SSRIs, Efficacy, Safety & Children: Ethical and Scientific Concerns Julie Magno Zito, PhD Associate Professor of Pharmacy and Psychiatry University of Maryland, Baltimore February 2, 2004 FDA Advisory Meeting
Ethical issues in pediatric pharmacology-1 <ul><li>IRB approved consent is an explicit contract between families and the study investigator to produce knowledge to advance science. When negative findings are suppressed, the contract is breached. </li></ul><ul><li>Assure participants that they will receive knowledge of the findings of the study . </li></ul><ul><li> </li></ul><ul><li> Derivan, et al., J Child Adolescent Psychopharmacology, 2003, in press </li></ul>
Ethical issues in pediatric pharmacology-2 <ul><li>Absence of knowledge on the extent of unpublished trial data creates uncertainty among the public and health professionals. </li></ul><ul><li>Registration of IRB approved trials should be required to improve awareness of the completeness of studies and subsequent publication. </li></ul><ul><li>Dickersin and Rennie, JAMA, 2003 </li></ul>
Ethical issues in pediatric pharmacology-3 <ul><li>Maintaining proprietary restrictions on the publication of selected clinical trial data has led to publication bias and it distorts meta-analysis. </li></ul><ul><li> Lexchin, et al. BMJ, 2003 </li></ul>
Scientific concern-1: Distortion <ul><li>Distorted information in medical journals leads to biased interpretation. </li></ul>
Scientific concern-2: Distortion <ul><li>For example, the abstract of the recent JAMA study on sertraline for depression in children and adolescents implies that favorable response occurred in both younger (6-11) and older (12-17) youths. </li></ul><ul><li>Wagner, et al., JAMA, 2003 </li></ul>
Scientific Concern-3: Sertraline Response by Age Group <ul><li>Ages 6-11 -24.05 sertraline p= n.s. </li></ul><ul><ul><li>-22.20 placebo </li></ul></ul><ul><ul><li>Ages 12-17 -21.55 sertraline </li></ul></ul><ul><ul><li> -18.20 placebo p=.01 </li></ul></ul>
Scientific concerns-4: Phase III and IV Safety Issues <ul><li>Activation, agitation, hyperactivity, and restlessness occur frequently (0%-55%) in SSRI trials in youths suggesting a lack of standardized measurements. </li></ul><ul><li>Behavioral toxicity research can separate symptoms associated with drug from underlying psychiatric symptoms. </li></ul><ul><li>Suicide is a rare event requiring surveillance research in large populations. </li></ul>
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