Clinical Research Compliance and Conflicts of Interest an Industry Perspective. Garry A Neil, MD Corporate Science and Technology Johnson and Johnson

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1 Clinical Research Compliance and Conflicts of Interest an Indstry Perspective Garry A Neil, MD Corporate Science and Technology Johnson and Johnson

2 DISCLAIMER The views presented here are my own and do not necessarily represent the views of Johnson & Johnson. Conflict of Interest Disclosre: I am an employee of Johnson & Johnson, I own stock in Johnson & Johnson and other pharmacetical companies and I am Vice Chair of the PhRMA Science and Reglatory Committee

3 Contemporary Clinical Research COI Report Bloomberg DOJ False Claims Theories Grassley Letter To HHS Health Care Compliance Clinical Trial Billing Conflicts of Interest Payments to Investigators Financial Reporting ICMJE Statements Hman Sbject Protection Research Integrity Bioethics International Trials Transparency of Reslts Doctors as Investigators Fidciary Obligations Settlements and Active Investigations DHHS Reglatory Agenda Good Clinical Practices UNESCO Bioethics Policy Data Integrity Meaningfl Risk Disclosre Bad Patient Otcomes Patient Recritment De Diligence NEJM Vioxx Stepped Up Agency Enforcement

4 Conflicts of Interest May be real or potential Conscios or nconscios Big or small Are biqitos in hman endeavors They cannot be entirely avoided bt mst be managed!

5 Indstry Relationships with Researchers: all potential sorces of COI Clinical investigation Nonclinical investigation Independent Data Safety Monitoring Boards Advisory and consltancy services Edcational and Research Grants Speaking arrangements Preceptorships

6 COI mst be Managed! Real, perceived or potential COI is inevitable in all hman endeavors Clinical R&D is no exception How? High ethical standards that pt patients first ALWAYS! Transparency Strong compliance programs

7 J&J Credo We believe or first responsibility is to the doctors, nrses and patients, to mothers and fathers and all others who se or prodcts and services. In meeting their needs everything we do mst be of high qality. We mst constantly strive to redce or costs in order to maintain reasonable prices. Cstomers' orders mst be serviced promptly and accrately. Or sppliers and distribtors mst have an opportnity to make a fair profit. We are responsible to or employees, the men and women who work with s throghot the world. Everyone mst be considered as an individal. We mst respect their dignity and recognize their merit. They mst have a sense of secrity in their jobs. Compensation mst be fair and adeqate, and working conditions clean, orderly and safe. We mst be mindfl of ways to help or employees flfill their family responsibilities. Employees mst feel free to make sggestions and complaints. There mst be eqal opportnity for employment, development and advancement for those qalified. We mst provide competent management, and their actions mst be jst and ethical. We are responsible to the commnities in which we live and work and to the world commnity as well. We mst be good citizens spport good works and charities and bear or fair share of taxes. We mst encorage civic improvements and better health and edcation. We mst maintain in good order the property we are privileged to se, protecting the environment and natral resorces. Or final responsibility is to or stockholders. Bsiness mst make a sond profit. We mst experiment with new ideas. Research mst be carried on, innovative programs developed and mistakes paid for. New eqipment mst be prchased, new facilities provided and new prodcts lanched. Reserves mst be created to provide for adverse times. When we operate according to these principles, the stockholders shold realize a fair retrn.

8 J&J Ethical Code for the Condct of Research and Development Preamble Or Ethical Code For the Condct of Research and Development is intended to complement or Credo by providing more specific standards of condct and behavior for physicians, clinical research scientists and others who are responsible for medical aspects of research and development. Or Ethical Code is intended to describe the principles that gide ethical decision-making to ensre the safe se of or prodcts, and the best interests of or patients and their families, doctors, nrses and health care providers. It is envisioned to be the standard for addressing all ethical dilemmas regarding research and its applications. Or Ethical Code It is or fndamental responsibility to place the well-being of the patient first by appropriately balancing risks and benefits and to ensre that the best interests of patients and physicians who se or prodcts receive tmost consideration. It is or responsibility to help ensre access to or prodcts in the commnities where we develop them. It is or responsibility to apply Credo-based vales and jdgment regarding the design, condct, analysis and interpretation of clinical stdies and reslts. It is or responsibility to adhere to the principles of good clinical practice. It is or responsibility to ensre all Company-based, medically relevant prodct information is fair and balanced, accrate and comprehensive, to enable well-informed risk-benefit assessments abot or prodcts. It is or responsibility to nderstand differences in vales across cltres and to adapt or behaviors in keeping with or ethical principles. It is or responsibility to challenge each other regarding medical and ethical concerns.

9 J&J Approach to Research Compliance Corporate fondation: the Credo Ethical Code for R&D PhRMA gidelines Transparency and disclosre Strong Compliance Programs Good Clinical Practices, Good Manfactring Practices, Good Laboratory Practices Health Care Compliance Frad and Abse, Prodct Promotion, and Integrity in Data relied on by the government for reglatory and payment decisions Bioethics

10 J&J Disclosre Policy Confidentiality Provisions Physicians and instittions have reporting obligations, so contracts mst inclde exceptions to allow disclosre of some information To state and federal officials as reqired by law or reglation To pblication editors To instittions (inclding boards and committees) To patients

11 Addressing Conflict of Interest Qestions at J&J Transparency and Disclosre policies FDA Financial Disclosre by Clinical Investigators Conscios verss sbconscios Conflicts Research design controls and review Reglatory oversight Internal peer review Examining totality of relationships Establishing internal firewalls and controls in a manner consistent with OIG Gidance Disclosre of financial arrangements in the consent form

12 Conclsion Conflict of interest mst be acknowledged, recognized and managed in all of or endeavors It is of particlar concern and mst be taken very seriosly in all aspects of clinical research Conflict of interest can be appropriately managed by Transparency Strong ethical codes Peer review Strong compliance and enforcement policies at all levels in the organization We mst sccessflly manage COI to permit contined development of new medicines and pblic private scientific partnerships

13 Back-ps

14 PhRMA Principles on Condct of Clinical Trials and Commnication of Clinical Trial Reslts A physician has discovered a potential prodct. The physician licenses the compond to Company B for a royalty payment for any ftre sales. Can the physician be a clinical investigator of that compond for Company B? No. Direct ownership interests in a prodct (sch as patent rights or rights to royalty payments) present an inherent conflict of interest, which cold introdce bias into the condct of the trial. Companies that acqire rights to prodcts which have arrangements that are in conflict with the above shold take reasonable steps to modify the relationship A voting member of a DSMB shold not have significant financial interests or other conflicts of interest that wold preclde objective determinations. Employees of the sponsor may not serve as members of the DSMB, bt may otherwise assist the DSMB in its evalation of clinical trial data

15 What is an investigator conflict of interest and how do clinical trial sponsors handle sch conflicts of interest? A conflict of interest exists, in the research setting, whenever an investigator s professional jdgment cold be inflenced by a secondary interest, sch as a potential financial gain, pblication opportnity, career development, otside employment, personal considerations or relationships, investments, gifts, payment for services and board memberships. In the strict sense some conflict of interest is inherent in all research settings in that physicians sally receive compensation for their work, often seek pblication opportnities, and are recognized professionally for advancing knowledge in their field. Moreover, physicians who are specialized and/or leaders in their field are often extensively engaged by both the private and pblic sectors to provide their expertise. Frther, by the natre of their practices, there are often a limited nmber of physicians who are best qalified to ensre that a specific trial will be able to reach and enroll the reqired nmber of patients. While physicians face conflicts of interest in all aspects of their work, they are expected to pt patient care above all other concerns. As sch, they are sbject to an array of professional standards and ethical obligations. Prsant to these PhRMA principles, sponsors may not se investigators if investigators or their immediate family have a direct ownership interest in the investigational prodct, and sponsors may not compensate investigators in company stock or stock options. In the U.S., FDA law reqires sponsors to collect and disclose information on investigators financial interests that exceed defined thresholds when the sponsor sbmits prodct for reglatory. Investigators mst also meet local reqirements imposed by their instittions and/or the instittional review board or ethics committee. Most medical jornals monitor conflicts of interest by reviewing the financial interests of investigator-athors, reqire the disclosre of affiliations and financial interests in the articles they pblish, and reserve the right to reject pblications involving significant conflicts of interest is also managed by sponsors sing doble-blind stdy designs(e.g. neither the physician nor the patient knows whether the patient is receiving the stdy drg or the placebo or comparator), mltiple investigators, contractal provisions in the sponsor-investigator clinical trial agreement, periodic aditing of investigator sites by third-parties, and other Good Clinical Practice reqirements that are commonly sed in clinical trials.