Recently, response-adaptive designs have been proposed in randomized clinical trials to achieve ethical and/or cost advantages by using sequential accrual information collected during the trial to dynamically update the probabilities of treatment assignments. In this context, urn models-where the probability to assign patients to treatments is interpreted as the proportion of balls of different colors available in a virtual urn-have been used as response-adaptive randomization rules. We propose the use of Randomly Reinforced Urn (RRU) models in a simulation study based on a published randomized clinical trial on the efficacy of home enteral nutrition in cancer patients after major gastrointestinal surgery. We compare results with the RRU design with those previously published with the non-adaptive approach. We also provide a code written with the R software to implement the RRU design in practice. In detail, we simulate 10,000 trials based on the RRU model in three set-ups of different total sample sizes. We report information on the number of patients allocated to the inferior treatment and on the empirical power of the t-test for the treatment coefficient in the ANOVA model. We carry out a sensitivity analysis to assess the effect of different urn compositions. For each sample size, in approximately 75% of the simulation runs, the number of patients allocated to the inferior treatment by the RRU design is lower, as compared to the non-adaptive design. The empirical power of the t-test for the treatment effect is similar in the two designs.

Urn models for response-adaptive randomized designs: a simulation study based on a non-adaptive randomized trial / A. Ghiglietti, M.G. Scarale, R. Miceli, F. Ieva, L. Mariani, C. Gavazzi, A.M. Paganoni, V. Edefonti. - In: JOURNAL OF BIOPHARMACEUTICAL STATISTICS. - ISSN 1054-3406. - 28:6(2018), pp. 1203-1215. [10.1080/10543406.2018.1452024]

Urn models for response-adaptive randomized designs: a simulation study based on a non-adaptive randomized trial

A. Ghiglietti;M.G. Scarale;F. Ieva;V. Edefonti
Ultimo
2018

Abstract

Recently, response-adaptive designs have been proposed in randomized clinical trials to achieve ethical and/or cost advantages by using sequential accrual information collected during the trial to dynamically update the probabilities of treatment assignments. In this context, urn models-where the probability to assign patients to treatments is interpreted as the proportion of balls of different colors available in a virtual urn-have been used as response-adaptive randomization rules. We propose the use of Randomly Reinforced Urn (RRU) models in a simulation study based on a published randomized clinical trial on the efficacy of home enteral nutrition in cancer patients after major gastrointestinal surgery. We compare results with the RRU design with those previously published with the non-adaptive approach. We also provide a code written with the R software to implement the RRU design in practice. In detail, we simulate 10,000 trials based on the RRU model in three set-ups of different total sample sizes. We report information on the number of patients allocated to the inferior treatment and on the empirical power of the t-test for the treatment coefficient in the ANOVA model. We carry out a sensitivity analysis to assess the effect of different urn compositions. For each sample size, in approximately 75% of the simulation runs, the number of patients allocated to the inferior treatment by the RRU design is lower, as compared to the non-adaptive design. The empirical power of the t-test for the treatment effect is similar in the two designs.
Non-adaptive trial design; randomized trials; randomly reinforced urn model; response-adaptive randomization; simulation study
Settore MED/01 - Statistica Medica
Settore MAT/06 - Probabilita' e Statistica Matematica
2018
22-mar-2018
Article (author)
File in questo prodotto:
File Dimensione Formato  
HEN_JBS_2018_final.pdf

Open Access dal 08/04/2019

Descrizione: Main text
Tipologia: Post-print, accepted manuscript ecc. (versione accettata dall'editore)
Dimensione 328.33 kB
Formato Adobe PDF
328.33 kB Adobe PDF Visualizza/Apri
Urn models for response adaptive randomized designs a simulation study based on a non adaptive randomized trial.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.36 MB
Formato Adobe PDF
1.36 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/609711
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 2
social impact