Scott Gavura

Association of hospital and physician case volumes with cardiac monitoring and cardiotoxicity during adjuvant trastuzumab treatment for breast cancer: a retrospective cohort study

BACKGROUND Adjuvant trastuzumab is the standard of care for patients with HER2 overexpressing breast cancer, but use of trastuzumab may lead to cardiotoxicity. Our goal was to evaluate the relationship between hospital and physician case volume and cardiac outcomes in this population. METHODS In this retrospective cohort study, we identified all female patients in Ontario with a breast cancer diagnosis in 2003-2009 who underwent treatment with trastuzumab through a provincial drug-funding program and linked these patients to administrative databases to ascertain patient demographics, treating hospital and physician characteristics, admissions to hospital, cardiac risk factors, cardiac imaging and comorbidities. Insufficient cardiac monitoring was defined as per the Canadian Trastuzumab Working Group guideline. Cardiotoxicity was defined as receiving fewer than 16 of 18 doses of trastuzumab because of heart failure admission, heart failure diagnosis or discontinuation of the drug after cardiac imaging. We constructed hierarchical multivariable logistic regression models to evaluate the effect of annual hospital volume, cumulative physician volume and treatment period on cardiac monitoring and cardiotoxicity. RESULTS Of 3777 women treated by 214 oncologists at 68 hospitals, 918 (24.3%) had insufficient cardiac monitoring and cardiotoxicity developed in 640 (16.9%). Cardiotoxicity occurred in 389 (42.4%) and 251 (8.8%) patients in the insufficient- and sufficient-monitoring groups, respectively. Higher annual hospital and cumulative physician volumes, and more recent calendar period, were all independent predictors for decreased cardiotoxicity. Adjustment for rates of cardiac monitoring annulled the relationships between case volume and cardiotoxicity. INTERPRETATION Greater hospital and physician case volumes are associated with reduced rates of trastuzumab-related cardiotoxicity, most likely because of better cardiac monitoring at higher volume centres.

Impact of physician and center case volume on the adequacy of cardiac monitoring during adjuvant trastuzumab in breast cancer.

128 Background: A recent study suggests that cardiotoxicity from adjuvant trastuzumab (T-mab) is associated with inadequate cardiac monitoring (Ng et al. SABCS 2012). Few studies have examined the impact of centre or physician (MD) case volume (vol) on the quality of care in systemic therapy, including the adequacy of cardiac monitoring during T-mab treatment. METHODS All breast cancer patients treated with adjuvant T-mab in Ontario between 2003-2009 were identified through a provincial drug funding program. Patient demographics, hospitalizations, cardiac risk factors, cardiac imaging, comorbidities, treatment centres and MDs were ascertained. Annual case vol was calculated as the number of patients treated per year with adjuvant T-mab by each MD and centre. Cumulative case vol was calculated as the total number of patients treated with adjuvant T-mab. Centre and MD vol were divided into terciles (T1, T2 and T3) by the year of diagnosis. Inadequate cardiac monitoring was defined as per recent guidelines and per Ng et al. Hierarchical multivariable logistic regression models were constructed to examine factors associated with inadequate cardiac monitoring. RESULTS Our cohort consisted of 3,777 patients, 214 MDs and 68 centres. Of the total patients, 16.5% were over age 65; 30.3%, 9.4%, and 1.2% had previous diagnoses of hypertension, diabetes, and heart failure (HF), respectively; 24.3% did not receive adequate cardiac monitoring. Inadequate cardiac monitoring was associated with lower cumulative MD vol (T1: 27.9%, T2: 23.3%, T3: 20.8%, p < 0.0001) and lower annual centre vol (T1: 32.5%, T2: 19.7%, T3: 20.7%, p < 0.0001) in univariate analyses, and remained significant after adjusting for age, comorbidities, previous HF, socioeconomic status based on income, rural residence and calendar period. After adjusting for patient clustering at the MD, centre, and regional levels, lower cumulative MD vol (p=0.012), but not annual centre vol, remained a significant predictor for inadequate cardiac monitoring. CONCLUSIONS Our findings suggest improved cardiac monitoring with greater MD experience, supporting the notion of centralization of systemic therapy to high vol MDs to optimize outcomes.

Managing chemotherapy drug shortages in Ontario.

192 Background: Chemotherapy drug shortages are common and unpredictable. The causes are multifactorial and the negative effects on patients and practitioners have been well described. In an effort to mitigate the impact of this problem, Cancer Care Ontario (CCO) has developed a coordinated approach to the management of chemotherapy drug shortages. Tactics have included a system level strategy to promote communication through a virtual collaborative workspace for providers to network and share management strategies and inventory, where feasible. Disease site experts have also developed clinical guidance for the management of specific drug shortages which have then supported public funding decisions that enabled the use of substitute chemotherapy agents in a number of instances. METHODS The impact and management of a recent shortage of liposomal doxorubicin (LD), a publically funded drug for patients with platinum refractory ovarian cancer is described for both new chemotherapy starts and for prevalent LD treated cases. Expert clinical guidance supported a funding policy amendment so patients already on treatment could switch to a recognized substitute drug, topotecan (TT). This also became the preferred funded option for new platinum refractory patients. RESULTS LD was in short supply between August 2011 and December 2012. In the quarter prior to shortage, 83 new platinum refractory patients started on LD and 1 on TT. During that time, the average number of monthly prevalent LD and TT treated cases was 80 and 4 respectively. For the first quarter post shortage, 20 new patients started on LD and 34 patients started on TT. The average monthly prevalent treated cases were 49 and 21 respectively. Funding for the switch from LD to TT was requested in only 7 cases. Therefore, the total number of new and prevalent treated cases on either preferred therapy dropped post LD shortage. This decline worsened with each subsequent quarter and immediately returned to baseline when the shortage resolved. Drug procurement costs were lower during the period of shortage. CONCLUSIONS Drug shortages have a significant impact on patients and providers. Even when appropriate substitutes are available, quality of care may be affected.

Ontario’s approach to tackling drug funding sustainability.

38 Background: One of the challenges facing Ontario relates to managing the rising costs of cancer drug treatments. The annual growth rate of cancer drug spending has increased by 10-20% since 2010, exceeding other therapeutic categories and is expected to continue to grow significantly faster than expenditures in other areas. Paradoxically, the price of a drug seems to have little relation to its demonstrated efficacy ( http://www.asco.org/practice-research/cancer-care-america-2015/focus-cost ). The Cancer Quality Council of Ontario (CQCO) and Cancer Care Ontario (CCO) embarked on a journey to systematically address this challenge. METHODS The CQCO and CCO focused on identifying and reviewing the critical success factors of a sustainable drug reimbursement program with international, pan-Canadian and internal input. Recognizing that drug funding sustainability is a challenge faced by health systems worldwide, the scope of this work was broadened from a provincial focus to one that was relevant across the Canadian context. RESULTS Ultimately, this work resulted in CQCO providing a core set of recommendations for CCO that may also be relevant to other reimbursement programs, in order to maximize the effectiveness of cancer drug use and support overall system sustainability in a patient-centred way. The recommendations to address drug funding sustainability included: (1) Transparency in drug funding decisions; (2) development of process to incorporate current best evidence to support system sustainability; (3) development of a consistent approach to gathering and analyzing real world evidence (RWE); (4) development of a consistent process for disinvestment and renegotiation of prices with buy-in from public, patients and clinicians; (5) development of a provincial process to maximize harmonization in cancer drug funding coverage decisions; (6) refinement of the algorithm and priority setting for review of drug submissions; and (7) incorporating RWE into funding decisions and downstream re-evaluation. CONCLUSIONS CCO is determining an action plan based on the above recommendations and developing partnerships to support successful implementation to improve sustainability in regards to cancer drug funding.

Systemic treatment patterns in small bowel and appendiceal adenocarcinomas (SBA and AA): A population-based study.

242 Background: There is uncertainty regarding the optimal systemic treatment for patients with SBA and AA due to the limited available evidence for these uncommon malignancies and conflicting recommendations in existing guidelines. However, on the basis of biologic similarities between SBA, AA and colorectal cancer (CRC), common practice is to use the same systemic therapies as for CRC. We compared the utilization of chemotherapeutic agents for SBA and AA to that of CRC patients in Ontario, Canada. Methods: The provincial tumour registry in Ontario, Canada was used to identify patients diagnosed with SBA, AA or CRC from 2010-2014. Subsequent chemotherapy utilization and costs were captured from single-payer government administrative databases. We studied the use of oxaliplatin, irinotecan, capecitabine, bevacizumab, cetuximab, panitumumab, and raltitrexed, which are funded for CRC treatment. Patients were excluded if they had multiple primary cancer sites, morphology codes inconsistent with adenocarcinom...

Automating a program for the evidence-based reimbursement of oncology drugs across a complex network: Benefits and challenges.

39 Background: Ontario hospitals are reimbursed for IV chemotherapy through Cancer Care Ontarios (CCO) New Drug Funding Program (NDFP). By 2009, 54 indications (annual budget

Non-Prescription Painkillers and Chronic Liver Disease:

195MM) were managed through largely paper based processes. A new web based system (eClaims) was developed focusing on clinic workflow and integration to chemotherapy ordering systems. Interfaces were developed for CCOs OPIS and commercial systems (HL7v3). eClaims provides users with clinical best practice, pre-approval, immediate adjudication and simple means of tracking outstanding claims. The benefits and challenges are described. METHODS Evaluation used several strategies: debriefs after each deployment; post-go live user surveys and lessons learned workshops. RESULTS eClaims was deployed in 80 hospitals over two years. At most sites (50/80) treatment data flows from CPOE systems to eClaims in near real time. Over 50% of claims are machine adjudicated. Newly approved indications can be posted within hours. The main learnings during the deployment process were the need to understand and adjust for hospital specific factors and the unique business relationships among clusters of hospitals. Survey responses were received at a 19% response rate. The later deployment groups reported greater satisfaction than earlier adopters with more positive responses in all categories. Workshop key theme was the need to match complex clinical workflows with design/build processes. Secondly, evaluation of historical data before migration is necessary. CONCLUSIONS Introducing an application into complex, varied clinical workflows is difficult. The phased approach to deployment and evaluation worked, allowing for increasingly smooth go lives. Future work revolves around balancing user needs through eClaims modifications vs simplifying clinical processes to make the tool more usable.

Pharmacy 2.0: A scoping review of social media use in pharmacy

Chronic liver disease is a general term that encompasses numerous hepatic illnesses of varying etiologies, ranging from mild hepatitis to cirrhosis. Chronic liver disease can be autoimmune (e.g., primary biliary cirrhosis, autoimmune hepatitis), hereditary (e.g., hemochromatosis, Wilson’s disease), or induced by toxins and drugs. Therapeutic goals include delaying the progression of the disease and minimizing the risk of further hepatic injury.1 The multiple effects of impaired hepatic function on drug action and disposition complicate product selection, even for the treatment of self-limiting conditions. This article reviews the factors influencing the selection of a painkiller in a self-medicating patient.