| refdata {replicateBE} | R Documentation |
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; 3rd 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; 2nd 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])))
}