Clinical trial ethics
Clinical research is carefully designed to evaluate the effects of a new medication, a medical or surgical intervention, or a new device, which can lead to improvements in people’s health. Clinical trials are one of the last steps in the process of bringing a new pharmaceutical product to market and before a new product can be approved by regulatory authorities, it must be proven to be efficacious and safe in the targeted patient population.
There are indeed ethical implications of involving people in the testing of investigational drugs and concerns have been raised and debated relating to issues such as principles for recruitment of volunteers, respect of patients’ rights, selection of countries where the research is performed and potential bias in publication of the obtained results. There have been specific concerns related to clinical research performed in developing countries and it has been questioned whether the pharmaceutical industry takes advantage of poor and illiterate people, whether research is undertaken in developing countries that would not have been permitted in developed countries, and whether the pharmaceuticals will be available to the population participating in research after marketing authorisation.
Novo Nordisk acknowledges and focuses on the ethical implications of clinical research and operates by high ethical global standards. We strive to continuously improve our performance and wish to contribute to an open dialogue on all aspects of our clinical research programme. This document outlines our position pertaining to ethics in clinical research.
Novo Nordisk sponsors clinical research in therapies that require inclusion of different ethnic populations. We support global exposure of investigational drugs to be able to observe ethnic, therapeutic and cultural differences in efficacy and safety. We anticipate a need to conduct an increasing number of clinical research activities as a result of our expanding development pipeline and local regulatory requirements.
Novo Nordisk’s position
- Clinical research sponsored by Novo Nordisk will always comply with applicable external guidelines and regulations having their origin in the Nuremberg Code, the Declaration of Helsinki (which describes human rights for patients participating in clinical research), other internationally accepted ethical guidelines, local laws, and the International Conference on Harmonisation (ICH) Guideline for Good Clinical Practice (GCP), Good Pharmacoepidemiology Practices (GPP), Good Laboratory Practice (GLP) and Good Manufacturing Practice (GMP). Furthermore, we will comply with all local regulations in the countries where we do clinical research.
- The above guidelines and regulations are the foundation for Novo Nordisk’s clinical Standard Operating Procedures (SOPs) including the SOP on the ‘principles of clinical research’. These standards are laid out to ensure the safety, rights, integrity, confidentiality and well-being of people involved in Novo Nordisk trials globally.
- Novo Nordisk applies the same global procedures wherever we sponsor clinical research. This means that all people enrolled in Novo Nordisk’s clinical research are protected by the same rights, high ethical standards and regulations irrespective of study location. The interests, safety and well-being of people enrolled in research studies will always prevail over the interests of science, society and commerce.
- Novo Nordisk respects that clinical research activities should only be done if they are scientifically and medically justified. Clear and detailed protocols are prepared for all clinical research activities, based on sound scientific and ethical considerations.
- Novo Nordisk will only conduct placebo-controlled research activities if scientifically and ethically justified, and research subjects will always be informed about potential implications of the placebo treatment.
- No research activity in Novo Nordisk-sponsored trials will start before approval is obtained from Independent Ethics Committees (IEC) or Institutional Review Boards (IRB), as applicable as well as from the responsible Regulatory Authorities.
- Novo Nordisk will always ensure that staff and investigators involved in executing Novo Nordisk-sponsored clinical trials are appropriately qualified and trained.
- Before any clinical research activities can take place, a freely given informed consent based on appropriately provided information must be obtained from the participants. In cases where trial participants are unable to consent, Novo Nordisk will follow national regulatory and legal requirements for obtaining consent. The processes for seeking consent from minors will be clearly defined in advance of the research taking place.
- Novo Nordisk fully respects that people enrolled in clinical research can withdraw at any time during a research activity without providing any reason.
- Investigational pharmaceuticals used in Novo Nordisk-sponsored clinical research will be manufactured and controlled according to international GLP and GMP guidelines and live up to all local standards.
- Novo Nordisk conducts frequent study site monitoring to ensure that interventional trials are executed according to the study protocol, and that data used in statistical analysis and reporting reflects the correct data obtained from all patients participating in the trials.
- All necessary and relevant patient safety information is continuously assessed by independent safety monitoring boards during all Novo Nordisk research activities and a study will immediately be stopped if risks are found to outweigh potential benefits to research participants.
- Research participants enrolled in a Novo Nordisk-sponsored interventional trial will after trial completion be offered the best possible and available treatment at the discretion of the investigator. Access to post-study trial medication will be described in the protocol and informed consent. Investigators may under special circumstances apply for use of a medication which has not yet obtained marketing authorisation approval, on a named patient basis.
- Novo Nordisk will ensure proper indemnification of research participants in case an investigational pharmaceutical or procedures in Novo Nordisk-sponsored research cause bodily harm to a research participant.
- Patients participating in a Novo Nordisk trial may be reimbursed for documented and reasonable travelling expenses and loss of income. In trials with healthy volunteers or in trials where patients obtain no health benefit, participants can also be financially compensated for inconvenience/discomfort during the trial. All agreements on financial compensation will be described in the protocol and approved by an EIC or an IRB.
- Novo Nordisk will ensure all Novo Nordisk-sponsored clinical trials are registered in a publicly accessible database before recruitment of the first subject. Novo Nordisk will further strive to ensure accurate and timely recording, verification, handling, interpretation, and reporting of all data and results from all Novo Nordisk-sponsored clinical research activities in accordance with accepted international guidelines and global and local requirements.
- Novo Nordisk will ensure transparency of all our clinical research activities by registering protocol information and trial results, regardless of outcome, on the external websites www.clinicaltrials.gov and www.novonordisk-trials.com, the Novo Nordisk online repository for clinical trials activities. Information on Novo Nordisk trials are also available via the EU Clinical Trials Register managed by the European Medicines Agency (EMA) and other national registries when required by local regulations. Collated information about other ethical issues related to Novo Nordisk research and development are available at http://www.novonordisk.com/science/bioethics
Novo Nordisk sponsors clinical research globally either in the form of interventional clinical trials or as non-interventional studies.
Interventional clinical trials are important steps in the research and development process to obtain market authorisation. A potential new medicine’s ability to treat a condition, its safety and its possible side effects must be assessed in controlled experimental settings involving both healthy volunteers and patients. After a marketing authorisation has been granted, Novo Nordisk may sponsor additional interventional clinical trials to investigate and document the safety and efficacy of new indications for a given medication or to support changes in the use of the medication in the approved indication. Authorities may also require additional interventional trials after market authorisation to further investigate and document the long-term safety of a product.
After marketing authorisation of a product Novo Nordisk may undertake a non-interventional study programme to gain further evidence on the use of the medicine in daily clinical practice. This may be done by collecting data on health care outcomes in a “real life” setting. These studies include registry studies and patient/healthcare provider surveys. Non-interventional studies are often conducted in collaboration with general practitioners and constitute an important step in collecting information on adverse events in clinical use of a given drug.
At any time pre- or post-approval of a product Novo Nordisk may further sponsor non-interventional epidemiological type studies to gain a better understanding of a disease, disease management, quality of life, health economics or other non-product related issues.
Novo Nordisk will ensure proper scientific principles and methods and statistical, regulatory and ethical principles will be applied in all our clinical research. For example, Novo Nordisk ensures a proper selection of patients, minimisation of the risk/benefit ratio for the volunteers, proper informed consent procedures, and independent ethical review of study protocols.
A set of ethical principles outlined in the Declaration of Helsinki (and its subsequent amendments) developed by the World Medical Association provides guidance to physicians and other participants in medical research involving human subjects. The declaration - together with other international guidelines, including the Nuremberg Code and international guidelines for GCP - serves as the primary point of reference when Novo Nordisk sponsors clinical research. This is reflected in Novo Nordisk’s global clinical research principles included in our SOPs and ensures due respect for the safety, rights, integrity, confidentiality and well-being of all people participating in Novo Nordisk-sponsored clinical research worldwide.
Novo Nordisk is committed to sharing knowledge and being transparent and the company communicates the results of clinical trials, regardless of outcome, through the publication of papers in scientific journals, abstract submissions at scientific meetings, on external websites or by other means.
Novo Nordisk’s clinical research governance system
Novo Nordisk has a governance structure in place which ensures that current and new regulations, directives and external guidelines are adhered to and that all clinical research activities are approved by both medically qualified staff and senior management.
- All new external guidelines are reviewed and implemented into SOPs as required.
- No clinical research activity in people will take place before approval by the Novo Nordisk Safety Committee, where all preclinical findings are assessed and reviewed.
- All Clinical Development Plans are reviewed and approved by an internal international challenge board with competencies within the therapy area.
- All protocols and amendments are approved by a review committee with representatives from the involved functions within the company.
- Novo Nordisk only permits research activities to take place in countries that can fulfil internal (resources, competencies and existence of an appropriate quality system) and external (regulatory and infrastructure) requirements.
- Feasibility and patient allocation are decided by an international group who must ensure that patient recruitment only happens in countries that can - and do - meet the above necessary requirements.
- All studies are monitored frequently by trained personnel with documented competencies and according to the same standards everywhere.
- Safety committees are established for all Novo Nordisk clinical research activities to follow up and take immediate action if needed on any safety aspects of our research activities.
- A cross-functional review committee approves all study reports.
- All research activities may be audited by the internal Clinical Quality Assurance function.
External clinical research governance system
- All protocols include information about informed consents and payments to investigators and must be approved by an IEC or an IRB, as applicable and Regulatory Authorities.
- In all trials both sponsor and trial sites can be audited at random by local health authorities and local ethics committees to ensure that regulations, GCP and protocols are adhered to.
- Novo Nordisk Global Development is certified according to the International Organization for Standardization (ISO) quality standard and accordingly audited on a regular basis.
For further reading about our approach to clinical trials please see our brochure ‘A responsible approach to clinical trials’.
References
1. Declaration of Helsinki
2. Nuremberg Code
3. ICH GCP
Updated 6 August 2011
