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
We conduct high-caliber clinical research that always complies with applicable laws and regulations. When performing clinical studies, we adhere to the highest ethical and scientific standards worldwide.
We only conduct clinical studies to investigate issues that are relevant to patients, healthcare professionals or society, and only when the medicines being tested show significant therapeutic promise and have a positive benefit-risk ratio. In addition, a sound, established scientific methodology must be available to investigate these scientific or medical questions. We only enroll the specific number of participants required to answer each of these 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 subjects to undue risk or irreversible harm. Personal data privacy is also very important to us, and we maintain a strong focus on data protection and confidentiality in compliance with statutory regulations.
We assure that no subject enrolling in a clinical study is discriminated against on the basis of ethnic origin, gender or socio-economic status.
Patient-focused drug development
We are improving our approach to research and development by committing to patient-focused drug development (PFDD) 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. We are also working to further develop the way in which our research work is communicated and how it can improve the healthcare people receive. At every level of our organization, we are additionally educating 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 all our clinical studies in accordance with local laws and regulations, and we adhere to all relevant international scientific and ethical standards, irrespective of the region or country. We are deliberately expanding our medicinal product development to more diverse markets in order 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 also applies:
- We only do so in an environment in which the principles of Good Clinical Practice can be upheld.
- We only investigate diseases and innovative medicines that are relevant to the local population.
- We only conduct clinical studies in countries where we expect that the drug 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 drug development, including clinical studies and the related governance process, are the responsibility of the Global Development unit. The Head of Global Development reports to the CEO Healthcare, who is a member of the Executive Board.
We review the progress of new drug 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 Development Studies Committee is responsible for the studies performed by the company on medicines that are under clinical development, while the Global Medical Decision Board is responsible for our own studies with approved medicines, 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. Each committee meets regularly to conduct a comprehensive review of the proposed concepts and ascertains 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 drug 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 subjects participating in our clinical studies and, as necessary, reviews the benefit-risk profiles of investigational drugs. You can find further information on the MSEB under Patient safety.
Issues may be submitted to the relevant committees by product teams or other committees (as defined in relevant standard operating procedures or committee charters). If individual employees wish to seek advice or report concerns on ethical questions, they can contact the chairperson or a permanent member of a committee directly.
Our commitment: International guidelines and requirements
Our Human Subjects Research and Development Policy provides the framework for conducting clinical studies and helps ensure that we adhere to all applicable legal, ethical and scientific standards. In addition to the relevant national laws and regulations, these standards 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
- The Belmont Report by the U.S. Office for Human Research Protections
- 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), the Japan Pharmaceutical Manufacturers Association (JPMA), 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 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 (for example, at vendors’ sites and investigational sites). We respond immediately to observations 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.
Due to the Covid-19 pandemic, we postponed some audits from 2020 to 2021. However, for all audit types we successfully implemented a remote audit approach. As a result, we were able to largely implement the audit plan for 2021, shifting only a small number of audits to 2022.
Conducting clinical studies responsibly
Prior to enrolling subjects, every clinical trial must first be assessed and approved by a qualified independent ethics committee. Furthermore, 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 trial in a language that they understand. This includes the potential risks and benefits from participating in the study and the opportunity to enquire 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 the highest 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. In 2021, regulatory authority inspections did not unveil significant issues which had any impact on patient rights, patient safety, or the data integrity of a study.
We continuously collect and communicate safety data on our investigational drugs and promptly provide clinical investigators with important new findings relevant to the safety of the study participants. In this way, we help to ensure the safe use of our medicines. 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 comply strictly with all statutory regulations.
Teaming up to get results
The clinical trial investigators participating in our clinical studies by enrolling and caring for patients are critical to the successful development of new medicines. Furthermore, in order 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 all our partners to abide by the same set of high standards in terms of ethical conduct and quality in clinical research.
As a member of TransCelerate, a consortium of 21 pharmaceutical companies, we are currently collaborating on several initiatives 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 when developing and conducting clinical studies. That is why we have established the Patient Advisory Boards (PAB) as one of our crucial communication channels. Our PAB Charter describes how to involve patient advocacy groups in our clinical research process. During Advisory Board meetings, patients, caregivers and representatives from patient advocacy groups are invited to share their experiences and perspectives related to clinical trials. We use this opportunity to discuss multiple aspects of the drug development process, including but not limited to protocol design, educational materials, technology and innovative approaches to clinical trials.
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.
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 do this publicly in a complete, accurate, balanced, transparent, and timely manner as laid out in our Clinical Trial Disclosure Policy. 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). 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 this way, we adhere in particular to the current version of the Good Publication Practice (GPP3) and follow the recommendations of the International Committee of Medical Journal Editors (ICMJE). Our Medical Publications Policy ensures compliance with all relevant standards, and we use defined standard procedures for scientific publications on our products. In addition, we reference our clinical trial publications on our website. Our Standard on Clinical Trial Data Transparency underscores our strong commitment in this matter.
These ongoing efforts to increase the transparency of our clinical studies have received credit from Bioethics International. The organization ranks bio-pharmaceutical companies and new drugs based on ethics and public health performance criteria, focusing on issues that are critical to patients. In 2021, we ranked in equal first place among seven of the 42 pharmaceutical companies that were rated.
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 medicines. 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 medicines 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 an ISS as “an unsolicited request for funding and/or supply of an investigational or marketed product by a third-party investigator/institution that initiates and conducts an independent 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.