Within the Fresenius Group, we distinguish our clinical research and clinical studies as follows:
- Clinical trial management (CTM) for pharmaceutical approval processes: Approval processes both for innovative pharmaceutical products and generics require support from trials. These encompass patient studies or even animal trials.
- Clinical studies to develop innovative treatment methods: The majority of clinical studies conducted in our business segments Fresenius Helios and Fresenius Medical Care are aimed at developing innovative treatment methods or the improvement of therapies both in ambulatory and inpatient care. While Fresenius Medical Care focuses on patients with kidney failure or related diseases, we focus on oncology and cardiovascular diseases in our acute care hospitals. But health services research is also an important area. Using real data from everyday hospital life, known as real world data (RWD), the structures and processes of hospitals are examined under everyday conditions. The analysis of pandemic effects on the various areas of patient care has played a major role in this context over the past three years.
Fresenius Medical Care
Fresenius Medical Care strives to continuously improve the care that it provides to patients. This includes facilitating clinical trials, which are a crucial step in developing new treatments. The business segment is also further exploring data-based methods that allow it to advance care by means of mathematic modelling and virtual clinical trial simulations. The research and development activities follow regulatory guidance for clinical research practices. They are conducted in compliance with ethical standards. In a global company position paper made available on the company’s website in 2022, Fresenius Medical Care outlined the bioethics principles. These include the commitment to upholding ethical standards while advancing healthcare and managing related risk, as well as advocating patient rights, and animal welfare. It is important to the company that its research partners follow guidelines that are similar to its own.
Progress and measures in 2022
In 2022, the business segment published 169 scientific documents worldwide. The Frenova Renal Research division provides research services to third parties. Currently, Fresenius Medical Care is working on a project aimed at developing the largest renal-focused genomic registry in the world. The goal is to enroll over 100,000 patients by 2025. This registry will contain genetic data from chronic kidney disease patients worldwide, which will help researchers improve their understanding of kidney disease and treatments.
Fresenius Medical Care also works with external organizations to facilitate scientific progress and explore new ways of improving quality of care. In 2022, the business segment was involved in 67 key partnerships with academia, research institutes, and peers. The focus areas included cardio-protection, personalized and precise medicine, public health, and the impact of COVID-19 on vulnerable patient populations.
At Fresenius Kabi, the knowledge and expertise from experts in clinical nutrition, pharmaceuticals, and medical devices are embedded in research and innovation projects with the goal of improving patients’ health and quality of life. As a manufacturer of generic drugs, clinical nutrition products, and infusion and transfusion therapies, as well as biosimilars and medical devices used to administer these products, Fresenius Kabi conducts clinical studies by commissioning qualified external contract research organizations (CROs) and university scientific institutions to do so. Some products require to conduct clinical studies sponsored by Fresenius Kabi to meet regulatory approval requirements. In addition, further studies are conducted regarding patient safety, in order to gain new medical-scientific insights or comparative clinical studies with other products available on the market. The clinical studies sponsored by Fresenius Kabi are always carried out in accordance with strict legal requirements, including, for example, the guidelines of the International Council of Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), of Good Clinical Practice (GCP), and of the relevant pharmaceutical regulatory authorities such as the U.S. Food and Drug Administration (FDAFDA (U.S. Food & Drug Administration)Official ​authority ​for ​food ​observation ​and ​drug ​registration ​in ​the ​United ​States.), the European Medicines Agency (EMA), the Declaration of Helsinki, and the EU GDPR. The primary goal is the protection of patients and the quality of the data obtained. Fresenius Kabi sponsors studies for registration in close cooperation with various CROs, scientists, and physicians and supports investigator-initiated trials. These studies pursue the goal of generating new scientific knowledge that is significant for patient care using approved and new products.
Fresenius Kabi has a Chief Medical Officer (CMO) and a Global Trial Committee that reviews, evaluates, and approves clinical trials before they begin. Responsibility for clinical study management is aligned with Fresenius Kabi’s product groups and is anchored in the management board areas. Compliance with the applicable regulations and guidelines prior to, during, and after clinical studies is ensured by a risk-based auditing program. Here, safety of the study participants and validity of the study data are considered the most important criteria. No clinical trials are conducted without a positive vote by the responsible ethics committee and approval from the respective competent authority, where required.
CROs contracted for the management of Fresenius Kabi-sponsored clinical studies are audited by the Quality Assurance Department of Fresenius Kabi to ensure that the applicable regulations and standards are followed throughout the duration of the clinical studies; Fresenius Kabi also conducts internal process and document audits regarding clinical studies as well as audits of investigator sites. Each employee involved in clinical research receives regulatory training on regulations via online training courses to ensure a uniform understanding of the requirements of GCP. In addition, employees receive training on the procedures applicable to clinical studies at Fresenius Kabi.
When selecting study participants, Fresenius Kabi also takes diversity into account, e. g., with regard to the population group for which a product in question is intended. Fresenius Kabi does not conduct studies without a prior positive benefit / risk assessment. Furthermore, safety events occurring during a clinical study are constantly monitored and evaluated. Study participants are fully informed prior to the start of the study and are enrolled only with their consent. Internally, clinical studies are documented in a central database and the results are published in accordance with the applicable regulations.
Fresenius Kabi's research and development activities are focused on biosimilarsBiosimilarsA ​biosimilar ​is ​a ​drug ​that ​is ​“similar” ​to ​another ​biologic ​drug ​already ​approved., clinical nutrition, and generic drugs, which are already well-established in markets and consequently need no, less or limited animal studies. They are also only conducted if required by national and international laws or regulations. Animal studies are restricted to the scale that is absolutely necessary and are conducted according to respective animal welfare legislations only.
Fresenius Kabi cooperates with professional non-clinical CROs or academic institutions that are accredited according to the standards of the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC) or a similar standard and follow the principles of the 3Rs (Reduce, Replace, Refine) regarding the use of laboratory animals. Moreover, non-clinical CROs are audited by the Quality Assurance department of Fresenius Kabi as well and re-qualified every three to five years based on the underlying risk. Like clinical trials non-clinical trials are evaluated and approved by a Fresenius Kabi internal scientific expert committee (the Global Trial Committee) which oversees, among other aspects, the ethical aspects of this area of activity.
To foster clinical research into malnutrition in countries around the world, Fresenius Kabi established the initiative United for Clinical Nutrition in 2014. This multinational initiative seeks to reduce hospital malnutrition through education, data collection, and clinical assessment in various regions. In 2018, the commitment continued in Europe, with a special focus on critically ill patients with the aim of gaining knowledge on the use of clinical nutrition in intensive care units of European hospitals, as well as assessing calorie and protein balance in critically ill adult patients. The relationship between clinical nutrition therapy and patient outcomes is also being investigated.
Fresenius Helios conducts clinical trials at many sites, partly in cooperation with CROs. In this way, the business segment aims to promote innovation processes in diagnostics and clinical treatment. The innovative strength in clinical study management not only influences its future success in the diagnosis and treatment of inpatients. It also opens up new ways of providing care, especially for the high proportion of chronic diseases. For example, studies are conducted to determine how effective and safe medicines are and whether medical devices are suitable for approval in accordance with internationally applicable ethical and scientific standards, such as GCP or the Declaration of Helsinki of the World Medical Association. In addition, clinical data is collected, analyzed and published to evaluate new, already approved technologies and treatments in everyday care. Based on a clear commitment to evidence-based medicineEvidence-based medicine (EBM)Evidence-based ​medicine ​(EBM) ​builds ​on ​expert ​knowledge, ​the ​experience ​of ​those ​treating ​patients ​and ​their ​needs, ​as ​well ​as ​on ​current ​scientific ​findings. ​The ​aim ​is ​to ​provide ​the ​best ​possible ​care ​for ​people ​who ​are ​ill., the division encourages its employees to engage in scientific and technological research activities. The aim is for them to develop personally and use their findings to enhance the well-being of patients.
Projects funded by public grants are also being carried out at the German Helios hospitals – supported by the Innovation Fund of the Joint Federal Committee (G-BA), the German Federal Ministry of Education and Research (BMBF), or ministries of further German federal states, among other bodies. These projects serve the benefit of Helios' patients. They focus on the development of new forms of care and process plans (treatment pathways) for medical treatments. In cooperation with manufacturers, the focus is on testing new technologies in clinical application and thus assessing their benefit. Such clinical data on the reality of care is important for evaluating technologies and determining their market price (HTA – health technology assessment). Helios Germany also provides data on severe acute respiratory infections (ICOSARI) to the Robert Koch Institute (RKI) in order to monitor the appearance of influenza virus and coronavirus in hospitals. Numerous analyses of the impact of the pandemic on different care settings have been conducted and published in both Spain and Germany.
Clinical research projects
In Germany, the newly established Helios Health Institute (HHI) is the central point of contact for all employees of Helios clinics and its subsidiaries who want to conduct research. The HHI validates the study design to ensure that all regulatory requirements that exist in research are met. The respective Group guideline on research (Helios Konzernregelung Forschung) mandatorily provides that every research project must first be submitted to the HHI for review, including all necessary documents, in order to protect its patients.
The HHI reviews research projects with regard to regulatory and content-related methodological requirements, as well as a legal review of project contracts and data protection advice. This enables clinics to ensure that scientific, ethical, and legal requirements are met and that the project complies with applicable guidelines or quality standards. All researchers are required to provide evidence of their qualification, i. e. to comply with knowledge and requirements of clinical studies and trials. These requirements are listed in the Helios Group regulation on research. In self-initiated studies, full responsibility lies with the persons who conduct the study. In sponsor-initiated clinical trials and studies, the CROs involved are audited by the sponsor.
HHI maintains a continuously developing quality management system with the aim of certification according to ISO 9001 in 2023, so that it can then also operate externally as a CRO.
The Helios Group regulation on research funding further specifies the framework conditions within which Helios specifically promotes research projects of its own employees that are expected to have a high level of benefit for patients.
Studies were reviewed for a total of 39 (2021: 48) hospitals or integrated healthcare facilities in Germany in 2022. The respective Helios clinics or facilities in question employ what are referred to as investigators and study assistants – specially trained nurses, medical documentation assistants, but also natural scientists specialized in biology, nutritional science or biochemistry. They support the investigators, coordinate examinations and interviews of the study participants and conduct non-medical services that are required by the study protocol. In addition, the HHI supports the clinics of Helios Germany along with the employees conducting research in studies initiated by the clinics themselves (known as investigator-initiated studies, IITs).
As the central office with experts in regulatory principles and methodology and in contract management, and supported by the Central Data Protection Service, the HHI conducts the central study review. More information on data protection can be found in the Data protection section.
Departments or clinics have special certifications, e. g., as certified organ cancer centers or as oncology centers of the German Cancer Society. Certification is based, for example, on quality of treatment or sufficient participation of patients in clinical trials. If a Helios clinic is selected by an external sponsor for a study, external audits are conducted in accordance with the sponsor’s respective guidelines. Likewise, individual Helios clinics are inspected according to the respective selection procedures of the state authorities.
The performance of clinical studies is subject to strict requirements. These include the internal Group guideline on research as well as numerous external guidelines, national regulatory requirements, and the Declaration of Helsinki issued by the World Medical Association, and the requirements of GCP. For both medical and non-medical staff conducting central study reviews, regular GCP training organized by HHI is mandatory.
Monitoring is ensured by audits as well as inspections by the state, higher and regulatory authorities. In case of complaints, appropriate corrective actions are initiated by the respective clinic and reported to the inspecting authority. No external inspections and audits took place in 2022 at the central function HHI.
A prerequisite for any study to begin is a vote or consultation from an independent ethics committee established under state law. In this sense, all clinical studies are reviewed by independent experts who are responsible for the respective state or the state medical association there. For research projects of Helios physicians with university affiliation, the ethics committee of the responsible university is responsible for the review of a study, depending on the state regulations. Within experimental studies, investigations can be carried out in the laboratory, e. g., using tissue samples or blood material, and are also reviewed by an ethics committee. All studies using sample material from patients must be evaluated by the ethics committee. Exceptions may be made in the case of completely anonymous processing of samples. This is reviewed on a case-by-case basis.
If patients are interested in participating in a clinical trial, they discuss all questions in advance with the responsible investigator. These discussions follow a guideline that includes study-specific, ethics committee-approved patient information and a declaration of consent. External sponsors are responsible for preparing these documents themselves. After evaluation by the ethics committee, the investigator may use the documents. The patients’ consent is obtained in writing after sufficient reflection time and the educational discussions are documented for the protection of the patients. The data protection requirements must be complied with.
Research makes Fresenius Helios more attractive to physicians and employees who are interested in improving existing forms of treatment and therapy and who thus have an affinity for research. For the organ cancer centers and oncology centers, participation in studies is a mandatory requirement for certification. Patients research on the Internet to find out which hospitals are running studies and then make a conscious decision to participate. The reason: By participating in studies, Helios patients can access innovative drugs or medical devices earlier and benefit from the latest scientific standards of treatment.
Progress and measures in 2022
Helios Germany and the holding company Helios Health decided at the end of 2021 to bundle all research-related areas and merge them into a separate subsidiary – the HHI. It comprises the areas of healthcare research, consisting of Real World Evidence (RWE) and HTA and the CTM. With the CTM division, the HHI takes over from the Helios Center for Research and Innovation, which was responsible until the end of 2021.
In 2022, a total of 337 studies (2021: 410) were reviewed centrally for the Helios clinics in Germany, the majority of which had the goal of improving therapies for patients. The decrease is due to an internal procedural change. This provides for certain studies (usually doctoral theses) to be processed directly in the clinics on a standardized basis using an SOP. They have not been subject to central review since 2022. Further, the impact of the pandemic has delayed recruitment of study patients.
Based on the data analyses during the pandemic, Fresenius Helios has been able to gain and publish significant insights into the impact of COVID-19 on the care situation in both Germany and Spain. This type of use of care data demonstrates how quickly, yet accurately, the status of the care situation can be provided. Given the many challenges facing healthcare systems, this is essential.
Further, Helios Germany has conducted around 90 COVID-19-related studies in its clinics since 2020.
Clinical studies centrally reviewed in 2022 by initiator (Germany)Download(XLS, 36 KB)
|Employees of Helios clinics as initiator||58|
|Participation in academically managed studies, publicly funded1||100|
|Participation in academically-led or publicly-sponsored studies with industry support; trial medication generally provided2||54|
|1 The majority of these studies are led by universities, mostly with public research funding.|
|2 The majority of these studies are led by universities / professional societies, but are supported by drug / medical devices manufacturers, which usually extends to the provision of the drugs / medical devices.|
|3 The majority of these studies are supported by the pharmaceutical industry; less than 20% are medical device manufacturers.|
In 2022, Helios Spain with more than 50 hospitals in the division were involved in scientific projects, including Spain, Colombia and Peru.
In total, the hospitals participated in more than 1,300 clinical trials, more than 300 observation studies, and more than 700 research initiatives, as well as opened 324 new clinical trials. The most important area of research has been oncology with approximately 55% of all clinical trials performed. Other important areas were infectious, inflammatory and chronic diseases, health technology and innovation, neurosciences and renal, metabolic and cardiovascular diseases as well as children and women's health area.
At the end of 2021, Helios Spain in collaboration with the U.S. company NEXT Oncology opened two new units in two different hospitals dedicated to Phase I cancer research, in addition to the existing START Unit. In the reporting year, 29 clinical trials were initiated in the new units.
Research results of Helios Spain were published in around 1,900 articles in international peer-reviewed journals in 2022. During the reporting year, the division has given support to researchers in 36 times regarding methodology and statistical analysis of their projects, medical writing for publications and access to scientific articles.
Helios Spain has been able to attract approximately €3.5 million of European Funds to develop projects in different areas such as the monitoring of elderly people with frailty and comorbidities, the search for imaging biomarkers for prostate cancer, the creation of new scores to predict sudden death after myocardial infarction, participation in European neuroscience infrastructures and the application of AI to prepare infrastructures for possible future catastrophic situations such as the pandemic.
At Fresenius Vamed’s Institute for Gender Medicine, all health issues that lead to an extension of the healthy years of life and to the improvement of quality of life are researched, with a particular focus on gender-specific aspects with regard to individualized medicine. These research activities encompass prevention, acute care, rehabilitation, and nursing. Further explanations can be found in the following section Gender-specific medicine.
The well-being of patients is Fresenius’ top priority. Within the Fresenius Group, great importance is therefore attached to a gender-specific view of people in research, prevention, diagnostics, and therapy.
From a medical perspective, women and men differ, for example, in their chromosomal makeup, sexual characteristics, and hormonal balance. These purely biological differences, as well as societal aspects such as environmental conditions, upbringing, culture, or social circumstances, have an impact on human health. This results, for example, in differences in the symptoms and courses of diseases and in the effectiveness of medications. Until the end of the 20th century, these differences were largely ignored in medical research and practice. The resulting knowledge gap needs to be closed in order to be able to offer our patients individually tailored advice, diagnosis, and treatment. In the business segments, we pursue gender-specific approaches corresponding to the respective business activities.
Fresenius Helios also investigates gender-specific issues as part of its studies and research projects. In 2021, for example, Fresenius Helios conducted a study on the gender- and age-specific differences in the course of the disease of different COVID-19 variants. The results were published in 2022. On the basis of the results, individual therapies can be developed in the future. Helios Germany also makes various gender-specific offers, such as heart consultation for women at the Heart Center Leipzig.
Fresenius Vamed’s study activities cover prevention, acute care, rehabilitation and nursing. Together, the Vamed Institute for Gender Medicine, the Medical University of Vienna and the Ludwig Boltzmann Institute for Rehabilitation Research (LBI) use findings from research and clinical data to develop and evaluate new standards. In this way, they aim to actively shape the practice and future of healthcare. The goal is to sustainably adapt new knowledge and promising applications to the possibilities and individual needs of a person. Research projects are currently underway – in collaboration with international experts – in particular on gender medicine and the identification of critical success factors, which are being worked on in various specialties such as musculoskeletal, pulmonology (e. g. Long COVID), geriatrics, neurology, psychiatry-psychosomatics (e. g. addictive diseases) and oncology. The knowledge gained from the studies is continuously incorporated into Fresenius Vamed’s prevention and rehabilitation offerings, e. g. in geriatric transitional care or in women-specific health offerings in the company’s own la pura health resort in Austria.