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Methods to analyse cost data of patients who withdraw in a clinical trial setting

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Abstract

Background: Missing data resulting from premature study withdrawal are a common problem in the analysis of longitudinal data in clinical trials. To date, this subject has received little attention in the context of economic evaluations and with regard to the analysis of cost data.

Objectives: To (i) demonstrate the impact of patients who drop out during the study on the outcomes of an economic evaluation, and (ii) to compare the mean and variation in costs after applying five different methods to deal with incomplete data: multiple imputation, complete cases analysis, linear extrapolation, predicted mean and hot decking.

Study design: The study was performed using cost data collected in two randomised clinical trials comparing patients with chronic obstructive pulmonary disease receiving either tiotropium bromide or ipratropium bromide. The overall dropout rate was 17%, with the daily costs of the dropouts approximately 4 times higher than the costs of the completers.

Methods: Multiple imputation is a principled method that deals with missing observations by replacing each missing observation with a set of multiple plausible values. The variance between the resulting multiple datasets is combined with the variance between the datasets to take account of the extra uncertainty that results from missing data. The outcomes after multiple imputation were compared with the results of four naive methods to deal with missing observations: complete cases analysis, linear extrapolation, predicted mean and hot decking. All costs were expressed in 2001 euros.

Results: In the tiotropium bromide group, mean (standard error) costs varied from €955 (137) after complete cases analysis to €1298 (198) after linear extrapolation. The corresponding estimates in the ipratropium bromide group were €970 (125) and €1561 (244), respectively. The difference in costs between treatment groups varied from -€15 (95% CI: -379 to 349) after complete cases analysis to -€402 (95% CI: -883 to 79) after predicted mean, in favour of the tiotropium bromide group. The difference in costs according to the other methods varied from -€263 (95% CI: -878 to 353) after linear extrapolation to -€265 (95% CI: -709 to 180) after multiple imputation to -€359 (95% CI: -771 to 54) after hot decking.

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Acknowledgements

The study was funded by Boehringer Ingelheim GmbH. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

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Authors and Affiliations

  1. Institute for Medical Technology Assessment, Erasmus Medical Centre Rotterdam, 3000 DR Rotterdam, PO Box 1738, Rotterdam, The Netherlands

    Jan B. Oostenbrink, Maiwenn J. Al & Maureen P. M. H. Rutten-van Mölken

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  1. Jan B. Oostenbrink
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  2. Maiwenn J. Al
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  3. Maureen P. M. H. Rutten-van Mölken
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Correspondence to Jan B. Oostenbrink.

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Oostenbrink, J.B., Al, M.J. & Rutten-van Mölken, M.P.M.H. Methods to analyse cost data of patients who withdraw in a clinical trial setting. Pharmacoeconomic 21, 1103–1112 (2003). https://doi.org/10.2165/00019053-200321150-00004

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