Meta-analyses (MA) based on individual patient data (IPD) are regarded as the gold standard for meta-analyses and are becoming increasingly common, having several advantages over meta-analyses of summary statistics. These analyses are being undertaken in an increasing diversity of settings, often having a binary outcome. In a previous systematic review of articles published between 1999–2001, the statistical approach was seldom reported in sufficient detail, and the outcome was binary in 32% of the studies considered. Here, we explore statistical methods used for IPD-MA of binary outcomes only, a decade later.

Individual patient data meta-analyses (IPD-MA) are often performed using a one-stage approach-- a form of generalized linear mixed model (GLMM) for binary outcomes. We compare (i) one-stage to two-stage approaches (ii) the performance of two estimation procedures (Penalized Quasi-likelihood-PQL and Adaptive Gaussian Hermite Quadrature-AGHQ) for GLMMs with binary outcomes within the one-stage approach and (iii) using stratified study-effect or random study-effects. We compare the different approaches via a simulation study, in terms of bias, mean-squared error (MSE), coverage and numerical convergence, of the pooled treatment effect (β 1) and between-study heterogeneity of the treatment effect (τ 1 2 ). We varied the prevalence of the outcome, sample size, number of studies and variances and correlation of the random effects. The two-stage and one-stage methods produced approximately unbiased β 1 estimates. PQL performed better than AGHQ for estimating τ 1 2 with respect to MSE, but performed comparably with AGHQ in estimating the bias of β 1 and of τ 1 2 . The random study-effects model outperformed the stratified study-effects model in small size MA. The one-stage approach is recommended over the two-stage method for small size MA. There was no meaningful difference between the PQL and AGHQ procedures. Though the random-intercept and stratified-intercept approaches can suffer from their underlining assumptions, fitting GLMM with a random-intercept are less prone to misfit and has good convergence rate.

There is limited knowledge on non-invasive lymphedema risk-reduction strategies for women with gynecological cancer. Understanding factors influencing the feasibility of randomized controlled trials (RCTs) can guide future research. Our objectives are to report on the design and feasibility of a pilot RCT examining a tailored multidimensional intervention in women treated for gynecological cancer at risk of lymphedema and to explore the preliminary effectiveness of the intervention on lymphedema incidence at 12 months. In this pilot single-blinded, parallel-group, multi-centre RCT, women with newly diagnosed gynecological cancer were randomized to receive post-operative compression stockings and individualized exercise education (intervention group: IG) or education on lymphedema risk-reduction alone (control group: CG). Rates of recruitment, retention and assessment completion were recorded. Intervention safety and feasibility were tracked by monitoring adverse events and adherence. Clinical outcomes were evaluated over 12 months: presence of lymphedema, circumferential and volume measures, body composition and quality of life. Fifty-one women were recruited and 36 received the assigned intervention. Rates of recruitment and 12-month retention were 47% and 78%, respectively. Two participants experienced post-operative cellulitis, prior to intervention delivery. At three and six months post-operatively, 67% and 63% of the IG used compression ≥42 h/week, while 56% engaged in ≥150 weekly minutes of moderate-vigorous exercise. The cumulative incidence of lymphedema at 12 months was 31% in the CG and 31.9% in the IG (p = 0.88). In affected participants, lymphedema developed after a median time of 3.2 months (range, 2.7–5.9) in the CG vs. 8.8 months (range, 2.9–11.8) in the IG. Conducting research trials exploring lymphedema risk-reduction strategies in gynecological cancer is feasible but challenging. A tailored intervention of compression and exercise is safe and feasible in this population and may delay the onset of lymphedema. Further research is warranted to establish the role of these strategies in reducing the risk of lymphedema for the gynecological cancer population.