Chapter 2: Treatment Uncertainties

People have suffered and died unnecessarily because uncertainties about the effects of treatments have not been addressed in research 4 5 6 .  Patients and the public have a right to expect that research funders, researchers and health professionals will identify uncertainties about whether treatments are doing more harm than good or whether one treatment is better than another, and should expect them to organise the research needed to reduce the most important of these uncertainties.

The JLA definition of a treatment uncertainty is that:

  • no up-to-date, reliable systematic reviews of research evidence addressing the uncertainty about the effects of treatment exist
  • up-to-date systematic reviews of research evidence show that uncertainty exists.

Systematic reviews are based on worldwide searches for reliable, relevant evidence.  They are comprehensive summaries and analyses of comparable published and unpublished studies of effectiveness, prepared by a team of authors.  Systematic reviews are used to inform health and social care service development, policy development, and research.

It is recognised that many PSPs now extend their scope beyond identifying and prioritising ‘treatment uncertainties’ and include other health care interventions like prevention, diagnosis, rehabilitation, care, and service organisation and delivery.  Many of these areas will require a different protocol for evidence checking, extending beyond searching for systematic reviews.  The different evidence checking methods for these PSPs need to be transparent and agreed with the PSP Steering Group and JLA Adviser.

More detailed information about systematic reviews and fair tests of the effects of treatments is available in the James Lind Library.  Further information is also available at

To help ensure that treatments do more good than harm, gaps in knowledge about their effects – i.e. uncertainties - must be identified, and those deemed sufficiently important must be addressed in research. 

4 Chalmers, I. Confronting therapeutic ignorance. BMJ 2008;337:a841
5 Chalmers, I. Well informed uncertainties about the effects of treatments. BMJ 2004;328:475-6
6 Evans, I., Thornton, H., Chalmers, I., Glasziou P. Testing Treatments: better research for better healthcare (2011)