1. Clinical Trials in PKU 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. Why a Clinical Trial?
The effect of a new drug or treatment can be influenced by the power of suggestion, random chance, and other factors
A clinical trial attempts to minimize these influences and give us a scientific way to determine if the drug or treatment really works

4. Why can’t I just have the treatment?
Blinding/randomization reduces bias
Investigator bias
Subject bias
Chance bias
The power of the human mind and expectation are not to be underestimated!

10. What do they mean by…?
Blind – one party does not know what treatment the subject is getting
Double blind – neither the subject nor the researcher know what treatment the subject is getting
Randomized: the patient is assigned to a study arm…. randomly

11. Why can’t I just have the treatment?
Blinding/randomization reduces bias
Investigator bias
Subject bias
Chance bias
The power of the human mind and expectation are not to be underestimated!

12. What does “arm” mean?
Subjects are divided into various treatment groups. Measures of outcome are planned (in this case changes in brain structure on MRI and changes in neurocognitive performance).
Randomization
Kuvan
Diet
Nonresponder
Responder
Outcome - MRI/Cognitive changes

13. Sample study schemes
Treatment A
Treatment B
Outcome

14. How do you decide how many study subjects are needed?
Short answer – ask a statistician
Long answer – depends on what size effect you are looking for
The larger the change, the smaller the sample size needed to see it
When sample size is small, there may
be some constraints to your conclusions

15. How do you decide if it worked?
There is always the possibility that the results were obtained by a fluke
Researchers use statistics to determine the chance that the result is real
Generally accepted standard is the likelihood that the result is real is ≥ 95%
So, if the chance of error is ≤ 5% (0.05 or less), then we trust the result
Try to make the chance that you missed a real effect ≤ 80%

16. Who are all these people?
Study overseen, and often developed, by the PI (Principal Investigator)
PI is assisted by study coordinators, nurses, technicians, and many others
Other people you may meet include psychologists, medical specialists, etc.
Statisticians, data entry assistants, student assistants and others may also see your data, but also undergo confidentiality training
Written document, must be provided and carefully reviewed prior to anyone agreeing to participate.
Review, ask questions, explain medical terms, understand all important info

17. Can I Learn More?
More basic information on clinical trials is available in a later session
Check out

18. Barriers to Clinical Trial Participation

19. Barriers to Clinical Trial Participation
Time!
Travel!
Executive Functions!

20. What Makes Studies Tick
Study Design
Study Funding
Study Execution
Study Subjects

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