The ICHS7B and E14 documents provide guidance on the assessment of risk of QT prolongation and cardiac arrhythmias by compounds undergoing preclinical and clinical development. Since the introduction of the EMEA CPMP "Points to Consider" document on this subject in 1998, the industry has been adopting testing paradigms to screen out, where possible, compounds with implicit potential to cause QT prolongation. However, from experience of testing large numbers of compounds from varied structural classes, 70% of the compounds screened for hERG channel blocking activity were positive. Although concentrations tested may be well in excess of the intended therapeutic concentrations, this has meant that some compounds are being taken into formal preclinical development and subsequently clinical development carrying a positive hERG signal. The E14 guidance requires that a thorough QT study is conducted that will detect a mean increase in corrected QT interval of 10 ms or around 2-3%. This study cannot be conducted until the therapeutic concentrations are well understood and therefore what they are likely to be during Phase II clinical trials.