Accounting for expected attrition in the planning of cluster randomized trials for assessing treatment effect heterogeneity

BMC Medical Research Methodology

Research

Michael O. Harhay¹  Jiaqi Tong²  Fan Li³  Guangyu Tong³ 

[1] Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;Department of Biostatistics, Yale School of Public Health, 135 College Street, 06510, New Haven, CT, USA;Department of Biostatistics, Yale School of Public Health, 135 College Street, 06510, New Haven, CT, USA;Center for Methods in Implementation and Prevention Science, Yale School of Public Health, New Haven, CT, USA;

关键词: Heterogeneity of treatment effect;    Missing data;    Missing at random;    Missing completely at random;    Power calculation;    Intracluster correlation coefficient;    Cluster randomized trial;   

DOI  :  10.1186/s12874-023-01887-8

 received in 2022-12-18, accepted in 2023-03-10,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundDetecting treatment effect heterogeneity is an important objective in cluster randomized trials and implementation research. While sample size procedures for testing the average treatment effect accounting for participant attrition assuming missing completely at random or missing at random have been previously developed, the impact of attrition on the power for detecting heterogeneous treatment effects in cluster randomized trials remains unknown.MethodsWe provide a sample size formula for testing for a heterogeneous treatment effect assuming the outcome is missing completely at random. We also propose an efficient Monte Carlo sample size procedure for assessing heterogeneous treatment effect assuming covariate-dependent outcome missingness (missing at random). We compare our sample size methods with the direct inflation method that divides the estimated sample size by the mean follow-up rate. We also evaluate our methods through simulation studies and illustrate them with a real-world example.ResultsSimulation results show that our proposed sample size methods under both missing completely at random and missing at random provide sufficient power for assessing heterogeneous treatment effect. The proposed sample size methods lead to more accurate sample size estimates than the direct inflation method when the missingness rate is high (e.g., ≥ 30%). Moreover, sample size estimation under both missing completely at random and missing at random is sensitive to the missingness rate, but not sensitive to the intracluster correlation coefficient among the missingness indicators.ConclusionOur new sample size methods can assist in planning cluster randomized trials that plan to assess a heterogeneous treatment effect and participant attrition is expected to occur.

【 授权许可】

CC BY   
© The Author(s) 2023. corrected publication 2023

【 图 表 】

Fig. 2

41116_2023_37_Article_IEq109.gif

41116_2023_37_Article_IEq108.gif

Fig. 1

41116_2023_37_Article_IEq106.gif

Fig. 3

41116_2023_37_Article_IEq104.gif

41116_2023_37_Article_IEq103.gif

41116_2023_37_Article_IEq102.gif

41116_2023_37_Article_IEq101.gif

41116_2023_37_Article_IEq100.gif

41116_2023_37_Article_IEq99.gif

41116_2023_37_Article_IEq97.gif

41116_2023_37_Article_IEq96.gif

41116_2023_37_Article_IEq95.gif

41116_2023_37_Article_IEq93.gif

41116_2023_37_Article_IEq92.gif

41116_2023_37_Article_IEq91.gif

Fig. 2

41116_2023_37_Article_IEq89.gif

41116_2023_37_Article_IEq88.gif

Fig. 1

41116_2023_37_Article_IEq86.gif

41116_2023_37_Article_IEq85.gif

41116_2023_37_Article_IEq83.gif

41116_2023_37_Article_IEq82.gif

Fig. 4

41116_2023_37_Article_IEq80.gif

41116_2023_37_Article_IEq79.gif

41116_2023_37_Article_IEq78.gif

Fig. 3

41116_2023_37_Article_IEq76.gif

41116_2023_37_Article_IEq74.gif

41116_2023_37_Article_IEq73.gif

41116_2023_37_Article_IEq72.gif

Fig. 2

41116_2023_37_Article_IEq69.gif

Fig. 2

41116_2023_37_Article_IEq67.gif

Fig. 2

41116_2023_37_Article_IEq65.gif

41116_2023_37_Article_IEq64.gif

41116_2023_37_Article_IEq63.gif

41116_2023_37_Article_IEq62.gif

41116_2023_37_Article_IEq60.gif

41116_2023_37_Article_IEq59.gif

41116_2023_37_Article_IEq58.gif

41116_2023_37_Article_IEq57.gif

41116_2023_37_Article_IEq56.gif

41116_2023_37_Article_IEq55.gif

41116_2023_37_Article_IEq54.gif

41116_2023_37_Article_IEq53.gif

41116_2023_37_Article_IEq52.gif

Fig. 1

41116_2023_37_Article_IEq50.gif

41116_2023_37_Article_IEq49.gif

41116_2023_37_Article_IEq48.gif

Fig. 2

41116_2023_37_Article_IEq46.gif

41116_2023_37_Article_IEq45.gif

41116_2023_37_Article_IEq44.gif

41116_2023_37_Article_IEq43.gif

41116_2023_37_Article_IEq42.gif

41116_2023_37_Article_IEq40.gif

Fig. 2

41116_2023_37_Article_IEq39.gif

Fig. 2

41116_2023_37_Article_IEq38.gif

41116_2023_37_Article_IEq37.gif

41116_2023_37_Article_IEq36.gif

Fig. 1

41116_2023_37_Article_IEq34.gif

41116_2023_37_Article_IEq33.gif

41116_2023_37_Article_IEq32.gif

41116_2023_37_Article_IEq31.gif

41116_2023_37_Article_IEq30.gif

41116_2023_37_Article_IEq29.gif

41116_2023_37_Article_IEq28.gif

41116_2023_37_Article_IEq27.gif

41116_2023_37_Article_IEq26.gif

41116_2023_37_Article_IEq25.gif

41116_2023_37_Article_IEq24.gif

41116_2023_37_Article_IEq22.gif

Fig. 3

Fig. 2

41116_2023_37_Article_IEq18.gif

40854_2023_491_Article_IEq27.gif

41116_2023_37_Article_IEq16.gif

Fig. 2

Fig. 1

Fig. 1

Fig. 1

41116_2023_37_Article_IEq14.gif

41116_2023_37_Article_IEq13.gif

Fig. 1

41116_2023_37_Article_IEq12.gif

Fig. 2

41116_2023_37_Article_IEq10.gif

41116_2023_37_Article_IEq9.gif

41116_2023_37_Article_IEq7.gif

41116_2023_37_Article_IEq6.gif

41116_2023_37_Article_IEq4.gif

41116_2023_37_Article_IEq3.gif

41116_2023_37_Article_IEq2.gif

41116_2023_37_Article_IEq1.gif

Fig. 1

Fig. 1

Fig. 7

Fig. 6

Fig. 2

Fig. 24

Fig. 7

Fig. 2

Fig. 4

Fig. 1

Fig. 3

Fig. 1

Fig. 2

Fig. 6

Fig. 12

Fig. 1

Fig. 4

Fig. 5

Fig. 6

Fig. 5

Scheme 1

Fig. 1

Fig. 6

Fig. 1

Fig. 22

Fig. 4

40854_2023_491_Article_IEq17.gif

Fig. 2

Fig. 21

40854_2023_491_Article_IEq12.gif

Fig. 1

Fig. 5

Fig. 20

Fig. 2

Fig. 5

40854_2023_491_Article_IEq4.gif

Fig. 3

Fig. 3

Fig. 4

Fig. 4

Fig. 4

Fig. 1

Fig. 2

Fig. 1

Fig. 11

Fig. 17

Fig. 10

Fig. 16

Fig. 3

Fig. 9

Fig. 2

12936_2023_4634_Article_IEq5.gif

12936_2023_4634_Article_IEq2.gif

Fig. 3

Fig. 2

Fig. 4

Fig. 2

Fig. 1

Fig. 13

Fig. 8

Fig. 1

Fig. 1

Fig. 3

Fig. 8

Fig. 1

Fig. 12

Fig. 11

Fig. 1

Fig. 10

Fig. 9

Fig. 8

Fig. 8

Fig. 1

Fig. 7

Fig. 7

12888_2023_4863_Article_IEq1.gif

12968_2023_940_Article_IEq3.gif

Fig. 3

Fig. 6

Fig. 3

Fig. 5

Fig. 4

Fig. 2

Fig. 4

Fig. 3

Fig. 3

Fig. 7

Fig. 3

Fig. 5

Fig. 1

Fig. 4

Fig. 5

Fig. 2

Fig. 2

Fig. 1

Fig. 3

Fig. 2

Fig. 3

Fig. 6

Fig. 1

Fig. 5

Fig. 7

Fig. 6

Fig. 6

Fig. 4

13690_2023_1130_Article_IEq62.gif

Fig. 1

13690_2023_1130_Article_IEq60.gif

13690_2023_1130_Article_IEq59.gif

Fig. 1

13690_2023_1130_Article_IEq57.gif

Fig. 4

13690_2023_1130_Article_IEq54.gif

13690_2023_1130_Article_IEq53.gif

13690_2023_1130_Article_IEq52.gif

13690_2023_1130_Article_IEq51.gif

13690_2023_1130_Article_IEq50.gif

13690_2023_1130_Article_IEq49.gif

Fig. 1

13690_2023_1130_Article_IEq47.gif

40517_2023_252_Article_IEq8.gif

Fig. 3

13690_2023_1130_Article_IEq45.gif

13690_2023_1130_Article_IEq44.gif

13690_2023_1130_Article_IEq43.gif

Fig. 2

13690_2023_1130_Article_IEq40.gif

13690_2023_1130_Article_IEq39.gif

Fig. 2

13690_2023_1130_Article_IEq36.gif

13690_2023_1130_Article_IEq35.gif

13690_2023_1130_Article_IEq34.gif

13690_2023_1130_Article_IEq33.gif

13690_2023_1130_Article_IEq32.gif

Fig. 1

Fig. 1

13690_2023_1130_Article_IEq29.gif

13690_2023_1130_Article_IEq28.gif

13690_2023_1130_Article_IEq18.gif

13690_2023_1130_Article_IEq17.gif

13690_2023_1130_Article_IEq16.gif

13690_2023_1130_Article_IEq15.gif

13690_2023_1130_Article_IEq14.gif

13690_2023_1130_Article_IEq13.gif

13690_2023_1130_Article_IEq12.gif

13690_2023_1130_Article_IEq10.gif

13690_2023_1130_Article_IEq9.gif

13690_2023_1130_Article_IEq8.gif

13690_2023_1130_Article_IEq7.gif

13690_2023_1130_Article_IEq6.gif

13690_2023_1130_Article_IEq5.gif

13690_2023_1130_Article_IEq4.gif

12938_2023_1116_Article_IEq11.gif

Fig. 3

Fig. 3