Lisdexamfetamine dimesylate (trade name: Elvanse) has been approved in Germany since March 2013 as part of a comprehensive treatment programme for attention deficit/hyperactivity disorder (ADHD) in children aged 6 years and over when response to previous treatment with the drug methylphenidate was inadequate. No added benefit of the drug versus the appropriate comparator therapy could be established in the assessment of the drug manufacturer's dossier according to the Act on the Reform of the Market for Medicinal Products (AMNOG). The manufacturer did not present any relevant studies. This was the result of the report published by the German Institute for Quality and Efficiency in Health Care (IQWiG) on 2 September 2013.
Medication only as part of a comprehensive treatment programme
Both lisdexamfetamine (short for lisdexamfetamine dimesylate) and the appropriate comparator therapy specified by the Federal Joint Committee (G-BA) atomoxetine are approved for administration as part of a comprehensive treatment programme (multimodal treatment for ADHD). According to the Summaries of Product Characteristics (SPC) of these drugs, a comprehensive treatment programme typically includes psychological, educational and social measures. The SPC of lisdexamfetamine additionally regards appropriate educational placement as "essential" and psychosocial intervention as "generally necessary".
Moreover, according to the G-BA's Pharmaceutical Directive, both drugs as stimulants in ADHD can only be prescribed at all as part of a comprehensive treatment programme for the treatment of ADHD.
In agreement with the G-BA, the manufacturer cited atomoxetine as appropriate comparator therapy, but did not present any relevant studies for the comparison with lisdexamfetamine.
ADHD drugs were not used in compliance with their approval
In the only study presented (SPD489-317), lisdexamfetamine and atomoxetine were only seen as drug treatment – without being part of a comprehensive treatment programme. This was neither sensible nor did it comply with the approval, and therefore did also not cover the appropriate comparator therapy.
There was no offer of psychological, educational or social measures, for example. There was also no consultation for the children (and parents) to adapt measures or take on other, more suitable measures, if necessary.
Moreover, it was only possible to a limited extent to continue previous ongoing non-drug treatment in the study: Only 8% of the children and adolescents continued receiving non-drug treatment. Only 22% of the study participants in total had received a non-drug treatment of ADHD before anyway.
Short-term study insufficient
ADHD is a chronic disease for which drug treatment over a longer period of time may be necessary according to the SPC of lisdexamfetamine. The study SPD489-317 had a treatment duration of 9 weeks in total and was therefore also too short to draw conclusions on an added benefit.
Hence there were several reasons why the study presented by the manufacturer was unsuitable. An added benefit of lisdexamfetamine is therefore not proven.
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 IQWiG's assessment, the G-BA conducts a commenting procedure, which may provide further information and result in a change to the benefit assessment. The G BA then decides on the extent of the added benefit, thus completing the early benefit assessment.