Drug safety definitions

Dorato MA, Engelhardt JA (2005) The no-observed-adverse-effect-level in drug safety evaluation use, issues, and definition(s). Regul Toxicol Pharmacol 42 265-274... 

Anaphylactic shock is rare, but has been reported with co-trimoxazole (20). However, it is possible that this reaction was due to the sulfonamide compound (21). The case histories of 13 patients (12 women, one man, aged 22-68 years) with anaphylactic reactions to trimethoprim alone that were reported to a national drug safety unit have been analysed (20). Nine were classified as probable anaphylaxis. The casual relation between exposure to trimethoprim and anaphylaxis was classified as definite in three reports, possible in four, and probable in six. In one patient, IgE antibodies against trimethoprim were demonstrated. 

CIOMS. Standardisation of definitions and criteria of causality assessment of adverse drug reactions - drug-induced cytopenia. Int J Clin Pharmacol Ther Toxicol 1991 29 75-81. CIOMS. Basic requirements for the use of terms for reporting adverse drug reactions. Pharmacoepidemiol Drug Safety 1992 1 39-45. 

Authors associated with the CONSORT statement on clinical trials (Altman et al, 2001) have recently made ten recommendations as regards the reporting of what they refer to as harms (loannidis et cd., 2004). Indeed, part of the purpose of their recommendations is to promote the use of the term hann, or harms, since they believe that talk of drug safety gives an unrealistic impression of the inevitable risks associated with pharmaceutical therapy. As they put it, We encourage authors to use the term harms instead of safety (p. 781). The definition they offer for this term is... 

While the term "signal" has been used commonly and widely in the area of pharmacovigilance for years, its definition has evolved over the past few years. Clearly defined terminology is critical to ensure clarity and consistency in communication of drug safety information to patients, prescribers, manufacturers, and regulators [6], and therefore, establishing a common and clear definition of a safety signal is essential. 

Information that arises from one or multiple sources An earlier definition of a safety signal [8] referred to "report(s) of an event," implying that adverse event reports are the primary, if not the only, source of safety signals. The QOMS VIII definition acknowledged that new information relevant to drug safety may arise from other sources, such as clinical and nonclinical experiments and published articles of clinical study results. 

Hauben M and Aronson JK. Defining signal and its subtypes in pharmaco-vigilance based on a systematic review of previous definitions. Drug Safety, 32(2) 99-110,2009. 

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. ... 

E1 The Extent of Population Exposure to Assess Clinical Safety for Drugs Intended for Long-Term Treatment of Non-Life Threatening Conditions E2A Clinical Safety Data Management Definitions and Standards for Expedited Reporting... 

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