Hostname: page-component-848d4c4894-m9kch Total loading time: 0 Render date: 2024-05-13T22:39:39.930Z Has data issue: false hasContentIssue false

The Numbers Needed to Treat for Neurological Disorders

Published online by Cambridge University Press:  02 December 2014

Miguel Bussière*
Affiliation:
Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada
Samuel Wiebe
Affiliation:
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
*
Division of Neurology, Department of Clinical Neurological Sciences, University of Western Ontario, 339 Windermere Road, Rm 7-GE6, London, Ontario, N6A 5A5, Canada
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Background:

Numerous therapeutic interventions have been developed in the neurosciences. Clinicians need summary measures about efficacy of therapies that derive from the best available evidence, and that can be readily extrapolated to clinical practice. The number needed to treat (NNT) is intuitive and clinically applicable. We provide clinicians with a single source that summarizes important therapies in the main neurological and neurosurgical areas.

Methods:

Critically appraised evidence about therapies in the neurosciences was obtained from meta-analyses in all neurosciences groups in the Cochrane library, and from critically appraised topics at the University of Western Ontario. Therapies were included if they were deemed relevant and if outcomes were dichotomous. For each therapy, we obtained absolute risk differences and their 95% confidence intervals (CI), the corresponding NNTs, control and experimental event rates, and the time-frame of the outcome assessment.

Results:

We assembled a table of NNTs for 87 interventions in ten disease categories, deriving from meta-analyses (70%) or randomized controlled trials (30%), and assessing surgical interventions (7%), procedures (9%) or pharmacological treatments (84%). The NNTs varied widely, ranging from 1 in the use of epidural blood patch for post-dural puncture headache to 4608 for meningococcal vaccination. Preventative interventions had substantially larger NNTs. Time-frames were inappropriately short for many chronic conditions.

Conclusions:

Large collections of NNTs provide useful, updateable summaries of therapeutic effects in the neurosciences, an increasingly interventional clinical field.

Résumé:

RÉSUMÉ:Contexte:

De nombreux traitements ont été développés en neurosciences. Les cliniciens ont besoin d’une synthèse fondée sur les meilleures données sur l’efficacité de ces traitements, qui peut être facilement appliquée en pratique clinique. Nous fournissons aux cliniciens une source unique qui fait un sommaire des traitements importants dans les principaux domaines de la neurologie et de la neurochirurgie.

Méthodes:

Des données ayant fait l’objet d’une évaluation critique ont été tirées de méta-analyses en neurosciences dans la bibliothèque Cochrane et de sujets ayant fait l’objet d’une évaluation critique à l’Université Western Ontario. Les traitements n’ont été inclus que s’ils étaient considérés pertinents et si les résultats présentaient une dichotomie. Pour chaque traitement, nous avons présentons les différences du risque absolu ainsi que l’intervalle de confiance de 95%, le nombre de patients devant être traités (NPT), le taux d’incidents thérapeutiques dans le groupe témoin et le groupe expérimental et la durée de l’étude.

Résultats:

Nous fournissons une table de NPT pour 87 interventions dans 10 catégories de maladies. Ces données proviennent de méta-analyses (70%) ou d’études contrôlées randomisées (30%) et évaluent des interventions chirurgicales (7%), des techniques (9%) ou des traitements pharmacologiques (84%). Les NPT variaient considérablement, allant de 1 pour le blood-patch épidural pour traiter la céphalée suite à une brèche de la dure-mère, à 4608 pour la vaccination anti-méningococcique. Les interventions préventives comportaient des NPT considérablement plus élevés. La durée des études sur plusieurs maladies était trop courte.

Conclusions:

Un recueil de NPT fournit un sommaire utile, qui peut être mis à jour, sur les effets des traitements en neurosciences, un champ clinique où il y a de plus en plus d’interventions.

Type
Original Article
Copyright
Copyright © The Canadian Journal of Neurological 2005

References

1. Bussiere, M, Wiebe, S. Measuring the benefit of therapies for neurological disorders. Can J Neurol Sci 2005; 32: 419424.Google Scholar
2. Yusuf, S, Sleight, P, Pogue, J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342:145153.Google Scholar
3. Wiffen, P, Collins, S, McQuay, H, et al. Anticonvulsant drugs for acute and chronic pain (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Oxford: Update Software.Google Scholar
4. Wiebe, S, Blume, WT, Girvin, JP, Eliasziw, M. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med 2001; 345:311318.Google Scholar
5. Mehndiratta, MM, Hughes, RAC. Corticosteroids for chronic inflammatory demyelinating polyradiculoneuropathy (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
6. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002; 346:549556.Google Scholar
7. Bernard, SA, Gray, TW, Buist, MD et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002; 346:557563.Google Scholar
8. Birks, JS, Harvey, R. Donepezil for dementia due to Alzheimer's disease (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
9. Olin, J, Schneider, L. Galantamine for Alzheimer's disease (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
10. Birks, J, Grimley Evans, J, Iakovidou, V, Tsolaki, M. Rivastigmine for Alzheimer's disease (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
11. Birks, J, Grimley Evans, J, Van Dongen, M. Ginkgo Biloba for Cognitive Impairment and Dementia (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
12. Als-Nielsen, B, Kjaergard, LL, Gluud, C. Benzodiazepine receptor antagonists for acute and chronic hepatic encephalopathy (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
13. Jacobs, LD, Beck, RW, Simon, JH, et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med 2000; 343:898904.Google Scholar
14. Comi, G, Filippi, M, Barkhof, F, et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 2001; 357:15761582.Google Scholar
15. CHAMPS Study Group. Interferon beta-1a for optic neuritis patients at high risk for multiple sclerosis. Am J Ophthalmol 2001; 132:463471.Google Scholar
16. Kaufman, DI, Trobe, JD, Eggenberger, ER, Whitaker, JN. Practice parameter: the role of corticosteroids in the management of acute monosymptomatic optic neuritis. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000; 54:20392044.Google Scholar
17. Brusaferri, F, Candelise, L. Steroids for multiple sclerosis and optic neuritis: a meta-analysis of randomized controlled clinical trials. J Neurol 2000; 247:435442.Google Scholar
18. Optic Neuritis Study Group. The 5-year risk of MS after optic neuritis. Experience of the optic neuritis treatment trial Neurology 1997; 49:14041413.Google Scholar
19. Filippini, G, Brusaferri, F, Sibley, WA, et al. Corticosteroids or ACTH for acute exacerbations in multiple sclerosis (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
20. Rice, GPA, Incorvaia, B, Munari, L, et al. Interferon in relapsing-remitting multiple sclerosis (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
21. Filippini, G, Munari, L, Incorvaia, B, et al. Interferons in relapsing remitting multiple sclerosis: a systematic review. Lancet 2003;361:545552.Google Scholar
22. Johnson, KP, Brooks, BR, Cohen, JA, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. Neurology 1995; 45:12681276.Google Scholar
23. Johnson, KP, Brooks, BR, Cohen, JA, et al. Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Copolymer 1 Multiple Sclerosis Study Group. Neurology 1998; 50:701708.Google Scholar
24. Mayo-Smith, MF. Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA 1997; 278:144151.Google Scholar
25. Marson, AG, Kadir, ZA, Hutton, JL, Chadwick, DW. Gabapentin add-on for drug-resistant partial epilepsy (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
26. Ramaratnam, S, Marson, AG, Baker, GA. Lamotrigine add-on for drug-resistant partial epilepsy (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Oxford: Update Software.Google Scholar
27. Chaisewikul, R, Privitera, MD, Hutton, JL, Marson, AG. Levetiracetam add-on for drug-resistant localization related (partial) epilepsy (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
28. Castillo, S, Schmidt, DB, White, S. Oxcarbazepine add-on for drug-resistant partial epilepsy (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
29. Pereira, J, Marson, AG, Hutton, JL. Tiagabine add-on for drug-resistant partial epilepsy (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
30. Jette, NJ, Marson, AG, Hutton, JL. Topiramate add-on for drug-resistant partial epilepsy (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
31. Chadwick, DW, Marson, AG. Zonisamide add-on for drug-resistant partial epilepsy (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
32. Privitera, MD, Welty, TE, Ficker, DM, Welge, J. Vagus nerve stimulation for partial seizures (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
33. First Seizure Trial Group. Randomized clinical trial on the efficacy of antiepileptic drugs in reducing the risk of relapse after a first unprovoked tonic-clonic seizure. Neurology 1993; 54: 478483.Google Scholar
34. Wiebe, S. An evidence based approach to the first unprovoked seizure. Can J Neurol Sci 2002; 29: 120124.Google Scholar
35. Duley, L, Gülmezoglu, AM, Henderson-Smart, DJ. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
36. Duley, L, Henderson-Smart, D. Magnesium sulphate versus diazepam for eclampsia (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
37. Duley, L, Henderson-Smart, D. Magnesium sulphate versus phenytoin for eclampsia (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd.Google Scholar
38. Schierhout, G, Roberts, I. Anti-epileptic drugs for preventing seizures following acute traumatic brain injury (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
39. Roberts, I, Schierhout, G, Wakai, A. Mannitol for acute traumatic brain injury (Cochrane Review). In: The Cochrane Library Issue 3, 2003, 2003. Oxford: Update Software.Google Scholar
40. Hancock, E, Osborne, J, Milner, P. Treatment of infantile spasms (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
41. Medical Research Council Antiepileptic Drug Withdrawal Study Group. Randomised study of antiepileptic drug withdrawal in patients in remission. Lancet 1991; 337:11751180.Google Scholar
42. Backonja, M, Beydoun, A, Edwards, KR, et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. JAMA 1998; 280:18311836.Google Scholar
43. McQuay, HJ, Tramer, M, Nye, BA, et al. A systematic review of antidepressants in neuropathic pain. Pain 1996; 68:217227.Google Scholar
44. van Tulder, MW, Touray, T, Furlan, AD, Solway, S, Bouter, LM. Muscle relaxants for non-specific low back pain (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
45. van Tulder, MW, Scholten, RJPM, Koes, BW, Deyo, RA. Non-steroidal anti-inflammatory drugs for low back pain (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
46. Smith, LA, Oldman, AD, McQuay, HJ, Moore, RA. Eletriptan for acute migraine (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
47. McCrory, DC, Gray, RN. Oral sumatriptan for acute migraine (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
48. Sudlow, C, Warlow, C. Epidural blood patching for preventing and treating post-dural puncture headache (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
49. Rowbotham, M, Harden, N, Stacey, B, Bernstein, P, Magnus-Miller, L. Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA 1998; 280:18371842.Google Scholar
50. de Gans, J, van de, BD. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002; 347:15491556.Google Scholar
51. Salinas, R, Prasad, K. Drugs for treating neurocysticercosis (tapeworm infection of the brain) (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
52. Whitley, RJ, Alford, CA, Hirsch, MS, et al. Vidarabine versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med 1986; 314:144149.Google Scholar
53. Patel, M, Lee, CK. Polysaccharide vaccines for preventing serogroup A meningococcal meningitis (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
54. Prasad, K, Volmink, J, Menon, GR. Steroids for treating tuberculous meningitis (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
55. Lima, AR, Soares-Weiser, K, Bacaltchuk, J, Barnes, TRE. Benzodiazepines for neuroleptic-induced acute akathisia (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
56. Rascol, O, Brooks, DJ, Korczyn, AD, et al. A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa. N Engl J Med 2000; 342:14841491.Google Scholar
57. Clarke, CE, Speller, JM. Pergolide versus bromocriptine for levodopa-induced complications in Parkinson's disease (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
58. Clarke, CE, Deane, KHO. Ropinirole for levodopa-induced complications in Parkinson’s disease (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
59. Clarke, CE, Speller, JM, Clarke, JA. Pramipexole for levodopa- induced complications in Parkinson's disease (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
60. Miller, RG, Mitchell, JD, Lyon, M, Moore, DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
61. Verdugo, RJ, Salinas, RS, Castillo, J, Cea, JG. Surgical versus non-surgical treatment for carpal tunnel syndrome (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
62. Van Schaik, IN, Winer, JB, de Haan, R, Vermeulen, M. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculopathy (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
63. Raphaël, JC, Chevret, S, Hughes, RAC, Annane, D. Plasma exchange for Guillain-Barré syndrome (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
64. van der Meche, FG, Schmitz, PI. A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barre syndrome. Dutch Guillain-Barre Study Group. N Engl J Med 1992; 326:11231129.Google Scholar
65. Patchell, RA, Tibbs, PA, Regine, WF, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 1998; 280:14851489.Google Scholar
66. Mintz, AH, Kestle, J, Rathbone, MP, et al. A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer 1996; 78:14701476.Google Scholar
67. The Prophylactic Cranial Irradiation Overview Collaborative Group. Cranial irradiation for preventing brain metastases of small cell lung cancer in patients in complete remission (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
68. Rinkel, GJE, Feigin, VL, Algra, A, Vermeulen, M, van Gijn, J. Calcium antagonists for aneurysmal subarachnoid haemorrhage (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
69. Molyneux, A, Kerr, R, Stratton, I, et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet 2002; 360:12671274.Google Scholar
70. Wardlaw, JM, del Zoppo, G, Yamaguchi, T. Thrombolysis for acute ischaemic stroke (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
71. Sandercock, P, Gubitz, G, Foley, P, Counsell, C. Antiplatelet therapy for acute ischaemic stroke (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
72. Stroke Unit Trialists' Collaboration. Organised inpatient (stroke unit) care for stroke (Cochrane Review). In: The Cochrane Library Issue 3, 2003. Oxford: Update Software.Google Scholar
73. Benavente, O, Hart, R, Koudstaal, P, Laupacis, A, McBride, R. Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks (Cochrane Review). In: The Cochrane Library Issue 3, 2003. Oxford: Update Software.Google Scholar
74. Segal, JB, McNamara, RL, Miller, MR, et al. Anticoagulants or antiplatelet therapy for non-rheumatic atrial fibrillation and flutter (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Oxford: Update Software.Google Scholar
75. Chambers, BR, You, RX, Donnan, G. Carotid endarterectomy for asymptomatic carotid stenosis (Cochrane Review). In: The Cochrane Library Issue 3, 2003. Oxford: Update Software.Google Scholar
76. Perry, HM Jr., Davis, BR, Price, TR, et al. Effect of treating isolated systolic hypertension on the risk of developing various types and subtypes of stroke: the Systolic Hypertension in the Elderly Program (SHEP). JAMA 2000; 284:465471.Google Scholar
77. Koudstaal, PJ. Anticoagulants for preventing stroke in patients with nonrheumatic atrial fibrillation and a history of stroke or transient ischemic attacks (Cochrane Review). In: The Cochrane Library Issue 3, 2003. Oxford: Update Software.Google Scholar
78. Hankey, GJ, Sudlow, CLM, Dunbabin, DW. Thienopyridine derivatives (ticlopidine, clopidogrel) versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
79. Diener, HC, Bogousslavsky, J, Brass, LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet 2004; 364:331337.Google Scholar
80. Diener, HC, Cunha, L, Forbes, C, et al. European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996; 143:113.Google Scholar
81. Gueyffier, F, Boissel, JP, Boutitie, F, et al. Effect of antihypertensive treatment in patients having already suffered from stroke. Gathering the evidence. Stroke 1997; 28:25572562.Google Scholar
82. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358:10331041.Google Scholar
83. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20, 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360:722.Google Scholar
84. Cina, CS, Clase, CM, Haynes, RB. Carotid endarterectomy for symptomatic carotid stenosis (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
85. Hilton, MPD. The Epley (canalith repositioning) manoeuvre for benign paroxysmal positional vertigo (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
86. Amaragiri, SV, Lees, TA. Elastic compression stockings for prevention of deep vein thrombosis (Cochrane Review). In: The Cochrane Library Issue 3, 2004. Oxford: Update Software.Google Scholar
87. US Modafinil in Narcolepsy Multicenter Study Group. Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy. Neurology 2000; 54:11661175.Google Scholar
88. Smeeth, L, Haines, A, Ebrahim, S. Numbers needed to treat derived from meta-analyses--sometimes informative, usually misleading. BMJ 1999; 318: 1548–51.Google Scholar
89. McAlister, FA, Straus, SE, Guyatt, GH, Haynes, RB. Users' guides to the medical literature: XX. Integrating research evidence with the care of the individual patient. Evidence-Based Medicine Working Group. JAMA 2000; 283: 28292836.Google Scholar
90. Sinclair, JC, Cook, RJ, Guyatt, GH, Pauker, SG, Cook, DJ. When should an effective treatment be used? Derivation of the threshold number needed to treat and the minimum event rate for treatment. J Clin Epidemiol 2001; 54: 253262.Google Scholar