Standardization, multicenter studies

Compiled from US. Modafinil in Narcolepsy Multicenter Study Group and Standard of Practice Committee of the American Sleep Disorders Association. Pradice parameters for the use of stimulants in the treatment of narcolepsy. Seep 1994 17 348-351. 

Modafinil is a stimulant medication used to improve wakefulness in patients with narcolepsy, obstructive sleep apnea/hypopnea syndrome (as adjunct to standard treatments for the underlying disorder), and shift work sleep disorder. Controlled and open trials provided data on the efficacy and safety of modafinil in patients with narcolepsy (Besset et al. 1996 Billiard et al. 1994 Broughton et al. 1997 Mitler et al. 2000 U.S. Modafinil in Narcolepsy Multicenter Study Group 1998, 2000). Modafinil has a long duration of action and low potential for dependence and may be a reasonable first choice in the treatment of mild to moderate narcolepsy (Silber 2001). There is also considerable interest in the potential use of modafinil in the treatment of ADHD, and studies are in progress. 

In a randomized, multicenter study in 94 patients, mesalazine 4 g/day for 12 weeks in a microgranular formulation was as effective as a standard dose of a glucocorticoid (6-methylpredisolone 40 mg/day) in mild to moderate Crohn s ileitis (Crohn s Disease Activity Index 180-350) (9). The group treated with methylpredisolone had a higher number of adverse events than those given mesalazine. The only adverse effect related to mesalazine was acute pancreatitis, which resolved on withdrawal. 

In the multicenter study of the Information Network of Departments of Dermatology, sensitization rates of preservatives in the standard series were all over 1% in the test population of 11485 patients. Thiomersal was rating highest (5.3%), chloromethyl-isothiazolinone/methyi-sothiazolinone, formaldehyde, and methyl-dibromo-glutaronitrile/phenoxyethanol were next at about 2%, and parabens rating lowest at 1.6%. Glutaral, a biocide... 

With evidence that monitoring BNP can be helpful in stratifying disease severity, whether treatments that lower BNP result in decreased morbidity and mortality has to be considered, and multicenter studies are imderway to address this question. The initial data from smaller trials and pilot studies look promising. A pilot study examined BNP in patients admitted with decompensated CHF and treated with the current standard of care. BNP was monitored regularly during hospitalization (hut bhnded to physicians) and correlated with the following endpoints mortality in hospital. 

One of the most important means of quality control of a clinical study is managed by frequent and thorough monitoring. A monitor s aim is first to protect the agenda of the sponsor/CRO who employs him/her. Monitors (often referred to as CRAs or Clinical Research Associates or Assistants in the pharmaceutical industry) must ensure maintenance of proper standards, compliance with the protocol, accurate and complete data capture and standardization across sites in a multicenter study. Basically, monitors will undertake the review noted in Table 12.8. 

The gold standard test for new therapeutic agent is the randomized control clinical trial (RCT) that occurs after early phase studies have been completed. Phase III trials are large, usually multicenter studies designed to compare a new agent that... 

X. Kapfer, W. Meichelboeck, F.M. Groegler, Comparison of carbon-impregnated and standard ePTFE prostheses in extra-anatomical anterior tibial artery bypass a prospective randomized multicenter study, Eur. J. Vase. Endovasc. Surg. 32 (2006) 155-168. 

Further standardization of test readings. Although participants of a multicenter study read patch tests according to International Contact Dermatitis Research Group (ICDRG) criteria, considerable differences were noted between the spectrum of reactions to certain allergens in different centers, as shown by... 

Schnuch A, Geier J, Uter W, et al. (1997) National rates and regional differences in sensitization to allergens of the standard series. Population-adjusted frequencies of sensitization (PAFS) in 40,000 patients from a multicenter study (IVDK). Contact Dermatitis 37 200-209... 

Endocrine Aripiprazole is said to stabilize the dopaminergic system and thus ameliorate schizophrenic symptoms without increasing serum prolactin [SEDA-31, 76]. Prolactin concentrations and sexual function in schizophrenic patients have been evaluated in an open, 26-week, multicenter study, in which 555 patients were randomized to aripiprazole ( = 284) or standard care (olanzapine, quetiapme, or risperidone n = 271) [69 ]. At 8 weeks, those who took aripiprazole reported significantly greater improvement in sexual function. Baseline mean serum prolactin concentrations were similar in the two groups (434 and 423 mg/1 respectively) however, at week 26, the mean fall in serum prolactin was 342 mg/1 with aripiprazole compared with 133 mg/1 with the other treatments. 

Unfortunately, not all products that are used in clinical trials are available in the United States. In a randomized, double-blind, multicenter European study, 1069 men with moderate benign prostatic hyperplasia were randomized to receive saw palmetto (Permixon" )1 160 mg twice daily (90% free and 7% esterified fatty acids) or finasteride 5 mg once daily for 6 months [32]. As determined by patients and physicians, Permixon offered similar improvement in symptoms related to benign prostatic hyperplasia compared to finasteride. Since Permixon is not available in the United States, it should be recommended to patients to use a product that is similar to Permixon that contains a standardized extract of saw palmetto containing 85-95% sterols and fatty acids [18]. 

Tapia, O., Colonna, F. and Angyan, J. G. Generalized self-consistent reaction field theory in multicenter-multipole ab initio LCGO framework. I. Electronic properties of the water molecule in a Monte Carlo sample of liquid water molecules studied with standard basis sets, J.ChimPhys., (1990), 875-903... 

Faure, E.D., Chantre, P. and Mares, P. (2002). Effects of a standardized soy extract on hot flushes a multicenter, double-blind, randomized, placebo-controlled study, Menopause, 9, 329-334. 

Diuretics and their mechanisms of action will be discussed in detail in Chapter 21. Loop diuretics, such as furosemide (Lasix), block the Na" -K" -2CLsymporter in the ascending limb of the loop of Henle.The resultant effect is delivery of more Na" to the distal tubule and enhanced urinary loss of Na" and water. Unfortunately, the resultant increase in urinary excretion of and K+ can lead to arrhythmias. The potential for arrhythmias is exacerbated by the loss of Mg++ and Ca++ and an underlying vulnerability of the myocardium in CHF. However, loop diuretics are still part of the mainstay of therapy for CHF despite these potential problems and the absence of well-controlled multicenter clinical trials. The rationale for their use is so compelling that placebo-controlled studies appear unethical. Moreover, furosemide was accepted as the standard of care in all of the clinical trials that form the basis for recommended therapy for CHF. The use of the potassiumsparing diuretic spironolactone has been shown to improve survival and is discussed below. 

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