Understanding the New Complexities of Clinical Trials from Results Reporting and FMV to Off-label Communication and Aggregate Spend

Transcription

1 Understing New Complexities Clinical Trials from Results Reporting FMV Off-label Communication Aggregate Spend Mark DeWyngaert, Ph.D. Kathleen Tench Huron Consulting Group Life Sciences Advisory Services FDA Regulary Symposium September 30, 2009 Huron Consulting Services LLC. All rights reserved.

2 Agenda I. Clinical Trials Results Reporting II. Clinical Trials Fair Market Value III. Clinical Trials Aggregate Spend IV. Clinical Trials Off-Label Communication V. Future Considerations Life Sciences Advisory Services 1

3 I. Clinical Trial Results Reporting 2

4 Laws Associated with Clinical Transparency Recent Guidance September 27, 2008: U.S. Food Drug Administration Amendments Act 2007 (FDAAA) Required that clinical trials results be made publicly available on Internet through an exped registry results data bank Non-compliance may result in penalties as well as possible loss funding Effective Ocber 1, 2009: PhRMA endorsement Measures increase transparency reporting requirements around clinical trials Provide medical research results summaries (safety effectiveness data) for all interventional clinical trials involving patients regardless wher medicines are approved or particular research programs have been discontinued Proposed June 9, 2009: changes Maine s clinical trial reporting regulations Would exp types trials number data elements that must be reported Would apply future prior postings Would result in revisions summaries currently in ICH-E3 format as well as reporting additional data elements for studies already posted Effective July 1, 2009: Vermont legislation bans gifts health care providers by any manufacturer a prescribed product. However, expenditures (i.e. payments) that are not banned include bona fide clinical trials. those provided in support Will government consider duplicative/non-actionable research be bona fide? Life Sciences Advisory Services 3

5 Laws Associated with Clinical Transparency (cont d) Recent Guidance 2008: Revised ICMJE Uniform Requirements for Manuscripts (URM) ICMJE member journals will require, as a condition consideration for publication in ir journals, registration in a public trials registry. The ICMJE does not advocate one particular registry, but registry Must be accessible public at no charge Must be open all prospective registrants managed by a not-for-prit organization Must have a mechanism ensure validity registration data Should be electronically searchable Obligation publish negative studies: Edirs should consider seriously for publication any carefully done study an important question, relevant ir readers, wher results for primary or any additional outcome(s) are statistically significant. Failure submit or publish findings because lack statistical significance is an important cause publication bias. Life Sciences Advisory Services 4

6 II. Clinical Trials Fair Market Value 5

7 Regulation related Fair Market Value (FMV) Recent Legislation Guidance OIG testimony regarding Fair Market Value Enforcement actions related Anti-Kickback Statute Federal False Claims Act OIG Compliance Program Guidance for Pharmaceutical Manufacturers Stark Laws : 42 CFR Parts regarding physician self-referral State Laws for: District Columbia ( Act A ) Maine ( 22 Me Rev. Stat. Ann A ) Vermont ( 18 Vt. Stat. Ann. 4632) West Virginia ( W.Va. Code 5A-3C-13 ) Massachusetts ( Mass S.B ) PhRMA Principles on Conduct Clinical Trials Communication Clinical Trials Results Food Drug Administration Amendments Act 2007 (FDAAA) Food Drug Administration Device Regulation Guidance Life Sciences Advisory Services 6

8 The Anti-Kickback Statute Constraints on Offer or Payment Anything Value Companies Companies should should be be aware aware federal federal Anti-Kickback Anti-Kickback Statute Statute constraints constraints it it places places on on marketing marketing promotion promotion products products reimbursable reimbursable by by federal federal health health care care programs, programs, including, including, but but not not limited limited,, Medicare Medicare Medicaid. Medicaid. In In health health care care secr, secr, sales, sales, marketing, marketing, discounting, discounting, purchaser purchaser relations relations potentially potentially implicate implicate Anti-Kickback Anti-Kickback Statute. Statute. The Anti-Kickback Statute is a criminal prohibition against payments (in any form, wher payments are direct or indirect) made purposefully induce or reward referral or generation federal health care business. The Anti-Kickback Statute addresses not only fer or payment anything value for patient referrals, but also fer or payment anything value in return for purchasing, leasing, ordering, or arranging for or recommending purchase, lease, or ordering any item or service reimbursable in whole or part by a federal health care program. Companies should be aware that, in addition any explicit payments received for work done on clinical research, HCPs may receive additional value from participating in a clinical trial by gaining publicity /or increased reputational value by publication results or by positive perception being involved in cutting edge treatments by ir patients. Life Sciences Advisory Services 7

9 Risks Associated with HCP Arrangements Considerations in Identifying Risk The The OIG OIG has has highlighted highlighted issues issues areas areas risk risk related related physician physician interactions. interactions. The The result result can can impact impact multiple multiple areas areas within within an an organization. organization. Within Within its its guidance, guidance, OIG OIG has has articulated articulated issues issues that that it it feels feels all all manufactures manufactures need need address address in in assessing assessing risk. risk. There are several considerations that can be useful in identifying activities at greatest risk prosecution. In particular, manufacturers should ask following questions, among ors, about any problematic arrangements or practices y identify: Does activity have a potential interfere with, or skew, clinical decision-making? Does it have a potential undermine clinical integrity a formulary process? If arrangement or practice involves providing information decision-makers, prescribers, or patients, is information complete, accurate, not misleading? Does arrangement or practice have a potential increase costs federal health care programs, beneficiaries, or enrollees? Does arrangement or practice have potential be a disguised discount circumvent Medicaid Rebate Program Best Price calculation? Does arrangement or practice have a potential increase risk overutilization or inappropriate utilization? Does arrangement or practice raise patient safety or quality care concerns? Life Sciences Advisory Services 8

10 Activity between HCPs Manufacturers AdvaMed & PhRMA Code Impact Between Between July July December December 2008, 2008, new new PhRMA PhRMA Code Code AdvaMed AdvaMed Code Code guidance guidance was was approved approved enhance enhance codes codes furr furr distinguish distinguish appropriate appropriate inappropriate inappropriate activity activity between between HCPs HCPs manufacturers. manufacturers. Life Sciences Advisory Services 9

11 Definition Bona Fide Clinical Research Bona Fide Clinical Research Based on Industry Guidance The OIG recognizes value importance manufacturers support for research conducted by institutions healthcare pressionals for advancement science medicine. (1) The bona fide purpose clinical research must be defined documented in order for consideration fair market value. Current legislative industry compliance references provide guidance on criteria that determine what constitutes bona fide clinical research. (1) OIG Compliance Program Guidance for Pharmaceutical Manufacturers. Federal Register / Vol. 68, No. 86 / Monday, May 5, 2003, p Life Sciences Advisory Services 10

12 Demonstrating Bona Fide Clinical Research Considerations for Demonstrating Bona Fide Clinical Research Determining or confirming FMV a clinical research arrangement requires demonstration bona fide purpose research. Companies should consider following four key areas documenting, moniring, reconciliation processes demonstrate bona fide purpose as well as delivery research activities. Companies may be at risk facing anti-kickback issues if clinical research is left unfinished or is never performed. Documenting Bona Fide Research Activities Process Process Purpose Purpose Need Need Does Does procol procol reflect reflect an an independent independent objective objective has has it it been been approved approved by by an an appropriate appropriate approver approver (e.g. (e.g. IND, IND, IRB, IRB, FDA, FDA, etc.) etc.) Why Why are are payments payments necessary? necessary? Who Who approves approves payment? payment? What What is is underlying underlying purpose purpose payment? payment? Payment Payment How How were were payments payments determined determined who who received received m? m? Service Service What What services services were were performed? performed? What What data data results results were were determined determined from from research? research? How How is is this this documented? documented? Life Sciences Advisory Services 11

13 III. Clinical Trials Aggregate Spend 12

14 State Reporting Compliance Guidance Mitigating Risk Managing State Filings Manufacturers Manufacturers should should identify identify track track key key issues issues related related state state reporting reporting tracking tracking aggregate aggregate spend. spend. Laws Laws vary vary by by state state manufacturers manufacturers must must carefully carefully follow follow new new legislation legislation as as it it is is enacted enacted make make appropriate appropriate change change remain remain compliant. compliant. Gift Disclosure Laws: MA, ME, MN, VT, WV, DC File a report identifying value, nature, purpose any gift, fee, payment, subsidy, or any economic benefit greater than $25 (greater than $50 in MA) Prohibition & Disclosure Law: MN Prohibits certain gifts over $50 any one HCP per year Requires disclosure compensation reimbursements valued at more than $100 Comprehensive Compliance & Reporting Law: CA Establish annual, per-physician limits on gifts, promotional marketing materials or items or activities (limits established by each company) Compliance with PhRMA Code OIG Guidelines MA NV Adopt a written marketing code conduct, a training program, identify a compliance ficer, conduct annual audits compliance with marketing code, adopt policies for investigating non-compliance with marketing code Pending Pending Grassley Grassley subcommittee subcommittee inquiries inquiries Federal Federal Sunshine Sunshine Act Act disclosure disclosure provisions. provisions. Life Sciences Advisory Services 13

15 The Sunshine Act Impact on Compliance Risk Operations The The Sunshine Sunshine Act Act is is a a federal federal law law that that would would require require reporting reporting payments payments on on a a national national level. level. However, However, federal federal law law may may not not pre-empt pre-empt state state laws, laws, creating creating furr furr compliance compliance operations operations issues issues as as companies companies work work track track spending spending that that adheres adheres both both state state federal federal legislation. legislation. Represents continued efforts Senar Grassley Kohl Would establish a nationwide requirement for reporting payments $100 or greater physicians Includes consulting fees, honoraria, gifts, entertainment, food, travel, education, research, charitable contributions, royalty or license payments, ownership or investment interests, compensation for serving as faculty or as a speaker for a continuing medical education program, grants Information would be posted on HHS website Penalties Subject CMPs $1,000 $10,000 per violation (maximum $150,000) Subject CMPs $10,000 $100,000 for knowing violations (maximum $1,000,000) Life Sciences Advisory Services 14

16 Recent Medical Device DPA Requirements DPA Requirements Are More Invasive Require More Public Reporting The The DPAs DPAs alleged alleged that that certain certain companies companies in in medical medical device device industry industry conspired conspired violate violate Anti- Anti- Kickback Kickback Statue, Statue, used used consulting consulting agreements agreements with with HCPs HCPs as as inducements inducements use use a a particular particular company s company s products, products, paid paid surgeons surgeons tens tens hundreds hundreds thouss thouss dollars dollars per per year year for for consulting consulting contracts contracts ten ten received received trips trips or or expensive expensive benefits. benefits. Code Conduct Requirements Commitment full compliance with all federal, state, local laws regulations All company s Covered Persons must comply with all federal health care program requirements with company s own policies procedures. All company s Covered Persons shall be expected report ir Compliance Officer, or or appropriate individuals designated by company, suspected violations any federal health care program requirements or company s own Policies Procedures. Required Policies & Procedures Tracking HCP contracts in a database An internal review approval process The The Big Big 5 5 medical medical device device companies companies are Tracking remuneration from sources are now now required required publish publish individual individual payments health care business or referrals. payments all all contracted contracted HCPs HCPs on on ir ir company company websites. websites. Reporting Requirements include: This All services made available by payment, per consultant, This information information is is now now available available for for scrutiny scrutiny by by any any individual, individual, company, company, by region by tal payments with a list services government government entity entity or or law law firm. firm. yet be rendered (HCP Payment tracking). Consulting payments must not exceed $500 per hour. Life Sciences Advisory Services 15

17 Recent Medical Device DPA Requirements DPA Requirements Are More Invasive Require More Public Reporting In In order order be be compliant compliant with with anti-kickback anti-kickback statute, statute, companies companies were were required required create create procedures procedures ensure ensure that that each each existing existing new new or or renewed renewed Arrangement, Arrangement, including including Contractual Contractual Non- Non- Contractual Contractual Arrangements, Arrangements, does does not not violate violate Anti-Kickback Anti-Kickback Statute Statute (taking (taking in in account account regulations, regulations, directives, directives, guidance guidance related related this this statute). statute). These These procedures procedures shall shall include include Creating maintaining a database all existing new or renewed Arrangements, Tracking remuneration from all parties. Tracking service activity logs ensure that parties an Arrangement are performing services required under applicable Arrangement. Moniring use leased space, medical supplies, medical devices, equipment, or or patient care items ensure that such use is consistent with terms Arrangement (if applicable). Establishing implementing a written review prior approval process for all Contractual Arrangements, including but The The Big Big 5 5 medical medical device device companies not limited, a legal review by counsel with expertise in Anti companies are are now now under under extreme extreme scrutiny scrutiny for for all Kickback Statute appropriate documentation all internal all ir ir HCP HCP arrangements. controls. arrangements. Compliance Compliance with with contractual Requiring Compliance Officer review Arrangements contractual obligations obligations must must be be documented documented Database, internal review approval process, or reviewed reviewed within within multiple multiple levels levels Arrangements Procedures at least quarterly provide a organizations. report on results Compliance Committee organizations. This This includes includes not not just just typical typical FFS Implementing effective responses when suspected violations FFS activities, activities, but but also also activities activities related related Anti-Kickback Statute are discovered including disclosing clinical clinical R&D R&D work. Reportable Events work. Life Sciences Advisory Services 16

18 IV. Clinical Trials Off Label Communication 17

19 Off Label Concerns Regulary Responses States AG s OIG FDA all are focused on Potential for Off-Label Discussions Industry Industry increasingly increasingly uses uses more more media media venues venues communicate, communicate, advertise advertise promote promote ir ir products products (i.e. (i.e. internet internet web web sites, sites, blogs, blogs, patient patient advocacy advocacy sites) sites) in in addition addition TV, TV, radio radio or or print print media. media. Areas potential risk include: Pre-approval discussions Off-label dissemination reprints or abstracts Lack fair balance in presentation product s benefits risk (e.g. false or misleading information) Medical Affairs activities must be consistent with FDA guidelines regarding education, advertising promotion Emphasis should be on education scientific exchange information less on product promotion FDA is more concerned about content activity less on title provider information Manufacturers may respond unsolicited requests for medical information (21 U.S.C. 360aaa-6(a) Request must be truly unsolicited Response must be tailored question asked Response must be balanced non-promotional See 59 F.R at (Nov. 18, 1994) Agents distriburs need appropriate training moniring ensure compliance Life Sciences Advisory Services 18

20 Recent Cases Scientific Misconduct Investigations Allegations Related Clinical Research Studies Issue Examples Cases Outcome Falsified Research The Army found that Dr. Kuklo, a former Army surgeon at Walter Reed, had forged names four or Walter Reed docrs he claimed be his co-authors on study, presented data that appeared have been fabricated because it did not match Walter Reed patient records. Medtronic received a subpoena in May 2009 regarding its financial relationship with surgeon. Ghostwriting Eli Lilly, Wyeth, Pfizer, Merck have all faced allegations ghostwriting, wherein se manufacturers, a varying degree, write paper or study n have a medical docr add his or her name publication provide appearance third party objectivity. DOJ Investigation (still open) Ghostwriting was a facr in several multi-million dollar settlements Failure Obtain IDE Inspection revealed that Stryker failed obtain an Investigational Device Exemption ( IDE ) prior initiating a clinical investigation. FDA Warning Letter False Claims The complaint against EBI alleged that King McNair, while implanting Ionic Spacers, ok studies that failed in laborary animals, n, without any reasonable basis conclude that y would be successful, began experiment on humans by implementing similar surgical techniques. After surgeries implantation Ionic Spacers, King McNair, with EBI s full knowledge, allegedly submitted claims for payment Medicare Medicaid for cost surgeries. Documented Research Needs Several medical device manufacturers were found be lacking adequate documentation/substantiation for multiple research educational grant related activities. Qui Tam Action Annual Needs Assessment is Required Life Sciences Advisory Services 19

21 Recent Corporate Integrity Agreements (CIA) Implications for Life Sciences Industry Recent settlement with Justice Department stemming from allegations f-label promotion Substantial requirements for internal controls moniring clinical research processes: Must develop policies procedures addressing sponsorship, funding, disclosures relating research development-related activities (including clinical trials, market research or authorship articles or publications) Must develop a moniring program for all continuing medical education certain charitable contributions healthcare related charitable organizations Must establish a needs assessment process develop a moniring program for publications activities Or disclosure initiatives All authors biomedical manuscripts expected fully comply with ICMJE criteria regarding authorship disclosure Company register every Companysponsored clinical Phase IIV interventional study in patients on Life Sciences Advisory Services 20

22 FDA Issues Warning Letters For Paid Internet Search Ads FDA Cracking Down on DTC Internet Advertising On On April April 3rd, 3rd, Food Food Drug Drug Administration Administration (FDA) (FDA) issued issued letters letters pharmaceutical pharmaceutical companies companies warning warning m m sp sp using using what what it it called called misleading misleading misbred misbred internet internet ads ads for for drug drug products. products. Sponsored web-links that accompanied internet searches failed communicate any risk information associated with use drug products. Application "one-click rule" for a product web ad that provides a link package insert or brief summary is not sufficient. As companies become involved in social media, re is greater responsibility address some technical aspects Internet, which FDA has responded with increased regulary parameters that are not always clearly defined. This continues be an evolving area regulation risk for both pharmaceutical device companies. Life Sciences Advisory Services 21

23 Recognizing Risks Responsibilities Social Media Identifying Mitigating Compliance Risk Current Current guidelines guidelines regarding regarding various various media media in in which which pharmaceutical pharmaceutical medical medical device device manufacturers manufacturers may may promote promote ir ir products products is is vague vague incomplete. incomplete. Social Social media media is is an an area area involving involving a a high high level level risk risk associated associated with with promotion promotion f-label f-label or or egregious egregious information. information. Social Media is not free- it still takes considerable resources (both financial human) The same rules DDMAC review apply as well. As with or mediums re is a continuum risk complexity. Social media sponsored by pharmaceutical companies appears represent highest level risk visirs are not controlled, y may leave f-label posts any edirial control may be viewed as an endorsement. Examples risks involving social media are: High Risk Developing corporate disease awareness social networks/bulletin boards-risk f-label discussions possible adverse event reporting Bred Corporate Wikis-risk f label promotion, adverse event reporting unfair balance Bred Participation in social media- leaving posts, comments in forums-concern with f-label fair balance being maintained Medium Risk Bred advertising on SM platform some risk for f label perception Non-bred disease awareness blogs Bred Blogs Low Risk Bred Corporate podcasts Non-bred advertising on SM platform Life Sciences Advisory Services 22

24 Suggestions Mitigate Risks Related Social Media Identifying Mitigating Compliance Risk To To mitigate mitigate risks risks involving involving social social media, media, clear clear guidelines guidelines should should be be set set reflect reflect Company s Company s views views wards wards f-label f-label unapproved unapproved promotion promotion Company s Company s products. products. Below Below are are a a list list actionable actionable measures measures take take in in order order prepare prepare your your company company prevent prevent social social media media abuse. abuse. Educate senior management, legal compliance staff on what is social media, your objectives, importantly your metrics. Create what if scenarios for discussion with legal compliance. Rules engagement what will you do with negative information or adverse event reports. Develop clear written guidelines for adverse event reporting, employee conduct on company sponsored sites ( or sites),presentation user-generated content, measurement trends in discussions. Provide adequate training designated individuals. Limit or avoid f label communications in any social media strategy Monir medical content on sponsored or supported web sites Support arms-length unbred educational web sites do not require content approval or review Have Legal Regulary review all content for company sponsored sites Don t circumvent your review approval process Life Sciences Advisory Services 23

25 Suggestions Mitigate Risks Related Social Media (cont d) Identifying Mitigating Compliance Risk Set up specific framework process review social media materials Clearly establish Company s interpretation FDA regulations. How will Company incorporate new rules in a rapidly changing environment? Ensure Compliance Clarity Develop criteria for assessing adverse event reporting. Train employees monir social media activity using specific criteria. Work with FDA develop a cusmized moniring procol that meets needs a specific medium. Discourage use personally identifiable information Add warnings terms use section Consider use independent moderars if you are considering facilitated or moderated discussion forums. Consider strict limitations on discussion pics on Company sponsored sites review postings (make sure this is transparent community). Consider reviewing links ensure Drug name is not included in conjunction with a claim. Consider disabling links post on your Twitter accts or sites prevent confusion until rules become more settled. Set strict guidelines on use information gared from social media sites particularly for sales or marketing purposes. Life Sciences Advisory Services 24

26 V. Future Considerations 25

27 Preparing for Future Requirements Enhancing Clinical Trial Transparency Manufacturers Manufacturers must must identify identify key key areas areas compliance compliance risk risk enhance enhance ir ir policies policies processes processes minimize minimize risk risk commonly commonly associated associated with with IIS IIS or or clinical clinical research research activity. activity. Prior Prior conducting conducting such such research, research, manufacturers manufacturers must must ensure ensure proper proper registration registration on on clinicaltrials.gov. clinicaltrials.gov. Prepare for future reporting requirements Identify which studies may need be revised effort it will require make se compliant Manufacturers can expect face similar regulary trends international, as seen in EMEA Proactively develop a transparent documented review approval process Ensure validity research avoid unnecessary duplication research Track all research, associated investigars, which is being conducted with manufacturer s products Incorporate appropriate language in contracts ensure compliant SAE reporting Conduct FMV determinations, where necessary, create supporting documentation Develop compliance policies related communicating via social media Life Sciences Advisory Services 26

28 Contact Details Life Sciences Advisory Services 27

29 Life Sciences Advisory Services 28