Entry criteria

Pre-entry criteria define the conditions and circumstances under which site characterization activities will be initiated and the manner in which these activities will proceed. At each stage of the process (i.e., approach to the site, on-site characterization activities, sample collection, and exiting the site), specific criteria may be defined for proceeding to the next stage. The pre-entry criteria may also specify the general makeup of the site characterization team under various circumstances. For example, under low-hazard conditions chemical facility teams may perform site characterization, while specially trained responders might be called upon to assist in the case of potentially hazardous conditions at the site. The criteria developed for a particular chemical facility should be consistent with the role that the facility has assumed in performing site characterization activities. 

Provision of adequate competent medical staff is essential for the safe and ethical conduct of studies in humans. Decisions about whether a volunteer fulfils the entry criteria for a healthy subject or should be withdrawn from a study, how to respond to an unexpected adverse event and when to discontinue a study can prove challenging to the most experienced physician. Similarly, research nurses need many organisational and other skills over and above those that they acquired during their basic clinical training. Scientific staff must be competent in the techniques that will provide the essential data. All must be properly briefed about what will be required of them during the course of a study, and must be fully familiar with local standard operating procedures (SOPs) in compliance with good clinical practice (GCP). 

Check that the volunteer fulfils aU entry criteria review screening tests... 

Phase IV. post-licensing studies in the target population, with widening of entry criteria to broaden experience in clinical practice study objectives are typically surveillance for safety or further comparisons with other therapies. The results of such trials are more likely to be used for marketing purposes than in support of applications to regulatory authorities. 

Bias in subject selection may not be avoided simply by randomisation. Randomisation will avoid weighted allocation to one treatment regimen rather than another, but it will not avoid selection of the wrong kind of subject in the first place, which will subsequently affect the degree to which the data can be extrapolated. Thus, an investigator may have a preconceived idea about the safety of a drug or about its effectiveness in a particular subset of subjects who nonetheless meet the entry criteria. This prejudice may be avoided by stratification of subjects... 

Because the above trials showed a >50% relative reduction in total mortality with ICD therapy, MADIT II used broader entry criteria for primary prevention of SCD, removing the criteria for NSVT and EPS 1,232 patients with a history of MI > 30 days prior and an EF < 30% were randomized to conventional therapy or ICD implantation [10]. Conventional therapy was comparable in both arms and included a high rate of use of beta blockers, angiotensin-converting enzyme inhibitors, and statins (over two thirds for all medications in both arms). The trial was stopped early at 20 months because the relative reduction in total mortality... 

Table 4.1 Entry criteria in randomized trials of cardiac resynchronization therapy...

Fig. 4.2 In Panel A, the effects of CRT on NYHA class is shown for three trials, all of which shared similar entry criteria and a 6-month randomized, double-blind study duration. In each graphic, control (no CRT) is represent in open boxes and patient treated with CRT (CRT) in hashed boxes. Panel B represents the effect of CRT on 6-min hall walk distance and Panel C represents the peak oxygen consumption on cardiopulmonary exercise testing...

A second method that has been used to overcome these problems is to collect data retrospectively from patients who are not in the trial but who would have met its entry criteria, using these data to estimate the likely costs and outcomes in usual care. These patients could have received their care prior to the trial (historical comparison group) or concurrent with it... 

Entry criteria the patients should preferably be at the moderate to severe end of the disease scale. 

How many individuals were screened to find those who qualified for our trials Does this indicate that there will be enough patients that meet the entry criteria to justify continuing this clinical program ... 

Regardless of physician resistance, Ayerst was forced to redesign propranolol s clinical trials several times in order to create a study protocol that would meet FDA requirements. For example, detailed negotiations were necessary to work out the entry criteria for a trial launched in 1973. The company wanted to accept patients who had two angina attacks per week, wliile the agency demanded five per week. Ultimately, both sides agreed that no more than one-fourth of any one test group could have fewer than five attacks per... 

Verify compliance with entry criteria and procedures, for all study subjects, as specified in the protocol. 

---