Agenda CCTCC & Provincial Clinical Trial Organizations’ Meeting

Friday, April 1, 2016 – 11:00 am to 3:00 pm EST Lord Elgin Hotel, 100 Elgin St., Lady Elgin Room

Toll Free: +1 888-506-2534 | Participant PIN Code: 900 488 32

Item Agenda Item Lead Time

1. Welcome and introductory remarks.

Moderator (Susan Marlin) & Elena Aminkova

11:00 - 11:10

2. Introductions. Moderator (Susan Marlin) 11:10 - 11:20

3. Ongoing projects and initiatives to raise awareness of, promote or find collaboration for:

Elena Aminkova & Alison Sargent

11:20 –12:00

a.) CCTCC -Marketing Canada as a go-to-destination for clinical trials at BIO 2016

b.) CCTAM - help with increasing awareness & data collection

Elena Aminkova

12:00-12:30

c.) CCTCC mCTA - collaboration for its implementation & uptake

d.) CCTCC Fair Market Value (FMV) Working Group (WG) - call for WG member nominations

Message from the CCTCC Presidents’ Committee Russell Williams, Chair of the CCTCC Presidents’ Committee

12:30-12:40

LUNCH BREAK 12:40-1:10

e.) CTO's Streamlined Research Ethics Review System - pilot outside Ontario

Susan Marlin

1:10 - 1:40

f.) BCCRIN's Clinical Research Engagement Initiatives:

• BCCRIN (now national) Clinical Trial Participation Survey - update

• BCCRIN's Permission To Contact (PTC)

demonstration project with the BC SPOR Support Unit - discussion

Heather Harris

1:40 - 2:10

4. Round-table updates. All

2:10 - 2:40

5. Other Business: • New investigator training

Shurjeel Choudhri/ all

2:40 - 2:55

6. Adjournment & Next Meeting. Moderator (Susan Marlin) 2:55 - 3:00

WELCOME

Welcome to the CCTCC & Provincial Clinical Trials

Organizations’ Meeting April 1, 2016

www.cctam.ca |cctam@cctcc.ca

AGENDA

1.Welcome and introductory remarks.

2. Introductions.

AGENDA

3. Ongoing projects and initiatives: CCTCC: – Marketing Canada as a go-to-destination for clinical

trials at BIO 2016. – CCTAM – mCTA – Fair Market Value (FMV) Working Group (WG)

AGENDA

3. Ongoing projects and initiatives:

CTO: – Streamlined Research Ethics Review System BCCRIN: – Clinical Trial Participation Survey – Permission To Contact (PTC) demonstration project

with the BC SPOR Support Unit

AGENDA

4. Round-table updates 5. Other:

• New investigator training

6. Adjournment & Next Meeting.

ABOUT CCTCC • Promoting Canada as a leading destination for the conduct

of clinical trials (CT) • Underpinnings in the recommendations of the Action Plan to

Help Attract More Clinical Trials to Canada • Funded by Innovative Medicines Canada, CIHR,

HealthCareCAN. Housed at Health Charities Coalition of Canada

• Visit – www.cctcc.ca CCTCC www.cctam.ca |cctam@cctcc.ca

FEATURES

Strategy 1: Establish short and longer term implementation capacity for this action plan and coordination of other clinical trial improvement activities. Strategy 2: Improve business operations through better cost, quality, and speed of clinical trial start up times. Strategy 3: Shape a positive future business environment and signal Canada’s interest globally with information and incentives.

PROJECTS

Key Projects:

• CCTAM - launched June, 2015, currently over 1000 assets • Model Clinical Trial Agreement (mCTA) – expected launch

Sept, 2016 • Fair Market Value WG – addressing clinical trial (CT)

budget issues • Investment case for conducing CTs in Canada • CCTCC CT round-table at BIO 2016

WELCOME

10

The purpose of this presentation is to provide a concise resource for Canadian clinical trials partners to communicate the landscape, advantages and continual advances being made to make Canada a desired destination for clinical trial investment. This presentation is designed to be delivered in person with much of the content in the speaking notes, however, it is also a credible source of information and could be posted or distributed electronically.

Clinical Trials: The Canadian Advantage

March 2016

The Canadian Landscape

12

Health and medical research is a priority for Canadians. A very strong majority (90%) say it makes an important contribution to health care while a strong majority (77%) say it makes an important contribution to the economy.

CanadaSpeaks 2015 poll, Research Canada

13

Canada boasts a high quality of life, stable business environment, educated workforce and diverse patient population.

15

We are in a global leadership position in areas that include basic and translational research:

•Cutting-edge genomics research in British Columbia •Exciting industry activity in virology in Alberta •World-class resources for R&D in virology in Saskatchewan •Groundbreaking infectious disease public health lab in Manitoba •Top-ranked research in cancer, stem cell and regenerative medicine in Ontario •Globally renowned centres for neuroscience and cardiovascular research in Quebec •Exceptional facilities for vaccinology in Atlantic Canada

17

There is a unique commitment between industry, government and the institutions to improve the operational environment for clinical trials in Canada. In 2013, the Canadian Clinical Trials Coordinating Centre (CCTCC) was launched to address challenges identified through the 2011 Canadian Clinical Trial Summit to make Canada a destination of choice for clinical trials.

The Canadian Advantage

19

Why Canada

Speed

Quality

Incentives ($)

SPEED 1) Fast Regulatory Approval

oRigorous 30-day Health Canada target to review clinical trial applications o In 2013 Health Canada achieved 99% target for study applicants received

2) Patient Enrollment oAverage time from trial set-up to First Patient First Visit is 3 months o 98% of subjects enrolled within the planned study period

3) Operational efficiency Improvements through the Clinical Trials Coordinating Centre (CCTCC)

oPan-Canadian Contract Template (mCTA 2016) oCanada Clinical Trails Asset Map (CCTAM) oProvincial leadership in REB efficiencies such as: (add examples provided

from CCTCC)

SPEED

SPEED Canadian Clinical Trials Asset Map (CCTAM)

o First pan-Canadian & pan-therapeutic database of Canadian clinical trial resources

oUpdated and comprehensive contact information oUser-friendly & customizable data searches o Free to data contributors & clinical trial sponsors

QUALITY

• • World class research institutes and academic hospitals

• Top 5 countries globally for research reputation in clinical medicine, biomedicine and overall science & technology

•The University of British Columbia in Vancouver

•The University of Toronto •McGill in Montreal

•98% patient recruitment success rate

•N2’s It Starts With Me program

•Among the 20 most ethnically diverse countries in the world

• Can accommodate trials in all therapeutic areas

Patient Diversity

Patient Recruitment

Reputation 3 of World’s

Top Universities

QUALITY

QUALITY

Clinical trials underway across all major treatment areas including cancer, CNS, metabolic and cardiovascular disease

QUALITY Universal Healthcare System

• Canada’s universal healthcare system provides quality and cost advantages for conducting clinical trials • On average, there are 2.1 doctors and 7.9 nurses per 1,000 people • Ensures a common and high standard of care for patients before, during

and after the clinical trial

• This results in superior data accuracy and quality from all trial sites

INCENTIVES

• Historically low CDN exchange rate

• Sustainable business environment

• Reasonable salary costs for highly-skilled personnel (Less expensive to place Global staff in Canada over the USA)

• Low R&D Tax Burden

1 KPMG Competitive Alternatives 2014 2 Total tax index is a measure of the total taxes paid by a company expressed as a % of the total taxes paid in the US.

INCENTIVES

• PwC and KPMG reported that Canada’s R&D tax treatment is one of the most favourable in the world2,3

• Canada’s SRED research tax credit can significantly reduce the cost of clinical trials in Canada

• SRED program can amount to a 15% tax credit for a company’s expenditures on eligible R&D1

• Individual provinces have additional tax credits for R&D ranging from 4.5% to 20%1

• Total tax credits from 15% to 32% on eligible R&D expenses1

1SRED April 2014 Factsheet; 2 KPMG. R&D incentives and services – adding value across the Americas. 2012 ed; 3 Presentation to R&D Tax Symposium, 23 May 2011. “Tax Policy – the role of R&D tax incentives” by Mark Parson, PwC Canada , Canada Revenue Agency website (accessed 23 Sept 2014)

Perceived Roadblocks for Investment • Geography – Canada is a large country.

• In reality, the bulk of the population is within 100 miles of the US border. • There are clusters of clinical trial sites in Canada.

• Contracts – The contracting process slows down start-up times. • The CCTCC will launch an updated version of the mCTA in 2016.

• A Fair Market Value working group has been formed to address budget negotiations.

• Fragmented Health Systems – Different rules in different provinces for multi-site trials make things complicated. • Provincial CT organizations are working together and sharing best

practices to reduce these challenges.

Opportunity

Industry, government and research institutions recognize that continual improvements to the business environment are required so that Canada maintains global advantages in Speed, Quality and Incentives.

Success Starts Here

Speed

Quality

Incentives ($)

Alternate Slides

Why Canada? Asset map

Why Canada? Efficiency

QUALITY

BRAINSTORM

The Canadian Advantage Brainstorming Session

• SPEED • COST • QUALITY

WHAT IS CCTAM? • One of CCTCC’s key outcomes • Web-based, “living”, easily searchable, interactive, comprehensive database of

Canadian clinical research capabilities – researchers, clinical research sites, hospitals, institutions, research ethics boards, CROs, SMOs , etc.

• Better enable sponsors of clinical trials to identify clinical research sites and investigators

• Position Canada as an attractive destination for the conduct of clinical trials in the global marketplace

CCTAM www.cctam.ca |cctam@cctcc.ca

CCTAM – UNIQUE

• First pan-Canadian & pan-therapeutic database • Regularly updated • Free to data contributors • Easy to use • Able to grow & develop

UNIQUENESS www.cctam.ca |cctam@cctcc.ca

CCTAM www.cctam.ca |cctam@cctcc.ca

CCTAM www.cctam.ca |cctam@cctcc.ca

CONTACT US. WE ARE ACCESSIBLE

WEB: www.cctam.ca EMAIL: cctam@cctcc.ca Phone: 1-844-452-5818 Twitter: @CCTAMap

CONTACT www.cctam.ca |cctam@cctcc.ca

THANK YOU! Thank You

CLINICAL TRIALS ONTARIO• Independent non-profit, established in June 2012 and funded by the Government

of Ontario

• Established to address the decline in clinical trials in Ontario and leverage Ontario’s clinical research capabilities to attract more investment

CTO REB QUALIFICATION PROGRAM

Provides REBs planning to participate in the CTO Streamlined Research Ethics Review System with an external review of their governance, membership, operations and review procedures.

Based on the Toronto Academic Health Sciences Network (TAHSN) qualification process.

REBs are reviewed against a transparent standard, the CTO REB Qualification Checklist, that is informed by the applicable regulations, policies and guidelines. REB Qualification Manual available at www.ctontario.ca.

CTO REB Qualification checklist aligned with the N2/CAREB REB SOPS.

Each full visit is conducted by a Qualification Team composed of: Auditor with specific training relating to review of REBs CTO Program Coordinator Two experienced members from the research ethics community (e.g., REB Chair/Vice-Chair

and REB Director/ Manager/ Coordinator) selected from the CTO College of Reviewers.

CTO STREAMLINED RESEARCH ETHICS REVIEW SYSTEM

Supports a single REB in providing research ethics review and oversight to multiple research sites; relies on a “REB of Record Model”

REB oversight responsibilities delegated by participating institutions to the REB of Record

Can be used for any multi-site clinical research, i.e. industry sponsored or investigator initiated

Currently can accept multi-site clinical trials; in future multi-site health research will be accepted as well

CTO STREAM

CTO Stream is a standalone web-based electronic platform:

Enables research ethics review, document management, and communication between multiple institutions and REB of Record

Common application forms – all REBs use it; template consent form

Designed and built by Infonetica (UK), CTO and the CT community

Supports any file type for uploads (i.e., word documents, excel documents, pdfs and text files)

Built using smart questions and smart forms; applications can be drafted by sponsors

Electronic signatures for all applications; User friendly

REB OF RECORD MODELInitial Application Process

REB application submitted by any registered investigator/site, i.e. “Provincial Applicant”

CTO assigns REB of Record (any Qualified REB in Ontario) and advances application

REB of Record reviews application and resolves any issues with applicant

Once issues are resolved REB of Record approves study

Recruiting Institution signs REB of Record Agreement, delegating ethics review and

oversight to REB of Record; Local PI adopts approved consent form and submits site

application focused on site specific information

Site application advances to REB of Record

REB of Record Host Institution signs REB of Record Agreement and REB reviews

application (usually expedited) and resolves any issues with site applicant

Step 1Applying for a New Multi-Centre

Clinical Trial

Step 2 Adding New Investigators /

Research Sites

Sites wishing to participate are notified and given access to REB materials in CTO

system

REB of Record issues approval for site to participate

Continuing Oversight and Approval

Documentation submitted by “Provincial Applicant”

REB of Record reviews submission and resolves issues with provincial applicant

Once issues are resolved, approval or acknowledgement is issued by REB of Record

and sent simultaneously to all approved participating sites

REB of Record reviews submission and resolves issues with research site

Approval or acknowledgement issued by REB of Record

New overall (study-level) event, e.g. amendment, Data Safety Monitoring

Board report, safety update

New site level event, e.g. continuing (annual) review, local Serious Adverse

Event, protocol deviation

Documentation submitted by research site

REB OF RECORD MODEL

CONTACT INFORMATION

Website: www.ctontario.ca

E-mail: erin.bell@ctontario.camatthew.dascanio@ctontario.casusan.marlin@ctontario.ca

@clinicaltrialON

linkedin.com/company/clinical-trials-ontario

Clinical Trials Ontario661 University Avenue, Suite 460MaRS Centre, West TowerToronto, Ontario Canada M5G 1M1 Tel / 416 673-6670

ENGAGE. LISTEN. ACT.

Learning From the Participant Experience: The Canadian Clinical Research Participation Survey

Alison Orth, BBA, CCRC - Project Manager, BCCRIN

45

The Recruitment Challenge

SITES

SPONSORS/CROS

REGULATIONS/PRIVACY

MEDIA

PUBLIC

Connect. Communicate. Learn.

SITES

PUBLIC

Public Engagement

The Canadian Clinical Research Participation Survey

www.bccrin.ca/survey

MEETING THE CHALLENGE

48

Survey Rationale

• Directly engage Canadians in discussion and feedback on clinical trials Engage

• Obtain current national and provincial data from those who have been offered to participate in a clinical trial Listen

• Develop evidence-based best practice recruitment & retention strategies

• Promote awareness of the essential contribution made by clinical trial participants

Act

49

THE GOAL: Improve recruitment success

Engage the public, researchers and industry

Translate knowledge

Evaluate success

Continuous Quality Improvement

50

Phase I – British Columbia 2012-2014

Collaboration

•Task force designed and peer reviewed

•Harmonized ethics review

•Paper and Web-based Survey

•REDcap hosted by Child and Family Research Institute

Outreach

•Connected with 74 sites to distribute survey to patients

•Visits, calls and regular emails with sites

•Disease advocacy/info groups engaged

Recruitment

•Advertising/Press Release

•Web/Social Media •Patient groups • Inform patients

when visiting a hospital, clinic or research site

51

What We Collected

Demographics Disease or medical condition

Type of treatment studied

Reasons for Declining

Reasons for Agreeing to Participate

The Screen Failure Experience

The Clinical Trial Experience

The Study Cancellation Experience

Impact of Physician Decision

to Withdraw

Reasons for Self-Withdrawal

•detailed and comprehensive •total of 62 questions •adult and pediatric (parent) cohorts

52

SURVEY RESPONDENTS

Extent of clinical trial involvement 596 were considered valid (answered at least both age and gender)

Completed 77%

Declined 13%

Discontinued Prematurely

10% N=596

53

SURVEY RESPONDENTS

Therapeutic area under study

0%2%4%6%8%

10%12%14%16%

54

DEMOGRAPHICS

Age and Gender

PARTICIPANTS Participant

Decliner

N 497 69 Gender : % Female 62% 75% % Male 38% 25% Age (Mean, range) 51 (14 to 88) 46 (18 to 81)

PARENTS ENROLLING CHILD Parent

Consenter Parent

Decliner N 24 06 Child’s Gender % Female

38% 17%

Child's Gender % Male 62% 83% Child's age (Mean, range) 5.7 (0 to 17) 4.7 (0 to 12)

55

DEMOGRAPHICS

Highest level of education completed

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

High Schoolnot completed

High Schooldiploma

SomeUniversity or

College

College/University

degree

Graduatedegree

Post-graduatedegree

1) Participant

2) Decliner

56

DEMOGRAPHICS

Household income level

0%

5%

10%

15%

20%

25% 1) Participant

2) Decliner

57

DEMOGRAPHICS

Ethnic/racial background

1) Participant 2) Decliner

Vancouver/Lower Mainland/South Coast 313 (63%) 51 (76%) Other parts of BC 184 (37%) 16 (24%)

497 67

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

% Respondents

% Census 2006

58

ADULT DECLINERS N=60

Reasons for declining

Did not have time due to work/commitments 50%

Trial too burdensome or demanding 37%

Did not feel health would benefit 34%

Wanted to be paid more for time and expenses 24%

Would if trial was outside of working hours 23%

Top 5 of 25 “Agree and Strongly Agree” Responses

59

ADULT DECLINERS N=60

Reasons with low impact on decision

• Required my GP be made aware and I did not want to agree to this

• Questions about study were not answered fully by the research staff

• Had concerns regarding the privacy of my personal information

• Did not understand English well

• Going on vacation/traveling

Low “Agree” and High “Disagree” responses

60

ADULT CONSENTERS N=497

Reasons for participating

Consent Form clear and easily understood 94%

Benefit others even if I didn’t benefit directly 87%

No commitments conflicting with study visits 69%

Doctor wouldn’t ask me if the risk was too great 64%

Thought participating would improve my health 63%

Top 5 of 12 “Agree and Strongly Agree” Responses

61

REASONS FOR PARTICIPATING

Conflicting commitments decrease by age

61% 61%

73% 81%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

14-39 40-51 52-62 >62

“I had no other commitments that made attending visits difficult”

Age Group in Years P-value = 0.00

62

REASONS FOR PARTICIPATING

Education level and expectation of health services

68%

47% 45% 38% 39% 38%

0%

10%

20%

30%

40%

50%

60%

70%

80%

No HighSchool

High School SomeUniv/Coll

Univ/Coll Graduate Post-graduate

“I felt I would have better access to health care services”

p-value = 0.01

63

REASONS FOR PARTICIPATING

Education level and expectation of health improvement

80% 75%

67%

57% 61%

54%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

No High School High School Some Univ/Coll Univ/Coll Graduate Post-graduate

“I felt participating would provide an improvement to my health”

p-value = 0.02

64

REASONS FOR PARTICIPATING

Education level and Consent Form comprehension

p-value = 0.02

84%

96%

91%

95%

91%

98%

75%

80%

85%

90%

95%

100%

No High School High School Some Univ/Coll Univ/Coll Graduate Post-graduate

“The informed consent form was clear and I understood it well”

65

THE CLINICAL TRIAL EXPERIENCE

Non-inclusive summary...

I felt well-cared for by the research staff 87%

The study team was available to answer my questions 86%

Participation had a positive impact on my health 46%

AGREED with:

DISAGREED with:

Research staff not as professional as I expected 85%

I experienced unpleasant side effects 66%

Study requirements more than I originally anticipated 61%

Note: Total of 15 questions

66

Impact of Experience on Future Trial Participation

89%

73% 67%

100%

81% 92%

83%

0%

20%

40%

60%

80%

100%

120%

Participated Declined ScreenFailure

WithdrewSelf

Withdrawn StudyCancelled

Parentconsenters

“Given my experience I would consider participating in another clinical trial”

67

Common Challenge - Collaborative Response

“The Canadian Clinical Trial Participation Survey”

Enrollment: 703/2000 March 2016 BC 674 Quebec 3 Ontario 20 Other 6

• Ability to look for regional differences in responses

• Increase sample size for our subsets (pediatric, screen failures, early discontinuations, study cancellation, ethnic/cultural diversity)

• Correlative analysis across therapeutic areas

• Potential for Quantitative analysis

68

• Dec 2015 Announcement via CCTCC, N2, BCCRIN and partners

• Feb 25, 2016 Revised materials approved by Harmonized REB in BC

• Mar 2016 Communications with sites, initiate institutional and REB approval process if required. Communications with disease advocacy groups and communications across institutions and networks

• Apr 2016 Work with CTO streamlined REB team, French version, additional communications material created, N2&BMC distribution

• May 2016 Independent sites outreach

• Jun 2016 Continued outreach and support of participating sites, networks

• Jul 2016 Evaluation of progress and report on enrollment

• Sep 2016 Planned completion of enrollment 2000 surveys

• Oct-Dec 16 Formalize knowledge translation plan

National Survey Timelines Update