Lost in Translation: Understanding the Failure of the Progesterone/Traumatic Brain Injury Phase III Trials

References

• Stein DG , GeddesRI, SribnickEA. Critical Developments in Clinical Trials for the Treatment of Traumatic Brian Injury. In: Handbook of Clinical Neurology, Traumatic Brain Injury Part 1 (Volume 127). GrafmanJ, SalazarAM ( Eds). Elsevier, NY, USA, 433–451 (2015).
   Google Scholar
• Wright DW , YeattsSD, SilbergleitRet al. Very early administration of progesterone for acute traumatic brain injury. N. Engl. J. Med.371(26), 2457–2466 (2014).
   PubMed Web of Science ®Google Scholar
• Skolnick BE , MaasAI, NarayanRKet al. A clinical trial of progesterone for severe traumatic brain injury. N. Engl. J. Med.371(26), 2467–2476 (2014).
   PubMed Web of Science ®Google Scholar
• Schwamm LH . Progesterone for traumatic brain injury – resisting the sirens’ song. N. Engl. J. Med.371(26), 2522–2523 (2014).
   PubMed Web of Science ®Google Scholar
• Jickling GC , SharpFR. Improving the translation of animal ischemic stroke studies to humans. Metab. Brain Dis.30(2), 461–467 (2014).
   PubMed Web of Science ®Google Scholar
• Garner JP . The significance of meaning: why do over 90% of behavioral neuroscience results fail to translate to humans, and what can we do to fix it?ILAR J.55(3), 438–456 (2014).
   PubMed Web of Science ®Google Scholar
• Gultekin R , HuangS, ClavisiO, PattuwageL, KonigTC, GruenR. Pharmacological interventions in traumatic brain injury: can we rely on systematic reviews for evidence?Injury doi:10.1016/j.injury (2015) ( Epub ahead of print).
   PubMed Web of Science ®Google Scholar
• Stein DG . On improving human clinical trials to the level of animal ischemic stroke studies. Metab. Brain Dis.30, 469–471 (2014).
   PubMed Web of Science ®Google Scholar
• Schumacher M , DenierC, OudinetJ-P, AdamsDH, GuennounR. Progesterone neuroprotection: the background of clinical trial failure. J. Steroid Biochem. Mol. Biol. doi:10.1016/j.jsbmb.2015.11.010 (2015) ( Epub ahead of print).
   Web of Science ®Google Scholar
• Howard RB , SayeedI, SteinD. Suboptimal dosing parameters as possible factors in the negative Phase III clinical trials of progesterone in TBI. J. Neurotrauma doi:10.1089/neu.2015.4179 (2015) ( Epub ahead of print).
   Web of Science ®Google Scholar
• Wali B , IshratT, WonS, SteinDG, SayeedI. Progesterone in experimental permanent stroke: a dose-response and therapeutic time-window study. Brain137(Pt 2), 486–502 (2014).
   PubMedGoogle Scholar
• Yousuf S , AtifF, SayeedI, TangH, SteinDG. Progesterone in transient ischemic stroke: a dose-response study. Psychopharmacology (Berl.)231(17), 3313–3323 (2014).
   PubMed Web of Science ®Google Scholar
• McCord JM . Superoxide dismutase, lipid peroxidation, and bell-shaped dose response curves. Dose Response6(3), 223–238 (2008).
   PubMed Web of Science ®Google Scholar
• Reynolds AR . Potential relevance of bell-shaped and U-shaped dose-responses for the therapeutic targeting of angiogenesis in cancer. Dose Response8(3), 253–284 (2010).
   PubMed Web of Science ®Google Scholar
• Owen SC , DoakAK, GaneshANet al. Colloidal drug formulations can explain “bell-shaped” concentration-response curves. ACS Chem. Biol.9(3), 777–784 (2014).
   PubMed Web of Science ®Google Scholar
• Sharma V , McNeillJH. To scale or not to scale: the principles of dose extrapolation. Br. J. Pharmacol.157(6), 907–921 (2009).
   PubMed Web of Science ®Google Scholar
• Herring JM , McMichaelMA, CorsiR, WurlodV. Intravenous lipid emulsion therapy in three cases of canine naproxen overdose. J. Vet. Emerg. Crit. Care (San Antonio)25(5), 672–678 (2015).
   PubMed Web of Science ®Google Scholar
• Lee HM , ArcherJR, DarganPI, WoodDM. What are the adverse effects associated with the combined use of intravenous lipid emulsion and extracorporeal membrane oxygenation in the poisoned patient?Clin. Toxicol. (Phila.)53(3), 145–150 (2015).
   PubMed Web of Science ®Google Scholar
• Taftachi F , Sanaei-ZadehH, SepehrianB, ZamaniN. Lipid emulsion improves Glasgow Coma Scale and decreases blood glucose level in the setting of acute non-local anesthetic drug poisoning – a randomized controlled trial. Eur. Rev. Med. Pharmacol. Sci.16(Suppl. 1), 38–42 (2012).
   PubMed Web of Science ®Google Scholar
• Manzanares W , DhaliwalR, JurewitschB, StapletonRD, JeejeebhoyKN, HeylandDK. Alternative lipid emulsions in the critically ill: a systematic review of the evidence. Intens. Care Med.39(10), 1683–1694 (2013).
   PubMed Web of Science ®Google Scholar
• Roozenbeek B , LingsmaHF, MaasAI. New considerations in the design of clinical trials for traumatic brain injury. Clin. Investig. (Lond.)2(2), 153–162 (2012).
   PubMedGoogle Scholar
• Shukla P , RaoGM, PandeyG, SharmaS, MittapellyNet al. Therapeutic interventions in sepsis: current and anticipated pharmacological agents. Br. J. Pharmacol.171(22), 5011–5031 (2014).
   PubMed Web of Science ®Google Scholar
• NIH Toolbox® . www.nihtoolbox.org/Pages/default.aspx.
   Google Scholar
• Green SM . Cheerio, laddie! Bidding farewell to the Glasgow Coma Scale. Ann. Emerg. Med.58(5), 427–430 (2011).
   PubMed Web of Science ®Google Scholar
• Lingsma HF , RoozenbeekB, LiBet al. Large between-center differences in outcome after moderate and severe traumatic brain injury in the International Mission on Prognosis and Clinical Trial Design in Traumatic Brain Injury (IMPACT) study. Neurosurgery68(3), 601–607 (2011).
   PubMed Web of Science ®Google Scholar
• Kruschke JK . What to believe: Bayesian methods for data analysis. Trends Cogn. Sci.14(7), 293–300 (2010).
   PubMed Web of Science ®Google Scholar
• Dragalin V . An introduction to adaptive designs and adaptation in CNS trials. Eur. Neuropsychopharmacol.21(2), 153–158 (2011).
   PubMed Web of Science ®Google Scholar
• Jang SH , YanZG, LazorJA. Therapeutic drug monitoring: a patient management tool for precision medicine. Clin. Pharmacol. Ther. doi:10.1002/cpt.298 (2015) ( Epub ahead of print).
   Web of Science ®Google Scholar
• Duffy DJ . Problems, challenges and promises: perspectives on precision medicine. Brief Bioinform. doi:10.1093/bib/bbv060 (2015) ( Epub ahead of print).
   Web of Science ®Google Scholar
• Cekic M , CutlerSM, VanLandinghamJW, SteinDG. Vitamin D deficiency reduces the benefits of progesterone treatment after brain injury in aged rats. Neurobiol. Aging32(5), 864–874 (2011).
   PubMed Web of Science ®Google Scholar
• Margulies S , HicksR. Combination therapies for traumatic brain injury: prospective considerations. J. Neurotrauma26(6), 925–939 (2009).
   PubMed Web of Science ®Google Scholar
• Geschwind N . Late changes in the nervous system: an overview. In: Plasticity and Recovery of Function in the Central Nervous System. SteinDG, RosenA, ButtersN ( Eds). Academic Press, NY, USA, 467–508 (1974).
   Google Scholar