Comparison of benefit assessments of CDK 4/6 inhibitors

CDK 4/6 inhibitors represent a relatively new group of agents for the treatment of metastatic breast cancer. The first representative of this group entered the market in November 2016. Subsequently, two additional CDK 4/6 inhibitors, ribociclib and abemaciclib, were approved. In the meantime, all representatives of the new class of active ingredients have been subjected to a benefit assessment. As a result, no additional benefit was recognized for any of the preparations. At the same time, it can be seen that very different standards were applied in the assessment.

Based on the most recent benefit assessment, a comparative presentation of the procedures was carried out.


It became apparent that IQWiG proceeded in a strikingly different manner when evaluating the individual active substances. The G-BA also shows inconsistencies in its assessments. For example, biases that may complicate the interpretation of a study result are assessed in strikingly different ways. While a clear effect in overall survival is negated due to conceivable biases, increased adverse events are taken into account in the assessment despite considerable concerns regarding the significance.

Critical evaluation of surrogate parameters also seems to focus on endpoints that might demonstrate the benefit of an agent. In the case of adverse events, no discussion of this topic is discernible. A significant line of argumentation by the G-BA in the balancing of benefits of CDK 4/6 inhibitors with increased adverse events relies heavily on asymptomatic neutropenia – an endpoint of at least questionable patient relevance.


The new form of health care “SmartAssistEntz” is designed to help patients who have completed an inpatient alcohol withdrawal program to identify, access, and use the appropriate follow-up measures sustainably.

Alcohol dependence is one of the most common mental disorders worldwide and is often characterized by a chronic course. The German healthcare system offers a wide range of treatment options for those affected. However, only a small proportion of patients make use of further care services after completing inpatient withdrawal. Consequently, patients do not receive adequate support in a phase characterized by a high risk of relapse.

The smartphone-based concept provides the following eCoach-accompanied components:

  1. Enhancement of abstinence motivation through app-based training of abstinence skills.
  2. App-based telediagnostics for the identification of individually tailored follow-up actions
  3. Transfer to selected follow-up programs on the basis of an individual sustainability plan, which is jointly developed in six weekly telephone calls between the patient and the eCoach.


The evaluation will compare SmartAssistEntz with the standard of care. The primary outcome parameter is the risk of relapse within six months after completion of withdrawal. Secondary parameters include the use of evidence-based follow-up treatments after inpatient withdrawal, severity of alcohol dependence, health-related quality of life, and (total) costs. Tertiary outcome parameters are usability and satisfaction with “SmartAssistEntz”. For this purpose, patients and treatment providers will be surveyed and routine data from the participating health insurance funds and the German pension insurance will be used.


For the three-year project period, there is funding of a total of approx. 2.4 million euros. If successful, the “SmartAssistEntz” care concept could be transferred to other regions or to standard care.


The aim of DELIVER-CARE is to develop a model for the delegation of medical activities to medical assistants (MFA) in chronic inflammatory diseases.

Chronic inflammatory diseases are complex clinical conditions requiring a high level of care. In the current health care setting, the vast amount of time required for optimal treatment cannot be provided. The lack of access to specialist care, or the severe delay in accessing it, often leads to a deterioration in prognosis and quality of life. This problem could be counteracted by delegating medical activities to medical assistants (MFA).

In this process, MFAs are expected to perform their own structured consultation. They identify current symptoms and the drug tolerability and serve as the primary point of contact in the event of special incidents, e.g., drug side effects. Subsequently, the results are discussed with the patient and the specialist. This provides patients with a more effective drug therapy, individualized information and faster access to specialists.


A randomized controlled trial will be conducted to evaluate DELIVER-CARE. Within the scope of the study, the effectiveness of the MFA consultation compared to the standard of care will be tested over a period of twelve months. For three disease categories (gastroenterology, rheumatology, dermatology), the study will determine the influence of the MFA consultation on disease activity and the extent to which patient-related factors such as disease management, quality of life or patient satisfaction improve. In addition, cost-effectiveness will be evaluated.


The project will be funded for four years with a total of ca. 2.2 million euros. If successful, the concept can be transferred to other regions as well as to other diseases (e.g. ophthalmology) with department-specific adaptation.


The aim of RubiN is to implement a care and case management system that supports geriatric patients to enable them to remain in their own homes for as long as possible.

The demographic change is accompanied by a growing number of chronically and multimorbidly ill patients. Especially among geriatric patients, acute and chronic (multiple) illnesses occur simultaneously. The term geriatrics therefore does not refer to the entirety of elderly people, but describes a condition associated with advanced age. This is compounded by age-related physiological changes, as a result of which the residual capacities of various bodily functions are increasingly limited and everyday activities can no longer be managed sufficiently. In addition, the fragmented structures and scarcely networked sectors of the German healthcare system are not designed for the care of elderly, chronically or multimorbidly ill patients.

Therefore, the project “RubiN – Regional uninterrupted care in a Network” aims to improve the identification, care setting and health status of geriatric patients; in particular, the independence of elderly patients is to be preserved. For this purpose, within accredited practice networks, a multiprofessional, cross-sectoral and assessment-based training curriculum for health professionals is to be used for the case management of geriatric patients. At the same time, the workload of primary care physicians in geriatric patient care should be reduced. To achieve this, legally secure delegation in care networks must be ensured by developing and introducing a set of general structural and process requirements.


The evaluation of the project is based on three levels: First, a quantitative evaluation with primary data is conducted. The data is collected using standardized measurement instruments. The primary patient-related endpoint is the ability to cope with everyday activities after twelve months, based on the Barthel Index. Furthermore, a formative process evaluation is carried out, in which the aspects of acceptance, feasibility and implementation of the intervention are examined. This will involve the use of both qualitative and quantitative survey methods. A health economic evaluation will also be conducted. The design of the evaluation is prospectively controlled.


The aim of the project is to test telemedical care for the treatment of patients with skin diseases in rural areas.

Both primary care and specialist care are steadily disappearing in rural areas. In Mecklenburg-Western Pomerania, for example, dermatologist practices are concentrated primarily in urban centers and mid-sized cities, while rural areas are increasingly threatened by insufficient care. The consequences for patients living in the state include long waiting times for an appointment and poor accessibility to dermatological specialist practices.

The project focuses on the implementation of a telemedical consultation between primary care physicians or physicians in emergency rooms and dermatologists (private practices or dermatology clinics) with the help of an app. Dermatology is particularly well suited for a telemedical consultation, as symptomatic skin changes can be easily communicated via images. The attending physician photographs the patient’s affected skin area and sends the image – along with information about the patient’s medical history and symptoms – to the dermatology specialist. The specialist then recommends the next course of action.


The evaluation of the dermatological teleconsultation is performed by analyzing routine data, patient and physician surveys, and focus group interviews as well as expert discussions.


The project is funded with ca. 1.8 million euros. If successful, the new form of care will be transferred to other structurally weak, rural regions. The app and the underlying telemedical concept could also be adapted for other medical disciplines in the future.


The Telemedicine Lifestyle Intervention Program (TeLIPro) aims to support patients diagnosed with type 2 diabetes mellitus in adopting a healthy lifestyle by providing patient-centered, individualized and personalized care. In this context, the adherence of patients also needs to be strengthened to achieve a sustainable improvement in health and quality of life.

The prevalence of diabetes in Germany continues to rise. Roughly seven million adults suffer from diabetes mellitus, with about 95 percent of them being diagnosed with type 2 diabetes. The treatment of the disease and its secondary conditions results in high healthcare costs. Since the development and progression of type 2 diabetes in particular is driven by low physical activity and a high-calorie diet, lifestyle interventions can contribute to improvements in health and quality of life.

In addition to the regular care provided by the attending physician, participants in TeLIPro receive individual health coaching over the phone. The coaches, who are specially trained in diabetes and motivation, set individual goals in cooperation with the patients and accompany them throughout the program, which runs for a total of twelve months. During the sessions, the coaches support the diabetes patients in permanently changing their eating and exercise behavior.

The program also includes monitoring of disease- and lifestyle-relevant parameters using a blood glucose meter, a scale and a pedometer. The patients and their coaches can access the respective values via the online portal of the German Institute for Telemedicine and Health Promotion (DITG). Step by step, patients are introduced to independent disease management and the independent implementation of lifestyle changes.


A randomized controlled single-blind trial will be conducted to evaluate the project. Primary data as well as routine data are processed within the scope of the study. Various medical parameters will be collected as endpoints, including the HbA1c level. Behavioral parameters and health-related quality of life will be obtained through validated questionnaires. Patient preferences are represented by a discrete choice experiment. The evaluation will also include a health economic analysis, in which the cost-effectiveness of TeLIPro will be examined on a service- and sector-specific basis.


The project “Back innovative pain therapy with e-health for our patients” (Rise-uP) systematically analyzes how the treatment of back pain, which to date has often been of little effectiveness, can be improved.

For many people in Germany, back pain is part of their everyday life; one in five people with Statutory Health Insurance (SHI) visits a doctor at least once a year because of it. Despite the high prevalence, there is still no target-oriented treatment path. Misuse and overuse of treatment are often the case.

The central idea of this intervention concept is to eliminate the currently existing fragmented structures for the treatment of back pain patients and to develop treatment pathways. The Rise-uP treatment concept is based on early use of an assessment tool to measure the risk of chronification (STartBack questionnaire), a telemedicine networking software (Therapienavigator) and a medical app (Kaia). The focus of this intervention program lies on patients with acute and subacute back pain.


Rise-uP is a prospective cohort study with an intervention group and a control group in terms of an observational study (health services research study), with an observation period of 18 months. The evaluation includes the analysis of quantitative primary data from several validated questionnaires, as well as secondary data from i) routine data from a statutory health insurance, ii) data from a health app, and iii) data from telemedicine software.

The primary endpoint relevant to the number of cases is the patients’ pain level, which is measured using a pain index (Visual Analogue Scale, VAS). In addition, functionality and general quality of life are assessed. Within the framework of a health economic evaluation, it will be examined whether a significant change in the total cost of care exists. Furthermore, an incremental cost-effectiveness analysis is performed. In the incremental cost-effectiveness analysis, the costs per reduced pain index are calculated.


Priebe, J.A., Haas, K.K., Moreno Sanchez, L.F., Schoefmann, K., Utpadel-Fischler, D.A., Stockert, P., Thoma, R., Schiessl, C., Kerkemeyer, L., Amelung, V.E., Jedamzik, S., Reichmann, J., Marschall, U., Toelle, T.R. (2020). Digital Treatment of Back Pain versus Standard of Care: The Cluster-Randomized Controlled Trial, Rise-uP. Journal of Pain Research 13: 1823–1838.

Optimizing care for people with diabetes mellitus using telemedicine

Diabetes mellitus affects around nine percent of the population in Germany, and forecasts predict that this percentage will increase in the future. Many patients receive intensified insulin therapy, which is time-consuming, organizationally complex and requires intensive doctor-patient contact. This study was initiated on the assumption that consistent monitoring combined with individual medical care supported by telemedicine can significantly contribute to improving or stabilizing the metabolism of people with diabetes mellitus. The telemedical approach was based on consistent glucose measuring, which was transmitted electronically to the physician.

The evaluation was to investigate whether the care of patients with diabetes mellitus and intensified insulin therapy using telemedicine leads to an improvement in the glycemic metabolic status. The primary endpoint was the HbA1c level. The secondary endpoints were the additional costs of the intervention, further indicators of the glycemic metabolic status, the feasibility of the approach in the daily practice and in the daily life of the patients, and the patients’ satisfaction with the therapy. Data collection and project implementation were conducted from 01.10.2018 through 31.07.2019. The target groups of the project were patients with diabetes mellitus type-1 and type-2 as well as the treating physicians.

To provide answers to the research questions, a quasi-experimental study with a pre-post design was conducted. Within the study period of six months, there were two (patients) and three (physicians) survey time points. For the interviews, both self-developed and standardized questionnaires were used. Depending on the research question and endpoint, descriptive and/or inferential statistical analyses were used. Statistical data analysis was performed using SPSS Subscription Version 2019.


Every year, more than 465,000 people suffer from heart failure. Due to the aging society, the rate is expected to increase. Growing cost pressure is a rising challenge for the German healthcare system. The majority of costs associated with heart failure occur in the hospital. The number of hospitalizations can be reduced by adequate management of office-based physicians and better coordination between the different sectors. Currently, many hospitalized cases could also be treated as outpatients. At the same time, some severe outpatient cases would benefit from a referral to the hospital. Thus, there is a lack of need-based guidance of patients to the appropriate outpatient or inpatient treatment. In addition, the different reimbursements in the outpatient and inpatient sectors set false incentives. While flat rates per patients are applied in the outpatient sector, flat rates per case are used in the inpatient sector. When in doubt, this difference in reimbursement systems reinforces the tendency to treat patients as inpatients.

The goal of sekTOR-HF is the need-based and resource-optimized cross-sectoral care of patients with heart failure. For this purpose, coordination and communication structures are established as a bridge between the sectors. These include an eHealth platform for communication between all parties involved, a electronic patient file, and a regional network office that supports the monitoring of patients and thus coordinates the available resources in the outpatient and inpatient sectors. The network office continuously monitors patients by evaluating digitally transmitted vital data. In the event of any deterioration, the network office can activate service providers at the appropriate level of care at an early stage.

The second objective of the project is to develop a new cross-sector reimbursement model that provides incentives for cost-efficient care. For this purpose, the inav is conducting a theoretical and empirical analysis of various international cross-sector payment models, such as bundled payments. This is being done in exchange with international experts who contribute their experience on already existing models.

The second objective of the project is to develop a new cross-sector reimbursement model that provides incentives for cost-efficient care. For this purpose, the inav is conducting a theoretical and empirical analysis of various international cross-sector payment models, such as bundled payments. This is being done in exchange with international experts who contribute their experience on already existing models. The data of the participating heart failure patients collected in the project are the basis for examining different models with regard to incentives, resource consumption and transferability to the German context.

The project will receive ca. 3.8 million euros in funding from the Innovation Fund over a period of three and a half years.

GefaS – Health professionals in schools

Today’s healthcare systems challenge people to make decisions regarding their health. In this context, the knowledge, motivation and competencies to access, understand, assess and apply the appropriate information are of high relevance. The underlying concept is defined as health literacy and is the requirement for making health-related decisions regarding appropriate care. Thus, health literacy is an important predictor of a person’s health status. In Germany, over one in two people has difficulty understanding health-related information. There is a correlation between limited health literacy and low social status.

The cities of Bremen and Bremerhaven are relevant locations for establishing programs to promote health literacy. In some city districts, inequalities are evident in living conditions and in terms of health and educational opportunities. To counteract these, the project “Health Professionals at Schools (GefaS)” has been implemented at Bremen and Bremerhaven elementary schools for some time. The goals of the current project include: strengthening the health resources of students, teachers and parents; creating a health-promoting school environment; increasing the school’s outreach to health-related services in the city district; and establishing and expanding network structures.

An in-process evaluation is often a central component of a complex intervention. The in-process evaluation of the project “GefaS” is funded by the SHI Alliance for Health and commissioned by the Federal Center for Health Education (BZgA) in the context of the evaluation of projects across different health insurance funds. The evaluation of “GefaS” will ascertain whether the underlying project has been successfully implemented and thus has the potential to be sustained to achieve long-term positive effects. Both qualitative and quantitative survey methods are used in a mixed methods approach. The focus is primarily on the evaluation of structures and processes. This includes, among other things, identifying the obstacles to project implementation at the schools, determining the factors that are beneficial to the implementation of the project, and assessing how the health professionals and the school staff and parents are cooperating with each other.


LeIKD is a lifestyle intervention project addressing high-risk patients with a combination of type 2 diabetes mellitus (DMT2) and coronary heart disease. A significant number of people develop common illnesses during their lifetime, such as diabetes or cardiovascular disease. A combination of these diseases increases the risk of higher morbidity and mortality exponentially. Therefore, the development and testing of new care models for these diseases is extremely important.


To evaluate the project, a multi-center randomized controlled trial will be conducted. The study will investigate if the patients’ lifestyle can be positively influenced and if health literacy and health-related quality of life can be increased. Results from medical examinations, patient surveys and routine data from the Techniker Krankenkasse will be used for the evaluation. The primary endpoint is the HbA1c level of the study participants. Health-related quality of life, health literacy and behavioral parameters will be assessed using validated questionnaires.


The project will be funded with ca. 4.5 million euros for a period of three years. If positive care effects can be identified in the course of the study, the aim is to transfer the project to other locations throughout Germany. The establishment of further locations is intended to contribute to this successively.

Electronic Patient Record

To increase the effectiveness and efficiency of care – that is the purpose of an electronic patient record (ePA). However, the introduction of ePA into the German healthcare system is proving to be extremely complex. Why is Germany having such a hard time with this change, and to what extent do ePA showcase countries like Denmark or Israel differ from Germany? The study conducted by inav consisted of a literature review, case studies and the development of a scorecard.

The focus of the literature review centered on the international evidence base on ePA, specifically the effects of ePA on health care delivery and existing evidence on implementation. The literature review was conducted using database queries on PubMed and Google Scholar. Systematic reviews published between January 1, 2010 and July 14, 2016 were considered.

In addition, the study included case studies to examine the situation and progress of ePA implementation and use in selected countries. The case studies were conducted for Denmark, Israel, the United States, and Austria. The selection was complemented by case studies on the corporate solutions of Apple and Google. The case studies were based on in-depth interviews with experts on a national and international level.

The third part of the study, the “European Scorecard”, was designed to classify the implementation status of the German ePA on a European scale and to compare it with selected countries. For the development of the scorecard, relevant indicators were identified that reflect the complexity of ePA implementation and are available and comparable for a wider range of countries. Once the scorecard was developed, a selection of 20 countries were rated in terms of ePA implementation and use using a traffic light system. In 2018, an update of the scorecard was conducted, also by the inav.

Based on the synopsis of the results of the three elements, recommended courses of action were determined in various subject areas.

Further Information (German language)

Application-accompanying data in benefit assessment

The aim of the project was to identify recommendations for evidence generation and evaluation by means of in-use data in the benefit assessment of orphan drugs and medicinal products.

With the GSAV, the G-BA was authorized to require application-accompanying data collection and evaluation for the purpose of benefit assessment for orphan drugs and drugs with conditional approval or approval granted under special conditions. According to the intention of the legislator, non-randomized studies and thus lower certainty of results are also to be accepted.

Based on an overview of the current handling of non-randomized studies on the part of relevant organizations as well as an overview of methodological evaluation procedures, recommendations were formulated regarding evidence generation and evaluation, which serve the objective of being able to generate usable data for a quantifiable additional benefit and thus improve the evidence situation.


Bleß, H.: „Anwendungsbegleitende Daten in der Nutzenbewertung – Empfehlungen zur Evidenzgenerierung und -auswertung“, in: „Monitor Versorgungsforschung“ (01/20), S. 47-54, doi: 10.24945/MVF.01.20.1866-0533.2202


“IGiB-StimMT” adapts inpatient and outpatient care capacities  in accordance with the changing population structure in the central area of Templin. The project introduces relevant interdisciplinary and intersectoral structures.

Demographic change in Germany is characterized by rising mortality rates, declining birth rates and an aging society. Rural areas in particular are reporting less and less young people and ever more elderly people – a development that is also reflected medically in an increase in chronic illnesses and/or multiple illnesses. Since a significant shift in the population structure is also predicted for the central area of Templin, it is necessary to develop and implement new and needs-based care structures.


Considering the multi-layered nature of the project, the evaluation will be carried out on several levels. Based on a mixed-methods approach, the evaluation is conducted on two levels. On the one hand, a structure and process analysis is performed, on the other hand, a health economic evaluation of the project is carried out. Furthermore, accompanying research based on qualitative scientific methods will be conducted. This is to find out whether the complex intervention can adapt the care structures and processes in the central area of Templin to existing challenges in a needs-oriented approach.


The project was funded by the Innovation Fund for a total of four years with ca. 14.5 million euros.



The Dimini prevention project aims to increase the health literacy of patients with an increased risk of developing DMT2. This way, long-term behavioral preventive changes are to be achieved.

Diabetes mellitus type 2 (DMT2) is one of the most prevalent common illnesses in Germany, with currently more than six million people affected. In addition, an estimated further three to five million people are affected by undetected DMT2 or elevated blood glucose levels. In the long term, DMT2 can lead to serious secondary diseases and result in high costs. It is therefore particularly important to identify relevant risk parameters in a timely manner and to address them early on with adequate preventive measures.

To identify individuals at high risk of DMT2 at an early stage, the project uses the so-called FINDRISK test, which determines the individual risk profile on the basis of eight easy-to-answer questions on, among others, height, weight and dietary habits. Based on this, those affected receive the needs-based Dimini lifestyle intervention over a period of three months. This contains a set of health-related information and a request to keep an analog diet and exercise diary. Optionally, affected individuals can also use an app to access and document all elements of the lifestyle change. General practitioners provide support and accompany the project through interim coaching sessions.


The effectiveness of the lifestyle intervention will be investigated by a randomized controlled trial. This will involve quantitative evaluations through validated questionnaires and qualitative evaluations through focus group and individual interviews. The primary endpoint is body weight. Additionally, abdominal circumference, HbA1c level, dietary and physical activity behavior as well as quality of life of the study participants will be investigated.


Püschner, F. , Urbanski-Rini, D., Dubois, C., Schliffke, M., Göhl, M., Petersen, C. (2022) Dimini (Diabetes mellitus? – Ich nicht!): Aktivierung der Gesundheitskompetenz von Versicherten mit erhöhtem Risiko für Diabetes mellitus Typ 2 mittels Coaching in der Vertragsarztpraxis. Diabetologie und Stoffwechsel.

Bertram, N., Püschner, F., Binder, S., Schliffke, M., Göhl, M., Petersen, C. (2020). Dimini – Diabetes Mellitus? Ich nicht! In: Hahn, U. & Kurscheid, C. (Hrsg.), Intersektorale Versorgung. Best Practices – erfolgreiche Versorgungslösungen mit Zukunftspotenzial (S. 213-231). Berlin: Springer Gabler.

Further information