Long term clinical studies

Patients more than 12 years of age - The effective dose is 900 to 1800 mg/day in divided doses (3 times/day) using 300 or 400 mg capsules or 600 or 800 mg tablets. The starting dose is 300 mg 3 times/day. If necessary, the dose may be increased using 300 or 400 mg capsules or 600 or 800 mg tablets 3 times/day up to 1800 mg/day. Dosages up to 2400 mg/day have been well tolerated in long-term clinical studies. Doses of 3600 mg/day also have been administered to a small number of patients for a relatively short duration, and have been well tolerated. The maximum time between doses in the 3 times/day schedule should not exceed 12 hours. 

The basis of this comparison was strongly challenged in a citizen petition claiming that (1) recombinant salmon calcitonin is not the same as the synthetic version which could potentially cause differences in product efficacy, safety, or both and (2) only a long-term clinical study (actual bone fracture data) would provide adequate support of sameness [28]. The FDA responded to this citizen petition by asserting its decision that the comparability data presented above collectively constituted sufficient demonstration of sameness [27,29],... 

The possible modes of action of indomethacin remain to be a subject of active interest. As a reference compound it has been found to be active in most of the in vitro and in vivo assays mentioned above. While none of these can be considered as the primary mode of action, certainly several are contributory. An earlier report of kallikrein inhibition was not confirmed.The suggestion37 that the antiinflammatory activity of indomethacin may be due to the displacement of tissue-bound corticosteroid has also been disputed. 3 The distribution cind metabolism of indomethacin in various species have been reported in detail39, and a number of long-term clinical studies have been published. 3... 

Institute for Health and Clinical Excellence (NICE) guidelines currently recommend it is only used in controlled long-term clinical studies. 

TG (7.3%), and increased HDL-C (3.0%), with higher intakes of soy isoflavones (>80 mg/d) producing more substantial effects on plasma lipids. However, both the AHRQ report (Balk et al., 2005) and the AHA Science Advisory on soy protein (Sacks et al., 2006) reported that isoflavone intake has no effect on LDL-C or other lipids. Nevertheless, more recent meta-analyses continue to suggest that soy isoflavones can independently lower TC (1.8%) and LDL-C (3.6%) (Taku et al., 2007), and, when combined with soy protein, may work synergistically or additively to lower LDL-C (soy protein + isoflavones, —4.98% versus soy protein without isoflavones, —2.77%). Additionally, oxidation of LDL is one area where isoflavones appear to exert potential protection (Balk et al., 2005), but large well-designed, long-term clinical studies are needed to confirm these observations. 

Malhotra, S.C., M.M. Ahuja, and K.R. Sundaram. 1977. Long term clinical studies on the hypolipidaemic effect of Commiphora mukul (guggulu) and clofibrate. Indian f. Med. Res. 65(3) 390-395. 

Long term clinical studies of composite restorations have been reported (2-4). These studies show that when placed in regions subjected to occlusal stress, composites are worn away and require replacement after two to four year of service. Composite restorations generally show little evidence of deterioration for abour one year (5), but rapid wear rates are observed after one year. From the clinical viewpoint, composite occlusal restorations uniformly lose substance over their entire exposed surfaces. There generally are no clinically obvious wear tracks or abrasion marks (6). 

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