Dose-finding blinding

Italian Group for Antiemetic Research. Double-blind, dose-finding study of four intravenous doses of dexamethasone in the prevention of cisplatin-induced acute emesis. J Clin Oncol 1998 16 2937-2942. 

Williams, R., James, O.F.W., Warnes, T.W., Morgan, M.Y. Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy a double-blind, randomized, dose-finding multi-centre study. Eur. J. Gastroenterol. Hepatol. 2000 12 203 - 208... 

The melanocortin Org 2766, an ACTH analogue, which is not yet available for clinical use, alleviates neurotoxicity due to vinca alkaloids and cisplatin, perhaps by enhancing neural repair. However, whereas preliminary results suggested some neuroprotection in women with ovarian cancer treated with cisplatin, these results were not confirmed in a randomized, multicenter, double-blind, placebo-controlled dose-finding study, even with higher doses of Org 2766 (113). 

Dodel R, Rominger A, Bartenstein P, Barkhof F, Blennow K, Forster S et al (2013) Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer s disease A phase 2, randomised, double-blind, placebo-controlled, dose-finding trial. Lancet Neurol 12 233-243... 

Gallagher JC, Baylink DJ, Freeman R, McClung M. Prevention of bone loss with tibolone in postmenopausal women Results of two randomized, double-blind, placebo-controlled, doses finding studies. J Clin Endocrinol Metab 2001 869 4717 726. 

Puhringer FK, Rex C, Sielenkamper AW, Claudius C, Larsen PB, Prins ME, Eikermann M, Khuenl-Brady KS. Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial. Anesthesiology 2008 109(2) 188-97. 

Tyring S, Wald A, Zadedds N, Dhadda S, Takenouchi K, Rorig R. ASP2151 for the treatment of genital herpes a randomized, double-blind, placebo- and valacydovir-controUed, dose-finding study. J Infect Dis 2012 205(7) 1100-10. 

Staerk-Laursen LS, Havelund T, Bondesen S et al (1995) Omeprazole in the long-term treatment of gastro-oesophageal reflux disease. A double-blind randomized dose-finding study. Scand J Gastroenterol 30 839-846... 

In theory, all microscopic evaluations should be performed blind (without the pathologist knowing from which dose group a particular animal came), but this is difficult to do in practice and such an approach frequently degrades the quality of the evaluation. Like all the other portions of data in the study, proper evaluation benefits from having access to all data that addresses the relevance, severity, timing, and potential mechanisms of a specific toxicity. Blind examination is best applied in peer review or consultations on specific findings. 

There should not be blind adoption of a checklist of assays and observations, but appropriate investigations should be selected, based on earlier findings in the singledose studies. Increasing the number of doses raises more concern about the immune response. There may be indications of this, such as lymphocyte infiltration at the site... 

Some questions have been raised about the relative efficacy of the SSRls, particularly in severe depression. The pooled analyses of the data from blinded, controlled trials have tended to find similar levels of efficacy between the SSRls and the comparator TCA, imipramine. Paroxetine and fluvoxamine were both found in subanalyses of patients with severe depression included in large placebo- and imipramine-controlled studies to be more effective than imipramine in severe depression (S. A. Montgomery 1992a Ottevanger 1991 Tignol et al. 1992 Wakelin 1988]. However, imipramine may not be the TCA that is most effective in severe depression or may not have been used in the trials at an adequate dose. 

Haloperidol is the best-studied antipsychotic medication in children and adolescents with schizophrenia. In a double-blind, placebo- and active-controlled study, haloperidol (2 to 16 mg per day) and loxapine (10 to 200 mg per day) were equally effective and superior to placebo ( 168). This finding was replicated in a placebo-controlled, crossover study of haloperidol (doses of 0.5 to 3.5 mg per day or 0.02 to 0.12 mg/kg per day) in children 5.5 to 12 years of age ( 169). In this study, haloperidol was more effective than placebo in reducing ideas of reference, persecutory ideas, hallucinations, and thought disorder. 

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