There are several key steps in translational medicine. Note, however, that there is no single “starting point” or “ending point”: translational medicine is a “circular” process, in that the treatment step often leads to repeated donation of biospecimens by patients, which in turn drives further research discoveries.

1. Definition of a hypothesis by a clinical researcher, such as the concept that patients with a particular genetic variation are likely to respond positively to certain medicines
• Clinical testing of a new approach, such as an experimental drug, in that sub-set of patients
• The discovery of a new insight, such as which genetic variation correlates with positive response to a drug, or which sub-groups of patients will suffer metastasis of disease following surgery
• Development of an approach to identify prospectively the patients that are predisposed to a disease, or to diagnose those patients early enough to be treated
2. Recruitment of patients to join the study, perhaps involving patients at all stages of the disease
• Collection of blood and solid tissue from patients who consent to participate
• Molecular profiling of patient biospecimens
• Identification of molecular signatures or “biomarkers”
3. Enrollment of additional patients to screen for the putative biomarker on a prospective basis to clinically validate the accuracy of the approach
4. Development of a molecular diagnostic test, based on the validated biomarker, that is economically and technically feasible for use in the clinical setting
5. Use of the biomarker by a drug innovator for the discovery and development of a new treatment
6. Implementation of pre-clinical studies of the drug (known as “ADME-tox”, for Absorption, Distribution, Metabolism, Excretion, and toxicity)
7. Implementation of “Phase 0” clinical trials, in which small numbers of patients are administered the drug
8. Collection and study of biospecimens from patients treated with the new drug, to assess biological activity

The research and clinical care process has changed in very fundamental ways in recent years. For example, the process of Translational Medicine involves many more people than traditionally were involved in clinical trials, both for the discovery steps and the clinical testing. Translational Medicine also provides an opportunity for patients to become involved in discovery science, and to do so in real time as discoveries are made. It also demands a willingness on the part of patients to participate in all aspects of research through clinical care – even when the enrollment process in clinical trials is uncertain due to molecular sub-grouping – reflecting the “patient-centric” nature of the translational process.