Hot Topics in Research Compliance

1. Hot Topics in Research Compliance June 5, 2007 F. Lisa Murtha

2. Agenda: June 5, 2007 • Session Summary & Objectives • CMS’s Proposed Clinical Research Policy • AAHRPP Accreditation • CTSA Initiatives • Summary and Conclusions • Questions

3. CMS’s Proposed Clinical Research Policy

4. Introduction and CMS Timeline for the Proposed Clinical Research Policy CMS announced reconsideration of the NCD on the Routine Costs of Clinical Trials July 10, 2006 CMS organized a Medicare Coverage Advisory Committee (MCAC) public meeting in Baltimore, Maryland to discuss the reconsideration. Dec 13, 2006 CMS released their proposed revisions to the NCD with a 30-day public comment period April 10, 2007 CMS deadline to publish the final NCD. The revised policy will be effective on the publication date. July 9, 2007

5. CMS Proposed Clinical Research Policy • The proposed Clinical Research Policy (CRP) address the following categories of issues: • General issues • Appropriate standards of a clinical trial that, if met, would ensure that the study is conducted pursuant to section 1142 of the Act • Appropriate processes that ensure that those standards are met • Items and services that are covered in studies meeting those standards

6. Proposed Changes • General Issues • Rename the NCD to “The Clinical Research Policy” (CRP). • Define research to add clarity to the Policy. • 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 protocol”.

7. Proposed Changes (continued) • 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”. • The eighth standard will be: “The research study must have a written protocol”. • Revise the “Qualifying Clinical Trial” criteria by: • Renaming them “Medicare-specific standards”; • Eliminating the first criteria; and • Combining and modifying the second and third requirements for greater clarity.

8. Proposed Changes (continued) • Standards of Clinical Research (continued) • Add the following Medicare-specific requirements: • The research study must be registered on the ClinicalTrials.gov website prior to the enrollment of the first study subject. • The research study protocol must specify and fulfill method and timing of public release of results. • 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. • 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).

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

10. Proposed Changes (continued) • Processes to ensure that those standards are met: (continued) • Medicare specific standards require that: • CMS will use routine processes to ensure that the Medicare-specific standards are met. • Items and services that are covered in studies meeting those standards: • Rename routine costs to “routine clinical services” and clarify the definition. • 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.

11. 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.

12. 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: • Have a written protocol; • Are registered on the ClinicalTrials.gov website prior to the enrollment of the first study subject; • 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.

13. Compliance and Cost Recovery Implications (continued) • A policy and process for assuring all studies: • Explicitly discuss inclusion criteria and considered relevant subpopulations (as defined by age, gender, race/ethnicity, socioeconomic or other factors) in the protocol. • Discuss how the results will generalize to the Medicare population in the protocol and to infer whether Medicare patients may benefit from the intervention. • 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.

14. 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 service/procedure. • Apply the appropriate criteria for determining coverage of the study • IDE studies are discussed in CMS Benefit Policy Manual Section 102 Chapter 14 • 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.

15. AAHRPP Accreditation Process

16. 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 responsibilities of the overall “HRPPP”

17. AAHRPP Background • Founded in 2001 with backing from PRIM&R and six other nonprofit organizations • 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 compliance • Approximately 500 Institutions in the AAHRPP accreditation pipeline • Currently the only organization offering Human Research Protection Program accreditation

18. 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 best-practices • 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

19. 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-practices • 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

20. 5 Phases of the Accreditation Process • Self-Assessment • Preliminary Application Preparation • Final Application Preparation • Site Visit • Final Response and Accreditation Status Determination

21. Example of a Preliminary Application Review

22. 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 offices • Annual reports describe problems and programmatic changes encountered or addressed within the year

23. Six Areas of Focus • Assessing HRPP-related organizational design and staffing • Evaluating HRPP-specific research and administrative processes • HRPP-related policy and procedure assessment/development • HRPP-related training and education • HRPP-related communication • Establishing measures for continuous improvement and sustainability

24. 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

25. 2-4 weeks 3-9 months 3 months 3-6 months 3 months 6-9 months after final app submission • Self-assessment • Pre-application development (policies, SOPs, and other supporting docs) and submission • Receipt of pre-application report from AAHRPP • Final application development and submission • AAHRPP site visit • Accreditation council meeting & accreditation status determination 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:

26. Each Phase has Different Time and Effort Requirements *Actual times will vary among institutions

27. Team Involvement in Corrective Phase Two different approaches to accreditation readiness: • 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 • Broad-based representation with numerous Subject Matter Experts involved 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

28. 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

29. Available Accreditation Resources • AAHRPP’s goal: a continuous educational process for those seeking accreditation • 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

30. 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

31. 4P’s Clinical & Translational Science Award (CTSA) Led to the CTSA Contributing to… 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” • New Pathways to Discovery • Research Teams of the Future • Re-engineering the Clinical Research Enterprise • Predictive • Personalized • Preemptive • Participatory “The Clinical and Translational Science Awards (CTSA) program is the result of the creative thought that focused on re-engineering clinical research.” – Elias Zerhouni

32. 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.

33. 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 spring up in any large organization • Advance the assembly of institutional academic “homes” that can provide integrated intellectual and physical resources for the conduct of original clinical and translational science • Create integrative academic structures • Provide a research environment that is more nimble, conducive to, and responsive to the the demands of modern translational and clinical research Expand Training & Education Support Innovation & Novel Methods • Transform clinical and translational research so that new medical treatments can be developed more efficiently and delivered more quickly to patients • Encourage the development of novel methods and approaches to clinical and translational research • Provide much-needed educational programs • Contribute to the growth of well-structured and well-recognized career pathways • Improve training and mentoring to ensure that new investigators can navigate the increasingly complex research system

34. MO1 General Clinical Research Center K12 Mentored Career Development K23 Mentored Patient Oriented Career Development K30 Clinical Research Curriculum Roadmap K12 Multidisciplinary Clinical Research Career Development Roadmap T32 Institutional Training Grants for Clinical and Translational Research Introduction: A New Funding Mechanism The consolidation of awards should be considered in constructing a CTSA budget To accomplish these goals, NCRR has combined several awards into a new, integrated program… U54 Clinical and Translational Science Award

35. 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

36. Questions?

37. Contact Information Contact Information F. Lisa Murtha Managing Director lmurtha@huronconsultinggroup.com (215) 497-0713