Identifying Valid Algorithms for Number of Lines of Anti-Neoplastic Therapy in the Danish National Patient Registry Among Patients with Advanced Ovarian, Gastric, Renal Cell, Urothelial, and Non-Small Cell Lung Cancer Attending a Danish University Hospital

Figures & data

Figure 1 Flowchart for selection of patients for the validation of lines of anti-neoplastic therapy.

Notes: Stage was defined according to the 7th Edition of the AJCC Cancer Staging Manual. In accordance with guidelines issued by the Danish Health Data Authority, we were not permitted to report counts with fewer than 5 observations. Therefore, we are not able to give more details about the reasons for exclusion in the last step of the flowchart.

Abbreviations: AJCC, American Joint Committee on Cancer; DCR, Danish Cancer Registry; DNPR, Danish National Patient Registry.

Table 1 Description of the Included Patients with Advanced Epithelial Ovarian Cancer, Gastric Adenocarcinoma, Renal Cell Carcinoma, Urothelial Cell Carcinoma, and Non-Small Cell Lung Cancer Diagnosed in Denmark 2012 to 2016

	Epithelial Ovarian Cancer (N=35)	Gastric Adenocarcinoma (N=36)	Renal Cell Carcinoma (N=36)	Urothelial Cell Carcinoma (N=36)	Non-Small Cell Lung Cancer (N=36)	All Cohorts Combined (N=179)
Year of cancer diagnosis, N (%)
2012	7 (20.0%)	7 (19.4%)	7 (19.4%)	7 (19.4%)	7 (19.4%)	35 (19.6%)
2013	8 (22.9%)	8 (22.2%)	8 (22.2%)	9 (25.0%)	8 (22.2%)	41 (22.9%)
2014	7 (20.0%)	7 (19.4%)	7 (19.4%)	7 (19.4%)	7 (19.4%)	35 (19.6%)
2015	7 (20.0%)	8 (22.2%)	8 (22.2%)	8 (22.2%)	8 (22.2%)	39 (21.8%)
2016	6 (17.1%)	6 (16.7%)	6 (16.7%)	5 (13.9%)	6 (16.7%)	29 (16.2%)
Stage at diagnosis, N (%)^a
Stage II	Not included	Not included	Not included	< 10	Not included	6 (3.4%)
Stage III	15 (42.9%)	< 10	< 10	< 5	< 15	50 (27.9%)
Stage IV	15 (42.9%)	24 (66.7%)	25 (69.4%)	20 (55.6%)	21 (58.3%)	105 (58.7%)
Undefined stage^b	5 (14.3%)	< 5	< 5	7 (19.4%)	< 5	18 (10.1%)
Female, N (%)	35 (100.0%)	10 (27.8%)	15 (41.7%)	12 (33.3%)	18 (50.0%)	90 (50.3%)
Age at diagnosis (years), Median (q1-q3)	68.3 (60.2–75.9)	66.3 (59.4–69.0)	62.8 (58.5–71.2)	68.8 (60.9–75.6)	68.5 (64.3–76.1)	67.7 (59.7–73.5)
Follow-up time (months), Mean (SD) ^c	30.0 (20.1)	17.2 (13.3)	23.3 (22.8)	28.0 (21.4)	18.2 (17.4)	23.3 (19.8)

Notes: In accordance with the data protection guidelines issued by the Danish Health Data Authority, we do not report cell counts with fewer than 5 observations. As well, the cell count may not be identifiable based on counts in the other cells; for this reason we also report “N<10” etc. in some cells. ^aStage was defined according to the 7th Edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual. ^bSome information on Tumor, Node, or Metastases codes was missing, but based on available information the patient had at least stage II (urothelial cell carcinoma)/III (epithelial ovarian cancer, gastric adenocarcinoma, renal cell carcinoma, non-small cell lung cancer). ^cTime from date of cancer diagnosis as registered in the Danish Cancer Registry until the first of the following events: death, emigration, new primary cancer, or August 1, 2018.

Abbreviations: N, numbers; q1, first quartile; q3, third quartile; SD, standard deviation.

Figure 2 Percentage agreement between the Time-based algorithm and the Drug-based algorithm, respectively, and the reference standard (medical records) for number of lines of anti-neoplastic therapy for all cancer cohorts combined.

Notes: The percentage agreement is the same for the drug-based algorithm irrespective of the number of days used in the algorithm, this occurred because all the treated patients selected for the validation study had recorded codes for specific anti-neoplastic drugs in the DNPR on all dates of administration of anti-neoplastic therapy.

Figure 3 Percentage agreement between the algorithms and the reference standard (medical records) for number of lines of anti-neoplastic therapy for patients with advanced epithelial ovarian cancer (A), gastric adenocarcinoma (B), renal cell carcinoma (C), urothelial cell carcinoma (D), and non-small cell lung cancer (E).

Table 2 Positive Predictive Values for the Number of Anti-Neoplastic Therapy Lines According to Type of Cancer and for All Cohorts Combined for the Time-Based Algorithm 45 Days (a) and the Drug-Based Algorithm 45 Days (b)

	PPV for the Number of Lines (95% CI)^a
	Epithelial Ovarian Cancer (N=35)	Gastric Adenocarcinoma (N=36)	Renal Cell Carcinoma (N=36)	Urothelial Cell Carcinoma (N=36)	Non-Small Cell Lung Cancer (N=36)	All Cohorts Combined (N=179)
a) Identify the line number according to Time-based algorithm 45 days
First line	100.0% (89.7–100.0%)	100.0% (90.3–100.0%)	100.0% (90.3–100.0%)	97.1% (87.1–99.7%)	100.0% (89.7–100.0%)	97.7% (94.7–99.2%)
Second line	78.3% (58.7–91.2%)	71.4% (45.5–89.5%)	35.3% (16.3–58.9%)	57.1% (31.9–79.7%)	78.3% (58.7–91.2%)	57.0% (46.0–67.5%)
Third line	NR	NR	NR	NR	NR	31.8% (15.5–52.6%)
b) Identify the line number according to Drug-based algorithm 45 days
First line	100.0% (89.7–100.0%)	100.0% (90.3–100.0%)	100.0% (90.3–100.0%)	97.1% (87.1–99.7%)	91.4% (78.9–97.5%)	97.7% (94.7–99.2%)
Second line	100.0% (80.5–100.0%)	92.9% (71.2–99.2%)	100.0% (59.0–100.0%)	90.0% (61.9–98.9%)	33.3% (10.4–65.2%)	86.0% (75.3–93.1%)
Third line	NR	NR	NR	NR	NR	78.3% (58.7–91.2%)

Notes: ^aThe PPV is estimated as N with the given line number both according to the algorithm and the reference standard divided by N with the given line number according to the algorithm.

Abbreviations: N, numbers; NR, not reportable (due to great uncertainty); PPV, positive predictive value.

Table 3 Positive Predictive Values for the Start Date of the Anti-Neoplastic Therapy Lines, and Duration of Anti-Neoplastic Therapy Lines According to the Time-Based Algorithm 45 Days (a) and the Drug-Based Algorithm 45 Days (b) for All Cohorts Combined

	PPV for the Start Date of the Line (95% CI)^a			Duration in Days of the Line According to the Algorithm, Median, q1-q3^b	PPV for the Duration of the Line (95% CI)^c
	±30 Days	±60 Days	±90 Days		±30 Days	±60 Days	±90 Days
a) Identify the line number according to Time-based algorithm 45 days
First line (N=175)	97.1% (93.9–98.9%)	97.1% (93.9–98.9%)	97.1% (93.9–98.9%)	111 (81–157)	65.7% (58.5–72.4%)	71.4% (64.4–77.7%)	76.0% (69.3–81.9%)
Second line (N=79)	36.7% (26.7–47.7%)	38.0% (27.9–49.0%)	41.8% (31.4–52.8%)	101 (66–164)	31.6% (22.2–42.4%)	40.5% (30.2–51.5%)	44.3% (33.7–55.3%)
Third line (N=22)	13.6% (4.0–32.1%)	18.2% (6.5–37.6%)	18.2% (6.5–37.6%)	94 (45–167)	13.6% (4.0–32.1%)	22.7% (9.2–42.9%)	31.8% (15.5–52.6%)
b) Identify the line number according to Drug-based algorithm 45 days
First line (N=175)	97.1% (93.9–98.9%)	97.1% (93.9–98.9%)	97.1% (93.9–98.9%)	133 (87–202)	86.9% (81.3–91.2%)	94.3% (90.1–97.0%)	95.4% (91.6–97.8%)
Second line (N=57)	80.7% (69.1–89.3%)	82.5% (71.1–90.6%)	82.5% (71.1–90.6%)	90 (66–144)	71.9% (59.4–82.3%)	82.5% (71.1–90.6%)	84.2% (73.2–91.9%)
Third line (N=23)	69.6% (49.3–85.2%)	69.6% (49.3–85.2%)	73.9% (53.9–88.3%)	71 (45–140)	60.9% (40.6–78.6%)	69.6% (49.3–85.2%)	69.6% (49.3–85.2%)

Notes: ^aThe PPV is estimated as N who have started the given anti-neoplastic therapy line number according to the algorithm and who have also started the given anti-neoplastic therapy line number according to the reference standard and for whom the start date of the given anti-neoplastic therapy line number according to the reference standard is within plus or minus 30/60/90 days from the start date according to the algorithm divided by N who have started the given anti-neoplastic therapy line number according to the algorithm. ^bDuration is estimated as the last date of that line minus the start date of that line. ^cThe PPV is estimated as N who have started the given anti-neoplastic therapy line number according to the algorithm and who have also started the given anti-neoplastic therapy line number according to the reference standard and for whom the duration of the given anti-neoplastic therapy line number according to the reference standard is within plus or minus 30/60/90 days from the duration according to the algorithm divided by N who have started the given anti-neoplastic therapy line number according to the algorithm.

Abbreviations: N, numbers; q1, first quartile; q3, third quartile; PPV, positive predictive value.