Pearls and Pitfalls of Clinical Trial Investigation: Should I Get Involved in the Drug Development Process?

Amy S. Chappell

doi:10.1055/s-2001-19413

Seminars in Neurology, Table of Contents

Semin Neurol 2001; 21(4): 417-424
DOI: 10.1055/s-2001-19413

Pearls and Pitfalls of Clinical Trial Investigation: Should I Get Involved in the Drug Development Process?

Amy S. Chappell

Lilly Research Laboratories, Lilly Corporate Center, and Department of Neurology, Indiana University Medical School, Indianapolis, Indiana

Abstract

ABSTRACT

The revolution in neurological therapeutics means that an increasing number of neurologists will have the opportunity to participate in a drug development process that is long and complicated. The opportunity provides challenges as well as rewards, and should be undertaken only after thoughtful review of the Clinical Investigator's Brochure and protocol. Key questions that the neurologist should address prior to participation are reviewed herein.

KEYWORD

Clinical trials - drug development

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References

REFERENCES

1 Posvar E, Sedman A. New drugs: first time in man. J Clin Pharmacol . 1989; 29 961-966
2 Faries D. Practical modifications of the continual reassessment method for phase1 cancer clinical trials. J Biopharm Statistics . 1994; 4 147-164
3 Goldstein D, Potter W. Determination of appropriate dosage in clinical development. In: Balant L, Benitez J, Dahl S, Gram L, Pinder R, Potter W, eds. Clinical Pharmacology in Psychiatry: Finding the Right Dose of Psychotropic Drugs Luxembourg: Office for Official Publications of the European Communities 1997: 305-322
4 Sang C, Hostetter M, Gracely R. Effects of an AMPA/Kainate antagonist in humans: reduction of hyperalgesia at subsedative doses. Anesthesiology . 1998; 89 1060-1067
5 Barinaga M. Neurotrophic factors enter the clinic. Science . 1994; 264 772-774
6 Partridge W, Kang Y, Buciak J. Transport of human recombinant brainderived neurotrophic factor (BDNF) through the rat blood-brain barrier in vivo using vector-mediated peptide drug delivery. Pharm Res . 1994; 11 738-746
7 Partridge W. CNS drug design based on principles of blood-brain barrier transport. J Neurochem . 1998; 70 1781-1792
8 Sramek J, Eldon M, Posvar E. Initial safety, tolerability, pharmacodynamics, and pharmacokinetics of Cl-1007 in patients with schizophrenia. Psychopharm Bulletin . 1998; 34 93-99
9 Cutler N, Sramek J. The bridging concept: optimizing dose for phase II/III in Alzheimer's disease. Neurodegeneration . 1996; 5 511-514
10 Sramek J, Cutler N, Kurtz N, Murphy M, Carta A. Optimizing the Development of Antipsychotic Drugs. Chichester, England: John Wiley & Sons 1997: 101-126
11 Sramek J, Fresquet A, MarionLandais G. Establishing the maximum tolerated dose of lesopitron in patients with generalized anxiety disorder: a bridging study. J Clin Psychopharmacol . 1987; 7 436-437
12 Goldstein D, Wang O, Saper J, Stoltz R, Silberstein S, Mathew N. Ineffectiveness of neurokinin1 antagonist in acute migraine: a crossover study. Cephalalgia . 1997; 17 785-790
13 Lenert L, Markowitz D, Blaschke T. Primum non nocere?. <~>Valuing of the risk of drug toxicity in therapeutic decision making. Clinical Pharm Ther . 1993; 53 285-291
14 Payne R, Pasternak G. Pain. In: Johnston M, MacDonald R, Young A, eds. Principles Of Drug Therapy In Neurology New York: F.A. Davis Company 1992: 268-301
15 Irish W, Macdonald D, Cairncross G. Measuring bias in uncontrolled brain tumor trials: to randomize or not to randomize?. Can J Neurol Sci . 1997; 24 307-312
16 Stone L, Frank J, Albert P. Characterization of MRI response to treatment with interferon beta-lb: contrast enhancing MRI lesion frequency as a primary outcome measure. Neurology . 1997; 49 862-869
17 Lublin F, Reingold S, and the National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Guidelines for clinical trials of new therapeutic agents in multiple sclerosis. Neurology . 1997; 48 572-574
18 Honig P, Wortham D, Zamani K, Conner D, Mullin J, Cantilena L. Terfenadine-ketoconazole interaction. JAMA . 1993; 12 1513-1518
19 Theodore W, Raubertas R, Porter R. Felbamate: a clinical trial for complex partial seizures. Epilepsia . 1991; 32 392-397
20 Ring B, Binkley S, Wrightman S A. In vitro interaction of LY300164 with human cytochrome P450 CYP3A, CYP2C9, and CYP1A2. Lilly Clinical Investigator's Brochure. Indianapolis: Eli Lilly & Company 2000
21 Jewell H, Lucas R. LY300164 single and multiple dose pharmacokinetics and initial one-week experience in patients with chronic epilepsy. Lilly Clinical Investigator's Brochure. Indianapolis: Eli Lilly & Company 2000