The chairman of the UK’s National Institute for Health and Clinical Excellence (NICE) has suggested randomised controlled trials (RCTs) should no longer be seen as the be-all and end-all of clinical research.
In a speech last night to the Royal College of Physicians, Professor Sir Michael Rawlins said such studies had been placed “on an undeserved pedestal”. He called for other types of research, including observational studies, to be given greater attention.
Professor Rawlins presides over an organisation that has regularly indicated its discontent with clinical evidence supplied by drug manufacturers. For its part, industry has been vocal in its criticisms of NICE’s cost-effectiveness models. More recently, Professor Rawlins has sharply criticised industry pricing practices
for new drugs.
All the same, some may be surprised at his willingness to question the value of RCTs, generally seen as the most rigorous tests for a new medicine, and talk up the benefits of other types of study.
In his speech Professor Rawlins said clinical trials were:
* Virtually impossible to conduct properly when studying treatments for rare diseases with very few patients
* Often prohibitively expensive. He cited a recent study of 153 trials completed in 2005 and 2006, which showed a median cost of over £3 million, with one trial costing £95 million. One manufacturer has estimated that the average cost per patient of a clinical trial rose from £6,300 in 2005 to £9,900 in 2007
* Even “unnecessary” when, as in the case of Novartis’ Glivec (imatinib) for chronic myeloid leukaemia , a treatment produced a particularly “dramatic” benefit
However, Professor Rawlins also expressed concern about the growing tendency, especially in cancer research, for clinical trials to be stopped early.
“The desire to stop trials early is understandable, but the possibility that an interim analysis is a ‘random high’ may be difficult to avoid,” he said. Moreover, there was “no consensus among statisticians as to how best to handle the problem”.
Prof Rawlins also had some criticism for his medical colleagues, many of whom adopted too rigid an approach to clinical research, he claimed, particularly in the trend towards ranking different types of clinical trial in terms of importance.
“Hierarchies attempt to replace judgment with an over-simplistic, pseudo-quantitative, assessment of the quality of the available evidence,” he commented.
Accoording to Professor Rawlins, observational studies, historical controlled trials and case-control studies are also important sources of information.
What is needed is for “investigators to continue to develop and improve their methodologies; for decision-makers to avoid adopting entrenched positions about the nature of evidence; and for both to accept that the interpretation of evidence requires judgment”, he concluded.
