1 / 67

Setting Up Clinical Trials

Setting Up Clinical Trials. Cynthia M. Otto, DVM, PhD DACVECC Associate Professor of Critical Care. What is a clinical trial?. A prospective evaluation in which the factor of interest is controlled by the investigator RANDOMIZATION Provides evidence of causality

jenaya
Download Presentation

Setting Up Clinical Trials

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. Setting Up Clinical Trials Cynthia M. Otto, DVM, PhD DACVECC Associate Professor of Critical Care

  2. What is a clinical trial? • A prospective evaluation in which the factor of interest is controlled by the investigator • RANDOMIZATION • Provides evidence of causality • Gold standard for clinical decisions about treatment efficacy

  3. Clinical Trial Subjects • Classically understood to be studies in humans • Veterinary Clinical Trials are studies in Client-owned animals

  4. Veterinary Clinical Trials • Test Drugs or Devices • Initiated by • Company • Human Pharma • Veterinary Pharma • Investigator Why Human Pharma?

  5. Clinical Trials in Spontaneous Disease of Companion Animals • Highly clinically relevant models • Heterogeneity, diversity • Spontaneous disease treated after clinical signs present • Directed and supportive care provided • Outcome = Survival • Takes advantage of advanced critical care facilities • Cost effective • Success may be more likely to predict positive human clinical trials

  6. Regulatory Requirements for Veterinary Clinical Trials Uncharted waters • Currently no government oversight of: • Investigator-initiated Veterinary Clinical Trials • Human Pharma conducting clinical trials in pet animals with drugs for human use. • Regulatory Agencies for Industry Sponsored Trials • FDA • Reviews safety data and approves clinical trial design • Approval required for animal drugs tested in animals • Center for Veterinary Medicine (CVM) • USDA (governs testing of biologicals)

  7. Requirements for Veterinary Clinical Trials • Patient Safety is Paramount! • Regardless of who initiates • informed client (owner) consent • Safeguards • Good Clinical Practice (GCP) compliance • Guidance document for the design and conduct of all clinical studies • Institutional approval (IACUC, IRB) • Independent board to review protocols and ensure patient safety

  8. Phases of Clinical Trials • Phase I • Safety – must be performed prior to any clinical trial in humans or client owned animals • Pharmacokinetics • Pharmacodynamics

  9. Phases of Clinical Trials • Phase II • Efficacy • Limited enrollment • may or may not be controlled

  10. Phases of Clinical Trials • Phase III • Large scale • Comparison of Drug/device • Randomized with controls • Phase IV • Large scale field trials • Post marketing

  11. Scenario 1 • Your department is approached by a Pharmaceutical Company, CatsRUS to test a new drug CR348 for the treatment of feline asthma

  12. Can You Participate? • How many asthma cats do you see in month? • Primary cases • Referral cases • Emergency cases • Do you have the staff to conduct a clinical trial . . . And are they interested? • Do you have experience with clinical trials?

  13. Can You Participate? • Do you have the space? • Drugs • Binders • Mailers • Samples collected • Office space for monitors/FDA inspections* • Do you have the time?

  14. What do you do? • Confidentiality agreement • A document clearly stating your obligations regarding the information shared with you • Defines what is confidential • Who can you share information with • How long you are obliged to maintain confidentiality • Do you have legal counsel to review this?

  15. The Protocol • Review the protocol carefully • Based on the specifics of what is expected • Do you have the necessary caseload • Do you still have the interest • Do you still have the time • Do you still have the staff • Do you have still the space • Are you comfortable with the protocol Cost/benefit?

  16. The Protocol • Protocol Deviations • Errors in data collection • Alteration in treatment • Missed timepoints • All lead to loss of $, time and potentially case data It makes FDA unhappy!

  17. What do you do? • Contract or sponsored research agreement • Defines Scope of Work (Protocol) • approved by the CVM at the FDA • Principal Investigator • The person RESPONSIBLE • Performance Period • Record Keeping and Access

  18. What do you do? • Contract or sponsored research agreement (cont.) • Cost and Payment • Confidential Information • Publications • Patents and Inventions • Use of the Institution or Sponsor’s Name

  19. Expectations • You will • Enroll a specified number of cases • In a specified period of time • You will be GCP compliant • Provide complete and accurate data • Report protocol deviations or adverse events • You will handle the test material appropriately • You will work with the study monitor • Provide a final report

  20. Expectations • They will provide • GCP training • The protocol • Client consent and regulatory assurances • Test agent • Data capture forms • Study monitor • Incentives/payment

  21. Scenario 2 • A faculty member would like to test the efficacy of the new human asthma drug “BreatheEZ” in cats with asthma

  22. Investigator Initiated Trial • Determine the safety of the material • Obtain the test material* • Design the trial • Provide Informed Client Consent • Regulatory approval* • Secure funding • Recruit and enroll cases • Collect and Analyze data • Write the paper!

  23. Designing a Trial • What is your question? • Standard of care • Placebo • What is your population? • Inclusion • Exclusion • What is your clinical outcome?

  24. Designing a Trial • Sample size – power • Outcome • Tracking subjects • Eligible • Randomized • Enrolled • Completed Study • Intent to treat population excluded eligible randomized control treatment Withdrawn LTF analyzed

  25. Limiting Bias • Randomization • Equal chance of being in treatment vs control group • Baseline data • Blinding or masking • Prevents differences in interpretation of outcomes or data collection between groups • Placebo controlled

  26. Regulations • Institutional Animal Care and Use Committees? • Institutional Review Board? • Privately owned animal protocols • Center for Veterinary Medicine? • Regulates manufacture and distribution of additives and drugs for animals

  27. Informed Consent • Why participate? • Participation is voluntary • Purpose of the study • In clear lay language • A Clarification that the drug/device is investigational • The duration of the study • The expectations of the owner and pet • Clarify experimental components vs standard of care • number of visits required, additional procedures required • requirement for a necropsy if the animal dies

  28. Informed Consent • The possible risks or discomfort to the pet • If there is no safety data in the population under study, this should be clearly stated. • Include a statement that the research may involve risks that are currently unforeseeable. • The possible benefits • “Your pet may not benefit from participation in this study. However, we may learn additional information about your pet’s disease which may affect how your pet is treated.”

  29. Informed Consent • The alternatives to participation • Treatment alternatives for the condition being investigated (eg supportive, palliative care) • A description of any compensation • Financial incentives or treatments costs covered • “Complications may happen during the study treatment because of your pet’s disease, as a result of treatment for the disease, or for unrelated reasons. You are responsible for all costs of tests and treatments except those specifically mentioned as being included in the study.

  30. Informed Consent • Detailed explanation of the owner’s financial responsibility • Impact of early termination of participation or of the study • Define when the overall study is to end. • Explain what events could lead to early study closure. • Note that the owner can elect to withdraw his pet from the study at any time. • If early withdrawal could expose the pet to medical risks, describe and how those risks will be minimized or prevented.

  31. Other considerations • Hospital Impact • Affect on caseload • Outside recruitment? • Affect on other services • Anesthesia, radiology etc • Nonmedical resources? • Faxing, copying etc • Cost recovery? • Overhead – cost of doing business • Public impact?

  32. Why Participate in Clinical Trials? • Advance animal health • Opportunity for clients • Intellectually stimulating • Challenging • Income source • Pharmaceutical funding • Grant funding • Recruit new cases

  33. Why Trials Fail • Inadequate recruitment • Poor data collection • Quality • Quantity • Poor design • Inadequate budget • Insufficient investigator benefit

  34. Study Design • What is your question? • Standard of care • Placebo • What is your population? • Dogs with parvovirus • What is your clinical outcome? • Survival

  35. Sample Size • How many cases needed to show an effect (or confirm NO EFFECT) • Power – 80% chance that the lack of effect is real • Survival rate: • 92% • 324 cases needed

  36. That’s a lot of puppies!!

  37. Wrong date format Need units, not # Errors! Inconsistent with each other Missing date

  38. Missing Data

  39. Where did all the trauma go???

  40. Too busy to enroll cases

  41. No Benefit to Enroll?

  42. Data Collection Time for the next study sample!!

  43. Data Quality Oh . . . you are supposed to add the calcium to the sample before you run it?

  44. Funding • I didn’t think it would cost so much • I didn’t think to include nursing time • I need to recruit cases? Advertising? • I was turned down because of no track record

  45. Successful Trials • Patient Recruitment • Incentives for Participation • Cost recovery • TIME!! • Resources • High quality data • Good Clinical Practice (GCP) • Dedicated staff $

  46. Structuring for Success • Trained personnel • Study Coordinators • Data collectors • PI’s role limited to expert clinical advice • Culture of Clinical Investigation • Appropriate Budget • Establishing a Reputation

  47. VCIC Structure Director Industry CTs NIH CTs Investigator CTs Clinical trial coordinator Clinical trial coordinator Clinical trial coordinator Study coordinator Study coordinator Study coordinator PI PI PI PI PI PI Data collector Data collector Data collector Data collector Data collector Data collector Data collector Data collector Data collector

  48. VCIC Structure Director(s) Who: Standing Faculty up to 50% time Role: Identification of PIs for potential compounds Reconciles issues regarding trials Identification of faculty generated protocols (discovery/PII) Facilitates trial management within hospital/University Protocol development related to hospital impact Clinical Trials Coordinator Who: Veterinarian (CVT) with clinical trials training Role: Working knowledge of all trials, can stand in for PI if needed Protocol development with PI Study coordinator and data collector management (recruiting, training etc, 1 vet for up to 5 coordinators) Quality control on data management and input Animal Use Protocol development Placebo/drug compounding protocols Quarterly reports on each trial

  49. Study coordinator Who: Nurse (vet/human) with CT training Role: Manage trial recruitment Manage Trial inquiries Initial screening/appts Data management Compliance management Coordinate trial supplies PI Role: Provide clinical expertise Protocol Initial patient assessment Data collector Who: AHT Role: Animal and client contact Data collector Who: AHT Role: Animal and client contact Data collector Who: AHT Role: Animal and client contact

More Related