Missing Data in Prediction Research: A Five-Step Approach for Multiple Imputation, Illustrated in the CENTER-TBI Study

• DOI: 10.1089/neu.2020.7218
• Publication Date: 2021-01-20T11:58:50Z
• Authors: Benjamin Yaël Gra...; Charlie Aletta Se...; Esmee Venema; Daan Nieboer; Ewout W. Steyerberg; ; Cecilia Åkerlund; Krisztina Amrein; Nada Andelic; Lasse Andreassen; Audny Anke; Anna Antoni; Gérard Audibert; Philippe Azouvi; Maria Luisa Azzolini; Ronald Bartels; Pál Barzó; Romuald Beauvais; Ronny Beer; Bo-Michael Bellander; Antonio Belli; Habib Benali; Maurizio Berardino; Luigi Beretta; Morten Blaabjerg; Peter Bragge; Alexandra Brazinova; Vibeke Brinck; Joanne Brooker; Camilla Brorsson; Andras Buki; Monika Bullinger; Manuel Cabeleira; Alessio Caccioppola; Emiliana Calappi; Maria Rosa Calvi; Peter Cameron; Guillermo Carbayo...; Marco Carbonara; Giorgio Chevallard; Arturo Chieregato; Giuseppe Citerio; Maryse Cnossen; Mark Coburn; Jonathan Coles; D. Jamie Cooper; Marta Correia; Amra Čović; Nicola Curry; Endre Czeiter; Marek Czosnyka; Claire Dahyot-Fiz...; Helen Dawes; Véronique De Keyser; Vincent Degos; Francesco Della C...; Hugo den Boogert; Bart Depreitere; Đula Đilvesi; Abhishek Dixit; Emma Donoghue; Jens Dreier; Guy-Loup Dulière; Ari Ercole; Patrick Esser; Erzsébet Ezer; Martin Fabricius; Valery L. Feigin; Kelly Foks; Shirin Frisvold; Alex Furmanov; Pablo Gagliardo; Damien Galanaud; Dashiell Gantner; Guoyi Gao; Pradeep George; Alexandre Ghuysen; Lelde Giga; Ben Glocker; Jagoš Golubovic; Pedro A. Gomez; Johannes Gratz; Benjamin Gravesteijn; Francesca Grossi; Russell L. Gruen; Deepak Gupta; Juanita A. Haagsma; Iain Haitsma; Raimund Helbok; Eirik Helseth; Lindsay Horton; Jilske Huijben; Peter J. Hutchinson; Bram Jacobs; Stefan Jankowski; Mike Jarrett; Ji-yao Jiang; Kelly Jones; Mladen Karan; Angelos G. Kolias; Erwin Kompanje; Daniel Kondziella; Evgenios Koraropo...; Lars-Owe Koskinen; Noémi Kovács; Alfonso Lagares; Linda Lanyon; Steven Laureys; Fiona Lecky; Rolf Lefering; Valerie Legrand; Aurelie Lejeune; Leon Levi; Roger Lightfoot; Hester Lingsma; Andrew I.R. Maas; Ana M. Castaño-León; Marc Maegele; Marek Majdan; Alex Manara; Geoffrey Manley; Costanza Martino; Hugues Maréchal; Julia Mattern; Catherine McMahon; Béla Melegh; David Menon; Tomas Menovsky; Davide Mulazzi; Visakh Muraleedharan; Lynnette Murray; Nandesh Nair; Ancuta Negru; David Nelson; Virginia Newcombe; Quentin Noirhomme; József Nyirádi; Otesile Olubukola; Matej Oresic; Fabrizio Ortolano; Aarno Palotie; Paul M. Parizel; Jean-François Payen; Natascha Perera; Vincent Perlbarg; Paolo Persona; Wilco Peul; Anna Piippo-Karja...; Matti Pirinen; Horia Ples; Suzanne Polinder; Inigo Pomposo; Jussi P. Posti; Louis Puybasset; Andreea Radoi; Arminas Ragauskas; Rahul Raj; Malinka Rambadagalla; Ruben Real; Jonathan Rhodes; Sylvia Richardson; Sophie Richter; Samuli Ripatti; Saulius Rocka; Cecilie Roe; Olav Roise; Jonathan Rosand; Jeffrey V. Rosenfeld; Christina Rosenlund; Guy Rosenthal; Rolf Rossaint; Sandra Rossi; Daniel Rueckert; Martin Rusnák; Juan Sahuquillo; Oliver Sakowitz; Renan Sanchez-Porras; Janos Sandor; Nadine Schäfer; Silke Schmidt; Herbert Schoechl; Guus Schoonman; Rico Frederik Schou; Elisabeth Schwend...; Toril Skandsen; Peter Smielewski; Abayomi Sorinola; Emmanuel Stamatakis; Simon Stanworth; Ana Kowark; Robert Stevens; William Stewart; Nino Stocchetti; Nina Sundström; Anneliese Synnot; Riikka Takala; Viktória Tamás; Tomas Tamosuitis; Mark Steven Taylor; Braden Te Ao; Olli Tenovuo; Alice Theadom; Matt Thomas; Dick Tibboel; Marjolein Timmers; Christos Tolias; Tony Trapani; Cristina Maria Tu...; Peter Vajkoczy; Shirley Vallance; Egils Valeinis; Zoltán Vámos; Gregory Van der S...; Joukje van der Naalt; Jeroen T.J.M. van...; Thomas A. van Essen; Wim Van Hecke; Caroline van Heugten; Dominique Van Praag; Thijs Vande Vyvere; Audrey Vanhaudenh...; Roel P.J. van Wijk; Alessia Vargiolu; Emmanuel Vega; Kimberley Velt; Jan Verheyden; Paul M. Vespa; Anne Vik; Rimantas Vilcinis; Victor Volovici; Nicole von Steinb...; Daphne Voormolen; Petar Vulekovic; Kevin K.W. Wang; Eveline Wiegers; Guy Williams; Lindsay Wilson; Stefan Winzeck; Stefan Wolf; Zhihui Yang; Peter Ylén; Alexander Younsi; Frederik A. Zeiler; Veronika Zelinkova; Agate Ziverte; Tommaso Zoerle
• Keywords: EXTERNAL VALIDATION; EFFICIENCY; PROGNOSIS; Biomedical Research; 330; Databases, Factual; IMPACT; Missing data; MODELS; MULTICENTER; TRAUMATIC BRAIN-INJURY; imputation; 551; Cohort Studies; missing data; tutorial; 03 medical and health sciences; Traumatic brain injury; 0302 clinical medicine; REGRESSION; Brain Injuries, Traumatic; Tutorial; Humans; Prospective Studies; Imputation; traumatic brain injury; prediction; Prognosis; 3. Good health; Europe; BIAS; imputation; missing data; prediction; traumatic brain injury; tutorial;; Data Interpretation, Statistical; MODERATE; Prediction; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology; Radboudumc 10: Reconstructive and regenerative medicine RIHS: Radboud Institute for Health Sciences

In medical research, missing data is common. In acute diseases, such as traumatic brain injury (TBI), even well-conducted prospective studies may suffer from missing data in baseline characteristics and outcomes. Statistical models may simply drop patients with any missing values, potentially leaving a selected subset of the original cohort. Imputation is widely accepted by methodologists as an appropriate way to deal with missing data. We aim to provide practical guidance on handling missing data for prediction modeling. We hereto propose a five-step approach, centered around single and multiple imputation: 1) explore the missing data patterns; 2) choose a method of imputation; 3) perform imputation; 4) assess diagnostics of the imputation; and 5) analyze the imputed data sets. We illustrate these five steps with the estimation and validation of the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury) prognostic model in 1375 patients from the CENTER-TBI database, included in 53 centers across 17 countries, with moderate or severe TBI in the prospective European CENTER-TBI study. Future prediction modeling studies in acute diseases may benefit from following the suggested five steps for optimal statistical analysis and interpretation, after maximal effort has been made to minimize missing data.