To the Editor: We write in response to recently published consensus recommendations for the off-label use of pharmaceuticals, which provide a common-sense, evidence-based approach to a commonly encountered clinical problem.1 The recommendations indicate that, other than for exceptional or research indications, off-label use of a medicine is generally not recommended unless there is high-quality evidence supporting such use. However, for some older pharmaceuticals, there is little incentive to perform additional trials to generate good evidence to support off-label use.

An example is rifampicin, which is commonly used in combination with fusidic acid to treat methicillin-resistant Staphylococcus aureus (MRSA) infection, but is not licensed or subsidised by the Pharmaceutical Benefits Scheme (PBS) for this indication. Rifampicin has a well defined toxicity profile, with a long history of use in treating tuberculosis and preventing meningococcal disease. Rifampicin-based combinations for staphylococcal infection are recommended by Australian and international guidelines,2,3 and supported by small clinical trials.4 For rifampicin, a generic drug, there is no financial incentive for the manufacturers to apply for an additional indication for treating MRSA infection.

Since 1998, an orphan drugs policy has encouraged sponsors of patented pharmaceuticals to apply for indications that may only involve small numbers of patients and has waived Therapeutic Goods Administration (TGA) fees for such marketing applications. A “rule of rescue” has also operated, lowering the regulatory bar for serious diseases that are otherwise untreatable. Despite these initiatives, no application to add the treatment of MRSA infection as an indication for rifampicin (in combination with another active agent) has been received by the TGA.5

A solution would be for the National Health and Medical Research Council (NHMRC) to commission clinical trials where further evidence is required. This proposal could see an expanded role for the National Institute of Clinical Studies (NICS), which will soon be incorporated into the NHMRC. The NICS/NHMRC could also make applications to the TGA for the approval of pharmaceuticals for particular indications, particularly for orphan diseases and generic drugs. Reviews of evidence could be generated from within the NHMRC or from external bodies such as professional Colleges and societies, or groups of experts such as those appointed by the Board of Therapeutic Guidelines Limited. Clinical trials could be performed in conjunction with overseas research agencies and draw from within the existing budget of the NHMRC.

This initiative would improve prescribing through the generation of appropriate evidence and may also redefine the utility of some established off-label indications. It could reduce out-of-pocket expenses for patients by facilitating PBS listing. As this initiative would focus on relatively low-cost generic drugs and/or uncommon orphan indications, it would be unlikely to have a significant impact on the cost of the PBS. It would also help focus the clinical research agenda on clinical practice and encourage the use of appropriate generic pharmaceuticals.