1. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. Challenges in Clinical Research Trials Christee G. Laster Smith Moore Leatherwood LLP 1180 W. Peachtree St. NW, Suite 2300 Atlanta, Georgia 30309 T (404) 962-1052 F (404) 962-1257 christee.laster@smithmoorelaw.com

2. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® PREVIEW Regulatory/Enforcement Framework Research Billing Fraud and Abuse Concerns Recent Enforcement Actions

3. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® Regulatory Framework Primary responsibility for regulation of clinical trials rests with agencies of the U.S. Department of Health and Human Services (HHS). These are:  Office for Human Research Protections (OHRP)  Office of Civil Rights (OCR)  Food and Drug Administration (FDA)  Office of Research Integrity (ORI)  National Institutes of Health (NIH)  Centers for Medicare and Medicaid Services (CMS) Over-arching regulatory concern: Protection and well-being of human subjects.

4. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® Regulatory/Enforcement Framework Three FDA centers regulate medical investigational products for human use: These are:  Center for Drug Evaluation and Research (CDER)  Center for Biologics Evaluation and Research (CBER)  Center for Devices and Radiological Health (CDRH) FDA’s Office of Regulatory Affairs (ORA) conducts onsite bioresearch monitoring inspections of sponsors, PIs and IRBs Enforcers: OIG/DOJ/FBI/State AGs/Health Care Fraud Prevention and Enforcement Action Team

5. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® PAYMENT FOR CLINICAL TRIALS Research Billing

6. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® PAYMENT FOR CLINICAL TRIALS Medicare Coverage for Clinical Trials CMS NCD 310.1: The Clinical Trial Policy CMS created the NCD in September 2000 (in response to Pres. Clinton’s Executive Order) to help Medicare beneficiaries participate more fully in clinical research. -There were two reconsiderations (06/07) with final revision effective July 2007. PAYMENT FOR CLINICAL TRIALS

7. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® PAYMENT FOR CLINICAL TRIALS NCD 310.1 states that Medicare will cover “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 all clinical trials. All other Medicare rules apply.” -NCD for Routine Cost in Clinical trials (310.1) Many commercial payers follow Medicare. Medicare Coverage for Clinical Trials PAYMENT FOR CLINICAL TRIALS

8. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® PAYMENT FOR CLINICAL TRIALS States That Require Health Plans to Cover Patient Care Costs in Clinical Trials Taken from the National Cancer Institute website, March 2011 http://www.cancer.gov/clinicaltrials/education/laws http://www.cancer.gov/clinicaltrials/education/laws

9. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® PAYMENT FOR CLINICAL TRIALS Medicare will cover routine costs of “qualified” clinical trials. Study is “qualified” if meets the desirable 7: 1. The principal purpose of the trial is to test whether the intervention potentially improves the participants’ health outcomes; 2. The trial is well-supported by available scientific and medical information or it is intended to clarify or establish the health outcomes of interventions already in common clinical use; 3. The trial does not unjustifiably duplicate existing studies; 4. The trial design is appropriate to answer the research question being asked in the trial; 5. The trial is sponsored by a credible organization or individual capable of executing the proposed trial successfully; 6. The trial is in compliance with Federal regulations relating to the protection of human subjects; and 7. All aspects of the trial are conducted according to the appropriate standards of scientific integrity.

10. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® PAYMENT FOR CLINICAL TRIALS A study may be “deemed qualified” if:  Funded by NIH, CDC, AHRQ, CMS, DOD, and VA;  Supported by centers/cooperative groups funded by these agencies;  Subject to review by FDA under IND application; or  IND exempt under 21 CFR § 312.2(b)(1).

11. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® PAYMENT FOR CLINICAL TRIALS Routine costs are those items and services that would ordinarily be provided to beneficiaries and covered by Medicare. However, the NCD includes additional items that may be covered, including:  Conventional care (items or services typically provided absent a clinical trial);  Items or services required solely for the provision of the investigational service or item (e.g. administration of non-covered chemotherapeutic agent);  Items or services needed for reasonable and necessary care arising from the provision of the investigational service or item – particularly for the diagnosis or treatment of complications.

12. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® PAYMENT FOR CLINICAL TRIALS Routine costs Do Not include the following:  Items which are statutorily excluded or for which there is a non- coverage decision;  Investigational item or service itself, unless otherwise covered outside of the clinical trial;  Items and services used solely to meet data collection and analysis requirements (e.g., monthly CT scans for a condition usually requiring only a single scan); and  Items and services customarily provided free of charge by the sponsor.

13. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® PAYMENT FOR CLINICAL TRIALS Medicare Coverage for Medical Devices The NCD clinical trials policy does not address device studies. Institutions/sites should work with their Medicare Contractor to determine coverage of all device studies.

14. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® PAYMENT FOR CLINICAL TRIALS Medicare Coverage for Medical Devices: Devices approved through FDA pre-market approval process Devices cleared through FDA 510(k) process FDA-approved IDE Category B devices IRB-approved medical devices

15. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® PAYMENT FOR CLINICAL TRIALS Medicare IDE Regulations: IDE device billing rules are found at 42 CFR §§ 405.201-215, 411.15. and 411.406. The Medicare process for coverage of category B IDEs is outline in Medicare Benefit Policy Manual Chapter 14. The rules address coverage of Category A & B devices and the routine care related to each IDE device.

16. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® PAYMENT FOR CLINICAL TRIALS Medicare IDE Regulations: Category A Devices: not covered Category B Devices: may be covered if approved by the Contractor What about items/services provided for the device? “Routine care services related to a [Category B] device that is furnished in conjunction with an FDA approved clinical trial” 405.407(b)(3)

17. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® PAYMENT FOR CLINICAL TRIALS CMS Modifiers for Research have changed : CMS requires the use of particular HCPCS modifiers for billing in clinical research. The modifiers are used to identify investigational and routine clinical services provided in research studies. CMS has discontinued the following HCPCS modifiers as of December 31, 2007: QA (FDA IDE), QR (Item or Service Provided in a Medicare Specified Study), and QV (Item or Service Provided as Routine Care in a Medicare QCT). Effective for dates of service after 01/2008, the following new modifiers are used solely to differentiate between routine and investigational clinical services: Q0 – Investigational clinical service provided in an approved; Q1 – Routine clinical service provided in an approved clinical research study. See, CMS Transmittal 1418, https://www.cms.gov/transmittals/downloads/R1418CP.pdf https://www.cms.gov/transmittals/downloads/R1418CP.pdf

18. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® PAYMENT FOR CLINICAL TRIALS Common Billing Errors: Billing for services not rendered Billing Medicare (or other payers) for free items/services Billing for non-reimbursable items/services

19. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® PAYMENT FOR CLINICAL TRIALS MEDICARE COVERAGE ANALYSIS A MCA is a review of clinical research items, services, procedures and Medicare billing rules to determine the appropriate payer for each item or service. Use of MCA and billing rules mitigates the primary compliance risk and provides most defined standards for research billing. Properly performed MCA can be used for budget development, to support contract negotiations, and for billing compliance.

20. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® COMPLIANCE Fraud and Abuse

21. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® COMPLIANCE: FRAUD AND ABUSE January, 2011: “We are pleased to have reached a settlement agreement with the DoJ that fully resolves the post-market study matter... the company maintains that its post-market studies and registries are legitimate clinical studies designed to gather important scientific data... the company entered into a settlement agreement to avoid the potential costs and risks associated with litigation.” -Spokesperson for St. Jude Medical COMPLIANCE: FRAUD AND ABUSE

22. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® COMPLIANCE: FRAUD AND ABUSE St. Jude Medical Investigation: Post-market studies (Allegedly) conducted 3 post-market studies and a device registry in which participating physicians were paid for each St. Jude pacemaker and implantable cardiac device used (up to $2000/pt). Research data was collected, but primary purpose was to increase device sales by soliciting new users of the product or converting physicians from competitor’s product. $16 Million Settlement

23. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® Medical device and pharmaceutical companies can use post-market studies legitimately to obtain information about how their products work in the field, but they cannot use those studies, and the honoraria associated with them, to induce physicians to select their products. -Government’s response COMPLIANCE: FRAUD AND ABUSE

24. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® COMPLIANCE: FRAUD AND ABUSE The Big 3: False Claims Act Stark Law Anti-Kickback Statute

25. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® False Claims Act COMPLIANCE: FRAUD AND ABUSE False Claims Act: Prohibits filing or causing the filing of false claims, or creating a false record to get a claim paid. The core of a false claims case is that the government was cheated in one form or another -- the “false claim.” Typically occurs in research by double billing or improper or unnecessary billing.

26. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® False Claims Act COMPLIANCE: FRAUD AND ABUSE False Claims Act: As of Jan. 4, 2011, there were 1,341 qui tam cases under investigation. Of these cases, 885 involve healthcare fraud. A total of 180 qui tam cases are under seal that allege pharmaceutical pricing and/or marketing violations. An additional 80 cases involve hospital fraud.

27. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® Pre-determine: –Who is performing which service –Who is responsible for payment for each service (MCA) –Identifying patients as research participants (particularly for hospitals providing services) COMPLIANCE: FRAUD AND ABUSE

28. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® Anti-Kickback Statute Anti-Kickback Statute: Prohibits paying, offering to pay, or receiving payment in exchange for the referral of services or devices that are covered under a federal health care program. (PP)ACA: Kickback violations result in FCA violations COMPLIANCE: FRAUD AND ABUSE

29. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® Anti-kickback Statute Kickback violations often arise: Post-market/data registry studies Waivers of co-payments and deductibles Inducements for future purchases, referrals Off-label promotions Investigator promotions COMPLIANCE: FRAUD AND ABUSE

30. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® COMPLIANCE: FRAUD AND ABUSE Stark Law: Prohibits referrals (and any related billing) of designated health services by a physician to an entity in which the physician or an immediate family member has a financial interest (compensation/ownership).

31. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® COMPLIANCE: FRAUD AND ABUSE Stark Law: Violations often arise when physician is not an employee of the hospital – any contracts for research services must take into account the Stark law exceptions or risk the ability to refer DHS to the hospital (even for DHS unrelated to the research).

32. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® Recent Enforcement/Settlement Actions Company made payments to physicians through clinical trials to induce physicians to prescribe off-label. Company promoted psychiatric drug for unapproved uses by recruiting physicians to author articles about studies physicians did not conduct. Paying illegal remuneration to health care professionals recruited to conduct studies for unapproved uses. Company conducted clinical trials of medical device w/out FDA authorization. Independent physician researcher conducted sham clinical study. Investigator quoted in magazines promoting an IND.

33. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® COMPLIANCE: FRAUD AND ABUSE Settlements: Criminal and Civil fines ranging from $24M to $600M CIAs with specific obligations addressing research- related activities Payments to be disclosed consistent with payments under Section 6002 of ACA Public disclosure of results, post-marketing commitments Exclusion

34. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® COMPLIANCE: FRAUD AND ABUSE What to look for in the CTA/Budget: –Payments for PI speaking – “sham” consults –Bonuses for enrollment of patients –Payments to patients –Check CTA and any addendum/amendment language carefully

35. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® On The Horizon: FDA Proposed Regulations and Draft Guidance 3/11/2011: FDA has issued a revised Compliance Program Guidance Manual for inspections of Sponsors, Contract Research Organizations and Monitors, http://www.fda.gov/ICECI/EnforcementActions/BioresearchMonitoring/ucm133777.htm. 1/7/2011: Guidance - Electronic Source Documentation in Clinical Investigations. Provides guidance to sponsors, CROs, data management centers, and clinical investigators on capturing, using, and archiving electronic data in FDA-regulated clinical investigations. Comments are due April 7, 2011 2/19/2010: Proposed rule - Reporting Information Regarding Falsification of Data. The proposed rule will require sponsors to report information indicating that any person has, or may have, engaged in the falsification of data involving studies including, but not limited to, clinical investigations, nonclinical laboratory studies, and clinical studies in animals. Comments are due May 20, 2010. 1/13/2010: Guidance - IRB Continuing Review After Clinical Investigation Approval. Guidance intended to assist IRBs in carrying out their continuing review responsibility under 21 CFR 56.108(a) and 56.109(f) by providing recommendations regarding the criteria, process, and frequency of continuing review to assure the protection of the rights and welfare of subjects in clinical investigations. The draft guidance should also help clinical investigators and sponsors better understand their responsibilities related to continuing review. Comments are due March 15, 2010.

36. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® Questions

37. © 2011 Smith Moore Leatherwood LLP. ALL RIGHTS RESERVED. ® CONTACT INFORMATION Christee G. Laster SMITH MOORE LEATHERWOOD LLP One Atlantic Plaza, Suite 2300 1180 W. Peachtree Street Atlanta, GA 30309 (404) 962-1052 Tel christee.laster@smithmoorelaw.com christee.laster@smithmoorelaw.com