Randomized controlled clinical trial

Data on antidepressant dmgs are available from a number of sources randomized, controlled clinical trials (RCTs) in both hospital and primary-care populations decision analytic models population-based naturalistic observational studies of usual... 

Randomized, controlled clinical trials reduce bias and variability by a process of selection, randomization and standardization of treatment, and often take place under artificial conditions isolated from those of routine clinical practice (Freemande et al, 1993 Simon et al, 1995b). Yet it is the uncontrolled interactions of a dmg technology with patients, health-care workers and the system of health care that ultimately lead to much of the variability in outcomes and expenditures in clinical practice. Thus the value of RCTs in evaluating cost-effectiveness in clinical practice maybe limited (Reeder, 1995 Simon et al, 1995b Hotopf et al, 1996). 

In randomized, controlled, clinical trials, calcium channel blockers were as effective as p-blockers at preventing ischemic symptoms. Calcium channel blockers are recommended as initial treatment in IHD when /3-blockers are contraindicated or not tolerated. In addition, CCBs may be used in combination with /3-blockers when initial treatment is unsuccessful. However, the combination of a (1-blocker with either verapamil or diltiazem should be used with extreme caution since all of these drugs decrease AV nodal conduction, increasing the risk for severe bradycardia or AV block when used together. If combination therapy is warranted, a long-acting dihydropyridine CCB is preferred. (3-Blockers will prevent reflex increases in sympathetic tone and heart rate with the use of calcium channel blockers with potent vasodilatory effects. 

The United States Pharmacopeial Convention, Inc. (USP) in 2000 issued the USP criteria for levels of evidence for botanical articles [117]. While issued for botanicals, the criteria have application to all therapeutic agents. The USP criteria rank evidence from I to IV, with Level I being the strongest. Within Level I, the randomized controlled clinical trial is ranked highest, followed by meta-analysis and epidemiological studies. Level II consists of the same designs, but with methodological flaws. Level III includes inconclusive studies, and Level IV is anecdotal evidence. 

Prantera C, Zannoni F, Scribano ML, Berto E, Andreoli A, Kohn A, Luzzi C An antibiotic regimen for the treatment of active Crohn s disease A randomized controlled clinical trial of metronidazole plus ciprofloxacin. Am J Gastroenterol 1996,91 328-332. 

The cautious approach to drug approval, as overseen by the federal Food and Drug Administration (FDA), has been described in detail elsewhere (Findlay, 1999). The risks and benefits of a new drug submitted for FDA approval are rigorously studied through randomized, controlled clinical trials. Despite the enormous effort put forth to study new drugs, and the huge financial investment required to support clinical trials, many questions are often left unanswered by the relatively small-scale preapproval studies that may fail to detect, or fully describe, low-incidence adverse effects. These adverse effects may become evident within the months or years immediately... 

Van Patten, C.L., Olivotto, I.A., Chambers, G.K., et al. (2002). Effect of soy phytoestrogens on hot flushes in postmenopausal women with breast cancer a randomized, controlled clinical trial, J. Clin. Oncol., 20, 1449-1455. 

The gold standard for human studies is called the randomized, controlled clinical trial. Such trials are close to experimental animal studies, but for obvious ethical reasons, they cannot be conducted to identify toxicity. They are, instead, designed to determine whether certain pharmaceutical or nutritional regimens, for example, reduce the risks of disease. They may provide information about adverse side effects, but they are not designed for studying toxicity. 

There is only one randomized controlled clinical trial of pacing therapy to increase heart rates in patients with chronic heart failure and that is the... 

Indirect comparisons are potentially subject to methodological flaws, mainly because, outside the confines of a single randomized controlled clinical trial, one cannot be sure that the patients enrolled in the various trials are equivalent in terms of baseline risk, the settings for the trials are comparable, and that endpoints are measured in the same way. Therefore, an apparent superiority for one therapy over another, in an indirect comparison, may be as much due to differences in the trials as to differences between the therapies themselves. 

T, Vestergaard, P.A., and Carbonell, C. (2000) A review of randomized, controlled clinical trials in acute mania./ Affect Disord 59 S31-S39. 

Castells X, Casas M, Vildal X, Bosch R, Roncero C, Ramos-Quiroga JA Capella D (2007) Efficacy of central nervous system stimulant treatment for cocaine dependence a systematic review and meta-analysis of randomized controlled clinical trials. Addiction, 102, 1871-87 Chaisson RE, Bacchetti P, Osmond D, Brodie B, Sande MA Moss AR (1989). Cocaine use and HIV infection in intravenous drug users in San Francisco. Journal of the American Medical Association, 261, 561-5 Chapleo CB Walter DS (1997). The bupre-norphine-naloxone combination product. Research and Clinical Forums, 19, 55-8 Cheskin LJ, Fudala PJ Johnson RE (1994). A controlled comparison of buprenorphine and clonidine for acute detoxification from opioids. Drug and Alcohol Dependence, 36, 115-21... 

Matsumoto AK et al A randomized, controlled, clinical trial of etoricoxib in the treatment of rheumatoid arthritis. J Rheumatol 2002 29 1623. [PMID 12180720]... 

Certain echinacea constituents have demonstrated anti-inflammatory properties in vitro. Inhibition of cyclooxygenase, 5-lipoxygenase, and hyaluronidase may be involved. In animals, application of Epurpurea prior to application of a topical irritant reduced both paw and ear edema. Despite these laboratory findings, randomized, controlled clinical trials involving echinacea for wound healing have not been performed in humans. 

A meta-analysis of randomized controlled clinical trials, which compared benzodiazepines against Zaleplon or other Z drugs such as... 

Quinidine is used for the maintenance of normal sinus rhythm in patients with atrial flutter or fibrillation. It is also used occasionally to treat patients with ventricular tachycardia. Because of its cardiac and extracardiac side effects, its use has decreased considerably in recent years and is now largely restricted to patients with normal (but arrhythmic) hearts. In randomized, controlled clinical trials, quinidine-treated patients are twice as likely to remain in normal sinus rhythm compared with controls. However, drug treatment was associated with a twofold to threefold increase in mortality. 

To assess the feasibility of angiogenic cell therapy for patients with peripheral artery diseases, we organized a randomized controlled clinical trial using CDI33+ cells implanted in ischemic limbs. The goal of the study is to demonstrate that intramuscular implantation of autologous human CD 133 + cells into ischemic limbs effectively induces collateral vessel formation, improving function, and trophic ischemic lesions (79-81). 

Simons M, Annex BH, Laham RJ, et al. Pharmacological treatment of coronary artery disease with recombinant fibroblast growth factor-2 double-blind, randomized, controlled clinical trial. Circulation 2002 105(7) 788—793. 

The randomized controlled clinical trials performed by Freis and his colleagues at the Veterans Administration Hospitals have provided some of the first solid evidence that moderate permanent hypertension has an improved prognosis when actively treated by sodium depletion (hydrochlorothiazide), by interruption of the sympathetic nervous system (reserpine) and with a vasodilator (hydralazine) (262). In parallel, the beneficial effects of this triple therapy were demonstrated in spontaneously hypertensive rats by the spectacular prevention and cure of their cardiac, vascular, and renal lesions (263). 

The randomized controlled clinical trial is the method of choice for the objective and quantitative demonstration of the efficacy and tolerability of a new medicine. None the less, such studies have limitations in discovering possible adverse events that may occur, in particular those that are rare or develop after prolonged use, in combination with other drugs, or perhaps due to unidentified risk factors. Clinical trials are inherently limited in duration and number of patients, and, significantly, patients are selected prior to inclusion. In other words, the conditions of a trial are artificial compared with the real-life use after the introduction of a medicine (p. 229). 

Matthews, J.N.S., 2006, Introduction to randomized controlled clinical trials, 2nd edition, Chapman Hall/CRC (283 pages, paperback). 

Simons, M., Annex, B.H., Laham, R.J., Kleiman, N., Henry, T., Dauerman, H., Udelson, J.E., Gervino, E.V., Pike, M., Whitehouse, M.J., Moon, M., and Chronos, N.A. 2002. Pharmacological treatment of coronary artery disease with recombinant fibroblast growth factor-2 doubleblind, randomized, controlled clinical trial. Circulation 105 788-793. 

Healthy subjects were immunized with the heat-killed J5 vaccine and then-sera harvested. In a multi-center, randomized controlled clinical trial, patients... 

The only two randomized controlled clinical trials performed so far did not result in a final proof of the efficacy of the oximes in the treatment of poisonings induced by the OP insecticides in humans due to methodological problems (Eddleston et al., 2002). However, experimental and clinical experience suggests that among the pyridinium oximes, obidoxime andtrimedoxime, although relatively toxic, could provide reactivation and antidotal protection against most of the OP insecticides. In addition, HI-6 has proved to be effective in the treatment of soman-poisoned animals and safe and effective in patients poisoned with diethoxy OPs. 

Tyring SK, Beutner KR, Tucker BA, et al. Antiviral therapy for herpes zoster. Randomized, controlled clinical trial of valacyclovir and famciclovir therapy in immunocompetent patients 50 years and older. Arch Earn Med 2000 9 863-869. 

VEGE Inhibition Smdy in Ocular Neovascularization (Vl.S.l.O.N.) Clinical Trial Group. Year 2 efficacy results os 2-randomized controlled clinical trials of pegaptanib for neovascular age-related macular degeneration. Ophthalmology 2006 113 1508. 

---