Download Evolution of a New Medication

Evolution of a New
Medication
So you have an idea for a new
drug that could help people….
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It is not as simple as manufacturing,
putting it a bottle and sitting on the
shelf.
The procedure is complicated, time
consuming and expensive.
The Pharmaceutical Industry is BIG
Business.
Many people spend a large portion of
their income on medications each month
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Americans will spend $100 billion on
prescription drugs this year, double what
they spent six years ago.
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Under current law, all new drugs need
proof that they are effective, as well as
safe, before they can be approved for
marketing.
But it's important to realize that no drug
is absolutely safe.
There is always some risk of an adverse
reaction.
It's when the benefits outweigh the risks
that the Food and Drug Administration
considers a drug safe enough to approve.
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In fact, it was little more than 30 years
ago that U.S. drug law first embraced
the idea of risk vs. benefit that is now the
key to new drug approval.
Providing evidence of safety before
marketing was first required by the
Federal Food, Drug, and Cosmetic
(FDC) Act in 1938, but not until the
Kefauver-Harris Drug Amendments of
1962 did firms also have to show a
drug's effectiveness before marketing.
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FDA's decision whether to approve a
new drug for marketing boils down to
two questions:
Do the results of well-controlled studies
provide substantial evidence of
effectiveness?
Do the results show the product is safe
under the conditions of use in the
proposed labeling?
Safe, in this context, means that the
benefits of the drug appear to outweigh
its risks.
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The process starts with a drug sponsor,
usually a pharmaceutical company, seeking
to develop a new drug it hopes will find a
useful and profitable place in the market.
Before clinical testing begins, researchers
analyze the drug's main physical and
chemical properties in the laboratory and
study its pharmacologic and toxic effects in
laboratory animals.
If the laboratory and animal study results
show promise, the sponsor can apply to
FDA to begin testing in people.
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It is a mistake to rely on the assumption that
the patient would not have become well in
the absence of intervention.
Pasteur’s rabies vaccine did not require a
controlled trial because the antecedent was
unmistakable (being bitten by a rabid
animal) and the disease was invariably fatal.
Survival demonstrated the treatment’s
efficacy because neither placebo effect nor
spontaneous remission were reasonable
alternative hypotheses.
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The development of psychotropic agents in
the 1950s met with considerable skepticism.
It was argued that apparent benefits could
be due to suggestion or spontaneous
remission.
This led to the rapid adoption of the
randomized, placebo-controlled trial.
Both treatment groups were, within chance
sampling fluctuations, equivalent with
regard to placebo effect and spontaneous
remission, providing an elegant control.
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Other alternative hypotheses such
as experimenter or patient bias or a
confound of patient differences with
treatment method were countered
by double-blinding and
randomization.
Understanding Controls
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In a controlled trial, patients in one
group receive the investigational drug.
Those in a comparable group--the
controls--get either no treatment at all, a
placebo (an inactive substance that looks
like the investigational drug), a drug
known to be effective, or a different dose
of the drug under study.
What is a placebo?
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A placebo is an inactive pill, liquid,
or powder that has no treatment
value.
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In clinical trials, experimental
treatments are often compared with
placebos to assess the treatment's
effectiveness.
In some studies, the participants in the
control group will receive a placebo
instead of an active drug or treatment.
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What is a control or control group?
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A control is the standard by which
experimental observations are evaluated.
In many clinical trials, one group of
patients will be given an experimental
drug or treatment,while the control
group is given either a standard
treatment for the illness or a placebo.
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Usually the test and control groups
are studied at the same time.
In fact, usually the same group of
patients is divided in two with each
subgroup getting a different
treatment.
That is the best way to be sure the
groups are similar.
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It's important that treatment and control
groups be as similar as possible in
characteristics that can affect treatment
outcome.
For instance, all patients in specific
groups must have the disease the drug is
meant to treat or same stage of the
disease.
Methods of Comparability
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Paired Research
Carefully pair each person in the
treatment group with a control patient
who has closely matching characteristics.
This method is rarely used today because
even in the best of circumstances, it's
difficult to match pairs of patients for
the myriad factors that could have a
bearing on results.
Randomization
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Patients are randomly assigned to either
the treatment or control group, rather
than deliberately selected for one group
or the other.
When the study population is large
enough and the criteria for participation
are carefully defined, randomization
yields treatment and control groups that
are similar in important characteristics.
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Because assignment to one group or
another is not under the control of
the investigator, randomization also
eliminates the possibility of
"selection bias," the tendency to
pick healthier patients to get the
new treatment.
“Blind”Study
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In conjunction with randomization, a
design feature known as "blinding"
helps ensure that bias doesn't distort the
conduct of a study or the interpretation
of its results.
Single-blinding consists of keeping
patients from knowing whether they are
receiving the investigational drug or a
placebo.
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In a double-blind study, neither the
patients, the investigators, nor the data
analysts know which patients got the
investigational drug.
Only when the closely guarded
assignment code is broken to identify
treatment and control patients do the
people involved in the study know which
is which.
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FDA reviewers assess the benefit-torisk relationship
The human studies also generate
information that will be in the
drug's professional labeling, the
guidance approved by FDA on how
to use the drug. This is the package
insert that accompanies a drug in all
shipments to physicians and
pharmacies.
What is a clinical trial?
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A clinical trial is a research study to answer
specific questions about vaccines or new
therapies or new ways of using known
treatments.
Clinical trials are used to determine whether
new drugs or treatments are both safe and
effective.
Carefully conducted clinical trials are the
fastest and safest way to find treatments that
work.
New therapies are tested on people only after
laboratory and animal studies show
promising results.
What is a protocol?
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All clinical trials are based on a set of
rules called a protocol.
A protocol describes what types of
people may participate in the trial; the
schedule of tests, procedures,
medications,and dosages; and the length
of the study.
While in a clinical trial,participants are
seen regularly by the research staff to
monitor their health and to determine
the safety and effectiveness of their
treatment.
Clinical trials of experimental
drugs proceed through four
phases:
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In Phase I clinical trials,
researchers test a new drug or
treatment in a small group of people
(20-80) for the first time to evaluate
its safety, determine a safe dosage
range, and identify side effects.
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Phase 1
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Number of Patients: 20-100
Length: Several months
Purpose: Mainly safety
Percent of Drugs Successfully Tested:
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70 percent
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In Phase II clinical trials, the study
drug or treatment is given to a
larger group of people (100-300) to
see if it is effective and to further
evaluate its safety.
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Phase 2
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Number of Patients: Up to several hundred
Length: Several months to 2 years
Purpose: Some short-term safety but
mainly effectiveness
Percent of Drugs Successfully Tested:
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33 percent
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In Phase III studies, the study drug
or treatment is given to large groups
of people (1,000-3,000) to confirm its
effectiveness, monitor side effects,
compare it to commonly used
treatments, and collect information
that will allow the drug or treatment
to be used safely.
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Phase 3
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Number of Patients: Several hundred to
several thousand
Length: 1-4 years
Purpose: Safety, dosage, effectiveness
Percent of Drugs Successfully Tested:
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25-30 percent
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Phase IV studies are done after the
drug or treatment has been
marketed. These studies continue
testing the study drug or treatment
to collect information about their
effect in various populations and
any side effects associated with longterm use.
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Of 100 drugs for which investigational new
drug applications are submitted to FDA,
about 70 will successfully complete phase
1 trials and go on to phase 2;
about 33 of the original 100 will complete
phase 2 and go to phase 3; and
25 to 30 of the original 100 will clear
phase 3
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about 20 of the original 100 will
ultimately be approved for marketing.
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More than 80 medications are in
development to treat mental
illnesses, including 18 for
depression, 15 for schizophrenia and
16 for anxiety disorders, according
to the Pharmaceutical Researchers
and Manufacturers of America
(1998).
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Last year, the FDA approved 66 new
drugs, 24 of which contained neverbefore-sold ingredients.
Ten were ``priority'' drugs, or potential
breakthroughs - and they still speeding
through the FDA.
The median approval time was six
months, unchanged from previous years.
One, a major advance in leukemia
therapy called Gleevec, set a record
when it won FDA approval in less than
three months.
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Median approval time for the other,
so-called ``standard'' drugs was 14
months.
That's not as fast as the 11.6 months
such drugs spent at FDA in 1999 but
a little faster than the 15.6 months
FDA spent such products in 2000,
FDA records show.
 Drug
industry is Big
Bucks
 And it does not
always go as planned
Cancer Drug
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“The FDA shocked Wall Street in late
December by rejecting the marketing
application for Erbitux, saying ImClone
failed to provide adequate data to
support its conclusion the drug was
effective among patients with colorectal
cancer who had failed earlier treatment
with Pharmacia Corp.'s Camptosar.
Erbitux……..
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The FDA had previously told ImClone it
would have to conduct new clinical trials of the
medicine to provide the missing clinical data, a
fact that ImClone failed to disclose in a Dec. 28
news release announcing the agency had
spurned the application.
Such new trials could delay approval of
Erbitux by as much as two years, according to
some industry analysts who had previously
forecast the medicine could become a
blockbuster with annual sales of over $1
billion.
Erbitux……
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The House panel said last week it would
seek records from the FDA, ImClone
and Bristol-Myers to establish the
validity of ImClone's research into
Erbitux.”
Oncolytics seeks clinical trials
for cancer drug
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TORONTO, Jan 24 (Reuters) - Oncolytics Biotech
Inc. said on Thursday it filed an application
to initiate clinical trials for Reolysin as a
treatment for recurrent malignant glioma,
the most aggressive form of brain cancer.
In Phase I, patients with a variety of
malignant gliomas will be enrolled, whereas
the Phase II trial will focus on patients with
recurring malignant gliomas.
Forest gets conditional U.S.
approval for Lexapro
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NEW YORK, Jan 24 (Reuters) - Drugmaker Forest
Laboratories Inc. on Thursday said it had
received conditional U.S. regulatory approval
to market its new antidepressant Lexapro, a
second-generation version of Celexa, Forest's
top-selling drug.
New York-based Forest said it expects to
begin marketing Lexapro by mid-year. It said
it filed for approval of the drug in March
2001.
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The company has said clinical trials proved
Lexapro to be safer and more effective than
Celexa, which had sales of more than $980
million in 2001.
Forest said it received an ``approvable
letter'' from the U.S. Food and Drug
Administration.
Such letters are normally issued when the
agency is prepared to approve a drug based
on its safety and efficacy but is engaged in
final negotiations over labeling or
manufacturing with the drugmaker.
Patent
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Patent expirations on major drugs have
stifled Bristol-Myers' drug sales, and deeper
cuts in future sales are expected. Cancer
drug Taxol and anti-anxiety treatment
BuSpar already face stiff competition from
generic competitors, and copycat versions of
diabetes treatment Glucophage are expected
to hit the market in 2002.
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NEW YORK, Jan 24 (Reuters)
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Bristol-Myers, the world's No. 5 drugmaker,
warned earnings will be off 10 percent to 15
percent in the first quarter on slowing sales
of key drugs. And it affirmed its forecast for
2002 earnings to fall to a range between
$2.25 and $2.35 per share, down from its
2001 profit of $2.41 a share.
``Bristol-Myers is struggling with products
coming off patent, and it looks like that will
hurt them for the next several quarters,''
said analyst Richard Lawrence of
Parker/Hunter Inc.
Generics
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Merck-Medco says that recent research
has found that although 83% of
Americans believe that generics are
generally as safe and effective as brandname drugs and that they cost less, they
represented only 41% of overall
prescription drug sales in 1998.
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The US National Consumers League has
launched a public education campaign to
encourage consumers to ask their
physicians and pharmacists about
generic drugs.
Watson says FDA approves
generic Glucophage
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CORONA, Calif., Jan 24 (Reuters) Drugmaker Watson Pharmaceuticals
Inc. said on Thursday it received final
approval from the U.S. Food and Drug
Administration (FDA) to make and
market a generic form of Glucophage,
the world's top- selling diabetes
medicine.
Over the Counter
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Unlike Rx drugs, OTC medicines are
usually used to treat self-limiting
conditions-that is, problems that will
eventually go away on their own.
Therefore, OTC drugs are focused
more on controlling symptoms of
various ailments, such as aches,
pain and colds.
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At present, there are more than 300, 000
OTC products on the market, and more
are being added every day.
The phenomenal growth in the OTC
market can be attributed to genuine
developments in pharmacology, as well
as to the public's growing insistence on
having a "ill for every ill."
Even though they are not as potent as
Rx medicines, OTC drugs nevertheless
have powerful main effects and often
serious side-effects.
Herbals
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Herbal medications do not have to
meet the specifications of FDA
The safety and validity of these
remedies is controversial.
More later on this subject……