Using non-randomized trials to assess the clinical benefit of systemic anti-cancer treatments: Viable or not?

BACKGROUND: The Dutch Committee for the Evaluation of Oncological Agents (cieBOM) assesses the clinical benefit of systemic anti-cancer treatments (SACTs). For SACTs tested in non-randomized trials (NRTs), cieBOM primarily utilizes response-related thresholds as assessment criteria. As sufficiency of NRT-based evidence for benefit assessments is questionable, this study investigated whether and how NRTs can be used to assess the clinical benefit of new SACTs initially appraised by cieBOM based on randomized controlled trials (RCTs). METHODS: Using the RCTs underpinning cieBOM recommendations issued between 2015 and 2017, we searched for matching NRTs and applied the NRT-related assessment criteria by cieBOM to them. We then compared the assessment outcomes to the respective RCT-based cieBOM recommendations. Further, we investigated how the assessments would change when applying different response-related thresholds and adding a progression-free survival (PFS) threshold. RESULTS: For 13 of the 37 eligible recommendations, a matching NRT was found. Two treatments were assessed positively and six negatively; five treatments were non-assessable. Two positive recommendations matched a positive NRT-based assessment; one matching negative assessment was found, and one treatment could not be assessed based on either trial results. Adding a > 6 months PFS threshold decreased the number of non-assessable NRTs (five to two). CONCLUSIONS: Limited publications and inconsistent data reporting hampered the viability of NRTs for clinical benefit assessments of SACTs beyond the scope of rare indications. Further, response-related assessment criteria alone might not fully grasp the clinical benefit of novel SACTs. NRT-based assessments should be considered with caution due to uncertainty of the trial results.

Difficult epidural placement in obese and non-obese pregnant women: a systematic review and meta-analysis.

INTRODUCTION: The increasing rates of obese pregnant women who receive epidural analgesia during delivery make it necessary to evaluate the rate of epidural failure and difficulties during epidural placement in these women. METHODS: PubMed, Embase, Medline and Google scholar were searched systematically until December 2017 for articles reporting epidural failure and/or difficulties in epidural placement in obese pregnant women and non-obese pregnant women. We excluded studies that used ultrasound during epidural placement. Outcomes were defined as first-pass success or multiple attempts. Quality assessment of the literature was performed in accordance with an adjusted Newland-Ottawa Scale. Two groups of women were defined (body mass index (BMI) ≥30 kg/m2 and BMI <30 kg/m2). Statistical analysis was performed using OpenMetaAnalyst software. RESULTS: Initially 221 articles were identified, of which we included eight in the systematic review and four in the meta-analyses. Five out of six studies reported an association between BMI and epidural failure and four out of five studies reported an association between BMI and difficult epidural placement or multiple attempts. The odds ratios (OR) for epidural failure were 1.82 [95% CI 1.23 to 2.68] and for multiple attempts 2.21 [95% CI 1.39 to 3.52], both of these ORs applying to obese pregnant women compared to non-obese pregnant women. CONCLUSION: The findings suggest that obesity in pregnant women increases the risk of epidural failure and difficult epidural placement during delivery at least two-fold, and that this risk increases with increasing BMI.