CTSA Lessons Learned by Zb0cdQt3


									Hot Topics in Research Compliance

 June 5, 2007

                                    F. Lisa Murtha
    Agenda: June 5, 2007

       Session Summary & Objectives
       CMS’s Proposed Clinical Research Policy
       AAHRPP Accreditation
       CTSA Initiatives
       Summary and Conclusions
       Questions

CMS’s Proposed Clinical Research Policy
    Introduction and CMS Timeline for the
    Proposed Clinical Research Policy

    July 10, 2006        CMS announced reconsideration of the NCD on the
                                 Routine Costs of Clinical Trials

                     CMS organized a Medicare Coverage Advisory Committee
    Dec 13, 2006
                         (MCAC) public meeting in Baltimore, Maryland
                                 to discuss the reconsideration.

    April 10, 2007         CMS released their proposed revisions to the
                            NCD with a 30-day public comment period

    July 9, 2007     CMS deadline to publish the final NCD. The revised policy will
                                 be effective on the publication date.

     CMS Proposed Clinical Research Policy

     The proposed Clinical Research Policy (CRP) address the following
      categories of issues:

       1. General issues

       2. Appropriate standards of a clinical trial that, if met, would ensure that the
          study is conducted pursuant to section 1142 of the Act

       3. Appropriate processes that ensure that those standards are met

       4. Items and services that are covered in studies meeting those standards

    Proposed Changes
    1. General Issues
       • Rename the NCD to “The Clinical Research Policy” (CRP).
       • Define research to add clarity to the Policy.
    2. Standards of Clinical Research
       • Continue the “seven highly desirable characteristics” and rename them
          “General Standards for a Scientifically and Technically Sound Clinical
          Research Study”.

           The eighth standard will be: “The research study must have a written

    Proposed Changes (continued)
    2.       Standards of Clinical Research (continued)

         •     Continue the “seven highly desirable characteristics” and rename them
               “General Standards for a Scientifically and Technically Sound Clinical
               Research Study”.

              a. The eighth standard will be: “The research study must have a written

         •     Revise the “Qualifying Clinical Trial” criteria by:

              a. Renaming them “Medicare-specific standards”;

              b. Eliminating the first criteria; and

              c. Combining and modifying the second and third requirements for greater
    Proposed Changes (continued)
    2. Standards of Clinical Research (continued)
       • Add the following Medicare-specific requirements:
          a. The research study must be registered on the ClinicalTrials.gov website
             prior to the enrollment of the first study subject.
          b. The research study protocol must specify and fulfill method and timing
             of public release of results.
          c. The research study must have explicitly discussed inclusion criteria and
             considered relevant subpopulations (as defined by age, gender,
             race/ethnicity, socioeconomic, or other factors) in the study protocol.
          d. The protocol must contain a discussion of how the results will
             generalize to the Medicare population.
       • The NCD process may establish additional standards through Coverage
          with Evidence Development (CED).
    Proposed Changes (continued)

    3. Processes to ensure that those standards are met:
       • General standards are met through studies approved by:
         a. DHHS Agencies, the Veterans Administration or the Department of
         b. Research centers or cooperative groups funded by one of the above
            Federal Agencies who have approved their process;
         c. the FDA and conducted under an Investigational New Drug (IND)
            application for which the protocol has been reviewed by the FDA;
         d. the FDA and required as a post-approval commitment; and
         e. CMS and required through CED.
       • Remove the following options for “deeming” studies:
         a. Self-certification process; and
         b. IND Exempt studies.

     Proposed Changes (continued)

     3. Processes to ensure that those standards are met: (continued)
            Medicare specific standards require that:
             a. CMS will use routine processes to ensure that the Medicare-specific
                standards are met.
     4. Items and services that are covered in studies meeting those standards:
        • Rename routine costs to “routine clinical services” and clarify the
        • Add a definition for “investigational clinical services” as well as cover them
           when the service is available to Medicare beneficiaries that are not
           participating in a study or when it is required through CED.
        • Add a definition of “administrative services” required to carry out studies
           and clarify that Medicare will not cover administrative services.
      Potentially Positive Implications

      Enhanced coverage for items and services in the future as a result of the
       Coverage for Evidence Development (CED) initiative from CMS to generate
       data on the utilization and impact of the item or service evaluated.

      Increased access to items and services as a result of the coverage of
       investigational clinical services in specific instances that are outlined above.

      The burden of proving “conventional care” is lifted if items and services are
       provided for the medical management of the patient.

     Compliance and Cost Recovery Implications

     Research Institutions may need to implement the following:
      A review of internal policies defining clinical research to ensure consistency
       with the CRP;
      A policy and process for assuring all studies:
        a.Have a written protocol;
        b.Are registered on the ClinicalTrials.gov website prior to the enrollment of
          the first study subject;
        c.Specify in the protocol and fulfill the method and timing of public release of
          all pre-specified outcomes to be measured including release of outcomes if
          outcomes are negative or study is terminated early.

     Compliance and Cost Recovery Implications (continued)

      A policy and process for assuring all studies:
        d.Explicitly discuss inclusion criteria and considered relevant subpopulations
          (as defined by age, gender, race/ethnicity, socioeconomic or other factors)
          in the protocol.
        e.Discuss how the results will generalize to the Medicare population in the
          protocol and to infer whether Medicare patients may benefit from the
      Create/update the policy on the coverage analysis / billing grid development
       process to include the requirements of the CRP;
      Develop a policy and/or process for managing IND exempt studies. Either an
       IND application will need to be submitted, and/or a process for managing loses
       on IND Exempt research should be developed; and
      Develop a training program on the Clinical Research Policy to educate
       research teams and billing staff on the changes.

     How to Conduct a Medicare Coverage Analysis

         Gather all of the relevant documents.
         Determine if this study is investigating a device, a drug, or a
         Apply the appropriate criteria for determining coverage of the study
         a. IDE studies are discussed in CMS Benefit Policy Manual Section 102 Chapter 14
         b. All other studies (including HUDs and other approved devices) will be governed by
            the General and Medicare Specific Standards of the CRP.
         Determine which items are paid for by the study sponsor and which items
          are promised free of charge to the patient in the informed consent form.
         Determine which of the remaining items are “routine clinical services” and
          their billable status.
         Document the results of the analysis.

AAHRPP Accreditation Process
     HRPP Accreditation History
        The shutdown of the human research conducted at several academic
         medical Centers and VA Hospitals by OPRR in the late 1990s brought
         the need for sound human research participant protections to the
         national spotlight

        Government committees begin debating the need for government-
         mandated accreditation of human research programs similar to JCAHO

        Preserving Public Trust: 2001 Report from the IOM’s Committee on
         Assessing the System for Protecting Human Research Subjects
          • Introduced concept of voluntary Human Research Participant Protection
            Program (HRPPP) accreditation and addresses the specific criteria that
            should be included in an accreditation program

        Responsible Research: 2002 Report from the IOM’s Committee on
         Assessing the System for Protecting Human Research Subjects
          • Expands on the “HRPPP” concept and discusses the various
16          responsibilities of the overall “HRPPP”
     AAHRPP Background

        Founded in 2001 with backing from PRIM&R and six other nonprofit

        Voluntary, proactive, educational accreditation model pre-empting
         potential prospect of mandatory, reactive, punitive government-
         enforced accreditation model

        Accreditation criteria based on Federal Regulations and Guidance, as
         well as industry best-practices that go above and beyond mere federal

        Approximately 500 Institutions in the AAHRPP accreditation pipeline

        Currently the only organization offering Human Research Protection
         Program accreditation
     AAHRPP Accreditation Model
        Evaluation Instrument based on initial PRIM&R HRPP criteria as well as
         criteria recommended by IOM in Preserving Public Trust

        77 AAHRPP “Elements” offer blueprint for criteria that must be met
         prior to accreditation
          • Elements based on Federal Regulations and Guidance and/or Industry

        Related elements are grouped into five main “Domains”:
          • Domain I: Organizational Domain (26 elements)
          • Domain II: Research Review Unit, including the IRB (31 elements)
          • Domain III: Investigator (11 elements)
          • Domain IV: Sponsored Research (5 elements)
          • Domain V: Participant Outreach (4 elements)

        Note that the IRB is a key component, but not the sole component of an
         institution’s Human Research Protection Program
     Earning AAHRPP Accreditation Adds Value from
     Both the Institutional and Researcher Standpoint
        Value to Institution:
          • Increases local and national credibility and limits potential for random
             audits by federal oversight offices

          • Brings institution in line with federal regulations and with industry best-

          • Limits potential for random federal audits

        Value to Researchers:
          • Makes their facilities more attractive to Sponsors

          • Improves the support services for processing and monitoring protocols

          • Improves policies and procedures, creating a more user-friendly
            interface for faculty and staff. Improves education programs for
            research staff
     5 Phases of the Accreditation Process

     1. Self-Assessment

     2. Preliminary Application Preparation

     3. Final Application Preparation

     4. Site Visit

     5. Final Response and Accreditation Status Determination

     Example of a Preliminary Application Review
     Element II.1.A: The Research    Suggestions:
     Review Unit has and follows     Policy & Procedure # 10
     written policies and             Modify to indicate that if members with adequate expertise cannot
     procedures requiring            be identified, consultation will be obtained
     protocols to be reviewed by
                                      If primary reviewer system is not used, describe the process
     individuals with appropriate
     scientific or scholarly         followed to ensure adequate expertise at eh meeting among IRB
     expertise.                      members

     Element II.1.B: The IRB has     Suggestions:
     a process for obtaining         Policy and Procedure #11:
     additional expertise when        Change statement from “IRB Members, Consultants, and
     reviewing a specific            Researchers” to “IRB Members and Consultants.”
     Element II.1.C: The Research    Suggestions:
     Review Unit has and follows     None.
     written policies and
     procedures so that IRB
     members and consultants do
     not participate in the review
     of protocols in which they
     have a conflict of interest,
     except to provide information
21   requested by the IRB.
     Ongoing: 3-year renewal
        Organization must submit annual reports to AAHRPP and must be
         revisited every three years to maintain AAHRPP accreditation

        AAHRPP also asks accredited organizations to keep AAHRPP informed
         of any sanctions or for-cause investigations from government oversight

        Annual reports describe problems and programmatic changes
         encountered or addressed within the year

     Six Areas of Focus

     1. Assessing HRPP-related organizational design and staffing

     2. Evaluating HRPP-specific research and administrative processes

     3. HRPP-related policy and procedure assessment/development

     4. HRPP-related training and education

     5. HRPP-related communication

     6. Establishing measures for continuous improvement and sustainability

     Key Considerations as you plan for AAHRPP

        Establishing a high level of organizational sanction and support

        Establishing a timeframe

        Securing influential work team sponsors

        Developing the corrective phase plan of attack

        Determining the number of stakeholders to be involved

        Composing work team membership

        Assessing and raising the level of institution-wide commitment

        Establishing close links to legal counsel

        Involving HR if organizational or staffing needs must be addressed
     Accreditation Timeframes

        Many currently accredited organizations have spend on average 18 – 30 months
         before achieving AAHRPP accreditation
          • More time required for institutions who receive a “Pending” accreditation
            status from the accreditation council

        Huron’s Experience:

                                                                                       6-9 months
                                                                                        after final
     2-4 weeks      3-9 months       3 months        3-6 months         3 months

     • Self-        • Pre-          • Receipt of pre- • Final         • AAHRPP site   • Accreditation
       assessment     application     application       application     visit           council
                      development     report from       development                     meeting &
                      (policies,      AAHRPP            and                             accreditation
                      SOPs, and                         submission                      status
                      other                                                             determination
                      docs) and
     Each Phase has Different Time and Effort Requirements

                                    Fin al R

                                             es pon

                                                       Self- As

                                             e     s

                   *Actual times will vary among institutions
     Team Involvement in Corrective Phase
     Two different approaches to accreditation readiness:
     1.   Single, small team handles all documentation/process changes needed
          for accreditation
          Pros: Group focus, speed, less consensus-building required
          Cons: Easier to miss key AAHRPP criteria, lack of institutional buy-in, more
             education and training required prior to site visit
     2.   Broad-based representation with numerous Subject Matter Experts
          Pros: Institutional buy-in, less education and training required prior to site
             visit, more likely to ensure that “all bases are covered”
          Cons: Consensus building more difficult, more time consuming

     Challenges that Might Surface
        Staff resistance to change

        Waning Faculty Interest

        Committee “Groupthink”

        Staff not empowered (or over-empowered)

        IRB or other departmental resistance

        Resource availability (Time, Effort, Money)

        Lack of Faculty/Senior Researcher participation

     Available Accreditation Resources
        AAHRPP’s goal: a continuous educational process for those seeking
        AAHRPP Website
         • News updates
         • Application guidance
         • Educational tools
        Policy guidance
         • AAHRPP Tip Sheets
         • Evaluation Instrument for Site Visitors
        Open lines of Communication
         • AAHRPP staff are reachable by phone and email
        Annual AAHRPP Conferences
         • Presentations by AAHRPP staff and by accredited institutions
                    CTSA Initiatives

“The development of this consortium represents the first systematic
      change in our approach to clinical research in 50 years .”
                  -Dr. Zerhouni, Director of NIH
     Introduction: Re-engineering the CR Enterprise
     Originating from the NIH Roadmap, the CTSA is contributing to an expanding vision

             NIH Roadmap: 3 Themes                         “Expanding Our Vision”

     1.   New Pathways to Discovery               1.   Predictive
     2.   Research Teams of the Future            2.   Personalized
     3.   Re-engineering the Clinical             3.   Preemptive
          Research Enterprise                     4.   Participatory

                                            Clinical &
                   Led to the             Translational                Contributing
                     CTSA                Science Award                    to…

      “The Clinical and Translational Science Awards (CTSA) program is the result of the
              creative thought that focused on re-engineering clinical research.”
                                        – Elias Zerhouni
     Introduction: Transformative Change
     The CTSA is intended to stimulate systematic change

        The Clinical and Translational Science Award program was conceived to “transform
         how clinical and translational research is conducted, ultimately enabling
         researchers to provide new treatments more efficiently and quickly to patients.”

        The integrated CTSA environment, intended to address “bidirectional information flow
         between basic and translational scientists,” can provide:
          • an academic home for CTS research;
          • support for protocol preparation, regulatory compliance and data management;
          • support for participant recruitment and human subject safety monitoring;
          • degree granting CTS programs;
          • specialized cores and services for translational research

        A major goal of the CTSA initiative is to develop a national consortium of CTSA
         institutions that will work together to transform the discipline of clinical and translational
         research across the country.

     Introduction: Designing Engines of Creativity
     NIH hopes to increase returns on investment in translational and clinical research

                 Enhance Coordination                            Foster Multidisciplinary Research
        Dissolve the artificial barriers that inevitably      Create integrative academic structures
         spring up in any large organization                   Provide a research environment that is more
        Advance the assembly of institutional                  nimble, conducive to, and responsive to the
         academic “homes” that can provide                      the demands of modern translational and
         integrated intellectual and physical resources         clinical research
         for the conduct of original clinical and
         translational science

             Expand Training & Education                        Support Innovation & Novel Methods

        Provide much-needed educational programs              Transform clinical and translational research
                                                                so that new medical treatments can be
        Contribute to the growth of well-structured and
                                                                developed more efficiently and delivered
         well-recognized career pathways
                                                                more quickly to patients
        Improve training and mentoring to ensure that
                                                               Encourage the development of novel methods
         new investigators can navigate the
                                                                and approaches to clinical and translational
         increasingly complex research system
     Introduction: A New Funding Mechanism
     The consolidation of awards should be considered in constructing a CTSA budget

            General Clinical Research Center

                           K12                        To accomplish these goals, NCRR
             Mentored Career Development              has combined several awards into
                                                         a new, integrated program…
            Mentored Patient Oriented Career
                     Development                                       U54
                                                         Clinical and Translational Science
                           K30                                         Award
              Clinical Research Curriculum

                    Roadmap K12
           Multidisciplinary Clinical Research
                  Career Development

                    Roadmap T32
         Institutional Training Grants for Clinical
                and Translational Research
     Promoting Collaboration
     CTSA encourages opportunities to develop internal and external partnerships

     Source: Anthony Hayward M.D., Ph.D., Director, Division for Clinical Research Resources,
     National Center for Research Resources
Contact Information
            Contact Information

                   F. Lisa Murtha
                  Managing Director
                   (215) 497-0713

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