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Introduction: Meta-analysis is the method to pool data from studies that report the same event in a comparable sample and, thus, summarize information from different populations. However, data extraction is limited to the information provided in the included studies. Frequently, individual patient information is not available, hence, real world data access is limited. Individual patient data (IPD) meta-analysis in a research area like health sciences constitutes the ideal method to analyse real world data, assuming a high level of evidence. (1) This method is based on a collaboration network in which variables can be merged among datasets once a single definition is determined reducing methodological heterogeneity. The use of IPD for meta-analysis has advantages, (allows adjustment for confounding factors), and limitations (obtaining individual patient data knowing that data collection and management are often unclear). (1, 2) To tackle high heterogeneity in a study-level meta-analysis, sensitivity analyses are recommended. Leave-one-out analysis is an option that evaluates the cumulative effect of each study by excluding one at a time, portraying its influence in the overall result (3). Considering the lack of long-term data on postoperative acute kidney injury (AKI) in coronary artery bypass grafting surgery (CABG) patients, paired with the expected study heterogeneity, we intend to summarize evidence regarding its effect on early and long-term survival, evaluate heterogeneity and perform sensitivity analysis. Methods: Systematic searches were performed in MEDLINE and ISI Web of Science, restricted by date of publication (January 1960–April 2021). Inclusion criteria comprised observational studies reporting incidence of postoperative AKI in adult patients, submitted to isolated CABG with at least 1-year of follow-up and survival estimates. Analyses were performed using Review Manager 5.4. and R environment. Random effects models were used to compute pooled HR and OR (95% CI), through generic inverse variance method and Mantel-Haenszel method or generalized linear mixed-effects model and logit-transformed proportions of AKI were used for analysis of prevalence data. Heterogeneity was defined using I2 statistics and was considered low (75%) (4). Between-study heterogeneity was studied using sensitivity analyses, namely, leave-one-out evaluations (metagen (meta R package)). Early and late survival were evaluated through this sensitivity analysis and were present according to each study impact on both effect size estimates and observed I2. (5) Results: Thirteen retrospective observational studies comprising 63209 patients were included, (N AKI=11366, N non-AKI=51843). AKI incidence ranged 0.6%-54% with a pooled incidence of 16%. Postoperative AKI was associated with higher early mortality (OR (95%CI): 7.59 (3.18-18.15), p 2 mg/dL according to preoperative renal function status, which differs from the most traditional criteria used by the other studies: increment of at least 0.3 mg/dL. Leave-one-out analysis showed that one must pay attention to real-world data, since different variable definitions, namely: different AKI definitions and the samples included in each study, influence overall measures. Acknowledgements: This study is funded by national funds through FCT - Portuguese Foundation for Science and Technology, under the scope of the Cardiovascular R&D Center – UnIC@RISE [grant numbers UIDB/00051/2020, UIDP/00051/2020]. R. Moreira is supported by FCT - Portuguese Foundation for Science and Technology, FSE – European Social Fund, NORTE 2020 - Programa Operacional Regional do Norte (POR-Norte), (UI/BD/150657/2020). References: Riley RD, Lambert PC, Abo-Zaid G. Meta-analysis of individual participant data: rationale, conduct, and reporting. Bmj. 2010;340. Kanters S, Karim ME, Thorlund K, Anis A, Bansback N. When does the use of individual patient data in network meta-analysis make a difference? A simulation study. BMC medical research methodology. 2021;21(1):1-13. Wallace BC, Schmid CH, Lau J, Trikalinos TA. Meta-Analyst: software for meta-analysis of binary, continuous and diagnostic data. BMC medical research methodology. 2009;9(1):1-12. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Bmj. 2003;327(7414):557-60. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane handbook for systematic reviews of interventions: John Wiley & Sons; 2019. Ivert T, Holzmann MJ, Sartipy U. Survival in patients with acute kidney injury requiring dialysis after coronary artery bypass grafting. Eur J Cardiothorac Surg. 2014;45(2):312-7. Di Mauro M, Gagliardi M, Iacò AL, Contini M, Bivona A, Bosco P, et al. Does off-pump coronary surgery reduce postoperative acute renal failure? The importance of preoperative renal function. The Annals of thoracic surgery. 2007;84(5):1496-502. Lv M, Hu B, Ge W, Li Z, Wang Q, Han C, et al. Impact of Preoperative Occult Renal Dysfunction on Early and Late Outcomes After Off-Pump Coronary Artery Bypass. Heart, Lung and Circulation. 2021;30(2):288-95. Di Mauro M, Gagliardi M, Iacò AL, Contini M, Bivona A, Bosco P, et al. Does off-pump coronary surgery reduce postoperative acute renal failure? The importance of preoperative renal function. Ann Thorac Surg. 2007;84(5):1496-502., Journal of Statistics on Health Decision, vol. 4 n.º 1 (2022): Special Issue - Statistics on Health Decision Making: Real World Data

Journal of Statistics on Health Decision, vol. 3 n.º 1 (2021): Special Issue - Statistics on Health Decision Making: Public Health

Background: The number of health-related publications has been exponential in the recent decade. Indeed, cardiovascular area includes more than 670k papers published at MEDLINE [((cardiovascular) NOT ((("Animals"[Mesh] NOT ("Animals"[Mesh] AND "Humans"[Mesh])))], of which, more than 20k are related to coronary artery bypass grafting (CABG). We are witnessing a 6% increase in publications per year. The growth in potential information content is a challenge to manage; one way to leverage the evidence level using such a vast amount of information is using systematic reviews and meta-analysis. These approaches allow health professionals to quickly synthesize and efficiently be up to date regarding their specific topics of interest and, eventually, identify major gaps in the evidence. Meta-analysis of randomized controlled trials (RCTs) is considered one of the highest levels of evidence since pooling the data of individual studies provide higher statistical power to detect differences even in low-frequency events(1, 2). Besides the common pitfalls of all systematic reviews, such as overlapping data, publication bias, the limited number of databases searched, low quality, and heterogeneity of the original studies included(2), the lack of easy access to data is a severe limitation to leverage the potential information present in many studies. Also, an overwhelming number of authors do not reply to the reviewers or community queries for delivering access to papers’ data, implying their exclusion from quantitative analysis due to the lack of information, impacting the growth of the evidence building negatively. However, the publication of figures that provide relevant information is not an uncommon practice. More specifically, Kaplan-Meier curves to estimate cumulative survival differences between studies groups are usually provided, but occasionally without the association measure, hazard ratio (HR), which is of high relevance for evidence assessment. For the cases where the HR is not provided, the incidence rate ratio (IRR) calculation could be an option since the number of deaths within each group is provided (IRR=((nr events exposed group)/(total patients in risk exposed group×follow-up time))/((nr events control group)/(total patients in risk control group ×follow-up time))). For RCTs this is not a constraining factor, but for observational studies, it is likely to be a source of bias since the results should be adjusted for potential confounding or unbalanced covariates. In these cases, the crude number of deaths within each group and IRR calculation would provide an unadjusted and inconclusive analysis of data. Adjusted HR or HR provided from previously matched (balanced) groups are the best estimations to pool within observational studies. Guyot et al(3) developed an algorithm to reconstruct and analyse Kaplan-Meier curves, providing survival statistics. It also delivers HR, but the authors pointed out that this was not the primary purpose of their algorithm. Indeed, their validation exercise resulted in excellent reproducibility and accuracy for reconstruction of survival statistics, such as median survival and probability of survival, while HR reproducibility and accuracy was less good mostly when less information about number at risk and number of events were available. The reason pointed by the authors for the lower accuracy of HR comparing with the other statistics is that the HR is a weighted average of ratios along the curve, while the other statistics are simple points estimates. Our aim was to assess and validate, with our data, Guyot et al. algorithm for HR computation, for long-term survival outcome, and to estimate the precision of this method according to different levels of provided data. Methods: Using GetData Graph Digitizer 2.26 (http://getdata-graph-digitizer.com/), we imported one survival curve from our cohort study (n=2414 patients) that compared long-term survival between a bilateral internal mammary artery (BIMA) and single internal mammary artery (SIMA) CABG surgery. A careful delineation of each curve after limiting X and Y axes was done, and two ASCII (text) files, one per group, were exported with all the supplied coordinates: time (X) and cumulative survival (Y) for each point. Three event tables were built: 1) the number of patients at risk provided for every single year (from 0 to 10 – 10 points); 2) the number at risk was provided only every two years (5 points); 3) the number at risk only at three distinct points: beginning, median and end of follow-up (3 points). Those data files were then imported by an R script that reads the number at risk at each time point, produce vectors and calculates approximations of number of censored on each interval, i; adjusts the total number at risk and number of events within each i according to Kaplan-Meier (K-M) estimates read from curves. Then it obtains the individual patient data (IPD) from the reconstructed Kaplan-Meier data including time, event and respective arm. Finally, it reads those K-M and coxph formula could be applied. Those results were compared with Cox regression data derived directly from our dataset. Results: We included 2414 patients(4), of which 1478 were subject to SIMA and 936 were subject to BIMA. During the follow-up, median of 5.5 years for a maximum of 12 years, 391 deaths were registered (20% SIMA vs. 10% BIMA). Kaplan-Meier curves marked an evident statistical difference between those groups as well as the Cox regression (HR for BIMA: 0.6046, CI 95%: 0.4771 – 0.7663). From the 3 methods we stated above we got the following HR [95% CI]: 1) 0.5994 [0.4735 – 0.7587]; 2) 0.6021 [0.4761 – 0.7614]; and 3) 0.5921 [0.4663 – 0.7518]. Conclusion: Even though the authors who provided the algorithm for reconstruction of Kaplan-Meier curves question its ability to compute HR, our own experience shows otherwise, corroborating with Saluja and colleagues who compared four methods developed to estimate HR from Kaplan-Meier curves and recommended the Guyot method(5). This algorithm has high potential and could be used to extract data from papers where quantitative data is absent. We recently used it to extract data from 9 studies avoiding to exclude them from a meta-analysis of RCTs and propensity score studies(6)., Journal of Statistics on Health Decision, vol. 2 n.º 2 (2020): Special Issue - Statistics on Health Decision Making: clinical trials