In order to determine the applicability of noninvasive magnetic resonance spectroscopy (MRS) to the study of a diseased tissue or organ in the human body, it is necessary to determine if MRS is safe and effective. This is the primary purpose of a clinical trial. A clinical trial for MRS may also reveal which technical approach works best for the specific application and characteristics of the population being studied. In this chapter, we discuss the legal, ethical, and scientific requirements to be considered prior to the start of a clinical trial of an MRS protocol, as well as constraints that may arise during its execution. MRS-specific issues arising from a couple of successful clinical MRS trials for classifying brain tumors with 1H MRS (INTERPRET and eTUMOUR) and body tumors with 31P MRS (the Cooperative Group on MRS Application in Cancer, CoGMAC), serve as illustrative examples.JRG thanks The University of Cambridge, CRUK [grant number C14303/A17197] and Hutchison Whampoa Limited. FAM thanks the National Cancer Institute (NIH) from the United States for their support through grants R01-CA118559 and R21-CA152858. FAM wish to thank Dr. Radka Stoyanova from the University of Miami for helpful contributions to the principal component analysis discussion. MJ is funded by SAF2014-52332-R from MINECO (ES) and CIBER-BBN (Centro de Investigación Biomédica en Red – Bioingeniería, Biomateriales y Nanomedicina [http://www.ciber-bbn.es/en]), an initiative of the Instituto de Salud Carlos III (Spain) co-funded by EU FEDER funds.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/9780470034590.emrstm147
