Intended for healthcare professionals


Commentary: Controversies in the Department of Health’s clinical guidelines for immunoglobulin use

BMJ 2008; 337 doi: (Published 20 October 2008) Cite this as: BMJ 2008;337:a1851
  1. Penny Fitzharris, clinical immunologist 1,
  2. Miriam Hurst, fellow in clinical immunology1
  1. 1Immunology, Auckland City Hospital, Grafton, Auckland 1023, New Zealand
  1. Correspondence to: P Fitzharris pennyf{at}

    Variable supply, high product costs, and an increasing demand for both established and off-label indications have made the Department of Health’s development of a management programme for intravenous immunoglobulin use in the United Kingdom essential. This programme includes three core elements: a demand management plan,1 clinical guidelines,2 and a national immunoglobulin database.

    Intravenous immunoglobulin is used in over 100 conditions by many different disciplines, and, although there is an adequate evidence base for some indications, this is not the case for many others, even where intravenous immunoglobulin is accepted as the most appropriate treatment. The need for improved clinical trial data is clear, but for rare conditions this is difficult. It is reassuring that feedback from neurologists indicates acceptance that the new national guidelines are similar in content to their existing specialty guidelines,3 but in many areas (such as specific antibody deficiency in clinical immunology) best practice is still unclear. Cost benefit data are also lacking; globally, human plasma is an expensive commodity that requires specialised and lengthy processing. A further complicating factor in the supply in the UK is the risk of variant Creutzfeldt-Jakob disease, which precludes the use of local plasma and requires the purchase of plasma from the United States.

    How well the guidelines will work is likely to vary from one healthcare trust to another and from one primary care trust to another. It is essential that potential prescribers understand the application process, which, in a rather odd decision, is published only in the demand management plan and not in the clinical guidelines.2 For “red” indications (considered the highest priority because of risk to life without treatment, such as selected primary immunodeficiencies, Kawasaki disease, Guillain-Barré syndrome) clinicians may prescribe without prior approval, with retrospective completion of the immunoglobulin request form for sign-off by a designated person, and subsequent database registration. Linking the release of product funding to database entry should encourage healthcare trusts to ensure that this process is completed.

    The process is more complex for other indications. For “blue” conditions (for which immunoglobulin is shown to be effective but alternatives exist) the local immunoglobulin assessment panel can approve use. For “grey” or unlisted indications (where there is insufficient evidence), approval from both the immunoglobulin assessment panel and the primary care trust is required. Emergency prescribing, sanctioned by at least two panel members, is possible for “blue” indications. The decision to use colour coding means that printing in black and white does not work well.

    Management of intravenous immunoglobulin use is a global problem. Recent Australian guidelines are broadly similar, with four categories of use: established, emerging, and exceptional, and a “not funded” category equivalent to the UK “black” list (indications for which immunoglobulin is not recommended).4 Inevitably, with the large number of diseases covered and poor evidence base, there are some differences in recommendations. The Australian guidelines, for example, list neonatal haemochromatosis as an established indication, but this rare condition is not listed in the UK guidelines. For other conditions the UK guidelines are more permissive. Immunologists from Asia and Pacific nations have also recently developed detailed regional guidelines, which provide an educational resource on immune deficiency diseases as well as information about the technicalities of intravenous immunoglobulin infusion and management of adverse reactions.5

    If healthcare trusts are motivated, panels readily accessible, and primary care trusts’ responses rapid, then these guidelines should be valuable and effective. However, serious delays in acquiring immunoglobulin are likely to result in resentment, complaint, and possible harm to patient care, as would lack of an appeal procedure. It is essential that feedback and responsive review of the guidelines continue and that the transition from commissioning by individual primary care trusts to commissioning by specialised commissioning groups, planned for April 2009, is smooth. Increased resources for clinical trials are needed to improve the quantity and quality of available data, especially for “grey” indications such as systemic lupus erythematosus and the systemic vasculitides. So far the score card reads “A for effort”—the score for efficacy is awaited.


    Cite this as: BMJ 2008;337:a1851


    • doi:10.1136/bmj.a1831
    • Contributors: Both authors contributed to the conception, drafting, and revision of the article and gave final approval of the version to be published. PF is the guarantor.

    • Competing interests: None declared.

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


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