Intended for healthcare professionals

Education And Debate

Using high quality clinical databases to complement the results of randomised controlled trials: the case of recombinant human activated protein C

BMJ 2001; 323 doi: (Published 20 October 2001) Cite this as: BMJ 2001;323:923
  1. Andrew Padkin, MRC training fellow in health services research (,
  2. Kathy Rowan, directorb,
  3. Nick Black, professor of health services researcha
  1. a Editorialby Hinds Health Services Research Unit, Department of Public Health and Policy, London School of Hygiene and Tropical Medicine, London WC1E 7HT
  2. b Intensive Care National Audit and Research Centre, Tavistock House, London WC1H 9HR
  1. Correspondence to: A Padkin
  • Accepted 7 September 2001

Understanding the generalisability (or applicability) of the results of randomised controlled trials in typical clinical practice remains one of the key methodological challenges to achieving a more scientific basis for health care.1 Little effort is made to use a scientific approach to assess generalisability, document the use of a new intervention systematically, or determine whether the trials' results are replicated in real life, either in the original patient groups studied or in other patients who receive the intervention.

To explore these issues, we use a case study to describe the practical difficulties that exist for policymakers and clinicians in interpreting the results of a randomised controlled trial evaluating recombinant human activated protein C, a new drug for treating severe sepsis in intensive care patients. We suggest how an existing, high quality, clinical database could provide information on the generalisability of the trial results and on the likely financial consequences of the drug's introduction, and how it could be used to monitor the diffusion and effectiveness of the drug in typical clinical practice.

Summary points

Randomised controlled trials may be performed in atypical settings with atypical patients, making it difficult to assess the generalisability of the results

High quality clinical databases could be used to facilitate this assessment and to provide evidence of clinical effectiveness in typical clinical practice

The case for using a high quality clinical database in the assessment of recombinant human activated protein C, a new drug for treating severe sepsis in intensive care patients, provides an important topical example

Limitations of randomised controlled trials

Evidence based medicine has focused on understanding the factors affecting the internal validity of randomised controlled trials but has paid far less attention to their generalisability. This is reflected in the many instruments for assessing the quality of trials, which concentrate predominantly on identifying factors that may challenge internal …

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