CLINICAL TRIALS DDD Mid Start
CLINICAL TRIALS DDD Mid Start
on human participants are designed to answer specific questions about biomedical or behavioral
interventions, including new treatments (such as novel vaccines, drugs, dietary choices, dietary
supplements, and medical devices) and known interventions that warrant further study and comparison
they are conducted only after they have received health authority/ethics committee approval in
the country where approval of the therapy is sought
these authorities are responsible for vetting the risk/benefit ratio of the trial—their approval
does not mean the therapy is 'safe' or effective, only that the trial may be conducted
depending on product type and development stage, investigators initially enroll volunteers or
patients into small pilot studies, and subsequently conduct progressively larger scale
comparative studies
Clinical trials can vary in size and cost, and they can involve a single research center or multiple
centers, in one country or in multiple countries
Clinical study design aims to ensure the scientific validity and reproducibility of the results
Costs for clinical trials can range into the billions of dollars per approved drug
certain functions necessary to the trial, such as monitoring and lab work, may be managed by
an outsourced partner, such as a contract research organization or a central laboratory
only 10 percent of all drugs started in human clinical trials become approved drugs
some clinical trials involve healthy subjects with no pre-existing medical conditions
other clinical trials pertain to people with specific health conditions who are willing to try an
experimental treatment
Pilot experiments are conducted to gain insights for design of the clinical trial to follow
there are two goals to testing medical treatments: to learn whether they work well enough,
called "efficacy" or "effectiveness"; and to learn whether they are safe enough, called "safety“
neither is an absolute criterion; both safety and efficacy are evaluated relative to how the
treatment is intended to be used, what other treatments are available, and the severity of the
disease or condition
Examples of clinical trial goals include assessing the safety and relative effectiveness of a
medication or device:
Clinical trials are classified by the research objective created by the investigators
• observational study
• interventional study
or other intervention to compare the treated subjects with those receiving no treatment or the
standard treatment
sponsor, the U.S. Food and Drug Administration (FDA) organizes and monitors the results of trials
according to type:
• Prevention trials
look for ways to prevent disease in people who have never had the disease or to prevent a
disease from returning
• Diagnostic trials
• Treatment trials
test experimental drugs, new combinations of drugs, or new approaches to surgery or radiation
therapy
evaluate how to improve comfort and quality of care for people with a chronic illness
• Genetic trials
are conducted to assess the prediction accuracy of genetic disorders making a person more or
less likely to develop a disease
• Epidemiological trials
have the goal of identifying the general causes, patterns or control of diseases in large numbers
of people
provide partially tested, unapproved therapeutics to a small number of patients who have no
other realistic options
usually, this involves a disease for which no effective therapy has been approved, or a patient
who has already failed all standard treatments and whose health is too compromised to qualify
for participation in randomized clinical trials
usually, case-by-case approval must be granted by both the FDA and the pharmaceutical
company for such exceptions
• Fixed trials
consider existing data only during the trial's design, do not modify the trial after it begins, and
do not assess the results until the study is completed
use existing data to design the trial, and then use interim results to modify the trial as it
proceeds
Modifications include dosage, sample size, drug undergoing trial, patient selection criteria and
"cocktail" mix
Adaptive trials often employ a Bayesian experimental design to
in some cases, trials have become an ongoing process that regularly adds and drops therapies
and patient groups as more information is gained
the aim is to more quickly identify drugs that have a therapeutic effect and to zero in on patient
populations for whom the drug is appropriate
when a drug reaches this point, the entity submits an application to get the consent of the Food
and Drug Administration (FDA) to begin these trials
this step is important as approval for the application allows a sponsor to ship
KEY TAKEAWAYS
an Investigational New Drug is a drug developed by a sponsor that is ready for clinical trials on
humans
IND application is submitted by the company or research group responsible for developing the
drug to the FDA
FDA reviews IND applications and decides whether they are safe for companies to progress to
the clinical trial stage
when a company develops a new drug, it must get approval from the FDA
It's up to the company—which is also called the drug sponsor—to run the required tests, gather
data, and to make sure patients aren't exposed to unnecessary risks when they take the drug
the FDA reviews the results after each phase and makes a determination of whether the drug is
safe for the public
One of the application steps is the Investigational New Drug (IND) stage
this exemption is a requirement since, in most cases, the sponsor must ship an investigational
drug to investigators in other states
to obtain the exemption, the sponsor must submit sufficient data through the IND,
documenting the safety of the drug for use in human testing
companies need to collect enough data from preclinical studies to establish whether the drug is
reasonably safe for initial tests in humans, as well as any previous experience involving human
use of the drug such as any usage in foreign markets
this step involves testing on animals to determine the drug's safety and its efficacy
Manufacturer Information:
Information needs to be included about the manufacturer to ensure that the company can
manufacture sufficient batches of the drug and has the proper controls in place to do so safely
detailed protocols are needed to determine if the initial trials will expose human subjects to
needless risks
this also includes qualifications of the clinical investigators who will oversee the administration
of the compound
IND is submitted after the sponsor determines that the proposed drug is reasonably safe for
initial use in humans and that it shows sufficient promise as a treatment to justify commercial
development
FDA reviews the IND application and decides whether it is safe for the
this is the clinical trial stage—the point at which the drug is tested on humans
the sponsor has to wait for 30 calendar days after submitting the IND before commencing any
clinical trials
IND application signifies that the sponsor is willing to make this huge investment
as such, investor reaction to an IND application—which is merely the first step in a long and
arduous process for drug approval—is typically neutral
Investor reaction to INDs tends to be neutral because it's just one step in the arduous process
to get approval for a drug
Investigational New Drugs (INDs) fall into two categories—commercial and research INDs
the big difference between these two categories is who does the application filing
as the name suggests, the commercial IND category is sought by a company that wants to test a
drug in order to bring it to market
any company can apply for this IND, whether it's a large pharma or biotech company, as well as
a nonprofit organization (NPO) such as a cancer research group
the application process for a commercial IND can be fairly lengthy and complicated
Commercial INDs are filed by companies to obtain marketing approval for a new drug
the research or non-commercial IND is the step investigators require to run tests on an existing
drug
researchers require approval when they want to test approved drugs that are already on the
market
testing may include new dosages or new applications for these drugs
the majority of INDs are filed for non-commercial research and are of three main types—
Investigator IND, Emergency Use IND, and Treatment IND
also called compassionate use or single-patient INDs, are filed for emergency
use of an unapproved drug when the clinical situation does not allow sufficient time to
submit an IND in accordance with 21 CFR
Treatment INDs
are filed to make a drug available for treatment of serious or immediately life-threatening
conditions prior to FDA approval
serious diseases or conditions are stroke, schizophrenia, rheumatoid arthritis, osteoarthritis,
chronic depression, seizures, Alzheimer's dementia, amyotrophic lateral sclerosis (ALS), and
narcolepsy.
Screening INDs
used for screening different salts, esters and other drug derivatives that are chemically
different, but pharmacodynamically similar
the application process is generally simpler than that of a commercial IND because testing is
normally done by a smaller group of people and in one location
United States Food and Drug Administration's Investigational New Drug (IND) program is the
means by which a pharmaceutical company obtains permission to start human clinical trials and
to ship an experimental drug across state lines (usually to clinical investigators) before a
marketing application for the drug has been approved
Regulations are primarily similar procedures followed in the European Union, Japan, and
Canada
1) Preclinical testing
also included are any previous experience with the drug in humans