May 26, 2021
High-risk medical devices: §137h assessments restarted in Germany with 7 new invasive procedures
Target destruction of brain tissue with focused ultrasound can offer advantages for severe tremor. For 6 procedures, the benefit is questionable and further studies are required.
For the first time in three years, IQWiG again received data for the assessment of new examination and treatment methods with high-risk medical devices according to §137h of the German Social Code Book (SGB) V. This involves seven invasive therapeutic procedures for the heart (three commissions), lung, brain, intestine and urethra (one commission each). The Institute for Quality and Efficiency in Health Care (IQWiG) and the Federal Joint Committee (G-BA) evaluated the clinical data for each of these methods, which had in each case been compiled by the hospital and the medical device manufacturer. In some cases, the manufacturer had already started its own study, so that the main decision to be made was whether an additional study in Germany was reasonable.
For six of the seven invasive procedures, due to a lack of meaningful data no robust conclusions can be drawn on the benefit, harm or ineffectiveness for patients. In each of these cases, IQWiG developed key points for well-founded testing studies, unless promising studies are already being conducted. However, the data indicate a benefit for transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) in patients with essential tremor who are ineligible for deep brain stimulation (DBS).
New momentum for assessment of particularly invasive procedures
After initial assessments in 2016 of invasive therapeutic procedures with high-risk medical devices according to §137h SGB V, there had been no new applications for new methods between 2017 and 2019. A change in the law in 2019 then revitalised the assessment process: Now a new high-risk method no longer has to show "at least potential" to be reimbursed by statutory health insurance (SHI) funds.
Stefan Sauerland, Head of IQWiG's Department of Non-Drug Interventions explains: "In §137h assessments, it will rarely be possible to determine benefit, harm or ineffectiveness, as the treatment methods are new and have been only partially investigated. So the main thing is to ensure that suitable studies on new therapeutic procedures are initiated in Germany."
The main purpose of the legal requirements was to examine new treatments in so-called testing studies, without depriving the members of SHI funds of these new, higher risk treatment options. After the change in the law, the (and not the medical device manufacturer) now primarily has to fund the testing study. In the past, the issue of funding had also caused manufacturers in particular to have a negative opinion of §137h assessments.
Provided that the makes the corresponding decisions on the basis of the IQWiG assessments, the new treatment methods can be reimbursed by the SHI funds. However, only a few hospitals currently offer the above-mentioned new treatment methods, which are primarily to be applied within the context of studies.
The targeted destruction of brain tissue by means of transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) aims to improve the (genetically determined) uncontrollable tremor of hands or legs in patients in whom the tremor no longer responds to medication and in whom unilateral treatment is sufficient. The results based on the available evidence vary for two different groups of patients, depending on whether they are eligible for deep brain stimulation (DBS) or not.
In patients who are ineligible for DBS, a randomized controlled trial (RCT) showed advantages of tcMRgFUS versus placebo or no treatment for some outcomes: tremor, activities of daily living and health-related quality of life. Therefore, based on the documents available, a benefit of tcMRgFUS versus conservative treatment alone can be identified. To a limited extent, these results can also be applied to patients who are eligible for DBS. Ultimately, however, it is questionable whether someone with severe tremor benefits at least as much from the targeted destruction of brain tissue using tcMRgFUS as from the implantation of a DBS probe. In order to be able to answer this question, a comparative testing study would be useful – possibly supplemented by data from a disease registry.
Since recently, narrowed urethras (urethral strictures) in men can also be dilated using a drug-coated balloon catheter (DCB). A urethral DCB can be used alone or in combination with other endourological procedures: Single short strictures are currently treated primarily by means of slitting the urethra (urethrotomia interna) ( A). If urethral strictures are radiogenically induced, i.e. caused by ionizing radiation (e.g. in the context of cancer therapy), currently the urethra is mostly reconstructed in an open surgical procedure (urethroplasty) ( B).
Overall, the evidence on this method versus the evidence on already existing treatment options is too sparse to be able to make an assessment. A testing study could provide the necessary findings for the benefit assessment of the method. Because it is still unclear whether a study already underway abroad (ROBUST-III) is suitable for a benefit assessment in A, IQWiG has designed key points for a testing study in Germany to examine the benefit of urethral DCB versus urethrotomia interna in men with short strictures in the anterior urethra.
Because a urethral DCB is less invasive than urethroplasty, when comparing these two procedures it is sufficient to demonstrate that urethral DCB is non-inferior to urethroplasty in men with symptomatic, short, and radiogenically induced urethral stenosis. RCTs with 100 to 500 patients are needed for both populations.
Irreversible electroporation (IRE) involves the endoscopic use of short high-frequency electrical signals to prevent the activity of airway cells that produce excessive secretions and cause constant coughing. In patients with moderate to severe chronic bronchitis (chronic obstructive pulmonary disease [COPD] severity score 1-3), in addition to previous standard treatment, the goal is to remove secretion-rich tissue layers and trigger the regeneration of functional airway cells. This aims to reduce the production of secretion and coughing, improve quality of life and prevent disease progression. Due to insufficient evidence, no conclusions can be inferred as to the advantages and disadvantages of IRE. Before starting a testing study in Germany, IQWiG recommends awaiting the results of a promising study that has just started abroad (RheSolve in Europe, the USA and Canada).
The assessment according to §137h focuses on the use of percutaneous implantation of an interatrial shunt in patients suffering from heart failure with reduced pumping function of the heart in the left ventricle (left ventricular ejection fraction, LVEF < 40%): The shunt is intended to create a permanent "short-circuit connection" between the two atria in order to reduce the increased blood pressure in the left atrium and thereby improve disease symptoms (e.g. shortness of breath). However, due to the lack of usable comparative data, no information on the advantages and disadvantages of the method can be derived from the studies and case series presented.
Of the three ongoing RCTs, the RELIEVE-HF study (with several German study centres) seems particularly suitable: If the study is conducted and completed as planned and provides usable analyses, the findings needed for the benefit assessment of percutaneous implantation of an interatrial shunt in patients with heart failure and limited pump function could be available in the foreseeable future. A separate testing study would then not be required.
Duodenal mucosal resurfacing (DMR) is an endoscopic procedure involving thermal ablation of the duodenal mucosa. According to the documents submitted, DMR aims to reduce insulin resistance in type 2 diabetes mellitus. In patients who are inadequately controlled despite antidiabetic therapy, DMR aims to improve blood sugar control and at the same time reduce or discontinue the insulin dose and the administration of oral antidiabetic drugs. In the best case, treatment leads to the disappearance of diabetes (remission). The four studies available only provide data on the frequency of (severe) side effects. However, a testing study could provide the findings needed for a benefit assessment: In order to be able to prove a difference in the diabetes remission rate, a medium-sized RCT comparing DMR and conservative treatment would be required.
Coronary intravascular lithoplasty aims to dissolve calcium deposits in the coronary arteries by using shock waves. This should enable the widening (dilation) of narrowed coronary vessels (coronary artery stenosis) by means of a stent. However, due to a lack of comparative data, no sound findings on the effect of coronary intravascular lithoplasty can be derived from the study results. Currently, severely calcified constrictions in coronary vessels are pre-treated using other procedures such as reaming (rotablation). A testing study in the form of an RCT with patients with calcified, non-pretreated coronary stenoses and a medical indication for percutaneous coronary intervention could provide the scientific basis for a benefit assessment. The study objective would be to compare coronary intravascular lithoplasty with alternative pre-treatment procedures, with the aim of preventing serious cardiovascular events.
In tricuspid valve insufficiency, more commonly called tricuspid regurgitation, the defective heart valve does not close properly, so that blood flows back from the right ventricle into the right atrium of the heart when the heart contracts (systole). A stent graft combines a stabilising wire mesh (= stent) and an artificial blood vessel made of plastic (= vascular prosthesis). Together with a valve element, this aims to compensate for the dysfunction caused by the defective tricuspid valve in such a way that backflow and thus excess pressure in the venous circulation no longer occurs. It is intended for endoscopic use in patients with severe tricuspid regurgitation who are in a poor general condition, the aim being to avoid a higher-risk operation. Due to a lack of comparative data, the advantages and disadvantages of the method remain unclear. To demonstrate a difference in health-related quality of life, a medium-sized RCT comparing endovascular implantation of the stent graft with sham treatment would be required as a testing study.
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