Risk Factors for Adverse Drug Events

Bates, D.W. Miller, E.B. Cullen, D.J. Burdick, L. Williams, L. Laird, N. Patient risk factors for adverse drug events in hospitalized patients. Arch. Intern. Med. 1999, 159, 2553-2560. 

Kando JC, Yonkers KA, Cole JO. Gender as a risk factor for adverse events to medications. Drugs 1995 50 1-6. 

A case-control study is a retrospective analysis it is generally easier to administer than a cohort study. Cases of diseases or events are identified. Controls and patients exposed to the treatment are selected from the source population. The exposure status of the two groups is compared using the odds ratio, an estimate of relative risk of exposure and non-exposure. Case-control studies are less expensive than cohort studies, but provide weaker empirical evidence than well-executed cohort studies. These studies are useful for identifying the relationship between drug treatments with one specific rare adverse event, or for identifying risk factors for adverse events. Risk factors can include renal and hepatic insufficiency that might modify the risk profile. 

Recent data suggest that COX-2 inhibitors, including rofe-coxib, valdecoxib, and celecoxib, may increase the risk for MI and stroke.47 There is also some evidence that the non-selective NSAIDs may increase the risk for cardiovascular events.47,48 Rofecoxib was withdrawn from the market in late 2004 because of safety concerns. The FDA requested the withdrawal of valdecoxib from the market in 2005. The FDA also asked the manufacturers of celecoxib and non-selective NSAIDs (prescription and over-the-counter) to include information about the potential adverse cardiovascular effects of these drugs in their product labeling. The cardiovascular risk with COX-2 inhibitors and NSAIDs may be greatest in patients with a history of, or with risk factors for, cardiovascular disease. The American Heart Association recommends that the use of COX-2 inhibitors be limited to low-dose, short-term therapy in patients for whom there is no appropriate alternative.48 Patients with cardiovascular disease should consult a clinician before using over-the-counter NSAIDs. 

Procedure Beta-lactam desensitization should be done in an intensive care unit and any concomitant risk factors for anaphylaxis, such as use of beta-blockers should be corrected. Protocols based on incremental use of the drug orally or parenterally have been described (190,193). The oral route is preferable and is associated with a lower incidence of adverse events, but mild transient reactions are frequent (171,194,195). Pregnant women with limited antibiotic choices have been treated with immunotherapy (196). Repeated administration will maintain a state of anergy, which is often lost after withdrawal (197). At the conclusion of therapy, patients must be informed that after withdrawal, they may once again become allergic to penicillin, with a new reaction to the first subsequent application (197). 

In a retrospective analysis of spontaneous adverse event reports encompassing more than 430, 000 patients who had received zoledronic acid between August 2001 and March 2003, only 72 cases of renal failure were identified by the US Food and Drug Administrahon [78, 79]. It should be noted, however, that patients with risk factors for renal deterioration, including advanced cancer, previous bisphosphonate exposure, and use of nonsteroidal anti-inflammatory medications, may have contributed to the progression of renal failure [79]. Because of the potentially serious nature of this adverse event, it is recommended to monitor renal funchon in patients with cancer before each infusion of zoledronic acid, provide adequate hydration, and modify or discontinue treatment if renal complications occur [30, 78, 79]. 

The randomized controlled clinical trial is the method of choice for the objective and quantitative demonstration of the efficacy and tolerability of a new medicine. None the less, such studies have limitations in discovering possible adverse events that may occur, in particular those that are rare or develop after prolonged use, in combination with other drugs, or perhaps due to unidentified risk factors. Clinical trials are inherently limited in duration and number of patients, and, significantly, patients are selected prior to inclusion. In other words, the conditions of a trial are artificial compared with the real-life use after the introduction of a medicine (p. 229). 

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