asco-aaci what is the problem? · survey of research sites multi-stakeholder workshop dissemination...
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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)
SeptSept JanJan MayMay SeptSept
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
SeptSept JanJan MayMay SeptSept
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 10/14/2016‐still open• 1 Amendment
Activation 11/10/2014‐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
Copy in Shadow chart
Pathology Reports Hospital EMR Shadow chart kept in research office
Copy in Shadow chart
Operative Reports Hospital EMR Shadow chart kept in research office
Copy in Shadow chart
Diagnostic Imagining / X-rays / Scans Hospital EMR Shadow chart kept in research office
Copy in Shadow chart
Physical Exams Office EMR Shadow chart kept in research office
Copy in Shadow chart
Vital Signs Office EMR Shadow chart kept in research office
Copy in Shadow chart
Performance Status Office EMR Shadow chart kept in research office
Copy in Shadow chart
Study Specific Assessment Forms (ex: tumor measurement forms)
Shadow chart kept in research office
Shadow chart
Local Laboratory Results Office EMR/ Hospital EMR
Shadow chart kept in research office
Copy in Shadow chart
Central Laboratory Results Shadow chart kept in research office
Copy in Shadow chart
Adverse Event / Serious Adverse Event Data Office EMR/ Hospital EMR
Shadow chart kept in research office
Copy in Shadow chart
Concomitant Medications Office EMR/ Hospital EMR
Shadow chart kept in research office
Copy in Shadow chart
IP Orders Office EMR Shadow chart kept in research office
Copy in Shadow chart
IP Prep / Administration Records Office EMR Shadow chart kept in research office
Copy in Shadow chart
IP Logs Pharmacy PharmacyProgress Notes Office EMR/ Hospital
EMR Shadow chart kept in research office
Copy in Shadow chart
Outside doctor’s notes Office EMR/ Hospital EMR
Shadow chart kept in research office
Copy in Shadow chart
Hospitalization Records Hospital EMR Shadow chart kept in research office
Copy in Shadow chart
Study Specific Source
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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?
ASCO Research Community Forum 2017 Annual Meeting