Health Technology Assessment 2000; Vol. 4: No. 27
View/Download full monograph in Adobe
Acrobat format (363 kbytes)
View/Download this 4-page summary in Adobe Acrobat format (suitable for printing)
West Midlands Development and Evaluation Service, The University of Birmingham,
* Corresponding author
Multiple sclerosis (MS) is an important problem both for people with the disease and for society. There is no cure, and alleviation of symptoms forms the cornerstone of care. Excessive fatigue that severely limits activity is experienced by at least two-thirds of the estimated 60,000 people with MS in the UK.
The review was carried out in two stages: a formal scoping review (to assess the range of interventions used by people with MS), and a systematic review for treatments that had been identified as promising and that had been investigated in clinical trials (as identified in the scoping review). A systematic review of research on costs and cost-effectiveness of those interventions identified as promising was also performed.
Electronic databases, including MEDLINE and EMBASE, were searched for the period 1991June 1999 (scoping review) and 1966December 1999 (systematic review). Reference lists from publications were also searched, and experts were contacted for any additional information not already identified.
Only two drugs, amantadine and pemoline, met the criteria for full systematic review.
One parallel and three crossover trials were found, involving a total of 236 people with MS. All studies were open to bias. All studies showed a pattern in favour of amantadine compared with placebo, but there is considerable uncertainty about the validity and clinical significance of this finding. This pattern of benefit was considerably undermined when different assumptions were used in the sensitivity analysis.
One parallel and one crossover trial were found involving a total of 126 people with MS. Both studies were open to bias. There was no overall tendency in favour of pemoline over placebo and an excess of reports of adverse effects with pemoline.
The drug costs of amantadine and pemoline are modest (£200 and £80 per annum, respectively). No economic evaluations were identified in the systematic review, and available data were insufficient to allow modelling of cost-effectiveness in this rapid review.
There is insufficient evidence to allow people with MS, clinicians or policy makers to make informed decisions on the appropriate use of the many treatments on offer.
Only amantadine appears to have some proven ability to alleviate the fatigue in MS, though only a proportion of users will obtain benefit and then only some of these patients will benefit sufficiently to take the drug in the long term.
The frequency, severity and impact of fatigue, the poverty of available research, and the absence of any ongoing research, suggest that new research is an urgent priority. People with MS, clinicians and policy makers should work together to ensure that the evidence required is collected as quickly as possible by encouraging involvement in rigorous research.
Research should not be restricted to the two drugs reviewed in depth in this report. All interventions identified in the scoping review (see above) should be considered, as should basic scientific research into the underlying mechanism of fatigue in MS.
Brañas P, Jordan R, Fry-Smith A, Burls A, Hyde C. Treatments for fatigue in multiple sclerosis: a rapid and systematic review. Health Technol Assess 2000;4(27).
The overall aim of the NHS R&D Health Technology Assessment (HTA) programme is to ensure that high-quality research information on the costs, effectiveness and broader impact of health technologies is produced in the most efficient way for those who use, manage and work in the NHS. Research is undertaken in those areas where the evidence will lead to the greatest benefits to patients, either through improved patient outcomes or the most efficient use of NHS resources.
The Standing Group on Health Technology advises on national priorities for health technology assessment. Six advisory panels assist the Standing Group in identifying and prioritising projects. These priorities are then considered by the HTA Commissioning Board supported by the National Coordinating Centre for HTA (NCCHTA).
The research reported in this monograph was commissioned by the HTA programme (project number 99/05/05) on behalf of the National Institute for Clinical Excellence (NICE). Rapid reviews are completed in a limited time to inform the appraisal and guideline development processes managed by NICE. The review brings together evidence on key aspects of the use of the technology concerned. However, appraisals and guidelines produced by NICE are informed by a wide range of sources. Any views expressed in this rapid review are therefore those of the authors and not necessarily those of the HTA programme, NICE or the Department of Health.
Reviews in Health Technology Assessment are termed systematic when the account of the search, appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others.
Criteria for inclusion in the HTA monograph series
Reports are published in the HTA monograph series if (1) they have resulted from work either prioritised by the Standing Group on Health Technology, or otherwise commissioned for the HTA programme, and (2) they are of a sufficiently high scientific quality as assessed by the referees and editors.
Series Editors: Andrew Stevens, Ken Stein and John Gabbay
Monograph Editorial Manager: Melanie Corris
The editors and publisher have tried to ensure the accuracy of this report but do not accept liability for damages or losses arising from material published in this report.
©2000 Crown Copyright