Clinical Trials in PKU Georgianne Arnold, MD Professor of Pediatrics University of Pittsburgh Medical Center Pittsburgh Children’s Hospital

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

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

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!

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

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!

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

Sample study schemes Treatment A Treatment B Outcome

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

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%

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

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

Barriers to Clinical Trial Participation

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

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

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