Making a decision to wait for more evidence: when the National Institute for Health and Clinical Excellence recommends a technology only in the context of research
Authors: Kalipso Chalkidou, Andrew Hoy, Peter Littlejohns
Journal: Journal of the Royal Society of Medicine (2007)

New treatments tested in randomized trials are as likely to be inferior as they are to be superior to standard treatments.1 The ethical implication of this empirical observation is that unevaluated new treatments should be assessed carefully in well-designed research before decisions are taken about whether or not they should become widely available. Indeed, the same principle applies when there are uncertainties about the effects of ‘standard’ treatments. The dangers of acquiescing when it is uncertain whether treatments do more good than harm has been illustrated dramatically by the results of the CRASH trial:2 tens of thousands of iatrogenic deaths have occurred because of decades of failure to address uncertainties about the effects of systemic steroids for patients with acute traumatic brain injury

It is against this background that some clinicians believe that unproven treatments should only be offered within the context of appropriately designed research. In the perinatal field, for example, obstetricians decided that chorionic villus sampling should be used in low-risk pregnancies only within the context of a randomized comparison with amniocentesis.3 Similarly, neonatologists restricted the use of neonatal extracorporeal membrane oxygenation (ECMO) to a randomized comparison with standard respiratory support,4,5 and they are currently restricting the use of prolonged whole-body cooling in term infants with perinatal asphyxial encephalopathy to a randomized comparison with standard treatment (the TOBY trial: Whole Body Hypothermia for the Treatment of Perinatal Asphyxial Encephalopathy)

Ethical considerations have been the main motivation for clinicians who have dealt with uncertainties about treatments in this way. But ethical considerations have also informed similar decisions made by agencies managing health service funds on behalf of defined populations to whom they are answerable for cost-effective use of resources.6 For example, the Centre for Medicare and Medicaid Services (CMS) in the USA decided that, until more was known about its relative merits and demerits, lung reduction surgery should only be supported if given within the context of a randomized comparison with non-surgical treatments.7 The Centre is currently formalizing the criteria for applying this principle,8 which has also been considered9 and implemented on a single occasion so far (personal communication, Professor Wing) by the Pharmaceuticals Benefit Scheme in Australia.10

The principle of recommending that when there are important uncertainties about a treatment's effects, that treatment should only be used in the context of research, was explicitly recognized by the National Institute for Health and Clinical Excellence (NICE) at its inception in 1999. NICE was set up to develop evidence-based guidance for the NHS and the broader public sector with the explicit objectives of promoting cost-effective use of resources while encouraging innovation, improving quality and reducing variation in practice.11 To do so, NICE and its advisory bodies were given three decision options, set out by the Department of Health shortly before NICE's establishment in 1999.12 When appraising health interventions (including health technologies, health promotion and disease prevention programmes, screening and diagnostic tests, surgical procedures, etc.), NICE would be able to recommend:



The routine use of an intervention in the NHS, either for all or specific licensed indications or patient subgroups;


That the intervention is not used in the NHS because of inadequate evidence of effectiveness, or more frequently cost-effectiveness; or


The use of the intervention in the NHS only in the context of appropriate research. This would be appropriate in the case of promising interventions not yet supported by sufficiently robust evidence to justify an unqualified recommendation. In those cases, NICE would ‘recommend that further research is carried out to see whether the potential promise of the intervention can be realized, indicate in broad terms the questions this research should address and advise clinicians that, in the meantime, they should only use the new intervention as part of a well-designed programme of research intended to answer these questions’ (paragraphs 33-36 in Faster Access to Modern Treatment: How NICE Appraisal Will Work12)