ASCO-AACI What is the problem? · Survey of Research Sites Multi-Stakeholder Workshop Dissemination of Findings Develop and Implement Solutions 20152015 20162016 20172017 Vose et

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Reducing Administrative and Regulatory Burden

Michael A. Thompson, MD, PhD, Aurora Health Care

Andrea Buchmeier, BS, CCRC, Catholic Health Initiatives

Kandie Dempsey, PhD, MS, RN, OCN, Christiana Care Health Services

Overview of Session

• Updates on ASCO Best Practices and RCF initiatives

• Challenges with federal and industry funded trials

Central IRBs

Protocol amendments

Interpretations of regulations

• Discussion

ASCO-AACIBest Practices in Cancer Clinical Trials Initiative

Michael A. Thompson, MD, PhDASCO RCF Council Past Chair

Aurora Health Care

What is the problem?

• Existing requirements on research are: Inefficient and costly to implement Interpreted conservatively by institutions/lawyers Slowing patient access to safe and effective treatments A headache!

ASCO Research Community Forum 2017 Annual Meeting

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ASCO-AACI Working Group

Julie Vose, MD, MBA (Chair) |

ASCO Past President, University of Nebraska

Dan Hayes, MD | ASCO Past President, University of Michigan

Steven D. Averbuch, MD | Bristol-Myers Squibb

Amy Burd | LLS Society

Kandie Dempsey, PhD, RN, OCN |

Christiana Care Health Services

Lee Ellis, MD | MD Anderson

Bill Hait, MD | Johnson & Johnson

Brenda Hann, RN, MBA |

Stanford Cancer Institute

Dax Kurbegov, MD |

Sarah Cannon Research Institute

Carrie Lee, MD, MPH | UNC Chapel Hill

Joan Levy, PhD | Multiple Myeloma Research Foundation Terry L. Murdock | QuintilesSheila Prindiville, MD, MPH | NCITatiana M. Prowell, MD | US FDADavid Smith, MD | University of MichiganTerri Stewart, MS, CRCP |

New Mexico Cancer Care AllianceConnie Szczepanek, RN, BSN |

Cancer Research Consortium West MichiganMichael A. Thompson, MD, PhD | Aurora Health CareTom Witzig, MD | Mayo ClinicDebra Wujcik, PhD, RN | Vanderbilt Ingram Cancer Center

ASCO Staff: Laura Levit, JD | Patricia Hurley, MSc | Caroline Schenkel, MSc | Suanna Bruinooge, MPH

AACI Staff: Janie Hofacker | C.J. Confair

Steps of the Initiative

Working GroupConvened

Survey of Research Sites

Multi-Stakeholder Workshop

Dissemination of Findings Develop and

Implement Solutions

20152015

20162016

20172017

Vose et al., Journal of Clinical Oncology, 2016

Identifying Solutions

Multi-StakeholderWorking Group

• ASCO• AACI• Research Sites (academic,

community)• Physician Investigators• Research Administrators• Industry Sponsors• CROs• Federal Sponsors• Patient Advocates

Survey ofResearch Sites

• Objective: Identify most burdensome administrative and regulatory aspects of conducting clinical trials

• Respondents (N=310)• Physicians, research nurses,

administrators• Range of research program types

(academic & community)• Conduct federally-sponsored and/or

industry-sponsored trials

• Priority areas identified to address administrative and regulatory burden

Multi-Stakeholder Workshop

• Objective: Identify tangible solutions to priority areas

• Over 60 attendees from stakeholder groups• Leading cancer research organizations,

academic centers, community oncology practices, patient advocacy groups, government, industry, and CROs

• Teams identified and worked on solutions to identified issues

Priority Areas Addressed at Workshop

Clinical Trial Contracts

Negotiation Processes

Specific Contract Clauses

Inter- & Intra- Institutional Contracts

Clinical Trial Coverage

& Budgeting

Coverage Analysis of

Funded Trials

Billing & Coverage of Procedures

Budgeting for Infrastructure & Research Aspects of Trials

Regulatory & Training Requirements

Training Requirements

AE/SAE Documentation & Reporting

Auditing/MonitoringVisits & QueriesDocumentation

Gaps and potential solutions were identified during Workshop

Note: Many topics had existing resources and initiatives, but they have not been effective. (Sites are still overwhelmed!)


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Three Priority Solutions Selected

• Identify and implement strategies to optimize AE reporting1) Reduce Volume

of AE Reports

• Develop a centralized portal for research sites streamline routine requests, provide access to resources

2) Streamline Sponsor/ CRO Requests

• Develop training and resources to facilitate insurance coverage analyses (determine routine- vs research-related services and costs and avoid coverage denials)

3) Facilitate Coverage Analysis

1) Reduce Volume of AE Reports Identify and implement strategies to optimize adverse events reporting

IdentifyExisting Initiatives

• Explore existing initiatives to identify gaps and determine role for ASCO (e.g., FDA, CTTI, etc.)

Meet with Stakeholders

• Stakeholder meeting in March 2017 (ASCO leadership, CTTI, FDA, sponsors)

• Discuss strategies for increasing compliance with AE reporting requirements

DevelopGuidance

• Develop recommendations and guidance document

Disseminate Solutions

• Publish ASCO Research Statement (Submitted Aug 2017)

• Promote recommendations at research meetings

SeptSept JanJan MayMay SeptSept

20162016 20172017 20182018

ASCO Recommendations for AE Reporting

1) Sponsors and CROs should adopt best practices for reporting AEs.

2) Researchers and research sites should adopt best practices for reporting AEs to sponsors.

3) International regulatory agencies should harmonize the regulations for AE reporting.

4) All stakeholders should use modern, digital technology to report AEs.

ASCO research statement in press.

2) Streamline Requests from Sponsors/CROsDevelop a centralized portal for research sites to streamline routine requests and provide access to important resources

Develop Concept

• Conduct gap analysis• Develop detailed concept document for centralized portal

Conduct Market Research

• Conduct market research with multiple stakeholders (sites, research networks, sponsors, CROs) to determine needs and interest in a centralized portal for research sites

• Explore scope and functional needs

Determine Next Steps

• Determine whether to proceed with developing a prototype for the portal, based on feedback from stakeholders (Fall 2017)

• If decision is to proceed… develop and submit business development plan and develop prototype (Spring 2018)


20162016 20172017 20182018


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Identify Gapsand Resources

• Identify gaps, and existing resources and initiatives around common language, clinical standards, and determining routine- vs. research-related services and costs

• Publish recommendations for sponsors to centralize coverage analyses (Szczepanek et al, JOP, 2017)

Develop Resources

• Develop content for a training workshop for research sites

• Compile resources for a toolkit• Solicit feedback from

stakeholders (sites, investigators, research and billing staff, trial sponsors, provider/payers, CMS, patients)

Disseminate Solutions

• Develop and conduct training workshop at ASCO Research Community Forum Meeting (Sept 2017) on best practices to prevent and address coverage denials

• Make toolkit/resource(s) available publicly (Dec 2017)

3) Facilitate Coverage AnalysisDevelop training and resources to facilitate insurance coverage analyses to help determine routine- vs research-related services and costs and avoid coverage denials


20162016 20172017 20182018

ASCO-Friends of Cancer ResearchBroadening Eligibility Criteria Project

• Goals Identify areas where eligibility criteria can be safely expanded Promote cultural change generalizability (patients enrolled = patients seen in practice) Advance generalizability of trial results

• Recommendations for Broadening Eligibility Criteria HIV/AIDS, minimum age, brain mets, and organ dysfunction, or prior or concurrent malignancies

• Plans for Implementation Joint ASCO-Friends research statement and four supporting manuscripts JCO (October 2017) ASCO and Friends will work with industry/sponsor, regulatory, and advocacy partners to:

1) Educate stakeholders about the recommendations 2) Support refinements to regulatory processes 3) Seek official endorsement from the NCI and Cooperative Groups

ASCO’s TAPUR study has already operationalized some recommendations (e.g., patients <18)

Reducing Administrative and Regulatory Burden

Andrea Buchmeier, BS, CCRC, LLSGBASCO RCF Council

Catholic Health Initiatives

HistoryNCI Protocol

Approval Process

Timelines: Goals and

ResultsAmendments

Impact


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Transition Period: Pediatric, Brain/CNS, & Melanoma Studies will not have SCs until end CY 2010, large Phase 2 and Phase 3 proposals will be evaluated by CTEP Concept or Protocol Review Committee until SCs up and running.Form v2.0 updated 8/6/10

Time to Trial Activation Current vs OEWG Target

Current median time includes CIRB approval, industry negotiations, and FDAapproval

Time to Trial Activation 2009 vs OEWG Target

NCI OEWG, 2009

Results = Improved timelines

Amendments

54

111

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CHI NCORP Protocol Portfolio

Open to Accrual

Maintenance

On Hold

CHI NCORP Grant Year 3 Processed 122 Amendments (August 1, 2016-July 31, 2017)

Cost of Amendments

Ave

rag

e

Co

ord

ina

tor

Co

st

pe

r H

ou

r

$45

Ave

rag

e h

ou

rs

per

Am

end

men

t

6.65

Per

A

men

dmen

t C

ost

$229.25

$16,470/year


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Overall Cost to ALL sites1 Amendment for ONE trial=

$229.25 X 1,000

= $229,290

Assume 1 NCI trial

Assume 1000 clinical

research sites

50,000 x $229.25 =

$11,465,500

50,000 amendments

processed each year

Assume 1 Amendment

each trial/year

Assume 50 trials at 1000

Sites

Research Base ExampleProtocol

Activation-February 27,

2014

7/24/14

10/24/15 6/8/15

8/17/15

11/30/15 12/14/15

3/21/16

5/31/16 9/16/16

5/15/17

1/16/17

Other Research Base examples

Activation 4/8/2013‐Closed to Accrual 3/17/2017• 10 Amendments• 90 accruals (goal 165)

Activation 11/15/2016• 1 Amendment

(6/15/2017• 53 accrual (goal 1000)

Activation 6/10/2013‐closed to accrual and treatment • 5 amendments• 294 accruals (goal 299)

Industry Examples

Activation 5/13/14‐still open• 1 Amendment



Activation 5/1/2015 ‐still open• 0

Amendments


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Site PrioritiesAdministrative Ops

Investigators and Clinical Ops

The #1 Priority is Keeping

trial open

Continuing reviews Amendments

New Treatment Options‐new trial

opportunities

Need and want a robust trial

portfolio

Resulting in consideration of all

patients for a clinical trials

Ultimate goal‐Enrolling patients

Reducing Administrative and Regulatory Research Burdens: A community research organizations experience

Kandie Dempsey, DBA, MS, RN, ONC

ASCO RCF Member

Delaware/Christiana Care NCORP

Christiana Care Health Services

Helen F. Graham Cancer Center & Research Institute

Newark, Delaware

Stakeholders Engaged in Identifying Solutions

• ASCO Develop & Implement Solutions – December 2017

• ASCO Community Research Forum– September 2017

• ASCO-ACCI Recommendations – 2016

• IOM – National Clinical Trial System for 21st Century– 2010

• NCI Operational Efficiency Working Group– 2008

• NCI Clinical Trials Working Group– 2005

• NCI - Armitage Report− 1997

Priority Solutions Selected

• Identify and implement strategies to optimize AE reporting

Reduce Volume

of AE Reports

• Develop a centralized portal for research sites to streamline routine requests and provide access to important resources

Streamline Sponsor/CRO

Requests

• Develop training and resources to facilitate insurance coverage analyses to help determine routine- vs research-related services and costs and avoid coverage denials

Facilitate Coverage Analysis


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ASCO’s Priority Solutions

Reduce Volume of AEs

Volume

Appropriateness

Electronic Systems

Streamline Sponsor/CRO Requests

Training

Regulatory Data

Monitoring/Audits

Facilitate Coverage Analysis

Specialized Resources

Coverage Variations

Lack of Standardization

Reduce Volume of AE Reports– AE’s reported regardless of the causality of

the agent being investigated.

– Events are reported that are not identified as potential SE of the investigational agent

– PI’s must sign off on all SAEs, even when there are no relationship to the study drug and no resulting in consent changes.

Reduce Volume of AE Reports– Electronic AE Reporting Systems

• PI only authorized user, must delegate research professional

• May take hours to log in, down load and sign off

• Reported individually, rather than in aggregate

• Many require monthly password changes

• Some continue to use paper submissions

– CROs upload SAEs for several trials using separate sponsors – difficult to attribute SAE to specific study

– Volume – Hundreds for life of study is not uncommon


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Streamline Sponsor/CRO Requests

• Contract Research Agonizations (Sekeres)

– “CROs are an invasive weed – an administrative kudzu – that infests

the clinical trial process”

• Advocating for a Return to Common Sense in Research (80 European Investigators)– “quality…synonymous with mindless, needless, and ultimately

counterproductive bureaucracy”

– CRO parasite…”a living being feeding itself at the expense of the organism that shelters it”

– Paperwork required is “descending into absurdity”

Streamline Sponsor/CRO Requests• Training Requirements

– Pre-SIVs; SIVs; Monitoring Visits

– Constant Webinars

– Amendments

• Regulatory Data

– US Date Format versus European Date Format

– Matching Signatures – Name Format

• Forms and More Forms– Site Contact; Data Source Log; Delegation of Duties Logs;

Policies/Procedures; Calibration Logs

– Audits – Requiring CAPAs after every monitoring site visit!

• Notes to File

Data Point Chart Location Physical Location Primary Source Document

Signed Informed Consent Forms Office EMR Shadow chart

Demographics Office EMR Shadow chart kept in research office

Copy in Shadow chart

Inclusion/Exclusion Confirmation Shadow chart kept in research office

Shadow chart

Medical History Office EMR Shadow chart kept in research office


Pathology Reports Hospital EMR Shadow chart kept in research office


Operative Reports Hospital EMR Shadow chart kept in research office


Diagnostic Imagining / X-rays / Scans Hospital EMR Shadow chart kept in research office


Physical Exams Office EMR Shadow chart kept in research office


Vital Signs Office EMR Shadow chart kept in research office


Performance Status Office EMR Shadow chart kept in research office


Study Specific Assessment Forms (ex: tumor measurement forms)

Shadow chart kept in research office

Shadow chart

Local Laboratory Results Office EMR/ Hospital EMR



Central Laboratory Results Shadow chart kept in research office


Adverse Event / Serious Adverse Event Data Office EMR/ Hospital EMR



Concomitant Medications Office EMR/ Hospital EMR



IP Orders Office EMR Shadow chart kept in research office


IP Prep / Administration Records Office EMR Shadow chart kept in research office


IP Logs Pharmacy PharmacyProgress Notes Office EMR/ Hospital

EMR Shadow chart kept in research office


Outside doctor’s notes Office EMR/ Hospital EMR



Hospitalization Records Hospital EMR Shadow chart kept in research office


Study Specific Source


10ASCO Research Community Forum 2017 Annual Meeting

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Electronic Medical Records Questionnaire (EMRQ)

Computerized System/Electronic Source Documents1. What is the computer system’s environment?

Stand Alone PC Local Area Network Internet Based

2.Primary use of this computer system:

Electronic-Medical Records System (EMR)

Lab Information System (ECG, Xray,Etc)

Specialized program that measures study endpoint-

3. Are the following controls in place to limit access to the system? [Check all that apply]a. Unique user accounts (User ID & password) Yes No

a. Automatically log off user after idle periods Yes No

a. Locks user account after several failed log in attempts Yes No

a. Site processes do not allow sharing of ID/password to access the system Yes No

4. Is there a site/institution SOP that addresses the use of an EMR and site source data collection?(CRA may request a copy for the study files.) Per institutional guidelines, CRA may view SOP on site, but not copy.

Yes No5. Are users assigned appropriate roles when accessing the data (i.e., Only PI can edit data)? Yes No Research nurses can print only, do not have ability to add or edit data.

6. Are users of this system trained on using the system? Yes No Research nurses have print only capability.

If yes: a. Is the training documented? Yes No

7. Is there a process for resolving problems during normal system use? Yes No

8. Is creation, deletion, and modification of electronic source data tracked or logged in an audit trail? Yes No [If No, proceed to Q9]

Facilitate Coverage Analysis• Research team members often do not have knowledge

of:

– Standard of care versus non-standard of care

– What is or isn’t eligible for insurance coverage

– Budgeting –

• Costs of activating and running a trial

• Hidden trial costs

• Ancillary department or practice fees

– Clinical trial coding and billing experience

– Lack of software application or centralized process

Facilitate Coverage Analysis• Funding announcements not provided at time of

study activation.

• Amendments – Revised Coverage Analysis not submitted simultaneously

• Reimbursement Ambiguity– “Most of the time insurance will cover it”

– “Submit to insurance, and if insurance doesn’t pay submit to sponsor for payment”

• Non-study drugs required, but not provided

• Tests frequencies, not per NCCN guidelines

Extras

• Unrealistic Inclusion/Exclusion Criteria

• Collecting Data that is not used

• Significant problems with CIRB amendments not included in consents

• Foundation Trials – Reimbursement higher for academic sites than community sites


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Research Cures Cancer

• Enhanced efficiencies in these priority areas are expected to– Reduce bureaucratic burdens

– Improve operational efficiencies

– Improve speed and efficiency of completing trials

– Translate clinical discoveries into clinical benefits for our patients!

Citations• (Vose) DOI: 10.1200/JCO.2016.69.6781 Journal of Clinical Oncology 34,

no. 31 (November 2016) 3796-3802.

• (Kaiser) DOI: 10.1200/JCO.2010.29.6608 Journal of Clinical Oncology 28, no. 34 (December 2010) 5046-5053.

• (Sargent)DOI: 10.1200/JCO.2010.31.7024 Journal of Clinical Oncology 28, no. 34 (December 2010) 5019-5021

• Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. https://doi.org/10.17226/12879.

• (Sekeres) ASH Clinical News. Contract Research Agonizations. https://www.ashclinicalnews.org/perspectives/editors-corner/contract-research-agonizations/

• ASH Clinical News. Advocating for a Return to Common Sense in Clinical Research https://www.ashclinicalnews.org/perspectives/advocating-return-common-sense-clinical-research/

Talking Points

• Priorities?

• Interest in Pursuing?

• Work Group Formation?

• Problems not being addressed that requires additional attention?

• Stakeholders to include?
