Gemeinsamer Bundesausschuss Research Articles

A Review and Comparative Case Study Analysis of Real-World Evidence in European Regulatory and Health Technology Assessment Decision Making for Oncology Medicines

ObjectivesReal-world evidence (RWE) is valuable in supporting regulatory and health technology assessment (HTA) decisions; however, the actual contribution to approvals remains elusive. This study aimed to review RWE approaches and use in oncology medicine approvals in Europe and understand cohesion and discrepancy in the acceptance of the RWE by the European Medicines Agency (EMA) and European HTA bodies. MethodsThis scoping review involved a search of the EMA database, National Institute for Health and Care Excellence (NICE), Gemeinsamer Bundesausschuss (G-BA), and Haute Autorité de Santé (HAS) websites to identify final reports and appraisals for oncology medicines with references to RWE. The selection was guided by research terms associated with RWE study designs, data sources, and outcomes. Qualitative analysis was used to systemize the data. Case studies assessed by more than one agency were selected for comparative assessment of RWE approach, use, and acceptability. ResultsRWE was mainly leveraged as an external control for indirect treatment comparisons or contextualization to support clinical trial results by the EMA, NICE, G-BA, and HAS. However, this approach was mostly rejected due to methodology biases. Comparative assessment of RWE acceptability for the same oncology medicines across agencies suggests discrepancies between EMA and European HTA bodies and among NICE, G-BA, and HAS. ConclusionsThere is diverging acceptance of RWE in EMA and European HTA bodies with no clear consensus on the most effective way to leverage RWE in approvals. With the introduction of the joint European Union Joint Clinical Assessment in 2025, it is crucial for European HTA bodies and EMA to develop synergetic standards for the use of RWE to ensure equitable and timely access to medicines.

The Cost of Lipoedema Treatment Exceeds the DRG Revenues - Evaluation of the Surgical Treatment Costs of Lipoedema (Stage III) at a German University Clinic

Liposuction for stage III lipoedema is a guideline-based but also time-consuming treatment, which can be carried out under specific conditions at the expense of the German statutory health insurance companies (SHI) based on a decision made by the German Federal Joint Committee ("Gemeinsamer Bundesausschuss", G-BA), the highest decision-making body in the German healthcare system, in 09/2019. We postulate that the treatment is not reflected in a cost-covering manner in the university cost system. This monocentric, retrospective study examined the economic aspects of 92 cases in 48 lipoedema patients treated during the period from 09/2019 to 08/2023 at the expense of the SHI. These cases were filtered out using DRG coding and the Operation and Procedure Classification system ("Operationen- und Prozedurenschlüssel", OPS), and the costs and revenues per patient were calculated using the data from our internal service accounting. After an inpatient stay of 2.64±1.33 days, the total revenue was € 4,726.79±680.98. This included € 1,532.92±856.99 inpatient costs, € 2,686.02±1,174.70 in operating costs, € 940.76±189.18 in anaesthesia costs and € 63.19±125.38 in other costs that had to be paid within the clinic. On average across all treatments, this resulted in a loss of -€ 875.22 /case. In 54 cases (59%), the costs exceeded the revenue. In total, the calculation of all cases resulted in a loss of € -80,520.63. If medical personnel costs are included, this amount rises to over € 100,000. The results show that the surgical treatment of lipoedema in the German DRG and university cost systems is not cost-covering. This could be relevant in the final economic assessment of the G-BA, which may result in an adjustment of the DRG revenue.

Updated analysis of the prescription and evaluation of protein kinase inhibitors for oncology in Germany.

A recent analysis from our group ( https://pubmed.ncbi.nlm.nih.gov/37014400/ ) has shown that the immense costs of the 20 protein kinase inhibitors for oncology approved from 2015 to 2019 are largely caused by drugs whose additional benefit has not been proven. We updated our analysis by adding the newly approved protein kinase inhibitors of the years 2020 and 2021. Based on the 2021 and 2022 Arzneiverordnungsreport (AVR), we expanded our analysis to include a total of nine protein kinase inhibitors newly approved by the European Medicines Agency (EMA) in 2020 and 2021. As a result, 29 protein kinase inhibitors were identified for an update of our analysis. For these 29 drugs, all additional benefit assessments published by the Gemeinsamer Bundesausschuss (GBA) were analyzed. The additional benefit assessments of the GBA were compared with the corresponding assessments of the European Society for Medical Oncology (ESMO), the Deutsche Gesellschaft für Hämatologie und Onkologie (DGHO, German Society for Hematology and Oncology) and the Arzneimittelkommission der deutschen Ärzteschaft (AkdÄ, Drug Commission of the German Medical Association). In addition, a total number of 91 drug advertisements published in the journal Oncology Research and Treatment in 2022 were analyzed. The number of protein kinase inhibitors for which no additional benefit can be found by the GBA is increasing, whereas the number of drugs for which a considerable additional benefit can be found is decreasing. Thus, in the current 2022 (re)assessment of additional benefit by the GBA, no additional benefit was identified for 50% of the drugs (2020, 46%). Nineteen percent were assessed with a minor additional benefit (2020, 18%) and also 19% with a considerable additional benefit (2020, 27%). For 12% of the drugs, the additional benefit could not be quantified by the GBA (2020, 9%). The benefit assessments by other medical societies often differ significantly from those of the GBA, mainly due to different evaluations of various endpoint parameters. In addition, more and more protein kinase inhibitors are being approved as orphan drugs. However, their additional benefit cannot be quantified by the GBA in most cases (78%). In 38% of the advertisements of an oncology journal, protein kinase inhibitors are promoted, which shows the pharmacoeconomic importance of these drugs. In summary, the current additional benefit assessment procedure in Germany is very questionable, and reforms are urgently needed to maintain the stability of the German healthcare system, which is being undermined by the high cost of medicines, particularly for drugs whose additional benefits have not been proven.

First experience in endoscopic lung volume reduction with the FreeFlow Coil #4: A case series with three patients

Lung volume reduction therapy is an established treatment for patients with severe emphysema of the lung. In Germany, the treatment with nitinol coils is the only method for endoscopic lung volume reduction in patients with positive collateral ventilation approved by the Gemeinsamer Bundesausschuss. Therefore this procedure can be performed as standard-of-care and has assured reimbursement. After the production of the initial coils was stopped for years, when the only manufacturer had been bought by a large corporation, by the end of 2022 there was a new nitinol-coil, the so called Coil #4, becme available in the European market. The new Coil #4 has a different shape, different application catheter and the implantation procedure differs from that of the original product. We report our experience in endoscopic lung volume reduction with the new Coil #4 in three patients with emphysema. The procedure was performed without complications. All three of them showed improvement in lung function parameters meeting minimal clinically important differences. In two of three patients, we also saw clinically relevant improvement in the 6MWT distance und improvements in SGRQ und CAT-Score. In our opinion, this case series is just a prospect of the possibilities that come with the Coil #4. With due caution, we will continue to offer the Coil #4 as a treatment for selected patients under constant evaluation of the outcome until more data is available.

Enucleations, eviscerations and orbital implants in German eye hospitals

Evaluation of the number of enucleations and eviscerations performed in Germany and the orbital implants used. Analysis of the quality reports of German ophthalmological clinics for the years 2012-2021 provided by the Federal Joint Committee (Gemeinsamer Bundesausschuss, G‑BA). Almost 10 times as many enucleations (8368) as eviscerations (975) are performed in Germany. After enucleation, alloplastic implants are used most frequently (44.6% alloplastic, no further specification, 30.0% alloplastic coated, no further specification; 14.1% microporous implants) and autologous dermis-fat grafts in 6.1% of the cases. In Germany, significantly more enucleations than eviscerations are performed. Alloplastic orbital implants are preferred for primary reconstruction following enucleation.

Implementation of PET/CT in radiation oncology—a patterns-of-care analysis of the German Society of Nuclear Medicine and the German Society of Radiation Oncology

BackgroundThe use of positron-emission tomography (PET)/computed tomography (CT) in radiation therapy (RT) has increased. Radiation oncologists (RadOncs) have access to PET/CT with a variety of tracers for different tumor entities and use it for target volume definition. The German Society of Nuclear Medicine (DGN) and the German Society of Radiation Oncology (DEGRO) aimed to identify current patterns of care in order to improve interdisciplinary collaboration.MethodsWe created an online survey on participating RadOncs’ use of PET tracers for different tumor entities and how they affect RT indication, dose prescription, and target volume definition. Further topics were reimbursement of PET/CT and organizational information (fixed timeslots and use of PET with an immobilization device [planning/RT-PET]). The survey contained 31 questions in German language (yes/no questions, multiple choice [MC] questions, multiple select [MS] questions, and free-text entry options). The survey was distributed twice via the DEGRO member mailing list.ResultsDuring the survey period (May 22–August 7, 2023) a total of 156 RadOncs (13% of respondents) answered the survey. Among these, 59% reported access to diagnostic PET/CT within their organization/clinic and 24% have fixed timeslots for their patients. 37% of survey participants can perform RT-PET and 29% have the option of providing a dedicated RT technician for planning PET. Besides [18F]-fluorodeoxyglucose (FDG; mainly used in lung cancer: 95%), diagnostic prostate-specific membrane antigen (PSMA)-PET/CT for RT of prostate cancer is routinely used by 44% of participants (by 64% in salvage RT). Use of amino acid PET in brain tumors and somatostatin receptor PET in meningioma is low (19 and 25%, respectively). Scans are reimbursed through private (75%) or compulsory (55%) health insurance or as part of indications approved by the German Joint Federal Committee (Gemeinsamer Bundesausschuss; 59%). 98% of RadOncs agree that PET impacts target volume definition and 62% think that it impacts RT dose prescription.DiscussionThis is the first nationwide survey on the role of PET/CT for RT planning among RadOncs in Germany. We find high acceptance of PET results for treatment decisions and target volume definition. Planning PET comes with logistic challenges for different healthcare settings (e.g., private practices vs. university hospitals). The decision to request PET/CT is often based on the possibility of reimbursement.ConclusionPET/CT has become an important tool for RadOncs, with several indications. However, access is still limited at several sites, especially for dedicated RT-PET. This study aims to improve interdisciplinary cooperation and adequate implementation of current guidelines for the treatment of various tumor entities.

Neugeborenen-Hörscreening in Deutschland – Ergebnisse der Evaluationen 2011/2012 und 2017/2018

ZusammenfassungHintergrundDas Neugeborenen-Hörscreening (NHS) wurde 2009 durch den Gemeinsamen Bundesausschuss (G-BA) mit Aufnahme in die Kinder-Richtlinie bundesweit eingeführt. Dabei wurden in der Kinder-Richtlinie auch Qualitätsziele festgelegt. Um die Qualität des NHS in Deutschland zu überprüfen, hat der G‑BA eine Bietergemeinschaft mit einer ersten Evaluation für die Jahre 2011/2012 und einer Folge-Evaluation für 2017/2018 beauftragt.MethodenGrundlage der Evaluationen waren Sammelstatistiken, die von allen geburtshilflichen und neonatologischen Abteilungen, als Leistungserbringer des NHS, geführt werden müssen und ggf. in Kooperation mit Hörscreening-Zentralen (HSZ) erstellt werden. Zusätzliche Daten wurden durch Fragebögen und Interviews erhoben und durch Routinedaten ergänzt, um den vollständigen Screeningprozess zu evaluieren.ErgebnisseIn 13 Bundesländern sind insgesamt 15 HSZ in den Screeningprozess eingebunden. Deutschlandweit wurde 2018 eine Screeningrate von 86,1 % (2012: 82,4 %) dokumentiert, die sich deutlich zwischen den Bundesländern unterschied. Die vorgegebenen Qualitätsziele konnten noch nicht überall umgesetzt werden. So erreichten nur knapp die Hälfte der Geburtsabteilungen die angestrebte Screeningrate von über 95 %. Beim Vergleich der Folge-Evaluation mit den Daten der ersten Evaluation konnte gezeigt werden, dass sich die Strukturqualität des NHS verbessert hatte, während die Prozessqualität eher gleich blieb oder schlechter geworden war, verdeutlicht insbesondere durch einen Anstieg der Refer-Rate (Kinder, die mit einem auffälligen Befund entlassen wurden) von 5,3 % auf 6,0 %.DiskussionZur Verbesserung der Qualität des NHS sollten flächendeckend HSZ etabliert und – wie in der Richtlinie vorgesehen – bei auffälligem Erstscreening ein zweites Screening noch vor Entlassung konsequenter durchgeführt werden.

Effectively Leveraging RWD for External Controls: A Systematic Literature Review of Regulatory and HTA Decisions.

Real-world data (RWD)-derived external controls can be used to contextualize efficacy findings for investigational therapies evaluated in uncontrolled trials. As the number of submissions to regulatory and health technology assessment (HTA) bodies using external controls rises, and in light of recent regulatory and HTA guidance on the appropriate use of RWD, there is a need to address the operational and methodological challenges impeding the quality of real-world evidence (RWE) generation and the consistency in evaluation of RWE across agencies. This systematic review summarizes publicly available information on the use of external controls to contextualize outcomes from uncontrolled trials for all indications from January 1, 2015, through August 20, 2021, that were submitted to the European Medicines Agency, the US Food and Drug Administration, and/or select major HTA bodies (National Institute for Health and Care Excellence (NICE), Haute Autorité de Santé (HAS), Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG), and Gemeinsamer Bundesausschuss (G-BA)). By systematically reviewing submissions to regulatory and HTA bodies in the context of recent guidance, this study provides quantitative and qualitative insights into how external control design and analytic choices may be viewed by different agencies in practice. The primary operational and methodological aspects identified for discussion include, but are not limited to, engagement of regulators and HTA bodies, approaches to handling missing data (a component of data quality), and selection of real-world endpoints. Continued collaboration and guidance to address these and other aspects will inform and assist stakeholders attempting to generate evidence using external controls.

10 Years of AMNOG: What is the Willingness-to-Pay for Pharmaceuticals in Germany?

The German Pharmaceutical Market Restructuring Act (AMNOG, 2011) is a two-stage process to regulate the price of new pharmaceuticals in which price negotiations are conducted based on evidence-based medical benefit assessments using data from prior clinical trials. Although the act does not explicitly set a willingness-to-pay (WTP) threshold, the process itself implicitly establishes a WTP for health improvement. We evaluated the implicit WTP for prescription pharmaceuticals post-AMNOG in the German healthcare system from the decision-maker/payer perspective. We extracted data on patient-group-specific annual treatment costs and endpoints from 2011 to 2021 from the dossiers assessed by the German Federal Joint Committee (FJC; Gemeinsamer Bundesausschuss). Using incremental cost-effectiveness ratios (ICERs), we calculated a WTP for the indications (I) diabetes, (II) cardiovascular disease, and (III) psoriasis weighted according to patient group size, first from the perspective of the decision-maker (approach A), and second from the perspective of the industry (approach B). To put clinical outcome measures into relation to one another, minimum clinically important differences (MCIDs) were derived from the literature and compared. The annual treatment costs of newly authorized drugs were substantially higher (both pre- and post-negotiation) than that of their comparators (e.g., psoriasis, pre-negotiation: €20,601.59, post-negotiation: €16,763.57; comparators: €5178.00). However, although newly launched drugs were more expensive than their comparators, they brought greater medical benefits and were more aligned with value (r = 0.59, P < 0.001) than older drugs. We estimated WTP to vary widely by indication group [€33,814.08 per 1 percentage point hemoglobin A1c (HbA1c) reduction for diabetes, €10,970.83 per life year gained for cardiovascular disease, and €663.46 per 1% PASI decrease for psoriasis; approach A]. WTP was converted to MCID thresholds: diabetes: €16,907.04; cardiovascular drugs: no MCID existent to convert; and psoriasis: €33,173.00. WTP remained constant over time for diabetes and cardiovascular drugs but increased for psoriasis drugs. This paper is one of the first to estimate the implicit WTP for prescription pharmaceuticals post-AMNOG and suggests that the WTP may vary between different therapeutic areas. Additionally, making different assumptions (approach A versus approach B) with regard to the assumed effectiveness in indication areas that had been declared as having no additional benefit by the FJC may explain the different perspectives of decision-makers and of the pharmaceutical industry on the value of a pharmaceutical.

Critical analysis of the prescription and evaluation of protein kinase inhibitors for oncology in Germany

The prices of oncology drugs have been rising progressively in recent years. Despite accounting for only a small share of prescriptions, oncology drugs are the most expensive drugs on the market. However, the association between drug price and clinical benefit often remains questionable. Therefore, we set out to analyze the development of prescription and benefit assessment of protein kinase inhibitors. We identified 20 protein kinase inhibitors with oncological indications that were newly approved by the European Medicines Agency (EMA) between 2015 and 2019, based on the Arzneiverordnungsreport (AVR, Drug Prescription Report). For these 20 drugs, the number of prescriptions, sales, defined daily dose (DDD), and DDD costs were identified for the year of approval and for 2020, respectively, based on data from the Wissenschaftliches Institut der Ortskrankenkassen (WIdO, Scientific Institute of the General Local Health Insurance Fund, AOK). Moreover, the additional benefit assessments by the Gemeinsamer Bundesausschuss (GBA, Federal Joint Committee) were considered for each drug. It is shown that the share of a drug in prescriptions, sales, and DDD does not correlate with the clinical benefit of the drug as measured by the additional benefit assessment by the GBA. Lastly, the advertisement pattern of protein kinase inhibitors in a representative oncology journal does not correlate with drug benefit. In conclusion, the immense costs of oncology drugs are therefore largely caused by drugs for which no additional benefit has been proven by the GBA. In order to ensure the long-term stability of health care systems, price-regulation measures are urgently needed, especially for drugs whose additional benefit has not been proven.

Health Technology Assessment–Informed Decision Making by the Federal Joint Committee/Institute for Quality and Efficiency in Health Care in Germany and the National Institute for Health and Care Excellence in England: The Role of Budget Impact

ObjectivesThis study aimed to test (official) evaluation criteria including the potential role of budget impact (BI) on health technology assessment (HTA) outcomes published by the Federal Joint Committee (Gemeinsamer Bundesausschuss [GBA]) and the Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen [IQWiG]) in Germany as well as the National Institute for Health and Care Excellence (NICE) in England. MethodsData were extracted from all publicly available GBA decisions and IQWiG assessments as well as NICE single technology appraisals between January 2011 and June 2018, and information with regard to evaluation criteria used by these agencies was collected. Data were analyzed using logistic regression to estimate the effect of the BI on the HTA outcomes while controlling for criteria used by GBA/IQWiG and NICE. ResultsNICE recommendations are largely driven by the incremental cost-effectiveness ratio and, if applicable, by end-of-life criteria (P < .01). While IQWiG assessments are significantly affected by the availability of randomized controlled trials and patient-relevant endpoints (P < .01), GBA appraisals primarily focus on endpoints (P < .01). The BI correlated with NICE single technology appraisals (inverted-U relationship, P < .1) and IQWiG recommendations (increasing linear relationship, P < .05), but not with GBA decisions (P > .1). Nevertheless, given that IQWiG assessments seem to be more rigorous than GBA appraisals regarding the consideration of evidence-based evaluation criteria, decisions by GBA might be negatively associated with the BI. ConclusionsResults reveal that GBA/IQWiG and NICE follow their official evaluation criteria consistently. After controlling for all significant variables, the BI seems to have an (independent) effect on HTA outcomes as well.

Quality contract ‘prevention of postoperative delirium in the care of elderly patients’ study protocol: a non-randomised, pre–post, monocentric, prospective trial

IntroductionPostoperative delirium (POD) is seen in approximately 15% of elderly patients and is related to poorer outcomes. In 2017, the Federal Joint Committee (Gemeinsamer Bundesausschuss) introduced a ‘quality contract’ (QC)...

Do France, Germany, and Italy agree on the added therapeutic value of medicines?

The Health Technology Assessment (HTA) of medicines is performed separately at the country level with some differences, but Italy, France, and Germany have implemented price and reimbursement systems strongly focused on the Added Therapeutic Value (ATV). This study investigates the level of agreement on ATV assessments by Agenzia Italiana del Farmaco (AIFA), Haute Autorité de Santé (HAS), and Gemeinsamer Bundesausschuss (G-BA). A database was created collecting all information about drugs with innovativeness status requests in Italy from July 2017 to December 2022 and populated with the corresponding HAS and G-BA ATV assessments. The primary comparative analysis was conducted by grouping the ATV ratings into "higher added value" and "lower or no added value", while a secondary analysis considered the Italian innovativeness status as a criterion to include the quality of evidence assessment. The concordance between ATV assessments was investigated through percentage agreement and unweighted Cohen k-value. 189 medicines/indications were included. The greatest agreement was found when comparing G-BA versus HAS (82 percent; k=0.61, substantial agreement). Lower levels of agreements were observed for AIFA versus HAS and AIFA versus G-BA (respectively 52 percent; k=0.17 and 57 percent; k=0.25). The secondary analysis led to a reconciliation to moderate agreement for AIFA versus HAS (72 percent; k=0.45) and AIFA versus G-BA (74 percent; k=0.47). A high degree of concordance between HTA organizations is reached when considering jointly ATV and quality of evidence, suggesting that the system is extensively mature to make a Joint Clinical Assessment, avoiding duplications and reducing access inequalities.

Is IQWiG's 15% Threshold Universally Applicable in Assessing the Clinical Relevance of Patient-Reported Outcomes Changes? An ISPOR Special Interest Group Report

This article discusses a recent methodological change to assess the additional benefit of drug intervention by the German Federal Joint Committee (Gemeinsamer Bundesausschuss), a key stakeholder in EUnetHTA21 (European Network for Health Technology Assessment joint consortium for future EU HTA regulation), methodological workstream. The German Federal Joint Committee (Gemeinsamer Bundesausschuss) set a universal individual response threshold at ≥ 15% of the scale range of the measurement instrument, for all patient-reported outcomes, to achieve an additional benefit rating for a given pharmaceutical intervention. This approach is originally based on a corresponding recommendation from the Institute for Quality and Efficiency in Health Care.The merits of this approach are reviewed from various perspectives, including the evidence basis, statistical and psychometric considerations, and regulatory perspectives by the ISPOR Clinical Outcomes Assessment Special Interest Group’s multistakeholder group of authors (academia, contract research organizations, and industry). Particular focus is placed on the patient perspective within the Institute for Quality and Efficiency in Health Care approach.The article development incorporated feedback from ISPOR members during well-attended ISPOR US and European conference presentations and 2 formal rounds of written review. The authors concluded that the ≥ 15% response threshold is incongruent with previously defined and scientifically established thresholds and is not well-suited for universal implementation. Further scientific evidence and discussion among all stakeholders are needed, especially should this universal rule be considered in the context of future joint clinical assessments of health technologies in the European Union scheduled from 2025 onward.

Analysis of the Results of Sonographic Screening Examinations According to the Maternity Guidelines Before and After the Introduction of the Extended Basic Screening (IIb Screening) in Hesse.

The aim of the study is to examine the detection rates of malformations before and after the introduction of extended basic screening in Hesse by the Federal Joint Committee (Gemeinsamer Bundesausschuss, GQH) on July 1, 2013. This is a retrospective, mainly exploratory data analysis of quality assurance data from the Office for Quality Assurance in Hesse (GQH). The data was collected in the period from January 1, 2010 to December 31, 2016 in the obstetric departments of the Hessian hospitals using documentation forms. The classification and evaluation of the diagnoses is based on ICD-10-GM-2019. At least one malformation is present in 0.7% of the cases. With a share of 30.0%, most of the congenital malformations are from the musculoskeletal system. 12.2% of the malformations come from the facial cleft, closely followed by malformations of the circulatory system with 11.3%. The highest prenatal detection rate (PDR) is found in congenital malformations of the nervous system at 56.8%. The lowest PDR is found in those of the genital organs with 2.1%. The PDR of cardiovascular malformations is 32.9%. Overall, a PDR of 25.2% is achieved. There was no change in the number of prenatal malformation diagnoses after the introduction of extended basic ultrasound. The distribution of malformation diagnoses not detected prenatally to the organ systems also has not changed after the introduction. The introduction of extended basic ultrasound did not bring the desired improvement with regard to the PDR in Hesse. Alternative approaches should be considered.

Hausärztliche Perspektiven auf eine multimodale Intervention zum adäquaten Einsatz von Antibiotika beim Harnwegsinfekt – eine qualitative Interviewstudie

IntroductionContrary to current guideline recommendations, second-line antibiotics are still frequently used in the ambulatory treatment of uncomplicated urinary tract infections (UTI), which are associated with a high risk of antibiotic resistance development. The REDARES project (REDuction of Antibiotic RESistance in uncomplicated urinary tract infections by treatment according to national guidelines in ambulatory care), funded by the Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA)/Innovation Fund is developing a multimodal intervention for primary care physicians to support them in a guideline-based approach. The intervention consists of the following components: (1) provision of local resistance data of pathogens of uncomplicated UTI (Robert Koch Institute), (2) concise guideline content on the therapy of uncomplicated UTI for patients (paper and online), and (3) prescription feedback on practice level and benchmarking among the study participants (anonymized). In a participatory approach and as part of the process evaluation, representatives of the intended target group were interviewed in advance about the acceptance and feasibility of the intervention. MethodsUsing guided individual interviews, Thuringian GPs were interviewed before the start of the intervention phase. Following a description of the study concept and the planned components of the intervention, the interviewees were asked about their assessment regarding acceptance and feasibility. The individual interviews were recorded, transcribed verbatim and qualitatively analyzed according to Mayring. ResultsA total of ten interviews with an average duration of 29minutes were conducted and evaluated. 40 per cent of the interviewed GPs were female and, on average, 45 years old. The interviewees described the uncomplicated UTI as an easily manageable condition. The practical nature of the research question was described as a reason to potentially participate in the intervention phase; lack of time or human resources were cited as potential barriers. Regarding the intervention elements, the provision of local resistance data of UTI pathogens was considered beneficial to their own work. The extraction of their own antibiotic prescription data from the practice software was basically assessed as feasible. The interviewees differed in their assessment of whether they would take account of the feedback on their prescribing behavior in their daily work. DiscussionThe interviews generated a detailed picture of the different diagnostic and therapeutic pathways used by respondents for uncomplicated UTI. Overall, they predominantly regarded both the study concept and the intervention components as feasible. Although the study population is small and not representative, some of the results seem to be transferable to other regions in Germany. ConclusionA research question relating to their daily routine can increase participation of primary care physicians in (intervention) studies. Starting the process evaluation before the intervention seems to be reasonable since the results will be integrated into the design of the intervention. The method of data extraction from practice software by practice teams seems to be promising.

Oncology drugs and added benefit: insights from 3 European health technology assessment agencies on the role of efficacy endpoints

Objective This study aimed to understand the impact of different efficacy endpoints on reimbursement decisions made by health technology assessment (HTA) bodies. Materials and methods European Medicines Agency (EMA) oncology product marketing authorizations were screened to identify products that completed review by 3 HTA bodies during 2016–2019: United Kingdom’s National Institute for Health and Care Excellence, Germany’s Gemeinsamer Bundesausschuss, and France’s Haute Autorité de Santé. Each decision’s endpoint information, including overall survival (OS) and progression-free survival (PFS), was extracted. Each endpoint’s influence on added benefits rating (the degree of added benefit as judged by the HTA agency) and full reimbursement (i.e. reimbursed population to label) decisions was tested using bivariate analyses. Results An increasing trend was observed toward HTA submissions with immature OS data (36.8% and 71.4% in 2016 and 2019, respectively), which was a predictor of limited added benefit (p < .001). Regarding data availability, 63% of submissions provided OS, 2% provided PFS without OS; and 35% provided neither. OS availability significantly influenced added benefit (p < .001) but not full reimbursement (p > .05) decisions, whereas PFS without OS had no significant impact compared with either OS or PFS data for either outcome (p = .99). Conclusions The trend toward fewer products filing mature OS data over time suggests sponsors may be increasingly confident achieving reimbursement with surrogate endpoint data, although mature OS data provided the strongest correlation to positive reimbursement decisions. Notably, in some locally advanced settings, OS data maturity will take a long time to obtain. To expedite patient access to new medicines, payers should consider the acceptance of surrogate endpoints predictive of clinical benefit.

Towards compatibility of EUnetHTA JCA methodology and German HTA: a systematic comparison and recommendations from an industry perspective

ObjectiveThe transferability of the EU joint clinical assessment (JCA) reports for pharmaceuticals for the German benefit assessment was evaluated by systematically comparing EU JCA and German clinical assessments (CA) based on established assessment elements for HTA and assessing the potential impact of differences on Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA) ability to derive the therapeutic added value.MethodsIdentification of all pharmaceuticals undergoing both, EU JCA and German CA between January 2016–June 2020. Qualitative review and data extraction from the assessments, assessment of methodological differences using a hierarchical model. Recommendations for harmonisation were developed and consented with pharmaceutical industry stakeholders.ResultsDifferences with potentially major impact: (1) View on differing treatment algorithms and definition of corresponding subpopulations/respective comparators. (2) Clinical relevance of surrogate/intermediate endpoints. Inclusion of different/surrogate morbidity endpoints resulting in different relative effectiveness conclusions. (3) Tolerance of study interventions not used according to marketing authorisation. (4) Different operationalisation and/or weighting of individual safety endpoints leading to differing relative safety conclusions. Differences with potentially minor impact: (1) Disagreement in risk of bias assessment for overall survival and its robustness against study limitations. (2) Use of patient-reported outcome symptom scales as measurements for health-related quality of life instruments.ConclusionWhile many synergies between EU JCA and German CA exist, we identified several aspects in HTA methodology that would benefit of harmonisation and ensure the transferability of future EU JCA to the German HTA process without duplicated evaluation requirements. For those, a set of recommendations was developed.

Health technology assessment (HTA) in England, France and Germany: what do matched drug pairs tell us about recommendations by national HTA agencies?

Aims: To explore health technology assessment (HTA) outcomes of matched drug pairs by national agencies in Germany (Gemeinsamer Bundesausschuss, GBA), France (Haute Autorité de Santé, HAS) and England and Wales (NICE). Methods: We considered published GBA decisions, HAS reports and NICE guidance from January 2011 to June 2018. HTAs of matched pairs were compared overall, and for non-cancer and cancer drugs separately. We further analyzed the role of additional attributes related to cancer therapies. Results: Matched pairs show higher concordance for GBA/HAS than for GBA/NICE and HAS/NICE. Overall, NICE evaluated technologies more favorably than GBA and HAS. GBA appraisals ofcancer drugs, however, tended to be more positive than cancer-related recommendations by NICE and HAS. Conclusion: The findings indicate substantial variations in HTAs, although cancer-related outcomes seem to diverge less than non-cancer results.

Decisions of the German Federal Joint Committee in situations with insufficient data : Decision-making options for new diagnostic and treatment methods

In accordance with legal requirements, the Federal Joint Committee (German: Gemeinsamer Bundesausschuss, G‑BA) decides based on the best available evidence which new diagnostic and treatment methods are reimbursed by statutory health insurance. If the benefit is proven with sufficient certainty, statutory health insurance providers pay for the new method, otherwise atrial study must be conducted. To present the G‑BA's decision-making options even in the case of insufficient evidence in the field of urology. Adocument search was conducted on the homepage of the G‑BA for the decisions about method evaluation and quality assurance in the field of urology of the last 10years. The respective decisions are presented in the light of the decision options available in each case. Using the example of the debate on low-dose rate brachytherapy for localised prostate cancer, the years-long, ultimately futile, effort to increase the evidence base for an innovative method is presented. Compared to the development of guidelines, for example, the G‑BA can only make dichotomous yes/no decisions and has to accept the often insufficient evidence situation, or (has to) try to increase the evidence base by initiating its own study. The latter is particularly difficult when specific methods are already established in routine care. Aparticular challenge is posed by new, especially invasive methods in the hospital sector, which has to be evaluated (benefit assessment) and, if necessary, tested by the G‑BA with atrial study. To what extent this will succeed in the future is not yet foreseeable.