data: Reference Datasets

In replicateBE: Average Bioequivalence with Expanding Limits (ABEL)

Reference Datasets

Description

Datasets of replicate designs from the public domain, edited, or obtained by simulations to be evaluated by method.A(), method.B(), or ABE().

Details

Design	Specification	Dataset	N	CVwR (%)	Evaluation
TRTR|RTRT	full	rds01	77	>30	method.A(), method.B()
TRTR|RTRT	full	rds06	77	>30	method.A(), method.B()
TRTR|RTRT	full	rds12	77	>30	method.A(), method.B()
TRTR|RTRT	full	rds14	77	>30	method.A(), method.B()
TRTR|RTRT	full	rds18	77	>30	method.A(), method.B()
TRTR|RTRT	full	rds21	77	>30	method.A(), method.B()
TRTR|RTRT	full	rds19	61	>30	method.A(), method.B()
TRTR|RTRT	full	rds20	61	>30	method.A(), method.B()
TRTR|RTRT	full	rds08	222	>30	method.A(), method.B()
TRTR|RTRT	full	rds09	222	>30	method.A(), method.B()
TRTR|RTRT	full	rds13	222	>30	method.A(), method.B()
TRTR|RTRT	full	rds15	222	>30	method.A(), method.B()
TRTR|RTRT	full	rds25	70	>30	method.A(), method.B()
TRTR|RTRT	full	rds29	12	<30	method.A(), method.B(), ABE()
TRRT|RTTR	full	rds26	54	>30	method.A(), method.B()
TRRT|RTTR	full	rds05	26	<30	method.A(), method.B(), ABE()
TRRT|RTTR	full	rds11	37	>30	method.A(), method.B()
TRRT|RTTR	full	rds16	38	>30	method.A(), method.B()
TTRR|RRTT	full	rds28	64	<30	method.A(), method.B(), ABE()
TRTR|RTRT|TRRT|RTTR	full	rds23	22	>30	method.A(), method.B()
TRRT|RTTR|TTRR|RRTT	full	rds24	39	>30	method.A(), method.B()
TRT|RTR	full	rds03	77	>30	method.A(), method.B()
TRT|RTR	full	rds17	19	>30	method.A(), method.B()
TRR|RTT	full	rds10	18	<30	method.A(), method.B(), ABE()
TR|RT|TT|RR	Balaam’s	rds27	312	>30	method.A(), method.B()
TRR|RTR|RRT	partial	rds02	24	<30	method.A(), method.B(), ABE()
TRR|RTR|RRT	partial	rds04	51	>30	method.A(), method.B()
TRR|RTR|RRT	partial	rds07	360	>30	method.A(), method.B()
TRR|RTR|RRT	partial	rds30	14	<30	method.A(), method.B(), ABE()
TRR|RTR	partial	rds22	36	>30	method.A(), method.B()

In full replicate designs both R and T are administered twice (in 3-period designs to ½ of the subjects).
Balaam’s design is a mixture of a conventional crossover (½ of the subjects) and a replicate design (¼ of the subjects receive either R or T twice).
In partial replicate designs only R is administered twice.

Author(s)

Helmut Schütz (R-code for simulations by Detlew Labes), Michael Tomashevskiy (simulations in Phoenix NLME)

Source

Dataset	Origin	Description
rds01	EMA	Data set in Annex II
rds06	rds01 edited	T and R switched
rds12	Phoenix NLME	Simulated with extreme variability
rds14	Phoenix NLME	Simulated with high variability and number of dropouts increasing with period
rds18	rds14 edited	Removed T data of subjects 63–78
rds21	rds01 edited	One extreme result of subjects 45 & 52 set to NA
rds19	rds18 edited	Removed data of subjects 63–78
rds20	rds19 edited	Outlier of R (subject 1) introduced: original value ×100
rds08	R	Simulated with slight heteroscedasticity
rds09	rds08	Wide numeric range (data of last 37 subjects multiplied by 1,000,000)
rds13	rds08 edited	Highly incomplete (approx. 50% of period 4 data deleted)
rds15	rds08 edited	Highly incomplete (approx. 50% of period 4 data coded as missing 'NA')
rds25	R	Simulated with heteroscedasticity
rds29	R	Simulated with heteroscedasticity; imbalanced and incomplete
rds26	Patterson & Jones 2016	Cmax data given in Tables 4.30 & 4.31
rds05	Shumaker & Metzler	Cmax data given in the Appendix
rds11	Hauschke et al.	Cmax data given in Table 9.6.
rds16	FDA, CDER	Cmax data of Drug 14a
rds28	R	Simulated with homoscedasticity
rds23	FDA, CDER	Cmax data of Drug
rds24	FDA, CDER	Cmax data of Drug 1
rds03	rds01 edited	Period 4 removed
rds17	rds03 edited	Highly unbalanced (twelve subjects in RTR and seven in TRT)
rds10	Chow & Liu	AUC data given in Table 9.3.3.
rds27	R	Simulated with homoscedasticity
rds02	EMA	Data set in Annex III
rds04	Patterson & Jones 2012	Cmax data of Table II
rds07	R	Simulated with homoscedasticity
rds30	R	Simulated with heteroscedasticity; imbalanced and incomplete
rds22	R	Simulated with homoscedasticity

References

European Medicines Agency. London, 21 September 2016. Annex II, Annex III.

Patterson SD, Jones B. Viewpoint: observations on scaled average bioequivalence. Pharm Stat. 2012; 11(1): 1–7. doi: 10.1002/pst.498

Shumaker RC, Metzler CM. The Phenytoin Trial is a Case Study of ‘Individual’ Bioequivalence. Drug Inf J. 1998; 32(4): 1063–72. doi: 10.1177/009286159803200426

Chow SC, Liu JP. Design and Analysis of Bioavailability and Bioequivalence Studies. Boca Raton: CRC Press; 3^rd edition 2009. p275.

Hauschke D, Steinijans VW, Pigeot I. Bioequivalence Studies in Drug Development. Chichester: John Wiley; 2007. p216.

Patterson SD, Jones B. Bioequivalence and Statistics in Clinical Pharmacology. Boca Raton: CRC Press; 2^nd edition 2016. p105–6.

U.S. Food and Drug Administration, Center for Drug Evaluation and Research. Bioequivalence Studies. Rockville, 1997. bioequivalence study files (archived 2017-07-23)

See Also

4-period full replicates
TRTR.RTRT, TRRT.RTTR, TTRR.RRTT, TRTR.RTRT.TRRT.RTTR, TRRT.RTTR.TTRR.RRTT
2-period replicate (Balaam’s design)
TR.RT.TT.RR
3-period full replicates
TRT.RTR, TRR.RTT
3-period partial replicates
TRR.RTR.RRT, TRR.RTR

Examples

# show structure of all data sets
ds <- substr(grep("rds", unname(unlist(data(package = "replicateBE"))),
                  value = TRUE), start = 1, stop = 5)
for (i in seq_along(ds)) {
  cat(ds[i], "\n")
  str(eval(parse(text = ds[i])))
}

replicateBE documentation built on May 3, 2022, 1:06 a.m.