Drug Discovery and Development Timeline
Figure 13: Drug Development: A Long, Difficult, and Complex Process. Drug targets and ideas for targets are identified in laboratory research in both
public and private laboratories during the pre-discovery phase of drug development (blue pre-discovery rectangle). In the early drug discovery phase,
chemical or biological agents are screened to identify the subset of molecules that effectively hit their targets (blue drug discovery rectangle); there may
be between 5 and 10,000 compounds during this stage yielding 250 that proceed to the next (blue preclinical rectangle). At this stage, these compounds
are subsequently screened for activity in disease-specific laboratory and animal models, which may yield only as few as 5 compounds that can be taken
into the clinic (olive clinical trial rectangle). At this stage, the company or companies bringing these molecules forward must get permission to test them
in humans. This is done via an investigational new drug application (IND) with the FDA; a successful IND allows the compound(s) to be tested in patients
on clinical trials (olive Phase 1, 2, and 3 rectangles). Clinical trials are multi-year assessments of the safety and efficacy of drugs, requiring increasing
amounts of patients as the trials proceed; see Molecularly Based Clinical Trials, and Figure 18. If a compound is successful for a given disease (indication),
then the company can file for a new drug application (NDA), at which time the FDA will review the application and either approve or reject the drug based
on the results of the clinical trials; in some cases, the FDA will require further testing before approval can be granted (green FDA review rectangles). If the
drug is granted approval, a market authorization is given, and the company can begin marketing and selling the drug (green FDA review rectangles), once
they have produced enough of the drug to meet patient demand (green scale-up rectangle). Once a drug is on the market, physicians and patients are
encouraged to report any adverse reactions so that they can be followed by the FDA and further investigation performed, if necessary; this is the post-marketing surveillance period, also known as pharmacovigilance (gold post-marketing surveillance rectangle). Adapted from www.phrma.org.
eliminate drug toxicity. Today’s advances in drug
development, clinical trial design, and treatment are the
result of our ability to identify the biomarkers associated
with the molecular subtypes of cancer and rationally design
drugs to precisely target them.
However, to fully realize the advantages of biomarkers in
research and care, the fundamental problems inherent in
turning discoveries into drugs that benefit patients must be
addressed. Typically, drug development is complex, high-risk, and time-consuming, and all too often new promising
agents never make it through to full development into the
clinic, becoming lost in a gap that some refer to as the
“valley of death.” This gap arises when promising
discoveries lack sufficient investment to develop them into
new FDA-approved therapeutics or diagnostics. Steps must
be taken to address this challenge.
One potentially effective way to bridge this gap would be to
increase pre-competitive collaboration among all sectors in
the field - academia, government, the biotechnology and
pharmaceutical industry, philanthropic organizations, and
patient advocacy groups - that are involved in the drug
development process. Other potentially synergistic, worthy
AACR Cancer Progress Report 2011
