Registry-based RCT could provide important answers on the optimal treatments and their sequencing for RRMS, but a lack of reimbursement hinders these studies
The G-BA had commissioned the IQWiG to assess multiple therapies approved for the treatment of highly active relapsing-remitting multiple sclerosis (RRMS). The approval of most of these treatments was based on placebo-controlled studies or trials comparing with interferon-beta. Therefore, it remains unclear how these treatment options compare against each other and what is the optimal sequence for using them in different patient populations.
The IQWiG is now trying to answer some of these open questions for the active substances alemtuzumab, dimethyl fumarate, cladribine, fingolimod, natalizumab, ocrelizumab, and teriflunomide used in RRMS. This is pursued by two different approaches:
- The IQWiG can conduct a NMA and ITC based on the available RCTs. However, the certainty results of this ITC might be low given that many of the included RCTs are comparing with placebo rather than an one of the active treatments.
- Alternatively, the IQWiG can run a pragmatic RCT.
Pragmatic RCTs for RRMS
In theory, it is possible to conduct a pragmatic RCT in RRMS fairly quickly and efficiently based on existing registries. For example, the German registry NeuroTransData can provide real-world data on the use and outcomes of the different therapy options. The main focus of this registry is the MS database. Currently, it includes records for 22,843 patients with MS (including 18,618 patients with RRMS) and has an average observation period of more than eight years. The input of the data and its analysis follow a standardized procedure that has been established for years and that is routinely used in everyday clinical practice.
Current situation
However, currently, the medication used in these pragmatic RCTs is not reimbursed by the SHI funds. Because the patients are allocated their treatment by randomization, these studies are considered intervention studies. The SHI funds do not reimburse the treatment used in these interventional studies, even though they would reimburse them outside the study, and therefore there would not be any additional costs. This means those conducting the study have to cover the costs of treatments, which they often can not afford. In addition, the costs for the implementation of the registry-based RCT, e.g. for establishing and running the registry as well as the scientific support, need to be covered.
IQWiG’s proposal
Registry-based RCTs can provide important answers on the optimal treatments and their sequencing, and thus better health care in general. The respective treatments are already reimbursed by SHI funds outside of studies. Thus, it would be justified that registry-based RCTs are funded by SHI funds. This is already possible for the off-label use of drugs in clinical trials. Therefore, the IQWiG proposes to amend the respective § 35c 2 SGB V to allow the reimbursement and thus enable registry-based RCTs.
Based on: Dtsch Arztebl 2021; 118 (38): A 1694–6