Evidence from clinical trials: can we do better?
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.
Siderowf
Andrew D
AD
Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania 19107, USA. adsiderowf@pahosp.com
D035843:Biomedical Research / Q000379:methods*; D006801:Humans; D009422:Nervous System Diseases / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
N Engl J Med. 1999 Sep 23;341(13):988-92
10498497
N Engl J Med. 1999 Sep 23;341(13):992-6
10498498
JAMA. 2003 Sep 24;290(12):1624-32
14506122
JAMA. 2003 Oct 1;290(13):1739-48
14519708
Lancet. 2003 Oct 11;362(9391):1211-24
14568745
Epilepsia. 2003 Nov;44(11):1425-33
14636351
Arch Neurol. 2003 Dec;60(12):1696-702
14676043
BMJ. 2003 Dec 20;327(7429):1459-61
14684649
Ann Neurol. 1995 Sep;38(3):379-88
7668823
Am J Epidemiol. 1995 Oct 15;142(8):820-7
7572958
Neurology. 1995 Oct;45(10):1808-14
7477973
N Engl J Med. 1995 Dec 14;333(24):1581-7
7477192
Lancet. 1996 Sep 7;348(9028):633-8
8782752
Ann Intern Med. 1996 Oct 1;125(7):605-13
8815760
J Neurol Sci. 1996 Nov;143(1-2):1-13
8981292
Brain. 1996 Dec;119 ( Pt 6):2097-103
9010013
N Engl J Med. 2000 Jun 22;342(25):1907-9
10861329
Neurology. 2000 Aug 22;55(4):465-6
10953174
N Engl J Med. 2000 Sep 28;343(13):898-904
11006365
JAMA. 2000 Oct 18;284(15):1931-8
11035889
Ann Neurol. 2000 Nov;48(5):809-12
11079549
N Engl J Med. 2001 Mar 8;344(10):710-9
11236774
Neurology. 2001 Jun 26;56(12):1628-36
11425926
N Engl J Med. 2001 Aug 2;345(5):311-8
11484687
Am J Epidemiol. 2001 Aug 1;154(3):276-84
11479193
Stroke. 2001 Sep;32(9):2058-74
11546898
N Engl J Med. 2001 Nov 15;345(20):1444-51
11794192
Control Clin Trials. 2001 Dec;22(6):659-73
11738122
Int J Technol Assess Health Care. 2002 Winter;18(1):127-38
11987436
Lancet. 2002 Apr 27;359(9316):1453-60
11988242
JAMA. 2002 Jul 3;288(1):49-57
12090862
Int J Technol Assess Health Care. 2002 Summer;18(3):497-507
12391943
Nat Neurosci. 2002 Nov;5 Suppl:1027-9
12403977
Neurology. 2002 Dec 10;59(11):1766-71
12473766
Ann Intern Med. 2003 Jan 7;138(1):40-4
12513043
JAMA. 2003 Mar 12;289(10):1278-87
12633190
Mov Disord. 2004 Feb;19(2):136-50
14978668
Arch Neurol. 2004 Apr;61(4):561-6
15096406
JAMA. 1977 Jul 18;238(3):224-7
406427
Neurology. 1982 Mar;32(3):280-2
7199638
Neurology. 1983 Nov;33(11):1444-52
6685237
N Engl J Med. 1990 Mar 22;322(12):863-8
2407959
N Engl J Med. 1991 Aug 15;325(7):445-53
1852179
N Engl J Med. 1992 Feb 27;326(9):581-8
1734247
N Engl J Med. 1992 Sep 10;327(11):765-71
1298221
JAMA. 1993 Dec 1;270(21):2598-601
8230645
Ann Neurol. 1994 Feb;35(2):172-80
8109898
Lancet. 1994 Mar 19;343(8899):687-91
7907677
Circulation. 1994 Sep;90(3):1588-601
8087974
Neurology. 1995 Jul;45(7):1277-85
7617182
Gen Hosp Psychiatry. 2003 Mar-Apr;25(2):115-23
12676425
Clin Ther. 2003 Feb;25(2):611-34
12749517
Am J Epidemiol. 2003 Jun 1;157(11):1015-22
12777365
JAMA. 2003 Jun 4;289(21):2810-8
12783911
JAMA. 2003 Jun 25;289(24):3241-2
12824204
Ann Neurol. 2003 Sep;54(3):403-14
12953276
Circulation. 1997 Feb 18;95(4):1072-82
9054772
Lancet. 1997 May 31;349(9065):1569-81
9174558
Lancet. 1997 Jun 7;349(9066):1641-9
9186381
Mayo Clin Proc. 1997 Sep;72(9):871-8
9294536
Alzheimer Dis Assoc Disord. 1997;11 Suppl 5:S10-21; discussion S37-9
9348423
JAMA. 1998 Feb 18;279(7):545-9
9480367
Neurology. 1998 Mar;50(3):701-8
9521260
Neurology. 1998 Jul;51(1):48-55
9674777
Arch Neurol. 1998 Aug;55(8):1089-95
9708959
J Nucl Med. 1998 Sep;39(9):1500-8
9744331
Chest. 1998 Nov;114(5 Suppl):441S-444S
9822056
Pharmacoeconomics. 1998 Nov;14(5):541-57
10344917
Epilepsy Res. 1999 Apr;34(2-3):135-43
10210028
Ann Intern Med. 1999 Aug 17;131(4):237-46
10454944
Neurology. 1999 Aug 11;53(3):448-56
10449103
JAMA. 1999 Aug 25;282(8):771-8
10463714