Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs

Chapter 33

Gene Therapy

Samantha L. Ginn and Ian E. Alexander

33.1 Introduction

Gene therapy is defined by the United Kingdom’s Gene Therapy Advisory Committee as “the deliberate introduction of genetic material into human somatic cells for therapeutic, prophylactic or diagnostic purposes” [1] and was conceived, originally, as an approach for the treatment of inherited monogenic diseases. Ongoing improvements in gene-transfer technologies and biosafety have been accompanied by a growing appreciation of the broader scope of gene therapy. Pathophysiological processes such as wound healing [2, 3], chronic pain [4] and inflammation [5, 6], cancer [7–9], and acquired infections such as HIV-1 [10] are now becoming realistic targets for this promising therapeutic modality.

The first authorised gene transfer study took place at the National Institutes of Health (NIH) in 1989. In this marker study, tumor-infiltrating lymphocytes were harvested, genetically tagged using a 7-retroviral vector, and reinfused with the intention of examining the tumor-homing capacity of these cells. This landmark study provided the first direct evidence that human cells could be genetically modified and returned to a patient without harm [11]. Since then, over 1800 trials have been approved, initiated, or completed worldwide [12], with the majority being in the United States [13, 14]. Most studies have focused on cancer, with monogenic and cardiovascular diseases the next most frequent indications (Table 1