A practical approach to a multi-level analysis with a sparse binary outcome within a large surgical trial.

OBJECTIVES: To assess the potential source of variation that surgeon may add to patient outcome in a clinical trial of surgical procedures. METHODS: Two large (n = 1380) parallel multicentre randomized surgical trials were undertaken to compare laparoscopically assisted hysterectomy with conventional methods of abdominal and vaginal hysterectomy; involving 43 surgeons. The primary end point of the trial was the occurrence of at least one major complication. Patients were nested within surgeons giving the data set a hierarchical structure. A total of 10% of patients had at least one major complication, that is, a sparse binary outcome variable. A linear mixed logistic regression model (with logit link function) was used to model the probability of a major complication, with surgeon fitted as a random effect. Models were fitted using the method of maximum likelihood in SAS. RESULTS: There were many convergence problems. These were resolved using a variety of approaches including; treating all effects as fixed for the initial model building; modelling the variance of a parameter on a logarithmic scale and centering of continuous covariates. The initial model building process indicated no significant 'type of operation' across surgeon interaction effect in either trial, the 'type of operation' term was highly significant in the abdominal trial, and the 'surgeon' term was not significant in either trial. CONCLUSIONS: The analysis did not find a surgeon effect but it is difficult to conclude that there was not a difference between surgeons. The statistical test may have lacked sufficient power, the variance estimates were small with large standard errors, indicating that the precision of the variance estimates may be questionable.

Psychometric properties of the Body Image Scale in women with benign gynaecological conditions.

OBJECTIVES: To evaluate the psychometric properties of the Body Image Scale (originally designed for use in cancer) in women with benign gynaecological conditions. STUDY DESIGN: Prospective completion of the Body Image Scale by women participating in the EVALUATE Hysterectomy Trial. The scale was completed pre-operatively, then 6 weeks, 4 and 12 months post-operatively. The psychometric properties were evaluated by assessing the reliability, response prevalence, discriminant validity and sensitivity to change. Factor analysis was also conducted to determine the scale structure. RESULTS: The Body Image Scale showed good reliability and clinical validity. Differences between sub-groups of women were detected, demonstrating good discriminant validity. The Body Image Scale was shown to be responsive to changes in body image. CONCLUSIONS: The Body Image Scale was shown to be a reliable and valid tool for assessing body image in women with benign gynaecological conditions and for use in clinical trials involving such women.

Cost effectiveness analysis of laparoscopic hysterectomy compared with standard hysterectomy: results from a randomised trial.

OBJECTIVE: To assess the cost effectiveness of laparoscopic hysterectomy compared with conventional hysterectomy (abdominal or vaginal). DESIGN: Cost effectiveness analysis based on two parallel trials: laparoscopic (n = 324) compared with vaginal hysterectomy (n = 163); and laparoscopic (n = 573) compared with abdominal hysterectomy (n = 286). PARTICIPANTS: 1346 women requiring a hysterectomy for reasons other than malignancy. MAIN OUTCOME MEASURE: One year costs estimated from NHS perspective. Health outcomes expressed in terms of QALYs based on women's responses to the EQ-5D at baseline and at three points during up to 52 weeks' follow up. RESULTS: Laparoscopic hysterectomy cost an average of 401 pounds sterling (708 dollars; 571 euros) more (95% confidence interval 271 pounds sterling to 542 pounds sterling) than vaginal hysterectomy but produced little difference in mean QALYs (0.0015, -0.015 to 0.018). Mean differences in cost and QALYs generated an incremental cost per QALY gained of 267 333 pounds sterling (471 789 dollars; 380 437 euros). The probability that laparoscopic hysterectomy is cost effective was below 50% for a large range of values of willingness to pay for an additional QALY. Laparoscopic hysterectomy cost an average of 186 pounds sterling (328 dollars; 265 euros) more than abdominal hysterectomy, although 95% confidence intervals crossed zero (-26 pounds sterling to 375 pounds sterling); there was little difference in mean QALYs (0.007, -0.008 to 0.023), resulting in an incremental cost per QALY gained of 26 571 pounds sterling (46 893 dollars; 37 813 euros). If the NHS is willing to pay 30 000 pounds sterling for an additional QALY, the probability that laparoscopic hysterectomy is cost effective is 56%. CONCLUSIONS: Laparoscopic hysterectomy is not cost effective relative to vaginal hysterectomy. Its cost effectiveness relative to the abdominal procedure is finely balanced.

The eVALuate study: two parallel randomised trials, one comparing laparoscopic with abdominal hysterectomy, the other comparing laparoscopic with vaginal hysterectomy.

OBJECTIVE: To compare the effects of laparoscopic hysterectomy and abdominal hysterectomy in the abdominal trial, and laparoscopic hysterectomy and vaginal hysterectomy in the vaginal trial. DESIGN: Two parallel, multicentre, randomised trials. SETTING: 28 UK centres and two South African centres. PARTICIPANTS: 1380 women were recruited; 1346 had surgery; 937 were followed up at one year. Primary outcome Rate of major complications. RESULTS: In the abdominal trial laparoscopic hysterectomy was associated with a higher rate of major complications than abdominal hysterectomy (11.1% v 6.2%, P = 0.02; difference 4.9%, 95% confidence interval 0.9% to 9.1%) and the number needed to treat to harm was 20. Laparoscopic hysterectomy also took longer to perform (84 minutes v 50 minutes) but was less painful (visual analogue scale 3.51 v 3.88, P = 0.01) and resulted in a shorter stay in hospital after the operation (3 days v 4 days). Six weeks after the operation, laparoscopic hysterectomy was associated with less pain and better quality of life than abdominal hysterectomy (SF-12, body image scale, and sexual activity questionnaires). In the vaginal trial we found no evidence of a difference in major complication rates between laparoscopic hysterectomy and vaginal hysterectomy (9.8% v 9.5%, P = 0.92; difference 0.3%, -5.2% to 5.8%), and the number needed to treat to harm was 333. We found no evidence of other differences between laparoscopic hysterectomy and vaginal hysterectomy except that laparoscopic hysterectomy took longer to perform (72 minutes v 39 minutes) and was associated with a higher rate of detecting unexpected pathology (16.4% v 4.8%, P = < 0.01). However, this trial was underpowered. CONCLUSIONS: Laparoscopic hysterectomy was associated with a significantly higher rate of major complications than abdominal hysterectomy. It also took longer to perform but was associated with less pain, quicker recovery, and better short term quality of life. The trial comparing vaginal hysterectomy with laparoscopic hysterectomy was underpowered and is inconclusive on the rate of major complications; however, vaginal hysterectomy took less time.