Ontario Cancer Research Ethics Board

Ontario Cancer Research Ethics Board

MaRS Centre, Suite 510 | 661 University Avenue

Toronto, Ontario | CanadaM5G 0A3

416-673-6649 or 1-866-678-6427 ext. 6649 | www.ocreb.ca

Monthly Teleconference Summary

June 5, 2015 @ 9am

ATTENDEES

Sites: / 1.  Hamilton Health Sciences (JCC)
2.  Health Sciences North (Sudbury)
3.  Lawson (London) - LRCP
4.  Niagara Health System
5.  The Ottawa Hospital – Cancer Program
6.  Royal Victoria Regional Health Centre
7.  Southlake Regional Health Centre / 8.  Sunnybrook Health Sciences Centre
·  Odette Cancer Centre
9.  Toronto East General
10.  Trillium Health Partners - Credit Valley Hospital
11.  UHN - Princess Margaret Cancer Centre
·  Clinical Trial Support Unit
12.  William Osler Health Centre
OCREB: / Aurora de Borja, Terry Liu, Janet Manzo, Safia Moosvi, Cindy Sandel, Richard Sugarman (Chair), Alison van Nie, Kathie Zeman

REGRETS

Sites: / 13.  Cambridge Memorial
14.  Grand River Hospital
15.  Humber River Hospital
16.  Kingston General Hospital
17.  Lakeridge Health (Oshawa)
18.  Mount Sinai Hospital
19.  North York General Hospital
20.  SickKids (Toronto) / 21.  St. Joseph’s Healthcare (Hamilton)
22.  St. Joseph’s Health Centre (Toronto)
23.  St. Michael’s Hospital
24.  Thunder Bay Regional Health Sciences Centre
25.  Trillium Health Partners - Mississauga Hospital
26.  Windsor Regional Hospital
27.  Women’s College Hospital
OCREB: / Yooj Ko (VC), Mark Whissell (VC),

If you temporarily have to leave the teleconference, please hang up and dial in again when you are able to re-join. Putting your phone on hold causes interference with all of the other lines.

If you no longer wish to receive the monthly teleconference agendas and minutes, please contact Alison van Nie at to be removed from the OCREB distribution list. NOTE. You will no longer receive communication from OCREB, with the exception of relevant business communication, as applicable. You may request to be reinstated in the distribution list at any time.

NOTEWORTHY ITEMS

A place for sharing new information, updates and other noteworthy items affecting the research community…

Regulatory/Guidance Updates:

Regulatory Issues of Interest:

1.  The Research Clinic. http://ori.hhs.gov/TheResearchClinic

The Office of Research Integrity (ORI) and the Office for Human Research Protections (OHRP) present The Research Clinic. The interactive training video educates clinical and social researchers on the importance of appropriately protecting research subjects and avoiding research misconduct.

2.  Quorum follow up to: the ResearchKit vs. FDA draft Guidance:

eConsent Mashup: FDA Guidance vs. ResearchKit

3.  What can go wrong with informed consent documents? Plenty ... news from the FDA

·  Lack of proper signatures and dates

·  Non-English speakers signing English consent documents

·  Lack of signatures from legally authorized representatives

·  Forged signatures

·  Consent obtained from subjects who lacked the capacity to give consent

·  Inadequate disclosure of risks associated with a trial protocol

·  Consent forms used without REB approval

Newsworthy/items of interest:

1.  International Clinical Trials Day

Below are news releases andlinks related to International Clinical Trials Day.

·  New Products and Partnership Agreements Mark International Clinical Trials Day at HealthCareCAN and the Network of Networks

·  Clinical Trials at Canada’s Academic Health Centres

·  What is the single greatest development that will help improve clinical trials? (Part One)

·  What is the single greatest development that will help improve clinical trials? (Part Two)

2.  Journal Article: Clinical trialist perspectives on the ethics of adaptive clinical trials: a mixed methods analysis BMC Medical Ethics (2015) 16:27

Summary:

One prerequisite of conducting any clinical trial is the careful consideration of the ethics of the trial procedures.

·  Trial design impacts scientific ethics (it is unethical to conduct an invalid study),

o  individual ethics (which patients are allowed to participate and what scientific and experimental procedures are they exposed to) and

o  collective ethics (the need to discover better treatments or treatments for untreatable conditions to improve future patient outcomes).

The ethical aspects of fixed RCTs and ACTs differ.

RCTs favour collective ethics:

·  The statistical focus of fixed RCTs, particularly those studies designed to change clinical practice or lead to drug or device approval (phase III or confirmatory), is to test hypotheses about treatment effect.

·  In such trials, the primary goal of a trial is to improve the treatment for the broader community, with individuals within the trial only conferring benefit if they are randomly allocated to the better treatment (if one is indeed found to be better).

·  Through informed consent, potential research participants decide themselves whether to be in a trial, or opt for conventional therapy.

ACTs favour individual ethics:

·  ACTs have different ethical nuances than more traditional, fixed RCTs.

·  In addition to the need for an informed decision whether to participate in the trial or choose conventional therapy, there are other ethical considerations.

·  For example, some adaptive design strategies increase the probability of receiving the more effective treatment while maintaining the scientific rigour of the trial. This emphasizes individual ethics because the objective is to treat as many patients effectively as is possible.

·  The potential advantage over fixed RCTs is that more patients will be assigned to the better-performing treatment arm(s), regardless of which arm(s) that turns out to be. This introduces one example of a potentially favorable ethical outcome not present in a fixed RCT.

·  A more recent review focused on the potential ethical risks of such trial designs, particularly highlighting the lack of equipoise that develops as the trial goes on and the inherent injustice that later enrolling subjects will get better treatments than earlier enrolling subjects.

·  Clinical trials in the critically ill are particularly challenging. Interesting, a hypothetical clinical trial scenario demonstrated greater participation when participants were offered a trial with response adaptive randomization.

3.  The Chronicle of Higher Education (from CAREB conference) U. of Minnesota Acknowledges Errors in a Second Psychiatric-Research Case

4.  NY Times article Company Creates Bioethics Panel on Trial Drugs Company Creates Bioethics Panel on Trial Drugs

5.  Do the dying have the right to experimental drugs?

NOTICES

Revised OCREB Main ICF (and harmonized consent) – v2015-June-01

Please note that the revised consent (developed and revised in tandem with the harmonized OCREB/NCIC ICF) has been posted on the O2 website. The harmonized OCREB/NCIC Main ICF has not been posted (since NCIC will submit the ICF to the provincial applicant using the approved template).

Note: The Memo for the Implementation of the OCREB NCIC ICF template (v2015-June-01), has been posted under MEMOS on the O2 webpage, and includes the additional language which must be added to the NCIC template when it is submitted (by the PA).

Use of OCREB Main ICF Template

Please note that the OCREB consent templates must be used and should be provided to the Sponsor or CRO as applicable for the submissions; initial submissions that do not include consents using the OCREB templates will be rejected.

Revised OCREB Consent Update – v2015-May-26

Please note that the Informed Consent Update Form has been revised. (minor changes to instructional text, etc.).

Revised SOP 701

The SOP was revised (5.1.9) to indicate that the Pregnant Partner ICF must be submitted only when/if there is a requirement for its implementation.

O2 Training

Hands-on new user, refresher training and advanced training sessions can be made available via webcast for provincial or centre applications. On-site training (i.e., at the centre) can be arranged if there are enough attendees. For those in the GTA, training at the OCREB office also can be arranged. The next training sessions are scheduled for June 11th, 10-2pm.

Please contact Kathie Zeman or Aurora de Borja to arrange O2 training.

REMINDERS

Implementing the approved Provincial ICFs

Please remember to use the approved ICF templates (and other participant materials) for the study as posted on the O2 workspace to ensure that the centre consent is the currently approved provincial consent (with applicable center-specific, pre-approved changes). Please refrain from revising the formatting other than to adjust for the addition of the letterhead to ensure that page breaks are in the appropriate place (e.g., a section header alone is not on one page and all of the content of the section on another). Formatting does not include changing the font size, type or case, wording changes or the correction of grammar errors.

Centre CR submissions

Please provide the most recent version of the ICFs in word format (i.e., not pdf) and all Consent Update ICF Forms at the time of the submission. The consents (required in word format) must be verified with the provincially approved versions.

IB and ICF changes

Please ensure that if there are changes to the risks, as part of the IB revisions, that a consent update is included, if applicable, and a revised main consent if enrolment is continuing.

Review of ICF and sponsor approval prior to implementation

Please ensure that your consents are reviewed by the sponsor prior to submission.

Sponsor correspondence

Please remember to include all related sponsor correspondence with reportable events/amendments as applicable.

OCREB MANDATE

Occasionally, OCREB is asked to accept multi-centre cancer research that does not fit our mandate. While we recognize that there is very important non-clinical trial research that could benefit from a centralized ethics review, we do not have the expertise, processes and resources to accept research that falls outside OCREB’s mandate. For the purposes of its current mandate, "multi-centre" is defined as more than one participating Ontario centre, and "clinical trial" is defined as any research that prospectively assigns human participants to one or more health-related interventions to evaluate the effects on health outcomes. Interventions are restricted to drugs and other biological products, surgical procedures, radiological procedures and devices.

Implementation at the Centre level of the OCREB ICF provincially approved ICF

Please remember to retain the version date on the provincially approved document when adding centre-specific (pre-approved) information.

OCREB Membership Changes

The OCREB membership roster was last updated on June 1, 2015. The current and archived membership lists can be accessed from https://ocrebonline.ca under “Membership”.

Project Submission Summary List

The list of studies with OCREB (project submission summary spreadsheet) is available on the O2 Home page https://ocrebonline.ca. The current version posted is from May 29, 2015.

OCREB ONLINE (O2)

Key Recent Enhancements

See also the “What’s New” section of O2 Home - https://ocrebonline.ca

A patch was applied to the system on June 4, 2015. The changes do not affect end users.

Outstanding issues (logged but not yet resolved):

·  Guidance text feature for application forms and workspaces;

·  Archiving for 25 years so system can be used as ethics study files.

STUDY SUBMISSION STATUS

For a list of all studies with OCREB, see the Project Submission spreadsheet at https://ocrebonline.ca

New studies submitted for the June meeting:

15-039 / Kathie / UHN / Carbo-Pem-MEK162-NSCLC / Leighl, Natasha / UHN / Maggie Sawczak
15-040 / Cindy / Incyte / INCB 18424-267 / Chen, Eric / UHN / Bonnie Kwan
15-041 / Aurora / OCOG / OCOG-2015-ATOM / Levine, Mark / OCOG / Beverly Pond
15-042 / Cindy / AZ / D5165C00001 / Goss, Glenwood / TOH / Amy Henderson
15-043 / Cindy / OCOG / OCOG-2013-PETMUSE / Levine, Mark / OCOG / Beverly Pond
15-044 / Kathie / NCIC / LY.17 / Kuruvilla, John / UHN / Nanthini Tharahan
15-045 / Aurora / NCIC / MA.32D / Bedard, Phillippe / UHN / Anna Malik
15-046 / Aurora / Pfizer / A5481034 / Verma, Shailendra / TOH / Yuhui Xu
15-047 / Aurora / PMHC / PHL-095 / Krzyzanowska, Monika / UHN / Bonnie Kwan
15-048 / Kathie / COG / AHOD1331 / Alexander, Sarah / HSC / Nivetha Ramachandran
15-049 / Kathie / COG / AHOD1221 / Alexander, Sarah / HSC / Catherine Deveault
15-050 / Cindy / NCIC / SRC.7 / Gupta, Abha / UHN / Nanthini Tharahan
15-051 / Aurora / UHN / ACDC-RP / Fleshner, Neil / UHN / Miran Kenk
15-052 / Aurora / IIS / TOPCOP / Alibhai, Shabbir / UHN / Henriette Breunis
15-053 / Aurora / UHN / LIGAND / Fleshner, Neil / UHN / Miran Kenk
15-054 / Cindy / AZ / D419AC00001 / Robinson, Andrew / KGH / Carrie Lindsaay

Studies in Pre Submission:

Sanofi / LPS14022 / Winquist, Eric / LHSC / Mary Beth Husson
Exelixis / XL184–401 / Krzyzanowska, Monika / UHN / Amirah Shahin
UHN / IMRT Phase III RCT-31 / Chung, Peter / UHN / Shawde Harris
COG / AEWS1221 / Gupta, Abha / HSC / Mandie Mio

Other Potential Studies:

CONTINUING REVIEW APPLICATIONS DUE FOR THE JULY MEETING – see next section

Be sure to keep track of the expiry dates of your studies. The system sends courtesy reminders 49 days, 15 days and 1 day prior to the expiry date.

There are approximately 49 studies involving 143 centre applications (approximately 192 continuing review applications) due by the June 25th deadline for the July 10th, 2015 OCREB Meeting, (i.e., expiring July 10th to August 13th 2015, inclusive), unless a study closure has been or will be submitted.

Next OCREB teleconference: July 3, 2015 @9am

Teleconference 2015-Jun-05 Page 5 of 17

CONTINUING REVIEW APPLICATIONS DUE FOR THE JULY MEETING

OCREB # / REC / Sponsor / Protocol # / PI / Centre / Centre Contact / Application Type / Expiry Date /
06-041 / Cindy Sandel / Ontario Clinical Oncology Group(OCOG) / 06-041 / Lukka, Himanshu R. / Hamilton Health Sciences / Yvonne Kinrade / Provincial / 8/8/2015
06-041 / Cindy Sandel / Ontario Clinical Oncology Group(OCOG) / 06-041 / Lukka, Himanshu R. / Hamilton Health Sciences / Yvonne Kinrade / Centre / 8/8/2015
06-041 / Cindy Sandel / Ontario Clinical Oncology Group(OCOG) / 06-041 / Bauman, Glenn S. / Lawson Health Research Institute(London) / Mary Beth Husson / Centre / 8/8/2015
06-041 / Cindy Sandel / Ontario Clinical Oncology Group(OCOG) / 06-041 / Malone, Shawn / The Ottawa Hospital / Lisa Turriff / Centre / 8/8/2015
06-046 / Cindy Sandel / NCIC Clinical Trials Group (NCIC CTG) / 06-046 / Bin, James / Toronto East General Hospital / Christine Stewart / Provincial / 8/8/2015
06-046 / Cindy Sandel / NCIC Clinical Trials Group (NCIC CTG) / 06-046 / Bin, James / Toronto East General Hospital / Christine Stewart / Centre / 8/8/2015