Draft -- September, 2009

Randomize

Agree?

Make Patients Aware of

Trial

Enroll &Start

Treatment

Screening Consent

Discussion

Interest?

Eligible?

Agree?

Done

Treatment Consent

Discussion

Yes

Yes

NoYes

No

Yes

No

Non-Eligibility

Letter

Decline Questionnair

e

I-SPY2 Patient

Portfolio

Decline Questionnair

e

Optional Peer Support

Call

Peer Support Call (s)

Done? Congratu-tions Letter

No

Yes

Welcome Letter

I-SPY2 Brochure

Exit Interview

Dropped Out

No

I-SPY2 Patient Website

I-SPY2 Patient Website

I-SPY2 Patient Website

Recruitment◦ Promotion◦ Consenting Patients◦ Overall Recruitment Expectations◦ Diversity Considerations◦ Tracking Accrual◦ Patient Decline Questionnaire

Retention◦ Patient Materials/Website◦ Network of Strength Hotline◦ Site Specific Support◦ Exit Questionnaire

Trial Site Education Sessions, especially with surgeons

Advocacy and Clinical Trials Websites Educational Sessions and Materials for Breast

Cancer Hotlines National Scientific and Advocacy Education

Sessions Local and National Press Release Local and National Press, TV, & Radio

Interviews Local and National Advocate Presentations Scientific and Patient Publications Broad Distribution of I-SPY2 Brochure

See draft brochure

Informed Consent documents have undergone careful review by a large number of experienced advocates

Training will be developed to reinforce best practices in consenting and summarize I-SPY2 specific information

FAQ questions will be made available to consenters

Patient website will have fact sheets, patient schedules, and other relevant information available as PDFs to support consenting process

ExpectationsWorst Case

Scenario

Best Case

Scenario

Other Scenario

Expected Number of Potential Patients Per Month 10 30Expected Percent of Patients Who are Offered Trial per Month 40% 80%Expected Percent of Patients Offered Who Accept Screening 50% 80%Expected Percent of Screened Patients Who are Eligible 70% 90%Expected Percent of Eligible Patients Who Accept Treatment Trial 50% 80%Expected Discount Factor 7.0% 46.1% 0.0%Expected Number of Patients Accrued per Month 0.7 13.8 0.0Total Months to Accrue 800 Patients 1142.86 57.87 #DIV/0!

Goal: Summing over trial sites, I-SPY2 patients should reflect the diversity of US women affected by breast cancer

Actions:◦ Travel reimbursement for research visits◦ Proactive recruitment of trial sites that over

represent minorities◦ Identify potential affiliate and/or satellite

hospitals that might partner with main I-SPY2 sites

◦ Proactive recruitment of patients from under represented minorities Targeted advocacy organizations (e.g., ICC) Targeted community outreach Targeted publications

Actions Continued:◦ Develop and deliver culturally sensitive and

targeted workshops on participation in clinical trials in general and I-SPY2 in particular

◦ Ensure that all of our patient materials are culturally sensitive and include pictures that reflect diverse populations

◦ Translate the Informed Consent and Recruiting Brochure into Spanish and/or other languages

◦ Identify language translation services that are available at each site

◦ Identify potential affiliate and/or satellite hospitals that might partner with main I-SPY2 sites

Trial SiteExpected Treated

Per Month

Expected Acrued to Trial Per Month

% Cauca-

sian

% African Ameri-

can

% Hispan-

ic

% Asian

% Other

% Older than 70

Emory University 0.0INOVA Health System 0.0Kansas U Medical Center 0.0Mayo Clinic 0.0MD Anderson 0.0UC at San Diego 0.0UC at San Francisco 0.0U of Arizona 0.0U of Chicago 0.0U of Colorado 0.0U of Minnesota 0.0U of Pennsylvania 0.0U of Texas Southwestern 0.0Other 0.0

0.00.00.0

Quarterly by Trial Site◦ Which sites are exceeding expectations? What

can we learn from them?◦ Which sites are failing to meet expectations?

How can we remedy this? Quarterly by Patient Biomarker Profile and

Treatment Plan Bi-annually for adequate diversity

Problem Potential Solution

Too few patients are offered trial

Educate clinicians at trial sites Recruit more trial sites Increase national publicity

Too many patients decline screening consent

Educate consenters Improve patient material Assess reasons for decline

Too many patients decline treatment consent

Educate consenters Improve patient material Assess reasons for decline Look for variation by treatment

arm

Problem Potential SolutionDistribution of patients by biomarker profile does not reflect distribution in population

Identify competing trials for specific profiles at specific sites

Over recruit from other sites

Distribution of patients declining treatment varies by treatment assignment

Clarify whether the issue is based on rejecting standard of care or a particular investigational agent

Consider over recruiting controls and/or dropping problematic investigational agents

Inadequate diversity Recruit sites in more diverse communities

Increase targeted promotion

Trial Site

Expected Treated

per Quarter

Actual Treated

Last Quarter

Expected Acrued to Trial

Per Quarter

Actual Accrued

Last Quarter

Treated - Accrued

Last Quarter

Number of

Decline Question

naires Last

Quarter

Not Offered

Last Quarter

Emory University 0.0 0 0INOVA Health System 0.0 0 0Kansas U Medical Center 0.0 0 0Mayo Clinic 0.0 0 0MD Anderson 0.0 0 0UC at San Diego 0.0 0 0UC at San Francisco 0.0 0 0U of Arizona 0.0 0 0U of Chicago 0.0 0 0U of Colorado 0.0 0 0U of Minnesota 0.0 0 0U of Pennsylvania 0.0 0 0U of Texas Southwestern 0.0 0 0Other 0.0 0 0

0.0 0 0

HR+ HR- HR+ HR-Her2+ Expected 16.0% 7.0% 4.0% 10.0%

ActualHer2- Expected 23.0% 6.0% 6.0% 28.0%

Actual

Hi-MP2Hi-MP1

Treatment

# of Randomized

Patients Assigned to Treatment

# of Randomized

Patients Accrued to Treatment

Decline Rate

Standard of Care #DIV/0!Agent A #DIV/0!Agent B #DIV/0!Agent C #DIV/0!Agent D #DIV/0!Agent E #DIV/0!Agent F #DIV/0!Agent G #DIV/0!Agent H #DIV/0!

#DIV/0!Total 0 0 #DIV/0!

Cauca-sian

African American Hispanic Asian Other Older

than 70Expected Treated Per Six MonthsActual Treated in Last Six MonthsDifferenceExpected Acrued Per Six MonthsActual Acrued in Last Six MonthsDifference% of Last Six Month Accrual% US Breast Cancer PatientsDifference

See draft Decline QuestionnaireFactor Major

Concern Minor

Concern Not a

Concern I want to have my surgery as soon as possible, rather than having chemo first.

I did not want to take any drugs that haven’t been fully tested

I do not want to have any treatment that includes Anthrecycline

I do not want my treatment decided by randomization

I do not want to have multiple MRIs

I do not want to have multiple needle biopsies

The trial site is too inconvenient

I do not want to have to make extra trips to the clinic

I do not want to change doctors

I am concerned about what my insurance will pay

I am concerned about possible financial consequences associated with being the this trial

I am concerned about possibly loss of privacy

I do not want to be a guinea pig

Other (please specific)

Recruitment◦ Promotion◦ Consenting Patients◦ Overall Recruitment Expectations◦ Diversity Considerations◦ Tracking◦ Patient Decline Questionnaire

Retention◦ Patient Materials/Website◦ Network of Strength Hotline◦ Site Specific Support◦ Exit Questionnaire

Recruiting Brochure New Patient Portfolio Website PDFs

◦ Fact Sheets◦ Patient Schedule◦ Trial Site Map, Support Services, Contact

Information Peer to Peer Letters

The right amount of the right information at the right time

Easy to navigate Attractive—white space, pictures Text and FAQs PDF of key pages for use by trial site

staff

See Prototype http://gemini-grp.com/ISPYPatientindex.htm

24x7 toll free hotline Staffed by trained and certified breast cancer

survivors Free to callers Spanish speaking counselors Interpretation available in over 150 languages E-mail option Match programs

◦ Patient specific requests (e.g., diagnosis, treatment, demographics)

◦ Male breast cancer matches◦ Partner’s match program

Screening and Treatment Informed Consent Forms request permission for Network of Strength counselor to call patient◦ Patient may, alternatively, take number and call if

and when they please A select group of experiences counselors

will be specifically trained about I-SPY2 (based on I-SPY2 Website)◦ Supporting, but not pressuring patients, who are

considering enrollment◦ Checking in on, encouraging, and supporting

patients who are undergoing treatment

Website will provide site specific information◦ Maps◦ Hospital investigators and contact information◦ Hospital services and contact information◦ Locally available advocacy and support groups

Encourage all sites to maintain regular communication with patients and continuous express appreciation for participations in I-SPY2

Optionally, local advocates will be identified to work with investigators at specific trial sites

Finalized Recruiting Brochure Develop detailed PR plan and pieces Develop training for consenters Reassess accrual assumptions Obtain site-specific recruitment, accrual,

and diversity expectations Finalize tracking reports and data collection

plan Finalize data collection and analysis plans

for patient declines

Ensure conformance of Informed Consent documents and plan◦ Hot-line support◦ Decline questionnaire

Follow-up on Patient Website◦ Finalize material◦ Construct site◦ Pilot test with advocates

Follow-up on Hot-line◦ Finalize budget◦ Negotiate terms◦ Select counselors◦ Develop and deliver training

Develop Site Specific Support information