Our company develops medicines that help people with serious diseases. Before obtaining regulatory approval, we conduct clinical studies with patients and, if necessary, also with healthy subjects to test the safety and efficacy of these products. These trials generally run for multiple years. Prior to doing so, extensive preclinical testing must first be performed to demonstrate that the drug poses no unacceptable risks. This preclinical test phase typically includes procedures such as animal testing. We only test medicines in patients if the compounds show great therapeutic promise and have a positive benefit-risk ratio.
Our contribution 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 as a whole. In addition to this prerequisite, 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 the respective questions.
Protecting the safety, wellbeing, 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 extremely important to us, and the confidentiality of all data and information collected is ensured in compliance with statutory regulations.
Clinical studies in developing countries
We conduct all our clinical studies in accordance with local laws and regulations. In addition, we also adhere to all relevant international scientific and ethical standards at all times. We are intentionally expanding our medicinal product development to more diverse markets in order to address the healthcare needs in various regions and countries and to support the development of their healthcare systems.
In performing clinical studies in developing countries, where there is usually a lower level of healthcare and less developed healthcare infrastructure, we adhere to the same principles that apply when conducting such trials in industrialized countries. When we perform studies in developing countries, we also:
- only do so in an environment in which the principles of Good Clinical Practice can be upheld; particularly in those places where ethics committees and well-trained Clinical Investigators are present.
- only investigate diseases and innovative medicines that are relevant to the local population.
- only conduct clinical studies in countries where we expect that the drug tested will be submitted for marketing authorization and made available to patients after we have proved its efficacy and safety.
- 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
Overall responsibility for pharmaceutical development as well as the related governance process is borne by our head of Global Research and Development, who, hand-in-hand with the Chief Marketing & Strategy Officer, co-chairs the Development Operations Committee (DOC). This top-ranking Biopharma committee ensures a cross-functional approach to the governance of drug development.
Under the umbrella of the DOC, two further committees oversee our clinical studies. The Integrated Clinical Study Committee (ICSC) is responsible for studies in pharmaceuticals that are under clinical development, while the Global Medical Affairs Decision Board is responsible for studies involving approved medicines. Both bodies consist of medical scientific experts and executives with long-standing experience in clinical research. Each committee meets regularly to conduct a comprehensive review of the proposed clinical study concepts to verify that our studies are scientifically sound, have a legitimate scientific purpose, and are performed according to the latest standards and best practices. Our therapeutic area review boards support the ICSC by conducting thorough scientific assessments of new drug/pharmaceutical study concepts.
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 profile. Only after diligently conducting extensive preclinical testing do we take the critical step of a first-in-human clinical trial. This important step of exposing humans to an investigational drug is governed by the Human Exposure Group chaired by our Global Chief Medical Officer.
Potential risks for subjects are carefully and continuously analyzed 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.
Our commitment: International guidelines and agreements
Our Clinical Research policy provides the framework for conducting clinical studies and ensures that we adhere to all 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 from the Office for Human Research Protections, USA
- 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
Regular supervision of clinical studies
Our clinical study procedures are regularly inspected by health authorities to ensure compliance with the applicable laws and guidelines. We also conduct our own internal quality assurance audits. In both cases, we respond immediately to any issues found by defining and implementing corrective and preventive actions to improve our processes accordingly.
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 subjects must give their explicit informed consent before enrolling in a clinical study. Subjects 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. All participants are given ample time and opportunity to inquire about details before deciding whether to participate. All questions are answered by the clinical investigator or another qualified healthcare professional familiar with the study. As far as possible, non-interventional (observational) studies are also assessed by an ethics committee. The subjects are further provided with thorough information.
Every study follows precisely defined procedures to ensure that studies are 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. This approach ensures in particular that studies are designed, conducted, recorded, and reported in line with all applicable requirements. In 2017, no significant issues regarding these clinical study procedures were raised by third parties or regulatory agencies.
We continuously collect and communicate safety data for our investigational drugs and promptly provide clinical investigators with important new findings relevant to the safety of subjects. In this way, we 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 risk. Product information, including the Investigator’s Brochure and Subject Information, is updated accordingly. You can find more information under Patient safety.
Conducting clinical trials in vulnerable populations
The implementation of clinical studies in vulnerable populations requires special attention and care in order to comply with the highest ethical and scientific standards. When a drug is intended for use in vulnerable populations, such as children or people with mental disabilities, in some cases clinical studies must be conducted in these populations. Their wellbeing is our utmost priority as, in general, these groups are relatively (or absolutely) incapable of protecting their own interests. We therefore only conduct studies with patients from vulnerable populations 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.
One example of a trial involving vulnerable populations is our praziquantel study in Africa to develop a formulation for children under the age of six. Praziquantel tablets are only suitable for adults and children older than six. Due to a lack of clinical data and no suitable pediatric formulation of praziquantel, pre-school aged children must currently go untreated. Within a public-private partnership, we are working to develop, register and provide access to a pediatric formulation of praziquantel that is suitable for children under the age of six. To this end, a Phase II study is currently ongoing in Côte d'Ivoire, and Phase I trials have been completed in South Africa and Tanzania. This clinical program was designed in line with U.S. Food and Drug Administration recommendations for pediatric development. It was planned and implemented with the support of regulatory authorities and a panel of international experts, including clinicians from endemic countries. Further details can be found under Infectious diseases.
Teaming up to get results
To provide a broad, in-depth basis for the development of new medicines, we frequently conduct clinical studies in collaboration with external partners in academia and industry, as well as with medical scientific advisory boards, service providers and vendors. We expect all our partners to abide by the same set of high standards when conducting clinical research. This applies especially to contract research organizations (CROs) performing studies on our behalf.
Our CROs, partners and suppliers are subjected to regular audits within our quality assurance strategy to verify their compliance with Good Working Practices (GxP, for example ICH GCP), other international guidelines and regulations, and the Declaration of Helsinki. This also applies to study centers (for example hospitals) involved in our clinical studies. In 2017, these audits did not reveal significant non-compliance with the above-mentioned standards.
Close dialogue with patients and advocacy groups
We want to ensure that patients’ voices and needs are adequately taken into consideration when planning and carrying out clinical studies. To this end, we established Patient Advisory Boards (PABs) in 2014. Our Patient Advisory Boards Charter describes the process on how to involve the Patient Advocacy Groups in our clinical research. During Advisory Board meetings, caregivers and representatives from patient advocacy groups are invited to provide feedback on clinical study matters. This advice and wealth of valuable insight applies to both the design of the clinical trial as well as its operational implementation. Cumulatively, we use this information to render clinical development and clinical studies more patient centric.
Furthermore, we are involved in the European Patients’ Academy on Therapeutic Innovation (EUPATI), a public-private partnership within the Innovative Medicines Initiative (IMI) that initially ran from 2012 to 2017. In 2017, we extended our participation in EUPATI for an additional three years. EUPATI is a pan-European project led by the European Patients Forum (EPF); it features partners from patient advocacy groups, universities and not-for-profit organizations, along with a number of pharmaceutical companies. This project focuses on helping patients better understand pharmaceutical research and development while also offering them a way to incorporate their needs into the development of clinical studies. EUPATI furthermore aims to improve the availability of objective and reliable information for the public.
Responsible data sharing
We support professional circles in advancing medical and scientific knowledge, thereby allowing for informed healthcare decisions for the benefit of patients. To this end, upon request we provide qualified researchers with study protocols, anonymized patient data, study data, and clinical study reports. In doing so, we share data and information in a manner that is consistent with the following 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 obliged to disclose information from our clinical studies, which we do 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 European Union 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. In 2017 we started providing our study participants with Lay Patient Summaries, which explain clinical study results in plain language.
We make sure that results from our clinical studies are published in medical journals in line with applicable laws and industry codes. In doing so, 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. Furthermore, we have defined standard procedures for scientific publications on our products.
Immuno-oncology: Major clinical research milestones
Immuno-oncology investigates the extent to which the body’s immune system can be activated or strengthened to mount an immune response against cancer. As part of a strategic alliance with the U.S. pharmaceutical company Pfizer, we are studying avelumab, an investigational anti-PD-L1 (programmed cell death ligand 1) antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany, as a potential treatment for a broad spectrum of tumor types. Under this collaboration, in 2015 we launched JAVELIN, our comprehensive international clinical study program in which we are investigating the potential therapeutic benefit of avelumab in multiple tumor types. By the end of 2017, more than 7,200 patients had been evaluated within this program.
In 2017, avelumab was granted its first marketing authorization in several countries (including the United States and Japan) and the European Union for treatment in patients with metastatic Merkel cell carcinoma (mMCC), a rare and aggressive form of skin cancer. Subsequently, avelumab was granted regulatory approval by the U.S. Federal Drug Administration for the treatment of patients with locally advanced or metastatic urothelial carcinoma (a malignant tumor of the urothelium that lines the urinary tract) that had progressed following platinum-containing chemotherapy. Meanwhile, avelumab continues to be evaluated in several ongoing registrational Phase III studies across multiple different tumor types, including lung, gastric, ovarian, renal cell, and head and neck cancers.
Enabling early access to new medicines
Not all patients can take part in a clinical study and so must wait for a new pharmaceutical product to be approved. Through our Early Access Program, we are, under specific circumstances, enabling patients to gain early access to new, potentially life-saving medicines. The offer is aimed at people with serious conditions who have already used all available therapies without success. It allows them to obtain medicines that have already been clinically tested but not yet obtained marketing approval. 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. We have published a position paper on the Early Access Program on our website.
Coming to terms with the past
In the 1950s and 1960s, drugs from various manufacturers were tested on children living in institutions in Germany. The majority of such clinical studies were performed in collaboration with (university) hospitals and general practitioners. By making files in our historical archives at our global headquarters in Darmstadt available, we are now supporting efforts to understand and come to terms with this episode in the history of science. As part of these efforts, we opened our archives to researchers in 2015. It is important that the findings and completion of their work be awaited before making a final assessment of this complex issue. We guarantee full transparency and will do everything necessary to help the affected institutions come to terms with the past.