CISN - Drug Development - Review of Bench-to-Bedside Research

Review of Bench-to-Bedside Research

We have already discussed in extensive detail what happens in each stage of the bench-to-bedside continuum in previous sections of this website. Below is a short review to help tie the three stages together.

Basic Research

Translational or Preclinical Research

Clinical Research

Basic Research

Basic research is designed to obtain or increase general fundamental scientific knowledge without needing to develop a direct application intended to solve a specific problem. Basic research establishes the foundation for subsequent research.

Basic researchers in cancer do not focus on finding a new treatment or developing a new drug.

Instead, they try to understand what makes cancer cells different from normal cells.

Scientists who conduct basic research observe and examine the various intracellular and extracellular processes that lead to the development of cancer in order to discover what goes wrong when cancer develops.

Sometimes during this basic process someone discovers a promising molecule or gene target or a promising biomarker. This information is then provided to their translational colleagues (either in academia or industry) for further research and possible testing.

Translational or Preclinical Research

The promising discoveries made in basic research, then move into the translational research arena. Work continues to be conducted in the labs in order to evaluate drugs for the treatment of cancer using different types of experiments.

The first category of study conducted in preclinical research includes tests using cell lines and/or cell cultures contained in petri dishes and test tubes
(in vitro, which literally means "in glass").

If a drug appears to be active against cancer, the second category of study involves testing in animals (in vivo) to collect information about the activity of the drug (pharmocodynamic testing), as well as absorption, distribution, excretion (pharmacokinetic testing) and toxicity.

Important Questions in Translational Research

1. What is the cost for basic and preclinical research?

Approximately 500 million dollars are spent on average for every successful new drug.

2. How long does the entire process take?

It can take up to one decade or longer.

3. How does drug development move out of the laboratory into the clinical setting?

An Investigational New Drug (IND) Application must be filed with the FDA prior to beginning treatment of cancer patients with the new drug: the drug then enters clinical trials. (We will cover this later)

Clinical Research

Once researchers file an IND, they can begin testing the compound in Phase I, II, and III clinical trials. Sometimes Phase IV trials are conducted. More detailed information about clinical trials is located in the CISN Clinical Research Section. We recommend that you read this to better under stand both the vocabulary used below and the clinical trial process itself.

Phase I Trials

Conduct safety assessment and identification of potential adverse events
Identify which dose is safe
Establish how the drug should be given - by mouth or injected into the blood or muscle
Pharmacology

Phase II Trials

Clinical activity assessed - is the drug effective?
Further safety testing
Finalize dose to be used for Phase III trials

Phase III Trials

Randomized comparative trials
Assess efficacy compared to standard of care
Further assess safety
Confirm effective dose

The chart below shows the bench-to-bedside process

Important Questions in Clinical Research

1. What is the cost for clinical research?

About half a billion dollars

2. How long does it take to develop a new drug and bring it to market?

Up to fifteen years

3. How do cancer drugs become available to the public?

All of the information from the clinical trials is presented to the FDA in a New Drug Application (NDA). (This will be covered later in this section)