Why is survival::tmerge suddenly giving error "neither a tstop argument nor an initial event argument was found"?

Question

I'm trying to run the following code, including survival::tmerge() to conduct survival analysis with time-varying covariates, but i always get the error

Error in tmerge(df.merge %>% select(CODE98, id), df.long, id = CODE98, : neither a tstop argument nor an initial event argument was found>

I wrote this code some months ago and it worked properly. I noticed that it started giving error after updating R to version 4.0.2

df <- 
structure(list(CODE98 = structure(c(4, 8, 9, 10, 13, 17, 18, 
                                    19, 20, 23, 26, 28, 30, 32, 33, 35, 37, 38, 41, 42, 45, 46, 47, 
                                    49, 50, 51, 53, 54, 56, 59, 61, 62, 65, 68, 69, 70, 72, 73, 77, 
                                    78, 80, 82, 84, 86, 87, 88, 89, 90, 91, 93), label = "Subject ID code/Codice di soggetto"), 
               X_DATEL = structure(c(10653, 10744, 10533, 10735, 10611, 
                                     10556, 10744, 10764, 10673, 10751, 10541, 10576, 10610, 10625, 
                                     10709, 10667, 10534, 10540, 10646, 10715, 10632, 10757, 10611, 
                                     10589, 10618, 10569, 10638, 10701, 10681, 10743, 10709, 10632, 
                                     10666, 10701, 10555, 10673, 10701, 10681, 10680, 10701, 10604, 
                                     10520, 10520, 10764, 10694, 10736, 10749, 10666, 10730, 10695
               ), label = "Date of Baseline fasting blood/urine", format.sas = "DATE", class = "Date"), 
               Y_DATEL = structure(c(11797, NA, 11748, 11792, NA, 11734, 
                                     11773, NA, 11779, 11811, 11734, 11748, NA, 11769, 11790, 
                                     11811, 11699, NA, 11734, 11839, NA, 11783, 11741, 11741, 
                                     NA, NA, 11786, 11783, NA, 11811, 11804, 11837, NA, 11839, 
                                     NA, 11839, NA, 11850, 11734, NA, 11837, 11699, NA, 11781, 
                                     NA, 11809, 11783, 11804, 11825, NA), label = "Date of Followup 1 fasting blood/urine", format.sas = "DATE", class = "Date"), 
               Z_DATEL = structure(c(12934, 12957, 12901, NA, NA, 12832, 
                                     NA, 12964, 12920, NA, 12831, 12831, 12874, 12861, 12944, 
                                     NA, 12896, NA, 12824, 12969, NA, 12957, 12891, 12852, NA, 
                                     NA, 12878, 12962, NA, 12885, NA, 12884, NA, 13277, NA, NA, 
                                     NA, 12922, 12852, NA, 12857, 12772, NA, NA, 12922, 12950, 
                                     13284, 12874, 12934, NA), label = "Date of Followup 2 fasting blood/urine", format.sas = "DATE", class = "Date"), 
               Q_DATEL = structure(c(13934, NA, 13977, NA, NA, 13976, NA, 
                                     14039, 13976, NA, 13948, 13934, 13969, 14057, 13969, NA, 
                                     13906, NA, 13941, 14046, 13969, 13993, NA, 13941, NA, NA, 
                                     13973, 13978, NA, NA, NA, 13990, NA, 13945, 13993, NA, NA, 
                                     NA, 14026, NA, 13913, 13913, NA, NA, NA, 13927, 13864, 13920, 
                                     13955, 14028), label = "Date of Followup 3 fasting blood/urine", format.sas = "DATE", class = "Date"), 
               C_DATEL = structure(c(NA, NA, NA, NA, NA, NA, NA, NA, NA, 
                                     NA, 15888, NA, NA, NA, 15860, NA, NA, NA, 15922, NA, NA, 
                                     NA, NA, 16003, NA, NA, NA, NA, NA, NA, NA, 15873, NA, NA, 
                                     16016, NA, NA, NA, 15965, NA, NA, 15980, NA, NA, NA, NA, 
                                     15952, NA, 15869, 15868), label = "Date of Followup 4 fasting blood/urine", format.sas = "DATE", class = "Date"), 
               X_AGEL = structure(c(79, 80, 78, 83, 90, 81, 78, 84, 74, 
                                    87, 75, 68, 71, 66, 73, 75, 67, 83, 66, 67, 75, 69, 83, 65, 
                                    67, 74, 85, 71, 73, 83, 85, 75, 88, 74, 85, 66, 82, 88, 69, 
                                    84, 66, 69, 86, 86, 74, 83, 72, 78, 66, 80), label = "Age at Baseline fasting blood/urine(yrs)"), 
               Y_AGEL = structure(c(82, NA, 81, 86, NA, 84, 81, NA, 77, 
                                    90, 78, 72, NA, 69, 76, 78, 70, NA, 69, 70, NA, 72, 86, 69, 
                                    NA, NA, 88, 74, NA, 86, 88, 78, NA, 77, NA, 69, NA, 91, 71, 
                                    NA, 70, 72, NA, 89, NA, 86, 75, 81, 69, NA), label = "Age at Followup 1 fasting blood/urine(yr"), 
               Z_AGEL = structure(c(85, 86, 84, NA, NA, 87, NA, 90, 80, 
                                    NA, 81, 74, 77, 72, 79, NA, 73, NA, 72, 73, NA, 75, 89, 72, 
                                    NA, NA, 91, 77, NA, 89, NA, 81, NA, 81, NA, NA, NA, 94, 74, 
                                    NA, 73, 75, NA, NA, 80, 89, 79, 84, 72, NA), label = "Age at Followup 2 fasting blood/urine(yr"), 
               Q_AGEL = structure(c(88, NA, 87, NA, NA, 91, NA, 93, 83, 
                                    NA, 84, 78, 80, 75, 82, NA, 76, NA, 75, 76, 84, 78, NA, 75, 
                                    NA, NA, 94, 80, NA, NA, NA, 84, NA, 83, 94, NA, NA, NA, 78, 
                                    NA, 75, 78, NA, NA, NA, 92, 80, 87, 75, 89), label = "Age at Followup 3 fasting blood/urine(yr"), 
               C_AGEL = structure(c(NA, NA, NA, NA, NA, NA, NA, NA, NA, 
                                    NA, 90, NA, NA, NA, 87, NA, NA, NA, 81, NA, NA, NA, NA, 80, 
                                    NA, NA, NA, NA, NA, NA, NA, 89, NA, NA, 100, NA, NA, NA, 
                                    83, NA, NA, 84, NA, NA, NA, NA, 86, NA, 80, 94), label = "Age at Followup 4 fasting blood/urine(yr"), 
               X_GPT = structure(c(20, 16, 11, 11, 12, 20, 16, 19, 32, 11, 
                                   13, 35, 15, 139, 14, 14, 20, 6, 10, 15, 11, 18, 10, 17, 15, 
                                   15, 15, 19, 49, 12, 13, 18, 9, 21, 12, 29, 29, 22, 22, 15, 
                                   23, 21, 10, 14, 20, 17, 18, 12, 24, 17), label = "BL GPT (also known as ALT) (U/L)"), 
               Y_GPT = structure(c(13, NA, 14, 10, NA, 15, 17, NA, 25, 10, 
                                   10, 35, NA, 59, 12, 11, 20, NA, 11, 141, NA, 22, 9, 25, NA, 
                                   NA, 11, 10, NA, 10, 24, 19, NA, 10, NA, 16, NA, 9, 18, NA, 
                                   18, 20, NA, 12, NA, 13, 18, 11, 18, NA), label = "F1 GPT (also known as ALT) (U/L)"), 
               Z_GPT = structure(c(12, 20, 16, NA, NA, 13, NA, 11, 24, NA, 
                                   6, 18, 18, 24, 15, NA, 17, NA, 16, 10, NA, 35, 8, 13, NA, 
                                   NA, 26, 11, NA, 14, NA, 17, NA, 17, NA, NA, NA, 11, 16, NA, 
                                   14, 20, NA, NA, 17, 11, 14, 8, 24, NA), label = "F2 GPT (also known as ALT) (U/L)"), 
               Q_GPT = structure(c(16, NA, 19, NA, NA, 12, NA, 9, 21, NA, 
                                   10, 18, 18, 60, 13, NA, 18, NA, 12, 11, 11, 19, NA, 41, NA, 
                                   NA, 247, NA, NA, NA, NA, 16, NA, 12, 7, NA, NA, NA, 20, NA, 
                                   16, 18, NA, NA, NA, 14, 22, 18, 18, 34), label = "F3 GPT (also known as ALT) (U/L)"), 
               C_GPT = structure(c(NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, 
                                   12, NA, NA, NA, 12, NA, NA, NA, 15, NA, NA, NA, NA, 20, NA, 
                                   NA, NA, NA, NA, NA, NA, 23, NA, NA, 9, NA, NA, NA, 14, NA, 
                                   NA, 16, NA, NA, NA, NA, 24, NA, 18, 21), label = "F4 GPT (also known as ALT) (U/L)", format.sas = "BEST"), 
               X_GOT = structure(c(17, 17, 21, 15, 20, 20, 14, 26, 22, 21, 
                                   29, 26, 14, 90, 15, 20, 21, 12, 16, 9, 17, 19, 15, 22, 20, 
                                   19, 23, 22, 55, 21, 23, 22, 23, 16, 22, 19, 26, 23, 18, 15, 
                                   30, 23, 19, 15, 22, 23, 16, 20, 22, 24), label = "BL GOT (also known as AST) (U/L)"), 
               Y_GOT = structure(c(12, NA, 13, 15, NA, 19, 16, NA, 25, 15, 
                                   24, 31, NA, 47, 12, 18, 17, NA, 20, 74, NA, 21, 12, 29, NA, 
                                   NA, 18, 16, NA, 18, 26, 21, NA, 15, NA, 18, NA, 13, 17, NA, 
                                   NA, 23, NA, 17, NA, 22, 18, 21, 21, NA), label = "F1 GOT (also known as AST) (U/L)"), 
               Z_GOT = structure(c(8, 18, 21, NA, NA, 21, NA, 19, 21, NA, 
                                   24, 19, 14, 24, 14, NA, 19, NA, 19, 9, NA, 22, 12, 17, NA, 
                                   NA, 23, 15, NA, 18, NA, 25, NA, 11, NA, NA, NA, 13, 18, NA, 
                                   26, 22, NA, NA, 18, 21, 16, 23, 22, NA), label = "F2 GOT (also known as AST) (U/L)"), 
               Q_GOT = structure(c(13, NA, 30, NA, NA, 21, NA, 19, 21, NA, 
                                   23, 18, 15, 53, 14, NA, 18, NA, 18, 8, 14, 21, NA, 30, NA, 
                                   NA, 311, NA, NA, NA, NA, 21, NA, 12, 20, NA, NA, NA, 21, 
                                   NA, 23, 22, NA, NA, NA, 22, 17, 28, 20, 36), label = "F3 GOT (also known as AST) (U/L)"), 
               C_GOT = structure(c(NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, 
                                   25, NA, NA, NA, 15, NA, NA, NA, 18, NA, NA, NA, NA, 21, NA, 
                                   NA, NA, NA, NA, NA, NA, 29, NA, NA, 16, NA, NA, NA, 18, NA, 
                                   NA, 20, NA, NA, NA, NA, 19, NA, 20, 28), label = "F4 GOT (also known as AST) (U/L)", format.sas = "BEST"), 
               DATA_ULT = structure(c(17395, 13372, 15951, 11908, 11600, 
                                      15237, 12312, 14941, 16578, 12355, 15988, 17139, 16059, 15955, 
                                      15891, 15672, 15986, 10828, 16751, 15838, 16043, 15917, 13338, 
                                      16049, 13072, 13412, 14158, 14719, 11697, 14984, 13668, 17257, 
                                      11534, 15277, 16217, 16059, 13525, 13405, 17254, 11334, 14777, 
                                      16049, 11737, 12711, 13352, 14321, 15958, 16021, 15888, 16941
               ), label = "Date of Last Contact as of FUP4 or death", format.sas = "DATE", class = "Date"), 
               DECEASED = structure(c(1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 0, 1, 
                                      0, 1, 0, 1, 0, 1, 1, 1, 0, 0, 1, 0, 0, 1, 1, 1, 1, 1, 1, 
                                      1, 1, 1, 1, 0, 1, 1, 1, 1, 1, 0, 1, 1, 1, 1, 0, 1, 0, 1), 
                                    label = "Deceased?/Deceduto(a)?")), row.names = c(NA,-50L), class = c("tbl_df", "tbl", "data.frame"))


df.long <- df %>% pivot_longer(cols = c(ends_with("DATEL"), ends_with("AGEL"), ends_with("GPT"), ends_with("GOT")), 
                               names_to = c("time", ".value"), names_sep = "(?<=[XYZQC])_", values_drop_na = TRUE) %>% 
  select(CODE98, DATEL, AGEL, GPT, GOT)

df.merge <- tmerge(df, df, id=CODE98, tstart=as.numeric(X_DATEL), tstop=as.numeric(DATA_ULT),
                   deceased=event(as.numeric(DATA_ULT), DECEASED))

df.merge <- tmerge(df.merge %>% select(CODE98, id), df.long, 
                   id=CODE98,
                   age=tdc(as.numeric(DATEL), AGEL), 
                   gpt=tdc(as.numeric(DATEL), GPT), got=tdc(as.numeric(DATEL), GOT))

Can anybody understand what it is going on? Thanks so much in advance

Answer 1

Solved by Prof. Terry Therneau by e-mail:

When you have chained tmerge statements, the second, third, etc should have a tmerge output as the first argument. You can't manipuate it and then pick up in the middle. You could limit the variable list for the first arg of the first tnerge call (I often do), but not thereafter. I find it hard to believe that this code ever worked. This, for instance, works.>

df.merge <- tmerge(df%>% select(CODE98), df, id=CODE98,
                   tstart=as.numeric(X_DATEL), tstop=as.numeric(DATA_ULT),
                   deceased=event(as.numeric(DATA_ULT), DECEASED))

df.merge <- tmerge(df.merge, df.long,
                   id=CODE98,
                   age=tdc(as.numeric(DATEL), AGEL),
                   gpt=tdc(as.numeric(DATEL), GPT), got=tdc(as.numeric(DATEL), GOT))

Answer 2

Had this same problem today and had it solved by this thread. Three cheers for asking this question and reaching out to Professor Therneau. Great package and vignette.