Objectives: The aim of this dissertation was to examine bias in randomized controlled trials (RCTs) and non-randomized studies (NRS) in surgery using the literature evaluating laparoscopy and conventional (i.e. open) surgery for the treatment of colon cancer as a case study. The objectives were 1) to develop a conceptual framework for bias in comparative NRS; 2) to compare effect estimates from NRS with those from RCTs at low risk of bias; 3) to explore the impact of NRS-design attributes on estimates of treatment effect.
Methods: The methods included a modified framework synthesis, systematic review of the literature, random-effects meta-analyses, and frequentist and Bayesian meta-regression. The Cochrane Risk of Bias Tool was used to classify trials as Strong RCTs (i.e. low risk of bias) or Typical RCTs (i.e. unclear or high risk of bias).
Results: A conceptual framework for bias in comparative NRS was developed and it contains 37 individual sources of bias or “items”. These items were organized within 6 overarching “domains”: selection bias, information bias, performance bias, detection bias, attrition bias, and selective reporting bias. Our analyses revealed that NRS were associated with more extreme estimates of benefit for laparoscopy than Strong RCTs when examining subjective outcomes. The odds ratios from NRS were 36% smaller (i.e. demonstrating more benefit for laparoscopy) than those from Strong RCTs for the outcome post-operative complications (Ratio of Odds Ratios, ROR 0.64, [0.42, 0.97], p=0.04). Similar exaggerated benefit was seen among NRS when assessing length of stay, (Difference in Mean Differences, -2.15 days, [-4.08, -0.21], p=0.03). This pattern was not observed with the objective outcomes peri-operative mortality and number of lymph nodes harvested. Analyses adjusted for period effects and between-study case-mix yielded similar findings. Finally, effect estimates in NRS did not consistently vary according to the presence or absence of nine design characteristics identified from the conceptual framework.
Conclusions: We have demonstrated that the results of surgical NRS can be significantly biased as compared with those of low risk of bias RCTs when evaluating subjective outcomes. However, none of the nine NRS-design characteristics examined was consistently associated with biased effect estimates.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/65452 |
| Date | 19 June 2014 |
| Creators | Sandhu, Lakhbir |
| Contributors | Urbach, David R |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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