title: Evidence from clinical trials: can we do better?
abstract: Randomized clinical trials provide the most internally valid evidence for medical decision-making. In many areas of neurology, results from clinical trials showing which therapies are and are not effective have had a substantial impact on patient care. Relative to observational methods, the central advantage of clinical trials is control of bias attributable to unmeasured differences between patients. However, trials also have clear limitations, including a historical failure to include a representative cross-section of patients with a given disease, and highly structured treatment regimes that are difficult to replicate in normal practice settings. These limitations tend to reduce the generalizability of results from clinical trials. This article reviews some ways in which the design and application of clinical trials could be improved so that the evidence produced would be more relevant to health-care providers and other decision makers.
authors.affiliation: Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania 19107, USA. adsiderowf@pahosp.com
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Siderowf
mesh_terms: D035843:Biomedical Research / Q000379:methods*; D006801:Humans; D009422:Nervous System Diseases / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
references.citation: N Engl J Med. 1999 Sep 23;341(13):988-92
references.pmid: 10498497
references.citation: N Engl J Med. 1999 Sep 23;341(13):992-6
references.pmid: 10498498
references.citation: JAMA. 2003 Sep 24;290(12):1624-32
references.pmid: 14506122
references.citation: JAMA. 2003 Oct 1;290(13):1739-48
references.pmid: 14519708
references.citation: Lancet. 2003 Oct 11;362(9391):1211-24
references.pmid: 14568745
references.citation: Epilepsia. 2003 Nov;44(11):1425-33
references.pmid: 14636351
references.citation: Arch Neurol. 2003 Dec;60(12):1696-702
references.pmid: 14676043
references.citation: BMJ. 2003 Dec 20;327(7429):1459-61
references.pmid: 14684649
references.citation: Ann Neurol. 1995 Sep;38(3):379-88
references.pmid: 7668823
references.citation: Am J Epidemiol. 1995 Oct 15;142(8):820-7
references.pmid: 7572958
references.citation: Neurology. 1995 Oct;45(10):1808-14
references.pmid: 7477973
references.citation: N Engl J Med. 1995 Dec 14;333(24):1581-7
references.pmid: 7477192
references.citation: Lancet. 1996 Sep 7;348(9028):633-8
references.pmid: 8782752
references.citation: Ann Intern Med. 1996 Oct 1;125(7):605-13
references.pmid: 8815760
references.citation: J Neurol Sci. 1996 Nov;143(1-2):1-13
references.pmid: 8981292
references.citation: Brain. 1996 Dec;119 ( Pt 6):2097-103
references.pmid: 9010013
references.citation: N Engl J Med. 2000 Jun 22;342(25):1907-9
references.pmid: 10861329
references.citation: Neurology. 2000 Aug 22;55(4):465-6
references.pmid: 10953174
references.citation: N Engl J Med. 2000 Sep 28;343(13):898-904
references.pmid: 11006365
references.citation: JAMA. 2000 Oct 18;284(15):1931-8
references.pmid: 11035889
references.citation: Ann Neurol. 2000 Nov;48(5):809-12
references.pmid: 11079549
references.citation: N Engl J Med. 2001 Mar 8;344(10):710-9
references.pmid: 11236774
references.citation: Neurology. 2001 Jun 26;56(12):1628-36
references.pmid: 11425926
references.citation: N Engl J Med. 2001 Aug 2;345(5):311-8
references.pmid: 11484687
references.citation: Am J Epidemiol. 2001 Aug 1;154(3):276-84
references.pmid: 11479193
references.citation: Stroke. 2001 Sep;32(9):2058-74
references.pmid: 11546898
references.citation: N Engl J Med. 2001 Nov 15;345(20):1444-51
references.pmid: 11794192
references.citation: Control Clin Trials. 2001 Dec;22(6):659-73
references.pmid: 11738122
references.citation: Int J Technol Assess Health Care. 2002 Winter;18(1):127-38
references.pmid: 11987436
references.citation: Lancet. 2002 Apr 27;359(9316):1453-60
references.pmid: 11988242
references.citation: JAMA. 2002 Jul 3;288(1):49-57
references.pmid: 12090862
references.citation: Int J Technol Assess Health Care. 2002 Summer;18(3):497-507
references.pmid: 12391943
references.citation: Nat Neurosci. 2002 Nov;5 Suppl:1027-9
references.pmid: 12403977
references.citation: Neurology. 2002 Dec 10;59(11):1766-71
references.pmid: 12473766
references.citation: Ann Intern Med. 2003 Jan 7;138(1):40-4
references.pmid: 12513043
references.citation: JAMA. 2003 Mar 12;289(10):1278-87
references.pmid: 12633190
references.citation: Mov Disord. 2004 Feb;19(2):136-50
references.pmid: 14978668
references.citation: Arch Neurol. 2004 Apr;61(4):561-6
references.pmid: 15096406
references.citation: JAMA. 1977 Jul 18;238(3):224-7
references.pmid: 406427
references.citation: Neurology. 1982 Mar;32(3):280-2
references.pmid: 7199638
references.citation: Neurology. 1983 Nov;33(11):1444-52
references.pmid: 6685237
references.citation: N Engl J Med. 1990 Mar 22;322(12):863-8
references.pmid: 2407959
references.citation: N Engl J Med. 1991 Aug 15;325(7):445-53
references.pmid: 1852179
references.citation: N Engl J Med. 1992 Feb 27;326(9):581-8
references.pmid: 1734247
references.citation: N Engl J Med. 1992 Sep 10;327(11):765-71
references.pmid: 1298221
references.citation: JAMA. 1993 Dec 1;270(21):2598-601
references.pmid: 8230645
references.citation: Ann Neurol. 1994 Feb;35(2):172-80
references.pmid: 8109898
references.citation: Lancet. 1994 Mar 19;343(8899):687-91
references.pmid: 7907677
references.citation: Circulation. 1994 Sep;90(3):1588-601
references.pmid: 8087974
references.citation: Neurology. 1995 Jul;45(7):1277-85
references.pmid: 7617182
references.citation: Gen Hosp Psychiatry. 2003 Mar-Apr;25(2):115-23
references.pmid: 12676425
references.citation: Clin Ther. 2003 Feb;25(2):611-34
references.pmid: 12749517
references.citation: Am J Epidemiol. 2003 Jun 1;157(11):1015-22
references.pmid: 12777365
references.citation: JAMA. 2003 Jun 4;289(21):2810-8
references.pmid: 12783911
references.citation: JAMA. 2003 Jun 25;289(24):3241-2
references.pmid: 12824204
references.citation: Ann Neurol. 2003 Sep;54(3):403-14
references.pmid: 12953276
references.citation: Circulation. 1997 Feb 18;95(4):1072-82
references.pmid: 9054772
references.citation: Lancet. 1997 May 31;349(9065):1569-81
references.pmid: 9174558
references.citation: Lancet. 1997 Jun 7;349(9066):1641-9
references.pmid: 9186381
references.citation: Mayo Clin Proc. 1997 Sep;72(9):871-8
references.pmid: 9294536
references.citation: Alzheimer Dis Assoc Disord. 1997;11 Suppl 5:S10-21; discussion S37-9
references.pmid: 9348423
references.citation: JAMA. 1998 Feb 18;279(7):545-9
references.pmid: 9480367
references.citation: Neurology. 1998 Mar;50(3):701-8
references.pmid: 9521260
references.citation: Neurology. 1998 Jul;51(1):48-55
references.pmid: 9674777
references.citation: Arch Neurol. 1998 Aug;55(8):1089-95
references.pmid: 9708959
references.citation: J Nucl Med. 1998 Sep;39(9):1500-8
references.pmid: 9744331
references.citation: Chest. 1998 Nov;114(5 Suppl):441S-444S
references.pmid: 9822056
references.citation: Pharmacoeconomics. 1998 Nov;14(5):541-57
references.pmid: 10344917
references.citation: Epilepsy Res. 1999 Apr;34(2-3):135-43
references.pmid: 10210028
references.citation: Ann Intern Med. 1999 Aug 17;131(4):237-46
references.pmid: 10454944
references.citation: Neurology. 1999 Aug 11;53(3):448-56
references.pmid: 10449103
references.citation: JAMA. 1999 Aug 25;282(8):771-8
references.pmid: 10463714