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Drug Development and Approval Process (USA)
Different stages of the drug development and approval process in the USA, lead from preclinical trials (testing in animals), first application in humans through limited and broad clinical tests, to postmarketing studies.

Years Test Population Purpose Success Rate
Preclinical Testing 3.5 Laboratory and animal studies Assess safety and biological activity 5,000 compounds evaluated
File IND at FDA
Phase I 1 20 to 80 healthy volunteers Determine safety and dosage 5 enter trials
Phase II 2 100 to 300 patient volunteers Evaluate effectiveness, look for side effects
Phase III 3 1000 to 3000 patient volunteers Verify effectiveness, monitor adverse reactions from long-term use
File NDA at FDA
FDA 2.5 Review process / Approval 1 approved
12 Total
Phase IV Additional Post marketing testing required by FDA

By Dale E. Wierenga, Ph.D. and C. Robert Eaton
Office of Research and Development
Pharmaceutical Manufacturers Association

'In reviewing this report, it is important to keep in mind the realities of the drug discovery and development process. The U.S. system of new drug approvals is perhaps the most rigorous in the world. On average, it costs a company $359 million to get one new medicine from the laboratory to the pharmacist's shelf, according to a February 1993 report by the Congressional Office of Technology Assessment.'

See also Phase 1 2 3 4 Drug Trials, Clinical Trial, Food and Drug Administration, and European Medicines Agency.
Fluoroscopy
Fluoroscopy is used to study moving body structures in real time. A fluoroscope is used to produce a continuous (advanced fluoroscopy machines provide pulsed techniques to lower the amount of radiation) x-ray beam, passing through the body part being examined and transmitted to a monitor so that dynamic images of deep tissue structures can be visualized. Fluoroscopy is primarily used for gastrointestinal exams, genitourinary studies, cardiovascular imaging and for invasive procedures performed by interventional radiologists and angiographers under fluoroscopic guidance. Fluoroscopy can also produce a static record of an image formed on the output phosphor of an image intensifier. The image intensifier is an x-ray image receptor that increases the brightness of a fluoroscopic image by electronic amplification and image minification. Modern fluoroscopy systems combine less radiation with better image quality due to digital image processing and flat-panel technology.
Roentgen's discovery of x-rays related directly to fluoroscopy, because fluorescence on the material in the room draws his attention to the x-ray's properties. In 1896, Thomas A. Edison created the first fluoroscope, consisting of a zinc-cadmium sulfide screen that was placed above the patient's body in the x-ray beam and provides a faint fluorescent image. In first-generation units, the exam room required complete darkness. The users wear red goggles for up to 30 minutes prior to the examination, to adapt the eyes to darkness. After this, the radiologist stared directly at a yellow-green fluorescent image through a sheet of lead to prevent the x-ray beam from striking the eyes.
Integral
An integral is a mathematical object that can be interpreted as an area or a generalization of an area. A number computed by a limiting process in which the domain of a function, often an interval or planar region, is divided into arbitrarily small units, the value of the function at a point in each unit is multiplied by the linear or areal measurement of that unit, and all such products are summed (summation in the limit). In CT, for example this mathematical function is used in the Fourier transformation.
Virtual Colonoscopy
Virtual colonoscopy provides a less invasive option to conventional polyp detection in the large intestine (colon and rectum). A virtual colonoscopy is a synthesis of a computed tomography (CT) scan, digital processing and virtual reality computer software.
A virtual colonoscopy is less invasive and more comfortable for patients than either conventional colonoscopy or a barium enema. No sedation is required and the examination takes less than 30 minutes.
A CT colonography offers a new option for a total colon evaluation and cancer detection and has the potential to be used for screening. A problem is the amount of information captured in a CT exam. Reviewing these images can be time-consuming and challenging.

See also Computed Tomography Enterography.
X-Ray
X-rays are a part of the electromagnetic spectrum. X-rays and gamma rays are differentiated on the origin of the radiation, not on the wavelength, frequency, or the energy. X-rays are emitted by electrons outside the nucleus, while gamma rays are emitted by the nucleus. X-rays have wavelengths in the range of about 1 nanometer (nm) to 10 picometer (pm), frequencies in the range of 10-16 to 10-20 Hertz (Hz) and photon energies between 0.12 and 120 kilo electron Volt (keV). The energy of rays increase with decreased wavelengths. X-rays with energies between 10 keV and a few hundred keV are considered hard X-rays. The cutoff between soft or hard X-rays is around a wavelength of 100 pm.
Because of their short wavelength, X-rays interact little with matter and pass through a wide range of materials. These interactions occur as absorption or scattering;; primary are the photoelectric effect, Compton scattering and, for ultrahigh photon energies of above 1.022 mega electron Volt (MeV), pair production.
X-rays are produced when high energy electrons struck a metal target. The kinetic energy of the electrons is transformed into electromagnetic energy when the electrons are abruptly decelerated (also called bremsstrahlung radiation, or braking radiation) similar to the deceleration of the circulating electron beam in a synchrotron particle accelerator. Another type of rays is produced by the inner, more tightly bound electrons in atoms;; frequently occurring in decay of radionuclides (characteristic radiation, gamma ray, beta ray). The energy of an X-ray is equivalent to the difference in energy of the initial and final atomic state minus the binding energy of the electron.
Wilhelm Conrad Roentgen discovered this type of rays (also called Roentgen-rays) in 1895 and realized that X-rays penetrate soft tissue but are absorbed by bones, which provides the possibility to image anatomic structures; the first type of diagnostic imaging was established. Radiographic images are based on this difference in attenuation for tissue and organs of different density. Today ionizing radiation is widely used in medicine in the field of radiology.

See also Exposure Factors, X-Ray Tube, and X-Ray Spectrum.
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