Our company discovers and develops medicines that help people with serious diseases. Before obtaining regulatory approval, we conduct clinical studies with patients and, if necessary, also with healthy volunteers to investigate the safety and efficacy of these products. Before they begin, extensive preclinical testing must be performed to demonstrate that the drug poses no unacceptable risks. This typically includes procedures such as animal studies.
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 number of participants required to answer each of the 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.
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.
- We assure that no subject enrolling in a clinical study is discriminated against on the basis of ethnic origin, gender or socio-economic status.
How we govern clinical studies
Clinical drug development, including clinical studies, and the related governance process are the responsibility of the Head of Global Development unit. The Head of Global Development reports to the Member of the Executive Board and CEO Healthcare.
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 (DSC) is responsible for the studies performed by the company on medicines that are under clinical development, while the Global Medical Decision Board (GMDB) 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 according to the latest standards and best practices.
Before administering a new drug to human subjects, 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 the course of 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 SOPs 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 procedures are regularly inspected by the relevant regulatory authorities to verify compliance with the applicable laws and guidelines. The Covid-19 pandemic had only a minimal impact on inspections by the regulatory authorities. They continued to carry out their inspections, yet virtually.
Our Research & Development Quality unit identifies areas for auditing based on a quality risk assessment approach. We perform quality assurance audits internally within Healthcare R&D as well as externally among our partners (for example, at vendors’ sites and investigational sites). We respond immediately to any issues found during audits by defining and implementing corrective and preventive actions to improve processes and promote compliance. Due to the Covid-19 pandemic, we paused business travel and postponed various on-site audits to 2021. We also developed virtual auditing concepts and suitable alternatives for the postponed audits.
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 study follows precisely defined procedures to ensure that it is conducted to the highest quality standards in line with good working practices for the development and manufacture of drugs (GxP), the ethical principles of the Declaration of Helsinki and other international guidelines and regulations. In 2020 there were no significant issues which had any impact on patient rights, patient safety or data integrity of a study raised by third parties or regulatory agencies.
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 pharmaceuticals. Potential adverse effects and risks are taken into consideration in an effort 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 in order 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.
Under our leadership and in collaboration with a consortium of partners, the Pediatric Praziquantel Program has conducted clinical trials with vulnerable populations in low- and middle-income countries. Our aim is to develop, register and provide access to a pediatric formulation of praziquantel for treating schistosomiasis in children younger than six years of age. The program is currently in Phase III of clinical development.
We collectively designed the clinical program in line with the recommendations of the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for pediatric development. Planning and implementation were undertaken in close cooperation with regulatory authorities and a panel of international experts, including clinicians from endemic countries. Further details can be found in the Health for all chapter.
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 20 pharmaceutical companies, we seek to drive the efficient, effective and high-quality delivery of new medicines. In this context, we are currently leading an initiative to modernize clinical trials with innovative solutions such as telemedicine, direct to patient medication, home health nursing services and others.
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 experience 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. Our Global Clinical Operations (GCO) unit values and leverages such information in multiple ways, with a clear focus on prioritizing patient centricity in everything we do.
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 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 Lay Patient Summaries, which explain the 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.
Our standard on clinical trial data transparency underscores our strong commitment in this matter.
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 to 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 for our collaboration with independent investigators are specified in our ISS Principle, which is available on our website, as well as in our corresponding policy and standard operating procedure.
Joining forces to combat the pandemic
The Covid-19 pandemic presented a major challenge for healthcare systems and clinical research in 2020. Researchers from academia, industry and supranational organizations initiated numerous research projects in an effort to find effective and safe therapies to treat Covid-19, the disease caused by the SARS-CoV-2 virus. We supported these initiatives by donating up to 300,000 units of Rebif® (interferon beta-1a) for use in Covid-19 clinical studies. This helped to enable the implementation of three major clinical trials with thousands of patients worldwide: the Solidarity trial performed by the World Health Organization (WHO), the Discovery trial undertaken by the French research institution INSERM, and the ACTT 3 trial initiated by the Unites States National Institute of Allergic and Infectious Diseases (NIAID). In addition, we are supporting several Covid-19-related studies performed by independent researchers. We have established a dedicated task force within our Healthcare R&D function to oversee the collaboration with independent external institutions and investigators studying Rebif® as a potential Covid-19 treatment.
We have also initiated our own Phase II randomized, controlled clinical study to evaluate the efficacy and safety of our investigational product M5049 in patients suffering from Covid-19 pneumonia. M5049 blocks the activation of two innate immune sensors that detect single-stranded RNA from viruses such as SARS-CoV-2. The activation leads to immune cell activation and inflammation, which when not properly controlled, can cause severe immunopathology. The aim of the study is to determine whether M5049 can reduce the life-threatening complications of Covid-19, including severe respiratory symptoms that often necessitate further medical interventions such as mechanical ventilation.
Managing the crisis
Soon after the news about the Covid-19 pandemic had been published around the world, it became apparent that the situation could have a major impact on our clinical research activities. First and foremost, our focus has been on the safety and well-being of the patients participating in our clinical studies and the continuity of their treatment and care.
A task force was established within Healthcare R&D in March 2020 to continuously monitor the impact of the Covid-19 pandemic on our ongoing and planned clinical studies, to guide the investigators, monitor clinical trial participants’ well-being, and safeguard the integrity of our clinical studies during the pandemic.