2020-04-01 tc155 M1SS computation engine doesn't generate error when duplicate time values appear with different concentration values

[TomTensfeldt]

• Datasets supporting this test case are loaded to onedrive
  There are two requirements relative to data/record duplication scenarios

1. If duplicate time but conc not exactly the same - ERROR condition - error message;fail the profile/run

2. if duplicate time but concentration exactly the same - warning message - use 1 of the records, continue to successful execution

This test case probes the first scenario with the same time in PKATPD_TEST and differing concentrations in PKCNCN. When the computation engine runs, it should generate an error message recording the details of the duplication: "Error: records 22 and 23 are duplicated with TIME=11.5 and CONC=18.1 and TIME=11.5 and CONC=18.2, respectively." and then exit gracefully.

However the STDOUT (see below) for this example indicates that it continues to run with no indication of what is occurring with duplicate values placing the parameter results in uncertain status, i.e. they cannot be trusted but there's no indication that there's anything wrong with the input data.

Computation engine must be updated to react as indicated to both record duplication scenarios above.

relevant portion of input dataset

   PKDATAROWID     SDEID PERIOD VISIT   SUBJID PKPTMS PKATPD PKATPD_TEST PKCNCN
         <int>     <dbl> <chr>  <int>    <int>  <dbl>  <dbl>       <dbl>  <dbl>
 1          16 250852597 <NA>      21 10011001    0     0           0    11.4  
 2          17 250852597 <NA>      21 10011001    1.5   1.5         1.5  16.7  
 3          18 250852597 <NA>      21 10011001    3     3           3    17    
 4          19 250852597 <NA>      21 10011001    4     4           4    15.5  
 5          20 250852597 <NA>      21 10011001    6     6           6    14.4  
 6          21 250852597 <NA>      21 10011001   10     9.97        9.97 13    
 7          22 250852597 <NA>      21 10011001   11.5  11.5        11.5  18.1  
 8          23 250852597 <NA>      21 10011001   13    13          11.5  18.2  
 9          24 250852597 <NA>      21 10011001   14    14          14    15.1  
10          25 250852597 <NA>      21 10011001   16    16          16    15.1  
11          26 250852597 <NA>      21 10011001   24    24          24    10.4  
12          27 250852597 <NA>      21 10011001   48    48          48     4.45 
13          28 250852597 <NA>      21 10011001   72    72          72     1.73 
14          29 250852597 <NA>      21 10011001   96    96          96     0.833

STDOUT

There were 26 warnings (use warnings() to see them)
[1] "openNCA: Model: M1 DosingType: SS AUCMETHOD: LINLOG"
TAU1  as defined in 'map', do not appear in input concentration dataset 
TOLD1  as defined in 'map', do not appear in input concentration dataset 
unit_conversion : Unit Class 1 (Time) time_col:  TMAX1 TMIN1 TLAST1 TLAG KELTMHI THALF LASTTIME1 MRTLAST1 MRTEVIFO1 MRTEVIFP1 TAU1 TOLD1  parameters are scaled from  HR  to  HR  via scaling factor:  1 
unit_conversion : Unit Class 3 (Dose) dose_col:  DOSE1  parameters are scaled from  MCG  to  MG  via scaling factor:  0.001 
unit_conversion : Unit Class 4 (Volume) volume_col:  VZFTAU1  parameters are scaled from  ML  to  L  via scaling factor:  0.001 
unit_conversion : Unit Class 5 (Amount/Volume) conc_col:  CMAX1 CMIN1 CLAST1 CTROUGH1 CTROUGHEND1 KELC0 CEST CAV1  parameters are scaled from  NG/ML  to  NG/ML  via scaling factor:  1 
unit_conversion : Unit Class 6 (1/Time) kel_col:  KEL  parameters are scaled from  1/HR  to  1/HR  via scaling factor:  1 
unit_conversion : Unit Class 7 (Volume/Time) cl_col:  CLFTAU1  parameters are scaled from  ML/HR  to  L/HR  via scaling factor:  0.001 
unit_conversion : Unit Class 8: (Amount.Time/Volume) auc_col:  AUCALL AUCLAST1 AUCLASTC1 AUC1 AUC2 AUC3 AUC4 AUC5 AUC6 AUC7 AUC8 AUC9 AUC10 AUC11 AUC12 AUC13 AUCINFO AUCINFO1 AUCINFOC AUCINFP AUCINFP1 AUCINFPC AUCTAU1  parameters are scaled from  NG.HR/ML  to  NG.HR/ML  via scaling factor:  1 
unit_conversion : Unit Class 9: (Amount.Time.Time/Volume) aumc_col:  AUMCLAST1 AUMCINFO1 AUMCINFP1 AUMCTAU1  parameters are scaled from  NG.HR.HR/ML  to  NG.HR.HR/ML  via scaling factor:  1 
unit_conversion : Unit Class 12: ([Amount/Volume]/Amount) concdn_col:  CMAXDN1 CMINDN1  parameters are scaled from  NG/ML/MCG  to  NG/ML/MG  via scaling factor:  1000 
unit_conversion : Unit Class 14: (Volume/Body Weight) volumew_col:  VZFTAUW1  parameters are scaled from  ML/LB  to  L/KG  via scaling factor:  0.001 
unit_conversion : Unit Class 15: (Volume/Time/Body Weight) clw_col:  CLFTAUW1  parameters are scaled from  ML/HR/LB  to  ML/HR/KG  via scaling factor:  1 
There were 13 warnings (use warnings() to see them)

[jhhughes256]

Just an FYI, I can't find this testcase, so am unable to close the issue.

[jhhughes256]

I think this issue is still present as of commit f5bfc3a. CE provides a warning message that the issue has occurred but still produces parameters for the SDEID that the warning is about, as shown below for SDEID == 250852597.

## Warning in doTryCatch(return(expr), name, parentenv, handler): Removing
## SDEID: '250852597' due to duplicate TIME but different CONC values
## Warning in doTryCatch(return(expr), name, parentenv, handler): Removing
## SDEID: '2004533073' due to duplicate TIME but different CONC values
## Warning in doTryCatch(return(expr), name, parentenv, handler): Removing
## SDEID: '2831342063' due to duplicate TIME but different CONC values

SDEID	DOSE1	DOSEC	DOSEC1	CMAX1	CMAXDN1	FLGACCEPTPREDOSE	CMIN1	CMINDN1	CLAST1	TMAX1	FLGACCEPTTMAX	TMIN1	TLAST1	TLAG	CTROUGH1	CTROUGHEND1	PTROUGHR1	PTROUGHREND1	KEL	KELC0	KELTMLO	KELTMHI	KELNOPT	KELR	KELRSQ	KELRSQA	FLGACCEPTKEL	THALF	THALFF	LASTTIME1	FLGACCEPTTAU	AUCALL	AUCALLDN1	AUCLAST1	AUCLASTDN1	AUMCLAST1	AUC1	AUC2	AUC3	AUC4	AUC5	AUC6	AUC7	AUC8	AUC9	AUC10	AUC11	AUC12	AUC13	AUC1DN	AUC2DN	AUC3DN	AUC4DN	AUC5DN	AUC6DN	AUC7DN	AUC8DN	AUC9DN	AUC10DN	AUC11DN	AUC12DN	AUC13DN	AUCINT1	AUCINT2	AUCINT3	AUCINT4	AUCINT5	AUCINT6	AUCINT7	AUCINT8	AUCINT9	AUCINT10	AUCINT11	AUCINT12	AUCINT13	AUCINFO	AUCINFO1	AUCINFODN	CEST	AUCINFP	AUCINFP1	AUCINFPDN	AUMCINFO1	AUMCINFP1	AUCTAU1	AUCTAUDN1	AUMCTAU1	MRTLAST1	MRTEVIFO1	MRTEVIFP1	AUCXPCTO1	AUCXPCTP1	AUMCXPTO1	AUMCXPTP1	CAV1	CLFTAU1	CLFTAUW1	PTF1	PTR1	VZFTAU1	VZFTAUW1	CONC1	CONC2	CONC3	CONC4	CONC5	CONC6	CONC7	CONC8	CONC9	CONC10	CONC11	CONC12	CONC13	CONC14	CONCTIME1	CONCTIME2	CONCTIME3	CONCTIME4	CONCTIME5	CONCTIME6	CONCTIME7	CONCTIME8	CONCTIME9	CONCTIME10	CONCTIME11	CONCTIME12	CONCTIME13	CONCTIME14	DI1	TAU1	TOLD1	CTOLDest1	AUMCLAST	AUMCINFO	AUMCINFP	TIMEU	AMOUNTU	DOSEU	VOLUMEU	CONCU	KELU	CLU	AUCU	AUMCU	AUCNORMU	AURCU	CONCNORMU	RATEU	VOLUMEWU	CLWU	STUDY	SITEID	SUBJID	RAND	TREATXT	TRTCD	PKCOLL	PKBDFLD	PKTERM	PERIODU	PERIOD	VISITU	VISIT	PHASE	DOSE	HT	WT	AGEDERU	AGEDER	WTUNI	WTRAW	HTUNI	HTRAW	RACEOTH	RACES	SEX	RACIALD	ETHNIC	PKRCOM	PKPCOM
242759741	1.0	1e+06	1e+06	12.00	12.00	0	1.170	1.170	1.170	14.000	1	96	96	0	7.96	1.170	1.507538	10.256410	0.0267452	13.234099	3	96	12	0.9724133	0.9455877	0.9401464	0	25.91670	0	96	0	435.2653	435.2653	435.2653	435.2653	12508.434	13.8450	29.0100	39.42000	60.82000	98.76435	113.35085	129.02585	140.37585	164.07458	238.41293	348.7070	400.9023	435.2653	13.8450	29.0100	39.42000	60.82000	98.76435	113.35085	129.02585	140.37585	164.07458	238.4129	348.7070	400.9023	435.2653	0_1.5	0_3	0_4	0_6	0_9.967	0_11.5	0_13	0_14	0_16	0_24	0_48	0_72	0_96	479.0115	479.0115	479.0115	1.0153751	473.2301	473.2301	473.2301	18343.732	17572.550	435.2653	435.2653	12508.434	28.73749	38.38594	37.11082	9.132594	8.022475	31.81086	28.81834	4.534014	2.2974493	31.26551	2.388612	10.256410	85.90139	1.1690142	7.96	10.50	9.72	11.10	10.30	8.83	10.20	10.70	12.00	11.70	7.24	2.690	1.730	1.170	0	1.5	3	4.000	6	9.967	11.5	13	14	16.000	24	48	72	96	0-96	96	0	NA	12508.434	18343.732	17572.550	HR	NA	MG	L	NG/ML	1/HR	L/HR	NG.HR/ML	NG.HR.HR/ML	NG.HR/ML/MG	NA	NG/ML/MG	NA	L/KG	ML/HR/KG	A3051106	1001	10011058	112	Varenicline Weekly Titration Scheme	B	POINT	PLASMA	CP-526,555	NA	NA	DAY	21	NA	1000	162	73.47	YR	77	LB	162.0	IN	63.9	NA	W	M	NA	NA	NA	NA
250852597	1.0	1e+06	1e+06	18.10	18.10	0	0.833	0.833	0.833	11.500	1	96	96	0	11.40	0.833	1.587719	21.728692	0.0333668	21.001861	3	96	11	0.9893352	0.9787841	0.9764268	0	20.77358	0	96	0	609.8762	609.8762	609.8762	609.8762	16161.078	21.0750	46.3500	62.60000	92.50000	146.84790	170.68605	212.07285	242.27285	343.10716	511.32452	580.4198	609.8762	NA	21.0750	46.3500	62.60000	92.50000	146.84790	170.68605	212.07285	242.27285	343.10716	511.3245	580.4198	609.8762	NA	0_1.5	0_3	0_4	0_6	0_9.967	0_11.5	0_14	0_16	0_24	0_48	0_72	0_96	NA	634.8411	634.8411	634.8411	0.8533388	635.4507	635.4507	635.4507	19305.912	19382.698	609.8762	609.8762	16161.078	26.49895	30.42866	30.52461	3.932473	4.024626	16.28949	16.62111	6.352877	1.6396771	26.97666	2.717981	21.728692	49.14102	0.8084888	11.40	16.70	17.00	15.50	14.40	13.00	18.10	15.10	15.10	10.40	4.45	1.730	0.833	NA	0	1.5	3	4.000	6	9.967	11.5	14	16	24.000	48	72	96	NA	0-96	96	0	NA	16161.078	19305.912	19382.698	HR	NA	MG	L	NG/ML	1/HR	L/HR	NG.HR/ML	NG.HR.HR/ML	NG.HR/ML/MG	NA	NG/ML/MG	NA	L/KG	ML/HR/KG	A3051106	1001	10011001	1	Varenicline Weekly Titration Scheme	B	POINT	PLASMA	CP-526,555	NA	NA	DAY	21	NA	1000	146	60.77	YR	68	LB	134.0	IN	57.5	NA	W	F	NA	NA	NA	NA
276697939	0.5	5e+05	5e+05	4.87	9.74	0	0.412	0.824	0.412	4.000	1	96	96	0	3.13	0.412	1.555910	11.820388	0.0291577	5.612612	3	96	12	0.9815110	0.9633639	0.9597002	0	23.77236	0	96	0	170.4263	340.8526	170.4263	340.8526	4750.391	4.8975	11.0475	15.88250	25.07193	40.58698	46.01374	52.18974	56.95466	66.05586	94.15575	139.1694	158.9292	170.4263	9.7950	22.0950	31.76500	50.14385	81.17396	92.02749	104.37948	113.90931	132.11173	188.3115	278.3388	317.8584	340.8526	0_1.5	0_3	0_4	0_6	0_9.967	0_11.5	0_13	0_14	0_16	0_24	0_48	0_72	0_96	184.5564	184.5564	369.1127	0.3415975	182.1418	182.1418	364.2836	6591.486	6276.880	170.4263	340.8526	4750.391	27.87358	35.83295	34.47286	7.656232	6.432087	27.93140	24.31922	1.775274	2.9338195	35.34410	2.511162	11.820388	100.61906	1.2121707	3.13	3.40	4.80	4.87	4.33	3.52	3.56	4.73	4.80	4.31	2.82	1.170	0.553	0.412	0	1.5	3	4.000	6	9.967	11.5	13	14	16.000	24	48	72	96	0-96	96	0	NA	4750.391	6591.486	6276.880	HR	NA	MG	L	NG/ML	1/HR	L/HR	NG.HR/ML	NG.HR.HR/ML	NG.HR/ML/MG	NA	NG/ML/MG	NA	L/KG	ML/HR/KG	A3051106	1001	10011048	33	Varenicline Two-Week BID Titration Scheme	C	POINT	PLASMA	CP-526,555	NA	NA	DAY	21	NA	500	167	82.99	YR	66	LB	183.0	IN	65.9	NA	W	M	NA	NA	NA	NA

[jhhughes256]

Assessing this issue with the latest commit cca452d this issue no longer occurs and this issue will be closed. Profiles with duplicate times where the concentrations differ now correctly provide NA as output for all variables. Example below.

knitr::kable(r[r$SDEID %in% c("250852597", "2004533073", "2831342063"),1:10])

	SDEID	DOSE1	DOSEC	DOSEC1	C0	CMAX	CMAX1	CMAXC1	CMAXDN	CMAXDN1
2	250852597	NA	NA	NA	NA	NA	NA	NA	NA	NA
18	2004533073	NA	NA	NA	NA	NA	NA	NA	NA	NA
27	2831342063	NA	NA	NA	NA	NA	NA	NA	NA	NA