Uncontrolled study

Formaldehyde causes eye, upper respiratory tract, and skin irritation and is a skin sensitizer. Although sensory irritation, eg, eye irritation, has been reported at concentrations as low as 0.1 ppm in uncontrolled studies, significant eye/nose/throat irritation does not generally occur until concentrations of 1 ppm, based on controlled human chamber studies. Odor detection has commonly been reported to occur in the range of 0.06—0.5 ppm (133—135). 

Controlled mirror-image studies of clozapine (Table 2.2) show primarily that all interventions evaluated seem to reduce healthcare costs by reducing hospitalization, but that the effect of clozapine is greater. These results are more compelling than those from the uncontrolled studies, not only because of the inclusion of a contemporary control, but also because these studies tended to be larger and longer. 

Randomization refers to the process of assigning subjects by chance to treatments. This eliminates known and unknown sources of bias that could interfere with accurate interpretation of the study results. The main problem that randomization is intended to prevent is bias in subject selection. Without randomization, investigators might consciously or subconsciously select subjects to receive the active treatment, which, they believe, are most likely to respond. History shows that uncontrolled studies are much more likely to provide exaggerated support in favor of the effectiveness of a treatment than properly controlled trials (Pocock, 1983). Therefore, whenever possible, randomization should be used in order to help insure a fair and unbiased evaluation of the intervention under study. 

A first open, uncontrolled study [46], performed in 12 patients with active IBD refractory to standard treatment who all had positive stool culture, suggested that adding rifaximin (800 mg daily) could be beneficial. A further small but controlled investigation performed in our unit [47] evaluated the efficacy and systemic absorption of rifaximin in patients with moderately to severely active UC refractory to steroid treatment. Patients were eligible if they had no response to intravenous corticosteroid therapy (methylprednisolone 1 mg/kg/day) after 7-10 days. Twenty-eight patients were randomized to receive rifaximin 400 mg b.i.d. or placebo for 10 days as an add-on... 

Metoclopramide may have some potential value (10 mg orally or IV 30 minutes before each meal and at bedtime) in nausea and vomiting of a variety of etiologies (uncontrolled studies report 80% to 90% efficacy), including emesis during pregnancy and labor (5 to 10 mg orally or 5 to 20 mg IV or IM, 3 times a day). 

Almost half (46%) of all post MI patients will have completed necrosis without remaining areas of viable myocardium of the remaining 54%, some will benefit from revascularization or from vigorous reversal treatment of atherosclerosis [79, 80], summarized by Fig. 2.9. The benefit of revascularization has been well established only in patients with moderate LV dysfunction (LVEF < 35%), whereas the survival benefit for those with regional LV dysfunction without reduced LVEF is suggested only by non-ran-domized or uncontrolled studies [81]. 

In an uncontrolled study of 24 patients with acute, decompensated heart failure unresponsive... 

Phenobarbitai is a very sedative barbiturate, with a iong eiimination haif-iife. It can cause drowsiness, coma, and respiratory depression. It is therefore safe to use it only where adequate facilities are available for mechanical ventilation if that is required. Sodium valproate infusion has been shown to be effective in children with status in a small uncontrolled study. 

Controlled and uncontrolled studies often are conducted after a drug is approved and marketed. Such studies are intended to broaden the experience with the drug and compare it with other drugs. 

Divalproex sodium has been reported to have acute antimanic properties (Bowden et ah, 1994) in at least six controlled studies of adults with BD (Post et ah, 1996). There is a paucity of controlled data for the use of DVP in children with psychiatric disorders. Case series (Papatheodorou et ah, 1993, 1995) and one controlled study (Kowatch et ah, 2000) suggest that DVP may be effective and well tolerated in acutely manic adolescents. Preliminary uncontrolled studies also suggest that DVP may play a role in the management of behavioral dyscontrol among adults... 

Kastner et al. (1993) evaluated valproic acid in 18 children and adults (mean age, 19.7 years) with self-injury or aggression, irritability, sleep disorder, and evidence of cycling. Fourteen (78%) responded positively as assessed by the CGI in this uncontrolled study. The authors found that 11 subjects with established or suspected epilepsy responded significantly better than participants with no evidence of epilepsy. 

Aman s (1993) review of lithium treatment for self-injury revealed that the drug has only inconsistently been shown to suppress such behaviors. The available case reports have been far more positive than the placebo controlled research. Kastner et al. s (1993) positive but uncontrolled study of lithium in adolescents and adults practicing aggression and self-injury was described earlier (see Conduct Disorder, above). Finally, single-subject studies of carbamazepine have yielded mixed results (Aman, 1993). 

TABLE 49.2 Uncontrolled Studies of Stimulants in Preschool-Aged Children... 

In the Zito et al. study (2000), antidepressants were the second most commonly prescribed psychotropic medication. There are a total of 10 studies or case reports in the literature examining antidepressant use in preschool children (Table 49.4). None of the 10 studies are randomized, double-blind, or placebo-controlled trials. The ten uncontrolled studies looked at a total of 37 preschool children. Six of the studies looked at a total of 29 preschoolers with autism or childhood schizophrenia (Campbell et ah, 1971a Petti and Campbell, 1975 Holttum et ah, 1994 Sanchez et ah, 1996 DeLong et ah, 1998 Hollander et ah, 2000). While these six studies are difficult to compare, given the small sample sizes and the different treatment medications, these open-label studies suggest that clomipramine, venlafaxine, and fluoxetine may be helpful to reduce some psychiatric symptoms found in autistic... 

There are a number of uncontrolled studies that indicate that clonidine may be effective in reducing aggression (Comings et al., 1990 Kemph et al., 1993 Schvehla et al., 1994). Transdermal clonidine decreased hyperarousal in nine children with autism in an uncontrolled study (Frankhauser et al., 1982). In a doubleblind study of eight FDD children with ADHD-like symptoms, Jaselski et al. (1992) reported that clonidine had nonsignificant overall effects compared to placebo, however, some of the ratings of aberrant (by teacher) and oppositional (by parent) behavior decreased. 

Because OCD is considered one of the anxiety disorders according to DSM-IV [American Psychiatric Association 1994] [but not according to ICD-10 [World Health Organization 1992]], it is not surprising that anxiolytics have been suggested for its treatment. Thus, alprazolam and clonazepam have been reported as efficient in several uncontrolled studies and case series [Hewlett et al. 1990 Tollefson 1985]. 

It is important to distinguish between acute (e.g., 1 day) and longer term treatment with a BZD. Most of the literature addressing this issue consists of anecdotal reports, retrospective chart reviews, and uncontrolled studies in small patient samples, plus a small number of controlled trials for short-term acute BZD therapy. To our knowledge, at least 12 studies (including more than 450 patients) have evaluated the efficacy of adjunctive BZDs in nonresponsive schizophrenics (Table 5-23). Two of three open studies showed positive results, as did two controlled, single-blind studies ( 343, 344, 345, 346 and 347). In seven double-blind, crossover studies (six with placebo controls), the results are more contradictory, in that five showed no advantage to an adjunctive BZD, and one of the two positive studies had a small sample size (188, 189, 348, 349, 350 and 351). 

Yorkston NJ, Zaki SA, Havard CWH. Propranolol in the treatment of schizophrenia an uncontrolled study with 55 adults. In Roberts E, Amacher P, eds. Propranolol and schizophrenia. New York Alan R. Liss, 1978 39-68. 

There are several double-blind studies that support melatonin administration. For example, rapid deployment aviation groups sent to the Middle East demonstrated longer sleep duration and better test performance on melatonin than did the placebo group ( 174, 175). Arendt (173), who has had extensive experience with both controlled and uncontrolled studies, summarized the overall experience in 386 subjects, showing a 60% reduction in jet lag for eastern travel and a 40% reduction for western travel. 

Data from unpublished, uncontrolled studies indicate favorable responses to SSRIs within 8 to 12 weeks in patients with chronic PTSD. The time to onset of therapeutic response in these patients is similar to that seen in patients with major depression. 

In acute hepatitis C, the rate of clearance of the virus without therapy is estimated at 15-30%. In one (uncontrolled) study, treatment of acute infection with interferon alfa-2b, in doses higher than those used for chronic hepatitis C (Table 49-6), resulted in a sustained rate of clearance of 95% at 6 months. Therefore, if HCV RNA testing documents persistent viremia 12 weeks after initial seroconversion, antiviral therapy is recommended. 

Ovarian hyperstimulation syndrome is far less common with gonadorelin receptor antagonists than agonists in induction of ovulation (2,7). Hot flushes are rare, in contrast to gonadorelin receptor agonists in a prospective, uncontrolled study of 346 women given cetrorelix, there was only one case of hot flushes (7). 

In 686 hypertensive men treated for 15 years, beta-blockers were associated with a higher incidence of diabetes than thiazide diuretics (200). This was an uncontrolled study, but the observation deserves further study. 

Uncontrolled clinical trials Table of all studies grouped by study type and reports of individual studies in each group. Other studies and information Reports of controlled or uncontrolled study of uses not claimed in the application, reports of commercial marketing experience. 

Another drug, ALA, has been used to treat restenosis of the superficial femoral artery. These have been small, uncontrolled studies. In one report, ALA was given orally in a clinical study of adjuvant PDT in patients undergoing femoral angioplasty (61). Patients left the hospital after an overnight stay and there were no reports of skin photosensitivity. The authors suggested a benefit and no evident safety concerns, leading... 

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