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Introduction

This document contains the algorithms necessary to code all the outcomes which measure “substance use reduction”. We only include outcomes which result in a single value per subject. These outcomes are:

Group Endpoint Class Reference Definition Missing is
Reduction Rate of negative UOS ratio Comer et al., 2006 Percentage of negative UOS during 8 weeks of treatment Positive
Reduction Opioid use rate ratio Eissenberg et al., 1997 subject retained in study at least 17 weeks AND subject showed 4 consecutive negative UDS between weeks 1-17 Imputed
Reduction Rate of negative UOS ratio Fiellin et al., 2006 Percentage of negative UOS Positive
Reduction Rate of negative UOS ratio Fudala et al., 2003 Percentage of negative UOS Missing
Reduction Rate of negative UOS ratio Haight et al., 2019 Percentage of negative UOS from week 5 to week 24 Positive
Reduction Rate of negative UOS ratio Jaffe et al., 1972 Percentage of treatment weeks characterized by negative UOS for patients who completed ≥8 weeks of the study Imputed
Reduction Rate of negative UOS ratio Johnson et al., 1992 Average percentage of negative UOS Positive
Reduction Rate of negative UOS logical Kosten et al., 1993 ≥70% negative UOS during the 24-week trial period Missing/not imputed
Reduction Rate of negative UOS ratio Ling et al., 1998 Mean percentage negative UOS Missing/not imputed
Reduction Rate of negative UOS integer Ling et al., 1998 no. of negative UOS (“treatment effectiveness score”) Missing/not imputed
Reduction Rate of negative UOS ratio Ling et al., 2010 Percentage of negative UOS during weeks 1-16 of the trial Positive
Reduction Opioid use rate ratio Ling, Charuvastra, Kaim, & Klett, 1976 Index of illicit morphine use ([0, 120]). Note: this is a complex definition; for details see the original paper. Positive
Reduction Rate of negative UOS ratio Lofwall et al., 2018 Mean percentage of negative UOS for weeks 1 to 24 Positive
Reduction Rate of negative UOS ratio Mattick et al., 2003 “Percentage of clean urines (PCU)”: Rate of negative UOS for the time that the patient remained in the study Missing/not imputed
Reduction Rate of negative UOS ratio Mattick et al., 2003 “treatment effectiveness percentage (TEP)”: Rate of negative UOS for the full 13‐week study (ITT) Missing/not imputed
Reduction Rate of negative UOS ratio Pani, Maremmani, Pirastu, Tagliamonte, & Gessa, 2000 PCC: Percentage ratio of negative UOS and the total number of UOS carried out for each patient during the period of treatment Missing/not imputed
Reduction Rate of negative UOS ratio Pani, Maremmani, Pirastu, Tagliamonte, & Gessa, 2000 TEC: Percentage ratio between the number of negative UOS and the number of UOS as per protocol Positive
Reduction Opioid use rate ratio Petitjean et al., 2001 Weekly proportion of positive UOS (intent-to-treat and completer analysis) Positive
Reduction Rate of negative UOS ratio Preston, Umbricht, & Epstein, 2000 “Mean intervention percent negative”: Percentage of negative UOS in the treatment phase Positive
Reduction Rate of negative UOS ratio Schottenfeld et al., 2005 Proportion of negative UOS Missing
Reduction Opioid use rate integer Schwartz et al., 2006 Number of positive UOS at 120-day follow-up Missing/not imputed
Reduction Opioid use rate ratio Shufman et al., 1994 Percentage of positive UOS Missing
Reduction Opioid use rate ratio Soyka, Zingg, Koller, & Kuefner, 2008 Monthly rates of positive UOS Missing/not imputed
Reduction Opioid use rate ratio Strain, Bigelow, Liebson, & Stitzer, 1999 Percentage of positive UOS Missing/not imputed
Reduction Opioid use rate ratio Strain, Stitzer, Liebson, & Bigelow, 1993 Rate of positive UOS through the end of the stable dosing period Not defined
Reduction Opioid use rate ratio Strain, Stitzer, Liebson, & Bigelow, 1994 Overall rate of positive UOS Missing/not imputed
Reduction Opioid use rate ratio Strain, Stitzer, Liebson, & Bigelow, 1996 Percentage of positive UOS – Overall AND summarized in consecutive 2-week blocks Missing/not imputed
Reduction Rate of negative UOS logical Strang et al., 2010 ≥50% negative UOS during weeks 14-26 Positive
Reduction Rate of negative UOS ratio Strang et al., 2019 Proportion of negative UOS at the end of the 12‐week post-randomization time point Positive
Reduction Rate of negative UOS NA Tanum et al., 2017 Rate of negative UOS: Number of negative UOS divided by the total number of attended tests (group proportion) Positive
Reduction Rate of negative UOS ratio Wolstein et al., 2009 Number of negative UOS per number of weeks of study participation Unknown
Reduction Opioid use rate ratio Woody et al., 2008 Percentage of positive UOS at weeks 4, 8, and 12 Imputed
Reduction Opioid use rate integer Zaks, Fink, & Freedman, 1972 Number of positive UOS Not defined

We will use the table of participant opioid use patterns from the ctn0094DataExtra package to calculate these endpoints (we have a copy of the endpoints in the dataset outcomesCTN0094). Importantly, if you wish to apply these algorithms to calculate endpoints for your data, the participants’ substance use patterns must be stored in the “substance use pattern word” format shown here. We also show a subset of the data to visualize a variety of different real substance use patterns.

We first define the following five-value legend:

  • +: positive for the substance(s) in a specified window of time (a day, week, month, etc.) by urine screen (or participant self report, if such data are of interest)
  • : negative for the substance(s)
  • o: subject failed to provide a urine sample
  • *: inconclusive results or mixed results (e.g. subject provided more than one urine sample in the time interval and they did not agree)
  • _: no specimens required (weekends, holidays, pre-randomization period, alternating visit days/weeks)
###  Full Data  ###
udsOutcomes_df <- 
    CTNote::outcomesCTN0094 %>% 
  select(who, usePatternUDS)

# Make a copy
outcomesRed_df <- udsOutcomes_df


###  Examples  ###
examplePeople_int <- c(1, 163, 210, 242, 4, 17, 13, 1103, 233, 2089)
outcomesRed_df %>% 
  filter(who %in% examplePeople_int)
## # A tibble: 10 × 2
##      who usePatternUDS                      
##    <dbl> <chr>                              
##  1     1 ooooooooooooooo                    
##  2     4 -------------------o-o-o           
##  3    13 ------------o-oooooooooo           
##  4    17 --++*++++++-++++++-+++-            
##  5   163 -o---o---o--o+----------           
##  6   210 -++++++++-+++-----------           
##  7   233 *+++++++++++o++++++++++o           
##  8   242 -----------------------            
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o
## 10  2089 ++++---+--------------o-

For example, participant 1 has a use pattern ooooooooooooooo (all missing UDS), which means that they dropped out of the study. In contrast, participant 233 has a use pattern *+++++++++++o++++++++++o (nearly all positive UDS): they did not drop out of the study, but the treatment was completely ineffective for them. Participant 2089 started the study in a rough patch, but greatly improved in treatment over time (++++---+--------------o-).


Substance Use Reduction Endpoints

Comer et al. (2006)

Definition: Percentage of negative UOS during 8 weeks of treatment

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
    mutate(
        Rd_comer_2006 = count_matches(
            use_pattern = usePatternUDS,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            # first 8 weeks of treatment
            start = 1, end = 8,
            proportion = TRUE
        )
    ) %>%
    select(who, Rd_comer_2006) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_comer_2006)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_comer_2006
##    <dbl> <chr>                                       <dbl>
##  1     1 ooooooooooooooo                            0     
##  2     4 -------------------o-o-o                   1     
##  3    13 ------------o-oooooooooo                   1     
##  4    17 --++*++++++-++++++-+++-                    0.312 
##  5   163 -o---o---o--o+----------                   0.75  
##  6   210 -++++++++-+++-----------                   0.125 
##  7   233 *+++++++++++o++++++++++o                   0.0625
##  8   242 -----------------------                    1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o        0.5   
## 10  2089 ++++---+--------------o-                   0.375

Definition: subject retained in study at least 17 weeks AND subject showed 4 consecutive negative UDS between weeks 1-17

From their paper, we read “Where urinalysis data were missing for an entire week (5 of 1836 data points; 0.3%) the average of that patient’s results from the 2 weeks surrounding the missing week was substituted for the missing value.” Also, because some of our trials only retained subjects for 15-16 weeks, we changed the cutoff to 15 weeks in order to apply this definition to our data.

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # Check for 15 weeks of participation
  mutate(
        completedProtocol = measure_retention(usePatternUDS) >= 15
    ) %>% 
    # Impute local missings
    mutate(
        useImputed = impute_missing_visits(
            use_pattern = usePatternUDS,
            method = "kNV",
            knvWeights_num = c(`o` = NA, `+` = 1, `*` = 0.5, `-` = 0),
            quietly = TRUE
        )
    ) %>% 
    # detect 4 consecutive negative UDS
    mutate(
        consecNeg = detect_subpattern(
            use_pattern = useImputed,
            subpattern = "----",
            # we use 15 weeks of study (instead of 17)
            start = 1, end = 15
        )
    ) %>% 
    # non-participation penalty: if the participant didn't stay in the study the
  #   whole time, then the treatment was a failure
    mutate(
        Rd_eissenberg_1997 = case_when(
            completedProtocol  ~ consecNeg,
            !completedProtocol ~ FALSE
        )
    ) %>% 
    select(who, Rd_eissenberg_1997) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_eissenberg_1997)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_eissenberg_1997
##    <dbl> <chr>                               <lgl>             
##  1     1 ooooooooooooooo                     FALSE             
##  2     4 -------------------o-o-o            TRUE              
##  3    13 ------------o-oooooooooo            FALSE             
##  4    17 --++*++++++-++++++-+++-             FALSE             
##  5   163 -o---o---o--o+----------            TRUE              
##  6   210 -++++++++-+++-----------            FALSE             
##  7   233 *+++++++++++o++++++++++o            FALSE             
##  8   242 -----------------------             TRUE              
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o TRUE              
## 10  2089 ++++---+--------------o-            TRUE

Fiellin et al. (2006)

Definition: Percentage of negative UOS

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  mutate(
        Rd_fiellin_2006 = count_matches(
            use_pattern = usePatternUDS,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            proportion = TRUE
        )
    ) %>%
    select(who, Rd_fiellin_2006) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_fiellin_2006)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_fiellin_2006
##    <dbl> <chr>                                         <dbl>
##  1     1 ooooooooooooooo                              0     
##  2     4 -------------------o-o-o                     0.875 
##  3    13 ------------o-oooooooooo                     0.542 
##  4    17 --++*++++++-++++++-+++-                      0.239 
##  5   163 -o---o---o--o+----------                     0.792 
##  6   210 -++++++++-+++-----------                     0.542 
##  7   233 *+++++++++++o++++++++++o                     0.0208
##  8   242 -----------------------                      1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o          0.571 
## 10  2089 ++++---+--------------o-                     0.75

Fudala et al. (2003)

Definition: Percentage of negative UOS; they exclude missing values.

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # Drop weeks with missing UDS
  mutate(
        usePatternPresent = recode_missing_visits(
            usePatternUDS,
            missing_becomes = ""
        )
    ) %>%
    mutate(
        Rd_fudala_2003 = count_matches(
            use_pattern = usePatternPresent,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            proportion = TRUE
        )
    ) %>% 
    select(who, Rd_fudala_2003) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_fudala_2003)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_fudala_2003
##    <dbl> <chr>                                        <dbl>
##  1     1 ooooooooooooooo                             0     
##  2     4 -------------------o-o-o                    1     
##  3    13 ------------o-oooooooooo                    1     
##  4    17 --++*++++++-++++++-+++-                     0.239 
##  5   163 -o---o---o--o+----------                    0.95  
##  6   210 -++++++++-+++-----------                    0.542 
##  7   233 *+++++++++++o++++++++++o                    0.0227
##  8   242 -----------------------                     1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o         0.769 
## 10  2089 ++++---+--------------o-                    0.783

Haight et al. (2019)

Definition: Percentage of negative UOS from week 5 to week 24

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  mutate(
        Rd_haight_2019 = count_matches(
            use_pattern = usePatternUDS,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            # The end-of-protocol for our trials is 15-16 weeks
            start = 5, end = 15,
            proportion = TRUE
        )
    ) %>%
    select(who, Rd_haight_2019) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_haight_2019)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_haight_2019
##    <dbl> <chr>                                        <dbl>
##  1     1 ooooooooooooooo                              0    
##  2     4 -------------------o-o-o                     1    
##  3    13 ------------o-oooooooooo                     0.818
##  4    17 --++*++++++-++++++-+++-                      0.136
##  5   163 -o---o---o--o+----------                     0.636
##  6   210 -++++++++-+++-----------                     0.273
##  7   233 *+++++++++++o++++++++++o                     0    
##  8   242 -----------------------                      1    
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o          0.545
## 10  2089 ++++---+--------------o-                     0.909

Jaffe et al. (1972)

Definition: Percentage of treatment weeks characterized by negative UOS for patients who completed ≥8 weeks of the study; and missing values were imputed to the mode for each participant.

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # Mark if participants completed 8 weeks of treatment; remove those who do not
  #   (but we will add them back in at the end)
  mutate(lastWeek_idx = measure_retention(use_pattern = usePatternUDS)) %>% 
    filter(lastWeek_idx >= 8) %>% 
    # For participants who stayed in the trials at least 8 weeks, impute their
  #   missing weeks to their personal most common UDS result; in the event of a
  #   tie between a negative and a positive result for the mode, the tiebreaker
  #   is a positive result.
    mutate(
        usePatternImputed = impute_missing_visits(
            use_pattern = usePatternUDS,
            method = "mode"
        )
    ) %>% 
    mutate(
        Rd_jaffe_1972 = count_matches(
            usePatternImputed,
            match_is = "-",
            mixed_results_are = "*",
            mixed_weight = 0.5,
            proportion = TRUE
        )
    ) %>% 
    select(who, Rd_jaffe_1972) %>% 
    left_join(outcomesRed_df, ., by = "who") %>% 
    # Lots of NAs from the participants who did not make it to week 8; replace
    #   these NAs with 0
    replace_na(list(Rd_jaffe_1972 = 0))

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_jaffe_1972)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_jaffe_1972
##    <dbl> <chr>                                       <dbl>
##  1     1 ooooooooooooooo                            0     
##  2     4 -------------------o-o-o                   1     
##  3    13 ------------o-oooooooooo                   1     
##  4    17 --++*++++++-++++++-+++-                    0.239 
##  5   163 -o---o---o--o+----------                   0.958 
##  6   210 -++++++++-+++-----------                   0.542 
##  7   233 *+++++++++++o++++++++++o                   0.0208
##  8   242 -----------------------                    1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o        0.829 
## 10  2089 ++++---+--------------o-                   0.792

Johnson, Jaffe, and Fudala (1992)

Definitions: Average percentage of negative UOS

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  mutate(
        Rd_johnson_1992 = count_matches(
            use_pattern = usePatternUDS,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            proportion = TRUE
        )
    ) %>% 
    select(who, Rd_johnson_1992) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_johnson_1992)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_johnson_1992
##    <dbl> <chr>                                         <dbl>
##  1     1 ooooooooooooooo                              0     
##  2     4 -------------------o-o-o                     0.875 
##  3    13 ------------o-oooooooooo                     0.542 
##  4    17 --++*++++++-++++++-+++-                      0.239 
##  5   163 -o---o---o--o+----------                     0.792 
##  6   210 -++++++++-+++-----------                     0.542 
##  7   233 *+++++++++++o++++++++++o                     0.0208
##  8   242 -----------------------                      1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o          0.571 
## 10  2089 ++++---+--------------o-                     0.75

Kosten et al. (1993)

Definition: ≥70% negative UOS during the 24-week trial period; missing UDS are excluded

Note: there are multiple definitions of treatment failure in this paper; we provide an algorithm for the definition which results in a single value for each participant.

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # Exclude missing visits
  mutate(
        usePatternPresent = recode_missing_visits(
            usePatternUDS,
            missing_becomes = ""
        )
    ) %>%
    mutate(
        kosten1993B_prop = count_matches(
            use_pattern = usePatternPresent,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            start = 1,
            end = 15,
            proportion = TRUE
        )
    ) %>% 
    mutate(Rd_kostenB_1993 = kosten1993B_prop >= 0.7) %>% 
    select(who, Rd_kostenB_1993) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_kostenB_1993)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_kostenB_1993
##    <dbl> <chr>                               <lgl>          
##  1     1 ooooooooooooooo                     FALSE          
##  2     4 -------------------o-o-o            TRUE           
##  3    13 ------------o-oooooooooo            TRUE           
##  4    17 --++*++++++-++++++-+++-             FALSE          
##  5   163 -o---o---o--o+----------            TRUE           
##  6   210 -++++++++-+++-----------            FALSE          
##  7   233 *+++++++++++o++++++++++o            FALSE          
##  8   242 -----------------------             TRUE           
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o TRUE           
## 10  2089 ++++---+--------------o-            FALSE

Ling et al. (1998) (A) and (C)

There are two definitions from this paper which we include in the reduction section our library: Mean percentage negative UOS and no. of negative UOS (“treatment effectiveness score”). Both of these outcome definitions exclude missing UDS. We also include an abstinence endpoint from this paper in our “abstinence and relapse endpoints” section.

Ling et al., 1998 (A)

Definition: Mean percentage negative UOS

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # Exclude missing UDS
  mutate(
        usePatternPresent = recode_missing_visits(
            usePatternUDS,
            missing_becomes = ""
        )
    ) %>%
    mutate(
        Rd_lingA_1998 = count_matches(
            use_pattern = usePatternPresent,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            start = 1, end = 15,
            proportion = TRUE
        )
    ) %>% 
    select(who, Rd_lingA_1998) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_lingA_1998)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_lingA_1998
##    <dbl> <chr>                                       <dbl>
##  1     1 ooooooooooooooo                            0     
##  2     4 -------------------o-o-o                   1     
##  3    13 ------------o-oooooooooo                   1     
##  4    17 --++*++++++-++++++-+++-                    0.233 
##  5   163 -o---o---o--o+----------                   0.933 
##  6   210 -++++++++-+++-----------                   0.267 
##  7   233 *+++++++++++o++++++++++o                   0.0333
##  8   242 -----------------------                    1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o        0.733 
## 10  2089 ++++---+--------------o-                   0.667

Ling et al., 1998 (C)

Definition: no. of negative UOS (“treatment effectiveness score”)

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  mutate(
        Rd_lingC_1998 = count_matches(
            use_pattern = usePatternUDS,
            match_is = "-",
            end = 15,
            mixed_results_are = "*",
            mixed_weight = 0.5
        )
    ) %>% 
    select(who, Rd_lingC_1998) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_lingC_1998)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_lingC_1998
##    <dbl> <chr>                                       <dbl>
##  1     1 ooooooooooooooo                               0  
##  2     4 -------------------o-o-o                     15  
##  3    13 ------------o-oooooooooo                     13  
##  4    17 --++*++++++-++++++-+++-                       3.5
##  5   163 -o---o---o--o+----------                     10  
##  6   210 -++++++++-+++-----------                      4  
##  7   233 *+++++++++++o++++++++++o                      0.5
##  8   242 -----------------------                      15  
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o           8  
## 10  2089 ++++---+--------------o-                     10

Ling et al. (2010)

Definition: Percentage of negative UOS during weeks 1-16 of the trial

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  mutate(
        Rd_ling_2010 = count_matches(
            use_pattern = usePatternUDS,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            # We only have 15 weeks of data from some arms
            start = 1, end = 15,
            proportion = TRUE
        )
    ) %>% 
    select(who, Rd_ling_2010) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_ling_2010)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_ling_2010
##    <dbl> <chr>                                      <dbl>
##  1     1 ooooooooooooooo                           0     
##  2     4 -------------------o-o-o                  1     
##  3    13 ------------o-oooooooooo                  0.867 
##  4    17 --++*++++++-++++++-+++-                   0.233 
##  5   163 -o---o---o--o+----------                  0.667 
##  6   210 -++++++++-+++-----------                  0.267 
##  7   233 *+++++++++++o++++++++++o                  0.0333
##  8   242 -----------------------                   1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o       0.533 
## 10  2089 ++++---+--------------o-                  0.667

Ling et al. (1976)

Definition: Index of illicit morphine use ([0, 120]). Note: this is a complex definition; for details see the original paper.

Original

The definition in this paper is quite complex, but very well thought out. It is one of our favorite MOUD treatment endpoints because of its flexibility.

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # Rule 1: mark induction failures
  # The Ling et al. protocol lasted 40 weeks while requiring 7 weeks of data for
  #   the subjects to be counted as "estimable participants"; our 3 studies each
    #   lasted at least 15 weeks. Therefore, we should require at least
  #   (7/40) * 15) ~= 3 weeks of data to consider a participant "estimable"
    mutate(
        inductFail = measure_retention(usePatternUDS) <= 3
    ) %>% 
    mutate(
        usePatternTrunc = str_sub(usePatternUDS, end = 15)
    ) %>% 
    # Rules 2-4: weighting and scaling visits. The flexibility here is amazing.
    #   If we think that dropout is worse than positive, then we can reflect that
    #   in the weights. Ling et al. counted a missing visit as 0.22 of a positive;
  #   and they use a step function to increase the penalty of a positive UDS 
  #   over time.
    mutate(
        ling1976o22_use = weight_positive_visits(
            use_pattern = usePatternTrunc,
            weights_num = c(`+` = 1.0, `*` = 0.5, `o` = 0.22, `-` = 0),
            posPenalty_num = rep(1:5, each = 3) # step function for 15 weeks
        )
    ) %>% 
    mutate(
        ling1976o22_use = case_when(
            inductFail  ~ 120,
            !inductFail ~ ling1976o22_use
        ),
        Rd_lingA_1976 = 120 - ling1976o22_use
    ) %>%
    select(who, Rd_lingA_1976) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_lingA_1976)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_lingA_1976
##    <dbl> <chr>                                       <dbl>
##  1     1 ooooooooooooooo                               0  
##  2     4 -------------------o-o-o                    120  
##  3    13 ------------o-oooooooooo                    119. 
##  4    17 --++*++++++-++++++-+++-                      18.7
##  5   163 -o---o---o--o+----------                    104. 
##  6   210 -++++++++-+++-----------                     40  
##  7   233 *+++++++++++o++++++++++o                     14.1
##  8   242 -----------------------                     120  
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o          88.9
## 10  2089 ++++---+--------------o-                     98.7

A Variant

We also include a variant of this definition which includes a greater penalty for missing values and a smooth function to increase weights of positive UDS.

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
    mutate(
        inductFail = measure_retention(usePatternUDS) <= 3
    ) %>% 
    mutate(
        usePatternTrunc = str_sub(usePatternUDS, end = 15)
    ) %>% 
    mutate(
        ling1976o100_use = weight_positive_visits(
            use_pattern = usePatternTrunc,
            # Higher weight for missing values
            weights_num = c(`+` = 0.8, `*` = 0.4, `o` = 1.0, `-` = 0),
            # Smooth penalty function for increasing positive UDS
            posPenalty_num = seq(
                from = 1, to = 5, length.out = str_length(usePatternTrunc)
            )
        )
    ) %>% 
    mutate(
      ling1976o100_use = case_when(
            inductFail  ~ 120,
            !inductFail ~ ling1976o100_use
        ),
        Rd_lingB_1976 = 120 - ling1976o100_use
    ) %>%
    select(who, Rd_lingB_1976) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_lingB_1976)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_lingB_1976
##    <dbl> <chr>                                       <dbl>
##  1     1 ooooooooooooooo                               0  
##  2     4 -------------------o-o-o                    120  
##  3    13 ------------o-oooooooooo                    113. 
##  4    17 --++*++++++-++++++-+++-                      20.6
##  5   163 -o---o---o--o+----------                     94.2
##  6   210 -++++++++-+++-----------                     38.5
##  7   233 *+++++++++++o++++++++++o                     10.4
##  8   242 -----------------------                     120  
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o          82.0
## 10  2089 ++++---+--------------o-                     96.9

Lofwall et al. (2018)

Definition: Mean percentage of negative UOS for weeks 1 to 24; but urine screens are collected each week for the first 12 weeks, then every other week for weeks 13-24. We project this onto a 15-16 week protocol by requiring UDS each week for the first 7 weeks, then every other week for the next 8. Then, we impute the skipped weeks to be whatever the value of the UDS was from the last visit.

###  Define a Visit Pattern (Lattice)  ###
lofwallLattice_char <- collapse_lattice(
    lattice_patterns = c("o", "_o"),
    # For the lattice as defined over 24 weeks, you need 12 weeks of weekly visits
    #   and 6 sets of alternating "no visit" and "visit" week pairs, or c(12, 6).
    #   For us, we want 7 weeks straight of weekly visits followed by 4 pairs of
    #   alternating visits (8 weeks) for a total of 15 weeks.
    times = c(7, 4)
)
lofwallLattice_char
## [1] "ooooooo_o_o_o_o"
###  Calculate the Endpoint  ###
outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # Mark all missing UDS as positive
    mutate(
        udsPattern = recode_missing_visits(usePatternUDS)
    ) %>% 
  # View the current use pattern "through" the Lofwall protocol
    mutate(
        udsLattice = view_by_lattice(
            use_pattern = udsPattern,
            lattice_pattern = str_sub(lofwallLattice_char, end = 15) # first 15 weeks
        )
    ) %>% 
  # Impute the visits from the "unobserved" weeks to the last observed week
    mutate(
        udsLatticeLOCF = impute_missing_visits(
            use_pattern = udsLattice,
            method = "locf",
            # This is only imputing values that we wouldn't have seen because of the
            #   protocol ("_" means missing by design; "o" means missing)
            missing_is = "_",
            quietly = TRUE
        )
    ) %>% 
    mutate(
        Rd_lofwall_2018 = count_matches(
            use_pattern = udsLatticeLOCF,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            start = 1, end = 15, # first 15 weeks
            proportion = TRUE
        )
    ) %>%
    select(who, Rd_lofwall_2018) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_lofwall_2018)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_lofwall_2018
##    <dbl> <chr>                                         <dbl>
##  1     1 ooooooooooooooo                              0     
##  2     4 -------------------o-o-o                     1     
##  3    13 ------------o-oooooooooo                     0.8   
##  4    17 --++*++++++-++++++-+++-                      0.167 
##  5   163 -o---o---o--o+----------                     0.733 
##  6   210 -++++++++-+++-----------                     0.133 
##  7   233 *+++++++++++o++++++++++o                     0.0333
##  8   242 -----------------------                      1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o          0.333 
## 10  2089 ++++---+--------------o-                     0.733

Mattick et al. (2003) (A) and (B)

There are also two definitions from this paper included in our library.

Mattick et al., 2003 (A)

Definition: “Percentage of clean urines (PCU)”: Rate of negative UOS for the time that the patient remained in the study

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # Find out how long the participant stayed in the study
  mutate(lastWeek_idx = measure_retention(use_pattern = usePatternUDS)) %>% 
    mutate(
        Rd_mattickA_2003 = count_matches(
            use_pattern = usePatternUDS,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            # Measure proportion of negative UDS only during study participation
            start = 1, end = lastWeek_idx,
            proportion = TRUE
        )
    ) %>%
    select(who, Rd_mattickA_2003) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_mattickA_2003)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_mattickA_2003
##    <dbl> <chr>                                          <dbl>
##  1     1 ooooooooooooooo                               0     
##  2     4 -------------------o-o-o                      0.913 
##  3    13 ------------o-oooooooooo                      0.929 
##  4    17 --++*++++++-++++++-+++-                       0.239 
##  5   163 -o---o---o--o+----------                      0.792 
##  6   210 -++++++++-+++-----------                      0.542 
##  7   233 *+++++++++++o++++++++++o                      0.0217
##  8   242 -----------------------                       1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o           0.588 
## 10  2089 ++++---+--------------o-                      0.75

Mattick et al., 2003 (B)

Definition: “treatment effectiveness percentage (TEP)”: Rate of negative UOS for the full 13‐week study (ITT)

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  mutate(
        Rd_mattickB_2003 = count_matches(
            use_pattern = usePatternUDS,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            # They used a 13-week protocol
            start = 1, end = 13,
            proportion = TRUE
        )
    ) %>%
    select(who, Rd_mattickB_2003) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_mattickB_2003)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_mattickB_2003
##    <dbl> <chr>                                          <dbl>
##  1     1 ooooooooooooooo                               0     
##  2     4 -------------------o-o-o                      1     
##  3    13 ------------o-oooooooooo                      0.923 
##  4    17 --++*++++++-++++++-+++-                       0.269 
##  5   163 -o---o---o--o+----------                      0.692 
##  6   210 -++++++++-+++-----------                      0.154 
##  7   233 *+++++++++++o++++++++++o                      0.0385
##  8   242 -----------------------                       1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o           0.462 
## 10  2089 ++++---+--------------o-                      0.615

Pani et al. (2000) (A) and (B)

There are also two definitions from this paper included in our library.

Pani et al., 2000 (A)

Definition: PCC: Percentage ratio of negative UOS and the total number of UOS carried out for each patient during the period of treatment

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # Remove weeks where participant failed to provide UDS
  mutate(
        usePatternPresent = recode_missing_visits(
            usePatternUDS,
            missing_becomes = ""
        )
    ) %>%
    mutate(
        Rd_paniA_2000 = count_matches(
            use_pattern = usePatternPresent,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            proportion = TRUE
        )
    ) %>% 
    select(who, Rd_paniA_2000) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_paniA_2000)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_paniA_2000
##    <dbl> <chr>                                       <dbl>
##  1     1 ooooooooooooooo                            0     
##  2     4 -------------------o-o-o                   1     
##  3    13 ------------o-oooooooooo                   1     
##  4    17 --++*++++++-++++++-+++-                    0.239 
##  5   163 -o---o---o--o+----------                   0.95  
##  6   210 -++++++++-+++-----------                   0.542 
##  7   233 *+++++++++++o++++++++++o                   0.0227
##  8   242 -----------------------                    1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o        0.769 
## 10  2089 ++++---+--------------o-                   0.783

Pani et al., 2000 (B)

Definition: TEC: Percentage ratio between the number of negative UOS and the number of UOS as per protocol

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  mutate(
        Rd_paniB_2000 = count_matches(
            use_pattern = usePatternUDS,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            proportion = TRUE
        )
    ) %>% 
    select(who, Rd_paniB_2000) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_paniB_2000)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_paniB_2000
##    <dbl> <chr>                                       <dbl>
##  1     1 ooooooooooooooo                            0     
##  2     4 -------------------o-o-o                   0.875 
##  3    13 ------------o-oooooooooo                   0.542 
##  4    17 --++*++++++-++++++-+++-                    0.239 
##  5   163 -o---o---o--o+----------                   0.792 
##  6   210 -++++++++-+++-----------                   0.542 
##  7   233 *+++++++++++o++++++++++o                   0.0208
##  8   242 -----------------------                    1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o        0.571 
## 10  2089 ++++---+--------------o-                   0.75

Petitjean et al. (2001)

Definition: Weekly proportion of positive UOS (intent-to-treat and completer analysis)

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  mutate(
        udsPattern = recode_missing_visits(usePatternUDS)
    ) %>% 
    mutate(
        petitjean2001_use = count_matches(
            use_pattern = udsPattern,
            match_is = "+",
            mixed_results_are = "*",
            proportion = TRUE
        )
    ) %>% 
    mutate(
        Rd_petitjean_2001 = 1 - petitjean2001_use
    ) %>% 
    select(who, Rd_petitjean_2001) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_petitjean_2001)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_petitjean_2001
##    <dbl> <chr>                                           <dbl>
##  1     1 ooooooooooooooo                                0     
##  2     4 -------------------o-o-o                       0.875 
##  3    13 ------------o-oooooooooo                       0.542 
##  4    17 --++*++++++-++++++-+++-                        0.239 
##  5   163 -o---o---o--o+----------                       0.792 
##  6   210 -++++++++-+++-----------                       0.542 
##  7   233 *+++++++++++o++++++++++o                       0.0208
##  8   242 -----------------------                        1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o            0.571 
## 10  2089 ++++---+--------------o-                       0.75

Preston, Umbricht, and Epstein (2000)

Definition: “Mean intervention percent negative”: Percentage of negative UOS in the treatment phase

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  mutate(
        Rd_preston_2000 = count_matches(
            use_pattern = usePatternUDS,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            # 13-week protocol used
            end = 13,
            proportion = TRUE
        )
    ) %>% 
    select(who, Rd_preston_2000) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_preston_2000)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_preston_2000
##    <dbl> <chr>                                         <dbl>
##  1     1 ooooooooooooooo                              0     
##  2     4 -------------------o-o-o                     1     
##  3    13 ------------o-oooooooooo                     0.923 
##  4    17 --++*++++++-++++++-+++-                      0.269 
##  5   163 -o---o---o--o+----------                     0.692 
##  6   210 -++++++++-+++-----------                     0.154 
##  7   233 *+++++++++++o++++++++++o                     0.0385
##  8   242 -----------------------                      1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o          0.462 
## 10  2089 ++++---+--------------o-                     0.615

Schottenfeld et al. (2005)

Definition: Proportion of negative UOS; exclude missing UDS

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # Exclude missing
  mutate(
        usePatternPresent = recode_missing_visits(
            usePatternUDS,
            missing_becomes = ""
        )
    ) %>%
  # Count negative
    mutate(
        Rd_schottenfeld_2005 = count_matches(
            use_pattern = usePatternPresent,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            proportion = TRUE
        )
    ) %>% 
    select(who, Rd_schottenfeld_2005) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_schottenfeld_2005)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_schottenfeld_2005
##    <dbl> <chr>                                              <dbl>
##  1     1 ooooooooooooooo                                   0     
##  2     4 -------------------o-o-o                          1     
##  3    13 ------------o-oooooooooo                          1     
##  4    17 --++*++++++-++++++-+++-                           0.239 
##  5   163 -o---o---o--o+----------                          0.95  
##  6   210 -++++++++-+++-----------                          0.542 
##  7   233 *+++++++++++o++++++++++o                          0.0227
##  8   242 -----------------------                           1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o               0.769 
## 10  2089 ++++---+--------------o-                          0.783

Schwartz et al. (2006)

Definition: Number of positive UOS at 120-day follow-up

This definition is a cohort-level definition, not an individual definition. The individual endpoint would be “was this participant abstinent from the substance of interest at the 120-day follow-up? (17 weeks from randomization). Our participants do not uniformly have 17 weeks of data, so we will assess them at week 15 instead. NOTE: while the authors classified their outcome as a”reduction” metric (and therefore we include it here in the “reduction” section of the outcomes library), we label this outcome with the prefix “Ab” for abstinence.

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  mutate(
    schwartz2006_abs = count_matches(
        use_pattern = usePatternUDS,
        match_is = "-",
        start = 15, end = 15,
        mixed_results_are = "*"
    )
  ) %>% 
    ungroup() %>% 
    mutate(
        Ab_schwartz_2006 = schwartz2006_abs == 1
    ) %>% 
    select(who, Ab_schwartz_2006) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Ab_schwartz_2006)
## # A tibble: 10 × 3
##      who usePatternUDS                       Ab_schwartz_2006
##    <dbl> <chr>                               <lgl>           
##  1     1 ooooooooooooooo                     FALSE           
##  2     4 -------------------o-o-o            TRUE            
##  3    13 ------------o-oooooooooo            FALSE           
##  4    17 --++*++++++-++++++-+++-             FALSE           
##  5   163 -o---o---o--o+----------            TRUE            
##  6   210 -++++++++-+++-----------            TRUE            
##  7   233 *+++++++++++o++++++++++o            FALSE           
##  8   242 -----------------------             TRUE            
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o TRUE            
## 10  2089 ++++---+--------------o-            TRUE

Shufman et al. (1994)

Definition: Percentage of positive UOS; missing is ignored

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # Count "+" UDS; 0 could be complete dropout or all negative
    mutate(
        shufman1994_useP = count_matches(
            use_pattern = usePatternUDS,
            match_is = "+",
            mixed_results_are = "*",
            proportion = TRUE
        )
    ) %>% 
    mutate(Rd_shufman_1994 = 1 - shufman1994_useP) %>% 
    select(who, Rd_shufman_1994) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_shufman_1994)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_shufman_1994
##    <dbl> <chr>                                         <dbl>
##  1     1 ooooooooooooooo                               1    
##  2     4 -------------------o-o-o                      1    
##  3    13 ------------o-oooooooooo                      1    
##  4    17 --++*++++++-++++++-+++-                       0.239
##  5   163 -o---o---o--o+----------                      0.958
##  6   210 -++++++++-+++-----------                      0.542
##  7   233 *+++++++++++o++++++++++o                      0.104
##  8   242 -----------------------                       1    
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o           0.829
## 10  2089 ++++---+--------------o-                      0.792

Soyka et al. (2008)

Definition: Monthly rates of positive UOS; missing is ignored

The paper is here.

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # Ignore missing UDS
    mutate(
        udsPattern = recode_missing_visits(
            use_pattern = usePatternUDS,
            missing_becomes = ""
        )
    ) %>% 
    # Count "+" UDS; 0 could be complete dropout or all negative
    mutate(
        soyka2008_use = count_matches(
            use_pattern = udsPattern,
            match_is = "+",
            mixed_results_are = "*",
            mixed_weight = 0.5,
            proportion = TRUE
        )
    ) %>% 
    mutate(Rd_soyka_2008 = 1 - soyka2008_use) %>% 
    ungroup() %>% 
    select(who, Rd_soyka_2008) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_soyka_2008)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_soyka_2008
##    <dbl> <chr>                                       <dbl>
##  1     1 ooooooooooooooo                            1     
##  2     4 -------------------o-o-o                   1     
##  3    13 ------------o-oooooooooo                   1     
##  4    17 --++*++++++-++++++-+++-                    0.239 
##  5   163 -o---o---o--o+----------                   0.95  
##  6   210 -++++++++-+++-----------                   0.542 
##  7   233 *+++++++++++o++++++++++o                   0.0227
##  8   242 -----------------------                    1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o        0.769 
## 10  2089 ++++---+--------------o-                   0.783

Strain et al. (1993)

Definition: Rate of positive UOS through the end of the stable dosing period; missing is not defined

Paper here

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # Count "+" UDS; 0 could be complete dropout or all negative
    mutate(
        strain1993_use = count_matches(
            use_pattern = usePatternUDS,
            match_is = "+",
            # The stable dosing period began in week 6
            start = 6, end = 15,
            mixed_results_are = "*",
            proportion = TRUE
        )
    ) %>% 
    mutate(Rd_strain_1993 = 1 - strain1993_use) %>% 
    select(who, Rd_strain_1993) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_strain_1993)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_strain_1993
##    <dbl> <chr>                                        <dbl>
##  1     1 ooooooooooooooo                                1  
##  2     4 -------------------o-o-o                       1  
##  3    13 ------------o-oooooooooo                       1  
##  4    17 --++*++++++-++++++-+++-                        0.1
##  5   163 -o---o---o--o+----------                       0.9
##  6   210 -++++++++-+++-----------                       0.3
##  7   233 *+++++++++++o++++++++++o                       0.1
##  8   242 -----------------------                        1  
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o            0.8
## 10  2089 ++++---+--------------o-                       0.9

Strain et al. (1994)

Definition: Overall rate of positive UOS; missing is ignored

Paper here

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
    # Ignore missing
    mutate(
        udsPattern = recode_missing_visits(
            use_pattern = usePatternUDS,
            missing_becomes = ""
        )
    ) %>% 
  # Count "+" UDS; 0 could be complete dropout or all negative
    mutate(
        strain1994_use = count_matches(
            use_pattern = usePatternUDS,
            match_is = "+",
            mixed_results_are = "*",
            proportion = TRUE
        )
    ) %>% 
    mutate(Rd_strain_1994 = 1 - strain1994_use) %>% 
    select(who, Rd_strain_1994) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_strain_1994)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_strain_1994
##    <dbl> <chr>                                        <dbl>
##  1     1 ooooooooooooooo                              1    
##  2     4 -------------------o-o-o                     1    
##  3    13 ------------o-oooooooooo                     1    
##  4    17 --++*++++++-++++++-+++-                      0.239
##  5   163 -o---o---o--o+----------                     0.958
##  6   210 -++++++++-+++-----------                     0.542
##  7   233 *+++++++++++o++++++++++o                     0.104
##  8   242 -----------------------                      1    
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o          0.829
## 10  2089 ++++---+--------------o-                     0.792

Strain et al. (1996)

Definition: Percentage of positive UOS – Overall AND summarized in consecutive 2-week blocks; missing is ignored

Because the “two-weeks blocks” definition results in more than one value per participant, we do not provide it in our library. This definition is now identical to that of Strain, Stitzer, Liebson, & Bigelow (1994).

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
    # Ignore missing
    mutate(
        udsPattern = recode_missing_visits(
            use_pattern = usePatternUDS,
            missing_becomes = ""
        )
    ) %>% 
    # Count "+" UDS; 0 could be complete dropout or all negative
    mutate(
        strain1996_use = count_matches(
            use_pattern = udsPattern,
            match_is = "+",
            mixed_results_are = "*",
            proportion = TRUE
        )
    ) %>% 
    mutate(Rd_strain_1996 = 1 - strain1996_use) %>% 
    select(who, Rd_strain_1996) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_strain_1996)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_strain_1996
##    <dbl> <chr>                                        <dbl>
##  1     1 ooooooooooooooo                             1     
##  2     4 -------------------o-o-o                    1     
##  3    13 ------------o-oooooooooo                    1     
##  4    17 --++*++++++-++++++-+++-                     0.239 
##  5   163 -o---o---o--o+----------                    0.95  
##  6   210 -++++++++-+++-----------                    0.542 
##  7   233 *+++++++++++o++++++++++o                    0.0227
##  8   242 -----------------------                     1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o         0.769 
## 10  2089 ++++---+--------------o-                    0.783

Strain et al. (1999)

Definition: Percentage of positive UOS

This paper gave no commentary on how the missing values would be processed, only that the statistical software SAS was capable of handling missing values. SAS, by default, excludes missing values from analyses. Therefore, this definition will also be identical to that of Strain, Stitzer, Liebson, & Bigelow (1994).

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
    # Ignore missing
    mutate(
        udsPattern = recode_missing_visits(
            use_pattern = usePatternUDS,
            missing_becomes = ""
        )
    ) %>% 
  # Count "+" UDS; 0 could be complete dropout or all negative
    mutate(
        strain1999_use = count_matches(
            use_pattern = usePatternUDS,
            match_is = "+",
            mixed_results_are = "*",
            proportion = TRUE
        )
    ) %>% 
    mutate(Rd_strain_1999 = 1 - strain1999_use) %>% 
    select(who, Rd_strain_1999) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_strain_1999)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_strain_1999
##    <dbl> <chr>                                        <dbl>
##  1     1 ooooooooooooooo                              1    
##  2     4 -------------------o-o-o                     1    
##  3    13 ------------o-oooooooooo                     1    
##  4    17 --++*++++++-++++++-+++-                      0.239
##  5   163 -o---o---o--o+----------                     0.958
##  6   210 -++++++++-+++-----------                     0.542
##  7   233 *+++++++++++o++++++++++o                     0.104
##  8   242 -----------------------                      1    
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o          0.829
## 10  2089 ++++---+--------------o-                     0.792

Strang et al. (2010)

Definitions: ≥50% negative UOS during weeks 14-26

Our protocols do not uniformly contain 26 weeks of data, so we apply this definition as “the last 12 weeks of the protocol.”

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  mutate(
        cleanProp = count_matches(
            use_pattern = usePatternUDS,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            # Syntax to select the LAST visits uses a negative sign; this means "12
            #   weeks before the end of the data" to "the last week of the data"
            start = -12, end = -1,
            proportion = TRUE
        )
    ) %>% 
    mutate(Rd_strang_2010 = cleanProp >= 0.5) %>% 
    ungroup() %>% 
    select(who, Rd_strang_2010) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_strang_2010)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_strang_2010
##    <dbl> <chr>                               <lgl>         
##  1     1 ooooooooooooooo                     FALSE         
##  2     4 -------------------o-o-o            TRUE          
##  3    13 ------------o-oooooooooo            FALSE         
##  4    17 --++*++++++-++++++-+++-             FALSE         
##  5   163 -o---o---o--o+----------            TRUE          
##  6   210 -++++++++-+++-----------            TRUE          
##  7   233 *+++++++++++o++++++++++o            FALSE         
##  8   242 -----------------------             TRUE          
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o FALSE         
## 10  2089 ++++---+--------------o-            TRUE

Strang et al. (2019)

Definition: Proportion of negative UOS at the end of the 12‐week post-randomization time point

Paper here

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  mutate(
        Rd_strang_2019 = count_matches(
            use_pattern = usePatternUDS,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            # Only look at the first 12 weeks after randomization
            start = 1, end = 12,
            proportion = TRUE
        )
    ) %>%
    select(who, Rd_strang_2019) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_strang_2019)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_strang_2019
##    <dbl> <chr>                                        <dbl>
##  1     1 ooooooooooooooo                             0     
##  2     4 -------------------o-o-o                    1     
##  3    13 ------------o-oooooooooo                    1     
##  4    17 --++*++++++-++++++-+++-                     0.292 
##  5   163 -o---o---o--o+----------                    0.75  
##  6   210 -++++++++-+++-----------                    0.167 
##  7   233 *+++++++++++o++++++++++o                    0.0417
##  8   242 -----------------------                     1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o         0.5   
## 10  2089 ++++---+--------------o-                    0.583

Tanum et al. (2017)

Definition: Rate of negative UOS: Number of negative UOS divided by the total number of attended tests (group proportion)

Note that this definition as written is a group outcome, not a participant outcome. Therefore, we calculate this for each subject as the “rate of negative UOS for the time that the patient remained in the study.”

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # How long was each subject retained?
  mutate(lastWeek_idx = measure_retention(use_pattern = usePatternUDS)) %>% 
    mutate(
        Rd_tanum_2017 = count_matches(
            use_pattern = usePatternUDS,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            start = 1, end = lastWeek_idx,
            proportion = TRUE
        )
    ) %>%
    select(who, Rd_tanum_2017) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_tanum_2017)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_tanum_2017
##    <dbl> <chr>                                       <dbl>
##  1     1 ooooooooooooooo                            0     
##  2     4 -------------------o-o-o                   0.913 
##  3    13 ------------o-oooooooooo                   0.929 
##  4    17 --++*++++++-++++++-+++-                    0.239 
##  5   163 -o---o---o--o+----------                   0.792 
##  6   210 -++++++++-+++-----------                   0.542 
##  7   233 *+++++++++++o++++++++++o                   0.0217
##  8   242 -----------------------                    1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o        0.588 
## 10  2089 ++++---+--------------o-                   0.75

Wolstein et al. (2009)

Definition: Number of negative UOS per number of weeks of study participation

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # Because we are measuring outcomes only while "participating", remove missing
    #   weeks from the use pattern
    mutate(
        usePatternPresent = recode_missing_visits(
            usePatternUDS,
            missing_becomes = ""
        )
    ) %>%   
    mutate(
        Rd_wolstein_2009 = count_matches(
            use_pattern = usePatternPresent,
            match_is = "-",
            # Mixed results weeks count as half of a negative week
            mixed_results_are = "*", mixed_weight = 0.5,
            proportion = TRUE
        )
    ) %>%
    select(who, Rd_wolstein_2009) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_wolstein_2009)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_wolstein_2009
##    <dbl> <chr>                                          <dbl>
##  1     1 ooooooooooooooo                               0     
##  2     4 -------------------o-o-o                      1     
##  3    13 ------------o-oooooooooo                      1     
##  4    17 --++*++++++-++++++-+++-                       0.239 
##  5   163 -o---o---o--o+----------                      0.95  
##  6   210 -++++++++-+++-----------                      0.542 
##  7   233 *+++++++++++o++++++++++o                      0.0227
##  8   242 -----------------------                       1     
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o           0.769 
## 10  2089 ++++---+--------------o-                      0.783

Woody et al. (2008)

Definition: Percentage of positive UOS at weeks 4, 8, and 12

This paper contains rather exotic methods for missing value imputation, but the authors remark that setting “missing is positive” did not change their final results. We may include their imputation method in future versions of this code library.

###  Define a Visit Pattern (Lattice)  ###
woodyLattice_char <- collapse_lattice(lattice_patterns = "___o", times = 3)
woodyLattice_char
## [1] "___o___o___o"
###  Calculate the Endpoint  ###
outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # Only observe scheduled UDS
  mutate(
        udsLattice = view_by_lattice(
            use_pattern = usePatternUDS,
            lattice_pattern = woodyLattice_char
        )
    ) %>% 
    # Remove the non-protocol weeks
    mutate(
        udsLattice2 = recode_missing_visits(
            use_pattern = udsLattice,
            missing_is = "_",
            missing_becomes = ""
        )
    ) %>% 
    # Mark missing UDS as "+"
    mutate(
        udsLattice3 = recode_missing_visits(use_pattern = udsLattice2)
    ) %>% 
    # Count "+" UDS; 0 could be complete dropout or all negative
    mutate(
        woody2008_use = count_matches(
            use_pattern = udsLattice3,
            match_is = "+",
            mixed_results_are = "*",
            proportion = TRUE
        )
    ) %>% 
    mutate(Rd_woody_2008 = 1 - woody2008_use) %>% 
    select(who, Rd_woody_2008) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_woody_2008)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_woody_2008
##    <dbl> <chr>                                       <dbl>
##  1     1 ooooooooooooooo                             0    
##  2     4 -------------------o-o-o                    1    
##  3    13 ------------o-oooooooooo                    1    
##  4    17 --++*++++++-++++++-+++-                     0.333
##  5   163 -o---o---o--o+----------                    1    
##  6   210 -++++++++-+++-----------                    0    
##  7   233 *+++++++++++o++++++++++o                    0    
##  8   242 -----------------------                     1    
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o         1    
## 10  2089 ++++---+--------------o-                    0.333

Zaks, Fink, and Freedman (1972)

Definition: Number of positive UOS; missing is ignored

outcomesRed_df <- 
    outcomesRed_df %>%
  rowwise() %>% 
  # Ignore missing
    mutate(
        udsPattern = recode_missing_visits(
            use_pattern = usePatternUDS,
            missing_becomes = ""
        )
    ) %>% 
    # Count "+" UDS; 0 could be complete dropout or all negative
    mutate(
        zaks1972_use = count_matches(
            use_pattern = udsPattern,
            match_is = "+",
            mixed_results_are = "*"
        )
    ) %>% 
  # For each participant, the "abstinent" metric is the number of total weeks
  #   of study participation - the number of positive weeks
    mutate(Rd_zaks_1972 = str_length(udsPattern) - zaks1972_use) %>% 
    ungroup() %>% 
    select(who, Rd_zaks_1972) %>% 
    left_join(outcomesRed_df, ., by = "who")

outcomesRed_df %>% 
  filter(who %in% examplePeople_int) %>% 
  select(who, usePatternUDS, Rd_zaks_1972)
## # A tibble: 10 × 3
##      who usePatternUDS                       Rd_zaks_1972
##    <dbl> <chr>                                      <dbl>
##  1     1 ooooooooooooooo                              0  
##  2     4 -------------------o-o-o                    21  
##  3    13 ------------o-oooooooooo                    13  
##  4    17 --++*++++++-++++++-+++-                      5.5
##  5   163 -o---o---o--o+----------                    19  
##  6   210 -++++++++-+++-----------                    13  
##  7   233 *+++++++++++o++++++++++o                     0.5
##  8   242 -----------------------                     23  
##  9  1103 ++--oo--o-+-+--o----------o-o-oo++o         20  
## 10  2089 ++++---+--------------o-                    18

Computing Environment

Here is the information concerning the system configuration, packages, and their versions used in this computation:

## R version 4.3.2 (2023-10-31)
## Platform: x86_64-pc-linux-gnu (64-bit)
## Running under: Ubuntu 22.04.3 LTS
## 
## Matrix products: default
## BLAS:   /usr/lib/x86_64-linux-gnu/openblas-pthread/libblas.so.3 
## LAPACK: /usr/lib/x86_64-linux-gnu/openblas-pthread/libopenblasp-r0.3.20.so;  LAPACK version 3.10.0
## 
## locale:
##  [1] LC_CTYPE=C.UTF-8       LC_NUMERIC=C           LC_TIME=C.UTF-8       
##  [4] LC_COLLATE=C.UTF-8     LC_MONETARY=C.UTF-8    LC_MESSAGES=C.UTF-8   
##  [7] LC_PAPER=C.UTF-8       LC_NAME=C              LC_ADDRESS=C          
## [10] LC_TELEPHONE=C         LC_MEASUREMENT=C.UTF-8 LC_IDENTIFICATION=C   
## 
## time zone: UTC
## tzcode source: system (glibc)
## 
## attached base packages:
## [1] stats     graphics  grDevices utils     datasets  methods   base     
## 
## other attached packages:
##  [1] lubridate_1.9.3  forcats_1.0.0    stringr_1.5.1    dplyr_1.1.4     
##  [5] purrr_1.0.2      readr_2.1.4      tidyr_1.3.0      tibble_3.2.1    
##  [9] ggplot2_3.4.4    tidyverse_2.0.0  kableExtra_1.3.4 readxl_1.4.3    
## [13] CTNote_0.1.3    
## 
## loaded via a namespace (and not attached):
##  [1] generics_0.1.3    sass_0.4.8        utf8_1.2.4        xml2_1.3.6       
##  [5] stringi_1.8.3     hms_1.1.3         digest_0.6.33     magrittr_2.0.3   
##  [9] timechange_0.2.0  evaluate_0.23     grid_4.3.2        fastmap_1.1.1    
## [13] cellranger_1.1.0  jsonlite_1.8.8    httr_1.4.7        rvest_1.0.3      
## [17] fansi_1.0.6       viridisLite_0.4.2 scales_1.3.0      textshaping_0.3.7
## [21] jquerylib_0.1.4   cli_3.6.2         rlang_1.1.2       munsell_0.5.0    
## [25] withr_2.5.2       cachem_1.0.8      yaml_2.3.8        tools_4.3.2      
## [29] tzdb_0.4.0        memoise_2.0.1     colorspace_2.1-0  webshot_0.5.5    
## [33] vctrs_0.6.5       R6_2.5.1          lifecycle_1.0.4   fs_1.6.3         
## [37] ragg_1.2.7        pkgconfig_2.0.3   desc_1.4.3        pkgdown_2.0.7    
## [41] bslib_0.6.1       pillar_1.9.0      gtable_0.3.4      glue_1.6.2       
## [45] systemfonts_1.0.5 highr_0.10        tidyselect_1.2.0  xfun_0.41        
## [49] rstudioapi_0.15.0 knitr_1.45        htmltools_0.5.7   rmarkdown_2.25   
## [53] svglite_2.1.3     compiler_4.3.2

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