Grand rounds in methodology: key considerations for implementing machine learning solutions in quality improvement initiatives.

Machine learning (ML) solutions are increasingly entering healthcare. They are complex, sociotechnical systems that include data inputs, ML models, technical infrastructure and human interactions. They have promise for improving care across a wide range of clinical applications but if poorly implemented, they may disrupt clinical workflows, exacerbate inequities in care and harm patients. Many aspects of ML solutions are similar to other digital technologies, which have well-established approaches to implementation. However, ML applications present distinct implementation challenges, given that their predictions are often complex and difficult to understand, they can be influenced by biases in the data sets used to develop them, and their impacts on human behaviour are poorly understood. This manuscript summarises the current state of knowledge about implementing ML solutions in clinical care and offers practical guidance for implementation. We propose three overarching questions for potential users to consider when deploying ML solutions in clinical care: (1) Is a clinical or operational problem likely to be addressed by an ML solution? (2) How can an ML solution be evaluated to determine its readiness for deployment? (3) How can an ML solution be deployed and maintained optimally? The Quality Improvement community has an essential role to play in ensuring that ML solutions are translated into clinical practice safely, effectively, and ethically.

Effect of Free Medicine Distribution on Health Care Costs in Canada Over 3 Years: A Secondary Analysis of the CLEAN Meds Randomized Clinical Trial.

Importance: Few interventions are proven to reduce total health care costs, and addressing cost-related nonadherence has the potential to do so. Objective: To determine the effect of eliminating out-of-pocket medication fees on total health care costs. Design, Setting, and Participants: This secondary analysis of a multicenter randomized clinical trial using a prespecified outcome took place across 9 primary care sites in Ontario, Canada (6 in Toronto and 3 in rural areas), where health care services are generally publicly funded. Adult patients (≥18 years old) reporting cost-related nonadherence to medicines in the past 12 months were recruited between June 1, 2016, and April 28, 2017, and followed up until April 28, 2020. Data analysis was completed in 2021. Interventions: Access to a comprehensive list of 128 medicines commonly prescribed in ambulatory care with no out-of-pocket costs for 3 years vs usual medicine access. Main Outcome and Measures: Total publicly funded health care costs over 3 years, including costs of hospitalizations. Health care costs were determined using administrative data from Ontario's single-payer health care system, and all costs are reported in Canadian dollars with adjustments for inflation. Results: A total of 747 participants from 9 primary care sites were included in the analysis (mean [SD] age, 51 [14] years; 421 [56.4%] female). Free medicine distribution was associated with a lower median total health care spending over 3 years of $1641 (95% CI, $454-$2792; P = .006). Mean total spending was $4465 (95% CI, -$944 to $9874) lower over the 3-year period. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, eliminating out-of-pocket medication expenses for patients with cost-related nonadherence in primary care was associated with lower health care spending over 3 years. These findings suggest that eliminating out-of-pocket medication costs for patients could reduce overall costs of health care. Trial Registration: ClinicalTrials.gov Identifier: NCT02744963.

Geographic variation and sociodemographic correlates of prescription psychotropic drug use among children and youth in Ontario, Canada: a population-based study.

BACKGROUND: Population-based research examining geographic variability in psychotropic medication dispensing to children and youth and the sociodemographic correlates of such variation is lacking. Variation in psychotropic use could reflect disparities in access to non-pharmacologic interventions and identify potentially concerning use patterns. METHODS: We conducted a population-based study of all Ontario residents aged 0 to 24 years who were dispensed a benzodiazepine, stimulant, antipsychotic or antidepressant between January 1, 2018, and December 31, 2018. We conducted small-area variation analyses and identified determinants of dispensing using negative binomial generalized estimating equation models. RESULTS: The age- and sex-standardized rate of psychotropic dispensing to children and youth was 76.8 (range 41.7 to 144.4) prescriptions per 1000 population, with large variation in psychotropic dispensing across Ontario's census divisions. Males had higher antipsychotic [rate ratio (RR) 1.40; 95% confidence interval (CI) 1.36 to 1.44) and stimulant (RR 1.75; 95% CI 1.70 to 1.80) dispensing rates relative to females, with less use of benzodiazepines (RR 0.85; 95% CI 0.83 to 0.88) and antidepressants (RR 0.81; 95% CI 0.80 to 0.82). Lower antipsychotic dispensing was observed in the highest income neighbourhoods (RR 0.72; 95% CI 0.70 to 0.75) relative to the lowest. Benzodiazepine (RR 1.12; 95% CI 1.01 to 1.24) and stimulant (RR 1.11; 95% CI 1.01 to 1.23) dispensing increased with the density of mental health services in census divisions, whereas antipsychotic use decreased (RR 0.82; 95% CI 0.73 to 0.91). The regional density of child and adolescent psychiatrists and developmental pediatricians (RR 1.00; 95% CI 0.99 to 1.01) was not associated with psychotropic dispensing. CONCLUSION: We found significant variation in psychotropic dispensing among young Ontarians. Targeted investment in regions with long wait times for publicly-funded non-pharmacological interventions and novel collaborative service models may minimize variability and promote best practices in using psychotropics among children and youth.

Assessment of Natural Language Processing Methods for Ascertaining the Expanded Disability Status Scale Score From the Electronic Health Records of Patients With Multiple Sclerosis: Algorithm Development and Validation Study.

BACKGROUND: The Expanded Disability Status Scale (EDSS) score is a widely used measure to monitor disability progression in people with multiple sclerosis (MS). However, extracting and deriving the EDSS score from unstructured electronic health records can be time-consuming. OBJECTIVE: We aimed to compare rule-based and deep learning natural language processing algorithms for detecting and predicting the total EDSS score and EDSS functional system subscores from the electronic health records of patients with MS. METHODS: We studied 17,452 electronic health records of 4906 MS patients followed at one of Canada's largest MS clinics between June 2015 and July 2019. We randomly divided the records into training (80%) and test (20%) data sets, and compared the performance characteristics of 3 natural language processing models. First, we applied a rule-based approach, extracting the EDSS score from sentences containing the keyword "EDSS." Next, we trained a convolutional neural network (CNN) model to predict the 19 half-step increments of the EDSS score. Finally, we used a combined rule-based-CNN model. For each approach, we determined the accuracy, precision, recall, and F-score compared with the reference standard, which was manually labeled EDSS scores in the clinic database. RESULTS: Overall, the combined keyword-CNN model demonstrated the best performance, with accuracy, precision, recall, and an F-score of 0.90, 0.83, 0.83, and 0.83 respectively. Respective figures for the rule-based and CNN models individually were 0.57, 0.91, 0.65, and 0.70, and 0.86, 0.70, 0.70, and 0.70. Because of missing data, the model performance for EDSS subscores was lower than that for the total EDSS score. Performance improved when considering notes with known values of the EDSS subscores. CONCLUSIONS: A combined keyword-CNN natural language processing model can extract and accurately predict EDSS scores from patient records. This approach can be automated for efficient information extraction in clinical and research settings.

SLEAP SMART (Sleep Apnea Screening Using Mobile Ambulatory Recorders After TIA/Stroke): A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Poststroke/transient ischemic attack obstructive sleep apnea (OSA) is prevalent, linked with numerous unfavorable health consequences, but remains underdiagnosed. Reasons include patient inconvenience and costs associated with use of in-laboratory polysomnography (iPSG), the current standard tool. Fortunately, home sleep apnea testing (HSAT) can accurately diagnose OSA and is potentially more convenient and cost-effective compared with iPSG. Our objective was to assess whether screening for OSA in patients with stroke/transient ischemic attack using HSAT, compared with standard of care using iPSG, increased diagnosis and treatment of OSA, improved clinical outcomes and patient experiences with sleep testing, and was a cost-effective approach. METHODS: We consecutively recruited 250 patients who had sustained a stroke/transient ischemic attack within the past 6 months. Patients were randomized (1:1) to use of (1) HSAT versus (2) iPSG. Patients completed assessments and questionnaires at baseline and 6-month follow-up appointments. Patients diagnosed with OSA were offered continuous positive airway pressure. The primary outcome was compared between study arms via an intention-to-treat analysis. RESULTS: At 6 months, 94 patients completed HSAT and 71 patients completed iPSG. A significantly greater proportion of patients in the HSAT arm were diagnosed with OSA (48.8% versus 35.2%, P=0.04) compared with the iPSG arm. Furthermore, patients assigned to HSAT, compared with iPSG, were more likely to be prescribed continuous positive airway pressure (40.0% versus 27.2%), report significantly reduced sleepiness, and a greater ability to perform daily activities. Moreover, a significantly greater proportion of patients reported a positive experience with sleep testing in the HSAT arm compared with the iPSG arm (89.4% versus 31.1%). Finally, a cost-effectiveness analysis revealed that HSAT was economically attractive for the detection of OSA compared with iPSG. CONCLUSIONS: In patients with stroke/transient ischemic attack, use of HSAT compared with iPSG increases the rate of OSA diagnosis and treatment, reduces daytime sleepiness, improves functional outcomes and experiences with sleep testing, and could be an economically attractive approach. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02454023.

Analyzing supply and demand on a general internal medicine ward: a cross-sectional study.

BACKGROUND: The capacity of general internal medicine (GIM) clinical teaching units has been strained by decreasing resident supply and increasing patient demand. The objective of our study was to compare the number of residents (supply) with the volume and duration of patient care activities (demand) to identify inefficiency. METHODS: Using the most recently available data from an academic teaching hospital in Toronto, Ontario, we identified each occurrence of a set of patient care activities that took place on the clinical teaching unit from 2015 to 2019. We completed a descriptive analysis of the frequencies of these activities and how the frequencies varied by hour, day, week, month and year. Patient care activities included admissions, rounds, responding to pages, meeting with patients and their families, patient transfers, discharges and responding to cardiac arrests. The estimated time to complete each task was based on the available data in our electronic medical record system and interviews with GIM physicians and trainees. To calculate resident utilization, the person-hours of patient care tasks was divided by the person-hours of resident supply. Resident utilization was computed for 3 scenarios corresponding to varying levels of resident absenteeism. RESULTS: During the study period, there were 14 581 consultations to GIM from the emergency department. Patient volumes tended to be highest during January and lowest during May and June, and highest on Monday morning and lowest on Friday night. Daily admissions to hospital from the emergency department were higher on weekdays than on weekends, and hourly admissions peaked at 8 am and between 3 pm and 1 am. Weekday resident utilization was generally highest between 8 am and 2 pm, and lowest between 1 am and 8 am. In a scenario in which all residents were present apart from those who were post-call, resident utilization generally never exceeded 100%; in scenarios in which at least 1 resident was absent owing to illness or vacation, it was common for resident utilization to approach or exceed 100%, particularly during daytime working hours. INTERPRETATION: Analyzing supply and demand on a GIM ward has allowed us to identify periods when supply and demand are not aligned and to demonstrate empirically the vulnerability of current staffing models. These data have the potential to inform and optimize scheduling on an internal medicine ward.

Projected impact of biosimilar substitution policies on drug use and costs in Ontario, Canada: a cross-sectional time series analysis.

BACKGROUND: Several Canadian provinces have introduced reimbursement policies mandating substitution of innovator biologics with lower-cost biosimilars. We estimated the number of patients affected and cost implications if such policy changes were to be implemented in Ontario, Canada. METHODS: We conducted a cross-sectional time series analysis of Ontarians dispensed publicly funded biologics indicated for inflammatory diseases (rheumatic conditions, inflammatory bowel disease: infliximab, etanercept, adalimumab) between January 2018 and December 2019, and forecasted trends to Dec. 31, 2020. The primary source of data was pharmacy claims data for all biologics reimbursed by the public drug program. We modelled the number of patients affected and government expenditures (in nominal Canadian dollars) of several biosimilar policy options, including mandatory nonmedical biosimilar substitution, substitution in new users, introduction of a biosimilar for adalimumab, and price negotiations. In a secondary analysis, we included insulin glargine. RESULTS: In 2018, 14 089 individuals were prescribed a publicly funded biologic for inflammatory diseases. A mandatory nonmedical biosimilar substitution would potentially have affected 7209 patients and saved $238.6 million from 2018 to 2020. A new-user substitution would have affected 757 patients and saved $34.2 million. If an adalimumab biosimilar were to become available, 12 928 patients would be affected by a mandatory nonmedical substitution and the 3-year savings would increase to $645.9 million (all biosimilars priced at 25% of innovator biologics). Finally, an expanded nonmedical substitution policy including insulin glargine would affect 115 895 patients and save $288.7 million (not including adalimumab). INTERPRETATION: Policies designed to curb rising costs of biologics can have substantially different effects on patients and government expenditures. Such analyses warrant careful consideration of the balance between cost savings and effects on patients.

Assessment of Stimulant Use and Cardiovascular Event Risks Among Older Adults.

Importance: Use of stimulants continues to increase among older adults for a variety of indications. An association between stimulant use and increased risk of cardiovascular (CV) events has been established among children and young adults, but few studies have explored the risk of CV events among older patients, a group with increased baseline risk. Objective: To evaluate the association between stimulant use and risk of CV events among older adults. Design, Setting, and Participants: This propensity score-matched cohort study, with 4 nonusers per 1 user, was conducted from July 1, 2017, to June 27, 2019, using data from population-based health care databases from Ontario, Canada, from January 1, 2002, to December 31, 2016. Included individuals were outpatients aged 66 years or older. Exposures: Initiation of a prescription stimulant. Main Outcomes and Measures: The primary outcome was a CV event, defined as a composite of emergency department visit or hospitalization for myocardial infarction, stroke or transient ischemic attack (TIA), or ventricular arrhythmia. Risk of CV event was assessed at 30 days, 180 days, and 365 days after initiation of stimulants from Cox proportional hazard models. A secondary analysis assessed each component of the primary outcome separately. Results: Among 6457 older adults who initiated a prescription stimulant (ie, the exposed group) and 24 853 older adults who did not initiate such treatment (ie, the unexposed group), the distribution of baseline patient characteristics was well balanced after matching (sex: 3173 [49.1%] men vs 12 112 [48.7%] men; standardized difference, 0.01; median [IQR] age: 74 [69-80] years vs 74 [69-80] years; standardized difference, 0.01). Within this cohort, there were 932 CV events during the 365-day follow-up (5.11 events per 100 person-years among individuals who initiated stimulants). In the primary analysis, stimulant initiation was associated with increased risk of CV events at 30 days (hazard ratio [HR], 1.4; 95% CI, 1.1-1.8) but not at 180 days (HR, 1.2; 95% CI, 0.9-1.6) or 365 days (HR, 1.0; 95% CI, 0.6 to 1.8). In the secondary analysis, stimulant initiation was associated with increased risk of ventricular arrhythmias (HR, 3.0; 95% CI, 1.1-8.7) and stroke or TIA (HR, 1.6; 95% CI, 1.1-2.1) at 30 days. Conclusions and Relevance: This cohort study found that stimulant use was associated with an early increase in CV events among older adults with no association for long-term use.

Inequities in access to primary care among opioid recipients in Ontario, Canada: A population-based cohort study.

BACKGROUND: Stigma and high-care needs can present barriers to the provision of high-quality primary care for people with opioid use disorder (OUD) and those prescribed opioids for chronic pain. We explored the likelihood of securing a new primary care provider (PCP) among people with varying histories of opioid use who had recently lost access to their PCP. METHODS AND FINDINGS: We conducted a retrospective cohort study using linked administrative data among residents of Ontario, Canada whose enrolment with a physician practicing in a primary care enrolment model (PEM) was terminated between January 2016 and December 2017. We assigned individuals to 3 groups based upon their opioid use on the date enrolment ended: long-term opioid pain therapy (OPT), opioid agonist therapy (OAT), or no opioid. We fit multivariable models assessing the primary outcome of primary care reattachment within 1 year, adjusting for demographic characteristics, clinical comorbidities, and health services utilization. Secondary outcomes included rates of emergency department (ED) visits and opioid toxicity events. Among 154,970 Ontarians who lost their PCP, 1,727 (1.1%) were OAT recipients, 3,644 (2.4%) were receiving long-term OPT, and 149,599 (96.5%) had no recent prescription opioid exposure. In general, OAT recipients were younger (median age 36) than those receiving long-term OPT (59 years) and those with no recent prescription opioid exposure (44 years). In all exposure groups, the majority of individuals had their enrolment terminated by their physician (range 78.1% to 88.8%). In the primary analysis, as compared to those not receiving opioids, OAT recipients were significantly less likely to find a PCP within 1 year (adjusted hazard ratio [aHR] 0.55, 95% confidence interval [CI] 0.50 to 0.61, p < 0.0001). We observed no significant difference between long-term OPT and opioid unexposed individuals (aHR 0.96; 95% CI 0.92 to 1.01, p = 0.12). In our secondary analysis comparing the period of PCP loss to the year prior, we found that rates of ED visits were elevated among people not receiving opioids (adjusted rate ratio (aRR) 1.20, 95% CI 1.18 to 1.22, p < 0.0001) and people receiving long-term OPT (aRR 1.37, 95% CI 1.28 to 1.48, p < 0.0001). We found no such increase among OAT recipients, and no significant increase in opioid toxicity events in the period following provider loss for any exposure group. The main limitation of our findings relates to their generalizability outside of PEMs and in jurisdictions with different financial incentives incorporated into primary care provision. CONCLUSIONS: In this study, we observed gaps in access to primary care among people who receive prescription opioids, particularly among OAT recipients. Ongoing efforts are needed to address the stigma, discrimination, and financial disincentives that may introduce barriers to the healthcare system, and to facilitate access to high-quality, consistent primary care services for chronic pain patients and those with OUD.

Impact of a Publicly Funded Herpes Zoster Immunization Program on the Burden of Disease in Ontario, Canada: A Population-based Study.

BACKGROUND: In September 2009, a live attenuated herpes zoster vaccine (ZVL) became available in Canada. Beginning in September 2016, ZVL was made available to all Ontario residents aged 65-70 through a publicly funded immunization program. We assessed the impact of ZVL availability and its subsequent public funding on herpes zoster burden in this population. METHODS: A population-based study of Ontario residents aged 65-70 between January 2005 and September 2018. We used interventional autoregressive integrated moving average models to examine the impact of ZVL market availability and the publicly funded ZVL program on monthly incidence rate of medically attended herpes zoster, defined as an outpatient visit for herpes zoster with a prescription for a herpes zoster antiviral dispensed ≤5 days before or after the visit, or a herpes zoster-related emergency department (ED) visit or hospitalization. In secondary analyses, we examined impacts on any herpes zoster-related ED visits and hospitalizations. RESULTS: We found no association between ZVL market availability and monthly incidence of herpes zoster (P = .32) or monthly rates of ED visits and hospitalizations (P = .88). Conversely, the introduction of publicly funded ZVL reduced the monthly rate of medically attended herpes zoster by 19.1% (from 4.8 to 3.8 per 10 000 population; P < .01) and herpes zoster-related ED visits and hospitalizations by 38.2% (from 1.7 to 1.0 per 10 000 population; P < .05). CONCLUSIONS: The introduction of a publicly funded immunization program for herpes zoster was associated with reduced disease burden and related acute healthcare service use.

What happens to drug use and expenditure when cost sharing is completely removed? Evidence from a Canadian provincial public drug plan.

OBJECTIVES: The role of cost-sharing for medicines is under active policy discussion, including in proposals for value-based insurance design. To inform this debate, we estimated the impact of completely removing cost-sharing on medication use and expenditure using a quasi-experimental approach. METHODS: Fair PharmaCare, British Columbia's income-based public drug plan, includes a household out-of-pocket limit. Therefore, when one household member starts a long-term high-cost drug surpassing this maximum, cost-sharing is completely removed for other family members. We used an interrupted time series design to estimate monthly prescriptions and expenditures of other household members, 24 months before and after cost-sharing removal. RESULTS: We studied 2191 household members newly free of cost-sharing requirements, most of whom had lower incomes. R emoving cost-sharing increased the level of drug expenditure and prescription numbers by 16 and 19%, respectively (i.e. $2659.43 (95%$1507.27-$3811.59, p < 0.001); 50.0 (95%CI 25.1-74.9, p < 0.001)) relative to prior expenditures and utilization without changing pre-existing trends. Much of this change was driven by 533 individuals initiating medication for the first time after cost-sharing removal. This initiation substantially increased average expenditure, especially for antiviral agents. CONCLUSIONS: Completely removing cost-sharing, independent of health status, significantly increased medication use and expenditure particularly due to medicine initiation by new users. While costs may be preventing use, the appropriateness of additional use, especially among new users, is unclear.

Characteristics of high-drug-cost beneficiaries of public drug plans in 9 Canadian provinces: a cross-sectional analysis.

BACKGROUND: Drugs are the fastest growing cost in the Canadian health care system, owing to the increasing number of high-cost drugs. The objective of this study was to examine the characteristics of high-drug-cost beneficiaries of public drug plans across Canada relative to other beneficiaries. METHODS: We conducted a cross-sectional study among public drug plan beneficiaries residing in all provinces except Quebec. We used the Canadian Institute for Health Information's National Prescription Drug Utilization Information System to identify all drugs dispensed to beneficiaries of public drug programs in 2016/17. We stratified the cohort into 2 groups: high-drug-cost beneficiaries (top 5% of beneficiaries based on annual costs) and other beneficiaries (remaining 95%). For each group, we reported total drug costs, prevalence of high-cost claims (> $1000), median number of drugs, proportion of beneficiaries aged 65 or more, the 10 most costly reimbursed medications and the 10 medications most commonly reimbursed. We reported estimates overall and by province. RESULTS: High-drug-cost beneficiaries accounted for nearly half (46.5%) of annual spending, with an average annual spend of $14 610 per beneficiary, compared to $1570 among other beneficiaries. The median number of drugs dispensed was higher among high-drug-cost beneficiaries than among other beneficiaries (13 [interquartile range (IQR) 7-19] v. 8 [IQR 4-13]), and a much larger proportion of high-drug-cost beneficiaries than other beneficiaries received at least 1 high-cost claim (40.9% v. 0.6%). Long-term medications were the most commonly used medications for both groups, whereas biologics and antivirals were the most costly medications for high-drug-cost beneficiaries. INTERPRETATION: High-drug-cost beneficiaries were characterized by the use of expensive medications and polypharmacy relative to other beneficiaries. Interventions and policies to help reduce spending need to consider both of these factors.

Effectiveness of Intrapleural Tissue Plasminogen Activator and Dornase Alfa vs Tissue Plasminogen Activator Alone in Children with Pleural Empyema: A Randomized Clinical Trial.

Importance: Clinical guidelines recommend that children with pleural empyema be treated with chest tube insertion and intrapleural fibrinolytics. The addition of dornase alfa (DNase) has been reported to improve outcomes in adults but remains unproven in children. Objective: To determine if intrapleural tissue plasminogen activator (tPA) and DNase is more effective than tPA and placebo at reducing hospital length of stay in children with pleural empyema. Design, Setting, and Participants: This multicenter, parallel-group, placebo-controlled, superiority randomized clinical trial included children diagnosed as having pleural empyema requiring drainage aged 6 months to 18 years treated at 6 tertiary Canadian children's hospitals. A total of 379 children were assessed for eligibility; 281 were excluded and 98 were randomized. One child was excluded after randomization for not meeting the inclusion criteria. Data were collected from March 4, 2013, to December 13, 2017. Interventions: Participants underwent chest tube insertion and 3 daily administrations of intrapleural tPA, 4 mg, followed by DNase, 5 mg (intervention group), or 5 mL of normal saline (placebo; control group). Participants, families, clinical staff, and members of the study team were blinded to allocation. Main Outcomes and Measures: The primary outcome was hospital length of stay from chest tube insertion to discharge. Secondary outcomes included time to meeting discharge criteria, time to chest tube removal, mean fever duration, additional pleural drainage procedures, hospital readmissions, and total health care cost. Results: Of the 97 analyzed children with pleural empyema, 52 (54%) were male, and the mean (SD) age was 5.1 (3.6) years. A total of 49 children were randomized to tPA and DNase and 48 were randomized to tPA and placebo. Treatment with tPA and DNase was not associated with decreased hospital length of stay compared with tPA and placebo (mean [SD] length of stay, 9.0 [4.9] vs 9.1 [5.3] days; mean difference, -0.1 days; 95% CI, -2.0 to 2.1; P = .96). Similarly, no significant differences were observed for any of the secondary outcomes. Of the 14 adverse events in the tPA and DNase group, 6 (43%) were serious; of the 21 adverse events in the tPA and placebo group, 8 (38%) were serious. There were no deaths. Conclusions and Relevance: The addition of DNase to intrapleural tPA for children with pleural empyema had no effect on hospital length of stay or other outcomes compared with tPA with placebo. Clinical practice guidelines should continue to support the use of chest tube insertion and intrapleural fibrinolytics alone as first-line treatment for pediatric empyema. Trial Registration: ClinicalTrials.gov identifier: NCT01717742.

Providing Data-Driven Equitable Palliative and End-of-Life Care for Structurally Vulnerable Populations: A Pilot Survey of Information Management Strategies.

BACKGROUND: Considerable gains are being made in data-driven efforts to advance quality improvement in health care. However, organizations providing hospice-oriented palliative care for structurally vulnerable persons with terminal illnesses may not have the enabling data infrastructure or framework to derive such benefits. METHODS: We conducted a pilot cross-sectional qualitative study involving a convenience sample of hospice organizations across North America providing palliative care services for structurally vulnerable patients. Through semistructured interviews, we surveyed organizations on the types of data collected, the information systems used, and the challenges they faced. RESULTS: We contacted 13 organizations across North America and interviewed 9. All organizations served structurally vulnerable populations, including the homeless and vulnerably housed, socially isolated, and HIV-positive patients. Common examples of collected data included the number of referrals, the number of admissions, length of stay, and diagnosis. More than half of the organizations (n = 5) used an electronic medical record, although none of the record systems were specifically designed for palliative care. All (n = 9) the organizations used the built-in reporting capacity of their information management systems and more than half (n = 6) augmented this capacity with chart reviews. DISCUSSION: A number of themes emerged from our discussions. Present data collection is heterogeneous, and storage of these data is highly fragmented within and across organizations. Funding appeared to be a key enabler of more robust data collection and use. Future work should address these gaps and examine opportunities for innovative ways of analysis and reporting to improve care for structurally vulnerable populations.

Comprehensive Drug-Class Review Framework for improved evidence-based drug policy and formulary modernization.

Formularies are used by payers to optimize access and ensure the appropriate use of medications. Lack of follow-up and re-evaluation can lead to outdated formularies that are not reflective of current evidence. Formulary modernization, an approach to re-align formularies with current evidence has proven successful. The Ontario Drug Policy Research Network (ODPRN) launched a framework for conducting comprehensive drug-class reviews. This commentary describes the individual components of this framework and lessons learned through completion of 12 reviews between 2013 and 2016. We present the ODPRN drug-class review of treatments for chronic hepatitis B as a case example to illustrate the components and impact. The incorporation of foundational health technology assessment components such as economic evaluations and knowledge synthesis with contextualizing evidence such as patient and clinician perspectives (through qualitative studies), real-world evidence (through data analytics), and cross-jurisdictional comparisons (through environmental scans and data analytics), successfully developed jurisdictionally specific policy recommendations grounded in up-to-date evidence. The ODPRN framework for conducting comprehensive drug-class reviews is a robust and feasible approach to conduct formulary modernization. This framework allows for actionable and specific policies which are likely to be considered by decision makers. Adoption of similar frameworks in other jurisdictions may improve uptake of evidence-informed policy recommendations.

Healthcare resource utilization and costs among patients with direct oral anticoagulant or warfarin-related major bleeding.

INTRODUCTION: Direct oral anticoagulants (DOACs) have expanded the options for antithrombotic therapy. DOAC-related major bleeds are associated with favorable outcomes compared to warfarin in clinical trials and routine practice. However, it is unclear whether management of DOAC-associated major bleeding incurs higher resource utilization and costs. MATERIALS AND METHODS: We screened medical records of patients ≥ 66 years with atrial fibrillation admitted to one of five tertiary care hospitals in Ontario, Canada with a hemorrhage. We abstracted bleeds involving DOACs or warfarin and linked them to administrative databases to capture length of hospital stay, blood product use, procedural interventions, intensive care unit (ICU) utilization and related direct medical costs. To control for confounders, multivariate logistic and linear regressions were used for binary and linear outcomes respectively. RESULTS: Among 19,061 records screened, 1978 (10.4%) cases involving 1632 patients met criteria of oral anticoagulant-associated bleeding. Baseline characteristics between DOAC and warfarin groups were similar. Blood product costs were higher for DOACs (all comparisons DOACs vs. warfarin, $1456 vs. $1109, mean difference $347, 95% CI $185 to $509), but length of stay and ICU use were similar. Mean direct medical costs did not differ ($9217 vs. $10,790, adjusted relative ratio 0.94, 95% CI 0.84-1.05). CONCLUSIONS: Prior to introduction of DOAC-specific reversal agents, resource utilization and medical costs were comparable between DOAC- and warfarin-associated major bleeds, despite marginally higher blood product costs incurred by the former. Resource intensity associated with anticoagulant-related bleeding remains high, and our data provide measures for cost-effectiveness evaluation of emerging DOAC antidotes.

Tramadol and the risk of seizure: nested case-control study of US patients with employer-sponsored health benefits.

OBJECTIVES: Tramadol is a widely prescribed analgesic that influences both opioid and monoamine neurotransmission. While seizures have been reported with its use, the risk in clinical practice has not been well characterised. We examined risk of seizure with tramadol relative to codeine, a comparable opioid analgesic. DESIGN: Retrospective nested case-control study. For each case, we identified up to 10 controls matched on age, sex, US state of residence and date of cohort entry (±365 days). We calculated ORs to determine the association between seizure and exposure to tramadol, codeine (≥15 mg), both or neither, in the preceding 30 days. SETTING: Cohort of patients, who had continuous health coverage and resided in the same state for≥3 years, identified from linked administrative health data in US MarketScan databases from 2009 to 2012. PARTICIPANTS: We identified 96 753 patients with seizure and 888 540 matched controls. PRIMARY AND SECONDARY OUTCOME MEASURES: In the primary analysis, we defined cases using a broad definition of seizure (based on either an outpatient physician claim for seizure disorder or a seizure-related emergency department visit or hospitalisation). In a secondary analysis, we used a more specific definition of seizure restricted to a hospital visit with a principal diagnosis of seizure. RESULTS: In the primary analysis, we found no association between risk of seizure and exposure to tramadol compared with codeine (OR 1.03, 95% CI 0.93 to 1.15). However, in the secondary analysis (using a more specific definition of seizure), this association was statistically significant (OR 1.41, 95% CI 1.11 to 1.79). CONCLUSIONS: Tramadol was not associated with an increased risk of seizure defined by inpatient and outpatient diagnoses. However, this finding was sensitive to the outcome definition used and requires further study.

Impact of delisting high-strength opioid formulations from a public drug benefit formulary on opioid utilization in Ontario, Canada.

PURPOSE: High-strength opioid formulations were delisted (removed) from Ontario's public drug formulary in January 2017, except for palliative patients. We evaluated the impact of this policy on opioid utilization and dosing. METHODS: We conducted a longitudinal study among patients receiving publicly funded, high-strength opioids from August 2016 to July 2017. The primary outcome measure was weekly median daily opioid dose (in milligrams of morphine or equivalent; MME) of (1) publicly funded and (2) all opioid prescriptions irrespective of funding source, evaluated using interrupted time series analyses and stratified by palliative care status. RESULTS: Following policy implementation, the weekly median daily dose of publicly funded opioids decreased immediately among non-palliative patients by 10 MME (95% confidence limit [CL], -16.8 to -3.1) from a pre-intervention dose of 424.5 MME (95% CL, 417.8-431.2) and fell gradually among palliative patients by 3.9 MME per week (95% CL, -5.5 to -2.3) from a pre-intervention dose of 450.1 MME (95% CL, 432.5-467.7). In contrast, among all opioid prescriptions, gradual reductions in weekly median daily doses were observed only for non-palliative patients, which decreased by 0.7 MME per week (95% CL, -1.3 to -0.2) from a pre-intervention dose of 426.2 MME (95% CL, 420.9-431.5). CONCLUSION: The delisting of publicly-funded, high-strength opioids was accompanied by changes in funding source and small reductions in the weekly median daily doses dispensed. Although observed dose reductions of less than 1 MME weekly are likely not clinically relevant, safety implications of these changes require further monitoring.

Large care gaps in primary care management of asthma: a longitudinal practice audit.

OBJECTIVES: Care gaps in asthma may be highly prevalent but are poorly characterised. We sought to prospectively measure adherence to key evidence-based adult asthma practices in primary care, and predictors of these behaviours. DESIGN: One-year prospective cohort study employing an electronic chart audit. SETTING: Three family health teams (two academic, one community-based) in Ontario, Canada. PARTICIPANTS: 884 patients (72.1% female; 46.0±17.5 years old) (4199 total visits; 4.8±4.8 visits/patient) assigned to 23 physicians (65% female; practising for 10.0±8.6 years). MAIN OUTCOME MEASURES: The primary outcome was the proportion of visits during which practitioners assessed asthma control according to symptom-based criteria. Secondary outcomes included the proportion of: patients who had asthma control assessed at least once; visits during which a controller medication was initiated or escalated; and patients who received a written asthma action plan. Behavioural predictors were established a priori and tested in a multivariable model. RESULTS: Primary outcome: Providers assessed asthma control in 4.9% of visits and 15.4% of patients. Factors influencing assessment included clinic site (p=0.019) and presenting symptom, with providers assessing control more often during visits for asthma symptoms (35.0%) or any respiratory symptoms (18.8%) relative to other visits (1.6%) (p<0.01). SECONDARY OUTCOMES: Providers escalated controller therapy in 3.3% of visits and 15.4% of patients. Factors influencing escalation included clinic site, presenting symptom and prior objective asthma diagnosis. Escalation occurred more frequently during visits for asthma symptoms (21.0%) or any respiratory symptoms (11.9%) relative to other visits (1.5%) (p<0.01) and in patients without a prior objective asthma diagnosis (3.5%) relative to those with (1.3%) (p=0.025). No asthma action plans were delivered. CONCLUSIONS: Major gaps in evidence-based asthma practice exist in primary care. Targeted knowledge translation interventions are required to address these gaps, and can be tailored by leveraging the identified behavioural predictors. TRIAL REGISTRATION NUMBER: NCT01070095; Pre-results.

Estimating the clinical cost of drug development for orphan versus non-orphan drugs.

BACKGROUND: High orphan drug prices have gained the attention of payers and policy makers. These prices may reflect the need to recoup the cost of drug development from a small patient pool. However, estimates of the cost of orphan drug development are sparse. METHODS: Using publicly available data, we estimated the differences in trial characteristics and clinical development costs with 100 orphan and 100 non-orphan drugs. RESULTS: We found that the out-of-pocket clinical costs per approved orphan drug to be $166 million and $291 million (2013 USD) per non-orphan drug. The capitalized clinical costs per approved orphan drug and non-orphan drug were estimated to be $291 million and $412 million respectively. When focusing on new molecular entities only, we found that the capitalized clinical cost per approved orphan drug was half that of a non-orphan drug. CONCLUSIONS: More discussion is needed to better align on which cost components should be included in research and development costs for pharmaceuticals.