Glossary

Part of the US National Institutes of Health. http://www.cancer.gov/"

A National Competent Authority “ or regulatory authority “ has the power to grant marketing authorisations for medicinal products in its territory.

National competent authorities are organisations that have the legally delegated or invested authority, or power to perform a designated function, normally monitoring compliance with the national statutes and regulations.

British health care system. http://www.nhs.uk/"

Part of the US National Institutes of Health. https://www.genome.gov/"

British agency for standardisation and control of biological medicines. http://www.nibsc.org/"

US medical research agency. http://www.nih.gov/"

Independent national procedures are strictly limited to medicines which are to be authorised and marketed in only one Member State (MS). This procedure is nowadays rarely followed for new products.

National Research Ethics Service

A New Drug Application (NDA) is a document submitted to the Food and Drug Administration (FDA) to request authorisation to market a medical product in the United States. The information in the NDA must allow the FDA to make the following judgements (quoted from FDA website):

- 'Whether the drug is safe and effective in its proposed use(s), and whether the benefits of the drug outweigh the risks
- Whether the drug's proposed labelling (package insert) is appropriate, and what it should contain.
- Whether the methods used in manufacturing the drug and the controls used to maintain the drug's quality are adequate to preserve the drug's identity, strength, quality, and purity.'

The NDA must include information about the medicine's ingredients, outcomes of the animal and clinical studies, how it behaves in the body, and how it is manufactured and packaged.

New Molecular Entities (NMEs) are compounds that emerge from the process of medicine discovery, that are not a version or derivative of an existing, previously investigated/approved substance. They have promising activity against a particular target thought to be important in a disease, however, little is known about the efficacy, safety, toxicity, pharmacokinetics and metabolism in humans. A full development programme of non-clinical and clinical trials must be performed to evaluate the potential of an NCE to become a medicinal product.

Next Generation Sequencing

The no observed adverse effect level (NOAEL) is the highest tested dose of a medicine at which there is no increase in the frequency of any adverse effects (biological or statistically significant) when compared to its control.

Although the NOAEL approach involves some consideration of pharmacokinetics and pharmacodynamics properties, its focus is on the estimation of the highest ˜safe™ dose, looking for a safety window based on toxicological threshold.

Non-clinical testing is conducted at a stage of medicines development that uses animals and/or cells or tissues. It does not involve testing in humans. The main goal of non-clinical tests is to determine the safety of a medicine. Non-clinical testing will investigate any harmful effects of the medicine on the body due to the medicine's pharmacology, such as:

• 
  
• Toxic effects - for example, on the reproductive system
  
• If the medicine causes genetic changes
  
• For some substances, whether they might cause cancerous growth.
  

Toxicity will be measured in relation to different doses, or length of use of the medicine. The reversibility of any toxicity will also be studied.

Information from non-clinical testing is used in planning clinical trials in humans. It is used to decide what the starting dose should be, and the range of does to be tested. It also suggests what clinical signs should be looked for in order to detect any adverse effects.

Non-Governmental Organisation

In epidemiology and statistics, an observational study draws conclusions about the possible effect of a treatment on participants, where the assignment of participants into a treatment group versus a control group is outside the control of the investigator. In a non-interventional observational study, no additional diagnostic or monitoring procedures are applied to the patients, and epidemiological methods are used for the analysis of collected data (as per Article 2(c) of 2001/20/EC). It is not a randomised, controlled trial (RCT).

However, in some cases, observational studies are the most appropriate design “ for example, if the condition being studied is rare. Sometimes non-interventional studies are the only ethical approach, for example if the effect of an environmental risk factor such as asbestos is being studied, it would be unethical to deliberately expose participants to asbestos.

There are three types of non-interventional study, which are defined separately in this glossary. They are:

• 
  
• Cohort studies
  
• Cross-sectional studies
  
• Case-control studies
  

Non-maleficence means to do no harm. Traditionally, this is at the heart of medical ethics and is part of the Hippocratic Oath (an oath that new doctors take in many countries). An example of a non-maleficent action would be stopping a medication known to be harmful or refusing to give a medication to a patient if it has not been proven to be effective.

However, ethical dilemmas often occur. In many medical situations, non-maleficence must be balanced with the principle of beneficence (an action done for the benefit of others). For example, many beneficial medications may also have serious side effects and so the risks and benefits must be carefully considered by doctors and patients. Ultimately, the patient must decide whether the benefits outweigh the risks before consenting to a treatment.

In a non-randomised clinical trial, participants are allocated to different treatment (or placebo) arms using a non-random method. Allocation is decided and managed by the investigator. Non-random allocation can lead to bias in the results of a trial.

In the description above, the non-randomised trial is controlled (arms receiving an intervention are compared with arms that are receiving different interventions or placebo). There are several other trial designs that are non-random, but controlled. These include prospective observational studies.

Norwegian National Competent Authority. http://www.legemiddelverket.no"

The word ˜null™ can be thought of as ˜no change™. A null hypothesis is typically the standard assumption and is defined as the prediction that there is no interaction between variables.

For example, the null hypothesis states that there is no causal relationship between a new treatment and a reduction in disease symptoms. In other words, this means that a new treatment does not offer an improvement over the standard of care treatment “ and that any observations of improvement are the result of chance.

Such a statement can be tested by a scientific study such as a clinical trial and the application of appropriate statistical tests. If a clinical trial finds that in fact there is a relationship, and the new treatment causes an improvement, the null hypothesis is disproved and can be rejected. In this case the alternative or research hypothesis can be adopted “ in this example, this means that the new treatment is better than the standard of care treatment.

The number-needed-to-treat (NNT) is a measure used to describe the effectiveness of an intervention, such as treatment with a medicine.

The NNT is the number of participants who will need to be treated in order for one person to recover, or show symptom reduction, or whatever outcome is being measured in the trial. A 'perfect' result would be that every patient has a good outcome, and this would give an NNT of 1 . A large NNT means that the treatment is only effective in a small number of people: An NNT of 100 means that of 100 people treated, only 1 will have a favourable outcome.

One advantage of NNTs is that they can be easily compared for different medicines or interventions.