Protocol Amendments and Probability of Success in Clinical Trials Open Access

Zhang, Lu (Spring 2021)

Permanent URL:


During a drug's clinical trial, outcomes should be defined before the trial starts and not amended after. However, the selective publication of studies with statistically significant results and selective reporting of favorable outcomes are not uncommon. Outcome amendments are also prevalent, which can influence the trials' results. This study's primary purpose is to investigate drugs' mid-trial endpoint amendments' effect on its trials' probability of success. A large dataset containing 13584 clinical trials associated with 313 drugs is analyzed by an automated algorithm capturing and categorizing different protocol amendments. Statistical analyses demonstrate the prevalence of multiple testing and protocol amendments in clinical trials. On average, each clinical trial declared 1.91 primary outcomes and 5.93 secondary outcomes. Around 18% of protocols are amended after pre-registration. Pearson correlation test shows that protocols with one type of changes are significantly more likely to have other types of amendments. Multiple linear regression shows that the number of protocol changes, especially changes in the primary outcome, significantly affects the drug's probability of success. This study suggests that the FDA should consider enforcing better regulation of protocol changes after the start of clinical trials.

Table of Contents

INTRODUCTION                                                                                  1

BACKGROUND                                                                                     1

LITERATURE REVIEW                                                                         2

DATA                                                                                                       4

METHODOLOGY                                                                                  6

RESULTS                                                                                                8

Prevalence of Multiple Outcomes                                                   8

Prevalence of Protocol Amendments                                              9

Correlation Matrix for different types of protocol amendments   12

Probability of Success                                                                      13

Multiple Linear Regression                                                             13

CONCLUSION AND DISCUSSION                                                   15

REFERENCES                                                                                      17

About this Honors Thesis

Rights statement
  • Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.
  • English
Research Field
Committee Chair / Thesis Advisor
Committee Members
Last modified

Primary PDF

Supplemental Files