Utilizing registry data in benefit assessments of new drugs: the IQWiG perspective
The Institute for Quality and Efficiency in Health Care (IQWiG; Cologne, Germany) has developed and published a set of criteria pertaining to how high-quality registry data could be analyzed and utilized to determine the extended benefit of novel drugs, particularly those for rare diseases.
Oftentimes, at the time of marketing of orphan drugs and drugs processed for accelerated approval, there is not enough evidence to assess the added benefits associated with these therapies. To help address this shortfall, the Institute for Quality and Efficiency in Health Care (IQWiG; Cologne, Germany) has developed a set of scientific concepts concerning how data generated in routine clinical practice could be analyzed and utilized to determine the early and extended benefits of novel drugs, particularly those for rare diseases. These may, in the future, lead the Federal Joint Committee (G-BA; Berlin, Germany) to commission the collection of such real-world registry data on selected drugs to support the quantification of their added benefit.
Jürgen Windeler, Director of IQWiG, stated: “Extensive analyses of the methodological literature and intensive discussions with registry operators and external statisticians have led us to the conclusion that, in the case of high-quality patient registries, it is possible to base studies on these registries and use the routine practice data collected for extended benefit assessments of drugs.”
Registry studies may or may not employ randomization in the study protocols, however, in either case, in order for the studies to be meaningfully utilized, it is imperative the data if of high quality. The new IQWiG rapid report addresses how these high-quality data should be generated and provides registry operators, sponsors of registry studies and health policy decision makers with specific recommendations on how registry data can be utilized in the benefit assessments of drugs.
Highlights of the report include that the use of routine practice data for benefit assessments of drugs must include a comparative effectiveness analysis of the new drug compared with a therapy specified by the G-BA. Four data collection tools are available for comparative studies: study-specific data collection, registry data, electronic patient record data and claims data.
The report authors maintain that the current quality of electronic patient record data and claims data is not of a high enough standard to allow for their use in such necessary comparative effectiveness studies. However, disease-related patient registries may be of benefit instead.
Further, the report emphasizes the importance of fair comparisons between study groups in benefit assessments of new drugs. The report authors stress the importance of adjusting for confounding factors in registry-based studies that do not employ randomization, in order to allow for fair comparisons to be made. The authors hold that conclusions pertaining to the benefit or harm of a new drug based on non-randomized registry studies cannot generally derive more than a hint of an effect, as one cannot exclude that unknown confounders may influence the results.
The possibility of employing retrospective study designs in the benefit assessment of new drugs depends again on the quality of the data; comparisons of patient populations receiving a new drug with patient populations comprising historical controls only appear realistic if the same data source is used for both.
In the report, the authors outline criteria that they insist should be consulted for ensuring that only registry data of sufficient quality are utilized in benefit assessment analyses. There are four categories of criteria: 1) mandatory criteria for ensuring data quality, 2) general criteria that are always relevant for registry studies used in benefit assessments of drugs, 3) general criteria that are sometimes, depending on the research question, relevant for registry studies used in benefit assessments of drugs and 4) criteria whose degree of fulfilment is to be assessed in relation to the research question.
Thomas Kaiser, Head of the Department of Drug Assessment at IQWiG, stated: “In the context of the suitability testing of a specific registry, this list should be used to evaluate for the respective research question whether all necessary data have been collected or whether possible deficits can be corrected with reasonable effort in a registry-based study.”
Windeler concluded: “The generation of routine practice data and their analysis is potentially feasible in the near future – but for the time being, in addition to study-specific data collection, only via data collection from registries. We have documented which data must be available in the registries and in what quality. The registry operators were very open-minded in their discussions with us, so I expect that the first data from high-quality registries will soon be available for use in benefit assessments of drugs.”