Table of Contents

INTRODUCTION ……………………………………………………………………………………1
The Role of Randomized Controlled Trials in Modern Medicine …………………1
RCT, Gold Standard with an Achille’s Heel. ………………………………………2
RCT, Gold Standard or Gold Trojan Horse?…………………………………… ……………4
FDAAA: Mandatory Registration and Results Reporting …………………………….5
STATEMENT OF PURPOSE ……………………………………………………..7
METHOD …………………………………………………………………9
Data Sources ……………………………………………………………..9
Novel Therapeutics Approved for Treating Neurological and Psychiatric Disorders, 2005-2014 …9
Efficacy Trials Supporting FDA New Neuropsychiatric Drug Approval ………..10
Determination of FDAAA Status ………………………………………………………………………………………11
Determination of Registration and Results Reporting Status on ClinicalTrials.gov ………11
Determination of Publication Status …………………………..12
Interpretation of Trial Results: Publication vs. FDA ……………………….12
Validating the Published Interpretations …………………………………..13
Calculating the Degree of Publication Bias ………………………….14
Data Collection and Data Validation ……………………………………………….14
Data Analysis ………………………………………………….15
RESULTS ……………………………………………………………….16
Characteristics of the Neuropsychiatric Drugs Approved between 2005-2014 …….16
Table 1. New Drug Applications (NDA) Approved by the FDA between 2005 and 2014 with
Indications for Neurologic and Psychiatric Conditions …………………..16
Clinical Trials Supporting FDA Approval ……………………………….18
Clinical Trial Registration and Results Reporting ………………………………….18
Publication and Published Interpretations …………………………………………………19
Table 2. Characteristics of 142 Efficacy Trials Supporting FDA Approval of NDA for
neuropsychiatric conditions, 2005-2014 …………………………………………..19
Table 3. Publication and Publication-FDA Agreement of Trials Supporting FDA Approval of
NDAs with Neuropsychiatric Indications with Positive, Equivocal, and Negative Results ………..20
Box 1 Examples of Trials Published with Interpretations Disagreeing with the Interpretations of the FDA medical reviewers. ……………………………………………………..21
Publication Bias ………………………………………………………………25
DISCUSSION ……………………………………………………………….26
Study Findings & Prior literature ……………………………………………………26
Implication for Understanding the Impact of FDAAA …………………………..27
Implications for Future Policy Development …………………………………..28
Implications for the Practice of Medicine ………………………..28
Limitations …………………………………………………….29
Conclusions ……………………………………………….30
REFERENCE………………………………………31
FIGURES, TITLES, AND LEGENDS ……………………………………………31
Figure 1. Identification of Trials Reviewed by the FDA for New Drug Applications with
Neuropsychiatric indications, 2005-2014 ……………………………….37
Figure 2 Registration and Results Reporting Status of Trials Supporting FDA Indications by
FDAAA applicability, 2005-2014 ………………………………………………………38
Figure 3. Publication Status and Publication-FDA Agreement of Neuropsychiatric Trials by
FDAAA Applicability and by Trial Results ………………………………………39