Clinical trials
For many years Novo Nordisk has been incorporating ethical practices into the procedures that govern the way the company conducts clinical research.
An increasing need for new participants in clinical studies raises a number of ethical issues that Novo Nordisk must address now and in years to come. The company must also honour demands from health authorities for safety and transparency in the conduct of trials.
Performance 2006
Activities in 2006 include:
Trial registry
Novo Nordisk has disclosed information on clinical trials since 2005. The information on initiated trials and trial results (after launch of the trial product) is published in two publicly available registries. As of 2006, this includes 80 trial protocols from phase 2 to phase 4 clinical intervention trials. An additional 24 trial protocols are registered by independent researchers mentioning Novo Nordisk as a contributor to the trial. These are published on ClinicalTrials.gov. Information about 106 Novo Nordisk trials for marketed products is available at ClinicalStudyResults.org.
To improve the transparency of the information on our clinical trial programmes, we will make all information provided to the above two sites available in a more easily accessible form through our own clinical trials portal. In addition to trial results and protocols, the site will include information on clinical trial procedures and ethical standards. The portal will be accessible via novonordisk.com and is expected to go live during the first half of 2007.
A global Standard Operating Procedure (SOP) for registration of clinical trial results was approved in 2006. This will help ensure timely and consistent disclosure of information.
Recruitment of trial participants
In 2006 Novo Nordisk conducted clinical trials in 47 countries, including the US and Canada, Brazil, Argentina, Russia, China, India, Australia, Saudi Arabia, Turkey, Egypt, and most of the European nations. These activities, which include four ongoing phase 3 trial programmes, involved nearly 16,500 trial volunteers; this is almost twice the number of participants in 2005, and the need is expected to increase even further in the next couple of years. This need must be satisfied while still meeting high ethical standards for the recruitment of participants.
Making sure that potential trial participants are aware of potential risks and benefits before they consent to participate in a given trial is a prime consideration for Novo Nordisk.The company’s ongoing trials of NovoSeven® for the indications of trauma and intracerebral haemorrhage (ICH) pose special challenges in this area, because the medical condition of potential participants is often so critical that they are unable to give this consent. Novo Nordisk policy is to follow local laws and regulations for how such patients can be included in a trial.
Such procedures are often time-consuming, and we believe speed is of the essence in treating trauma and ICH patients with NovoSeven®. For this reason, Novo Nordisk has initiated discussions with the US Food and Drug Administration (FDA) on how waived consent procedures might be streamlined in the US, where regulations also vary from state to state.
In 2006 Novo Nordisk adopted a guideline for initiation of core trial activities in countries not on the current roster of participating nations. Among other things, the guideline stipulates that investigators must be experienced and trained in clinical trial activities, and ethical committees must be present and appropriately trained. Novo Nordisk staff must also be available to monitor the progress of all trials taking place.
Safety procedures
In 2006 a much-debated first human dose trial (not conducted by Novo Nordisk) in which six healthy volunteers nearly died as a result of a severe immunological reaction with multi-organ failure caused much self-examination in the pharmaceutical industry. Novo Nordisk initiated a thorough examination of its safety procedures in first human dose clinical trials, particularly in the biopharmaceutical area where new mechanisms involving the immunological system are targeted. No changes in these procedures have been deemed necessary, but we will always ensure complete documentation is available to show that relevant safety procedures have been followed.
Post-marketing studies
Studies involving products already on the market, also referred to as phase 4 trials, are becoming increasingly common; health authorities sometimes require so-called Post Marketing Surveillance (PMS) studies comparing the effects of one marketed product to another as part of a conditional approval. Another type of post-marketing activity is the Clinical Experience Programme (CEP), which examines the effects of a single product in large numbers of patients. Such studies, while not conducted according to clinical interventional protocols, can provide good epidemiological data, including information on rare side effects.
In 2006 Novo Nordisk conducted its largest-ever CEP programme, observing the effects of Levemir® in approximately 40,000 people with diabetes around the world, and work on another even larger CEP was begun. In light of the trend towards more observational studies of this kind, a global Standard Operating Procedure (SOP) was finalised at the end of 2006 to ensure uniform principles for how these studies are conducted.
Novo Nordisk’s approach
Novo Nordisk fully supports transparency of clinical trial results and is committed to a high ethical standard in all aspects of conducting clinical trials. For us, this is a matter of being respectful of the integrity of people participating in clinical trials.
Global ethical practices
Some of our clinical trials take place in the developing world. We recognise that clinical trials carried out in developing countries have prompted media debate over the ethical conduct of these trials. However, all persons enrolled in Novo Nordisk-sponsored trials are protected by the same rights, high ethical standards and regulations, regardless of whether they live in the developed or the developing world. The clinical trials that Novo Nordisk sponsors are conducted according to:
- The World Medical Association's Helsinki Declaration describing human rights for patients participating in clinical trials
- The Belmont Report, International Ethical Guidelines for Biomedical Research Involving Human Subjects
- The Nuremberg code, Directives for Human Experimentation
- The Council for International Organizations of Medical Sciences (CIOMS), (WHO’s International Ethical Guidelines for Biomedical Research Involving Human Subjects)
- The International Conference on Harmonisation (ICH) for current Good Clinical Practice (cGCP)
- Local regulatory guidelines
- Novo Nordisk's own internal Standard Operating Procedures
Other ways in which ethical conduct is assured before the start of any trial or procedure include:
- Approval by an external local ethical committee and local health authority
- Informed consent of all trial participants
Novo Nordisk personnel audit trial sites on a regular basis to ensure that these guidelines are met. Furthermore, all trials are randomly audited by external health authorities. We have never experienced critical findings in such audits.
The need for global trials
Novo Nordisk conducts clinical trials globally because it is necessary to test products in the populations where the product is going to be marketed. Indeed, the countries' regulatory authorities often require pharmaceutical companies to do this. Physicians in the developing countries also wish to take part in Novo Nordisk's trials, wanting to be involved in front-line research. The number of patients who are willing and suitable for involvement in clinical trials also requires an expansion of the countries involved in the global recruitment base. Novo Nordisk will apply the same procedures wherever we sponsor clinical trials. This means that all participants enrolled in Novo Nordisk trials are protected by the same rights, high ethical standards and regulations, irrespective of the location of the study.
Informed consent
Participants in Novo Nordisk-sponsored trials are informed verbally and in writing about the purpose of the trial and its potential risks and benefits. This information is given in the patient's native language, and the patient and the investigator must both sign an informed consent form. Novo Nordisk strives to ensure that literacy, poverty or cultural barriers do not prevent a person from fully understanding the issues involved in participating in a clinical trial. A trial participant can withdraw at any time without providing a reason.
We also do not conduct a trial unless the investigator or physician has the necessary competences. Investigators are paid for their time, and most often this money is paid into a research fund at the given hospital. GCP prohibits companies conducting clinical trials from paying patients directly for participation in a trial.
Off-label use
In 2006 there was much media debate about the use of NovoSeven® as a haemostatic agent for wounded British soldiers in Iraq despite the fact that clinical trials for the trauma indication are not yet complete. Novo Nordisk recognises that physicians have the option of prescribing this type of off-label usage; however, the company does not and cannot actively promote such use of its products.
This page has been assessed by PricewaterhouseCoopers as part of its assessment of Novo Nordisk’s statement that it reports ‘in accordance’ with GRI. Please refer to Audit and assurance for a full description of the nature of assurance offered.
