Mixed treatment comparisons inform clinical guidelines

A new technique for comparing healthcare treatment options is helping policy makers in the UK, Canada, Germany, and South Korea.

When a decision has to be made about whether or not the NHS should use a new drug or fund a new treatment, it is the job of the National Institute for Health and Care Excellence (NICE) to offer unbiased guidance on which option is most effective and cost-effective.

While comparing two healthcare treatment options (A versus B) can be relatively straightforward, when there are many treatment options (eg A,B,C,D and placebo) it is more difficult to determine which is the best, particularly when many of them have never been compared directly in clinical trials.

A new methodology

Researchers at University of Bristol’s School for Social and Community Medicine recognised there was a problem and developed a methodology that enables multiple treatment options to be compared accurately, based on the trial evidence. Called mixed treatment comparisons (MTC), or network meta-analysis, the technique has informed clinical guidelines issued by NICE and is used in decision making by NICE’s equivalents in other countries including Canada, Germany, and South Korea, as well as by consultancy firms that conduct analyses for pharmaceutical companies.

“MTC methods allow information from all the trials of all the treatments of interest to be compared simultaneously (A versus B versus C versus D, etc),” explains Dr Nicky Welton, from the University’s Multi-Parameter Evidence Synthesis (MPES) research group. “The simplest example of an MTC is an ‘indirect comparison’, where in the absence of trials comparing A versus B, the effect of A versus B is inferred from trials comparing A versus C and trials comparing B versus C. More generally, our methods combine the “direct” and “indirect” evidence on all the comparisons in networks of evidence that may involve as many as 40 treatments.”

Comparing treatments 

Because MTC methods allow more evidence to be combined, relative treatment effects can be estimated more precisely than with standard meta-analysis methods. Treatments can also be ranked according to both efficacy and cost-effectiveness, allowing policymakers and guideline development groups, whether in insurance- or state-funded health systems, to make better-informed decisions, supporting equitable and optimum resource allocation by health service purchasers.

“MTC methods are now used in around half of NICE’s Technical Appraisals covering a wide range of clinical areas,” says Dr Welton. “Previously, comparisons between healthcare options were often naïve and had methodological flaws. It is very satisfying to know that our work is being used by policy makers to make informed decisions about the allocation of precious resources in the NHS.” The methods are also used to develop NICE Clinical Guidelines, and the MPES group has a long-standing contract to provide technical support to NICE’s guideline developers.

Direct impact on healthcare policy

Members of the MPES group, Professor Tony Ades, Dr Deborah Caldwell, Dr Sofia Dias, Guobing Lu and Dr Nicky Welton, developed general computer code to conduct MTC and made this code freely available through its website and the NICE Decision Support Unit website. These methods are now widely accepted, and were adopted in the 2008 and 2013 updates of the NICE Guide to the Methods of Technology Appraisal. NICE, through its Decision Support Unit, commissioned the MPES group to write a series of Technical Support Documents, including general code for a range of different types of outcomes and evidence structures to guide those making submissions to NICE.

“NICE Technology Appraisals determine whether new technologies are cost-effective for the UK National Health Service (NHS), and if they are then they must be adopted by law within three months of the guidance being issued,” explains Dr Welton. “NICE Technology Appraisals therefore impact directly on healthcare policy governing which new treatment options are available to health professionals to treat patients. Because NICE guidance is primarily based on cost-effectiveness, it secures more health-related quality of life per pound spent by the NHS.”

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