I have read the journal's policy and the authors of this manuscript have the following competing interests: JBG has received research grants from GSK and Hoffmann-LaRoche for antiviral resistance studies, and from Pfizer Inc. to conduct microbiological surveillance of Streptococcus pneumoniae. AJM has received research funds from GSK and Sanofi-Pasteur. MS has received research grants from Janssen Canada for respiratory virus clinical trials. DT has received research grants from GSK for influenza burden studies and payment for the development of an online course on influenza immunization from Family Physician Airways Group of Canada. All other authors report no conflicts. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Uncertainty remains regarding the magnitude of effectiveness of influenza vaccines for preventing serious outcomes, especially among young children. We estimated vaccine effectiveness (VE) against laboratory-confirmed influenza hospitalizations among children aged 6–59 months. We used the test-negative design in hospitalized children in Ontario, Canada during the 2010–11 to 2013–14 influenza seasons. We used logistic regression models adjusted for age, season, and time within season to calculate VE estimates by vaccination status (full vs. partial), age group, and influenza season. We also assessed VE incorporating prior history of influenza vaccination. We included specimens from 9,982 patient hospitalization episodes over four seasons, with 12.8% testing positive for influenza. We observed variation in VE by vaccination status, age group, and influenza season. For the four seasons combined, VE was 60% (95%CI, 44%-72%) for full vaccination and 39% (95%CI, 17%-56%) for partial vaccination. VE for full vaccination was 67% (95%CI, 48%-79%) for children aged 24–59 months, 48% (95%CI, 12%-69%) for children aged 6–23 months, 77% (95%CI, 47%-90%) for 2010–11, 59% (95%CI, 13%-81%) for 2011–12, 33% (95%CI, –18% to 62%) for 2012–13, and 72% (95%CI, 42%-86%) for 2013–14. VE in children aged 24–59 months appeared similar between those vaccinated in both the current and previous seasons and those vaccinated in the current season only, with the exception of 2012–13, when VE was lower for those vaccinated in the current season only. Influenza vaccination is effective in preventing pediatric laboratory-confirmed influenza hospitalizations during most seasons.
Rates of influenza-attributable hospitalizations are as high among young children as older adults [
In addition, the impact of repeated vaccination on VE has been a topic of recent controversy,[
The objective of this study was to evaluate influenza VE against hospitalizations for young children aged 6–59 months for the 2010–11 to 2013–14 seasons in Ontario, Canada. We also assessed the impact of repeated influenza vaccination in young children.
We studied children aged 6–59 months who were hospitalized during the 2010–11 to 2013–14 influenza seasons in Ontario. Individual-level laboratory data were collected from a network of laboratories and linked using unique encoded identifiers to health administrative data, including hospital records and physician billing claims, at the Institute for Clinical Evaluative Sciences (ICES).
We estimated VE using the test-negative design (TND) [
Ethics approval for this study was obtained from the Sunnybrook Health Sciences Centre Research Ethics Board and the Office of Research Ethics at the University of Toronto, Toronto, Canada. Written or verbal informed consent was not required from the subjects in this study, as ICES is permitted to obtain and use personal health information without patient consent for specific purposes, as outlined in Ontario’s
We included respiratory specimens tested at five hospitals and 11 public health laboratories distributed across the province. We included specimens tested using monoplex and multiplex polymerase chain reaction (PCR), viral culture, direct immunofluorescence assay (DFA), or enzyme immunoassay tests (EIA). In this dataset, 62.3% of children were tested using PCR, 22.0% with viral culture, 15.8% with DFA and 0.3% with EIA.
Hospitalizations were identified using the Canadian Institute of Health Information Discharge Abstract Database. We restricted the analysis to individuals with specimens collected within three days of hospital admission (96% of the sample) to minimize the inclusion of hospital-acquired influenza infections. We included one hospitalization with a specimen collected per individual per season. For individuals with multiple specimens collected during multiple hospitalizations within a season, we included the first hospitalization with a specimen positive for influenza (cases), or the first hospitalization if all specimens collected within the season were negative (controls).
We used physician billing claims recorded in the Ontario Health Insurance Plan (OHIP) database to ascertain influenza vaccination status. Children were classified as fully vaccinated if they had two influenza vaccination billing claims in the current season with administration dates ≥28 days apart, or one billing claim in the current season with another billing claim in any prior season, and if the administration date of the dose(s) in the current season was ≥14 days before specimen collection date. Children were classified as partially vaccinated if they received two doses in the current season with the second <28 days after the first or <14 days before specimen collection date, or if they received only one of two recommended doses in the current season (≥14 days before specimen collection date). Both trivalent (TIV) and quadrivalent (QIV) inactivated vaccines are recommended for those aged 6–23 months but only TIV products were available in Ontario during the study period. For the 2011–12 to 2013–14 seasons, live attenuated inactivated vaccines (LAIV) were preferentially recommended over inactivated vaccines for healthy children aged 24–59 months, but they were not part of the publicly funded immunization program and therefore had minimal uptake [
We used health administrative data to identify demographic characteristics, underlying health conditions (including asthma, diabetes, and cancer), and prior healthcare use, including past hospitalizations and continuity of care (defined as the percentage of primary care visits assigned to the child’s primary care provider). We used postal code of residence to assign neighbourhood income quintile (based on census-derived neighbourhood income) and rurality. We modified Feudtner et al.’s methodology [
We used logistic regression to estimate VE by comparing the odds of vaccination in the cases to the odds of vaccination in the controls. VE was calculated as (1–ORadjusted)x100%. We estimated VE for full and partial vaccination status separately.
We tested for a difference in VE between fully and partially vaccinated children by calculating the odds ratio with those partially vaccinated as our reference [
To assess the impact of repeated vaccination, we estimated VE for any vaccination in those aged 24–59 months by vaccination history using a categorical indicator variable for those vaccinated in both the current and prior seasons, the current season only, the prior season only, and neither season (i.e., four mutually exclusive groups).
We tested two main assumptions of the TND: 1) influenza testing is not associated with vaccination status; and 2) vaccination status is not associated with non-influenza respiratory viruses [
All analyses were conducted using SAS Enterprise Guide 6.1 (SAS Institute Inc., Cary, NC). All tests were two-sided and used p<0.05 as the level of statistical significance.
We included 9,982 hospitalization events during which a respiratory specimen was collected and tested for influenza for 9,547 unique children. A minority of children (4.1%) were included in more than one season. A total of 1,280 (12.8%) individuals had specimens that tested positive for influenza (range across seasons: 11.5%-14.5%). Across seasons, 1,151 (11.5%) children were classified as having received at least one influenza vaccination (range across seasons: 10.0%-13.8%), with 6.0% fully vaccinated and 5.6% partially vaccinated. Of the 882 individuals who tested positive for influenza A, 451 were subtyped, with 163 positive for A/H1N1 only, and 286 positive for A/H3N2 only. There were 402 individuals who tested positive for influenza B (including ≤5 influenza A/B coinfections); lineage information was not available. Influenza-positive children were more likely to be unvaccinated, older, reside in urban areas, and to be admitted during the peak influenza month (
Characteristic | Test-positive patients (n = 1,280) | Test-negative patients (n = 8,702) | p-value |
---|---|---|---|
Vaccination status | <.001 | ||
Fully vaccinated | 36 (2.8%) | 559 (6.4%) | |
Partially vaccinated | 45 (3.5%) | 511 (5.9%) | |
Unvaccinated | 1,199 (93.7%) | 7,632 (87.7%) | |
Influenza season | <.001 | ||
2010–11 | 369 (28.8%) | 2,168 (24.9%) | |
2011–12 | 223 (17.4%) | 1,330 (15.3%) | |
2012–13 | 359 (28.0%) | 2,681 (30.8%) | |
2013–14 | 329 (25.7%) | 2,523 (29.0%) | |
Age (months), Median (IQR) | 25 (15–41) | 19 (12–31) | <.001 |
Age group | <.001 | ||
6–23 months | 618 (48.3%) | 5,421 (62.3%) | |
24–59 months | 662 (51.7%) | 3,281 (37.7%) | |
Male sex | 754 (58.9%) | 4,971 (57.1%) | 0.23 |
Rural residence | 85 (6.6%) | 858 (9.9%) | <.001 |
Neighbourhood income quintile | 0.25 | ||
1 (lowest) | 321 (25.1%) | 2,047 (23.5%) | |
2 | 281 (22.0%) | 1,777 (20.4%) | |
3 | 253 (19.8%) | 1,741 (20.0%) | |
4 | 252 (19.7%) | 1,737 (20.0%) | |
5 (highest) | 170 (13.3%) | 1,331 (15.3%) | |
No. of outpatient visits in past year, Mean ± SD | 10.70 ± 8.45 | 10.83 ± 8.88 | 0.61 |
No. of hospitalizations in past year, Mean ± SD | 0.83 ± 1.78 | 0.78 ± 1.43 | 0.28 |
Continuity of care, Mean ± SD | 59.01 ± 27.89 | 62.86 ± 27.87 | <.001 |
Risk factors for influenza complications | |||
Any complex chronic condition | 344 (26.9%) | 2,245 (25.8%) | 0.41 |
Cancer | 33 (2.6%) | 188 (2.2%) | 0.34 |
Diabetes | ≤5 (≤1.0%) | 32 (0.4%) | 0.61 |
Asthma | 392 (30.6%) | 3,280 (37.7%) | <.001 |
Preterm birth | 185 (14.5%) | 1,452 (16.7%) | 0.02 |
Low birthweight | 179 (14.0%) | 1,253 (14.4%) | 0.22 |
Month of influenza test |
<.001 | ||
2 months before | ≤5 (≤0.4%) |
48 (0.6%) | |
1 month before | 90 (7.0%) | 1,037 (11.9%) | |
Peak month | 413 (32.3%) | 1,832 (21.1%) | |
1 month after | 420 (32.8%) | 1,701 (19.5%) | |
2 months after | 152 (11.9%) | 1,680 (19.3%) | |
3 months after | 130 (10.2%) | 1,324 (15.2%) | |
4 months after | 60 (4.7%) | 763 (8.8%) | |
5 months after | ≤15 (≤1.2%) | 317 (3.6%) |
aTime relative to peak month of influenza circulation.
bSome cells suppressed because of small cell size (direct or by inference), which cannot be reported as per privacy regulations.
IQR, interquartile range; SD, standard deviation
Characteristic | Fully vaccinated (n = 595) | Partially vaccinated (n = 556) | Unvaccinated (n = 8,831) | p-value |
---|---|---|---|---|
Influenza season | <.001 | |||
2010–11 | 122 (20.5%) | 131 (23.6%) | 2,284 (25.9%) | |
2011–12 | 102 (17.1%) | 87 (15.6%) | 1,364 (15.4%) | |
2012–13 | 169 (28.4%) | 147 (26.4%) | 2,724 (30.8%) | |
2013–14 | 202 (33.9%) | 191 (34.4%) | 2,459 (27.8%) | |
Age (months), Median (IQR) | 25 (16–40) | 17 (12–26) | 20 (12–33) | <.001 |
Age group | <.001 | |||
6–23 months | 279 (46.9%) | 402 (72.3%) | 5,358 (60.7%) | |
24–59 months | 316 (53.1%) | 154 (27.7%) | 3,473 (39.3%) | |
Male sex | 345 (58.0%) | 319 (57.4%) | 5,061 (57.3%) | 0.95 |
Rural residence | 30 (5.0%) | 38 (6.8%) | 875 (9.9%) | <.001 |
Neighbourhood income quintile | ||||
1 (lowest) | 118 (19.8%) | 110 (19.8%) | 2,140 (24.2%) | <.001 |
2 | 105 (17.6%) | 113 (20.3%) | 1,840 (20.8%) | |
3 | 126 (21.2%) | 105 (18.9%) | 1,763 (20.0%) | |
4 | 132 (22.2%) | 116 (20.9%) | 1,741 (19.7%) | |
5 (highest) | 114 (19.2%) | 111 (20.0%) | 1,276 (14.4%) | |
No. of outpatient visits in past year, Mean ± SD | 14.44 ± 9.47 | 15.32 ± 11.25 | 10.29 ± 8.47 | <.001 |
No. of hospitalizations in past year, Mean ± SD | 0.88 ± 1.59 | 1.06 ± 1.98 | 0.76 ± 1.43 | <.001 |
Continuity of care, Mean ± SD | 61.34 ± 26.80 | 60.80 ± 27.28 | 62.53 ± 28.01 | 0.24 |
Risk factors for influenza complications | ||||
Any complex chronic condition | 247 (41.5%) | 193 (34.7%) | 2,149 (24.3%) | <.001 |
Cancer | 9 (1.5%) | 13 (2.3%) | 199 (2.3%) | 0.48 |
Diabetes | 6 (1.0%) | ≤5 (≤1.0%) | 28 (0.3%) | 0.03 |
Asthma | 268 (45.0%) | 223 (40.1%) | 3,181 (36.0%) | <.001 |
Preterm birth | 140 (23.5%) | 112 (20.1%) | 1,385 (15.7%) | <.001 |
Low birthweight | 135 (22.7%) | 102 (18.3%) | 1,195 (13.5%) | <.001 |
Month of influenza test |
<.001 | |||
2 months before | ≤5 (≤0.8%) |
≤5 (≤0.9%) | 43 (0.5%) | |
1 month before | 51 (8.6%) | 54 (9.7%) | 1,022 (11.6%) | |
Peak | 99 (16.6%) | 133 (23.9%) | 2,013 (22.8%) | |
1 month after | 109 (18.3%) | 112 (20.1%) | 1,900 (21.5%) | |
2 months after | 132 (22.2%) | 114 (20.5%) | 1,586 (18.0%) | |
3 months after | 106 (17.8%) | 79 (14.2%) | 1,269 (14.4%) | |
4 months after | 69 (11.6%) | 41 (7.4%) | 713 (8.1%) | |
5 months after | ≤30 (≤5.0%) | ≤20 (≤3.6%) | 285 (3.2%) |
aTime relative to peak month of influenza circulation.
bSome cells suppressed because of small cell size (direct or by inference), which cannot be reported as per privacy regulations.
IQR, interquartile range; SD, standard deviation.
The overall adjusted VE against laboratory-confirmed influenza hospitalization was 60.4% (95%CI, 44.0%-72.1%) for fully vaccinated children and 39.2% (95%CI, 16.6%-55.6%) for partially vaccinated children (
Analysis (cases/total) | Fully vaccinated | Partially vaccinated | Any vaccination |
---|---|---|---|
Overall (1280/9982) | 60.4 (44.0, 72.1) | 39.2 (16.6, 55.6) | 50.8 (37.6, 61.2) |
2010–11 (369/2537) | 77.2 (46.9, 90.2) | 69.1 (32.5, 85.9) | 73.4 (52.5, 85.1) |
2011–12 (223/1553) | 59.0 (12.8, 80.8) | 45.3 (−22.5, 75.5) | 53.5 (18.5, 73.4) |
2012–13 (359/3040) | 33.1 (−18.4, 62.2) | −16.6 (−95.7, 30.6) | 11.6 (−30.7, 40.3) |
2013–14 (329/2852) | 71.9 (42.1, 86.4) | 47.0 (5.2, 70.4) | 60.3 (37.1, 74.9) |
Influenza A (882/9584) | 60.7 (38.9, 74.7) | 50.5 (26.0, 66.9) | 55.6 (40.0, 76.2) |
A/H1N1 (164/8866) | 82.1 (27.3, 95.6) | 31.5 (−41.4, 66.8) | 56.2 (16.3, 77.1) |
A/H3N2 (287/8989) | 53.3 (3.5, 77.4) | 69.6 (25.2, 87.7) | 61.3 (31.6, 78.1) |
Influenza B (402/9104) |
58.0 (28.3, 75.4) | 11.8 (−44.8, 46.2) | 40.8 (14.3, 59.2) |
6–23 months (618/6039) | 47.6 (11.9, 68.8) | 27.6 (−5.0, 50.0) | 35.6 (12.4, 52.6) |
24–59 months (662/3943) | 67.1 (47.5, 79.4) | 58.8 (24.7, 77.5) | 64.4 (48.2, 75.5) |
Females (526/4257) | 63.8 (35.7, 79.6) | 49.3 (13.1, 70.4) | 57.2 (36.2, 71.2) |
Males (754/5725) | 58.9 (36.2, 73.5) | 32.8 (0.5, 54.6) | 47.1 (28.8, 60.7) |
Yes (344/2589) | 62.9 (36.2, 78.4) | 45.1 (6.5, 67.8) | 55.4 (34.2, 69.8) |
No (936/7393) | 57.7 (33.3, 73.1) | 36.8 (6.4, 57.4) | 47.6 (29.1, 61.2) |
Yes (392/3672) | 57.1 (26.1, 75.1) | 23.0 (−28.0, 53.7) | 43.3 (17.1, 61.2) |
No (888/6310) | 60.9 (38.4, 75.2) | 45.5 (18.2, 63.7) | 53.5 (36.7, 65.8) |
Yes (413/2245) | 68.4 (33.8, 84.9) | 44.4 (1.6, 68.6) | 56.2 (30.8, 72.3) |
No (867/7737) | 59.8 (40.6, 72.8) | 36.8 (8.1, 56.6) | 50.2 (34.4, 62.6) |
Restricted to ARI-coded hospitalizations (1183/8760) | 59.9 (42.6, 72.0) | 34.4 (9.1, 52.6) | 48.6 (34.4, 59.8) |
Included term for any comorbidity in model (1280/9982) | 58.6 (41.4, 70.8) | 37.0 (13.6, 54.1) | 48.8 (35.0, 59.6) |
Other respiratory virus positive (1600/3927) |
15.2 (−12.1, 35.9) | 16.2 (−10.5, 36.5) | 15.8 (−3.2, 31.2) |
an = 24 specimens were not tested for influenza B.
bRestricted to those who were tested for respiratory syncytial virus, parainfluenza virus, adenovirus, and human metapneumovirus.
VE estimates were unchanged when we restricted to children with specimens collected during an ARI-coded hospitalization and when we included any comorbidity in our model (
When examining the influence of prior vaccinations status in children aged 24–59 months, VE estimates for those vaccinated in the current season only versus two sequential seasons were similar (
Vaccine effectiveness estimates are presented for children vaccinated in the current and prior season (circles), the current season only (squares), and the prior season only (triangles).
For patients who had an ARI code associated with their hospitalization, 46% were tested for influenza. Among these ARI-coded hospitalizations, 12.6% of patients who were tested for influenza were vaccinated, compared to 12.4% of patients who were not tested for influenza (p = 0.56), confirming the absence of an association between influenza testing and vaccination status. Using the 95% of our sample that were tested for at least one other respiratory virus, 32.2% of unvaccinated children tested positive for another respiratory virus compared to 32.1% of children with any vaccination (p = 0.96), confirming the absence of an association between vaccination status and non-influenza respiratory viruses. This assumption held for fully, partially, and unvaccinated children, as well as between age groups and across seasons.
During the 2010–11 to 2013–14 influenza seasons, vaccination reduced the risk of laboratory-confirmed influenza hospitalizations by 60% for fully vaccinated children aged 6–59 months and by 39% for partially vaccinated children in Ontario. We observed statistically significant VE for fully vaccinated children for all seasons except 2012–13, and for all subgroups except those infected by A/H3N2. We did not detect statistically significant VE for partially vaccinated children during the 2011–12 and 2012–13 seasons, or for those aged 6–23 months, those with asthma, and those with influenza A/H1N1 or B infections.
Our estimates are generally consistent with previous studies that have assessed VE among young children for these four seasons (
Influenza season | Author, Year | Setting | Location | Age group | Adjusted VE (95% CI) | Ontario VE |
---|---|---|---|---|---|---|
Cowling, 2014 [ |
Inpatient | Hong Kong | 6mo-17 years | 84 (44, 96) | ||
Chung, 2016 [ |
Outpatient | USA (Flu VE Network) | 2–8 years | 70 (53, 81) | ||
Kafatos, 2013 [ |
Outpatient | United Kingdom | <5 years | 72 (12, 91) | ||
Englund, 2013 [ |
Outpatient | Germany | 0–14 years | 84 (24, 97) | ||
Turner, 2014 [ |
Inpatient | New Zealand | 6mo-5 years | 75 (–100, 97) | ||
Cowling, 2014 [ |
Inpatient | Hong Kong | 6mo-17 years | 51 (10, 74) | ||
Menniti-Ipolito, 2014 [ |
ED/Inpatient | Italy | 6mo-16 years | 41 (–126, 84) | ||
Chung, 2016 [ |
Outpatient | USA (Flu VE Network) | 2–8 years | 51 (22, 69) | ||
Skowronski, 2014 [ |
Outpatient | Canada | 1–19 years | 64 (23, 84) | ||
Pebody, 2013 [ |
Outpatient | United Kingdom | <5 years | 52 (–446, 96) | ||
Kissling, 2013 [ |
Outpatient | Europe (I-MOVE) | <15 years | 19 (–170, 76) | ||
Wang, 2016 [ |
Outpatient/ED | China | 6–59 months | 67 (41, 82) | ||
Turner, 2014 [ |
Inpatient | New Zealand | 6mo-17 years | 78 (2, 95) | ||
Cowling, 2014 [ |
Inpatient | Hong Kong | 6mo-17 years | 81 (37, 94) | ||
Menniti-Ipolito, 2014 [ |
ED/Inpatient | Italy | 6mo-16 years | 26 (–153, 78) | ||
Chung, 2016 [ |
Outpatient | USA (Flu VE Network) | 2–8 years | 46 (27, 60) | ||
Kissling, 2014 [ |
Outpatient | Europe (I-MOVE) | 0–14 years | 36 (–41, 71) |
||
Fu, 2015 [ |
Outpatient | China | 8mo-6 years | 67 (58, 74) |
||
Skowronski [ |
Outpatient | Canada | 1–19 years | 87 (65, 95) | ||
Ohmit, 2015[ |
Outpatient | USA (HIVE) | <9 years | –4 (–110, 49) | ||
Blyth, 2016 [ |
Inpatient | Australia | 6mo-16 years | 56 (12, 78) | ||
Pierse, 2016 [ |
Inpatient | New Zealand | 6mo-17 years | –30 (–212, 46) | ||
Chung, 2016 [ |
Outpatient | USA (Flu VE Network) | 2–8 years | 61 (34, 77) | ||
Skowronski, 2015 [ |
Outpatient | Canada | 1–19 years | 77 (47, 90) | ||
Valenciano, 2015 [ |
Outpatient | Europe (I-MOVE) | 0–14 years | 64 (–86, 93) | ||
Ohmit, 2016 [ |
Outpatient | USA (HIVE) | <9 years | 68 (10, 88) |
*Estimate is for H3N2 only;
†Estimate is for H1N1 only.
ED, emergency department
In contrast, our estimate for the 2012–13 season was consistent with some estimates (that may have included outpatients and/or older children) from USA and Europe [
Given the interest in examining whether influenza vaccination impacts severity of infection, we compared the estimates from our inpatient study to other Canadian outpatient estimates (for children aged 1–19 years) [
We found higher VE against A/H3N2 in partially vaccinated children relative to those fully vaccinated, which is consistent with previous work [
Among children aged 24–59 months, we found no difference in VE between those vaccinated in the current season only compared to those vaccinated in both prior and current seasons. However, we were limited by our sample size from evaluating the impact of repeated vaccination by subtype. This analysis could also only consider vaccination in two consecutive seasons rather than serial vaccination, although the number of vaccines in this age group would be limited. Our results may not generalize to older individuals with longer histories of both influenza and influenza vaccine exposure.
Our study has several strengths. We were able to test some of the assumptions that are routinely mentioned in test-negative studies but never evaluated. Specifically, we confirmed that vaccination status was not associated with influenza testing and that influenza vaccination was not associated with testing positive for other respiratory viruses. Pooling data across several years allowed for the evaluation of VE in selected subgroups of interest, and the nature of the vaccination data permitted evaluation of the impact of repeated vaccination in a population with limited previous vaccine exposure. The size of our study population was enhanced by including numerous types of high-specificity laboratory tests. While values for sensitivity and specificity may vary by testing method, in TND studies with laboratory-confirmed outcomes, specificity is more important in terms of bias [
This study had several limitations. Symptom onset date was only available for the minority (16%) of specimens, but since children shed higher levels of virus for longer periods of time and we restricted to those tested within three days of hospital admission, absence of symptom onset date is less likely to be an issue in this age group [
Our study demonstrates VE against laboratory-confirmed influenza hospitalizations for children aged 6–59 months. Despite variation across subgroups, we observed substantial protection for vaccinated children, particularly if fully vaccinated. These results support current recommendations to promote vaccination in this high-risk group.
This study was supported by the Institute for Clinical Evaluative Sciences (ICES) and Public Health Ontario (PHO), which are funded by annual grants from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results, and conclusions reported in this paper are those of the authors and are independent from the funding sources. Parts of this material are based on data and information compiled and provided by the Canadian Institute of Health Information (CIHI) and by Cancer Care Ontario (CCO). However, the analyses, conclusions, opinions, and statement expressed herein are those of the authors, and not necessarily those of CIHI or CCO. No endorsement by ICES, PHO, MOHLTC, CIHI, or CCO is intended or should be inferred.
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