In the commenting procedure on early benefit assessment pursuant to the German Act on the Reform of the Market for Medicinal Products (AMNOG), under certain circumstances drug manufacturers may submit to the Federal Joint Committee (G-BA) additional documents for dossiers. The Institute for Quality and Efficiency in Health Care (IQWiG) has now assessed such additional information for two studies comparing the antibiotic fidaxomicin, which is used for diarrhoea caused by Clostridium difficile infections, with vancomycin.
In contrast to the first dossier assessment, the Institute now sees proof of a minor added benefit of fidaxomicin versus the appropriate comparator therapy in patients with severe or recurrent disease. An added benefit is still not proven in patients with mild disease; the manufacturer provided no new data for this indication.
Manufacturer dossier did not allow an overall conclusion
The antibiotic fidaxomicin (trade name: Dificlir) has been approved in Germany since December 2011 for the treatment of adults with diarrhoea caused by Clostridium difficile. IQWiG already presented an assessment pursuant to AMNOG in April 2013.
On the basis of the dossier submitted by the manufacturer, an advantage of fidaxomicin for the outcome "global cure" could be inferred for severe cases and recurrences. However, the magnitude of this advantage could not be inferred from the data presented. In addition, it could not be excluded that more severe side effects occurred precisely in these cases, thus outweighing advantages with regard to global cure. An overall conclusion on added benefit was therefore not possible.
Greater harm not proven in patients with severe disease
In the commenting procedure the manufacturer subsequently provided study results in a form that allows the weighing of positive and negative effects. Whereas no statistically significant difference between fidaxomicin and vancomycin was shown for all-cause mortality, the data provide proof of an added benefit for the outcome "global cure" in patients with severe or recurrent disease. In addition, in these subpopulations there is no suggestion of greater harm from fidaxomicin than from vancomycin.
An overall conclusion is thus possible: an added benefit of fidaxomicin versus the appropriate comparator therapy (vancomycin) is now proven for the treatment of patients with severe or recurrent Clostridium difficile infections. IQWiG classifies the extent of added benefit as minor.
An added benefit in patients with mild disease was not claimed by the manufacturer.
G-BA decides on the extent of added benefit
The dossier assessment is part of the overall procedure for early benefit assessments supervised by the G-BA. After publication of the manufacturer's dossier and the IQWiG dossier assessment, the G-BA conducted a commenting procedure in which the manufacturer submitted additional information. The G-BA subsequently commissioned IQWiG on 28 May 2013 to undertake a new assessment including the additional data.
If, in the course of the discussions on a commission of the G-BA, a need for further revision arises, IQWiG presents its report in the form of an addendum. The Institute sent this addendum to the contracting agency (the G-BA) on 12 June 2013. The G-BA then decides on the extent of the added benefit in each case, thus completing the early benefit assessment.
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