Karen began her professional career first as a researcher and subsequently as a lecturer in medical and social studies. She joined the Office for Population Census and Surveys (OPCS) in 1974, and during her time there, helped to lead OPCS through a period of tremendous technological change, culminating in the merger of the OPCS with the Central Statistical Office to form the Office for National Statistics (ONS) in 1996.

At ONS, Karen was first a Divisional Director and subsequently rose to Group Director of the Social Directorate. Prior to being appointed as the National Statistician Karen was the Executive Director with responsibility for Surveys and Administrative Sources, including the Statistical Modernisation Programme.

Besides her work at ONS, Karen has published widely on statistical topics, including three books on health and demographics. She is active in professional as well as academic life. She is a Fellow of the Royal Statistical Society and has been chair of the Society for Social Medicine, visiting professor at the London School of Hygiene and research associate at the London School of Economics.

On 1 April 2008 Karen became the UK Statistics Authority's chief executive in charge of reporting to the Authority Board on National Statistics, while establishing quality and good practice between ONS and the Statistics Authority. She continues to be Head of the Government Statistical Service.

Karen is an advisor to the Mapping Needs Project.