Development and integration of molecular genetic tests into clinical practice: the US experience

The issues that arise in the development of genetic tests for prediction and diagnosis are described in the context of the authors' experience as laboratory directors in the USA. The goal is to identify gaps and weaknesses in the test validation process and to define the pivotal issues. Variables that influence a laboratory director's decision to develop a particular molecular genetic assay, including motivation, economics, intellectual property and the regulatory environment, are described. Issues of clinical and analytic validation are discussed, providing examples of tests with both good (cystic fibrosis carrier screening) and poor (apolipoprotein E genotyping for Alzheimer's disease) clinical utility. The decision-making process that occurs during the considered transition of a research-based molecular genetic assay into routine use in the clinical laboratory is summarized. Different factors will be weighted differently depending on the nature of the disease being tested, the complexity of its gene and mutations, the available technical platforms, potential regulatory and intellectual property restrictions, and whether the proposed test is to be offered by an academic or a commercial laboratory.