Rational Therapeutics for Infants and Children Workshop Summary (2000) / Chapter Skim
Currently Skimming:
4 Extrapolation of Safety and Efficacy Data to Children
4 Extrapolation of Safety and Efficacy Data to Children
Pages 61-70
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 61... ...
Because of their distinctive properties, the use of biologics results in unique safety concerns that require different types of monitoring, such as for adventitious agents that occur as a result of treatment with the biologic, or for reactogenicity. There is some concern about therapeutic biologics because little is known about the long-term effects of treatment with such agents, especially their effects on developing children.
|
From page 62... ...
Recently, the FDA centers responsible for drugs and biologics reviewed their approved products to identify those with inadequate clinical information to support pediatric labeling and published a list calling for pediatric studies. Contemplating a similar task for devices is daunting.
|
From page 63... ...
The evidence needed to establish the safety and effectiveness of devices is somewhat different from the evidence needed to establish the safety and effectiveness of drugs and biologics. Device evidence is graded appropriate to the level of risk, ranging from nonclinical product performance standards to rigorous clinical trials.
|
From page 64... ...
But concerns arose over the proarrhythmic effects of these agents, and, notably, after a heart attack antiarrhythmic drugs were found to be lethal in some settings, thus these drugs are not being approved even for symptomatic treatments without evidence that they do not decrease survival. The FDA also approves drugs that lower blood pressure or lipids without premarketing evidence of other effects.
|
From page 65... ...
For example, increased exercise tolerance in patients with heart failure or decreased symptoms of hyperglycemia in patients with diabetes are valuable clinical benefits, but in both groups of patients a decrease in the rate of morbidity is hoped for as the final endpoint. The main problem with surrogate endpoints is that they may not predict the desired outcomes.
|
From page 66... ...
In early childhood, when synapses are forming, the use of drugs may have very subtle effects. Commonly occurring disorders involving neuropsychologic and neurophysiologic abnormalities can serve as surrogates for what could happen to a typically developing child who is exposed to drugs.
|
From page 67... ...
Slow performance is associated with left hemisphere dysfunction and traumatic brain injury. The Wisconsin card sort test assesses frontal and prefrontal functioning.
|
From page 68... ...
Director, Division of Clinical Trial Design and Analysis, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration The definition of a biologic, as set forth in the Public Health Service Act, is "any virus, serum, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product or analogous product, or arsphenamine or its derivative, or any other trivalent organic arsenic compound applicable to the prevention, treatment or cure of diseases or injuries in man." That definition does not fully express the diversity of therapeutic products currently regulated by the Center for Biologics Evaluation and Research (CBER)
|
From page 69... ...
Examples of investigational gene therapies include an adenoviral vector containing the char (cystic fibrosis transmembrane regulator) gene for cystic fibrosis and plasmids containing fibroblast growth factor for the treatment of coronary artery disease.
|
From page 70... ...
of treatment with therapeutic biologics, especially the effects on growing children. As more and more biologics are licensed for use for chronic treatment, it will be important to collect and examine data from postmarketing use, including studies from registries and Phase 4 clinical trials (controlled studies following market approval)
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.