 |
 |
New study challenges statistical design and conclusions of Amgen’s Phase II GDNF study. A detailed statistical analysis by Dr. Michael Hutchinson, NYU Medical School, Dr. Susan Gurney, Columbia University School of Public Health, Dept of Epidemiology, and Dr. Roger Newsome, biostatistician at Imperial College, London, finds the Amgen sponsored study that concluded it could "rule out with good power a large beneficial clincial effect" of infused GDNF, actually was underpowered (too much variability among subjects and too few subjects) and therefore "incapable of concluding anything meaningful about the effect of GDNF on Parkinson’s Disease." (See abstract below) Yet the trial results were cited by Amgen as a reason for halting further GDNF treatment and trials. ---------------------------------------------------- Pub Med Abstract : Journal of Neuroscience Methods. 2006 Jul 27; [Epub ahead of print] GDNF in Parkinson disease: An object lesson in the tyranny of type II. Hutchinson M, Gurney S, Newson R. Department of Neurology, New York University School of Medicine, 400 E. 34th Street, Suite RR 311, New York, NY, USA. Type II errors may be having a significant impact on drug discovery. This is of particular importance in the clinical neurosciences, where endpoints are often subjective scores of disability rather than unequivocal events such as survival. Here we examine a recently published study [Lang AE, Gill S, Patel NK, et al. Randomized controlled study of intraputamenal glial cell-derived neurotrophic factor infusion in Parkinson disease. Ann Neurol 2006;59:459-66] in an area of immense importance to neuroscience. This small study found no detectable clinical benefit from infused intraputamenal GDNF as a treatment for Parkinson disease. However the standard deviation of the accrued data turned out to be considerably higher than had been anticipated in the power analysis performed prior to the study. In order to determine what impact, if any, this had on the conclusions that could be drawn, the actual data were analyzed by means of both the t-test and the rank-based Somers'D. The study was found to be underpowered and thus incapable of ruling out a large effect of GDNF on Parkinson disease. It therefore does not contradict the large effects seen in previous open-label studies. PMID: 16876872 [PubMed - as supplied by publisher] ------------------------------------------------------------ Patients, all of us, have the most to loose from these Type II errors in clinical trials (where effective interventions incorrectly appear ineffective), since they can lead to effective treatments being overlooked or shelved, as was the case for infusion delivery of GDNF. THe research should be restarted. Linda ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn