Digital Health Applications (DiHA): Approaches to develop a reimbursement process for the statutory health insurance in Austria.

Purpose: To elaborate a concept for implementing digital health applications (DiHA), including prioritisation criteria (PC) for the Austrian context and an overview of available prioritised DiHAs. Methods: Based on European DiHA-listings and input by Austrian experts, a categorised meta-directory of DiHAs was created. PC were developed to reflect, inter alia, the provisions of the Austrian General Insurance Act, and were applied to the meta-directory to identify DiHAs potentially relevant for the Austrian statutory health insurance. An iterative process with expert involvement was used to tailor an existing reimbursement framework to the Austrian setting. Results: The meta-directory comprised 132 DiHAs. Developed PC focused on plausibility (German language) and legal aspects (treatment/monitoring of chronic conditions), while other criteria (e.g. interoperability standards) were considered optional. After applying the PC, 38 DiHAs were potentially relevant in the Austrian setting. Of these, only seven supported current health record integration. Most of the prioritised DiHAs reported on CE marking (29/38) and data protection (35/38), while reporting on risk class (10/38) and technical algorithms (0/38) was sparse. For DiHA reimbursement, a four-step process is proposed: identification (ideally based on needs assessment); filtering based on PC; review of technical, regulatory and evidentiary requirements; and health technology assessment. Conclusion: The proposed concept can offer guidance for policy makers (e.g., on prioritising available DiHAs) and may further foster scientific debate with regard to DiHA implementation. Further discussion on how to fully incorporate regulatory, technical, and evidentiary criteria is needed. Attention should be given to national implementation requirements, re-assessment criteria, and appropriate remuneration schemes.

Wearable cardioverter defibrillator for preventing sudden cardiac death in patients at risk: An updated systematic review of comparative effectiveness and safety.

Objectives: To synthesise the available evidence of wearable cardioverter defibrillator (WCD) therapy as an add-on measure to optimal medical therapy (OMT) or as a replacement of hospital stay. Methods: An update systematic review (SR) of comparative effectiveness and safety of WCD therapy was conducted. We included randomised controlled trials (RCT), prospective comparative studies and prospective uncontrolled studies with at least 100 patients. A narrative synthesis of the evidence was conducted. Results: One RCT (n = 2348) and further eleven observational studies (n = 5345) fulfilled our inclusion criteria. In the only available RCT, the use of the WCD was not statistically associated with a clinical benefit on arrhythmic mortality in post-myocardial infarction (MI) patients with an ejection fraction of ≤35%. The compliance with WCD therapy was low in the RCT and high in observational studies, with ten observational studies reporting on a daily wear time between 20 and 23.5 h. The range of percentage of patients receiving at least one appropriate shock was 1-4.8% and the rate of first shock success was reported to be 100% in three studies. Serious adverse events (SAEs) such as inappropriate shocks occurred rarely, with between 0% and 2% of patients being inappropriately shocked within ten observational studies. In one of the observational studies, two patients (2%) were allergic to nickel developing skin rash and false alarms occurred in 58 patients (57%) in this study. Another registry study (n = 448) reported milder AEs, such as dermatitis and pressure marks, occurring in 0.9% and 0.2% of enrolled patients, respectively. Conclusion: The only available RCT failed to show superiority of add-on use of WCD in post MI patients. Observational evidence shows that the compliance with WCD is good, but the evidence is afflicted with selection bias and the inclusion of diverse mixed patient populations diluting the ability to draw indication-specific conclusions on the utility of the device. More comparative data is needed to justify continuing or expanding use of WCD therapy.

Reimbursement decisions for medical services in Austria: an analysis of influencing factors for the hospital individual services catalogue between 2008 and 2020.

OBJECTIVES: To (1) describe the (evidence-based) reimbursement process of hospital individual services, (2) evaluate the accordance between evidence-based recommendations and reimbursement decision of individual services and (3) elaborate potential aspects that play a role in the decision-making process in Austria. METHOD: The reimbursement process is described based on selected relevant sources such as official documents. Evidence-based recommendations and subsequent reimbursement decisions for the annual maintenance of the hospital individual service catalogue in Austria between 2008 and 2020 were analysed using a mixed methods approach, encompassing descriptive statistics and a focus group with Austrian decision makers. RESULTS: 118 evidence-based recommendations were analysed. There were 93 (78.8%) negative and 25 (21.2%) positive evidence-based recommendations. In total, 107 out of 118 evidence-based recommendations (90.1%) did not lead to a deviating reimbursement decision. We identified six aspects that may have played a role in the decision-making process for the annual maintenance of the hospital individual service catalogue, with clinical evidence being the most notable. Further aspects included quality assurance/organisational aspects (i.e., structural quality assurance), costs (if comparable to already existing medical services, not: cost-effectiveness), procedural aspects (e.g., if certain criteria for adoption have not been met formally through the proposals), "other countries" (i.e., taking into account how other countries decided) and situational aspects (such as the COVID-19 pandemic). CONCLUSIONS: There is good accordance between evidence-based recommendations and reimbursement decisions regarding hospital individual services in Austria. Beyond clinical evidence, organisational aspects seem to be considered often with regard to quality assurance but costs do not appear to play a major role. The Austrian system has mechanisms in place that can restrict widespread adoption of novel hospital individual services with uncertain clinical benefits. Future studies could investigate how well these mechanisms work and how they compare to other health systems in Europe.

Extracorporeal Cytokine Adsorption Therapy As a Preventive Measure in Cardiac Surgery and As a Therapeutic Add-On Treatment in Sepsis: An Updated Systematic Review of Comparative Efficacy and Safety.

OBJECTIVES: Evaluating whether there is a clinical benefit of using extracorporeal cytokine adsorption therapy in two indications. DESIGN: Systematic review. SETTING: Search on four databases, Medline, Embase, The Cochrane Library, and the European Network for Health Technology Assessment planned and ongoing projects database. PATIENTS: Patients with sepsis/septic shock; patients undergoing cardiac surgery. INTERVENTIONS: Cytokine adsorption. MEASUREMENTS AND MAIN RESULTS: Randomized controlled trials and prospective studies with concurrent control were eligible for the evidence synthesis. The quality of the individual studies and the strength of the available evidence were assessed using the Cochrane risk of bias tool and the Grading of Recommendations, Assessment, Development, and Evaluation approach, respectively. For the preventive treatment of extracorporeal cytokine adsorption therapy in patients undergoing cardiac surgery, we found very low-quality inconclusive evidence for mortality (five randomized controlled trials, n = 163), length of stay in the ICU (five randomized controlled trials, n = 163), and length of hospitalization (three randomized controlled trials, n = 101). Very low-quality inconclusive evidence was found for (serious) adverse events (four randomized controlled trials, n = 148). For the therapeutic treatment of extracorporeal cytokine adsorption therapy in patients with sepsis/septic shock, we found very low-quality inconclusive evidence for mortality up to 60-day follow-up (two randomized controlled trials, n = 117), organ function (two randomized controlled trials, n = 117) and length of stay in the ICU (one randomized controlled trial, n = 20). Very low-quality inconclusive evidence was found for (serious) adverse events (two randomized controlled trials, n = 117). CONCLUSIONS: Given the available evidence, the efficacy and safety of extracorporeal cytokine adsorption therapy in combination with standard care in the investigated indications was not established. We strongly recommend considering well-powered studies with patient-relevant endpoints instead of investing further research funds on studies that may not shed light on the clinical benefit of extracorporeal cytokine adsorption therapy.

Allograft for Anterior Cruciate Ligament Reconstruction (ACLR): A Systematic Review and Meta-Analysis of Long-Term Comparative Effectiveness and Safety. Results of a Health Technology Assessment.

PURPOSE: To evaluate whether allograft anterior cruciate ligament reconstruction (ACLR) is superior or inferior to autograft ACLR or conservative management in terms of effectiveness and safety. METHODS: A systematic review of the evidence for allograft ACLR was conducted. Randomized controlled trials with a minimum mean follow-up time of 5 years were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the EUnetHTA-Core-Model were used as reporting standards. A meta-analysis was conducted for selected crucial outcomes using a random-effects model. The strength of the available evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Six randomized trials were included comparing allograft with autograft. Patients were on average between 28 and 32.8 years of age (allograft group) and 28.9 and 31.7 years of age (autograft group). Based on the crucial outcomes, the meta-analyses showed no statistically significant differences in Lysholm score, Tegner score, and Cincinnati Knee Score between groups. A small statistical difference favoring autografts was found across studies in the subjective International Knee Documentation Committee score (-2.25; 95% confidence interval -3.02 to -1.47; I2 = 0%; range of all scores: 73.7-90). Two of six studies reported on graft failure, with a statistically significant difference to the detriment of using allografts (13/49 [26.5%] vs 4/48 [8.3%] in one study, 13/43 [30.2%] vs 3/40 [7.5%] in the other study). CONCLUSIONS: Although no substantial difference in patient-reported function, activity level, and symptoms was demonstrated, evidence from the included studies showed a greater risk for graft failure or revision that may make allograft a less safe treatment modality in ACLR. The strength of available evidence is low based on the crucial outcomes due to the lack of high-quality research and the present increased risk of bias in primary studies. Priority should be shifted toward reflecting on whether there is a subpopulation for whom allograft ACLR may still be advantageous in theory (e.g., less-active older patients) and further conduct RCTs in this population. LEVEL OF EVIDENCE: Level II, systematic review of Level II evidence studies.

Comparative Effectiveness and Safety of Allografts and Autografts in Posterior Cruciate Ligament Reconstruction Surgery: A Systematic Review.

PURPOSE: To evaluate the evidence of the effectiveness and safety of allografts compared to autografts in posterior cruciate ligament reconstruction. METHODS: Four electronic databases were systematically searched for eligible randomized controlled studies. Crucial effectiveness outcomes included patient-reported function, activity level and symptoms, clinical knee stability, health-related quality of life, and patient satisfaction. Safety was evaluated through graft failures, revisions, reruptures and complications. The internal validity of the studies was assessed by the Cochrane risk of bias tool, and the strength of the evidence was judged according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). RESULTS: Two randomized controlled studies were included: 50 patients were analyzed in the allograft group and 58 in the autograft group. No statistically significant postoperative differences were reported between the groups for patient-reported function, activity levels or symptoms. One study reported a statistically significant difference in instrumented postoperative anteroposterior knee laxity favoring stability in autografts. This difference is, however, not relevant in the clinical setting. Insufficient evidence was found to judge safety outcomes and because complications were poorly measured, and none of the studies reported on graft failure, revision or rerupture rates. The studies were judged with unclear to high risk of bias. The strength of the evidence for effectiveness and safety was judged to be low to very low, according to GRADE. CONCLUSIONS: Allografts may be comparable to autografts for crucial effectiveness outcomes, but insufficient evidence was found to judge crucial safety outcomes due to poor reporting of safety measures and outcomes. Results should be interpreted with caution because there is lack of good-quality evidence to support the superiority of allografts over autografts due to the high risk of bias in the primary studies and overall very low strength of the body of evidence according to GRADE. LEVEL OF EVIDENCE: Systematic review of Level II studies.

Health Technology Assessment of Carbon-ion Beam Radiotherapy: A Systematic Review of Clinical Effectiveness and Safety for 54 Oncological Indications in 12 Tumour Regions.

BACKGROUND/AIM: Due to the unique physical dose distribution of carbon-ion radiotherapy (CIRT), CIRT can be regarded as a novel tumour irradiation technique - potentially advantageous for various tumour types. Yet it is unclear in how far, superiority or inferiority can be claimed when comparing CIRT to standard irradiation. This study aimed to assess the scientific evidence regarding the effectiveness and safety of CIRT. MATERIALS AND METHODS: A systematic literature review was performed using the European Network for Health Technology Assessment (EUnetHTA) Core Model® for rapid relative effectiveness assessment. The literature search for clinical outcome studies on CIRT was performed using four databases [Cochrane (Central), Centre for Research and Dissemination (CRD), Embase and OVID MEDLINE]. The Cochrane Risk of Bias Tool (for randomised controlled trials) and the Institute of Health Economics (IHE-18) Checklist (for observational studies) were used to assess the risk of bias of the included studies. The evidence synthesis was restricted to 54 oncological indications in 12 broad tumour regions and studies with a low or moderate risk of bias, published between 2005 and 2017. RESULTS: Twenty-seven studies were eligible for the qualitative synthesis of the evidence regarding the effectiveness and safety of CIRT: One randomised controlled trial that primarily focused on the feasibility of CIRT, three case-control studies, three before- and after- studies with a focus on quality of life, and 20 further studies of case series. Overall, insufficient scientific evidence was found for superiority or inferiority of CIRT when compared to standard irradiation for 13/54 oncologicaI indications in 7/12 tumour regions (skull base tumours, brain cancer, cancer in the ear-nose-throat region, bone and soft-tissue tumours, lung cancer, prostate cancer, gastrointestinal tumours). No scientific evidence was found for the remaining 41/54 oncological indications. CONCLUSION: CIRT is undoubtedly, theoretically, a promising cancer treatment. To date, however, it lacks randomised controlled trials assessing the long-term effectiveness and harms associated with the use of CIRT. CIRT must be considered as an experimental treatment due to the lack of high-quality clinical research.