Drug risk-benefit relationship

The overall objective of clinical trials is to establish a drug therapy that is safe and effective in humans, to the extent that the risk-benefit relationship is acceptable. The ICH process has developed an internationally accepted definition of a clinical trial as Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of one or more investigational medicinal product(s), and/or to identify any adverse reactions to one or more investigational medicinal product(s) and/or to study absorption, distribution, metabolism and excretion of one or more investigational medicinal product(s) with the object of ascertaining its (their) safety and/or efficacy. ... 

Phase 3 studies are performed after evidence of the effectiveness of the drug has been obtained. These are expanded clinical trials intended to gather additional data regarding safety and effectiveness, as well as to determine the risk-benefit relationship of the drug. Phase 3 studies may include a range from several hundred to several thousand patients. Often a bioequivalence (BE) or bioavailability (BA) study is included to demonstrate comparability of the proposed market formulation to the clinical formulation(s) used in the previous safety and efficacy studies. Plans for NDA preparation are initiated in anticipation of favorable clinical results from the phase 3 trials. 

Excipients are inert pharmaceutical ingredients that are used in product formulations. Excipients may perform a variety of functional roles in the pharmaceutical product. In the vast majority of cases, excipients have limited (if any) pharmacological activity, unlike the API. Because of this difference in the expected biological activity and the risk/benefit relationship between excipients and active drug substances, the approaches for the safety assessment of excipients and API will differ. ... 

The success of D-penicillamine as an antirheumatic drug have prompted the search for other thiols with improved risk/benefit relationship. Recently 5-thio-pyridoxine f5 was shown to have therapeutical value in rheumatoid arthritis. This thiol caused no increased urinary copper excretion, had no antipyridoxin effect, had no effect on skin collagen and did not enter into SH/SS exchange with the amino acid cystine. Thus, the redox potential and reactivity of thiopyridoxine appears to be somewhat different from that of D-penicillamine. 

Pharmaceuticals are intended to have human exposure. Furthermore, pharmaceuticals are intended to have biological effects on the people that receive them. Frequently, the interpretation of results and the formulation of decisions about the continued development and eventual use of a drug are based on an understanding of both the potential adverse effects of the agent and its likely benefits, as well as the dose separation between these two. This makes a clear understanding of dose-response relationship critical, so that the actual risk/benefit ratio can be identified. It... 

Virtually all other models used to assure the safety of ingested or inhaled substances are variations of the food and drug safety models (described below) the nutrients model based on dose-response relationships the in-market monitoring and surveillance model the novel foods and food additives models, based on a reasonable certainty of no harm and the drug model, based on risk-benefits assessments. 

Research participants are the true pioneers of medicine. Through their participation, novel therapeutic cures and treatments have been made possible. Furthermore, their participation also protects the public from approval of drugs that have a poor benefit-to-risk relationship. Thus, data obtained via research volunteers may be used to provide medical advances or to protect against insidious drugs entering the marketplace. 

Lead exposure Not a substitute for effective abatement of lead exposure. Neutropenia Mild to moderate neutropenia has been observed in some patients receiving succimer. While a causal relationship to succimer has not been definitely established, neutropenia has been reported with other drugs in the same chemical class. Obtain a complete blood count with white blood cell differential and direct platelet counts prior to and weekly during treatment. Withhold or discontinue therapy if the absolute neutrophil count (ANC) is below 1200/mcL and follow the patient closely to document recovery of the ANC to above 1500/mcL or to the patient s baseline neutrophil count. There is limited experience with reexposure in patients who have developed neutropenia. Therefore, rechallenge such patients only if the benefit of succimer therapy clearly outweighs the potential risk of another episode of... 

Healy, David. Let Them Eat Prozac The Unhealthy Relationship between the Pharmaceutical Industry and Depression. New York New York University Press, 2004. The psychiatrist author prescribed Prozac when it first came out but found that many patients who took it became agitated and a few attempted suicide. His book reviews the history of Prozac and similar antidepressants, describes the controversies over the drugs, and ultimately criticizes the pharmaceutical industry for overstating the benefits and minimizing—or hiding—the risks. 

For food safety purposes the overriding aim is that food contamination should be reduced to the lowest practicable level, bearing in mind the potential costs and benefits involved. Since it is difficult to establish cause and effect relationships following long-term (chronic) exposure at low concentrations, it may be necessary to base action on prudence rather than on proven harm to health. However, if this approach is to maintain the confidence of both consumers and producers of food, a rational evaluation of all relevant information is required so that the balance between the risks and benefits of veterinary drugs can be assessed. Information on the incidence of potentially harmful drug residues is fundamental to this cost-benefit analysis so too is the consumption of the commodities involved (particularly for susceptible consumers or those consumers who eat more). Account must also be taken of the potential fall in food production if a drug is controlled or prohibited, and also the animal health and welfare implications that may result from the restriction of an animal medicine for which there may be no effective alternative. 

The most recently reported UK results on surveillance for veterinary drug residues in meat and animal products show that traces of these compounds can, and sometimes do, arise in food. As all of these compounds are biologically potent in order to be effective in use, it is necessary to ensure that any residual activity in a food product does not present a risk to the consumer. The use of veterinary medicines inevitably leads to the presence of trace residues in food and the purpose of toxicological safety evaluation is to determine at what concentration the residues of a particular compound becomes a cause for concern with regard to human health. Thus, dose-response relationships have to be established and used to determine the concentration of a dmg at which the risks to human health become acceptable and are outweighed by the benefits from the use of the drug. This is in essence the process involved in the setting of Acceptable Daily Intakes (ADIs) and... 

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