Risk-benefit test

Although drug manufacturer liability under a theory of design defect products tort was relatively easy to prove, especially in courts adopting the Barker risks benefits test, some DES plaintiffs were barred from recovery by limitations placed on the unborn plaintiff liability doctrine that originated with the thalidomide cases. While thalidomide s teratogenicity affected only fetuses exposed... 

No drug is completely safe or without potential side effects. Before a drug is approved for marketing, tests that show a drug is "safe" under the conditions on the proposed label. "Safety," therefore, is determined case-by-case and reflects the risk-benefit ratio. 

Monitor patients who develop abnormal liver function tests during concomitant therapy with cyclosporine, and evaluate the risk/benefit of continuing therapy. Pregnancy Category C. 

People who volunteer to be subjects in a drug study have a right to know what can and will happen to them if they participate (informed consent). The investigator is responsible for ensuring that each subject receives a full explanation, in easily understood terms, of the purpose of the study, the procedures to be employed, the nature of the substances being tested, and the potential risks, benefits, and discomforts. 

These authors (17) then assert that, in practice, competency is usually determined by the interplay of one or more of these tests and two other variables the risk-benefit ratio of treatment and the valence of the patient s decision (i.e., consent to or refusal of treatment). We include valence as a factor in our guidelines, because agreement or lack of agreement between the patient and the clinician may dictate different courses of action, given the overriding preference to be in accord with the expressed wishes of the patient. We exclude the risk—benefit ratio as a factor, however, because ideally this consideration should occur before or after an assessment of capacity, but not as part of the actual determination. 

Sometimes, Phase 4 trials are conducted after a product is already approved and on the market to find out more about the treatment s long-term risks, benefits, and optimal use, or to test the product in different populations of people, such as children. 

Recruitment. Subjects will be recruited by advertisement (posters displayed in town) as well as from existing files of participants in other taste tests conducted at Gotham City. A consent form, approved by the Gotham City institutional review board, will be signed before participation, indicating the nature of the study, materials to be tasted, time involved, right to withdraw at any time without prejudice, risks, benefits and reimbursement. 

For risk estimation based on information most closely related to the expected human impact, the mouse test for dominant skeletal abnormalities (possibly supplemented by a cataract test) is appropriate. Because these tests have not been validated by comparisons in different laboratories, different species, and different cell stages in both sexes, and because the similarity of humans to mice remains uncertain, we recommend that the risk aspect of any risk-benefit decision be based on all relevant mutational and toxicologic information. 

Classification as a presumed mammalian mutagen or nonmutagen may itself be sufficient information for a risk-benefit evaluation. If the screening test results are negative, this is ordinarily taken as evidence that the chemical is not a mammalian mutagen, because the short-term tests are very sensitive and encompass a number of relevant end points. However, if the chemical is to be widely used or if people are likely to be exposed to large amounts, additional tests may be desirable. Likewise, a compound that produces positive results in one or more tests may have benefits that could outweigh a small risk and therefore necessitate further tests. 

Carcinogenic risk may be sufficient for a decision to control the use of a chemical in this case, a mouse mutation test is not needed. The combination of carcinogenicity information and results from short-term mutagenicity tests may be sufficient for a decision. In some cases, if the risk-benefit calculation based on cancer is equivocal, even an uncertain mutational increment may be enough to tip the balance. 

It would be highly desirable to make comparisons with other small mammals. Without such information, an assessment of the human dominant-mutation risk is very uncertain. In view of this, we recommend that in any risk-benefit decision the risk component take into account all relevant test and pharmacologic information. 

For a drug that has never been used in humans previously, the initial step that a pharmaceutical company must take is to perform preclinical toxicity studies involving appropriate in vitro systems or whole animals. The FDA usually requires that dose-related toxicity be determined in at least two mammalian species (routinely rodents). The toxicity information obtained from these studies can then be used to make risk/benefit assessments and help determine the acceptability of the drug for testing in humans, and to estimate a safe starting dose. 

Approval Approval process for biological medicinal products is the same as other chemically synthesized small molecules. The legal test is firmly based upon an assessment of risk-benefit balance. However, in assessing risk-benefit balance of a biological medicinal product, EU law requires the applicant to provide certain additional information. If the medicinal product contains a new biological active substance, the applicant must comply with the requirements set out in article 8(3) of Directive 2001/83/EC by providing results of the pharmaceutical and nonclinical testing, and clinical trials. 

---