Human tissue samples are commonly thought of as the “bridge” between molecular and clinical studies, and as such serve a critical role in helping to understand the origins of disease and the pathways to intervention.

Among the studies that require human samples are biomarker or “molecular signature” studies, pre-clinical studies of drug candidates, and categorizing of patients and healthy volunteers into clinical trials:

Molecular signature studies

In such studies, researchers profile biospecimens in order to understand how disease can be differentiated at the biochemical level. Such sub-groups of disease are based on a molecular “signature” rather than on visible clinical appearance. Researchers can then associate that signature with how patients respond to various treatments, so that a predictive profile can be developed.

Pre-clinical studies of new drug candidates

As part of the drug innovation process, researchers need to know as much as possible about a drug candidate’s biological activity prior to full-scale human clinical trials of safety and efficacy that are required for regulatory approval.

For example, a patient with suspected disease may undergo a biopsy, and a small sample of the removed tissue may be frozen for future assessment. That patient, if diagnosed with cancer, may be treated with a drug candidate. The drug therefore has the opportunity to have a certain biochemical effect. After the patient undergoes surgery, another tissue sample may be obtained from the removed tumor. That tissue can then be examined and compared with the original tissue from the biopsy to assess whether the drug had the desired effect at the biochemical level, well before such an effect would be detectable at the visible clinical level.

Such preliminary pre-clinical tests are known as “Phase 0”, in contrast with the traditional Phase I, II, and III stages of clinical development of new pharmaceuticals.

Patient categorization for clinical trials

Some clinical trials of new drugs start with a previously identified biomarker, such as Her-2-neu or EGFR, and only enroll patients who test positive for that biomarker. However, it is now becoming feasible to initiate a trial of a new drug, and to seek a biomarker associated with a positive response during the trial itself. Once such a marker is found, it can be used as an entry criterion for additional patients, in essence constituting a “real-time” system for targeting the right drug to the right patient.

Enhancing drug safety

It has been determined that certain genetic characteristics may predispose individuals for adverse drug effects, either because they metabolize drugs too rapidly or not rapidly enough. It would be very helpful, therefore, to have a system that could prevent unnecessary suffering or even accidental death from drugs, by screening out those patients who are unlikely to benefit or are likely to be harmed.

Studies using human tissue samples – in the process described above for identifying markers and applying them in clinical trials – may serve to avoid drug recalls due to safety issues, or to “rescue” drugs that were abandoned prior to clinical trial completion and regulatory submission because they were shown to be unsafe in a small percentage of those tested.