Adverse events types

Adverse events type, severity, duration, action taken, outcome, likelihood of attributabiUty to study drug... 

Adverse event type. Usually a general description of the event that would allow you to look it up in a reference source, e.g. acute renal failure, diarrhoea. Does not usually include all details of the event. 

Although of limited value in isolation, these reports can be important in aggregate. By definition, spontaneously reported adverse events are deemed possibly treatment related by the reporter, even when the motivation is to inquire into the possibility that the subject drug could be associated with the adverse event type that has been observed... 

Whilst the conditions under which large simple trials can provide efficacy data are fairly well worked out, it is important to consider whether (or which) tolerability issues can be precisely addressed in this way. If a tolerability factor (adverse event) relates to the efficacy variable of interest (e.g. a fatal adverse event in a patient survival study), then a simple case report form may provide relevant information. However, if the adverse event type is rare or unanticipated (e.g. the test drug causes unanticipated, significant anemia in 0.1% of patients, and the protocol and case report form do not collect hemoglobin values before and after treatment), then it is very likely that the adverse event will be missed. Large simple studies can thus create undue confidence in product tolerability ( thousands of patients were exposed to the agent during clinical trials ). 

Japanese labeling regulations require that animal data and data from other members of the same chemical or pharmacological class of drugs should be included, even when these allude to adverse drug reactions (ADR) that have not actually been observed for the product that is labeled. When direct drug attributability of an ADR has not been established, it remains a requirement that other indirectly obtained information must still be included this would include epidemiological information or pharmacodynamic effects observed in normal volunteer studies. ADR frequencies (section 4, Table 1) may be presented in a table, usually for all adverse event types reported with frequencies > 5%, between 0.1-5%, and < 0.1%. 

All these observations and findings will be included in the Clinical Investigators Brochure (CIB). Indeed, the initial guidance for clinical hazard potential may depend almost entirely on safety pharmacology findings because of an unspectacular toxicology profile, the lack of human exposure, and the fact that normal volunteers are unlikely to be capable of exhibiting certain adverse event types... 

Expert opinion is a source, frequently elicited by survey, that is used to obtain information where no or few data are available. For example, in our experience with a multicountry evaluation of health care resource utilization in atrial fibrillation, very few country-specific published data were available on this subject. Thus the decision-analytic model was supplemented with data from a physician expert panel survey to determine initial management approach (rate control vs. cardioversion) first-, second-, and third-line agents doses and durations of therapy type and frequency of studies that would be performed to initiate and monitor therapy type and frequency of adverse events, by body system and the resources used to manage them place of treatment and adverse consequences of lack of atrial fibrillation control and cost of these consequences, for example, stroke, congestive heart failure. This method may also be used in testing the robustness of the analysis [30]. 

Additional examples of variability in data collection (which, in turn, affects data interpretation) include questionnaires and physical exam forms. Questionnaires often utilize open-ended questions that allow great variability in the type and extent of adverse event information gathered. Physical exam forms—even when designed in a checklist format—may elicit variable collection of adverse event data what is a serious event to one clinician may not be serious to another. 

The most commonly used corticosteroids are methylpred-nisolone (IV and oral) and prednisone (oral), although prednisolone and dexamethasone also have been shown to be effective for organ transplantation. Corticosteroid doses vary by center-specific protocols, organ type, and patient characteristics. A typical taper would include an IV 100 to 500 mg bolus of methylprednisolone at the time of transplant and then a taper over 5 to 7 days to a maintenance dose of prednisone 20 mg/day or complete cessation.2,7 It is important for practitioners to know that approximately 4 mg methylprednisolone is equivalent to 5 mg prednisone and 0.75 mg dexamethasone.11 At most transplant centers, therapeutic drug monitoring of corticosteroids is not employed. Corticosteroids are associated with a variety of acute and chronic toxicides. The most common adverse events have been summarized in Table 52-5. 

Verify the patient s allergy history and the type of reaction experienced. Attempt to discern between true allergy and adverse event. (3-Lactam-allergic patients may receive clindamycin, vancomycin, or other antimicrobials. Crossreactivity between penicillin allergy and cephalosporins is low but cephalosporins should be avoided in patients with a history of anaphylaxis to penicillins. 

The use of the reticulo-endothelial system (RES) was the first approach to liver contrast agents. As an adjunct, spleen imaging would also be possible with a contrast agent that is taken up by the RES. The Kupffer cells of the liver, which represent 10% of all hepatic cells, constitute the major portion (80-90%) of all fixed macrophages and they are extremely effective in the phagocytosis of all types of particles. The downside of the use of this mechanism, however, is the concomitant release of toxic mediators that might and - as a matter of fact - often has made this approach non-feasible. Adverse events provoked by the mediators are changes in blood pressure (most often hypotension) and fever. 

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