Table 2.
Classification of Methodological Errors and Biases
| # | Methodological errors in the trials reviewed | #s of reviews/protocols (from Table 1) |
|---|---|---|
| 1 | In a meta-analysis of non-inferiority trials, the control group is not evidence-based to be safe and effective. Consequently, non-inferiority does not indicate safety or efficacy. | 1, 2, 4, 5, 6, 7, 8, 11, 12, 13, 18, 19, 20, 25, 30, 31, 34, 39, 45, 46, 47, 50, 54, 55 |
| 2 | The control group of the RCT is evidence-based to do harm. | 19, 35, 50 |
| 3 | Placebo or no treatment control is used (proposed for protocols) when clearly effective or probably effective nonanticoagulation treatment is either standard therapy or used widely. | 37, 40, 41, 48 |
| 4 | RCTs are (for protocols will be) too small to evaluate risk for HITT and observational studies not (for protocols will not be) evaluated for HITT. | 1, 3, 11, 12, 13, 25, 29, 34, 37, 38, 39, 40, 41, 42, 44, 45, 47, 48, 49, 51, 54, 55, 56, 57, 58 |
| 5 | Rebound hypercoagulability was not (for protocols will not be) assessed by collecting study data for an appropriate length of time after anticoagulant withdrawal in most patients (VTE treatment and prophylaxis, 2 months; heparins for acute coronary syndromes, 24 hours; clopidogrel for acute coronary syndromes or postpercutaneous coronary intervention, 90 days). | 1, 3, 5, 6, 10, 11, 12, 24, 25, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 46, 47, 48, 49, 50, 51, 52, 53, 54, 56, 58 |
| 6 | Because of excluding observational, population-based, and/or case-control studies from consideration in the safety analysis, bleeding complications were (for protocols will be) very likely understated. | 1, 3, 9, 10, 11, 13, 24, 25, 29, 30, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 51, 52, 53, 54, 55, 56, 57, 58 |
| 7 | The primary endpoint, which determines the main conclusions of the review, is a surrogate rather than a clinical endpoint. | 3, 5, 6, 10, 12, 37, 38, 41, 42, 48, 49 |
| 8 | The primary endpoint, which determines the main conclusions of the review, should include safety endpoints rather than just efficacy endpoints. | 1, 3, 7, 11, 25, 37, 40, 41, 42, 43, 52, 53, 54, 55, 56, 57, 58 |
| 9 | Fatal bleeding and/or intracranial bleeding were not (for protocols will not be) separately included in the primary or secondary endpoints. | 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 44, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 |
| Biases in data collection or interpretation by Cochrane reviewers | ||
| 10 | Conclusions of review were based on data from RCTs with patients who are not representative of patients in general clinical practice. | 3, 24, 25, 32, 33, 43 |
| 11 | A patented, expensive treatment (not the subject of the review) that is not evidence-based to work is endorsed in the Implications for Practice section. | 5, 6, 46 |
| 12 | The review has not been updated to include crucial recent RCTs or other data. | 14, 33, 47, 48, 49, 50 |
| 13 | Biases exist in the selection of trials for inclusion in the review. | 44, 54, 55 |
HITT = heparin induced thrombocytopenia with thrombosis; RCT = randomized, controlled trial; VTE = venous thromboembolism