In 2025, oncology drugs with new active substances and advanced therapy medicinal products will undergo joint clinical assessment (JCA). The comparative analysis of the clinical evidence as defined in the Regulation (EU) 2021/2282 on health technology assessment (HTAR) will save national/regional submissions of the same evidence. JCA will be available early supporting appraisal and decision-making, which remains within the responsibility of member states (MS).

Targeted searches on JCA and statements from stakeholders were performed and analyzed. We conducted interviews with current and former national payers, as well as members of HTA agencies, across Germany, France, Italy, and Eastern Europe to explore their perspectives on the anticipated implications of JCA on decision-making processes and reimbursement strategies in Europe. Focus was on reduced/additional effort for authorities and health technology developers (HTDs), required national amendments, and potential discrepancies between JCA outcome and MS benefit evaluations.

Stakeholders appreciate the standardized methodology and guidance on HTA, which, especially in countries without an established HTA system, could enhance patients’ access to new treatments by considering JCA in decision-making. The comprehensive evidence compilation may also save resources in pursuing national/regional submissions. On the other hand, country-based appraisals within the MS could lead to diverse conclusions, and there is uncertainty as to which extent national authorities will adopt JCA and how its integration into decision-making will be handled. Some stakeholders challenge an impact on local patients’ access as reimbursement and pricing processes remain within MS responsibility.

JCA is a long-desired achievement and will set the groundwork for timely access of new treatments in the MS. However, presently there are several uncertainties on how JCA will impact decision-making and whether MS appraisal could lead to contradictory value conclusions for a given treatment. Future adjustments to national/regional procedures and refinement of the JCA framework are expected.

Treatment options for men with moderate-to-severe lower urinary tract symptoms due to benign prostatic hyperplasia (BPH) include medical therapy, minimally invasive surgical therapies (MISTs), and invasive surgical procedures. While these treatments are recommended by American Urological Association Guidelines, they have different clinical profiles impacting both efficacy and durability outcomes. Using an indirect comparison approach, this study assessed the clinical effects of combination therapy (CT) using alpha-blockers and 5-alpha reductase inhibitors, two emerging MISTs (prostatic urethral lift [PUL] and water vapor thermal therapy [WVTT]), and two invasive surgical procedures (photoselective vaporization of the prostate [PVP] and transurethral resection of the prostate [TURP]).

A systematic search of Medline, Embase, Cochrane Library, and relevant health technology assessment (HTA) databases was conducted to identify randomized and non-randomized clinical trials of the five treatments published prior to December 2020. Trials were included if they reported changes in International Prostate Symptom Score (IPSS) and retreatment rates, without any country or language restrictions. A random-effects network meta-analysis (NMA) with an aggregate regression model was performed to account for the baseline BPH severity and characteristic differences among men from the different trials.

A total of 237 of 3,104 retrieved abstracts were included for full-text review. Of these, 16 randomized and four non-randomized clinical trials were included in the NMA. The random-effects NMA showed among medical and minimally invasive therapies, WVTT had the greatest one-year IPSS improvement (-∆11.7), followed by PUL (-∆10.4) and CT (-∆10.3). The one-year IPSS improvement for TURP and PVP was comparable (-∆14.1 vs. -∆13.8, respectively; p-value=0.675). The one-year retreatment rates were lowest for WVTT (3.0%), followed by CT (3.6%), TURP (6.3%), PVP (7.8%), and PUL (8.0%).

WVTT provided greater clinical and durability benefits compared to other less invasive treatment options for men with BPH. Given NMA is increasingly used in HTA processes, this study provided systematically synthesized evidence that could facilitate decision-makers in determining new technology coverage decisions globally.

Diagnostic testing and patient monitoring are important to diagnose potential diseases and to evaluate treatment regimens. Since diagnosis and treatment monitoring have no intrinsic effects, an economic evaluation of biomarkers is inevitably linked to the resulting therapeutic interventions, which depend on both physicians’ decisions and diagnostic accuracy of the test (i.e., sensitivity, specificity). In this review we analyzed the methodology of economic studies evaluating the management of the five most relevant non-communicable diseases, that is, obesity, cancer, diabetes, cardiovascular and chronic respiratory diseases.

A systematic search in Medline and the National Health Service Economic Evaluation Database (NHS EED) covering the last ten years served to identify health economic analyses of biomarkers used in diagnosing / monitoring. Findings were reviewed with respect to analytical method, reported outcomes and comparability.

The search yielded 680 abstracts in total out of which 280 full texts were reviewed and 77 sources included following predefined criteria. Most economic analyses (94%) evaluated the clinical outcome and costs of testing / monitoring in correlation to a corresponding intervention, 6 percent of the sources focused on the accuracy of the test or monitoring methods only. There were 61 studies that included an economic model; overall, 15 sources presented the outcome as cost per life year gained (CEA), 37 sources as cost per QALY gained (CUA), and 12 provided the outcome as both a CEA and CUA. In 16 analyses the outcome was presented in other economic terms as, for example, cost per additional case detected.

Determining the value of biomarkers requires consideration of the clinical consequences of a test result (incorrect treatment decisions, impact on morbidity, mortality, or quality of life) as well as the corresponding economic outcomes. Most of the identified studies considered at least one of these aspects. Results are presented in manifold ways but do not necessarily address decision makers’ needs. Thus, clear guidelines on economic evaluations of biomarkers are needed and should include broader health system views like affordability or the number of unnecessary interventions avoided.

Advanced Therapy Medicinal Products (ATMPs) comprise medicines for human use based on gene therapy, somatic cell therapy or bioprocessed tissue products. ATMPs are pharmaceutically manufactured drugs and mostly subject to central authorization requirements. In terms of social law, it is an ambiguous situation and more heterogeneously dealt with. ATMPs are assigned to method evaluation as well as to the Arzneimittelmarkt-Neuordnungsgesetz (AMNOG) procedure designated for drugs.

Guidelines from Gemeinsame Bundesausschuss (G-BA), Institute for Quality and Efficiency in Health Care (IQWiG) and respective legislation, consultation results and methods/medical devices (MDs) evaluations according to §137h and for drugs according to AMNOG were reviewed and analyzed. Decision criteria and reasoning, assessment outcomes and potential impact on price negotiations were the main aspects for comparison.

ATMPs are subject to benefit assessment, with a decision at first on whether to be evaluated as a drug (e.g., Alofisel) or a method/device (e.g., Holoclar). By definition, an ATMP is classified as a treatment method, if the correct administration has at least the same significance for a successful therapy outcome as its mode of action. Depending on the respective decision, an evaluation as method follows or it must undergo the AMNOG process. According to G-BA's and IQWiG's point of view, randomized controlled trials (RCTs) are the “gold standard” for a benefit assessment of new therapies, including ATMPs. However, conduction of RCTs is not always possible for ATMPs which creates a disadvantage in the assessment right from the beginning. Otherwise no distinction is made between drugs and ATMPs in terms of reimbursement modalities. Outcomes based agreements could help overcoming inequalities and lead to quality-oriented reimbursement.

ATMPs represent a grey zone causing difficulties in classifying them either as method or drug. For individualized therapies evidence beyond RCTs and new reimbursement possibilities should be considered. Until new regulations are in place it is advisable to enter early into respective discussions with authorities.

Medical devices (MDs) differ regarding their risk class (I to III), operational area (in-, outpatient), intended use (diagnostic, monitoring, intervention), and with regard to available clinical evidence. Therefore, the market access processes as well as the approach of gaining reimbursement differ significantly. From a variety of potential approaches the underlying analysis illustrates five MD-specific processes.

Based on a systematic search of publicly available regulations the main pathways of potential reimbursement for MDs were evaluated.

MDs to be used in the in-patient setting can be divided into three categories: an innovative MD (a) is exceeding a current reimbursement framework (German Operations and Procedures Key (OPS) / diagnosis related groups (DRG)), (b) falls within an existing reimbursement rate, or (c) the MD is based on a known mode of action (MoA) for which already adequate reimbursement exists. Due to less empirical data from MDs for a) and b), a health technology assessment (HTA) is required before inclusion in a DRG, whereas a MD with known concept (c) will be grouped into existing price structures. Initiators of these processes are hospitals through a so-called NUB application. MDs entering the outpatient sector are covered by another reimbursement catalogue (EBM/GOÄ) and have to pass an assessment by the G-BA (rapid HTA) if based on new MoA (d). Such an assessment can only be initiated by respective umbrella organizations of service providers (e.g. KBV (National Association of Statutory Health Insurance Physicians)). MDs not being positively recommended by the G-BA are not reimbursable. For MDs (e) with known MoA no HTA is required.

For a successful market launch including sufficient reimbursement not only the market potential, but also the specific regulatory pathways have to be considered carefully. New and innovative MDs in the outpatient sector may have a longer application process to gain a positive reimbursement decision than MDs used in inpatient setting.

In 2017, the European Union (EU) commission released the final versions of the Medical Device Regulation (MDR) and In-vitro Diagnostic Device Regulation. These regulations will replace the EU directives (Medical Device Directive [MDD], In-vitro Diagnostic Device [IVDD], and Active Implantable Medical Device [AIMD]). EU regulations are effective in all EU countries at date of publication. In contrast, the EU directives must be implemented in national law first.

Guidelines and respective legislation, consultation results and methods/medical device (MD) evaluations were reviewed and analyzed. Decision criteria and reasoning, assessment outcomes and potential impact on price negotiations were the main aspects for comparison.

Manufacturers have to be aware of the importance of clinical data for demonstrating the compliance of their products. This applies both to the approval of the products and the “post-market activities” and particularly to the “post-market clinical follow-up” for which requirements for Class I and II products need to be further developed. The MDR requires manufacturers to collect clinical data before and after approval, which could lead to excessive documentation requirements. The term “sufficient clinical data” from the MDR is unclear. A functional Eudamed specification is necessary, which enables an automated processing of relevant data. A stronger involvement in the evaluation process is needed as well as more transparency in the Joint Federal Committee (G-BA) and faster evaluation processes.

The MDR increases the burden especially for small businesses, and it is doubtable that the ultimate goal – improving patient safety – will be achieved. The increased demands and rising costs of the new EU MDR and bottlenecks at Notified Bodies can be a risk for the MD industry. Due to the general reduction in the remuneration for services with a high proportion of technical services, it is feared that products will be withdrawn from the market for economic reasons or that they will not be marketed.

Constantly rising healthcare costs and the increasing incidence of antimicrobial resistance represent a growing burden on public health, affecting patients, physicians, payers, and health authorities. This analysis assessed the economic impact of improved diagnostic accuracy among septic patients.

A cost-consequence model was developed to evaluate two different scenarios for the treatment of severe sepsis: scenario one represents the current status of diagnostic performance used for an antimicrobial treatment; scenario two is based on the assumption that a more accelerated diagnostic process results in 15 percent more patients being treated with an efficient antimicrobial drug early in their therapy. Data for the average patient-related cost for diagnostics (EUR 1,182) and overall cost (EUR 12,090), length of hospital stay (average 18.7 days), and number of patients affected annually (n = 771) were derived from the German Diagnosis-Related Group Catalog for 2017. Further, the impact of optimal versus inadequate therapeutic approaches on length of hospital stay (38% decrease), hospitalization cost (40% decrease), and mortality rate (28% decrease) were derived from published sources.

By using more efficient tests to enable earlier detection of sepsis in patients who otherwise would not receive appropriate treatment, 36 additional patients were appropriately treated. The overall annual length of hospital stay can be shortened by 319 days and the number of sepsis-related deaths reduced by three. The overall annual costs in scenarios 1 and 2 amounted to EUR 11.4 and EUR 11.2 million, respectively. The main savings resulted from reduced expenses for hospital stay, drugs, readmissions, and progression to septic shock.

Increasing cost pressure and the rise in multi-resistant germs are a burden, which will increase over the next decade. The present analysis showed that a willingness to intervene early and stop detrimental developments, and to invest in effective technologies, can promote affordable health care.

Since 2005, new treatment and diagnostic methods (NUBs) were reimbursed by individual supplementary fees. The assessment procedure for NUBs is induced by hospitals submitting a request for additional compensation of healthcare treatment to the Institute for the Fee System in the Hospital (InEK). In 2016, the legal norm §137h SGB V was introduced to evaluate medical devices (MD) of high risk classes by the Federal Joint Committee (G-BA). InEK grants a status that is valid for twelve months and impacts additional compensation as well as assessment required by G-BA. The effects of this rating seem to differ between hospitals and Statutory Health Insurance (SHI).

The published InEK decisions on NUBs were analyzed according the decision criteria and possible impact on price negotiations with SHI.

In 2018, 705 NUB requests were assessed by InEK. NUB Status 1, granting negotiation of additional coverage, was assigned to 171 procedures. Status 2 – no additional reimbursement possible - was given in 472 cases, the remaining had not sufficient information. Most NUBs (n = 368) requests did not fall under §137h; however, those with sub-Status “B” (allocated to 12) led to controversies; no participant had requested an evaluation according to §137h for the NUB. Two consultation requests receiving Status 1 B were regarded as not eligible according to § 137h by the G-BA. To avoid price negotiation delays, early consultations according to § 137h are recommended by G-BA during the NUB application.

The NUB process enables hospitals to receive a supplemental payment when using innovative technologies not listed in the existing German healthcare system. The question of which requirements must be fulfilled to guarantee the reimbursement should be asked at an early stage. Consultation requests to the G-BA in due time are strongly recommended. Contact between manufacturers and hospitals are advisable to support the NUB application.

In 2011 the Arzneimittelmarkt-Neuordnungsgesetz (AMNOG) evaluation process for new drugs was implemented in Germany. Since then, the evidence requirements follow high standards and results impact reimbursement price negotiations. More recently, in 2016, a legal norm (§137h SGBV) to evaluate new treatment and diagnostic methods (MDs) of high risk classes by the Federal Joint Committee (G-BA) was introduced. The requirements, involved stakeholders, timing and results for both processes are outlined and compared.

Methodological guidelines from G-BA and Institute for Quality and Efficiency in Health Care (IQWiG), consultations and evaluations for MDs according to §137h and for drugs according to AMNOG were reviewed and compared. Published assessment results were analyzed according the decision criteria and impact on price negotiations with Statutory Health Insurance.

Hospitals need to submit jointly with the manufacturer comparative evidence on clinical efficacy, safety and cost when applying for additional compensation (Neue Untersuchungs- und Behandlungsmethoden [NUB] application) for new high risk class MDs being subject to §137h. A fast track assessment by IQWiG/G-BA follows within four months resulting in benefit proven, potential benefit or no benefit compared to alternatives. The latter can lead to exclusion from reimbursement. Until now one MD was granted a benefit, two treatments were assigned a potential benefit and six MDs no benefit, while 55 percent of drugs evaluated under AMNOG were granted an additional benefit. Compared to drugs, the required evidence for MDs is similar. Whereas assessment time is shorter, manufacturers can seek advice from G-BA upfront for free and need to collaborate closely with hospitals.

Half of MDs examined did not qualify for an assessment under §137h. Unlike for drugs evaluated under AMNOG, the majority of new MDs failed to be granted potential benefit as a treatment alternative and might be excluded from reimbursement. Manufacturers are challenged to generate high quality, comparative evidence within their studies.

Since 2005, new hospital examination and treatment methods (NUB) were reimbursed by hospital individual supplementary fees as long as they were not sufficiently covered by a DRG. In 2016, the NUB procedure was decisively changed by legal norm §137 h SGB.V to evaluate medical devices (MD) of high risk classes, particularly invasive, or new theoretical-scientific concepts versus treatment alternatives by the Federal Joint Committee (G-BA). Hospitals and manufacturers have to submit detailed information on the application of the MD and the scientific evidence to G-BA along with a NUB application. This assessment may lead to exclusion of the method from reimbursement by the statutory health insurance (SHI).

The published MD consultation submissions, assessments and G-BA resolutions (to date) were analyzed regarding evaluation criteria, treatment potential and study obligation.

In 2017, nineteen procedures were reviewed by G-BA with respect to §137 h. Two ultra-controlled high-intensity focused ultrasound (HIFU) indications were regarded as having potential benefit but not sufficient evidence yet, thus respective studies have to be initiated. Three procedures were regarded as eligible according to §137 h but not yet evaluated. Six procedures (ultra-controlled HIFU in five indications, targeted lung denervation in chronic obstructive pulmonary disease) were rated as having no potential benefit, while eight procedures were regarded as not eligible according to §137 h.

Initially put into place for high risk class and primarily invasive devices, consultations and assessments under §137 h show that there is some uncertainty around applicability criteria. The majority of those procedures which fell under the assessment law failed to be granted potential benefit as treatment alternative. Currently consultations are ongoing which could possibly lead to the exclusion of these methods from the performance spectrum of the SHI. Manufacturers should revise their study concepts in order to fulfill the specific demand for robust evidence.