1. NATIONAL CLINICAL TRIAL (NCT) NUMBER Clinical Trials Management Office December 17, 2014

2. ClinicalTrials.gov BACKGROUND Food and Drug Administration Modernization Act of 1997 (FDAMA) –Investigational New Drug (IND) applications to test the effectiveness of experimental drugs for serious or life-threatening diseases or conditions –Federally or Privately funded Trials –Co-operation from NIH and the Food and Drug Administration (FDA) February 2000 : Launch of ClinicalTrials.gov FDA Amendments Act of 2007 (FDAAA) –Section 801 of FDAAA (FDAAA 801): Expands registry (more types of trials need to be registered and additional trial registration information have to be submitted) Add Results Reporting requirement. September 2008: Launch of the Clinicaltrials.gov results database Establish penalties for failing to register or submit the results of trials.

3. WHY TO REGISTER TO ClinicalTrials.gov? Human Subject Protections –Allows potential participants to find studies –Assist ethical review boards and others in determining appropriateness of the studies being reviewed –Promote fulfillment of ethical responsibility to human volunteers – research contributes to medical knowledge Research Integrity –Facilitates tracking of protocol changes –Increases transparency of research enterprise Evidence Based Medicine –Facilitates tracking of studies and outcome measures –Allows for more complete identification of relevant studies Allocation of Resources –Promotes more efficient allocation of resources

4. WHAT CAN I FIND ON ClinicalTrials.gov? Summary InformationResults of the study Submitted at Trial InitiationSubmitted after Trial Completion Summarize information about Trial Protocol Summarize Trial Results Disease or condition Intervention Title, description, and design of the study Requirements for participation (eligibility criteria) Locations where the study is being conducted Contact information for the study locations Relevant Bibliography Description of study participants (the number of participants starting and completing the study and their demographic data) Outcomes of the study Summary of adverse events experienced by study participants Full history of changes One record per Trial

5. LOCATION OF REGISTERED STUDIES Location # of Registered Studies and % of Total* Non-U.S. Only 81,951 (45%) U.S. Only 70,977 (39%) Not Specified 16,721 (9%) Both U.S. and Non-U.S. 10,819 (6%) Total 180,468 Non-U.S. Only (45%) U.S. Only (39%) Not Specified (9%) Both U.S. and Non-U.S. (6%) Source: https://clinicaltrials.gov/ct2/resources/trends *as of December 10, 2014

6. LOCATION OF REGISTERED STUDIES Source: https://clinicaltrials.gov/ct2/resources/trends

7. TYPE OF REGISTERED STUDIES Study and Intervention Type # of Registered Studies and % of Total* Total 180,468 Interventional145,671 (80%) Type of Intervention Drug or biologic93,847 Behavioral, other38,780 Surgical procedure15,874 Device14,431 Observational33,967 (18%) Expanded Access282 *as of December 10, 2014 Source: https://clinicaltrials.gov/ct2/resources/trends

8. NUMBER OF REGISTERED STUDIES OVER TIME Source: https://clinicaltrials.gov/ct2/resources/trends

9. WHO IS RESPONSIBLE FOR REGISTERING TRIALS AND SUBMITTING RESULTS? The Responsible Party is defined as: The sponsor of the clinical trial or The principal investigator (PI) of such clinical trial if so designated by a sponsor, grantee, contractor, or awardee Registration Deadline The Responsible Party for an Applicable Clinical Trial must submit the required clinical trial information no later than 21 days after enrollment of the first participant

10. WHICH STUDIES MUST BE REGISTERED AND HAVE RESULTS SUBMITTED. Registration is required for trials that meet the FDAAA 801 definition of an "applicable clinical trial" and were either initiated after September 27, 2007, or initiated on or before that date and were still ongoing as of December 26, 2007. Applicable Clinical Trials include the following: Trials of drugs and biologics: Controlled clinical investigations, other than phase 1 clinical investigations, of drugs or biological products subject to Food and Drug Administration (FDA) regulation Trials of devices:1) Controlled trials with health outcomes of devices subject to FDA regulation, other than small feasibility studies, and 2) pediatric postmarket surveillance required by FDA Applicable Clinical Trials generally include interventional studies (with one or more arms) of FDA-regulated drugs, biological products, or devices that meet one of the following conditions: The trial has one or more sites in the United States The trial is conducted under an FDA investigational new drug application or investigational device exemption The trial involves a drug, biologic, or device that is manufactured in the United States or its territories and is exported for research

11. EXCLUSIONS Phase 1 drug trials, including studies in which investigational drugs are used as research tools to explore biological phenomena or disease processes Small clinical trials to determine the feasibility of a device or a clinical trial to test prototype devices, where the primary outcome measure relates to feasibility and not to health outcomes Trials that do not include drugs, biologics, or devices (such as behavioral interventions) Non-interventional (observational) clinical research (such as cohort or case-control studies) Trials that were ongoing as of September 27, 2007, and reached the Completion Date before December 26, 2007

12. Another term for the ClinicalTrials.gov registry number Unique to each record The format for the ClinicalTrials.gov registry number is “NCT” followed by an 8-digit number, e.g.: NCT00000419 NATIONAL CLINICAL TRIAL NUMBER

13. August 9, 2013 CMS Transmittal Changes to Claims Processing Manual, Chapter 32 “Effective for claims with dates of service on or after January 1, 2014, it is mandatory to report a clinical trial number on claims for items/services provided in clinical trials/studies/registries, or under CED” (emphasis in original) NATIONAL CLINICAL TRIAL NUMBER

14. MEDICARE Medicare may pay items and services in clinical research studies under three policies: The Clinical Trial Policy (CTP) The Investigational Device Exemption (IDE) Coverage with Evidence Development (CED) 14

15. NATIONAL COVERAGE DETERMINATION (NCD) FOR ROUTINE COSTS IN CLINICAL TRIAL (310.1) A decision issued by the Centers for Medicare and Medicaid Services to allow Medicare to cover the routine costs of qualifying clinical trials, as well as reasonable and necessary items and services used to diagnose and treat complications arising from participation in the clinical trial. Evaluation Points to determine if costs of a trial are coverable: –Is the Clinical Trial a Qualifying Trial? –Are the Services & Items Routine Costs? –Are the Routine Costs reasonable & necessary (i.e. are they generally covered by Medicare outside a clinical trial)? Source: http://www.cms.gov/manuals/downloads/ncd103c1_Part4.pdf 15

16. INVESTIGATIONAL DEVICE EXEMPTION (IDE) 16 Medicare Coverage Regulations for Investigational Device Exemption (IDE) are different: Devices must be identified as either Category A (experimental) or Category B (proven technologies that have had questions about its safety and effectiveness resolved) Providers that participate in an IDE Trial must notify the Medicare Administrative Contractor (MAC) to approve the study as a Qualifying Trial. New CMS rules for device studies effective January 1, 2015, study sponsors will be responsible obtaining CMS approval for reimbursement

17. CED allows coverage of certain items or services where additional data gathered in the context of clinical care would further clarify the impact of these items and services on the health of Medicare beneficiaries. Medicare coverage may be extended to patients enrolled in a clinical research study. Medicare may make an NCD that requires participation in certain Clinical Trials, Longitudinal Studies, or registries for coverage of an investigational item/service and routine and related items/service. 17 COVERAGE WITH EVIDENCE DEVELOPMENT (CED)

18. MEDICARE COVERAGE OF CLINICAL TRIALS, PROSPECTIVE STUDIES, AND REGISTRIES CTPIDECED CMS Approval requiredNo – must qualify under NCD 310.1 Yes –each specific study approved by FDA before 1/1/2015, requires MAC approval; for each specific study approved by FDA after 1/1/2015, requires CMS approval Yes – requires CMS approval for each specific study Public notificationNo – provider determines qualification Each specific study approved by FDA after 1/1/2015 appears on CMS IDE Website Each specific study approved by CMS appears on CMS IDE Website Routine Services (Q1)Covered if otherwise coverable by Medicare in qualified study Covered if study is approved by CMS and otherwise coverable by Medicare Covered if study is approved by CMS and otherwise coverable by Medicare Investigational Item/Service (Q0) Covered if otherwise coverable by Medicare in qualified study Covered if study is Category B, and approved by CMS Covered if study is approved by CMS 18

19. WHEN DOES THE NCT HAVE TO BE REPORTED? If a study is registered on ClinicalTrials.gov and is assigned an NCT identifier number, and includes billable charges, the NCT Identifier Number should be reported on all related claims as long as the patient is a study participant The NCT identifier number is required on the claim transmitting items/services provided relative to the trial/study/registry if it qualifies for the CTP, is an IDE study, or is a CED study. –The individual line-items will be identified with an appropriate -Q0 or - Q1 modifier to identify coverage –In case of overlapping with another Identifier, the NCT Identifier Number is still needed –For recruiting, active, or not recruiting Clinical Trial 19

20. WHEN DOES THE NCT HAVE TO BE REPORTED? Only applies for routine Items/Services that are part of the Clinical trial, including routine care for the condition in the Clinical Trial, need to be submitted with a NCT Identifier Number Providers should use their professional judgment in determining Medicare coverage of individual items/services and what is and is not related to a given trial (for example a care considered routine care that they would receive regardless) The 99999999 number can be used for claims only when: –The NCT number is not known –The study is not an IDE study or a CED study The NCT identifier number is required on every trial-related item/service claim, encounter, and/or date of study visit. It is not required on every line item. 20

21. WHEN DOES THE NCT HAVE TO BE REPORTED? The NCT Identifier Number does not have to be reported for: –Non-trial related Items and Services Claims –Follow-up visits (Active Treatment Phase over) –Observation-only Trials –Any Services to a Patient participating in a Clinical Trial BUT not dictated by the Trial –Complications arising from participation in a Clinical Trial 21

22. ONCOLOGY / PEDIATRICS Determine whether the study qualifies for the CTP before billing for services for Clinical Trial (e.g. Cancer Control Trial) These policies apply to all Medicare beneficiaries regardless of age (e.g. includes Pediatrics) 22

23. FAILURE TO REPORT A VALID NCT IDENTIFIER NUMBER In case of failure to report a valid NCT Identifier Number, claims should not be denied as long as there is a valid or generic number in the appropriate field of the trial-related claim BUT if the capabilities are there to report the actual clinical trial number that is the number that should be reported 23

24. ANY QUESTIONS? 24