[Federal Register Volume 60, Number 147 (Tuesday, August 1, 1995)]
[Notices]
[Pages 39180-39181]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-18877]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
[Docket No. 95N-0230]
Statement Regarding the Demonstrations of Effectiveness of Human
Drug Products and Devices
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is announcing its
position regarding demonstrations of product effectiveness in new drug
applications (NDA's) and premarket approval applications (PMA's). In
evaluating NDA's and PMA's, FDA weighs the product's demonstrated
effectiveness against its risks and considers other factors such as the
seriousness and outcome of the disease being treated and the adequacy
of existing treatments. The agency does not require new human drug
products or medical devices to be more effective than existing
therapies nor does it necessarily require the product to be compared to
other products. However, for products intended to treat life-
threatening diseases, diseases with irreversible morbidity, and
contagious diseases that pose serious health risks to others, it is
essential for public health protection that a new therapy be as
effective as existing, approved therapies.
DATES: Written comments by October 30, 1995.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, rm. 1-23, 12420 Parklawn Dr.,
Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT:
Philip L. Chao, Office of Policy (HF-23), Food and Drug Administration,
5600 Fishers Lane, Rockville, MD 20857, 301-443-2831.
SUPPLEMENTARY INFORMATION: On March 4, 1995, President Clinton
announced plans for reforming the Federal regulatory system as part of
his ``Reinventing Government'' initiative. Part of this reform is aimed
at reviewing regulatory processes to determine which requirements could
be reduced or eliminated without lowering health and safety standards.
Pursuant to the President's ``Reinventing Government'' initiative,
FDA made several recommendations with respect to the regulation of
human drug products and medical devices. One recommendation was the
issuance of a public statement clarifying certain aspects of the
standards for the effectiveness of human drug products and medical
devices.
The Federal Food, Drug, and Cosmetic Act (the act) requires NDA's
and PMA's to contain full reports of information demonstrating that the
drug or device is safe and effective under conditions of use in the
product's proposed labeling. (See sections 505(b) and 515(c) of the act
(21 U.S.C. 355(b) and 360e(c)).) The agency must deny approval of a NDA
or a PMA if it finds that the application does not demonstrate that the
product is safe and effective for the uses indicated in the product's
proposed labeling. (See sections 505 (c) and (d) and 515(d) of the
act.)
Pharmaceutical and device manufacturers have sometimes claimed that
the agency requires new human drug products and especially class III
devices (devices for which insufficient information exists to assure
that general controls and special controls provide reasonable assurance
of safety and effectiveness; in general, these are the higher risk
devices) to be more effective for their intended uses than comparable
therapies that are already approved for marketing. These firms assert
that FDA's requirements for demonstrating effectiveness present
unreasonable difficulties in developing new therapies and bringing
those new therapies to market.
This notice is intended to address the concerns about a comparative
effectiveness standard that have been raised. In evaluating the safety
of a new drug or medical device, FDA weighs the product's demonstrated
effectiveness against its risks to determine whether the benefits
outweigh the risks. This weighing process also takes into account
information such as the seriousness and outcome of the disease, the
presence and adequacy of existing treatments, and adverse reaction and
other safety data.
In evaluating effectiveness, FDA reviews new drug products and
devices on their merits. FDA does not require new drug products or
devices to be more effective than approved therapies for the same
disease or condition. In general, both new drug products and class III
devices must be shown to be effective through evidence consisting of
clinical investigations that provide a basis on which it can be
concluded that the new drug product or class III device will be safe
and have the effect that it is represented to have.
For most new drug products and new class III devices intended to
treat serious
[[Page 39181]]
illness or provide symptomatic relief, a showing of effectiveness is
usually based on a clinical trial comparing the product to a placebo.
Such a showing does not necessarily involve a comparison to another
active treatment or a product that is known to be effective.
In certain circumstances, however, it may be important to consider
whether a new product is less effective than available alternative
therapies, when less effectiveness could present a danger to the
patient or to the public. For example, it is essential for public
health protection that a new therapy be as effective as alternatives
that are already approved for marketing when: (1) The disease to be
treated is life-threatening or capable of causing irreversible
morbidity (e.g., stroke or heart attack); or (2) the disease to be
treated is a contagious illness that poses serious consequences to the
health of others (e.g., sexually transmitted diseases).
It should be noted that new products are often developed for
particular subpopulations who either do not respond to or are not able
to tolerate an existing approved therapy. FDA will generally approve
for use in such a subpopulation a product that is shown to have
effectiveness in this group, regardless of whether the product can be
shown to be as effective in the broad target population as the
alternative therapy. This is because, in effect, there is no available
alternative therapy for the subpopulation. For example, a number of
patients cannot tolerate a widely used therapy for an acquired immune
deficiency syndrome (AIDS)-related pneumonia. FDA approved atovaquone
for use in these patients even though the drug had been shown to be
less effective than the standard therapy when tested in a broad
population.
An additional issue related to product effectiveness concerns the
assertion, by some industry officials, that the act not be interpreted
as requiring multiple clinical studies when one ``pivotal'' study could
suffice.
FDA believes good science dictates that a showing of effectiveness
must be methodologically sound and provide a high level of confidence
in the validity of the result. For human drug products, this ordinarily
is achieved by independently replicating the result in a second study,
to constitute an adequate demonstration of effectiveness for a new
product. While a second study may well be needed to replicate results
demonstrated in a first study, in some instances, it is possible to
replicate results within one large, well-designed, multi-center study.
FDA emphasizes that this approach can be successful only when results
are strong. The agency has, in the past, approved new human drug
products on the basis of a single, multi-center study. Examples include
dornase alfa for the treatment of cystic fibrosis, timolol for
treatment of people after a heart attack, and zidovudine for AIDS. A
statistically marginal result, even in a very large study, cannot
provide convincing evidence without replication.
For medical devices, where the mechanism of action is a result of
product design and substantially verified by in vitro performance
testing, the agency has routinely relied on single studies evaluated
for internal and across-center consistency to provide this high level
of confidence in the result.
Dated: July 27, 1995.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 95-18877 Filed 7-31-95; 8:45 am]
BILLING CODE 4160-01-F-M
