Several Medical Letter readers have asked about the meaning of non-inferiority trials. A non-inferiority trial is a comparison with an active control to determine whether the difference in response between the new drug and the active control is small enough (less than some pre-specified margin) to demonstrate that the new treatment is not less effective (or is only slightly less effective) than the control in achieving the primary outcome.1,2 Non-inferiority trials are appropriate when a proven effective treatment already exists and assigning some patients to a placebo group would be unethical because the treatment is life-saving or prevents irreversible injury.3 The FDA recently issued guidelines on how to interpret a non-inferiority trial, how to choose a non-inferiority margin and how to analyze the results.4

1. Guidance for industry non-inferiority clinical trials. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM202140.pdf. Accessed December 17, 2010.

2. ICH Harmonised Tripartite Guideline. Choice of control group and related issues in clinical trials E10. http://private.ich.org/LOB/media/MEDIA486.pdf. Accessed December 17, 2010.

3. R Temple and SS Ellenberg. Placebo-controlled trials and active-control trials in the evaluation of new treatments. Part 1: ethical and scientific issues. Ann Intern Med 2000; 133:464.

4. FDA issues first draft guidance on noninferiority trial. http://www.fdanews.com/newsletter/article?articleId=124913 &issueId=13475. Accessed December 17, 2010.

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Antiviral drugs can be used for treatment of patients with influenza and for prophylaxis when exposure to the disease occurs before or less than 2 weeks after vaccination. They can also be used to control institutional outbreaks of influenza. In recent years, the susceptibility of circulating influenza strains has evolved rapidly and treatment recommendations have changed during the influenza season. The CDC influenza web site provides frequently updated information on antiviral resistance (www.cdc.gov/flu)

The FDA has approved the use of ulipristal acetate (ella – Watson) as an emergency contraceptive that can be taken up to 5 days after unprotected intercourse. It is available only by prescription.

Glycopyrrolate (Robinul, and others), a synthetic muscarinic receptor antagonist, has been used off-label for many years for treatment of excessive drooling in patients with Parkinson’s disease, in patients taking clozapine for schizophrenia, and in developmentally disabled children.1-3 It has now been approved by the FDA as Cuvposa (Shionogi) for use specifically in children 3-16 years old with severe chronic drooling due to a neurologic condition, such as cerebral palsy. It is being marketed as an oral solution, which will permit more precise weight-based dosing than was possible with the oral tablets used in the past. As with other anticholinergic drugs, dry mouth, constipation, flushing and nasal congestion can occur. Since glycopyrrolate decreases secretion not only of saliva, but also of sweat, overheating due to high ambient temperatures or excessive exercise could be dangerous for patients who take it.

1. ME Arbouw et al. Glycopyrrolate for sialorrhea in Parkinson disease: a randomized, double-blind, crossover trial. Neurology 2010; 74:1203.

2. CS Liang et al. Comparison of the efficacy and impact on cognition of glycopyrrolate and biperiden for clozapine-induced sialorrhea in schizophrenic patients: a randomized, double-blind, crossover study. Schizophren Res 2010; 119:138.

3. RJ Mier et al. Treatment of sialorrhea with glycopyrrolate: a double-blind, dose-ranging study. Arch Pediatr Adolesc Med 2000; 154:1214.

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