Before obtaining regulatory approval for our medicines, we conduct clinical studies with patients and, if necessary, also with healthy volunteers to investigate the safety and effectiveness of our products. We also perform extensive preclinical research, including animal testing, to demonstrate that our treatments pose no unacceptable risks to humans.
Our approach to safe and transparent clinical studies
Our aim is to conduct high-caliber clinical research that is in compliance with applicable laws and regulations. We set Group-wide requirements that aim to ensure that high ethical and scientific standards are met when conducting clinical trials.
We only conduct clinical studies to investigate issues relevant to patients, healthcare professionals or society, and only when our established methodology finds the given medicines show significant therapeutic promise and a positive benefit-risk ratio. Accordingly, to ensure patient safety and avoid interrupting the development of promising products, we carefully select patients based on known risk factors. These include age and comorbidities, which we reflect in the design of our clinical studies. Notably, we only enroll the specific number of patients needed to answer the posed scientific and medical questions. We reconcile and review the safety reports from our clinical studies and marketed products and immediately address any unforeseen risks. Senior boards such as the Pharmacovigilance Advisory Board and the Medical Safety and Ethics Board maintain oversight of any emerging safety concerns. In addition, cross-functional Benefit Risk Assessment teams adapt the benefit-risk assessment and development strategy of each product to ensure it delivers maximum safety and efficacy to our patients. In addition, a sound, established scientific methodology must be available to investigate these scientific or medical questions.
Protecting the safety, well-being, dignity, and rights of the patients and healthy volunteers participating in our clinical studies is of utmost importance to us. We do not intentionally expose study participants to undue risk or irreversible harm. Data privacy is also very important to us, and we maintain a strong focus on data protection and confidentiality in compliance with statutory regulations.
Diversity, equity and inclusion in clinical trials
Based on our Standard on Human Research, we aim to conduct clinical studies that adequately represent the diverse patient populations expected to use our products once they are approved. To ensure fair, balanced and scientifically justified study representation, we cemented our commitment to Diversity, Equity and Inclusion (DE&I) in clinical trials by collaborating with healthcare providers and community advocates to eliminate common barriers to clinical trial participation. We have also reviewed our internal processes to enable more inclusive research practices. Additionally, to publicly disclose our views on DE&I, including in clinical trials, we published our very first DE&I report in 2023. It reinforces our commitment to ensuring study participants face no discrimination due to factors such as their gender, ethnic origin, religion, disability, gender identity, or socio-economic status.
Our ongoing efforts to increase diversity in our clinical studies have been formally recognized by Bioethics International. In 2023, we received a gold badge and ranked equal first among seven of the 25 rated pharmaceutical companies. The rating considered important factors in oncology studies, including the fair and equitable representation of diverse patient populations.
Patient-focused drug development
We are improving our approach to research and development by committing to patient-focused drug development that more actively involves patients, caregivers, and their advocates in our work. Their valuable insights into disease and treatment management will help us make more informed decisions at each stage of the medicine development process. We aim to make our studies easy for patients to understand while ensuring all participants have positive experiences as they contribute to our understanding of the particular disease and its treatment. At every level of our organization and based on the function, we are additionally either offering or mandating to educate staff about the value of a close, more consistent patient interaction and the requirements to protect our patients’ independence and privacy.
Clinical studies in low- and middle-income countries
We conduct our clinical studies in accordance with local laws and regulations, and we aim at adhering to the relevant international scientific and ethical standards, irrespective of the region or country. We are deliberately expanding our medicinal product development to more diverse markets to address pressing healthcare needs in low- and middle-income countries and support the development of their healthcare systems.
When performing clinical studies in low- and middle-income countries where there is usually a lower level of healthcare and limited healthcare infrastructure, the following directives also apply:
- We only do so in an environment where the principles of Good Clinical Practice can be upheld.
- We only investigate diseases and innovative products that are relevant to the local population.
- We only conduct clinical studies in countries where we expect that the product being tested will be submitted for marketing authorization and made available to patients after we have proven its efficacy and safety.
Roles and responsibilities
Clinical development, including clinical studies and their related governance processes, are the responsibility of our Global Development unit. The Head of Global Research & Development reports to the CEO Healthcare, who is a member of the Executive Board.
We review the progress of new product development at defined milestones and make decisions about the continuation, modification or discontinuation of development, depending on the results of clinical studies.
We have established two internal committees to oversee our clinical studies. The Integrated Protocol Review Committee is responsible for the studies performed by the company on products that are under clinical development, while the Global Medical Decision Board is responsible for our own studies with approved products as well as for all studies performed by independent investigators and supported by us (so-called investigator-sponsored studies). Both bodies consist of medical-scientific experts and executives with long-standing experience in clinical research. Our development and study teams present clinical study concepts to the appropriate committee. The committees meet regularly or as needed to conduct a comprehensive review of the proposed concepts and ascertain that our studies are scientifically sound, have a legitimate scientific purpose and are performed in accordance with the latest standards and best practices.
Before administering a new product to humans, there must be sufficient evidence that it offers a potential therapeutic benefit, is sufficiently safe for use in humans and has a positive benefit-risk ratio. We only take the critical step of a first-in-human clinical trial after diligently conducting extensive preclinical testing. The decision lies with a separate committee, the Human Exposure Group, chaired by our Global Chief Medical Officer.
We continuously analyze potential risks for study participants before and during our clinical studies. Our Medical Safety and Ethics Board (MSEB) oversees the safety of the participants in our clinical studies and, as necessary, reviews the benefit-risk profiles of investigational products. Further information on the MSEB can be found under Patient safety.
Emerging issues related to a clinical study may be submitted to the relevant committees by product teams or other committees, as defined in relevant standard operating procedures or committee charters. Also, if individual employees wish to seek advice or report concerns on ethical questions, they can contact the members of a committee directly.
Our commitment: International guidelines and requirements
Our Quality Policy defines the strategic framework that ensures our products, services and systems deliver high quality, safety and efficacy to our patients. It details the most relevant laws and codes, criteria and guidance (e.g. for product development and manufacturing), and our senior management’s responsibility to ensure quality is embedded in everything we do.
Our Standard on Human Research provides the framework for conducting clinical studies and helps ensure we adhere to all applicable legal, ethical and scientific standards. Further quality documents detail for instance the strategic direction of all quality related activities or disclose our position on data privacy. In addition to the relevant national laws and regulations, these documents also include:
- The Good Clinical Practice (GCP) guidelines of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)
- The Declaration of Helsinki, published by the World Medical Association
- Good Pharmacovigilance/Laboratory/Manufacturing/Distribution Practices (GVP/GLP/GMP/GDP)
- The International Ethical Guidelines for Health-related Research Involving Humans, published by the Council for International Organizations of Medical Sciences (CIOMS)
- The Joint Position on the Disclosure of Clinical Trial Information via Clinical Trial Registries and Databases and the Joint Position on the Publication of Clinical Trial Results in the Scientific Literature, published by the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA), the European Federation of Pharmaceutical Industries and Associations (EFPIA), and the Pharmaceutical Research and Manufacturers of America (PhRMA)
- The Principles for Responsible Clinical Trial Data Sharing, published by EFPIA and PhRMA, and the IFPMA Principles for Responsible Clinical Trial Data Sharing.
Regular supervision of clinical studies
Our clinical study processes and procedures are regularly inspected by relevant regulatory authorities to verify their compliance with applicable laws and guidelines.
The Research & Development Quality and Risk Management (RDQRM) unit applies a risk-based identification strategy to determine areas that need to be audited. Quality assurance audits are performed internally within Healthcare R&D (for example, process audits) and externally (e.g., investigator sites and vendor audits). We respond immediately to observations made during audits by investigating their root causes and, according to their criticality, defining and implementing corrective and preventive actions to improve processes, prevent reoccurrence of irregularities and ensure compliance. As planned, in 2023, RDQRM concluded most of the audits of the Annual Audit Plan.
Conducting clinical studies responsibly
Prior to enrolling participants, every clinical trial must first be assessed and approved by a qualified independent ethics committee. Additionally, all regulatory authorizations required in the respective country must be obtained. In accordance with Good Clinical Practice guidelines (ICH-GCP), all study participants must give their explicit informed consent before enrolling in a clinical study. Participants are fully informed about all aspects of the clinical study in a language that they understand. This includes the potential risks and benefits from participating in the study and the opportunity to inquire about details. As far as possible, non-interventional (observational) studies are also assessed by an ethics committee.
Every clinical study follows defined procedures to ensure it is conducted to high quality standards in line with good working practices (GxP) for the development and manufacturing of drugs, the ethical principles of the Declaration of Helsinki and other international guidelines and regulations. As in the previous year, in 2023, none of the regulatory inspections conducted on our clinical research activities resulted in regulatory action.
We continuously collect and communicate safety data on our investigational products and promptly provide clinical investigators with important new findings relevant to the safety of study participants. In this way, we help to ensure the safe use of our products. Potential adverse effects and risks are taken into consideration to evaluate the benefit-risk ratio of our products and manage any risk. Product information, including the investigator’s brochure and information for study participants, is updated accordingly. More information is available under Patient safety.
Conducting clinical trials in vulnerable populations
The implementation of clinical studies in vulnerable populations, such as children or people with disabilities, requires special attention and care to comply with the highest ethical and scientific standards. The well-being of the individual is our highest priority. For this reason, we only conduct studies with participants from vulnerable population groups if scientifically justified and if there is no other way to achieve conclusive results. When performing such studies, especially when informing study participants and obtaining their consent, we take statutory regulations into account.
Teaming up to get results
The clinical study investigators participating in our clinical studies by enrolling and caring for patients are critical to the successful development of new products. Furthermore, to achieve a broad, in-depth basis for the development of new treatments, we seek advice from medical-scientific advisory boards and frequently conduct clinical studies in collaboration with external partners in academia and industry. We also rely on the support of contract research organizations (CROs) and other service providers and vendors. We expect from our partners that they apply the same high standards in terms of ethical conduct and quality in clinical research.
As a member of TransCelerate, a consortium of 22 pharmaceutical companies, we are currently collaborating on several initiatives to identify, prioritize, design and facilitate implementation of solutions designed to drive the efficient, effective and high-quality delivery of new medicines.
Close dialogue with patients and advocacy groups
We want to ensure that the voices and needs of patients and their caregivers are adequately heard and taken into consideration throughout the entire lifecycle of our products. We have a strong internal policy as well as compliance guidance documents, which provide clarity on how to ensure that such engagements take place within an ethical framework. In addition, we established the Patient Advisory Boards (PAB) as one of our crucial communication channels. Our PAB guidance document describes how to involve patients and caregivers in our clinical research process. During Advisory Board meetings, patients, caregivers and representatives from patient advocacy groups are invited to share their experiences related to clinical studies. We use this opportunity to discuss multiple aspects of the product development process, including but not limited to protocol design, educational materials, technology and innovative approaches to clinical studies.
Furthermore, we are involved in multiple activities that focus on this relevant aspect of patient centricity in clinical studies. For example, in the United States, we are an active member of the Clinical Trials Transformation Initiative (CTTI), which focuses on quality and efficiency in clinical trials. For instance, in 2023 we engaged with the CTTI to develop industry recommendations for increasing diversity in clinical trials, as mentioned above.
Responsible data sharing
We support professional circles in advancing medical and scientific knowledge, thereby enabling informed healthcare decisions for the benefit of patients. Upon request, we provide qualified researchers with study protocols, anonymized individual patient data, study data, and clinical study reports. We share data and information in a manner that is consistent with the joint Principles for Responsible Clinical Trial Data Sharing of the EFPIA and PhRMA:
- Safeguarding the privacy of patients
- Respecting the integrity of national regulatory systems
- Maintaining incentives for investment in biomedical research
Disclosure of clinical studies and publication of results
We are obligated to disclose findings from our clinical studies. We strive to do this publicly in a complete, accurate, balanced, transparent, and timely manner as laid out in our Standard on Clinical Trial Data Transparency. Our clinical study designs and results are made public in the international ClinicalTrials.gov database run by the U.S. National Institutes of Health (NIH), which can also be accessed via the World Health Organization’s International Clinical Trials Registry Platform (ICTRP). Furthermore, in accordance with EU regulations, we publish results from our clinical studies in the EU Drug Regulating Authorities Clinical Trials (EudraCT) database, which is run by the European Medicines Agency (EMA). Additionally, new applications for clinical studies in scope of the EU Clinical Trials Regulation were submitted through the Clinical Trials Information System (CTIS) and will be published on the public CTIS portal. We will transition all ongoing studies to CTIS by January 2025. If required by local laws and regulations, we publish study results on other publicly accessible platforms. We provide clinical study report synopses and summaries of study results in plain language on our clinical trials website.
We publish results from our clinical studies in medical journals in line with applicable laws and industry codes. In particular, we adhere to the current version of the Good Publication Practice (GPP3) and align with the recommendations of the International Committee of Medical Journal Editors (ICMJE). Our Medical Publications Policy helps us to consider relevant standards and use defined standard procedures for scientific publications on our Healthcare’s products. In addition, we reference our clinical study publications on our website. Our Standard on Clinical Trial Data Transparency underscores our strong commitment in this area.
Enabling early access to new medicines
Not all patients have the opportunity to take part in a clinical study and must therefore wait for a new pharmaceutical product to be approved. Through our Early Access Program, we can, under specific circumstances, enable patients to gain early access to new, potentially life-saving products. The offer is aimed at people with serious conditions who have already received all available therapies without success. It allows them to be treated with products that have already been clinically tested but have not yet been approved. Furthermore, we offer patients who participated in one of our clinical studies post-study access to the investigational product, provided that certain conditions are met. Here, too, we meet stringent statutory, ethical and scientific standards. By performing a thorough assessment of all available data, we ensure that the potential benefits outweigh the potential risks for patients. Position papers on early access and post-study access are available on our website.
Supporting independent human subject research
In addition to conducting our own clinical research programs and studies, we also support studies proposed by independent investigators, so-called investigator-sponsored studies (ISS). Our ISS Principle defines ISS as unsolicited request for funding and/or supply of an investigational or marketed product by independent investigator/institution that initiates and conducts a scientific investigation as the regulatory sponsor. By granting financial or material support for independent human subject research, we seek to stimulate the advancement of clinical and medical knowledge and patient care in our therapeutic areas of interest and support the safe and effective use of our products. We give priority to research that is innovative and has the potential to address specific unmet medical or scientific needs. Our principles, framework and standards for granting support for ISS and our collaboration with independent investigators are specified in our ISS Principle, which is available on our website and in our corresponding policy and standard operating procedure.