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Meta-Analysis
. 2022 Feb;10(1):54-72.
doi: 10.1002/ueg2.12183. Epub 2021 Dec 14.

Composite outcomes in observational studies of ulcerative colitis: A systematic review and meta-analysis

Fernando Magro  1   2   3 , Catarina Alves  4 , Mafalda Santiago  5 , Paula Ministro  6 , Paula Lago  7 , Luís Correia  8 , Raquel Gonçalves  9 , Diana Carvalho  10 , Francisco Portela  11 , Cláudia Camila Dias  5   12 , Axel Dignass  13 , Silvio Danese  14   15 , Laurent Peyrin-Biroulet  16 , Maria Manuela Estevinho  2   17 , Paula Moreira  3 ; on behalf GEDII (Portuguese IBD Group)
Affiliations
Meta-Analysis

Composite outcomes in observational studies of ulcerative colitis: A systematic review and meta-analysis

Fernando Magro et al. United European Gastroenterol J. 2022 Feb.

Abstract

Background: Ulcerative colitis (UC) has been the focus of numerous observational studies over the years and a common strategy employed in their design is the use of composite and aggregate outcomes.

Objective: This systematic review and meta-analysis aims to identify composite and aggregate outcomes of observational studies in UC and to evaluate how the number and type of variables included and the length of follow-up affect the frequency of patients that achieve these outcomes.

Methods: A systematic literature search was carried out using MEDLINE [via PubMed], Scopus, and Web of Science online databases. Observational studies that included UC patients and reported composite or aggregate outcomes were identified. A set of variables considered to be representative of progressive or disabling UC was defined, the proportion of patients attaining the outcomes was determined and a random-effects meta-analysis was performed by dividing the identified studies into subgroups according to different criteria of interest.

Results: A total of 10,264 records were identified in the systematic search, of which 33 were retained for qualitative analysis and 20 were included in the meta-analysis. The mean frequency for composite outcomes was 0.363 [95% confidence interval (CI) 0.323-0.403]. The frequency of composite outcome for the subgroup of studies that included the variable "Biologics" was significantly higher than for those in which this variable was not reported [0.410; 95% CI 0.364-0.457 versus 0.298; 95% CI 0.232-0.364; p = 0.006]. Composite outcomes were also more frequent as the follow-up duration increased.

Conclusion: The frequency of composite outcomes in observational studies of UC is dependent on the specific identity of the variables being reported. Moreover, longer follow-up periods are associated with higher frequencies of composite outcomes. The evidence provided here is useful for the design of future observational studies of UC that aim to maximize the frequency of patients that achieve composite outcomes.

Keywords: aggregate outcomes; composite outcomes; meta-analysis; observational studies; systematic review; ulcerative colitis.

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Conflict of interest statement

Fernando Magro received a fee for presenting from: AbbVie, Ferring, Falk, Hospira, PharmaKern, MSD, Schering, Laboratórios Vitoria, Vifor Pharma, OM Pharma. Axel Dignass reports fees for participation in clinical trials, review activities, such as data monitoring boards, statistical analysis, end point committees from Falk, Abbvie, Janssen, Gilead, Pfizer; consultancy fees from Abbvie, MSD, Ferring, Roche/Genentech, Takeda, Vifor, Pharmacosmos, Boehringer‐Ingelheim, Falk, Janssen, Pfizer, Sandoz/Hexal, BMS/Celgene, Tillotts, Galapagos, Amgen and Fresenius Kabi; payment from lectures including service on speakers bureaus from Falk Foundation, Ferring, MSD, Abbvie, Vifor, Janssen, Pfizer, Tillotts, Takeda, Gilead/Galapagos; payment for manuscript preparation from Falk Foundation, Thieme, Takeda and UniMed Verlag. Silvio Danese has served as a speaker, consultant and advisory board member for Schering‐Plough, AbbVie, MSD, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alphawasserman, Genentech, Grunenthal, Pfizer, Astra Zeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor and Johnson & Johnson, Nikkiso Europe GMBH, Theravance. Laurent Peyrin‐Biroulet has served as a speaker, consultant, and advisory board member for Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, Hospira/Pfizer, Celltrion, Takeda, Biogaran, Boerhinger‐Ingelheim, Lilly, HAC Pharma, Index Pharmaceuticals, Amgen, Sandoz, Forward Pharma GmbH, Celgene, Biogen, Lycera, Samsung Bioepis, Theravance.

Figures

FIGURE 1
FIGURE 1
Flow diagram of study selection and data collection process
FIGURE 2
FIGURE 2
(a) Frequency of composite outcomes, n = 21 (b) Frequency of composite outcomes according to the number of variables reported in the study. n = 21
FIGURE 2
FIGURE 2
(a) Frequency of composite outcomes, n = 21 (b) Frequency of composite outcomes according to the number of variables reported in the study. n = 21
FIGURE 3
FIGURE 3
Frequency of composite outcomes according to the presence of individual predefined variables reported in the study. (a) Subgroups determined by the presence or absence of the variable “Biologics”, n = 21. (b) Subgroups determined by the presence or absence of the variable “Clinical Assessment,” n = 21
FIGURE 3
FIGURE 3
Frequency of composite outcomes according to the presence of individual predefined variables reported in the study. (a) Subgroups determined by the presence or absence of the variable “Biologics”, n = 21. (b) Subgroups determined by the presence or absence of the variable “Clinical Assessment,” n = 21
FIGURE 4
FIGURE 4
Frequency of composite outcomes according to length of the follow‐up period. (a) Subgroups determined by a total duration of the follow‐up above or below one year. (b) Subgroups determined by a total duration of the follow‐up above or below two years. FU: follow‐up
FIGURE 4
FIGURE 4
Frequency of composite outcomes according to length of the follow‐up period. (a) Subgroups determined by a total duration of the follow‐up above or below one year. (b) Subgroups determined by a total duration of the follow‐up above or below two years. FU: follow‐up
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References

    1. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474:307–17. - PMC - PubMed
    1. Peyrin‐Biroulet L, Sandborn W, Sands BE, Reinisch W, Bemelman W, Bryant RV, et al. Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat‐to‐target. Am J Gastroenterol. 2015;110:1324–38. - PubMed
    1. Goldberg R, Gore JM, Barton B, Gurwitz J. Individual and composite study endpoints: separating the wheat from the chaff. Am J Med. 2014;127:379–84. - PMC - PubMed
    1. Williamson PR, Altman DG, Blazeby JM, Clarke M, Devane D, Gargon E, et al. Developing core outcome sets for clinical trials: issues to consider. Trials. 2012;13:132. - PMC - PubMed
    1. Ferreira‐González I, Permanyer‐Miralda G, Busse JW, Bryant DM, Montori VM, Alonso‐Coello P, et al. Methodologic discussions for using and interpreting composite endpoints are limited, but still identify major concerns. J Clin Epidemiol. 2007;60:651–7. - PubMed

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