1. Understanding Clinical Trials – Part 2 Georgianne Arnold, MD Professor of Pediatrics University of Pittsburgh Medical Center Pittsburgh Children’s Hospital

2. Disclosure I am a member of the PKUDOS advisory board I am involved in Kuvan and PEG-PAL clinical research funded by Biomarin I have been an advisor for Biomarin

3. Phases of Clinical Trials Phases happen in succession Build on each other Can participate in any phase.

4. Phases of Clinical Studies Phase 1: dose of study drug, how it works in body, first time assess safety in people. Phase 2: first attempt to see whether the study drug is effective and continue to look at safety – usually few patients

5. Phases of Clinical Studies 3 Phase 3: Large study using placebo to test effectiveness and safety of study drug. Used to obtain approval from FDA, Health Canada and other health agencies in other countries.

6. Phases of Clinical Studies 3 Usually random regarding who gets study drug and who gets placebo Anatomy of Phase 3 Trials –Half get study drug, half get placebo –Half get study drug and half get placebo for first half of the study, and then cross over to the other product –Half get study drug and half get placebo for first half of study, then all get study drug

7. Phases of Clinical Trials Phase 4: Study after health agency approved, usually tracks the drug over time for additional safety information. Often called “post-marketing”. After Phase 3 or 4 – evidence is presented to the Food and Drug administration in the US, Health Canada or other regulatory agencies for approval

8. Evidence-Based Medicine How do we decide how good a clinical trial is, or how well a drug works? Oxford Centre for Evidence Based Medicine has created guidelines for grading how well studies are designed and conducted. Goal is to have the strongest level of evidence, balancing benefit against level of risk.

9. Protecting Safety: Role of IRB Independent Review Board (IRB) - review all aspects of study and approve conduct. Highest priorities: –Safety –Communication of risk and procedures BEFORE choosing to participate Committee of medical professionals, ethicists, and others with no connection to the study.

10. IRB Consent form –Purpose of study –Risk & Benefit –What is involved (Protocol) Written document, must be provided and carefully reviewed prior to anyone agreeing to participate. Review, ask questions, explain medical terms, understand all important info

11. Future of Clinical Studies is You! Participation is always voluntary, really a partnership between you and investigators We don’t think badly of you or let your care suffer if you choose not to participate Make sure to ask lots of questions. We would never want you to be uncomfortable about being in a study. You may qualify right now for a clinical trial!

12. Future is You! Hope today helps in understanding of clinical studies. Owe debt of gratitude to study participants Without their participation, we would be unable to move forward in getting better approved treatments for PKU.

13. Clinical Trials Central Additional information on clinical trials is available from the National Institutes of Health Clinicaltrials.gov Medlineplus.gov