One of the key elements in gaining approval of a drug by the US Food and Drug Administration (FDA) involves clinical research. There are two primary avenues of such research: clinical trials and observational studies. The latter involves monitoring subjects within normal settings, with data gathered over time and health changes evaluated and compared with others in the group.

1. Clinical Studies -
Foundational to the
Drug Approval Process

2. One of the key elements in gaining approval of a drug by the US Food and
Drug Administration (FDA) involves clinical research. There are two primary
avenues of such research: clinical trials and observational studies. The latter
involves monitoring subjects within normal settings, with data gathered over
time and health changes evaluated and compared with others in the group.
For example, researchers might ask older adults to monitor their eating
habits over a year and deliver memory tests every month to explore how
cognitive health and diet intersect.

3. While observational studies do not focus on
medical interventions (whether a device or
drug), they often provide insights that lead to
new prevention and treatment approaches,
which are then studied in clinical trial settings.
Clinical trials focus on a specific drug, device,
or behavioral or surgical intervention and
ascertain whether it is safe and effective.
Such trials involve volunteers and use existing
treatments as a comparison point. They begin
with a discovery process involving
researchers learning about the targeted
disease and proposing a novel treatment
pathway.

4. In the case of a drug, a classical process defines drug development. It starts
with identifying the specific molecular target associated with the disease and
screening chemical compounds from a library to identify potential
candidates. When a promising compound is found, it's optimized in the
laboratory.
Two major criteria must be met: the drug must block the molecular target
effectively without impacting non-target cells, and it must be absorbable and
transportable via blood in acting upon affected organs. When the drug
candidate fulfills these benchmarks, it’s ready for safety and efficacy testing,
initially on animals and then on people through clinical trials.

5. The plan that guides clinical trials is known as a protocol and covers elements such
as the type of patients used in the study, the schedule of tests and procedures, and
the drug involved. The amount of drug administered, or dosage, is also defined, along
with the length of study and makeup of the cohort (including those administered
placebos). Study participants must sign off on the protocol, agreeing to abide by its
rules throughout the trial.
There are three phases of clinical trials, with Phase I trials used to generate
preliminary safety data and determine the optimal dosage. Phase II trials focus on
safety, as well as efficacy (as with the earlier animal studies), while Phase III trials
use a larger cohort of people in continuing to test drug efficacy and safety.

6. Following a successful Phase III trial, the
vaccine or drug is readied for submission
to the FDA for further review and potential
approval. In the case of drugs treating
complex and rare diseases such as
cancer, the full approval process often
takes between six and 12 years. While two
years may be the norm for each phase,
this is often extended in rare diseases, as
it’s challenging to find enough patients to
participate.

7. Only 10 percent of drug candidates make it from clinical trial testing to FDA
regulatory approval. As many as half of failures are due to unmet clinical
efficacy thresholds, with patients not receiving the intended effect. Another
30 percent of failures have to do with drug side effects or toxicity that
proves unmanageable, while 10 to 15 percent have to do with suboptimal
pharmacokinetic properties (issues with how the drug is absorbed and
excreted by the body). The remaining 10 percent of failures are strategic
planning deficiencies and a general lack of commercial applicability.