Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis

Autor: Pedro Rafael Dimbu, Marit De Wit, Kamala L. Thriemer, Sarah G. Staedke, Filomeno Fortes, Salim Abdulla, Julie A. Simpson, Oliver James Pratt, Bart Janssens, Andreas Mårtensson, Veronique Sinou, Steffen Borrmann, Walter R. J. Taylor, Ingrid van der Broek, Christopher J. M. Whitty, Meghna Desai, François Bompart, Zulfikarali Premji, Theonest K. Mutabingwa, Aarti Agarwal, Anupkumar R. Anvikar, Emmanuel Arinaitwe, Petra F. Mens, Piero Olliaro, François Nosten, Maman Laminou Ibrahim, Birgit Schramm, Hasifa Bukirwa, Michèle van Vugt, Jane Achan, J. Pedro Gil, Timothy M. E. Davis, Ogobara K. Doumbo, Michel Cot, Grant Dorsey, Michael Ramharter, Sue J. Lee, Sodiomon B. Sirima, Ambrose O. Talisuna, Poul-Erik Kofoed, Brian Greenwood, Catherine O. Falade, Valerie Lameyre, Mayfong Mayxay, Andre Toure Offianan, Hervé Ei Menan, Teun Bousema, Erasmus Kamugisha, Chris J. Drakeley, Elizabeth Juma, Johan Ursing, Abul Faiz, Emmanuel Temu, Carol Hopkins Sibley, Patrice Piola, Philip J. Rosenthal, Frank Smithuis, Mateusz M. Plucinski, Marco Corsi, Anastasia Grivoyannis, Richard Allan, Elizabeth A. Ashley, Harald Noedl, Jean François Faucher, Issaka Zongo, Corine Karema, Cornelis Winnips, Kamal Hamed, Umberto D'Alessandro, Venkatachalam Udhayakumar, Michael D. Edstein, Fred Kironde, Harin Karunajeewa, Philippe Deloron, Quique Bassat, Patrick Sawa, David P. Hughes, Ishag Adam, Michel Van Herp, Christopher V. Plowe, Ghulam Rahim Awab, Caterina I. Fanello, Joel Tarning, Stephan Duparc, Jean Bosco Ouedraogo, Emmanuelle Espie, Tran Tinh Hien, Jean R. Kiechel, Anders Björkman, Abdoulaye Djimde, Billy E. Ngasala, Nahla B. Gadalla, Prabin Dahal, Kasia Stepniewska, Lars Rombo, Nhien Nguyen Thuy, Philippe J Guerin, Verena I. Carrara, Babacar Faye, Christophe Rogier, Peter G. Kremsner, Oumar Gaye, Inge Sutanto, Jean-Louis A Ndiaye, Bernhards Ogutu, Mary Oguike, Vincent Jullien, Jimee Hwang, Kevin Marsh, Djibrine Djalle, Ric N. Price, Yavo William, Georgina S Humphreys
Přispěvatelé: WorldWide Antimalarial Resistance Network (WWARN), University of Oxford [Oxford]-Churchill Hospital Oxford Centre for Haematology, Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies infectieuses et tropicales [CHU Limoges], CHU Limoges, Membranes et cibles thérapeutiques (MCT), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées (IRBA), University of Oxford-Churchill Hospital Oxford Centre for Haematology, CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Infectious diseases, AII - Infectious diseases, APH - Global Health, APH - Quality of Care
Rok vydání: 2019
Předmět:
[SDV]Life Sciences [q-bio]
Network Meta-Analysis
Infektionsmedicin
Plasmodium falciparum/drug effects
Polymerase Chain Reaction
0302 clinical medicine
Dihydroartemisinin/piperaquine
Recurrence
Cumulative incidence
030212 general & internal medicine
Antimalarials/pharmacology
Malaria
Falciparum
biology
Malaria
Falciparum/drug therapy
food and beverages
3. Good health
Infectious Diseases
Meta-analysis
Regression Analysis
Competing risk even
Risk
Treatment efficacy study
Infectious Medicine
medicine.medical_specialty
lcsh:Arctic medicine. Tropical medicine
lcsh:RC955-962
030231 tropical medicine
Plasmodium falciparum
Malària
Competing risks
lcsh:Infectious and parasitic diseases
Antimalarials
03 medical and health sciences
Internal medicine
parasitic diseases
medicine
Humans
lcsh:RC109-216
business.industry
Methodology
medicine.disease
biology.organism_classification
Malaria
Competing risk event
Parasitology
Tropical medicine
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
business
Zdroj: Dipòsit Digital de la UB
Universidad de Barcelona
Malaria Journal, Vol 18, Iss 1, Pp 1-14 (2019)
Malaria Journal
Malaria Journal, BioMed Central, 2019, 18 (1), pp.225. ⟨10.1186/s12936-019-2837-4⟩
Recercat. Dipósit de la Recerca de Catalunya
instname
Malaria Journal, 2019, 18 (1), pp.225. ⟨10.1186/s12936-019-2837-4⟩
WorldWide Antimalarial Resistance Network Methodology Study Group & Kofoed, P-E 2019, ' Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria : a WorldWide Antimalarial Resistance Network individual participant data meta-analysis ', Malaria Journal, vol. 18, 225 . https://doi.org/10.1186/s12936-019-2837-4
Malaria journal, 18(1):225. BioMed Central
ISSN: 1475-2875
Popis: Background Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections. Methods Antimalarial studies typically report the risk of recrudescence derived using the Kaplan–Meier (K–M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K–M method (1 minus K–M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K–M curves was assessed using the log-rank test, and the equality of CIFs using Gray’s k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray’s sub-distributional hazard model. Results Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K–M approach was 0.04% (interquartile range (IQR): 0.00–0.27%, Range: 0.00–3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson’s correlation coefficient (ρ): 0.38, 95% Confidence Interval (CI) 0.30–0.46] or new infection [ρ: 0.43; 95% CI 0.35–0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K–M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold. Conclusions The 1 minus K–M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings. Electronic supplementary material The online version of this article (10.1186/s12936-019-2837-4) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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