Treatment emergent signs and symptoms

In guidance document ICH E3, Structure and Content of Clinical Study Reports, the FDA defines treatment-emergent signs and symptoms (TESS) as events not seen at baseline and events that worsened even if present at baseline. As simple as that may sound, it can sometimes be quite difficult to program. The important data variables that come into play are dosing record dates and times, adverse event start and stop times, and adverse event severity. All of these data variables need to be completed accurately for TESS to be calculated properly. 

A popular way to present adverse events in a clinical trial is in terms of treatment emergent signs and symptoms (Nilsson and Koke, 2001). The idea behind this is that if an adverse event was being experienced by a patient before he or she took the treatment, then it cannot have been caused by the treatment. Thus, in order to compare a treatment with its control in terms of adverse events it is only necessary to record those adverse events which have either arisen since the beginning of the trial or become worse. 

Table 23.1 Illustration of treatment emergent signs and symptoms (TESS). In the crossclassification by baseline and outcome, patients with TESS nnmber c for the experimental group and g for the control gronp. Thus c patients with TESS out of on the one hand are compared with g patients out of on the other. A more conventional analysis would compare a + c patients with adverse events in the treatment group with e -I- g in the control group. A more sophisticated analysis might stratify by baseline state and compare treatment and control using the Mantel-Haenszel procednre.

Placebo-controlled studies In a doubleblind, randomized, placebo-controlled study of the use of once-daily atomoxetine up to 1.8 mg/kg/day in 105 patients aged 6-16 years with ADHD, the most common treatment-emergent signs and symptoms were anorexia (atomoxetine 18% placebo 6%), somnolence (15% versus 9%), abdominal pain (13% versus 3%), and nausea (11% versus 3%) [52 ]. 

There were inadequate facilities in the Emergency Department at St Luke s to permit a large number of casualties to remove contaminated clothing and to shower formal decontamination was, therefore, impossible. In addition, the ventilation in the patient reception area was poor. Consequently, some of the medical staff complained of eye or throat pain, nausea, or miosis (Okumura et al, 1996). This was relieved by improving ventilation and by rotation of affected staff to other locations within the hospital. Secondary exposure of medical staff from patients affected by sarin vapour was limited. No medical staff required pharmacological treatment for their signs and symptoms. 

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Additional examinations. If the employee for any reason develops signs or symptoms commonly associated with exposure to inorganic arsenic the employer shall provide an appropriate examination and emergency medical treatment. 

The initial measure of severity of asthma in a patient is based on the frequency and duration of respiratory symptoms and the degree of airflow limitation. Once asthma is well controlled, one of the best ways to judge severity is to determine the level of treatment needed to maintain acceptable control. Signs of severe or poorly controlled asthma also include a prior near-fatal episode, recent hospitalization, or visit to the emergency room nighttime symptoms limitation of daily activities need for inhaled P2-adrenoceptor agonist several times per day or at night and FEVi or PEF of <60% of predicted value. 

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