Patient safety adverse events

Following a patient safety adverse event or near miss, stress debriefing is provided, using peer counselors or other means. 

In a pooled analysis of safety data from double-bUnd, placebo-controUed add-on trials of levetiracetam (1-3 g/ day) in adults with refractory partial seizures, adverse events occurring in at least 3% of patients and with at least 3% higher incidence in the active treatment group were tiredness (14 versus 10%), somnolence (15 versus 10%), dizziness (9 versus 4%), and common cold or upper respiratory tract infections (13 versus 7%) (11). The proportions of patients requiring withdrawal of treatment or dosage reduction owing to adverse events were 15% with levetiracetam and 12% with placebo. The efficacy and tolerability of levetiracetam monotherapy in refractory partial seizures have been studied in a double-blind, pla-cebo-controUed study in 286 patients (12). Adverse events that were more common with levetiracetam and that occurred in more than 5% of cases included weakness, infection, and somnolence. Of 181 patients who took levetiracetam, 36 completed the study compared with only 10 of 105 who took placebo. The tolerability and efficacy of levetiracetam, 2 or 4 g/day, as add-on therapy have been studied in 119 patients with refractory epilepsy (13). Somnolence was the most common reason for withdrawal and occurred more often with levetiracetam than placebo, as did weakness. Somnolence was more common with the higher dose, which was not more effective than... 

The safety and efficacy of terbinafine 250 mg/day and itraconazole 200 mg/day given for 12 weeks for toenail onychomycosis have been compared in a randomized, double-blind study in 372 patients (19). Adverse events were reported in 39% of the terbinafine-treated patients and in 35% of the itraconazole-treated patients. The mean values of biochemical parameters of liver and kidney function did not change significantly. Terbinafine produced higher rates of clinical cure (76 versus 58%) and mycological cure (73 versus 46%) than itraconazole. 

The primary study end-point was incidence of DVT and other thromboembolic events assessed clinically and by both locally and centrally assessed ultrasonography. The duplex-ultrasounds of the lower extremities were used to confirm or exclude the occurrence of DVT. These procedures were performed and interpreted by qualified specialists within the same hospi-tal/institution on a real-time basis for the timely and appropriate chnical care of the patient Furthermore, duplex ultrasound studies were videotaped for a subsequent standardized bhnded interpretation by a quahfied, independent laboratory that provided an unbiased evaluation of the incidence of DVT. ThromboemboHc events other than DVT that occurred during the study period were assessed, and the investigator estabhshed the clinical relationship of the event to treatment with rhAT. Secondary end-points were safety, adverse events and immunogenicity. 

Table 31.2. Percentage of patients reporting adverse events in a 90-day safety trial ...

A prospective study evaluated the safety and efficacy of levetiracetam for perioperative anticonvulsive therapy of patients with suspected brain tumors undergoing neurosuigery [89 ]. Thirty patients received levetiracetam 500 mg twice daily for 72 h, after which the dose was increased to 1000 mg twice daily. Two of the 30 patients had adverse events potentially attributable to the medication. One developed paresthesias and a visual field defect. The other also... 

In general, for smokers with cardiac disease, the benefits of nicotine replacement therapy outweigh the potential risks. In a safety and efficacy study that included veterans with cardiac disease, smoking concurrently with the nicotine patch was not associated with an increase in adverse events (Joseph et al. 1996). Although bupropion SR is generally well tolerated by smokers, it has not been adequately studied in persons with cardiac disease, and definitive conclusions regarding its safety in this patient population cannot currently be made (Society for Research on Nicotine and Tobacco 2003). 

Reconfiguration of Data. Drug safety data from different sources are often pooled or combined in databases. Reasons for combining data vary. In the case of premarketing studies, data from different sites are routinely combined because one site may not be able to recruit enough patients for a study. Data from different studies are often combined to increase sample size and therefore statistical power for detecting an uncommon adverse event. 

The adverse event form is a cornerstone of patient safety monitoring, and as such it contains very important data. There are several data issues for the statistical programmer to be concerned about here. 

Just as there is an adverse event form, there is usually a serious adverse event (SAE) form. Note here that serious as defined by the FDA is different from severe on the adverse event form. A patient can have a severe headache that may not be considered serious. The ICH guideline (also in ICH E3) entitled Clinical Safety Data Management Definitions and Standards for Expedited Reporting defines serious adverse events as follows ... 

The study termination form data may be used for efficacy or safety analysis purposes. With regard to safety, if patients discontinue a study medication earlier than patients on standard therapy or placebo, then that is important to know. For efficacy analyses, patients who withdraw due to a lack of efficacy or adverse event may be precluded from being considered a treatment responder or success. Also, often the study termination date is used as a censor date in time-to-event analyses for therapy efficacy. Study termination forms play a key role in patient disposition summaries found at the start of a clinical study report. From a CDISC perspective, the study termination form is a finding. 

When a patient wants to use a dietary supplement, the following points should be addressed inadequate regulations for quality, safety, or efficacy, differences in preparations from different manufacturers, and insufficient reporting of adverse events. 

The safety of rifaximin, 200 mg 3 times daily, was evaluated more recently in 320 patients from two placebo-controlled clinical trials [34], All the adverse events for either rifaximin or placebo that occurred at a frequency > 2% are shown in table 14. With the exception of flatulence, which occurred significantly (p = 0.0071) less frequently after drug treatment, the adverse event profile of rifaximin overlapped that of placebo. 

Postmarketing surveillance is critical to ensuring the safety of medications because of the limitations of Phase 2 and 3 studies to identify rare, serious adverse events. Typically, these studies are too short and the study population is fairly healthy. Once a drug is marketed, the population of patients using the drug expands to include sicker patients, older patients, and other populations. 

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