IQWiG assessed information subsequently provided by the manufacturers on two dossiers

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 to studies for two drugs. Due to the new data, the result of the benefit assessment of crizotinib has changed: In contrast to the first dossier assessment, the Institute now considers there to be a hint of a considerable added benefit in symptoms and in quality of life of crizotinib in comparison with chemotherapy. Regarding the fixed combination of saxagliptin and metformin, however, the Institute maintains its original assessment, according to which an added benefit is not proven.

Saxagliptin/metformin: still no proof of added benefit

The manufacturer of the fixed combination of saxagliptin and metformin, an oral antidiabetic, submitted additional data on a study already included in the dossier, as well as an additional study on the dual combination therapy to the G-BA. The G-BA subsequently commissioned IQWiG to undertake a new assessment of the added benefit.

Under inclusion of this additional information, however, IQWiG did not come to a different conclusion than in the dossier assessment. The main reason for this is that not only two drug combinations were compared with each other, but two therapeutic regimens. Differences in the effects can therefore not be clearly attributed to the respective drugs used. They may also have been caused by the different therapeutic regimens. An added benefit of the fixed combination of saxagliptin and metformin is therefore still not proven.

Crizotinib: new assessment of two outcomes commissioned

For crizotinib, a drug for the treatment of advanced, non-small cell lung cancer, the pharmaceutical company had provided the G-BA with information including additional data on results for symptoms and quality of life. However, they only apply to patients for whom further chemotherapy is an option, called "chemotherapy population". The G-BA therefore commissioned IQWiG to undertake a new assessment of the added benefit for the two outcomes "symptoms" and "quality of life", considering the additional data.

The manufacturer did not submit any new data regarding a second group, namely patients for whom chemotherapy would not be an option due to their poor general condition. IQWiG therefore only draws conclusion on the chemotherapy population.

Additional data changed recommendation

In its dossier, the manufacturer of crizotinib had cited a study (PROFILE 1007), where also data on symptoms had been recorded with questionnaires. But at first it had not presented any evaluable analyses. It subsequently provided these analyses in the commenting procedure. Considering these results in its assessment, IQWiG now considers there to be a hint of a considerable added benefit of crizotinib in comparison with chemotherapy. Particularly, there is an advantage regarding dyspnoea, pain, and cough.

Moreover, certain data on health-related quality of life recorded in the study had been lacking in the dossier at first, which were now subsequently provided. They also show – with the exception of cognitive functioning – a difference in favour of crizotinib, with an extent varying between "minor" and "major" for the subscales of the questionnaire. Overall, IQWiG derives a considerable added benefit of crizotinib in comparison with chemotherapy for the outcome "quality of life".

Assessment procedure should not be unnecessarily bloated

"It is unfortunate that the manufacturer provided this information only subsequently, and not already together with its dossier", says Jürgen Windeler, Director of the Institute. "In the patients' interest, all necessary information should be available at an early stage. Otherwise doctors and patients get a wrong idea. And in the interest of all parties involved, the procedure should not be unnecessarily bloated. After all, conducting a second assessment takes working time and money", says the IQWiG Director.

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 manufacturers' dossiers and the IQWiG dossier assessments, the G-BA conducted commenting procedures, in which the respective manufacturers submitted additional information. The G-BA subsequently commissioned IQWiG to undertake new assessments, with the additional data included (commission for saxagliptin/metformin on 27th March, for crizotinib on 2nd April 2013).

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 these addenda to the contracting agency on 12th April (saxagliptin/metformin), and on 15th April (crizotinib). The G-BA then decides on the extent of the added benefit in each case, thus completing the early benefit assessment.