In our quest to thoroughly understand our pharmaceutical products throughout their entire life cycle, we ensure that patient needs are foremost at all times. We conduct top-quality clinical research in compliance with the applicable laws and regulations. When conducting multinational, multi-site trials in both the industrialized as well as developing countries, we follow the highest legal, ethical and scientific standards.

Merck KGaA, Darmstadt, Germany only conducts clinical trials if a sound, established scientific methodology is available to investigate a scientific or medical question of relevance to patients, medical professionals and society as a whole. We only enroll the number of participants required to answer the scientific questions being investigated.

The "Pharma Compliance Policy Clinical Research", released in October 2013, serves as a basis for the conduct of clinical trials.

Adhering to the highest standards

In all its research and development activities, Merck KGaA, Darmstadt, Germany adheres to the most stringent international legal, ethical, scientific and quality standards. These include:

• The Good Clinical Practice  (GCP) guidelines of the International Conference on Harmonization (ICH)
• The Declaration of Helsinki  from the World Medical Association
• The Belmont Report
• Good Pharmacovigilance/Laboratory/Manufacturing/Distribution Practice (GVP/GLP/GMP/GDP)
• The "International Ethical Guidelines for Biomedical Research Involving Human Subjects ” of 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 ”,  both issued 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 the Pharmaceutical Research and Manufacturers of America (PhRMA )
• The EFPIA & PhRMA “Principles for Responsible Clinical Trial Data Sharing ”

To provide a broad, in-depth basis for the development of new medicines, the company frequently works in collaboration with external partners in academia and industry, as well as with medical-scientific advisory boards, service providers and vendors. We expect and verify that all our partners – especially contract research organizations (CROs), licensing partners and suppliers – abide by the same set of high standards when conducting clinical trials.

In 2013, the biopharmaceuticals business entered into a partnership with a CRO for the exclusive conduct of all the biopharmaceuticals business’ global trials. Within this partnership with Quintiles, the Articles of Association as well as a comprehensive manual clearly define our expectations and escalation paths. Our aim is to promote the highest quality and compliance when conducting clinical trials. The biopharmaceuticals business retains ultimate accountability for any issues that pertain to the quality or procedural compliance of the trials.

In 2014, we entered into a strategic alliance with Pfizer on the joint clinical development of an anti-PD-L1 antibody, which is currently being developed by Merck KGaA, Darmstadt, Germany as a potential treatment for multiple tumor types. Up to 20 high-priority immuno-oncology clinical development programs are expected to commence in 2015, including pivotal registration studies. In this alliance, just as in all of our partnerships, we adhere to our high standards for the conduct of clinical trials.

Responsible clinical trial data sharing

Information sharing related to company-sponsored clinical trials is central to Merck KGaA, Darmstadt, Germany’s mission and enables the medical and scientific community to further develop their medical and scientific knowledge base. We are committed to enhancing public health by responsibly sharing clinical trial data in a manner that is consistent with: (a) safeguarding the privacy of patients, (b) respecting the integrity of national regulatory systems, and (c) maintaining incentives for investment in biomedical research.

We are increasing our commitment to responsible clinical trials data sharing in alignment with the European Federation of Pharmaceutical Industries and Associations and the Pharmaceutical Research and Manufacturers of America. Since 2014, the company has been fulfilling its EFPIA and PhRMA commitment to share study protocols, anonymized patient-level data, study-level data, and redacted clinical study reports from clinical trials with qualified scientific and medical researchers; this applies to all drugs of the company approved in the EU and United States from January 1, 2014 onwards.

Publication of clinical trials

Merck KGaA, Darmstadt, Germany is committed to the transparency of clinical trial information and to publicly communicating clinical trial results in an accurate, objective and complete manner. The company furthermore ensures that publications arising out of its clinical trials are produced in a responsible, ethical fashion in accordance with applicable laws and industry codes, and published in a timely manner.

We publish clinical trial information and results in the Global Clinical Trials registry and results database run by the U.S. National Institutes of Health , which can also be accessed via the World Health Organization Clinical Trials Registry Platform . Since 2014, we have also been registering clinical trials and publishing results in the EudraCT  (European Union Drug Regulating Authorities Clinical Trials) database in accordance with EU regulations.

Clinical trial governance

The Head of Global Research and Development, supported by the corresponding operating committees, has overall responsibility for product development and the related governance process.

Merck KGaA, Darmstadt, Germany has two dedicated clinical trial governance committees, those being the Integrated Clinical Study Committee responsible for development studies and the Global Medical Affairs Decision Board responsible for studies with marketed products. Chairs and members of both committees are senior medical/scientific experts and executives with long-standing experience in clinical research. Each meet on a regular basis to conduct a comprehensive review of the proposed clinical trial designs in order to verify that our trials are scientifically sound, have a legitimate scientific purpose and are undertaken according to the latest standards and best practices.

Furthermore, independent quality assurance audits are conducted regularly, thus ensuring that our investigational sites and contract research organizations (CROs) continuously adhere to Good Clinical Practice (GCP) standards. In 2013 and 2014, there were no findings giving rise to concerns that trials were not being conducted in line with ICH-GCP standards and the Declaration of Helsinki.

Our Medical Safety and Ethics Board (MSEB) investigates safety issues and benefit-risk profiles of our marketed and investigational products in order to ensure their safe and appropriate use by patients. The MSEB is chaired by the Chief Medical Officer and consists of senior physicians and scientists with long-standing experience in drug safety and clinical research.

Conducting clinical trials responsibly

Protecting the rights, safety, dignity and wellbeing of volunteers and patients participating in our clinical trials is of utmost importance to us. Individuals enrolled in our clinical trials will not be intentionally exposed to undue risk or irreversible harm. Privacy of all personal information is respected and confidentiality is ensured in compliance with statutory regulations.

Prior to enrolling participants in an interventional clinical trial, a qualified independent ethics committee/institutional review board (EC/IRB) must review and approve each and every trial. All local regulatory or governmental authorizations required in the respective country must furthermore be obtained. In accordance with Good Clinical Practice guidelines (ICH-GCP), every participant must give their informed consent before enrollment in a clinical trial. 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 trial. They also are given ample time and opportunity to inquire about details of the trial before deciding whether or not to participate. All questions posed by potential participants are answered by the clinical investigator or another qualified health care professional familiar with the study.

Once a trial has started, precisely defined procedures are followed to ensure that the study is conducted to the utmost standards in accordance with Good Clinical Practice  and that the data are accurately generated, documented and reported in line with all applicable requirements. In the 2013-2014 period, we received no significant complaints regarding this clinical trial procedure from third parties or regulatory agencies.

We continuously collect and communicate safety data for our products, promptly providing clinical investigators with important new findings relevant to the patients. This aims to ensure the safe use of our pharmaceutical products. Potential safety issues and risks are taken into consideration in order to evaluate the benefit/risk of our products and manage risk. Product information, including the Investigator’s Brochure and Subject Information, is updated accordingly.

We engage patient advocacy groups in a discourse on our clinical trials. For example, EMD Serono, one of our subsidiaries in the U.S., is the National Sponsor of AWARE for All, an educational outreach model by the non-profit Center for Information and Study on Clinical Research Participation (CISCRP). AWARE for All educates the public about the importance of clinical research; it is driven by the premise that awareness, realizing the value of participation, and ongoing engagement are the keys to generating public support and attracting more clinical research volunteers. Ultimately, CISCRP hopes to empower patients and the public to make more informed decisions about participating in clinical research. During the 2013-2014 period, EMD Serono collaborated with the Lupus Research Institute  in a pioneering effort to make our Lupus Clinical Trials more patient-centric.

We are planning to expand the dialogue with patient organizations, especially for therapeutic areas in which we are conducting clinical trials. For instance, we would like to increase the degree of informed consent and make clinical trials more patient-friendly in order to ensure that the trials are designed and conducted around patient needs.

Clinical trials conducted in developing health care systems

Regardless of location, all Merck KGaA, Darmstadt, Germany’s clinical trials are conducted in compliance with international scientific and ethical standards, in addition to the locally applicable laws and regulations. We are actively shifting our development activities to more diverse markets in order to address the healthcare needs in various regions and to support the development of their health care systems.

In performing clinical trials in developing health care systems, we apply the same principles that apply when conducting such trials in developed countries. When we conduct clinical trials in a developing health care system:

• We only do so in an environment that can follow Good Clinical Practice, i.e. where ethics committees and well-trained clinical investigators are present.
• We only address diseases and test innovative medicines that are relevant for the local population.
• We conduct clinical trials 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 proof of efficacy and safety.
• We assure that enrollment into a clinical trial does not discriminate against participants on the basis of ethnic origin, gender or socio-economic status.

Within the scope of our Praziquantel Donation Program (MPDP), we are partnering with the World Health Organization (WHO) to combat the parasitic worm disease schistosomiasis in African school children. Praziquantel tablets in their current form are suitable for adults and children over the age of six. For children younger than six, it is currently not possible to properly treat the disease. Within the scope of a public-private partnership (PPP), Merck KGaA, Darmstadt, Germany is researching a liquid formulation of praziquantel that is intended to be suitable for small children. This project makes it necessary to conduct clinical trials involving children in Africa. Further details are described under Neglected Diseases.