Clinical trials placebo control

Control. A term which can be used in a number of ways in clinical trials but which is always related to the idea of controlling for various sources of bias. In a controlled (parallel) clinical trial, the control group is a group of patients otherwise presumed similar to the patients given the experimental treatment, but who are given an alternative treatment (for example, a placebo) in order to provide a standard of comparison for the experimental treatment. 

Several clinical trials have been conducted with streptokinase adrninistered either intravenously or by direct infusion into a catheterized coronary artery. The results from 33 randomized trials conducted between 1959 and 1984 have been examined (75), and show a significant decrease in mortaUty rate (15.4%) in enzyme-treated patients vs matched controls (19.2%). These results correlate well with an ItaUan study encompassing 11,806 patients (76), in which the overall reduction in mortaUty was 19% in the streptokinase-treated group, ie, 1.5 million units adrninistered intravenously, compared with placebo-treated controls. The trial also shows that a delay in the initiation of treatment over six hours after the onset of symptoms nullifies any benefit from this type of thrombolytic therapy. Conversely, patients treated within one hour from the onset of symptoms had a remarkable decrease in mortaUty (47%). The benefits of streptokinase therapy, especially in the latter group of patients, was stiU evident in a one-year foUow-up (77). In addition to reducing mortahty rate, there was an improvement in left ventricular function and a reduction in the size of infarction. Thus early treatment with streptokinase is essential. 

It has been proposed that the development of the complications of diabetes mellitus may be linked to oxidative stress and therefore might be attenuated by antioxidants such as vitamin E. Furthermore, it is discussed that glucose-induced vascular dysfunction in diabetes can be reduced by vitamin E treatment due to the inactivation of PKC. Cardiovascular complications are among the leading causes of death in diabetics. In addition, a postulated protective effect of vitamin E (antioxidants) on fasting plasma glucose in type 2 diabetic patients is also mentioned but could not be confirmed in a recently published triple-blind, placebo-controlled clinical trial [3]. To our knowledge, up to now no clinical intervention trials have tested directly whether vitamin E can ameliorate the complication of diabetes. 

Kranzler HR, Wesson DR, Billot L Naltrexone depot for treatment of alcohol dependence a multicenter, randomized, placebo-controlled clinical trial. Alcohol Clin... 

Nestler EJ, Hyman SE, Malenka RC Molecular Neuropharmacology A Foundation for Clinical Neuroscience. New York, McGraw Hill, 2001 Novick DM, Pascarelli EE, Joseph H, et al Methadone maintenance patients in general medical practice a preliminary report. JAMA 259 3299—3302, 1988 Nunes EV, Quitkin EM, Donovan SJ, et al. Imipramine treatment of opiate-dependent patients with depressive disorders a placebo-controlled trial. Arch Gen Psychiatry 55 153-160, 1998... 

Kranzler HR, Bauer LO, Hersh D, et al Carbamazepine treatment of cocaine dependence a placebo-controlled trial. Drug Alcohol Depend 38 203-211, 1995 Levin FR, Lehman AF Meta-analysis of desipramine an adjunct in the treatment of cocaine addiction. J Clin Pharmacol 11 374-378, 1991 Lima MS, Reisser AA, Soares BG, et al Antidepressants for cocaine dependence. Cochrane Database Syst Rev 4 CD002950, 2001 Ling W, Shoptaw S, Majewska D Baclofen as a cocaine anti-craving medication a preliminary clinical study 0etter). Neuropsychopharmacology 18 403 04, 1998... 

Highly selective COX-2 inhibitors - coxibs (rofecoxib, celecoxib, or less popular - valdecoxib, etoricoxib parecoxiband lumiracoxib) - were found to be well tolerated in a series of placebo-controlled clinical trials [8]. However, rofecoxib and valdecoxib have been withdrawn from the market because of an increased incidence... 

Tollefson GD, Sanger TM (1997). Negative symptoms a path analytic approach to a double blind, placebo controlled clinical trial with olanzapine. Am J Psychiatry 154,... 

Yamaguchi T, Sano K, Takakura K, Saito I, Shinohara Y, Asano T, Yasuhara H. Ebselen in acute ischemic stroke a placebo-controlled, double-blind clinical trial. Ebselen study group. Stroke 1998 29 12-17. 

The mean dietary intake of soy isoflavones in Asian populations consuming soy-based diets ranges from 20-40 mg isoflavones/day, with upper percentile consumer intakes of 70 mg/day (corresponding to around 1 mg/kg body weight). In the six month intervention studies in Western postmenopausal women, the effective dose for improved BMD was around 80-90 mg/day, while in the one year, randomized, double-blind, placebo controlled clinical trial, the effective dose was 54 mg/day. Overall, the dietary recommendation is to consume 50 mg isoflavones/day in combination with standard nutritional requirements for calcium and vitamin D. 

For any intervention intended to impact favorably upon human health, it is important to evaluate its safety and efficacy in order to demonstrate that it does not cause harm and it does provide the expected benefit. The gold standard method for evaluating any intervention, whether it be a botanical product, dietary supplement, drug, medical device or medical procedure, is the randomized, clinical trial (RCT). A clinical trial is a type of experiment conducted in human subjects where the effects of at least two interventions are compared. Often, the clinical trial takes the form of an active treatment compared to an inactive control or placebo. 

There are two main types of clinical trial design, parallel and cross-over. In a parallel study, subjects are assigned to one of two or more treatments, e.g. active and placebo, and proceed through the trial concurrently. In a cross-over design, subjects act as their own controls, undergoing two or more treatments in sequence (see Fig. 12.1). 

PORKKALA-SARATAHO E K, NYYSSONEN K M, KAIKKONEN J E, POULSEN H E, HAYN E M, SALONEN R M, SALONEN J T (1998) A randomized, single-blind, placebo controlled trial of the effects of 200 mg a-tocopherol on the oxidation resistance of atherogenic hpoproteins, American Journal of Clinical Nutrition, 68, 1034-41. 

KLIPPEL K F, HiLTL D M, scHipp B (1997) A multicentric placebo controlled double-blind clinical trial of beta-sitosterol for the treatment of benign prostate hyperplacia. British J Urology, 80(3) 427-32. 

Clemens, J.A., Bulkley, G.B., Cameron, J.L., Milligan, F.L., Hutcheon, L., Horn, S.D. and MacGowan, S.W. (1991). Effect of xanthine oxidase inhibition with allopurinol on the incidence and severity of post-ERCP pancreatitis and hyper-amylasaemia in a prospective, randomized, double-blind, placebo-controlled clinical trial of 168 patients. Gastroenterology 100, A270. 

Bellomo R, Chapman M, FinferS, et al. Low-dose dopamine in patients with early renal dysfunction a placebo-controlled randomized trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 2000 356 2139-2143. 

In placebo-controlled clinical trials, alendronate, ibandronate, and risedronate increased bone mineral density by up to 5% to 8% in the lumbar spine and up to 3% to 5% in the hip.13-16 Additional data suggest that bone mineral density continues to increase with long-term therapy of 7 to 10 years.17,18... 

Zhang, Z., Wang, X., Chen, Q. etal. (2002). Clinical efficacy and safety ofhuperzine Ain treatment of mild to moderate Alzheimer disease, a placebo-controlled, double-blind, randomized trial. National Medical Journal of China, 82( 14), 941-5. 

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],... 

Moore s idea of analysing the data that had been sent to the FDA seemed brilliant, and I proposed that we work on it together. So we began. Moore wrote to the FDA invoking the Freedom of Information Act and requested the medical and statistical reviews of every placebo-controlled clinical trial for the treatment of depression by what, at that time, were the six most widely used new-generation antidepressant drugs Prozac, Seroxat (Paxil in... 

Because of the power of the placebo effect, almost anything that is believed in seems to work for some types of medical problems. That is why the late Arthur K. Shapiro described the history of medicine as largely the history of the placebo effect.4 It is also why clinical experience alone cannot tell us whether a particular physical substance is an effective treatment. Placebo-controlled trials are required to demonstrate drug efficacy before drugs are approved for marketing. 

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