May 27, 2022
Routine practice data collection according to German law when several drugs of the same drug class enter the market: IQWiG presents concept
The Institute recommends platform studies under a master protocol
The German Law for More Safety in the Supply of Medicines (GSAV) includes several measures to improve drug safety. Among other things it stipulates that, for certain drugs, the Federal Joint Committee (G-BA) can require the collection of routine practice data from pharmaceutical companies to inform benefit assessments of new drugs.
On behalf of the G-BA, the Institute for Quality and Efficiency in Health Care (IQWiG) has addressed the question of how routine practice data collection according to the GSAV (RPDC-GSAV) should be implemented when several drugs of the same drug class enter the market. In its concept published today, in such cases the Institute advocates conducting RPDC-GSAV as an adaptive platform study under a master protocol. This study design allows the successive introduction of new drugs as study arms into the data collection.
Beate Wieseler, Head of IQWiG’s Drug Assessment Department, notes: “The situation of market entry of several drugs of the same drug class for a given therapeutic indication represents a particular challenge for the implementation of RPDC-GSAV with the aim of a benefit assessment of these drugs. Investigating all of these drugs in separate data collections is not efficient and, depending on the number of patients affected, not feasible.
Structures need to be created here to accelerate data collection and provide consistent high-quality data within the therapeutic indication."
A drug with added benefit would become the new appropriate comparator therapy
According to the IQWiG concept, RPDC-GSAV for several drugs with the aim of assessing their benefit should be conducted as an adaptive platform study. In such a study, a platform for data collection is established once, and new drugs can then be successively introduced into the ongoing data collection as new study arms. This can accelerate the start of data collection for subsequent drugs. In addition, a common control group can be used for the different drugs, reducing the number of patients required. At the same time, this study design also allows for the controlled termination of a study arm when sufficient data are available for a benefit assessment.
If an added benefit is proven for a drug, treatment with this drug can become the new standard care (called “appropriate comparator therapy”) in this design and the common control group is adjusted accordingly. The fact that the entire data collection takes place under a common master protocol also ensures that the data are collected in a uniform manner and are therefore comparable.
Platform studies can be conducted both without and with randomization. By law, RPDC-GSAV is currently only possible as studies without randomization. In this context, Stefan Lange, IQWiG’s Deputy Director, notes: "Without random assignment to the study arms, however, high demands are placed on the data collection if reliable conclusions are to be inferred for the benefit assessment. Among other things, risk differences in the populations must be recorded to be able to adjust for confounders to ensure a fair comparison of the interventions. Ultimately, it is a fallacy to believe that purely observational registry studies are a simple solution. Randomized trials could provide more reliable results with fewer resources required for data collection."
RPDC-GSAV for CAR-T cell therapies in the treatment of haemato-oncological diseases
The specific reason for IQWiG's commissioning of a concept on RPDC-GSAV in the case of market entry for several drugs of the same drug class was the current situation in the treatment of haemato-oncological diseases. Here, several CAR-T cell therapies have already been approved for the treatment of adults with B-cell lymphoma; further drugs are likely to follow. Beate Wieseler explains: "Such a dynamic development in a therapeutic indication is actually not uncommon. When new research findings on a disease become available, several pharmaceutical companies subsequently develop new drugs in parallel on the basis of these findings."
In its report, IQWiG shows that the concept of a platform study can also be applied to RPDC-GSAV for CAR-T cell therapy in adults with B-cell lymphoma.
Promotion of evidence-based patient care
In its concept, IQWiG describes the use of platform studies to conduct comparative studies from the time of market entry, i.e. after approval. This means that evidence-based patient care is only possible with delay after these studies have been completed. Beate Wieseler explains: "In principle, however, such platform studies could of course also be conducted before approval. As a result, comparative data could already be available at the time the new drugs enter routine care. Such an approach would accelerate evidence-based patient care."
In this context, IQWiG points out that various platform studies are already available that identify candidates for drug development prior to approval. Some of these studies are also conducted as randomized controlled trials and demonstrate the feasibility of cross-company studies. Beate Wieseler notes: "Extending these concepts to later phases of drug development is an innovative and very sensible approach to improving the evidence base – both for approval and for benefit assessments."
Process of report production
On 1 April 2021, the G-BA commissioned IQWiG with the development of a scientific concept for RPDC-GSAV and the analysis of these data for the purpose of benefit assessments according to §35a of the German Social Code, Book V (SGB V) in the situation of market entry for several drugs of the same drug class. According to the commission, the report was to be prepared in an accelerated procedure as a so-called rapid report. Interim products were therefore not published and not made available for a hearing. The present rapid report was sent to the contracting agency, the G-BA, on 28 April 2022.