Our company develops medicines that help people with serious diseases. Before obtaining regulatory approval, we conduct clinical studies with patients and, if necessary, healthy subjects to test the safety and efficacy of these products. Prior to doing so, extensive preclinical testing must first be performed to demonstrate that the drug poses no unacceptable risks. This preclinical test phase may include procedures such as animal testing. We only test medicines in patients if the compounds show great therapeutic promise and have a positive risk-benefit ratio.
Adhering to the highest standards
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 and 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 scientific questions.
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 include:
- The Good Clinical Practice (GCP) guidelines of the International Council on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use
- The Declaration of Helsinki published by the World Medical Association
- The Belmont Report
- Good Pharmacovigiliance/Laboratory/Manufacturing/Distribution Practices (GVP/GLP/GMP/GDP)
- The International Ethical Guidelines for Biomedical Research Involving Human Subjects 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 Japanese Pharmaceutical Manufacturers Association (JPMA), and Pharmaceutical Research and Manufacturers of America (PhRMA)
- The “Principles for Responsible Clinical Trial Data Sharing” published by the EFPIA and PhRMA
Clinical research governance
Our Head of Global Research and Development bears overall responsibility for pharmaceutical development as well as the related governance process. Two committees support this individual in overseeing 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. Furthermore, in 2015 we also established therapeutic area review boards, which assess proposed study concepts and use their expertise in the various therapeutic areas to advise the ICSC.
Before administering a new drug in human subjects for the first time, we conduct extensive preclinical testing to demonstrate that the medicine has the potential to offer clinical benefits, is sufficiently safe for use in humans, and has a positive risk-benefit profile. Potential risks for subjects are carefully and continuously analyzed before and during the clinical study. Our Medical Safety and Ethics Board (MSEB) oversees the safety of subjects participating in our clinical studies and, as necessary, also reviews the risk-benefit profiles of the investigational drugs. You can find further information on the MSEB under Drug safety and Bioethics.
Our clinical study procedures are regularly audited 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 adapting our processes accordingly.
Conducting clinical studies responsibly
Protecting the safety, wellbeing, dignity, and rights of the volunteers and patients 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, and the confidentiality of all data and information collected is ensured in compliance with statutory regulations.
Prior to enrolling subjects, every clinical trial must 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 informed consent before enrolling in a clinical study. We fully inform subjects 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 posed by potential participants are answered by the clinical investigator or another qualified healthcare professional familiar with the study. As far as possible, non-interventional studies (observational studies) are also assessed by an ethics committee, and subjects are provided with thorough information.
Once started, every study follows precisely defined procedures. This ensures that the study 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. This approach also ensures that the data are accurately generated, documented and reported in line with all applicable requirements. In the 2015-2016 period, we received no significant complaints regarding this clinical study procedure from 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 risk-benefit 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 Drug safety.
Conducting clinical trials in vulnerable populations
When a drug is intended for use in vulnerable populations, we must sometimes conduct clinical studies in populations such as children or underprivileged individuals. Their wellbeing is one of our top priorities 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 in other, less vulnerable study participants. When performing such studies, especially when informing subjects and obtaining their consent, we comply with all statutory regulations throughout the entire process.
More information can be found under Infectious diseases.
Clinical study collaboration
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 – especially contract research organizations (CROs) performing studies on our behalf – to abide by the same set of high standards when conducting clinical studies.
To verify their compliance with Good Clinical Practices (ICH-GCP), our CROs, partners and other vendors are subjected to regular audits as part of our quality assurance efforts. We also arrange for audits of study centers involved in our clinical studies.
In the 2015-2016 period, these audits did not show any indication of studies that were failing to comply with ICH-GCP standards or the Declaration of Helsinki.
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 for clinical studies in 2014. During advisory board meetings, caregivers and representatives from patient advocacy groups are invited to provide feedback on clinical study issues. 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 five-year public-private partnership within the Innovative Medicines Initiative (IMI) launched in 2012. 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 scientific circles and academic institutes in advancing medical and scientific knowledge. To this end, we provide them with data from our clinical studies to use in their own research. When disclosing data from clinical studies, the privacy of our patients is always safeguarded; national legal systems are always respected, and incentives are always provided for investments in biomedical research.
To ensure responsible clinical study data sharing, we also collaborate with the European Federation of Pharmaceutical Industries and Associations (EFPIA) as well as the Pharmaceutical Research and Manufacturers of America (PhRMA). In accordance with their voluntary commitments, we provide qualified researchers from medicine and science with study protocols, anonymized patient data, study data, and clinical study reports.
Publication of clinical studies
We are obliged to disclose information from our clinical studies. We communicate this information publicly in a complete, accurate, balanced, transparent, and timely manner. We publish clinical study designs and results in the international database ClinicalTrials.gov 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. Furthermore, in accordance with EU regulations, we publish results of our clinical studies in the European Union Drug Regulating Authorities Clinical Trials (EudraCT) database, which is run by the European Medicines Agency (EMA).
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.
Clinical studies in developing countries
We conduct all our clinical studies in accordance with local laws and regulations, irrespective of the region or country. In addition, we 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 support the development of their healthcare systems.
In performing clinical studies in developing countries, we apply the same principles that apply when conducting such studies 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; in particular, 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 there is a reasonable expectation that the drug tested will be submitted for marketing authorization and be 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.
Under our Praziquantel Donation Program, we are partnering with the World Health Organization to combat the parasitic disease schistosomiasis in African school children. However, in their currently available form, praziquantel tablets are only suitable for adults and children older than six. For children younger than six, it is currently not possible to properly treat the disease. Within a public-private partnership (PPP), we are researching a new formulation of praziquantel that is also suitable for infants and toddlers. As part of this research, we are currently conducting clinical studies with children in Africa. Further details can be found under Infectious diseases.
Immuno-oncology: Strategic alliance with Pfizer
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 the antibody avelumab as a potential treatment for various tumor types. In 2015, we thus launched JAVELIN, our expansive international clinical study program in which we are investigating the potential therapeutic benefit of avelumab in multiple tumor types. By October 2016, more than 3,000 patients had been evaluated as part of this program, which is investigating avelumab in more than 15 tumor types.
In 2016, we achieved important milestones in the indication of metastatic Merkel cell carcinoma (mMCC), a rare and aggressive form of skin cancer. We submitted the Biological License Application (BLA) for mMCC to the U.S. Food and Drug Administration (FDA) in the third quarter, and the FDA accepted it for Priority Review in November. In October, the European Medicines Agency (EMA) validated for review our Marketing Authorization Application (MAA) for mMCC. To date, there is no approved therapy available for this kind of tumor.
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 the most 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 our patients. We published a position paper on this topic in 2015.
Coming to terms with the past
In the 1950s and 1960s, drugs from various manufacturers were tested on orphans in Germany. The majority of such clinical studies were performed in collaboration with (university) hospitals and general practitioners. By making available files in our historical archives at Group headquarters in Darmstadt, we are now supporting efforts to understand and come to terms with this episode in the history of science. In 2015, we granted a historian access to the files in our corporate archives so that she could do in-depth research for her dissertation. Her scholarly endeavor will ultimately help us all to navigate this complex issue. We guarantee full transparency and will do everything necessary to help the affected institutions come to terms with the past.