British Medical Journal
7 May 2011 Volume 342, Issue 7805
http://www.bmj.com/content/current

Analysis
The true cost of pharmacological disease prevention
Teppo L N Järvinen, Harri Sievänen, Pekka Kannus, Jarkko Jokihaara, Karim M Khan
BMJ 2011;342:doi:10.1136/bmj.d2175 (Published 19 April 2011)

Extract
Despite widespread use of preventive drugs such as statins, antihypertensives, and bisphosphonates, there is no valid evidence that they represent value for money, argue Teppo Järvinen and colleagues

Large randomised clinical trials are considered to represent the strongest form of evidence in assessing whether a particular healthcare intervention works. However, little attention has been paid to the fact that people treated in large multicentre randomised trials may not accurately reflect the population receiving the drug in real world settings.

Recently, van Staa and colleagues assessed the external validity of published cost effectiveness studies of selective cyclo-oxygenase-2 (COX 2) inhibitors by comparing the data used in these studies (typically from randomised trials) with observed clinical data.   2 The trial data suggested that the cost of avoiding one adverse gastrointestinal event by switching patients from conventional non-steroidal anti-inflammatory drugs to COX 2 inhibitors would be about $20 000 (£12 500; €14 000). However, when the same analysis was performed using the UK’s General Practice Research Database, comprising anonymised medical records of general practitioners, the cost of preventing one bleed was fivefold greater ($104 000). 2 The authors concluded that the published cost effectiveness analyses of COX 2 inhibitors neither had external validity nor represented the patients treated in clinical practice. They emphasised that external validity should be an explicit requirement for cost effectiveness analyses that are used to guide treatment policies and practices.

Efficacy versus effectiveness

This striking difference between the results from randomised trials and the real world clinical implications was recognised by Archie Cochrane, the pioneering clinical epidemiologist. Almost 40 years ago, Professor Cochrane introduced a specific hierarchy of evidence required from any healthcare intervention before it can be applied to real life situations (table ⇓ ). Three simple questions summarise Cochrane’s scheme: can it work (efficacy)? does it work (effectiveness)? and is it worth it (cost …