There are three IND types:
- An Investigator IND - submitted by a physician who both initiates and conducts the investigation, and under whose immediate direction the investigational drug is administered or dispensed
- An Emergency Use IND - authorize use of an experimental drug in an emergency situation that does not allow time for submission of an IND
- A Treatment IND - for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions
Although it may take 6 months or more to prepare an application, once the IND is
submitted, the FDA has only 30 days to respond. During this time, the FDA has an
opportunity to review the IND for safety to make sure that research subjects will not
be exposed to unreasonable risk.
2. Access to Investigational Drugs (faster route than traditional IND process)
Group C Drugs (also called Treatment INDs)
In the 1970's, researchers from the NCI became concerned about the lag time
between the date when an investigational drug was found to have anti-tumor activity
and the time that drug became available on the market. Working with the FDA, the
NCI established the Group C classification system to allow patients access to certain
investigational drugs.
Group C drugs are provided to properly trained physicians who have registered using
a special form to assure that their patients qualify under guidelines or protocols for
the drug. Each Group C drug protocol specifies patient eligibility, drug use, and how
information about the patients' use of the drug should be reported.
Group C designation (now called Group C/Treatment INDs) speeds new drugs to
patients who need them most. The process also allows the NCI to gather important
information on the safety and activity of the drugs as they are used in the "real world"
prior to their final FDA approval. Group C drugs are always provided free of charge,
and the Centers for Medicare and Medicaid Services provides coverage for care
associated with Group C therapy.
Application Needed After Clinical Trials
The process of new drug development has many stages. In the United States, until a
drug has been approved by the FDA, it can usually be obtained only through several
mechanisms: enrollment in a clinical trial studying the drug, an expanded access
program, or special exemption/compassionate use programs.
1. New Drug Application (NDA)
If the treatment or drug makes it through the clinical trials process - that is, if the
studies show the treatment is safe and effective - the sponsor may submit
another application to the FDA. In the case of drugs, it's a New Drug Application
(NDA); for biologics, it's a Biologics License Application (BLA). The application must
include the following:
- Safety data
- Efficacy (does it work) data documented through clinical trials
- Chemical makeup
- How the drug or biologic is made, processed, and packaged
- Quality control standards
An FDA Advisory Board Committee analyzes the data in the application to assess if a
specific indication (standard use) is worthy of approval for public use.
For more information on the regulatory process go to:
FDA U.S. Federal Food and Drug Administration - New Drug Application (NDA)
Types of FDA review for a New Drug Application (NDA)
Although the approval process is long and arduous, the FDA has tried to cut through
the some of the red tape by providing several different approval routes.
| |
|
 |
- Standard Review
- Priority review
- Accelerated review
- Fast Track Review
|
| |
|
Standard Review
Standard reviews are given to NDA's that do not represent an advance in the
treatment for a disease. A standard review must be completed within 10 months of
the application.
Priority Review
A priority review is granted for a new drug that, if approved, would be a significant
improvement over current treatment options for a disease fulfilling an unmet medical
need. While a standard review must be completed in 10 months, a priority review
must be completed in 6 months. Drugs that receive a priority review designation are
often approved in much less than 6 months. Gleevec was approved in 8 weeks in June
2001, and Eloxatin was approved in 7 weeks in August 2002.
Accelerated Approval
To be considered for accelerated approval, a drug must treat a serious or life
threatening illness and provide a meaningful increase in therapeutic benefit to
patients over existing treatments.
Accelerated approval uses surrogate endpoints that measure treatment effects that
may correlate with clinical benefit. As an example, tumor shrinkage that occurs when
using a drug may or may not correlate with increased survival.
However, even though a new drug may be approved with an accelerated approval, the
drug company must conduct Phase IV clinical trials to demonstrate meaningful clinical
benefit, such as prolonging patients' lives or improving their quality of life. Generally,
any accelerated approval drug receives a priority review.
Fast Track
A drug may receive a fast-track designation if it is intended to treat a serious or life-threatening
condition and demonstrate the potential to address an unmet medical
need.
| |
|
|
 |
|
Fast tracking actually has little effect on
the patient's access to the drug.
It means that the drug company is engaged
in continuous discussions with the FDA
about the drug's development plan. The
company may also submit its NDA to the
FDA in sections that can be reviewed while
the company prepares other sections of the
application for submission to the FDA. This
is also known as a "rolling submission." |
| |
|
|
Other Issues
Funneling Data into Numbers
- For every 50,000 to 5 million compounds screened, about one thousand will be
deemed worthy of pursuing, and only about 10 will be tested using clinical
trials.
- Only about one out of every ten new drugs that enter clinical trials will have
adequate safety and efficacy data for FDA approval.
What is 'Off-Label" Use?
Off-label use refers to the use of an approved treatment for any purpose, or in any
manner, other than what is described in the treatment's labeling.
A cancer treatment rarely receives approval for general use against cancer. Instead, a
treatment is approved for treatment at a specific stage of a particular kind of cancer
for which it has been tested in patients. The specific approved use is called an "indication".
The indication is described in the labeling for the drug or biologic, consisting of a
printed insert included in the treatment's packaging. The insert also describes in
detail the chemical composition of the treatment, how it works in the body, and the
possible adverse effects of taking it.
However, the FDA - although responsible for ensuring that a treatment is safe and
effective for the specific approved indication - does not regulate the practice of
medicine. This means that once the FDA approves a treatment, licensed physicians
can prescribe it for any purpose they consider medically appropriate.
Off-label uses may include giving an approved treatment:
- For a disease other than the disease it is approved for
- At a different dose or frequency than specified in the product's labeling
- To treat a child when the product is approved only for treatment of adults.
CISN TIP
What questions should I ask my doctor about off-label drug use?
- What evidence is there to support the off-label use of this drug to treat the type
of cancer I have?
- Is the off-label use of this drug likely to be more effective that the use of an
approved drug?
- What are the risks and benefits of off-label treatment with this drug?
- Will my health insurance cover off-label treatment with this drug?
- If my treatment involves a multidrug regimen and one of the drugs is being
used off label, will my health insurance cover it?
A 1997 survey of 200 cancer doctors by the American Enterprise Institute and the
American Cancer Society found that 60 percent of them prescribed drugs off label.
Frequently the standard of care for a particular type or stage of cancer involves the off
label use of one or more drugs.
