REB REB Harmonization An idea whose time has come? EHIL Jack - - PDF document

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REB REB Harmonization

An idea whose time has come?

21/09/2011v2.2 EHIL Jack Corman IRB SERVICES

Objectives

 To provide insight into reasons for the current focus on

harmonization of ethics review in Canada harmonization of ethics review in Canada

 To provide historical perspective on past efforts  To further understanding of the meaning of

harmonization of REB review

 To promote an understanding of current initiatives in

p g North America re: REB harmonization

 To share views on impact of current & future efforts

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Overview

 Harmonization – why now?

 Past efforts at ethics governance reform  Past efforts at ethics governance reform  Impetus for change  Current initiatives  Prognostication

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Canadian Past efforts

• Governance of Research

– Chaiton Report – Chaiton Report – Law Society Report – PRE Research Governance Initiative – AB College of Physicians & Surgeons – FRSQ/Article 21 – NCEHR Task Force on Accreditation

• 2 reports
• Standard sub-committee

– Expert Committee on HRPP in Canada

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Impetus for Change

 Canada’s deteriorating CT position

 20% decline in new trial CTAs  20% decline in new trial CTAs  Losing ≈ 12% p.a.  Global ranking has dropped from 2nd to 3rd/4th

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Where are the CTs going?

Source: ClinicalTrials.gov, 2011

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International distribution of studies for 1 big pharma co. - disproportionate share to our market size?

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‘NE Asia is … becoming the most competitive region for industry‐sponsored clinical trials, owing to its population size, financial attractiveness & good track

• records. … this development will lead all 4 countries in

NE Asia to become the most important industry‐ sponsored emerging clinical trial region. There are …signs that the industry is … decreasing its clinical research development program activities in the established regions of North America & Europe & also in some emerging regions i e Latin America Africa and

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some emerging regions, i.e. Latin America, Africa and South East Asia including India. …. the winner will be China, Japan, Taiwan or South Korea...’ CT Magnifier May 2011

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How is the US Responding?

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CTTI: ‘Increasingly clinical trials are being conducted outside the US. The reasons behind this shift need to be understood so that US patients can continue to be represented in international clinical trials. Reasonable #s of US patients being included in trials is critically patients being included in trials is critically important to address the appropriate use of products by US citizens. [Therefore], the FDA’s Office of Critical Path Programs & Duke joined together as founding members of a PPP, the Clinical Trials Transformation Initiative (CTTI) CTTI brings

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Transformation Initiative (CTTI). CTTI brings together all interested stakeholders to identify practices that through broad adoption [to] increase quality & efficiency of CTs.’

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CTTI = Clinical Trials Transformation Initiative Jan. 2011

“Background
The willingness of institutions to defer full IRB review to a central IRB in defer full IRB review to a central IRB in multicenter trials continues to vary despite a 2006 Food and Drug Administration guidance recommending this approach. It is not yet clear what effect may result from a more recent endorsement of the use of central IRBs in multicenter trials by the U.S. Office for Human Research Protections.1”

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US Responding by:

 CTTI  Harmonization of FDA/DHHS regs & guidance  Attempts to simplify rules/regs for IRBs

 E.g., new guidance on unanticipated problem reporting

 Promotion of central models of ethical review  Increasing use of private sector central IRBs  Stepped up regulatory agency activity  Growing importance of accreditation

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Further US response: HHS ANPRM

1) Revise existing risk-based framework to more accurately calibrate the level ofreview to level of risk. calibrate the level ofreview to level of risk. 2) Using a single IRB review for all domestic sites of multi- site studies. 3) Updating forms & processes for informed consent. 4) Establishing mandatory data security & information ) g y y protection standards for all studies involving identifiable or potentially identifiable data.

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ANPRM (cont.)

5) Implementing systematic approach to data collection and analysis of data on unanticipated problems & AE’s and analysis of data on unanticipated problems & AE s across all trials to harmonize the definitions and reporting requirements & to make the collection of data more efficient. 6) Extending federal regulatory protections to apply to all research conducted at U.S. institutions receiving funding f th C R l i from the Common Rule agencies. 7) Providing uniform guidance on federal regulations.

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Why Not Central Review: Five key challenges (ASCO 2005)

 assurance of review quality;  sensitivity to local context;  liability;  control and accountability (incl. education of

researchers & monitoring); and l f

 loss of resources.

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What is Harmonization?

Harmonization does not always mean Central Review

Central review most efficient

.

Other models possible, e.g.,  Collaborative review  Mutual Recognition  “Reciprocal review”  Specialized REBs  Regional/National REBs

 Experts Committee recommendation:

 Mixed REB model, no exclusion (‘big tent’)  New agency to cover Policy, Education & PEERH Accreditation

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Changing OHRP Perspective on Harmonized/Central Review

The Paradoxical Problem with Multiple-IRB Review

Jerry Menikoff, M.D. J.D. NEJMed 2010; 363:1591-1593 Oct 21, 2010

The federal system for protecting research subjects was designed decades ago, when most research studies took place at [one]

• institution. These days, if a study is conducted

at multiple sites, an ethics review by an [IRB] may be repeated many times. This practice has b iti i d f b th ti d been criticized for both wasting resources and leading to inappropriate delays in the conduct

• f research.

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Changing Canadian Perspective: “Do It Once & Do It Well”

‘...simple calculation suggests [for] a 20-centre trial, some 300–500 person-hours in total may , p y be required of the parties involved in the ethics review process. Given this significant

• pportunity cost, one would hope to find clear

evidence that such a labour-intensive process protects patients effectively. Yet no such data i exist….

Research ethics review: Do it once and do it well Paul Hébert, MD MHSc and Raphael Saginur, MD, CMAJ March 17, 2009; 180 (6).

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Canadian Developments

 TCPS second edition  REB/IRB Standards  Provincial activities

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Canadian Response

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TCPS2

 Still mainly focused on 1 institution/1 REB, but

recognizes alternative ethics review recognizes alternative ethics review mechanisms for multicentre studies

 Clarifies potential for collaborative, even out-

sourced REB reviews by institutions

 Can be clearer on ways/means for

Can be clearer on ways/means for collaborative activities b/n & among REBs to

• ccur

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REB Accreditation

Canada Gazette II 2001-06-20, RIAS: “At the present time,there is no accreditation system in Canada for REBs. This situation is being reviewed by Health Canada in conjunction with the Canadian Institutes of Health Research (CIHR), the National Council on Ethics in Human Research (NCEHR) and other stakeholders in the Canadian clinical research community”

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Canadian clinical research community

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Case for Accreditation

 Foundational for MRA, especially in absence of HC

authority over REB operations/no verification authority over REB operations/no verification

 No accreditation without standards  “Standard” is technical

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REB Standard: An Accreditation Necessity

 CGSB Committee to set Standards for REBs reviewing biomedical

research – established 4 years ago, work is ongoing

 Struck to set a voluntary standard for REBs that review biomedical

research regulated by HC  REBs are outside HC inspectorate mandate  National Standard of Canada is something entities could be held to

 E.g., CSA electrical, helmets, etc.

 CGSB Standard voted on recently, work still underway  Assuming a standard is approved by the Committee, need to test

uptake & adherence to the standard

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Federal/National REBs

 There are several National REBs

 CBS  CBS  Stem Cell  PHAC  NRC  Health Canada

 Primarily review in-house research

Primarily review in house research

 Potential for more National REBs but jurisdictional and

• ther issues exist

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Provincial Initiatives - NL

 NL – Legislation creating a Health Research Ethics

Authority with its own REB on the books for 2+ yrs Authority with its own REB on the books for 2 yrs  Created because of foreign ‘helicopter researchers’  Recognizes existing MUN & other public REBs in the

province (3 for the province)

 No private REBs  No ‘for-profit’ REBs allowed  Proclaimed July 1, early stages

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Atlantic Region

 PEI, NB, NS working to accept each other’s reviews  Capital Health in NS

variable interpretations of scope

 Capital Health in NS – variable interpretations of scope

 Willing to collaborate

 NB Regions, e.g., Horizon

 No apparent intent to block central private review

 COI of private sector is a big concern  NS Privacy legislation is an issue – (Patriot Act concerns)

NS Privacy legislation is an issue (Patriot Act concerns)

 Does not necessarily mean action to ‘harmonize’ Atlantic

with other regions

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Quebec

 MSSS Multi-centric system

 Originally 2 or more sites  Originally 2 or more sites  Now 4 or more  Does NOT apply to private research sites

 FRQ-S Central review for Article 21 research  No intention to designate private sector REBs  Interested in developments elsewhere  National Accreditation system important to QC if

streamlining is to be even considered

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Ontario

 Life Science Programs, Ministry of Research &

Innovation - $11 million Innovation $11 million

 Plan to perhaps build on OCREB model  Looking to have 8 ‘hubs’

 OCREB + med schools?  No intent to exclude private sector REB  Institutions seem not keen on PPP

Collaboration/outsourcing

 OPHAC for public health/emergency research

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Manitoba/Sask

 Privacy legislation

 Has a limitation on who can review research  Has a limitation on who can review research  Pressure to have University review but not absolute

 No intent to harm competitiveness  IRB SERVICES now designated by Sask. MOH to

review research there

 Discussions underway with Univ. Sask, UM, UA, UC

and UBC for possible collaboration/mutual recognition

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Alberta: ‘Fly-over’ Province?

 New legislation in January 2010 eliminates Health Regions 

Alberta Health Research Ethics Reciprocity Agreement Alberta Health Research Ethics Reciprocity Agreement announced February 28, 2011  harmonized ethics review process for multi-jurisdictional health

research in 3 phases:

• 1. Implementing the Reciprocity Agreement
• 2. Implementing common approaches to informed consent guidelines

/ templates and a common ethics review application form

• 3. Establishing system-level capture and flow of appropriate

information supported by technology to inform ethics review involving more than one Board and to meet system level needs.

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BCEHI

 Harmonization efforts underway for at least 4 years

 Local vs central issues  Local vs. central issues

 Led by Michael Smith Foundation  Incorporates public sector

 UBC  BC Cancer Agency  BC Women’s & Children’s  Coastal Health Authority

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BCEHI

 Moving forward on:

• developing common processes and tools for use by all REBs;

developing common processes and tools for use by all REBs;

• create reciprocity agreements between

REBs; and

• a centralized provincial approach with one ethics review

mechanism.

No move at this time to exclude private sector or to prevent private sites from using central REB private sites from using central REB

• A Big Issue is Privacy Law – no MOH data is supposed to go

to the US (Patriot Act fears)

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Summary

 Increasing concern about loss of CTs to developing world is

driving a move to reduce/remove obstacles to competitiveness competitiveness

 Multi-centre REB review is considered an important

impediment to competitiveness

 Nationally, CIHR is taking the lead, partnered with Rx&D &

ACAHO  endorsing REB accreditation as critical to trust building  Recognizes no one-size-fits all approach works

 Individual provinces still taking Silo approaches –

CIHR/Rx&D/ACAHO initiative seeks to break down barriers

 Looking to UK as most likely model

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Summary

 A successful CGSB Standard is crucial to trust building

and potential breaking down of inter-provincial barriers and potential breaking down of inter provincial barriers

 Standard will lead to made in Canada accreditation  Willingness to out-source to independent central REB

still weak-nonexistent in Canada (unlike US)

 Will see more web/e-based submission systems

y  Platforms are coalescing around a small number  Big regulatory issue is validation/Part 11 Compliance

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Prognostication

 While finally progress is being made, it will take time before

substantial national change comes about

 Provinces still creating silos, early experimentation with

mechanisms for mutual recognition/reciprocity

 Private sector role slowly being recognized but may be

squeezed by new REB/review mechanisms that intrude into private office research P t f th t i t

 Pressure to reform the system is great:  “Law of Unintended Consequences” – risk that reform will

create more ‘Canada = fly-over country’ conditions

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Hopeful Signs

 Finally serious attention to finding solutions to Balkanized REB

review and other challenges

 Canada federally is working to find ways to improve our

competitiveness

 Clinical Trials Office & Inspectorate continue to present challenges  High C$ and other costs to conduct research is at least as

signficant an issue as fragmented ethics review, BUT costs of research in the developing world are rapidly rising

 Canada continues to be a preferred destination for research, and

we are finally aggressively acting to preserve and enhance our position

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Thank you

Questions?

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