Why is the approval status of a drug important for the benefit assessment?
Drugs are usually used as prescribed in the marketing authorization and as stated in the summary of product characteristics (and in abbreviated form in the package leaflet). There is often little or no evidence of efficacy for the use of a drug outside the authorized therapeutic indication.
The Federal Joint Committee (G-BA) usually commissions IQWiG to assess the benefits of drugs on the basis of their marketing authorization – i.e. according to therapeutic indication, dosage, contraindications, prior and concomitant treatments. If the comparator therapy in the assessment of non-drug treatments is a drug, the basis here is also the approval status. For this reason, the Institute's recommendation to the G-BA, which is included in the conclusion of the benefit assessment report, usually refers to the use of a drug within the existing approval status.
Studies that examine drugs outside their authorized use (“off-label use”) may overestimate or underestimate the benefits or harms compared to the usual use in accordance with the approval status. It can therefore lead to misjudgements if the results of such studies are transferred to the usual use in accordance with their approval status.
If studies are submitted that do not reflect the current approval status or where compliance with the approval status is unclear, IQWiG assesses the extent to which the study results can be transferred to patients who are treated within the approval requirements. These results can only be used for the assessment if it is proven or sufficiently plausible that the off-label use does not notably impact the results of patient-relevant outcomes.
As a rule, study results are not considered eligible for assessment, e.g.
- if the age group treated is outside that defined in the approval status
- if unauthorized combinations with another active ingredient are used,
- if patients with a severity of disease outside the scope of the approval status are treated, or
- if studies are conducted in patients with a contraindication to the intervention under investigation.
Fundamental aspects of benefit assessments explained simply
IQWiG's methods are described in detail in its methods paper. But why does IQWiG work the way it does? What is so important about a direct comparison? And what exactly is the appropriate comparator therapy? We explain these and other aspects of our methods briefly on these pages.