PMID- 26072464
OWN - NLM
STAT- MEDLINE
DCOM- 20160609
LR  - 20220318
IS  - 1878-1632 (Electronic)
IS  - 1529-9430 (Linking)
VI  - 15
IP  - 10
DP  - 2015 Oct 1
TI  - The fragility of statistically significant findings from randomized trials in 
      spine surgery: a systematic survey.
PG  - 2188-97
LID - S1529-9430(15)00577-X [pii]
LID - 10.1016/j.spinee.2015.06.004 [doi]
AB  - BACKGROUND CONTEXT: Randomized controlled trials (RCTs) are the most trustworthy 
      source for evaluating treatment effects, but RCTs of spine surgery interventions 
      often produce discordant results. The Fragility Index is a novel metric to inform 
      about the robustness of statistically significant results. PURPOSE: The aim was 
      to determine the robustness of statistically significant results from RCTs of 
      spine surgery interventions. STUDY DESIGN/SETTING: This was a systematic survey. 
      PATIENT SAMPLE: The sample included RCTs of spine surgery interventions. OUTCOME 
      MEASURES: The Fragility Index is the minimum number of patients in a trial whose 
      status would have to change from a nonevent to an event to change a statistically 
      significant result to a nonsignificant result. Events refer to the occurrence of 
      any dichotomous outcome, such as successful fusion, incident fracture, adjacent 
      segment degeneration, or achievement of a certain functional score. A small 
      Fragility Index indicates that the statistical significance of a result hinges on 
      only a few events, and a large Fragility Index increases one's confidence in the 
      observed treatment effects. METHODS: We systematically reviewed a database for 
      evidence-based orthopedics and identified all the RCTs that reported at least one 
      positive outcome (ie, p<.05). Two reviewers independently assessed eligibility 
      and extracted data. We used the Fisher exact test to compute Fragility Index 
      values and multivariable linear regression to evaluate potential associated 
      factors. RESULTS: We identified 40 eligible RCTs with a median sample size of 132 
      patients (interquartile range [IQR] 79-208) and a median total number of outcome 
      events for the chosen outcome of 31 (IQR 13-63). The median Fragility Index was 
      two (IQR 1-3), which means that adding two events to one of the trial's treatment 
      arms eliminated its statistical significance. The Fragility Index was less than 
      or equal to three events in 75% of the trials, and was less than or equal to the 
      number of patients lost to follow-up in 65% of the trials. Fragility Index values 
      correlated positively with total sample size (r=0.35; p<.05). When adjusted for 
      losses to follow-up and risk of bias, increasing Fragility Index values were 
      associated only with increasingly significant reported p values (p<.01). 
      CONCLUSIONS: Statistically significant results in spine surgery RCTs are 
      frequently fragile. The addition of only a small number of outcome events can 
      completely eliminate significance. Surgeons, researchers, and other evidence 
      users should exercise caution when interpreting the findings from RCTs with low 
      Fragility Index values and applying these results to patient care.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Evaniew, Nathan
AU  - Evaniew N
AD  - Division of Orthopaedics, Department of Surgery, McMaster University, Hamilton, 
      Ontario, Canada; Department of Clinical Epidemiology and Biostatistics, McMaster 
      University, Hamilton, Ontario, Canada. Electronic address: 
      nathan.evaniew@medportal.ca.
FAU - Files, Carly
AU  - Files C
AD  - Division of Orthopaedics, Department of Surgery, McMaster University, Hamilton, 
      Ontario, Canada.
FAU - Smith, Christopher
AU  - Smith C
AD  - Division of Orthopaedics, Department of Surgery, McMaster University, Hamilton, 
      Ontario, Canada.
FAU - Bhandari, Mohit
AU  - Bhandari M
AD  - Division of Orthopaedics, Department of Surgery, McMaster University, Hamilton, 
      Ontario, Canada; Department of Clinical Epidemiology and Biostatistics, McMaster 
      University, Hamilton, Ontario, Canada.
FAU - Ghert, Michelle
AU  - Ghert M
AD  - Division of Orthopaedics, Department of Surgery, McMaster University, Hamilton, 
      Ontario, Canada.
FAU - Walsh, Michael
AU  - Walsh M
AD  - Department of Clinical Epidemiology and Biostatistics, McMaster University, 
      Hamilton, Ontario, Canada.
FAU - Devereaux, Philip J
AU  - Devereaux PJ
AD  - Department of Clinical Epidemiology and Biostatistics, McMaster University, 
      Hamilton, Ontario, Canada.
FAU - Guyatt, Gordon
AU  - Guyatt G
AD  - Department of Clinical Epidemiology and Biostatistics, McMaster University, 
      Hamilton, Ontario, Canada.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
DEP - 20150611
PL  - United States
TA  - Spine J
JT  - The spine journal : official journal of the North American Spine Society
JID - 101130732
SB  - IM
MH  - Humans
MH  - Neurosurgical Procedures/*adverse effects/statistics & numerical data
MH  - Orthopedic Procedures/*adverse effects/statistics & numerical data
MH  - Randomized Controlled Trials as Topic/standards/*statistics & numerical data
MH  - Spinal Injuries/*surgery
OTO - NOTNLM
OT  - Clinical epidemiology
OT  - Fragility Index
OT  - Outcomes
OT  - Randomized controlled trials
OT  - Spine surgery
OT  - Statistical significance
EDAT- 2015/06/15 06:00
MHDA- 2016/06/10 06:00
CRDT- 2015/06/15 06:00
PHST- 2015/01/28 00:00 [received]
PHST- 2015/04/27 00:00 [revised]
PHST- 2015/06/01 00:00 [accepted]
PHST- 2015/06/15 06:00 [entrez]
PHST- 2015/06/15 06:00 [pubmed]
PHST- 2016/06/10 06:00 [medline]
AID - S1529-9430(15)00577-X [pii]
AID - 10.1016/j.spinee.2015.06.004 [doi]
PST - ppublish
SO  - Spine J. 2015 Oct 1;15(10):2188-97. doi: 10.1016/j.spinee.2015.06.004. Epub 2015 
      Jun 11.