Multiple testing, dose-finding

Bauer P (1997) A note on multiple testing procedures in dose finding. Biometrics 53 1125-1128. 

Budde M, Bauer P (1989) Multiple test procedures in clinical dose finding stndies. Journal of the American Statistical Association 84 792-796. 

A later study supported the findings that methylphenidate s benefits are most apparent in sleep-deprived/sleep-restricted volunteers. Roehrs et al. (52) compared the effects of 09 00 doses of 10 mg methylphenidate to placebo on sleepiness (Multiple Sleep Latency Test, MSLT), Profile of Mood States (POMS) ratings, and divided-attention performance after either 4 or 8 hr of sleep. After these test days, the 4- and 8-hr sleep conditions were repeated, but this time subjects were given their choice of drug or placebo. Results indicated that performance was improved by methylphenidate, most notably after the 4-hr condition. Methylphenidate also improved sleep latency and mood, but only after restricted sleep. During the choice phase of the study, subjects showed a preference for methylphenidate after 4 hr sleep (in 88% of opportunities), but not after 8 hr sleep (in only 29% of opportunities), suggesting that the preference for methylphenidate depended on the perceived sleepiness level of the individual. 

The mid and low doses for a carcinogenicity study are to provide information for assessing the relevance of the study findings to humans. The low dose should be equal to, or a multiple of, the maximum dose proposed for human testing. The rationale for the selection of the low and mid dose needs to be provided on the basis of pharmacokinetic linearity and saturation of metabolic pathways, human exposure and therapeutic dose, pharmacodynamic response in the test species, alteration in the normal physiology of the test species, mechanistic information and the potential for threshold effects, and the unpredictability of toxicity progression observed in other toxicology studies. 

Microneedles can also be used to extract samples, thus finding significant applications in the field of health monitoring and biochemical analysis. For example, with diabetic patients, frequent use of needles is necessary for blood sampling to test glucose levels and to administer multiple doses of insulin. The use of microneedles can make it a virtually pain-free and a much more palatable experience to patients. 

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