Intended for healthcare professionals

Practice Uncertainties Page

Research to decrease areas of clinical uncertainty

BMJ 2011; 342 doi: (Published 04 February 2011) Cite this as: BMJ 2011;342:d369
  1. Andrew Farmer, professor of general practice1,
  2. Ruairidh Milne, senior clinical lecturer in public health2,
  3. Tom Walley, professor of clinical pharmacology, director of NIHR HTA programme3
  1. 1NIHR School for Primary Care Research, Department of Primary Health Care, University of Oxford, Oxford OX3 7LF, UK
  2. 2NIHR Evaluation, Trials and Studies Coordinating Centre (NETSCC), University of Southampton, Southampton, UK
  3. 3Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 3GF, UK
  1. Correspondence to: A Farmer andrew.farmer{at}

Uncertainties abound in healthcare. The 2008 editorial by Chalmers that launched the BMJ’s Uncertainties Page series highlighted the enormous harms that can come from failure to identify and reduce them.1 In the United Kingdom, the National Institute for Health Research’s Health Technology Assessment (HTA) programme is charged with producing independent and rigorous research about the effectiveness of different healthcare technologies to resolve important areas of uncertainty. The HTA programme was established in 1993 and is funded by the Department of Health as part of the National Institute for Health Research ( The article this week in the BMJ’s Uncertainties Page series is the first of several articles in this series that will focus on areas of clinical uncertainty being investigated by HTA research.2

The HTA programme aims to meet the information needs of the NHS and works by consulting widely to identify topics for research. Suggestions are made through a web based suggestion system (; the HTA also identifies topics by reviewing reports and systematic reviews from bodies such as the National Institute for Health and Clinical Excellence and the Cochrane Collaboration. A priority setting exercise is conducted to decide which research to commission. Requests for research into these topics (commissioning briefs) are framed using the PICO structure (Population (what is the population of interest?), Intervention (what are the interventions of interest?), Comparison (what are the comparisons of interest?), Outcome (what are the outcomes of interest?))3 to emphasise their relevance to patients and clinicians. The commissioning brief asks for evidence synthesis or new primary research, usually in the form of a randomised trial. Researchers can also apply directly to the HTA programme for funding, but the topics proposed are first assessed for NHS importance; only if the topic meets this criterion will the proposal proceed for scientific assessment. When the research is complete, the findings are published in the journal series Health Technology Assessment (, providing a record of the research that complements shorter articles in journals such as the BMJ.

Most HTA trials seek to establish the benefit of a treatment or investigation in routine practice rather than under ideal conditions. Trials are therefore usually conducted in a clinical setting, with interventions delivered wherever possible as they would be in routine clinical practice. Measures, including independent randomisation and intention to treat analysis in randomised trials, are needed to avoid bias. The key outcomes sought in such studies are patient outcomes, not surrogates, as measures of effectiveness and cost effectiveness.

Many research projects commissioned by the HTA programme have been highly influential in changing clinical practice and healthcare policy. The Cooksey review, which has guided much of the recent development of NHS research policy, identified the HTA programme’s success in providing NHS decision makers with a high quality evidence base and suggested that much of the escalating information needs of the NHS could be met by expanding the programme.4 Individual trials commissioned by the HTA programme have also helped to resolve uncertainties around specific issues. For example, the Venus II trial showed that larval therapy is effective as a debridement agent in leg ulcers, although it did not speed up healing.5 The CRASH-2 trial showed that a short course of tranexamic acid, a low cost treatment, in the management of trauma patients reduced the percentage of people dying from 16.0% to 14.5%.6 The DiGEM trial highlighted the lack of evidence for clinical benefit from routine self monitoring of blood glucose for people with type 2 diabetes not treated with insulin.7 Although primary research may take many years, it can if necessary be delivered quickly—for example, in response to the recent influenza pandemic, information about the spread and prevalence of the condition was rapidly available to clinicians and policy makers.8

We hope that the BMJ series, in highlighting HTA projects that have been commissioned in response to clinically important uncertainties, can achieve three objectives. Firstly, raising awareness of the current uncertainty can encourage clinicians and patients in relevant areas to support the research and take part where possible. Secondly, the series will help to ensure that when the results are published they can be rapidly taken into clinical practice. Finally, we hope that by making the process of funding research more transparent we can encourage individuals to identify new areas of clinical uncertainty and report them to the HTA programme, so that these topics can enter the commissioning process, helping to resolve that uncertainty and improve the care received by patients.


Cite this as: BMJ 2011;342:d369


  • doi=10.1136/bmj.d234
  • Contributors: All authors contributed to the writing and are guarantors.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; the following financial relationships with organisations that might have an interest in the submitted work in the previous three years: AF is deputy chair of the National Institute for Health Research (NIHR) HTA Commissioning Board, RM is employed by the NIHR Evaluation, Trials and Studies Coordinating Centre at the University of Southampton, and TW is director of the HTA Programme; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Commissioned; not externally peer reviewed.


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