Clinical trials

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ANALIGHT My Notes 27-Sep-15
26-Sep-2015
Composed by : G Rama Kumar Reddy
MY NOTES
Research Public Health

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Clinical trials are research studies that explore whether a medical strategy, treatment, or device is
safe and effective for humans. These studies also may show which medical approaches work best for certain
illnesses or groups of people. Clinical trials produce the best data available for health care decision making.
The World Health Organization (WHO) definition for a clinical trial is :
"Any research study that prospectively assigns human participants or groups of humans to one or more
health related interventions to evaluate the effects on health outcome."
A clinical study involves research using human volunteers (also called participants) that is intended to add to
medical knowledge. In a clinical trial, participants receive specific interventions according to the research plan
or protocol created by the investigators. These interventions may be medical products, such as drugs or de-
vices; procedures; or changes to participants' behavior, such as diet. Clinical trials may compare a new medi-
cal approach to a standard one that is already available, to a placebo that contains no active ingredients, or to
no intervention. Some clinical trials compare interventions that are already available to each other.
Pre-clinical studies
Clinical trials are one of the final stages of a long and careful research process. The process often begins in a
laboratory (lab), where scientists first develop and test new ideas. Clinical trials are done only after pre-
clinical studies suggest that the proposed treatment is likely to be safe and will work in people. Pre-clinical
studies, also called laboratory studies, include:
Cell studies: These are often the first tests done on a new treatment. To see if it might work, researchers look
for effects of the new treatment on cancer cells that are grown in a lab dish or a test tube. These studies may
be done on human cancer cells or animal cancer cells.
Animal studies: Treatments that look promising in cell studies are tested next on cancers in live animals. This
gives researchers an idea of how safe the new treatment is in a living creature.
Pre-clinical studies give a lot of useful information, but they don’t give all the answers that are needed. After
all, humans and mice can be very different in the way they absorb, process, and get rid of substances. A treat-
ment that works against cancer in a mouse may or may not work in people. And there could be side effects
and other problems that didn’t show up when the treatment was used in mice.
If the pre-clinical studies are completed and the treatment still seems promising, the U.S. Food and Drug Ad-
ministration (FDA) must give permission to test it in humans.

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The investigational new drug (IND) application
Before a clinical trial can be started, the research must be approved. An investigational new drug or IND appli-
cation orrequest must be filed with the FDA when researchers want to study a drug in humans. The IND appli-
cation must contain certain information, as described below. The FDA reviews this information before human
clinical trials start. Here’s some of the information required on an IND request:
Pre-clinical studies: Results from studies, including those on animals, allow the FDA to decide whether the
product is reasonably safe for testing in humans. This part may also include any experience with the drug in
humans (if the drug has been used or studied in another country, for example).
Manufacturing information: This explains how the drug is made, who makes it, what’s in it, how stable it is,
and more about the physical qualities of the drug. The FDA uses this information to decide whether the com-
pany can make batches of the drug that will always be exactly the same.
Clinical protocols and investigator information: Detailed outlines for the planned clinical studies, called study
protocols, are looked at to see if the study might expose subjects to unnecessary risks. Information on the clini-
cal investigators who will supervise the study is reviewed to find out if they’re qualified to run clinical trials.
Finally, the research sponsor must commit to getting informed consent from the research subjects, having the
study reviewed by an institutional review board (IRB), and following all the rules required for studying investi-
gational new drugs.
The FDA may ask for more information or even require that more studies be done. This can extend the approv-
al process to more than 5 years.
Based on its review, the FDA decides if the treatment is OK to be used in patients with the type of illness the
drug was tested on. If it is, the new treatment often becomes the standard of care, and newer drugs must
then be tested against it before being approved. But, in some cases, the clinical trials are still not over and
phase IV trials continue.
Phases of Clinical Trials
Clinical trials used in drug development are sometimes described by phase. These phases are defined by the
Food and Drug Administration (FDA).
PHASE 0:
Officially named at the FDA as an exploratory investigational new drug study and also known as a
“microdosing” study. Exploratory trials to establish whether the agent behaves in humans as was expected
from preclinical animal studies, to gather preliminary data on pharmacodynamics or pharmacokinetics, to
select promising lead candidates, or to explore biodistribution characteristics. Phase 0 studies do not re-
place formal Phase I drug safety testing and do not offer any possibility of patient benefit. Intended to
speed drug development as part of the FDA Critical Path Initiative by quickly weeding out ineffective drugs
early in the development process. (No therapeutic or diagnostic intent.)
PHASE I:
Initial studies to determine the metabolism and pharmacologic actions of the agent in humans, the side
effects associated with increasing doses, and to gain early evidence of effectiveness; may include healthy
participants and/or patients.
PHASE I/II (Device – Pilot):
Some trials combine Phase I and Phase II, and test both efficacy and toxicity (safety, dosage levels, and
response to new treatment).

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PHASE II:
Controlled clinical studies conducted to evaluate the effectiveness of the agent for a particular indication
or indications in patients with the disease or condition under study and to determine the common short-
term side effects and risks.
PHASE II/III:
Some trials combine Phase II and Phase III, and test for both efficacy and overall benefit-risk relation-
ship. The new treatment is compared to a standard treatment regimen.
PHASE III (Device – Pivotal):
Expanded controlled and uncontrolled trials after preliminary evidence suggesting effectiveness of the
agent/test article has been obtained and are intended to gather additional information to evaluate the
overall benefit-risk relationship and provide an adequate basis for physician labeling. Compares new
agent/test article against commonly used agents/test articles.
PHASE IV:
Post-marketing studies to delineate additional information including the agent’s risks, benefits, compara-
tive effectiveness, and optimal use. These studies are designed to monitor the effectiveness of the ap-
proved intervention in the general population and to collect information about any adverse effects associ-
ated with widespread use.
Importance of clinical trials
Doctors and other healthcare professionals and patients need evidence from clinical trials to know which
treatments work best. Without this evidence, there's a risk that people could be given treatments that have
no advantage, waste resources, and might even be harmful.
Clinical trials help to find out if:
 treatments are safe
 treatments have any side effects
 new treatments are better than the standard available treatments
Clinical trials show us what works (and what doesn’t) in medicine and health care. They are the best way to
learn what works best in treating diseases like cancer. Clinical trials are designed to answer 2 important ques-
tions:
 Does the new treatment work in humans?
 Is the new treatment safe?
Sponsors of Clinical Trials
Every clinical study is led by a principal investigator, who is often a medical doctor. Clinical studies also have a
research team that may include doctors, nurses, social workers, and other health care professionals.
Clinical studies can be sponsored, or funded, by pharmaceutical companies, academic medical centers, volun-
tary groups, and other organizations, in addition to Federal agencies such as the National Institutes of Health,
the U.S. Department of Defense, and the U.S. Department of Veterans Affairs. Physicians, health care provid-
ers, and other individuals can also sponsor clinical research.

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Location of Clinical Studies
Clinical studies can take place in many locations, including hospitals, universities, doctors' offices, and
community clinics. The location depends on who is conducting the study.
Participants in Clinical Studies
Clinical studies have standards outlining who can participate, called eligibility criteria, which are listed in the
protocol. Some research studies seek participants who have the illnesses or conditions that will be studied,
other studies are looking for healthy participants, and some studies are limited to a predetermined group of
people who are asked by researchers to enroll.
Eligibility : The factors that allow someone to participate in a clinical study are called inclusion criteria, and the
factors that disqualify someone from participating are called exclusion criteria. These are based on things such
as age, gender, the type and stage of a disease, previous treatment history, and other medical conditions.
Children (aged 18 and younger) get special protection as research subjects. Almost always, parents must give
legal consent for their child to take part in a clinical trial.
When researchers think that a trial's potential risks are greater than minimal, both parents must give permis-
sion for their child to enroll. Also, children aged 7 and older often must agree (assent) to take part in clinical
trials.
What To Expect During a Clinical Trial
During a clinical trial, doctors, nurses, social workers, and other health care providers might be part of volun-
teer's treatment team. They will monitor volunteer's health closely. volunteer may have more tests and medi-
cal exams than he would if he is not taking part in a clinical trial.
volunteer's treatment team also may ask him to do other tasks. For example, he may have to keep a log about
his health or fill out forms about how he feels.
Some people will need to travel or stay in hospitals to take part in clinical trials. For example, the National In-
stitutes of Health Clinical Center in Bethesda, Maryland, runs clinical trials. Many other clinical trials take place
in medical centers and doctors' offices around the country.
Last words
Clinical trials can offer benefits for many people suffering with cancer like diseases. These may include access
to newer or more treatment options, getting more involved medical care, and having a greater sense of con-
trol over one’s situation. But by their nature, clinical trials involve some possible risks and downsides, too, and
they may not be right for everyone. Volunteer’s decision on whether to look into or enter a clinical trial should
be based on a realistic understanding of the possible risks and benefits.

Clinical trials

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