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Drug Information Summaries
NCI's drug information summaries provide consumer-friendly information about certain drugs that are approved by the U.S. Food and Drug Administration (FDA) to treat cancer or conditions related to cancer.
Protecting Participants in Clinical Trials
A collection of material about the ways in which clinical trials participants are protected before and during the conduct of a study.
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A Short History
The present system of FDA regulation has evolved over the course of this
century. Before 1906, there were no laws guaranteeing the quality of medicines
and no regulations requiring a doctor's prescription for medications. So-called
"patent" medicines, many containing dangerous ingredients, were
advertised with outlandish health claims and widely marketed in the United
States.
By the turn of the century, it was apparent that some form of regulation was
necessary. The following major developments in U.S. drug laws and FDA
regulations demonstrate how the federal power to regulate drugs, which began as
a simple effort to identify fraudulent medicine, has evolved into a complex
system dedicated to ensuring the health and safety of the public. They also
suggest how the government has tried to balance public safety with the desire
to widen access to promising drugs for life-threatening illnesses.
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Food and Drugs Act (1906): This law targeted false and fraudulent
"patent" medicines and required that drugs meet standards of strength
and purity. A few years later, this act was extended to cover not only a ban on
false or misleading labeling pertaining to ingredients, but also to claims of
effectiveness. The 1906 act lacked "teeth"it was difficult to
enforce and was very narrowly applied.
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Federal Food, Drug, and Cosmetic Act (1938): It was not until 1937, when
107 people died from a poison in the patent medicine marketed as "Elixir
Sulfanilamide," that Congress passed a more stringent drug law. The
so-called FDC Act required manufacturers to prove the safety of drugs,
authorized factory inspections, and established penalties for fraudulent claims
and misleading labels.
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Durham-Humphrey Amendment (1951): This was the first federal law
requiring a physicians prescription for drugs "unsafe for
self-medication."
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Kefauver-Harris Drug Amendments (1962): In Western Europe, thousands of
babies were born with birth defects because their mothers had taken the
sedative thalidomide during pregnancy. A delayed review process prevented the
drug from being marketed in the United States, where it was being studied in a
large number of subjects.
In response to this tragedy, the Kefauver-Harris amendment mandated that
manufacturers prove their drugs were effective for specific medical purposes,
as well as safe, through "adequate and well-controlled" studies. This
law applied retroactively to all drugs introduced since the 1938 FDC Act. Firms
were also required to report all adverse reactions to the FDA and to include
complete information (about adverse effects as well as benefits) for physicians
in advertisements. For the first time, informed consent was required from
patients participating in studies of a new drug.
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Orphan Drug Act (1983): Orphan drugs are intended to treat rare diseases
and conditions for which adequate drugs have not yet been developed. In the
past, manufacturers had been reluctant to produce such drugs: the complex
process of research and marketing a drug for only a small group of potential
users may bring little or no profit. This law provided manufacturers with tax
benefits for portions of their research and development costs. Furthermore, if
a company developed an orphan drug, it was granted exclusive marketing rights
for seven years.
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Drug Price Competition and Patent Term Restoration Act (1984): This law
made generics, often sold at lower prices than brand-name drugs, more easily
available. It also allowed drug manufacturers to "restore" part of
the time spent researching drugs before approval to the patent life of the
drug.
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Revision of Regulations for New Drug Application Regulations (1985):
Changes in requirements for manufacturers called for better organized
applications, clearer data, more information on adverse reactions, quicker
problem-solving, and in some instances provided for approval based on foreign
studies.
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Treatment Use of Investigational Drugs (1987): New regulations allowed
"expanded access" protocols for promising investigational drugs. In
less-restricted studies, researchers could learn more about the drug while also
providing treatment for people with no effective alternative. These regulations
still required researchers to formally investigate the drugs in well-controlled
studies and provide reasonable evidence of effectiveness.
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Accelerated Approval (1987): Before this rule, drugs could be judged
only according to their effect on the illness or patients length of
survival. This regulation allowed the FDA to approve drugs based on a
reasonable "surrogate endpoint" -- that is, an effect of the drug on
some physiological process associated with the disease (an example would be CD4
cell counts, which measure the strength of the immune system).
The "surrogate" is used to predict whether a new drug will offer
therapeutic benefit. The regulation offered a way of making an apparently
promising drug available without having to wait until the end of the clinical
trials process. Under these rules, the FDA approves the drug only on the
condition that the sponsor confirm actual clinical benefit through
well-controlled studies.
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Procedures for Subpart E Drugs (1988): These procedures were designed to
encourage early cooperation among manufacturers, clinical researchers, and the
FDA to get new drugs to patients with life-threatening or severely debilitating
illnesses as quickly as possible. For example, manufacturers may request to
meet with the FDA early in the drug development process to reach agreement on
the design of preclinical and clinical studies. Similar meetings may also be
called after phase I testing to discuss how to design phase II clinical trials,
with the goal that the data from phase II trials will provide sufficient data
on the drug's safety and effectiveness for a decision about approval of the
drug.
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Parallel Track Mechanism (1992): This U.S. Public Health Service policy
made promising investigational drugs for AIDS and other HIV-related diseases
more widely available under "parallel track" protocols at the same
time that
controlled clinical trials continued. The system is designed to make
the drugs available to patients who have no therapeutic alternatives and cannot
participate in the controlled clinical trials.
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Generic Drug Enforcement Act (1992): This law imposed disbarment and
criminal convictions for fraudulent and illegal activities in new drug
applications for generic drugs.
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Prescription Drug User Fee Act (1992): Manufacturers were now required
to pay fees for certain new drug applications. The funds generated have been
used to add review staff at the FDA to accelerate new drug reviews. Review
times for new drug applications were set at 12 months for standard applications
and at six months for priority applications; in other words, the FDA had to
take action on the application within that time frame. The order in which
applications are looked at is determined with the aid of a classification
system, which gives priority to drugs with the greatest potential benefit.
For example, all AIDS drugs receive the highest priority, and all drugs that
offer a significant medical advance over existing therapies for any disease are
considered "priority drugs." The breast cancer drug Herceptin,
approved in September 1998, was assigned to priority review.
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Food and Drug Administration Modernization Act (1997): Extended the
User Fee Act another five years and lowered the review times for standard new
drug applications to 10 months.
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