>> Prof. Mühlbacher, you argued that the sole consideration of traditional clinical study designs, i.e. RCTs, is not sufficient to reflect the complexity of today's care decisions with multiple clinical endpoints. Is this really a new finding? Or is this perhaps one that has simply been forgotten under the RCT dogma?
The requirement relates to the weighting of patient-relevant outcomes. Patient preferences should be taken into account as part of the benefit assessment. The difference between measuring and evaluating is essential for benefit assessment: the subject of the measurement can be clinical and non-clinical effects. However, it should first be clarified which clinical target variables are used to assess the clinical benefit. When assessing health technologies, it is no longer only necessary to include “objective” clinical effect parameters; it is also about weighing up benefits and harms. This consideration by the regulatory authorities should be informed by the patient perspective. Desired or undesirable effects determine the value of a measure for the patient. Scientific studies on preferences can establish this valuation or the weighing of benefits and harms on a solid basis. But this requirement is really not new. It was David Sackett of McMaster University, the father of evidence-based medicine, who highlighted the importance of patient preferences. All the worse that to date there has been no systematic, scientific and transparent survey of patient preferences in early benefit assessment.

Prof. Schachtrupp, what was your motivation as managing director of the B. Braun Foundation to start and finance a two-year project to discuss the “value of medical devices”? A rogue who thinks of the foundation donor's own interests?
One of the funding priorities of our independent foundation is medical technology. This purpose of the foundation can be traced back to the Braun foundation family, which has a successful medical technology
manages the company. To ensure that medical technology remains attractive and promoted for young talent, the B. Braun Foundation actively supports seminars and innovation processes in medical technology. She is also involved in the high-tech start-up fund, which supports startup companies, for example in marketing innovative medical technologies. In Prof. Mühlbacher's research project, decision-making criteria are developed that can be used to evaluate the benefits of a medical device. We need this basis so that innovative products can continue to be developed in a transparent process in the future and receive reimbursement in healthcare.

And the question for you too, Prof. Schachtrupp: What can RCTs do and what can't they?
RCTs can prove a causal relationship and are therefore rightly considered the standard. However, there are interesting approaches to prove the cause and effect of a therapy using other types of studies. In addition, the implementation of RCTs in the area of therapies with medical devices must meet more complex requirements than in pharmaceutical studies. Then they are also very cost-intensive, especially when it comes to longer follow-up periods. In relation to a benefit assessment, mortality, complication rates and quality of life are currently taken into account, but how do you bring these dimensions together so that benefits for the patient can be recorded and compared? Overall, RCTs are an important element, but cannot be the only component of a benefit assessment.  

Prof. Mühlbacher, but what use is it all if the G-BA and IQWiG simply do not want to deviate from the noble RCT, probably out of the justified fear of having to evaluate poor study quality?
Studies on patient preferences have nothing to do with the quality of clinical studies. Critics of the rigid IQWiG policy often ask how many of the therapy options that save lives or improve the quality of life of patients today would have met the current requirements of IQWiG. The fear that we will see less and less innovation has led institutions such as the EMA and the FDA to test new approval and decision-making processes. However, the “all or nothing decision” is seen as problematic. The concept of adaptive licensing (accelerated assessment, adaptive pathways) is currently being tested. In 2015, we prepared a report for BVmed and proposed incorporating the basic idea of adaptive licensing as part of the benefit assessment of new examination and treatment methods with high-class medical devices. Concepts of adaptive benefit assessment focus on a flexible weighing of evidence and potential for benefit or harm. Models of adaptive benefit assessment and conditional reimbursement decisions could be used to balance rapid access, safety and cost-effectiveness.

Thinking about it and remembering what Prof. Busse said at the event: How good are RCTs really?
Professor Busse did a very good job of identifying the international situation regarding the use of RCT. In addition, it is undeniable that evidence of causal effects of an intervention (if any) can be demonstrated on the basis of an RCT. However, the question behind this is whether we should promise conditional remuneration in certain situations, even if only potential and no benefit can be seen. The basic principles of this idea have already been initiated by the legislature. In medical technology, clinical data is only available to a limited extent, especially at the time of product launch. Adaptive approaches could be used to address the problems and peculiarities of conducting an RCT with medical devices. Three implementation strategies are conceivable.
1. Implementation across the population with a high unmet medical need and the gradual expansion of the target population over time.
2. Testing in specialized centers in order to reduce the risk of application or use. After positive effects have been proven from clinical studies, the decision would be gradually expanded to all service providers.
3: Implementation via staggered evidence generation regarding clinical benefits and harms. In this case, early conditional reimbursement would be planned based on surrogate endpoints or a lower level of evidence. Moving forward, uncertainty could be gradually reduced by conducting studies with higher levels of evidence to assess clinical effects and patient preferences.

Prof. Schachtrupp and Prof. Mühlbacher, thank you for the interview. <<

The interview was conducted by MVF editor-in-chief Peter Stegmaier.