Tomography
 Multi-detector, using a scanner with a minimum of 8 detector rows
 Power injector
 4 phase imaging
•
•
Magnetic Resonance Imaging
 1.5T or greater, phase array torso coil, current generation high speed gradients
 Dual chamber power injector
 For contrast-enhanced scanning, standard extracellular gadolinium chelates that do not have
dominant hepatobiliary excretion (No Eovist)
 Scanning protocol should be per institutional standards, but should include at a minimum:
o Pre-contrast and dynamic post-extracellular-gadolinium T1-weighted (T1W) gradient echo
sequence (3D preferable)
o T2 (with and without FAT SAT)
o T1W in and out of phase imaging
Are the inclusion imaging studies feasible for this institution? Select
If no, please explain:
Do these modalities fall within the institution’s standard of care? Select
Will patient recruitment be adversely affected? Select
If yes, please explain:



Timeline of required imaging:
 Complement imaging within 30 days of initial imaging
 Repeat serial imaging every 90 days (CT and MRI)
 If ablative therapy performed, imaging (SOC + complement imaging, no less than 28 days and no
more than 60 days after completion of ablation)
Does the study specific timeline conflict with the clinical care timeline? Select
If yes, please explain:

2011 ACRIN Annual Meeting
Performed by RA and/or PI
Step-by-step
–
–
–
•
Review of the brief study summary
Assess study requirements and match to
site’s resources
Estimate patient recruitments
The Mock Screen
– Identify radiology department personnel
and conferences
– Identify referring clinicians and
coordinators
– Identify tumor boards and other sources of
patient recruitment
• If the site assessment is successful, the
activation and recruitment phases should
go more rapidly.
#2 Site pre-activation phase
MOCK SCREEN FOR PATIENT RECRUITMENT ANALYSIS
Overview
The Mock Screen is a tool used to determine whether a potential site institution can be successful in recruiting
patients for a specific ACRIN study. Generally it is the research associate (RA) who will perform this site specific
screen to identify study team co-investigators, sources of patient referrals and make the best estimate of the number
of patients who will fit the study eligibility requirements.
An aggressive approach to analyzing the potential number of patients that fit the ACRIN study eligibility requirements
will determine whether the institution can feasibly be involved in the study. By performing a Mock Screen first, the
obstacles specific to the institution may be identified, thus facilitating the decision to apply as an ACRIN study site (or
not). Because the Mock Screen identifies the clinical contact pathways for patient recruitment, the study is already
organized and ready to accrue, pending approval by the local IRB and other regulatory committees
Individual site assessment
•
•
–
–
INSTRUCTIONS
Contact and Clinic Identification
The ACRIN Study PI/RA will identify the clinical services they deem necessary for the success of this study. Each
institution has their unique organization of clinical services; therefore, the PI/RA must identify clinical services and
contact information appropriate for this ACRIN study as outlined below.
1.
Identify the radiology subspecialty/division that the study naturally falls into. It is best to select the organ based
specialty, rather than the modality based specialty. The decision should be based on which radiology
subspecialties have the greatest interaction with the clinical services. Select radiology division from the pull
down list. If other is chosen, enter the division in the active field. Enter the name and email address for the
division’s administrative assistant in the active fields;
Example:
Abdominal
Contact Name: Veronica Ramirez
Email/phone #: vramirez@usc.edu, 442.8721
Choose division:
If other:
Division Administrative Assistant:
Contact Name
2.
Email/phone #:
Contact the selected division’s administrative assistant for the following information:
a. Names, days and times of all interdepartmental conferences that pertain to the ACRIN study patient
population and/or disease process being studied
Example:
Conference Name: Liver tumor board
Tuesday/wk
Time: 2:30pm
Conference Name
Conference Name
Conference Name
b.
Select / week:
Select / week:
Select / week:
Time:
Time:
Time:
Names and contact information of the radiologists attending these conferences
Example:
Radiologist Name: Suzanne Palmer
Email/phone #: spalmer@usc.edu,
Radiologist Name: Ed Grant
Email/phone #: edgrant@usc.edu,
Radiologist Name:
Radiologist Name:
Radiologist Name:
Email Address
Email Address
Email Address
2011 ACRIN Annual Meeting
Performed by RA and/or PI
Step-by-step
–
•
Review of the brief study summary
Assess study requirements and match to
site’s resources
Estimate patient recruitments
The Mock Screen
– Identify radiology department personnel
and conferences
– Identify referring clinicians and
coordinators
– Identify tumor boards and other sources of
patient recruitment
• If the site assessment is successful, the
activation and recruitment phases should
go more rapidly.
#2 Site pre-activation phase
Estimate Patient Recruitment
Information from the Clinical Conferences:
1. The RA should start attending the targeted interdepartmental conference to introduce themselves and
present the ACRIN study to the group
2. If the ACRIN study is in conjunction with a cooperative group study (ECOG,GOG, SWOG, RTOG, etc) ask
whether the clinical service is involved in the cooperative study. If they are not, ask whether they are
interested. If they are not interested, determine why, because if the referring clinical services are not part of
the cooperative group study, it is not feasible for the institution to be involved in the ACRIN arm.
If the study is in conjunction with a cooperative group study, is the site participating in the
cooperative study? Select
Individual site assessment
•
•
If no, explain:
3.
–
–
Acquire and review the past 6 weeks of agendas/conference minutes to determine the number of patients
who meet the eligibility criteria for the study. This means that the patient must meet not only the tumor
type/pathological process being studied, but also meet the diagnosis, imaging and treatment timelines
required by the study protocol.
a. The protocol schema has the study timeline requirements/restrictions
b. The RA must screen whether the institution’s timelines for patient diagnostic and therapeutic
procedures correlate to the ACRIN protocol schema.
c. Determine the number of eligible patients identified at the conference/month
Estimated number of eligible patients for the ACRIN study derived from subspecialty
conference:
/month
Realistic estimate of number of patients based on site specific recruitment history and
infrastructure limitations:
/month
Information from Alternate Resources
Clinic patient population review
1. RA to meet one-on-one with the clinical faculty treating the target patient population and their clinic
coordinator.
a. Present the study and answer any questions
b. Assess ability to recruit target patients from the clinic
c. Determine approach to patient first contact
d. Determine whether there are any competing studies that would take the target patient population
out of consideration for the ACRIN study
e. Assess ability to facilitate study consents at time of first contact
f. Determine the number of eligible patients identified at the clinic/month
Estimated number of eligible patients for the ACRIN study derived from subspecialty clinic:
/month
Realistic estimate of number of patients based on site specific recruitment history and
infrastructure limitations:
/month
Electronic Medical Record survey
1. Perform a filtered search of clinical data bases for the specific disease process. This gives a general idea of
the size of the targeted disease population seen at your institution.
a. Radiology: Anonymized search for study type that qualify the patient for enrollment
b. Pathology: Anonymized search for tumor type that qualifies the patient for enrollment
Estimated number of eligible study patients derived from alternative sources (i.e. scheduling
calendar):
/month
Realistic estimate of number of patients based on site specific recruitment history and
infrastructure limitations:
/month
2011 ACRIN Annual Meeting
Performed by RA and/or PI
Step-by-step
–
•
Review of the brief study summary
Assess study requirements and match to
site’s resources
Estimate patient recruitments
The Mock Screen
– Identify radiology department personnel
and conferences
– Identify referring clinicians and
coordinators
– Identify tumor boards and other sources of
patient recruitment
• If the site assessment is successful, the
activation and recruitment phases should
go more rapidly.
Data extraction capability:
Examples of sample tables:
Important information for the ACRIN Study Group
Protocol #: 6695
ACRIN PI: Chaan Ng
ACRIN project manager: Bernadine Dunning
Site number
PI name/contact
RA name/contact
Target pop
available
Inc/excl
feasible
Interest in
participating
Why no?
4206
Jeffrey Brody
jbrody@lifespan.org
Wendy Smith
wsmith@lifespan.org
yes
yes
no
Don’t have the time
4567
Ronald McDonald
rmcdonald@restaurant.com
Hamburglar
hamburglar@restaurant.com
no
no
yes
4317
Suzanne Palmer
Spalmer@usc.edu
Tammie Possemato
tpossema@usc.edu
yes
no
no
Site number
Estimated # of patients
4206
2/ month
4567
0/month
4317
1/month
2011 ACRIN Annual Meeting
Site not
participating in
GOG 0262
Data extraction capability:
Different forms/format examples:
Important information for the Study Site
Protocol#: 6690
ACRIN PI: Christoph Wald
ACRIN project manager: Donna Hartfeil
ACRIN 6690 SITE PERSONNEL OVERVIEW
RADIOLOGY:
P.I. Suzanne Palmer
Email/Phone #: spalmer@usc.edu 323-442-8541
Responsibilities: PI responsible for all aspects of the study.
RA Tammie Possemato Email/Phone #: tpossemat@usc.edu 323-442-7263
Responsibilities: Assists PI with all aspects of study.
CLINICAL SERVICES:
Abdominal Transplant
John Donovan
Email Address: jdonovan@usc.edu
Responsibilities: Access to UNOS database, ordering of UNOS recertification CT 90 days.
UNOS Contact:
Jennifer Pena
Email Address: jpena@usc.edu
Responsibilities: Notification of MELD Listing
Pathology
Lydia Petrovich
Email Address: lpertrov@usc.edu
Responsibilities: Comparison of imaging to explant.
Oncology:
Anthony ElKhoureiy
Email Address: aelkhou@usc.edu
Responsibilities: Patient referral
Surgery:
Yuri Genyk
Email Address: ygenyk@usc.edu
Responsibilities: Patient referral
PATIENT IDENTIFICATION/RECRUITMENT SOURCES:
Source
Time/Location
Contact
Liver tumor board
Tuesday/wk/ 2pm - UH
Jennifer Pena
UNOS Website
https://portal.unos.org
Password
2011 ACRIN Annual Meeting
Clinical Services Attending
Data extraction capability:
Different forms/format examples:
Important information for the Study Site
STUDY SUMMARY
ACRIN Study #: 6690
ACRIN Study Name: Comparison of multiphase contrast-enhanced CT and MRI for
diagnosis of HCC and liver transplant allocation
Study Contact Information :
ACRIN PI: Christoph Wald, MD, Ph.D, 781-744-8170 christoph.wald@lahey
ACRIN Project Manager:
Donna Hartfeil, 215 717-2765, dhartfeil@acr.org
Site Number: 4317
Site PI: Suzanne Palmer, M.D., 323.442.8721, spalmer@usc.edu
Site RA: Tammie Possemato, 323.442. 7263, tpossemat@usc.edu
ACRIN Schema:
Study objectives and end points: The main objective of the ACRIN 6690 trial is to
compare modern multiphase contrast-enhanced CT and MRI with pathologic liver
findings to establish the performance characteristics of these imaging modalities to
accurately detect, diagnose, and stage HCC in patients with chronic liver disease.
The CT and MRI examinations acquired within 90 days of transplantation will be
compared with the explant pathology findings.
The primary analysis will compare CT to MRI results at the lesion level using core
laboratory interpretations of the imaging studies; secondary analysis will be
performed at the patient level.
Patient eligibility: Patients diagnosed with HCC and listed for liver transplant surgery
with priority MELD (Model for End-Stage Liver Disease) points based on their
cancer diagnosis will participate.
Eligible patients include those who may be waiting for a liver to become available
from a deceased donor or be scheduled to undergo a living donor adult liver
transplant.
Patients must enroll in the trial within 30 days after initial listing with HCCexception points to the United Network for Organ Sharing (UNOS) waitlist.
Basic protocol: Each site will image a participant with CT or MRI approximately every
90 days (or earlier) per the OPTN/UNOS HCC-exception point update
requirements for their region. This imaging to evaluate disease is considered
standard of care.
This research trial requires that complement imaging (CT or MRI, whichever
imaging was not done as the standard of care) be completed at each 90-day
interval. This imaging must be completed within 7 days of the standard-of-care
imaging for that time interval.
The goal is to compare the CT and MRI examinations acquired within 90 days of
transplantation with explant pathology findings.
Should a participant undergo local ablative therapy, CT and MRI should be
completed no less than 28 days and no more than 60 days after each completed
ablative therapy scheme.
Enrollment: A total of 440 participants will be accrued to the ACRIN 6690 trial. Number
per site was not included in available protocol
2011 ACRIN Annual Meeting
Significant outcomes, to date:
USC results using our tool
USC Study
Accrual
2010
2011
(as of 9/15)
Problems Identified through
Mock Screen
Solutions/Outcomes
6678
1
3
Difficulty identifying potential patients; multiple
competing studies; oncology in charge of study
assignment and interested in accruing to competing
studies
Change in PI. Tumor boards identified and
attended; contact made with referring MD’s;
potential patients identified at conferences
6682
0
8
Difficulty identifying potential patients;
disinterested PI; no communication with clinical
services; requirements for imaging not reviewed for
access to radiotracer and equipment needs
Added PI with interest in gynecologic
imaging; regular attendance at weekly tumor
boards; imaging road blocks identified and
resolved
6685
0
1
Difficulty identifying patients for study; potential
patients not interested in participating due to QOL
questionnaire; inclusion criteria for N0 neck not
well defined; reimbursement inadequate
Working with clinical MD’s to recruit
patients from clinic and tumor boards;
working with ACRIN for clarification of
eligibility; attempt to convince USC to
drop tithing for this study.
6688
0
3
Difficulty identifying patients for study; multiple
competing studies; failure of RA to follow-up on
patients identified in tumor boards.
Replaced recruiting RA
5
Timing for patient recruitment critical.
Knowledge of MELD exception application and any
scheduled or completed treatment.
RA at weekly conference where patients are
listed for MELD exception, and recruited to
study with clinical support.
One of the first 10 sites to open.
6690
2011 ACRIN Annual Meeting
And finally……….
Congratulations
to Tammie Possemato for being honored as the
recipient of the Jo-Ann D’Amato Award!
2011 ACRIN Annual Meeting