1 / 81

Oncology Rounds

Oncology Rounds. Protecting Patients or Stifling Research? The Swing of the Research Pendulum October 2011 Jack Holland MD FRCP FRCP(C). The Research Ethics Pendulum. Protecting the patient. Stifling Research. Themes to be explored over the next 45 minutes or so….

ivan
Download Presentation

Oncology Rounds

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Oncology Rounds Protecting Patients or Stifling Research? The Swing of the Research Pendulum October 2011 Jack Holland MD FRCP FRCP(C)

  2. J Holland OCREB The Research Ethics Pendulum Protecting the patient Stifling Research

  3. J Holland OCREB Themes to be explored over the next 45 minutes or so…. • Advancement in science is a good thing…. • for the man in the street • for our institutions • for business • for Ontario, for all of Canada • Losing the ethical compass may be deadly! • The Research Ethics Board can be your ally • The Research Ethics Board can be a royal pain in the ass! • Working together - for the man in the street, the institution, for business, for Ontario, for Canada

  4. J Holland OCREB The Impact of ResearchAAHRPP, Fall 2005 • 83% of adults believe it is either “essential” or “very important” that prescription drugs and new treatments be tested in humans • Each year, several million Americans participate in clinical trials • Currently, there are more than 41,000 active industry-and government-sponsored clinical trials PARTICIPATION IN ETHICALLY SOUND RESEARCH IS IN THE BEST INTEREST OF THE PUBLIC

  5. J Holland OCREB ……. and in 2011, it’s getting more and more exciting • Targeted drug therapy • Sloane Kettering is testing 40 mutations in 7 genes in all patients with lung or colon cancer • Inhibition of mutated, activated BRAF in metastatic melanoma • Pharmacogenomics and drug/patient specificity • “Point of Care Testing” • “SPARTAN” – in 45 minutes - 25 genes regulating CYP2C19, influencing projected response to clopidogrel • High Impact Clinical Trials Program at OICR • Translational research; team building

  6. J Holland OCREB ….. and it’s getting more and more complex

  7. J Holland OCREB The Complexity of Modern Genetics

  8. J Holland OCREB

  9. J Holland OCREB The research maze………

  10. Clinical Research: Process, Policy, Procedures J Holland OCREB CLINICAL RESEARCH Medical Advisory Committee Integrated Research Services VP research PRINCIPAL INVESTIGATOR Clinical Departments STUDY MANAGEMENT SCIENCE DISSEMINATION APPROVALS OVERSIGHT • Health Care Team: • - Clinical Practice • - Rounds • Research Subjects • Patients: • Individual Results • Summary Results Education Study Audit & Monitoring Patients Patient Care policy Safe Location Division / Dept Clinical Services Clinical Program Clinical Department Research Directors Clinical Research Site (Nursing, Beds, Exercise Lab) Staff Education Template SOPs Study Budgets Data Management & Biostatistics Study Design (Sponsor; PI) Grants Contracts Peer Scientific Reviews • Colleagues: • - Conferences • - Peer review journals • Public: • Advocacy Groups • Granting Agencies • Media HEALTH CANADA ( &/or FDA ) RESEARCH ETHICS BOARD RESEARCH ETHICS BOARD RESEARCH ETHICS BOARD

  11. J Holland OCREB …and it’s getting worse, capturing the attention of our provincial governments across the country

  12. J Holland OCREB

  13. J Holland OCREB

  14. J Holland OCREB

  15. J Holland OCREB

  16. J Holland OCREB

  17. J Holland OCREB

  18. J Holland OCREB

  19. J Holland OCREB NCIC CTG Data: Average Time (Days) for First Centre Activation 1995-2009

  20. J Holland OCREB Ontario Data: Proportion New Treatment Cases Enrolled on Clinical Trials 8.9% 11.2% 11.9% 9.0% 12.4% 8.5% % New Cancer Treatment Cases Enrolled on Trials OICR Infrastructure Funding

  21. J Holland OCREB Ontario Data: Actual Number of Patients Enrolled on Trials 2004-2009

  22. J Holland OCREB Annual Average # of ‘Activated’ CDN Centres per Trial

  23. J Holland OCREB Summary Trial Activation Trends • In Institutions, increasing times to trial activation and first patient enrolled (data not shown) • Up to 50% of all centres opening a trial never enrol a patient (NCIC CTG data)

  24. J Holland OCREB Ontario’s Clinical Trials Enterprise • April 30, 2010 - Ontario Government • $161 million Life Sciences Commercialization Strategy. • provides $17 million for three clinical trials related initiatives, including“A New province-wide coordinating infrastructure to streamline administrative processes and ethics reviews across multiple clinical trial sites in order to increase the speed of patient recruitment.” • November 2010 - key stakeholders group established by the Ministry of Research and Innovation (MRI) • BIOTECanada (National Biotechnology Industry Group) • CAHO (Council of Ontario Academic Hospitals of Ontario) • COFM (Council of Ontario Faculties of Medicine) • MEDEC (Canada’s Medical Technology Companies) • OCUR (Ontario Council on University Research) • Rx&D (Canada’s Research-based Pharmaceutical Companies)

  25. J Holland OCREB Clinical Trials and the Economy • In 2008, global clinical trials market, estimated at $50 billion; estimated to grow by 10% per year • Canada’s market share 4.1% ($2.05 billion) • But, 12% drop in the average annual growth rate of clinical trials activity in Canada between 2002 and 2007 (Clinicaltrials.gov) • transfer of clinical trial work to low-cost economies • decreasing competitiveness in Canada compared to the U.S. and Western Europe. • Provincial and federal governments are looking closely at ways of providing industry with a streamlined approach to ethics review and contracting for multi-centred clinical trials

  26. J Holland OCREB Ontario’s Clinical Trials Enterprise • Phase 1: Proof of Concept • designate REB “nodes” to undertake province-wide ethics review • establish a set standards acceptable across all sites • Phase 2: Development of an online application and data management system • Phase 3: Establishment of a centralized office (“Clinical Trials Ontario”) for linkage and coordination

  27. J Holland OCREB Phase 1: Project Management • Creation of a Project Management Office (PMO) • to support planning and implementation • to liaise with project sponsors in alignment with local, provincial and national initiatives • to hold the funding for the entire project • to provide project updates to stakeholders and project sponsors, including detailed costing at the end of each phase of the project • Creation of an Oversight Committee • to provide day to day direction/governance to the PMO; engage the broader Stakeholder Committee for input on substantive decisions required in Phase 1 • two research hospital representatives from the Stakeholder Committee • two university representatives from the Stakeholder Committee • two industry representatives chosen by Rx&D.

  28. J Holland OCREB Phase 1: Selection of Phase I Nodes Following a number of defined primary and secondary criteria the following sites/nodes were identified:

  29. Alberta J Holland OCREB • Research Ethics Reciprocity Agreement signed February 2011 • 6 REBs which are legislated under the Health Information Act • Agreement applies only to multi-jurisdictional research, does not obviate the need for local ethics review • Still need to implement and develop common SOPs, applications, guidelines and an IT infrastructure to support • Of the 3000 active studies in the University of Alberta REB database what % are multi-jurisdictional?

  30. Saskatchewan J Holland OCREB • 5 REBs with ministerial approval, 4 have agreed to share in the harmonization process • Bottom up approach with limited reciprocity • Applications and Consent forms have been harmonized • 6 REBs which are legislated under the Health Information Act • Trust-building exercise

  31. J Holland OCREB The clinical contractEthical reviewVillains?

  32. J Holland OCREB

  33. J Holland OCREB Success Factors in the Research Enterprise REB Brilliance Buck$ More Buck$ Brains Buildings

  34. J Holland OCREB Why is REB approval a big deal?Are REBs doing a good job? Two questions for you to consider

  35. J Holland OCREB It’s all about developing a culture of ethical integrity “You do as you’re told, we pay you as we please. You work like a slave, we punish you at random. That, in a nutshell, is our corporate culture”

  36. J Holland OCREB Developing a Culture of Personal Ethical Integrity

  37. J Holland OCREB Mandate of the REB To protect the rights, safety and well-being of any patient or healthy volunteer who participates in research at…….

  38. J Holland OCREB Foundations of Research Ethics • Historical precedent • Recent disasters - screw ups!! • The importance of maintaining “trust” with the public • It’s just the right thing to do • You should agree • The institution should agree

  39. J Holland OCREB Joseph Mengele & The Eva Kor Story • Eva Kor, living testament to the absolute requirement for informed consent of subjects in medical experimentation

  40. J Holland OCREB More Recent Disasters

  41. J Holland OCREB Hospital for Sick Children 2007

  42. J Holland OCREB CLINICAL TRIALS GONE WRONG – THE TEGENERO STORY AND CRISIS COMMUNICATIONS February 2007 • Only six years after being spun out of the University of Würzburg, TeGenero AG had a US$19 million war chest thanks to venture capitalists and a promising new drug about to enter human trials - AG TGN1412 • Less than five months after the catastrophic failure of its trial, the company was bankrupt.

  43. J Holland OCREB WHAT HAPPENED? • In the early hours of the morning of March 15th six men were rushed to a London hospital after being dosed with the experimental drug – TGN 1412. • During the course of the first day, shortly after the dosing was complete, a trial participant complained of a headache, fever and pain. He took his shirt off, saying he felt like he was burning. • His fellow trial participants followed suit shortly thereafter. All the test subjects who got the real drug (two got a placebo) ended up in an intensive care unit.

  44. Contd. Sept 14th 2000 J Holland OCREB “The death of 18-year-old Jesse Gelsingerin a gene-transfer trial led to the discoveryby the National Institutes of Health (NIH) of many hundredsof unreported adverse events among volunteers enrolled in gene-transferexperiments”

  45. J Holland OCREB Background* • 18 year old volunteer (for corrective gene study) • Jesse Gelsinger died during study • The complaint alleged that: • The University was to receive ownership stake in the sponsor company • The University and various physicians associated with research had substantial financial and equity interests with respect to research products • The extent of financial interests were not disclosed to Gelsinger in the informed consent process • Case settled for an undisclosed amount * Gelsinger v. Trustees of the University of Pennsylvania- http://www.skrplaw.com/links/healthcare2.html

  46. Sept 14th 2000 J Holland OCREB “To put it simply, if we cannot guarantee sound researchin general — and patients' safety in particular —public support for gene therapy and other potentially lifesavingtreatments will evaporate. Volunteers will not show up, andthe generous stream of Government research dollars……..may shrink. So clinicalresearchers and the institutions that support them must, withoutexception, maintain the public's confidence in our work, ourcompetence, and most important, our ethics”. Donna Shalala US Dept of Health and Human Services (on the death of 18 yr old Jesse Gelsinger)

  47. Suspensions of Federally Supported Research What if, 2011 UHN??; Ottawa Hosp Res Institute??? J Holland OCREB

  48. J Holland OCREB National Post February 2004

  49. J Holland OCREB National Post February 2004

  50. J Holland OCREB Death of Ryan Lucio Children’s Hospital Of Eastern Ontario September 2003

More Related