General Introduction

  • Ton J. Cleophas
  • Aeilko H. Zwinderman


The current chapter reviews the history of adverse effects of modern medicines from the era of pharmageddon to the current era of precision medicine. Adverse drug effects are classified significant, if their 95% confidence interval is significantly different from zero or control. They are classified dependent, if they are significantly dependent not only on the efficacy variable of the study but also on the main outcome variable. They may be harder to recognize and may go undetected if not special methods for assessment have been used.

A brief review is given of the detection and assessment of different types of dependent adverse effects.

Mechanisms of dependency may be:
  • causally,

  • pharmacologically,

  • through interaction,

  • through a subgroup mechanism,

  • through a pleiotropic drug effect,

  • through carryover effect,

  • through a categorical effect,

  • through confounding.

Particular attention will be given to structural equation modeling for the purpose of a rapid identification of types of relationships.


Pharmageddon Precision medicine Significant and insignificant adverse effect Dependent and independent adverse effect Structural equation modeling 

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Ton J. Cleophas
    • 1
  • Aeilko H. Zwinderman
    • 2
  1. 1.Albert Schweitzer HospitalDepartment MedicineSliedrechtThe Netherlands
  2. 2.Department of Biostatistics and EpidemiologyAcademic Medical CenterAmsterdamThe Netherlands

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