Clinical outcome studies

In recent years, there has been a growth in the field of mega-studies, usually clinical outcome studies involving 5000-25 000 patients, with a simple primary endpoint such as mortality and a number of secondary morbidity endpoints. The potential for studies of this magnitude to throw up less frequent side effects than those seen in the preregistration programme is clear. 

Several clinical outcome studies using AmnioStat have been reported. Although positive PG results are about 99% predictive of maturity, negative results are highly unpredictive (RDS develops in about 25% of cases with a negative PG, depending on the population) and are therefore not useful chnically. A positive PG result is very usefiil in low-risk pregnancies that require cesarean section. Determination of PG is also usefijl for specimens contaminated with blood or meconium. PG is not found in either blood or meconium, and therefore results are not affected by the presence of either of these contaminants. ... 

The maturity decision cutoff varies from 19,000 to 60,000/p.L. TypicaEy 35,000/p.L is used, " but this is affected strongly by the instrument used. AH clinical outcomes studies have reported that LBC has high sensitivity (95% to 100%) but low specificity (about 70%) for prediction of RDS. A recent meta-analysis reported that at a fixed sensitivity of 95%, the LBC specificity was 80%, whereas the L/S ratio specificity was 70%. 

In support of this, several recent studies have evaluated the clinical outcomes observed in flavivirus-infected patients that carry the CCR5A32 allele. One group... 

Beaulieu C, de Crespigny A, Tong DC, Moseley ME, Alhers GW, Marks MP. Longitudinal magnetic resonance imaging study of perfusion and diffusion in stroke evolution of lesion volume and correlation with clinical outcome. Arm Neurol 1999 46 568-578. 

The PRO ACT-11 trial was designed to assess the clinical efficacy and safety of lA r-pro-UK. In this study, 180 patients were enrolled in a 2 1 randomization scheme to receive either 9 mg lA r-pro-UK plus 4 hours of low-dose IV heparin, or low-dose IV heparin alone. The primary clinical outcome, the proportion of patients with slight or no disability at 90 days (mRS of < 2), was achieved in 40% of the 121 patients in the r-pro-UK treatment group, compared to 25% of the 59 patients in the control group (absolute benefit 15%, relative benefit 58%, number need to treat = 7 p = 0.04). The recanalization rate (TlMl 2 and 3) was 66% for the r-pro-UK group and 18% for the control group (p < 0.001). Symptomatic ICH within 24 hours occurred in 10% of r-pro-UK patients and 2% of control patients (p = 0.06). All symptomatic ICHs occurred in patients with a baseline NIHSS... 

No direct comparison trials have been reported between the different thrombolytic agents in acute ischemic stroke. In a retrospective review of the results for acute stroke lAT performed at our center, we have found significantly higher rates of recanalization and good clinical outcome in the era in which lA UK was used versus the era in which UK was not available and lAT with rt-PA was the primary treatment. Conversely, in another retrospective study, Eckert et al. found no major difference between the recanalization rates of UK and rt-PA. 

Jonsson N, Asplund K. Does pretreatment with statins improve clinical outcome after stroke A pilot case-referent study. Stroke 2001 32 1112-1115. 

Because the severity of the vascular lesion contributes to the size of the infarction and thus the clinical outcome, CTA results may be expected to predict outcome. One study assessed the utihty of CTA in 40 patients with acute stroke syndromes and an NIHSS score of >8. The extent of leptomeningeal collaterals on CTA correlated with the outcome from thrombolysis. In 40 hyperacute stroke patients who received rt-PA, those with CTA evidence of poor collaterals, autolysed thrombi, and T lesions showed little benefit from treatment. ... 

Antihypertensive drug name and dose is associated with compelling indications which are based on benefits from outcome studies or clinical guidelines. For example, the drug class aldosterone antagonists have eplerenone dosed at 25-50 mg per day which is indicated for heart failure patients after an Ml and supported by the EPHESUS trial. 

Many patients cannot tolerate chronic ACE inhibitor therapy secondary to adverse effects outlined below. Alternatively, the angiotensin receptor blockers (ARBs), can-desartan and valsartan, have been documented in trials to improve clinical outcomes in patients with heart failure.68,69 Therefore, either an ACE inhibitor or candesartan or valsartan are acceptable choices for chronic therapy for patients who have a low ejection fraction (EF) and heart failure following MI. Since more than five different ACE inhibitors have proven benefits in MI while only two ARBs have been studied, the benefits of ACE inhibitors are generally considered a... 

Phase II investigates the compound s efficacy and safety in controlled clinical trials for a specific therapeutic indication. To eliminate as many competing factors as possible, Phase II trials are narrowly controlled. They are characterized as small—several hundred subjects with the indicated disease or symptoms—and are closely monitored. The control may be either a placebo study arm or an active control arm. The endpoint measured may be the clinical outcome of interest or a surrogate. Phase II trials may last for several months or even several years. Early pilot trials to evaluate safety and efficacy are called Phase Ila. Later trials, called Phase lib, are important tests of the compound s efficacy. These trials may constitute the pivotal trials used to establish the drug s safety and efficacy. At least one pivotal trial (most frequently a large, randomized Phase III study) is done. Only about one third of compounds entered into Phase II will begin Phase III studies [61],... 

Cuijpers, Pirn, Annemieke van Straten, Gerhard Andersson and Patricia van Oppen, Psychotherapy for Depression in Adults A Meta-Analysis of Comparative Outcome Studies , Journal of Consulting Clinical Psychology 76, no. 6 (2008) 909-22... 

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