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    Can you keep up with ever changing evidence based medicine?
    One issue that comes up frequently that the evidence changes in such a way that decision making with patients is significantly influenced: this has a great bearing on how we can put in place mechanisms to ensure that guidelines and decision tools are constantly updated in real time.

    Last week we “knew” that probiotics produce large reductions in the rate of antibiotic-associated diarrhoea (cut by 40%) and of C difficile infection in particular (cut by 60%).
    These figures come from two meta-analyses of the existing trials, which were mostly small and of mixed quality.
    But this week we have the results of the first really large-scale (n=2941), well-conducted, placebo-controlled randomised trial of 21-day treatment with a combined preparation oflactobacilli and bifidobacteria: and it had no effect at all.
    So do we simply feed these results into a new meta-analysis? If we do, according to an editorial on this study (PLACIDE), the aggregated effect size from all the trials hardly changes: probiotics still produce a large reduction in C diff. On the other hand, if we believe the results of the best and biggest trial, probiotics are useless.

    “Evidence-based” medicine is far from straightforward.

    But here’s a more straightforward example of the value of EBM.

    Systematic reviewing can be a tiresome business, but this is what it discovers about the agents used to reduce blood phosphate in people with advanced renal disease:
    “Our search identified 847 reports, of which eight new studies (five randomised trials) met our inclusion criteria and were added to the ten (nine randomised trials) included in our previous meta-analysis. Analysis of the 11 randomised trials (4622 patients) that reported an outcome of mortality showed that patients assigned to non-calcium-based binders had a 22% reduction in all-cause mortality compared with those assigned to calcium-based phosphate binders (risk ratio 0•78, 95% CI 0•61—0•98).
    In other words, we have probably been killing renal patients by using calcium-based phosphate binders.

    A major problem for EBM is that the many important questions have never been addressed in head-on, well conducted randomised trials.

    Most interventions are tested by their manufacturers against the comparator most favourable to them, including placebo (and even placebos can be tampered with).
    I am constantly amazed that health systems are willing to throw away billions to pay for such treatments, but are usually reluctant to spend more than a few millions on objective comparative effectiveness research.
    The Health Technology Assessment unit of the UK has a budget of £70 million, about a tenth of the amount most large drug companies would spend on promoting a single new product.
    Yet this article shows that it has supported research of immense practical value.
    By showing that bevacizumab is as effective for age-related macular degeneration as ranibizumab, it has saved the NHS more than its own budget, every year (see the IVAN trial).

    And that is only one of numerous examples:
    the use of tranexamic acid in major trauma, shown to be beneficial in the CRASH-2 trial, is probably saving 100,000 mostly young lives annually around the world.

    Comments and experience most welcome.

    G Mohan.

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