Definition of biomarkers and efficacy end-points

1. Introduction

1.1. Aims of biomarker use

Biomarkers can be used to measure:

  • Normal biological (physiological) processes in the body.
  • Pathological (disease) processes in the body.
  • A person’s response to a treatment or a medicine.

The two main goals of biomarkers in medicines development are:

  • To streamline medicines development. In a clinical study, researchers want to directly measure the patient’s response to a treatment. But when this is not directly possible, biomarkers may offer another way to measure an outcome (a so-called surrogate endpoint). Biomarkers can also help select which patients are most suited to take part in a clinical study.
  • To tailor treatment to individual patients. Biomarkers help researchers improve how to predict a person’s risk of disease, how a disease might progress once it is diagnosed, and how an individual will respond to a medicine. Also, healthcare professionals are beginning to use biomarkers to make decisions on safer and more effective treatment. (1)

There are many established biomarkers that are known to have clinical use. That is, they are proven to give reliable measures of underlying biological processes. Therefore, their use in medicines development is well accepted. For example, a clinical endpoint in a clinical trial (such as relief of symptoms, survival, or disappearance of a tumour) can in some cases be replaced with an established biomarker. This is known as a surrogate endpoint. For the medicine to receive a marketing authorisation, there must be good evidence that the biomarker used is a valid substitute for the clinical endpoint.

Examples of established biomarkers:

  • Glucose levels in a patient’s blood (blood sugar level) can be used to monitor if an individual patient is responding to diabetes treatment. Uncontrolled glucose levels are one of the major problems in diabetes patients who are not treated properly. 
  • Magnetic resonance imaging (MRI) of a patient’s brain can help assess disease status in multiple sclerosis. This might be monitored instead of clinical disease progression, or the patient experiencing relapses.

In addition, many new exploratory biomarkers are being discovered and used during the development of new medicines. Many of these use so-called ‘omics’ technologies: genomics, proteomics and metabolomics:

  • Genomics is a branch of genetics. It applies various methods to sequence, assemble, and analyse the function and structure of genomes.
  • Proteomics is the large-scale study of proteins, particularly their structures and functions and quantity. Proteins are vital parts of living organisms, as they are the main components of the metabolic pathways of cells.
  • Metabolomics is the scientific study of chemical processes that involve ‘metabolites’. Metabolites are small molecules which are left behind after a chemical process has taken place in a cell. In other words, they are the ‘product’ of the process.
  • Pharmacogenetics or pharmacogenomics specifically use genetic or genomic information (i.e. genetic or genomic biomarkers) in the development and use of medicines.

(1) Industry Pharmacogenomics Working Group (I-PWG). Understanding the Intent, Scope, and Public Health Benefits of Exploratory Biomarker Research.  A Guide for IRBs/IECs and Investigational Site Staff.