Inclusion criteria

ECASS-II was designed to test a lower dose of rt-PA (0.9 mg/kg) during the same 0-6-hours time period after stroke onset, using similar inclusion criteria as in ECASS-I. ° The primary endpoint was the proportion with a favorable outcome on the mRS scale (defined as a score of 0 or 1). There was no difference in this outcome between rt-PA-treated and placebo controls (40% vs. 37%, p = 0.28). A separate analysis of the 158 subjects enrolled within 3 hours of stroke onset also showed no difference in the proportion with a favorable outcome (42% vs. 38%, p = 0.63) this result, however, must be treated with caution because in ECASS-II there was a substantially lower number of patients treated within 3 hours of stroke onset, compared to the 1995 NINDS rt-PA study. Parenchymal hematoma on post-treatment CT was seen in 12% of rt-PA-treated and 3% of placebo patients (p < 0.001). The 90-day mortality rate was 11 % for the rt-PA group and 11 % for the placebo group (p = 0.54). Protocol violations were much less frequent in ECASS-II compared to ECASS-I (9% vs. 18%), probably because of standardized training in CT interpretation at the study sites. 

The number of study sites to be used for a clinical trial depends on the characteristics and number of subjects that need to be recruited. Often, a sufficient number of participants cannot be enrolled from a single site, especially if the study inclusion criteria are restrictive and the timeframe for recruitment is limited. In order to complete the study within a reasonable period of time, an inclusion of multiple research centers is often necessary (Chow and Liu, 1998). The selection of study sites depends on several factors including ... 

Alteplase initiated within 3 hours of symptom onset has been shown to reduce the ultimate disability due to ischemic stroke. A head CT scan must be obtained to rule out hemorrhage before beginning therapy. The patient must also meet specific inclusion criteria and no exclusionary criteria (Table 13-2). The dose is 0.9 mg/kg (maximum 90 mg) infused IV over 1 hour after a bolus of 10% of the total dose given over 1 minute. Anticoagulant and... 

Inclusion Criteria (all YES boxes must be checked before treatment)... 

Pharmacogenetics provides a rational framework to minimize the uncertainty in outcome of drug therapy and clinical trials and thereby should significantly reduce the risk of drug toxicity. The reader is referred to the Internet sources in Table 20.1 for more details on pharmacogenetics and drug development. Potential improvements in patient inclusion criteria will be addressed later in this chapter. 

Eligibility Ages eligible for study, 50-85 years genders eligible for study, both Inclusion Criteria ... 

Criteria for use (or not) of data from patients who do not meet the protocol s inclusion criteria or who failed to provide complete data sets should ideally be defined before the study starts and definitely before the final analysis is initiated. 

Subject selection Number of subjects Inclusion criteria Exclusion criteria Withdrawal criteria... 

The budget must be set, the means of payment agreed and contractual arrangements for premature trial termination decided. In addition, the legal contract should include payments, if any, when a study subject drops out or when it is impossible to evaluate an individual subject (e.g. protocol violations by an investigator, such as recruitment of subjects who do not meet the inclusion criteria - which are an indication for extra clarification of protocol requirements). There should be a clear understanding of the costs and expenses that the site s institution or hospital will absorb and what the sponsor will pay for either directly or indirectly. 

Do the inclusion criteria identify a representative sample of the patients to whom the study results will be relevant ... 

To ensure compatibility with the Royal Society of Chemistry s food composition tables, predetermined screening procedures were used (Table 4.6), which were derived from those outlined for the nutrient tables." All publications and reports on flavonoid content of foods were subsequently evaluated employing the screening procedures (Table 4.6). In brief, inclusion criteria were (a) randomly selected food items purchased from various commercial outlets during different seasons of the year, (b) food samples prepared using normal domestic... 

The patients in the Zielinski et al. (1993) study developed more severe cardiac complications than did those of Rice et al. (1994). This discrepancy may result from the former study requiring rigorous evaluation of cardiac illness, with strict inclusion criteria, and thus may have involved relatively sicker patients. Nonetheless, even in the Zielinski et al. (1993) study, 38 of 40 cardiac patients completed a course of ECT. Indeed, with proper monitoring and management, patients with cardiac disease can be safely treated with ECT (American Psychiatric Association Task Force on Electroconvulsive Therapy 1990). 

The previous course of a disorder and its resolution with treatment can be a key element of patient selection. Investigation of the effects of a drug in de novo diagnosed, first-episode patients will lead to different conclusions than a trial in mainly chronic, multitreatment-exposed patients. Some key inclusion criteria can be defined according to the treatment response history of patients a study with clozapine in treatment resistant schizophrenic patients (Kane et ah. 1988 see Chapter 2) is an example for this. 

Shift inclusion criteria to an acute/subchronic rather than a very chronic population. But patients in the acute phase of an episode may show spontaneous recovery. 

The risk of relapse in discontinuation trials depends on many non-pharmacological, often poorly controllable factors, notably the expectations of the patients, doctors and nurses, other environmental factors, the duration of hospitalization and prior treatment, and the time interval since the last acute psychotic episode. On the basis of an analysis of 14 discontinuation trials, Kane and Lieberman (1987) found that the relapse rate varied greatly from study to study depending on the trial, relapse rates of 30 86% with clustering around 60 70% have been reported in the first 12 months after placebo substitution. According to Kane and Lieberman, this scatter is a result of the different inclusion criteria applied and the different definitions of relapse . 

Only 20% to 33% of metastatic breast carcinomas robustly express HER2, and tumors that do not overexpress the protein are unlikely to benefit from treatment. Hence demonstration of clinical benefit in unselected breast cancer patients was a challenging task [24]. The need to keep patients on other chemotherapies added to the complexity of clinical trials. Nevertheless, the decision to first demonstrate overexpression of HER2 antigen levels as one of the key clinical trial inclusion criteria, reached in consultation with the FDA, allowed the investigators to demonstrate efficacy (Table 14.2). 

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