we conducted a population - based , secular trend study of women with newly diagnosed hgsc from january 1 , 1997 , through december 31 , 2011 , using linked health care databases in ontario , canada . analysis was limited up to 2011 , because this represented a time point prior to the widespread launch of parp inhibitor trials in our region . in the province of ontario , local health integration networks are responsible for regional health care administration and funding ; the province is divided into 14 such geographically defined administrative health regions . based on the 2011 census , ontario has approximately 6.58 million female residents older than 18 years . all ontario residents are eligible to receive universal access to hospital care and physician services . we conducted this study in accordance with a prespecified protocol that was approved by the institutional review board at sunnybrook health sciences centre , toronto , ontario , canada . this study used datasets that were linked using unique encoded identifiers and analyzed at the institute for clinical evaluative sciences ( ices ) . our report conforms to guidelines for observational studies.20 we used records from 6 linked databases to identify patient characteristics , covariate information , and outcome data : ( 1 ) registered persons database , which contains demographic and vital statistics information on all beneficiaries of the single - payer , publicly funded health insurer in ontario ; ( 2 ) ontario health insurance plan ( ohip ) , which tracks all fee - for - service health claims for inpatient and outpatient physician services ; ( 3 ) ontario cancer registry ( ocr ) , which maintains records on diagnoses of invasive cancer ; ( 4 ) canadian institute for health information ( cihi ) discharge abstract database and same - day surgery database , which contain information about all discharges and procedures conducted during admission from all acute care facilities and hospital - based same - day surgery units ; ( 5 ) ices physician database , which allows for identification of physician specialty ; ( 6 ) the yearly ontario intercensal and postcensal population estimates ( intellihealth ontario ) , which was used to identify population estimates of adult women over the study period.21 in addition to the ices physician database , we utilized the methodology of elit et al22 to identify gynecologic oncologists in the province of ontario . ontario health insurance plan billing codes were used to identify genetics consultations . to determine patient comorbidity , we utilized the john hopkins adjusted disease groupings ( adgs).23 to derive the cohort , all women 18 years or older with a diagnosis of hgsc were identified using the ocr . to separate the carcinomas from borderline and benign serous tumors patients were excluded if they were coded as male , had a missing sex value , were older than 105 years old at time of diagnosis , had a recorded death preceding diagnosis , or were not a resident of ontario at time of diagnosis . in the event where more than 1 record was identified , we restricted to the first date of diagnosis . population incidence rates were calculated per study year ( number of incident hgsc patients divided by the year - specific estimated adult female population in ontario ) . we used a retrospective period of 5 years to identify genetics consultations occurring prior to diagnosis and an additional 2-year period after diagnosis . ascertainment of a genetics consultation per patient was therefore a composite of a 5-year look - back and 2-year follow - up , until the study endpoint of december 31 , 2013 . a genetics consultation was identified through a billing claim by a medical geneticist . in the province of ontario , genetics consultations can occur with a medical geneticist , genetics counselor , or a combination of both providers , depending on the location of the genetics clinic . when a patient has a consultation with a genetics counselor only , no billing claims are made , and the cost of this service is paid for through the global budget of the hospital where the genetics counselor is employed . for patients attending genetics clinics operating in this way , therefore , the referral rates might not be captured using our defined methodology . to address this issue , we surveyed all of the cancer genetics clinics within the province to gauge our ability to universally capture the utilization of billing claims for the provision of genetics consultations , including when the patient was seen by a genetics counselor ( panabaker k , personal communication , february 3 , 2016 ) . we performed a secular trend ( time trend ) analysis using the cochran - armitage test for trend over the 15-year period . a multivariable analysis was undertaken using logistic regression to identify predictors of genetics consultation using a restricted dataset of patients treated in centers where genetics consultation billings were universally captured in ohip . predictors included patient age , adg score , surgeon specialty ( gynecologic oncology , obstetrics / gynecology , or other ) , local health integration network of residence , rural / urban status , history of breast cancer , neighborhood income quintile , and era of diagnosis . predictors were assessed for colinearity , and where substantial collinearity is observed , the investigators made the decision to exclude 1 factor or combine the dependent factors . model results are expressed as odds ratios ( ors ) and 95% confidence intervals ( 95% cis ) . we performed all hypothesis tests using a 2-sided test and interpreted a p < 0.05 as statistically significant . all statistical analyses were conducted with sas for unix version 9.2 ( sas institute , cary , nc ) . we conducted a population - based , secular trend study of women with newly diagnosed hgsc from january 1 , 1997 , through december 31 , 2011 , using linked health care databases in ontario , canada . analysis was limited up to 2011 , because this represented a time point prior to the widespread launch of parp inhibitor trials in our region . in the province of ontario , local health integration networks are responsible for regional health care administration and funding ; the province is divided into 14 such geographically defined administrative health regions . based on the 2011 census , ontario has approximately 6.58 million female residents older than 18 years . all ontario residents are eligible to receive universal access to hospital care and physician services . we conducted this study in accordance with a prespecified protocol that was approved by the institutional review board at sunnybrook health sciences centre , toronto , ontario , canada . this study used datasets that were linked using unique encoded identifiers and analyzed at the institute for clinical evaluative sciences ( ices ) . we used records from 6 linked databases to identify patient characteristics , covariate information , and outcome data : ( 1 ) registered persons database , which contains demographic and vital statistics information on all beneficiaries of the single - payer , publicly funded health insurer in ontario ; ( 2 ) ontario health insurance plan ( ohip ) , which tracks all fee - for - service health claims for inpatient and outpatient physician services ; ( 3 ) ontario cancer registry ( ocr ) , which maintains records on diagnoses of invasive cancer ; ( 4 ) canadian institute for health information ( cihi ) discharge abstract database and same - day surgery database , which contain information about all discharges and procedures conducted during admission from all acute care facilities and hospital - based same - day surgery units ; ( 5 ) ices physician database , which allows for identification of physician specialty ; ( 6 ) the yearly ontario intercensal and postcensal population estimates ( intellihealth ontario ) , which was used to identify population estimates of adult women over the study period.21 in addition to the ices physician database , we utilized the methodology of elit et al22 to identify gynecologic oncologists in the province of ontario . ontario health insurance plan billing codes were used to identify genetics consultations . to determine patient comorbidity to derive the cohort , all women 18 years or older with a diagnosis of hgsc were identified using the ocr . to separate the carcinomas from borderline and benign serous tumors patients were excluded if they were coded as male , had a missing sex value , were older than 105 years old at time of diagnosis , had a recorded death preceding diagnosis , or were not a resident of ontario at time of diagnosis . in the event where more than 1 record was identified population incidence rates were calculated per study year ( number of incident hgsc patients divided by the year - specific estimated adult female population in ontario ) . we used a retrospective period of 5 years to identify genetics consultations occurring prior to diagnosis and an additional 2-year period after diagnosis . ascertainment of a genetics consultation per patient was therefore a composite of a 5-year look - back and 2-year follow - up , until the study endpoint of december 31 , 2013 . a genetics consultation was identified through a billing claim by a medical geneticist . in the province of ontario , genetics consultations can occur with a medical geneticist , genetics counselor , or a combination of both providers , depending on the location of the genetics clinic . when a patient has a consultation with a genetics counselor only , no billing claims are made , and the cost of this service is paid for through the global budget of the hospital where the genetics counselor is employed . for patients attending genetics clinics operating in this way , therefore , the referral rates might not be captured using our defined methodology . to address this issue , we surveyed all of the cancer genetics clinics within the province to gauge our ability to universally capture the utilization of billing claims for the provision of genetics consultations , including when the patient was seen by a genetics counselor ( panabaker k , personal communication , february 3 , 2016 ) . we performed a secular trend ( time trend ) analysis using the cochran - armitage test for trend over the 15-year period . a multivariable analysis was undertaken using logistic regression to identify predictors of genetics consultation using a restricted dataset of patients treated in centers where genetics consultation billings were universally captured in ohip . predictors included patient age , adg score , surgeon specialty ( gynecologic oncology , obstetrics / gynecology , or other ) , local health integration network of residence , rural / urban status , history of breast cancer , neighborhood income quintile , and era of diagnosis . predictors were assessed for colinearity , and where substantial collinearity is observed , the investigators made the decision to exclude 1 factor or combine the dependent factors . model results are expressed as odds ratios ( ors ) and 95% confidence intervals ( 95% cis ) . we performed all hypothesis tests using a 2-sided test and interpreted a p < 0.05 as statistically significant . all statistical analyses were conducted with sas for unix version 9.2 ( sas institute , cary , nc ) . a total of 5419 patients with a diagnosis for hgsc between 1997 and 2011 were identified from the ocr . following exclusions , 5412 remained for analysis . baseline characteristics are outlined in table 1 , with the study period divided into 5 eras ( 19971999 , 20002002 , 20032005 , 20062008 , 20092011 ) . the mean age at diagnosis across all years was 62 years , with 47.4% of patients having received a diagnosis between ages 45 and 64 years . comorbidities as assessed using the adg were consistent across groupings over the entire time period . diagnosis did not discriminate across income quintiles ; however , there was a trend toward hgsc diagnosis ( 22.4% ) in the highest - income quintile ( p = 0.057 ) . reflecting population distribution in ontario , the majority of patients hailed from urban residences ( 86.6% ) . the population incidence of hgsc increased across the study period , from 6.82 per 100,000 in 19971999 to 8.28 per 100,000 adult women in 20092011 ( table 2 ) . a diagnosis of breast cancer preceded the hgsc diagnosis in 5.7% of patients . for patients with a diagnosis of hgsc , the mean number of hospitalizations decreased from 6.68 in 19971999 to 3.84 in 20092011 ( p < 0.001 ) . an average of 30.9% of patients died within 2 years of hgsc diagnosis , and this did not change over the study time period ( p = 0.068 ) . over the study time period , genetics consultations to a medical geneticist increased from 3.2% to 13.3% between 1997 and 2011 ( p < 0.001 ) , with 7.72% of all patients seeing a geneticist ( fig . characteristics of patients with high - grade serous ovarian carcinoma in ontario , 19972011 consultation characteristics of patients with a diagnosis of hgsc in ontario , 19972011 rate of genetics consultation . in a subgroup of patients where universal ohip billing for genetics consultation was confirmed , 156 of the 1187 patients with hgsc ( 13% ) underwent genetics consultation during the study time period . factors shown to be predictive of consultation included history of breast cancer ( or , 3.56 ; 95% ci , 1.876.78 ) and era of diagnosis ( 20092011 vs 19971999 ; or , 10.59 ; 95% ci , 5.0222.32 ) . advancing age was predictive of a lower likelihood of consultation ( or , 0.95 ; 95% ci , 0.940.97 for each year ) . rural habitation , income quintile , patient comorbidity , and surgeon specialty did not influence referral rates for genetics consultation . our analysis shows a positive increase in the provincial rate of genetics consultation since the late 1990s , peaking at 13.3% in 2011 . unfortunately , the rate of consultation was lower than the previously reported 32% and 23% at 2 individual tertiary care centers in the province.18,19 in a restricted dataset where genetics counseling and genetic testing services could more reliably be ascertained using ohip billings , only 13% of patients with a diagnosis of hgsc completed a genetics consultation within 2 years of diagnosis . predictors of consultation in this subset of women included later era of diagnosis , a personal history of breast cancer , and younger age at diagnosis . our study has some limitations . with our methodology , it was not possible to capture those women who were referred to cancer genetics but never attended a cancer genetics appointment ( i.e. furthermore , we were unable to capture the percentage of women seen by cancer genetics who pursued brca1/2 testing , nor could we ascertain the final test result in those patients who consented to have testing . we do know , however , from other published reports that women with hgsc who are referred for genetics counseling and genetic testing will accept brca1/2 gene analysis 86% to 100% of the time.18,19,24,25 furthermore , for women with hgsc who have brca1/2 gene analysis in the province of ontario , 32% were found to have a brca1 or brca2 gene mutation.19 finally , because of the administrative nature of our data , predictors of referral such as positive family history or documented genetics discussion were not available for comparison to previous studies . despite an increase in frequency toward genetics consultation over the study time period , our analysis shows that the majority of women with hgsc in ontario are not seen for cancer genetics consultation . predictors of consultation in our study included later era of diagnosis , a prior personal history of breast cancer , and younger age . the latter 2 factors show tendencies among physicians to refer patients with traditional risk factors for a familial cancer syndrome . the increasing consultation rate across eras suggests increasing awareness by physicians of the association between hgsc and brca1/2 mutations . we saw a trend toward no genetics consultation in patients with hgsc who never underwent surgery . patients with hgsc undergo aggressive surgical debulking procedures and intensive chemotherapy regimens . despite these efforts , prognosis overall for the disease is poor , as shown by a 30.9% mortality within the first 2 years of diagnosis in our cohort . absence of referral , as seen in the study of bell et al , suggests that with increasing acuity or complexity of the patient s condition a genetics consultation may lose priority.18 another potential barrier to consultation is the shared care for patients with hgsc that can exist in the province of ontario , whereby patients return closer to home to receive chemotherapy in a center separate from where they received their surgical care . with no clear direction as to which care provider is responsible for making the referral to genetics , patients risk missing out on this important opportunity for themselves and their families . in ontario , surgical care for patients with hgsc is highly concentrated in academic centers , in the hands of gynecologic oncologists.26 this centralization of care may provide an opportunity for assignment of responsibility for cancer genetics referrals to the gynecologic oncology team . furthermore , as recognition of the link between primary peritoneal , fallopian tube , and serous ovarian carcinoma has broadened over time , potentially some of the cases diagnosed as primary peritoneal or fallopian tube serous carcinomas may not have been referred because of a lack of recognition of this association . while care of hgsc patients is concentrated in academic centers , the model for referring patients and the process whereby patients are seen in genetics clinics are unique to each individual cancer center . proposed solutions to the low attendance of hgsc patients to cancer genetics clinics have included adding a provision to the synoptic pathology report that outlines the cancer care ontario recommendation for referral of all hgsc patients , as well as embedding an individual from cancer genetics into the multidisciplinary tumor board process.19 in addition , a role for testing of hgsc tumors for brca mutations has been suggested.2730 tumor testing will not , however , differentiate germline from somatic mutations . prior to the widespread application of tumor testing , germline mutation testing must be maximized . to address the low genetics consultation rate within the london regional cancer program , the genetics referral process for patients with hgsc was altered in 2015 from an  opt - in  to an  opt - out  process . each month , the pathology department generates a list of all new hgsc patients from the synoptic pathology report and forwards this list directly to the cancer genetics clinic . at a point 2 months from the surgery date , the patient is sent a letter acknowledging their cancer genetics referral by their surgeon , including an appointment date for a genetics consultation to discuss genetic testing . this 2-month lag allows ample time for the physician to see the patient postoperatively , discuss the diagnosis and future plans for treatment , and , if not already done , introduce the idea of genetic testing . at this first postoperative appointment , patients with a diagnosis of hgsc are provided with an information letter outlining the association between brca1/2 gene mutations and hgsc . in the first year of implementation of this opt - out strategy , 77% of patients with hgsc at the london regional cancer program completed genetics consultation.31 as of 2012 , 97.5% of hospitals in ontario utilized synoptic pathology reporting , making this a feasible referral process for all tertiary care centers in the province.32 this study represents the real - world experience of women in the province of ontario with a diagnosis of hgsc . the low consultation rates , as ascertained in our restricted dataset , suggest that a large gap exists between cancer care ontario s intention with the expansion of genetic testing in 2001 and the practice patterns in the province of ontario . improvements in pathways to cancer genetics consultation are required to maximize the benefits of brca1/2 gene analysis .
objectivein 2001 , the province of ontario expanded cancer genetic testing eligibility to include all women with high - grade serous ovarian carcinoma ( hgsc ) of the ovary , fallopian tube , and peritoneum . 
 the aim of this study was to determine the proportion of women who attended genetics counseling for consideration of brca1/2 gene analysis . 
 we also sought to examine if regional differences in consultation rate exist across administrative health regions in the province of ontario.methodswe identified all women with a pathological diagnosis of hgsc in the province of ontario between 1997 until 2011 . 
 our primary outcome was the 2-year rate of genetics consultation following a diagnosis of hgsc . 
 we compared consultation rates over time and geographical regions and applied multiple logistic regression to identify predictors of genetics consultation.resultsof the 5412 women with a diagnosis of hgsc over the study period , 6.6% were seen for genetics consultation within 2 years of diagnosis . 
 factors predictive of genetics consultation included history of breast cancer ( odds ratio [ or ] , 3.56 ; 95% confidence interval [ ci ] , 1.876.78 ) , era of diagnosis ( 20092011 vs 19972000 ; or , 10.59 ; 95% ci , 5.0222.33 ) , and younger age at diagnosis ( or , 0.95 ; 95% ci , 0.940.97 for each additional year ) . 
 no regional differences in consultation rate were seen.conclusionsdespite an increasing rate across eras , a small proportion of women with hgsc undergo genetics consultation . 
 efforts are required to increase cancer genetics consultation in patients with hgsc in the province of ontario .