Randomized trial advantages over

The Cochrane group examined (a) whether the addition of UFH or LMWH to antiplatelet agents offers any net advantage over antiplatelet monotherapy for acute stroke, and (b) the effectiveness of anticoagulants compared to antiplatelets in acute ischemic stroke. They included 4 trials of 16,558 patients, each of which specified aspirin (160-333 mg daily) as the control, and all of which randomized patients within 14 days of stroke onset. The anticoagulants tested were UFH and LMWH. Almost 98% of the patients were followed up for 6 months. 

The third approach is the introduction of another type of radiation quality high-LET radiation. Clinical experience with neutrons has demonstrated that high-LET radiations are superior to low-LET radiations for some tumor types or sites. Fast neutrons were indeed the first high-LET radiations to be applied clinically (see Sec. 4.1). Although in the first studies they were applied in suboptimal conditions from a technical or dose distributions point of view, their advantage for some types of tumors is well established, particularly for slowly growing, well-differentiated tumors. Randomized trials have indeed shown their superiority over conventional photons for salivary gland tumors and prostatic adenocarcinomas. 

Oxcarbazepine is a keto derivative of carbamazepine but offers several advantages over carbamazepine. Oxcarbazepine does not require blood cell count, hepatic, or serum drug level monitoring. It causes less cytochrome P450 enzyme induction than does carbamazepine (but may decrease effectiveness of oral contraceptives containing ethinyl estradiol and levonorgestrel). As opposed to carbamazepine, oxcarbazepine does not induce its own metabolism. These properties, combined with its similarity to carbamazepine, led many clinicians to use this medication for the treatment of bipolar disorder. Randomized controlled trials suggested efficacy in the treatment of acute mania compared with lithium and haloperidol, but these trials were quite small and did not include a placebo control (Emrich 1990). 

Harms DO, Gobel U, Spaar HJ et al. COALL Study Group. Thioguanine offers no advantage over mercaptopurine in maintenance treatment of childhood ALL results of the randomized trial COALL-92. B/oott 2003 102 2736-2740. 

Differences in response rates were substantial in small studies, and especially between single-institution and large cooperative group trials. The major reason for these discrepancies is attributed to selection of patients for study those entered in single-institution studies tended to have better performance status and perhaps to have less extensive disease. These conclusions were reinforced by a comparison of the NCI Canada study that demonstrated a survival advantage for chemotherapy over best supportive care with two other randomized trials that failed to show such a difference. The negative trials included patients with performance status of 2, while the NCI... 

However, such large treatment effects are rare. Most treatments used in medicine have smaller effects that require assessment in randomized controlled trials if they are to be reliably quantified. Specifically, randomization has two main advantages over a non-randomized comparison. First, it ensures that clinicians do not know which treatment the patient will receive, and cannot select certain types of patient for one particular treatment. Second, it tends to result in an equal balance of baseline risk across the treatment groups. 

Recent meta-analyses of randomized trials of colloid administration to human critical care patients demonstrated no advantage of colloids over crystalloids and concluded that colloids increased mortality when used in some clinical syndromes (Choi et al 1999, Schierhout Roberts 1998). When trauma patients were studied as a subpopulation, a 12.3% difference in mortality rate was identified in favor of crystalloid therapy. Conversely, analysis of pooled data from nontrauma patients identified a 7.8% difference in mortality rate in favor of colloid treatment (Velanovich 1989). The majority of clinical trials in these meta-analyses compared albumin with crystalloid solutions and thus these results should not discourage the use of hydroxyethyl starches in horses. 

Friedman and colleagnes condncted a post hoc pharmacoeco-nomic evalnation of two mnlticenter, randomized trials comparing the combination of ipratropium and albnterol with both dmgs used as monotherapy. Patients who received a combination of ipratropium and albnterol had lower rates of exacerbations, lower overall treatment costs, and improved cost-effectiveness compared with either drng nsed alone. With the introdnction of new bronchodilator therapies, and with no clearly consistent advantage of one class of agents over another, pharmacoeconomic analyses may be nsefnl for clinicians in determining the most appropriate therapy for their patients. 

Saarenmaa E, Huttunen P, Leppaluoto J, et al. Advantages of fentanyl over morphine in analgesia for ventilated newborn infants after birth A randomized trial. J Pediatr 1999 134 144-150. 

On May 19, 2004, docetaxel was approved for the treatment of metastatic prostate cancer. The approval was based on the TAX327 study, a randomized, multicenter global clinical trial enrolling over 1000 men with metastatic, hormone-refractory prostate cancer. The study compared docetaxel 75 mg/m every 3 weeks and prednisone 5 mg twice a day with docetaxel 35 mg/m weekly five out of six weeks and prednisone 5 mg twice a day and mitoxantrone 75 ng/m every 3 weeks and prednisone 5 mg twice a day. Docetaxel, in combination with prednisone, given every 3 weeks showed a survival advantage of approximately 2.5 months over the control group in the trial p =. 009). The most common adverse events reported were nausea, alopecia, and bone marrow suppression. In addition, fluid retention and peripheral neuropathy, known effects of docetaxel, were... 

Because clot-bound thrombin is less effectively inhibited by UFH (attachment of fibrin to the fibrin-binding domain makes the heparinbinding domain inaccessible), it was proposed that the direct antithrombins had an advantage over UFH in STEMI patients treated with a fibrinolytic because of their greater ability to block both fluid-phase and clotbound thrombin. This thrombin hypothesis was the basis for several randomized trials. After the TIMI 9A, GUSTO Ila, and HIT 3 trials that tested hirudin as an adjunct to fibrinolytic therapy were... 

Topical NSAID preparations are used infrequently in North America. Theoretically, administration via a topical vehicle targets the joints involved and decreases systemic exposure. Randomized, controlled trials, typically of less than 4 weeks duration, have suggested that topical NSAIDs are superior to placebo in relieving OA pain in the first 2 weeks of treatment, but the effect may decline over time.33 Moreover, data are lacking to quantify the theoretical safety advantage of administering NSAIDs topically. 

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