Pharmacists' chronic disease management in chronic obstructive pulmonary disease: Effect on health services utilization.

BACKGROUND: There is limited real-world evidence on evaluation of chronic disease management initiatives provided by pharmacists to patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To evaluate changes in COPD-related health care resource utilization between patients with COPD who had pharmacist-provided chronic disease management (comprehensive annual care plan [CACP]) vs those who did not have CACP. METHODS: Patients with COPD who received a CACP in Alberta between 2012 and 2015 were identified within the Alberta Health administrative data. Each of these patients were matched with 2 control patients with COPD based on age, sex, provider, date of service, and qualifying comorbidities. Controlled interrupted time series analysis was used to evaluate changes in COPD-specific hospitalizations, emergency department (ED) visits, physician visits, and claims for pulmonary function test. Immediate and temporal changes were calculated for the difference in outcomes 1 year before and 1 year after receiving the CACP for the intervention group and matched controls. RESULTS: Eligible patients (N = 74,365), of whom 28,795 (38.7%) had received CACPs, were matched to a total of 45,570 controls. In 1 year after the CACPs implementation, the number of COPD-related hospitalization visits decreased by 174 (95% CI = -270.8 to -76.5) per 10,000 patients per month, COPD-related ED visits decreased by 123 (95% CI = -294.9 to 49.6) per 10,000 per month, general practitioner visits decreased by 153.9 per 10,000 per month (95% CI = -293.3 to -14.5), and pulmonary function test claims decreased by 19.5 per 10,000 per month (95% CI = -70.1 to 31.2) when compared with the matched controls. However, significant difference between the 2 groups was found for COPD-related hospitalizations only, which was not confirmed by the sensitivity analysis. CONCLUSIONS: In patients with COPD who were provided with care plans by their community pharmacists, there was no significant decrease in COPD-related hospitalizations or ED visits over 1 year compared with the matched controls who did not have a pharmacist-provided care plan. Physician visits and pulmonary function tests did not change significantly for those who had CACP compared with those who did not. There is a need to further understand how care plans can better impact other outcomes that are important in COPD management. DISCLOSURES: This study was supported by a grant from the M.S.I. Foundation (Grant#895) based in Alberta, Canada. Dr Bhutani has consulted for Astra Zeneca, GlaxoSmithKline, Boehringer Ingelheim, Valeo, Covis, and Sanofi. The authors declare no other relevant conflicts of interest or financial relationships. This study is based on data provided by Alberta Health. The interpretation and conclusions of the results are those of the researchers and do not necessarily represent the views of the government of Alberta nor the funder (M.S.I. Foundation). All authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors.

Cost-utility analysis of normothermic machine perfusion compared to static cold storage in liver transplantation in the Canadian setting.

To estimate the incremental cost-effectiveness of a liver transplant program that utilizes normothermic machine perfusion (NMP) alongside static cold storage (SCS) compared to SCS alone (control). A Markov model compared strategies (NMP vs. control) using 1-year cycle lengths over a 5-year time horizon from the public healthcare payer perspective. Primary micro-costing data from a single center retrospective trial were applied along with utility values from literature sources. Transition probabilities were deduced using the retrospective trial cohort, local transplant data, and supplemented with literature values. Scenario and probabilistic sensitivity analysis (PSA) were conducted. The NMP strategy was cost-effective in comparison to the control strategy, which was dominated. The mean cost for NMP was $456 455 (2021 US$) and the control was $519 222. The NMP strategy had greater incremental quality-adjusted life years (QALYs) gains over 5 years compared to the control, with 3.48 versus 3.17, respectively. The overarching results remained unchanged in scenario analysis. In PSA, NMP was cost-effective in 63% of iterations at a willingness-to-pay threshold of $40 941. The addition of NMP to a liver transplant program results in greater QALY gains and is cost-effective from the public healthcare payer perspective.

Disparities in adherence to diabetes screening guidelines among males and females in a universal care setting: A population-based study of 1,380,697 adults.

Background: National guidelines recommend that all adults over the age of 40 years undergo screening for diabetes at least once every 3-years. We examined the adherence to these guidelines among males and females after accounting for age, urban/rural residence, and material deprivation. We also examined the incidence of prediabetes and diabetes in adherent and non-adherent individuals. Methods: Our study is based on a retrospective population-level inception cohort of adults aged 40-79 years without pre-existing diabetes or cardiovascular disease on April 1, 2013. Adherence during a 3-year screening period (2013-2016) and prediabetes and diabetes during a 4-year follow-up period were examined. Multivariate logistic regression was used to examine the adjusted association between sex and adherence. Findings: Among 1,380,697 individuals (49·2% male, 50·8% female) adherence rates were 69·9% in males and 79·8% in females. Sex-differences in adherence were largest in younger individuals (58·0% and 72·6% and in males and females aged 40-44 years, respectively) and consistent across rural/urban residence and material deprivation. Females were more adherent (adjusted odds ratio 1·92; 95% confidence interval 1·89 to 1·95) than males. Prediabetes and diabetes rates among individuals who adhered to screening guidelines were 15·7% and 2·6% among males and 13·4% and 1·5% among females. During the follow-up period, an additional 3·2% and 1·9% of adherent males and females had diabetes. Incidence rates of prediabetes and diabetes during the follow-up period among individuals who did not adhere to screening guidelines were 8·8% and 2·1% among males and 7·3% and 1·3% among females. Interpretation: Adherence to diabetes screening guidelines is sub-optimal, especially among young males. Despite lower rates of adherence to screening, males have higher rates of prediabetes and diabetes compared to females. There is a need for education campaigns to improve diabetes screening rates in young adults, especially males. Funding: This study was funded by the Canadian Institutes of Health Research Sex and Gender Science Chair (Recipient: Kaul).

CT-based assessment of body composition and skeletal muscle in melanoma: A systematic review.

BACKGROUND/OBJECTIVES: Sarcopenia (low skeletal muscle index) and myosteatosis (low skeletal radiodensity) have been associated with poor outcomes in melanoma. This systematic review was performed to summarize and critically evaluate current literature surrounding body composition in melanoma. METHODS: MEDLINE and Embase databases were searched for studies of melanoma patients with computed tomography (CT) based body composition analysis from 2000 to 2020. Outcomes of interest were survival, including overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS), as well as treatment-related adverse events (AEs). RESULTS: Nine studies of 914 patients were included in the final review. The majority of studies were of metastatic melanoma patients treated with immunotherapy. Studies demonstrated a variety of CT analysis techniques and cut-offs to define sarcopenia and myosteatosis. Associations of sarcopenia or myosteatosis with survival (OS, PFS, DFS) or risk of treatment-related AEs were conflicting. Multiple studies had low quality of evidence due to small sample sizes, use of non-validated CT measures, and lack of multivariable analyses. CONCLUSIONS: Due to methodologic heterogeneity and low quality of evidence, impacts of CT-derived body composition parameters on outcomes in melanoma are unclear. Further research should be conducted to elucidate impacts of body composition in melanoma.

Adopting and implementing an innovative model to organize diabetes care within First Nations communities: A qualitative assessment.

BACKGROUND: Diabetes care remains suboptimal in First Nations populations. Innovative and culturally relevant approaches are needed to promote systematic and proactive organization of diabetes care for people living with diabetes on-reserve in Canada. The RADAR model is one strategy to improve care: an integrated disease registry paired with an electronic health record for local community healthcare providers with remote care coordination. We qualitatively assessed adoption and implementation of RADAR in First Nations communities in Alberta to inform its potential spread in the province. METHODS: We used the RE-AIM framework to evaluate adoption and implementation of RADAR in 6 First Nations communities. Using purposeful sampling, we recruited local healthcare providers and remote care coordinators involved in delivering RADAR to participate in telephone or in-person interviews at 6- and 24-months post-implementation. Interviews were digitally recorded, transcribed, and verified for accuracy. Data was analyzed using content analysis and managed using ATLAS.ti 8. RESULTS: In total, we conducted 21 semi-structured interviews (6 at 6-months; 15 at 24-months) with 11 participants. Participants included 3 care coordinators and 8 local healthcare providers, including registered nurses, licensed practical nurses, and registered dietitians. We found that adoption of RADAR was influenced by leadership as well as appropriateness, acceptability, and perceived value of the model. In addition, we found that implementation of RADAR was variable across communities regardless of implementation supports and appropriate community-specific adaptations. CONCLUSIONS: The variable adoption and implementation of RADAR has implications for how likely it will achieve its anticipated outcomes. RADAR is well positioned for spread through continued appropriate community-based adaptations and by expanding the existing implementation supports, including dedicated human resources to support the delivery of RADAR and the provision of levels of RADAR based on existing or developed capacity among local HCPs. TRIAL REGISTRATION: Not applicable to this qualitative assessment.  ISRCTN14359671 .

The Actual Operative Costs of Liver Transplantation and Normothermic Machine Perfusion in a Canadian Setting.

BACKGROUND: Liver transplantation is an effective treatment for end-stage liver disease. However, waiting lists continue to lengthen as demand exceeds supply. Use of extended criteria donors has helped but is associated with increased rates of complications. The application of normothermic machine perfusion (NMP) has been shown to be protective, especially in more marginal grafts. Despite this benefit, no cost-effectiveness studies have been published. OBJECTIVE: This study serves as a prelude to a cost-effectiveness analysis of the costs of liver procurement, transplantation, and machine perfusion in a Canadian setting. METHODS: The total costs were calculated for 106 in-province procurements, the set cost for 237 out-of-province procurements, and 343 liver transplantations. These costs include overheads, supplies, anaesthesia technologist and nursing salaries, and physician billings. Base and modified costs for all procedures were calculated, with consideration of physician billing modifiers. The total cost per run of NMP was calculated, with a range based on variations in the exchange rates for Great British pounds (£) to Canadian dollars ($Can), year 2019 values. RESULTS: Costs were $Can30,770.22 for in-province and $Can44,636.73 for out-of-province liver procurement and transplantation. These increased to $Can35,659.22 and 48,076.18 when considering modifiers. The minimum cost per NMP run was $Can18,593.02. CONCLUSIONS: Although the cost per run is substantial, NMP could potentially lead to cost savings by decreasing night-time salary premiums, complications, and patient length of stay. A formal cost-effectiveness study of NMP in liver transplantation is underway to help clarify the financial benefit or burden of this new technology.

Financial advantage or barrier when deprescribing for seniors: A 'case based' analysis.

OBJECTIVE: Deprescribing has several barriers, including financial implications; the purpose of this study is to determine the financial impact of deprescribing on the pharmacy, public payer (government), and the patient, across Canadian provinces and territories. METHODS: A case was developed to reflect a typical senior in Canada. Eight different deprescribing scenarios were studied financially before and after each intervention. Detailed drug costs were obtained from the government plans covered in each province or territory, and were used to calculate the annual average pharmacy margin and total government and patient share. RESULTS: Before deprescribing, the patient share for the regimen ranged between $1511.47 (Quebec) and $4342.75 (British Columbia) per year. The scenario with the greatest cost saving to the patient and greatest loss to the pharmacy was switching to a lower cost medication from liraglutide to prefilled detemir, with highest savings in patient share of $3699.95 and highest loss in pharmacy margin of $473.84 in Alberta. CONCLUSION: There is a range in costs and coverage for medications across Canada. The scenarios demonstrated a small impact on the pharmacy's gross margin, in some cases a significant financial impact on patient costs, but minimal impact to government. Deprescribing initiatives and policies should include financial considerations for pharmacies and patients.

Working towards a better understanding of type 2 diabetes care organization with First Nations communities: a qualitative assessment.

BACKGROUND: Diabetes care is suboptimal in First Nations populations. Innovative and culturally-relevant approaches are needed to promote proactive organization of diabetes care for diabetes patients on-reserve in Canada. The Reorganizing the Approach to Diabetes care through the Application of Registries (RADAR) model is one strategy to improve care: an integrated disease registry and electronic health record for community healthcare workers with centralized care coordination. The aim of this study was to qualitatively assess the organization of type 2 diabetes care in participating communities in Alberta, Canada, at baseline prior to implementing RADAR. METHODS: Using qualitative description, we purposefully sampled healthcare workers involved in diabetes care at each health center. We used the 5Rs framework (i.e., Recognize, Register, Resource, Relay, Recall) to inform the baseline assessment and conducted group interviews in 6 communities with 16 healthcare workers. Detailed notes were taken and validated by participants. Data was managed using ATLAS.ti 8 and analyzed using content analysis. RESULTS: We found strong commitment and effort by local healthcare workers to support people living with type 2 diabetes in their communities. However, healthcare workers were limited in their ability to identify (i.e., recognize), track (i.e., register and relay) and manage (i.e., resource and recall) people with type 2 diabetes as proposed by the 5Rs framework. The organization of diabetes care was often reactive and dependent on patients' abilities to navigate the health system. Interestingly, participants talked about the 5Rs in relationship to one another, not in a linear or isolated manner. CONCLUSIONS: Overall, the organization of diabetes care in participating communities did not align with the recommended approach of the 5Rs framework. In addition, we propose "reimagining" the 5Rs to reflect the interdependence and mediation of components situated within human and financial resources. This will better equip healthcare workers to assess, plan and execute organized and proactive diabetes care. However, the onus on people living with type 2 diabetes to engage with healthcare services remains a concern. TRIAL REGISTRATION: ISRCTN.com, ISRCTN14359671.

Validation of drug prescription records for senior patients in Alberta's Tomorrow Project: Assessing agreement between two population-level administrative pharmaceutical databases in Alberta, Canada.

PURPOSE: To assess agreement between the Pharmaceutical Information Network (PIN), a newly implemented medication data repository in Alberta, Canada, and the Alberta Blue Cross (ABC) database, a long established database with medication records of all senior patients in Alberta. METHODS: PIN data (2008-2015) were cross-validated with ABC medication records for senior participants (older than 65 years old) in Alberta's Tomorrow Project (ATP), a longitudinal cohort study in Alberta. The completeness and accuracy of PIN were respectively calculated as the percentage of ABC records coexisting (concordant) in PIN and the percentage of concordant records having mutually agreeable information on drug quantity. Generalized linear models were used to examine potential association of PIN completeness and accuracy with sociodemographic factors. RESULTS: A total of 1 218 191 drug prescription records from 13 143 ATP participants were captured by PIN and ABC in 2008-2015, among which 91.6% were from PIN, 82.5% from ABC, and 74.2% coexisted in PIN and ABC. The overall completeness of PIN in capturing ABC medication records was 89.9%, with small variations (less than ±5%) across types of drugs. The completeness of PIN was improved on average by 1.3% annually over time (P < .001). PIN had 100% accuracy as defined by drug quantity data agreeable with ABC records. No significant associations were observed with age, sex, ethnicity, rural/urban areas, and socioeconomic status of the participants. CONCLUSIONS: Cross-validated with the ABC dataset, our study showed that irrespective of drug type, PIN has a fairly good completeness (approximately 90%) and accuracy (100%) in capturing the ABC claimed medications for senior patients in Alberta.

The frequency and availability of population-specific patient reported outcome measures and minimal clinically important differences among approved drugs in Canada.

BACKGROUND: Patient reported outcome measures (PROMs) and minimal clinically important differences (MCIDs) are included in Canada's Common Drug Review (CDR) process to approve new drugs. Often, the measures report on the health-related quality of life (HRQoL), but can also describe the symptoms, efficacy and harms important to patients. They can be generic or population/condition specific, validated or not. We examined the frequency, availability and accessibility of validated, specific PROMs and MCIDs reported in the CDR reports. METHODS: We searched the Canadian Agency for Drugs and Technologies in Health (CADTH) on-line database for completed Common Drug Review, Clinical Review Reports (CDR-CRR) between November 2013 and February 2017. Two independent reviewers examined the reports and references for PROMs and MCIDs. Both reviewers separately categorized the PROMs and MICDs according to purpose, validation, availability and funding received. Discrepancies were rectified by consensus with a third investigator. RESULTS: One-hundred and five unique PROMs were extracted from 39 CDR-CRR, 57% with a HRQoL component. 91/105 (87%) referenced a validation study and 62/105 (59%) referenced a validation study in the study population of interest. Fifty-seven MCID references were extracted from 39 CDR-CRR. 34/57 (60%) were specific to the study population of interest, and 36% had a HRQoL component. 50% of PROM and 53% of MCID references were publicly available. CONCLUSIONS: PROMs and MCIDs referenced in CDR-CRR show similar trends. The majority are validated, but not necessarily in the study population of interest. Continued critical examination is required to evaluate new drugs specific to the population of interest.

An analysis of redactions in Canada's Common Drug Review Clinical Review Reports and how they relate to the patients' voice.

IMPORTANCE: Canada's Common Drug Review (CDR) evaluates drug data from published and unpublished research, as well as input from patient groups, to recommend provincial coverage. Currently, the CDR process gives manufacturers the opportunity to redact information in the final publicly available report. Patients often have strong feelings regarding the efficacy, harms, health-related quality of life (HRQL), and cost associated with the drugs under review and their redacted data. Highlighting Canada's approach will hopefully build on the growing international concern regarding transparency of clinical study data. OBJECTIVE: The purpose was to objectively examine and classify completed, publicly available CDR-Clinical Review Reports (CRR) for redactions, and compare them to the patients' reported interests as patient-centred outcomes. METHODS: Two independent reviewers searched for and examined publicly available CDR-CRR from November 2013-September 2016 through the Canadian Agency for Drugs and Technologies in Health (CADTH) on-line database. Both reviewers separately classified the redactions and patient-reported interests into the following categories: efficacy, harms, HRQL and costs. All discrepancies were rectified by consensus involving a third reviewer. RESULTS: Fifty-two completed CDR-CRR were reviewed. 48 (92%) included patient-reported interests and 40 (77%) had redactions classified in the following categories: efficacy (75%), costs (48%), harms (38%), HRQL (23%). 89% of redactions were outcomes identified as patient-reported interests (69% efficacy, 42% harms, 36% cost, 33% HRQL). When examining drug characteristics, biological agents were statistically associated with increased odds of redactions with respect to either efficacy (OR 3.4, 95% CI 1.0 to 11.6) or harms (OR 3.5, 95% CI 1.02 to 12.4) compared with non-biological agents. CONCLUSIONS: Whether data from the CDR-CRR used in the decision-making should be fully disclosed to the public is controversial. Our findings suggest clinical data (efficacy, harms, HRQL) matters to patients and should be publicly available within the CDR-CRR. Canada trails Europe and the USA regarding the transparency of clinical study data. This lack of transparency relates to the patient voice, and limits movement towards patient-centred care and patient-engaged research, restricting real-world value measurement.

Limited Effectiveness of Diabetes Risk Assessment Tools in Seniors' Facility Residents.

BACKGROUND: Undiagnosed diabetes can create significant management issues for seniors. OBJECTIVES: To evaluate the effectiveness of two diabetes risk surveys-the Canadian Diabetes Risk Assessment Questionnaire (CANRISK) and the Finnish Diabetes Risk Score (FINDRISC)-to identify elevated blood glucose levels in seniors. METHODS: A cross-sectional study was conducted in senior living facilities in Edmonton, Alberta, Canada. Those with known diabetes, without capacity, considered frail, or unable to communicate in English were excluded. Participants completed the CANRISK and FINDRISC surveys and had their glycated hemoglobin A1c (HbA1c) measured. Correlations between seniors with elevated risk on the surveys and an HbA1c value of 6.5% or higher or 6.0% and higher were assessed. RESULTS: In this study, 290 residents participated; their mean age was 84.3 ± 7.3 years, 82 (28%) were men, and their mean HbA1c level was 5.7% ± 0.4%. Mean CANRISK score was 29.4 ± 8.0, and of the 254 (88%) considered to be moderate or high risk, 10 (4%) had an HbA1c level of 6.5% or higher and 49 (19%) had an HbA1c level of 6.0% or higher. Mean FINDRISC score was 10.8 ± 4.2, and of the 58 (20%) considered to be high or very high risk, 4 (7%) had an HbA1c level of 6.5% or higher and 15 (26%) had an HbA1c level of 6.0% or higher. The area under the receiver-operating characteristic curve was 0.57 (95% confidence interval 0.42-0.72) for the CANRISK survey identifying participants with an HbA1c level of 6.5% or higher and 0.59 (95% confidence interval 0.51-0.67) for identifying participants with an HbA1c level of 6.0% or higher. Similar characteristics were observed for the FINDRISC survey. CONCLUSIONS: In this group of seniors with no known diabetes history, mean HbA1c level approximated that in the general population and neither survey effectively identified those with elevated blood glucose levels. These findings should be confirmed in a larger study; nevertheless, routine use of these surveys as a diabetes screening strategy does not appear to be warranted at this time.

Risk of heart failure after community acquired pneumonia: prospective controlled study with 10 years of follow-up.

Objective To determine the attributable risk of community acquired pneumonia on incidence of heart failure throughout the age range of affected patients and severity of the infection.Design Cohort study.Setting Six hospitals and seven emergency departments in Edmonton, Alberta, Canada, 2000-02.Participants 4988 adults with community acquired pneumonia and no history of heart failure were prospectively recruited and matched on age, sex, and setting of treatment (inpatient or outpatient) with up to five adults without pneumonia (controls) or prevalent heart failure (n=23 060).Main outcome measures Risk of hospital admission for incident heart failure or a combined endpoint of heart failure or death up to 2012, evaluated using multivariable Cox proportional hazards analyses.Results The average age of participants was 55 years, 2649 (53.1%) were men, and 63.4% were managed as outpatients. Over a median of 9.9 years (interquartile range 5.9-10.6), 11.9% (n=592) of patients with pneumonia had incident heart failure compared with 7.4% (n=1712) of controls (adjusted hazard ratio 1.61, 95% confidence interval 1.44 to 1.81). Patients with pneumonia aged 65 or less had the lowest absolute increase (but greatest relative risk) of heart failure compared with controls (4.8% v 2.2%; adjusted hazard ratio 1.98, 95% confidence interval 1.5 to 2.53), whereas patients with pneumonia aged more than 65 years had the highest absolute increase (but lowest relative risk) of heart failure (24.8% v 18.9%; adjusted hazard ratio 1.55, 1.36 to 1.77). Results were consistent in the short term (90 days) and intermediate term (one year) and whether patients were treated in hospital or as outpatients.Conclusion Our results show that community acquired pneumonia substantially increases the risk of heart failure across the age and severity range of cases. This should be considered when formulating post-discharge care plans and preventive strategies, and assessing downstream episodes of dyspnoea.

Addressing the gaps in diabetes care in first nations communities with the reorganizing the approach to diabetes through the application of registries (RADAR): the project protocol.

BACKGROUND: Type-2 diabetes rates in First Nations communities are 3-5 times higher than the general Canadian population, resulting in a high burden of disease, complications and comorbidity. Limited community nursing capacity, isolated environments and a lack of electronic health records (EHR)/registries lead to a reactive, disorganized approach to diabetes care for many First Nations people. The Reorganizing the Approach to Diabetes through the Application of Registries (RADAR) project was developed in alignments with federal calls for innovative, culturally relevant, community-specific programs for people with type-2 diabetes developed and delivered in partnership with target communities. METHODS: RADAR applies both an integrated diabetes EHR/registry system (CARE platform) and centralized care coordinator (CC) service that will support local healthcare. The CC will work with local healthcare workers to support patient and community health needs (using the CARE platform) and build capacity in best practices for type-2 diabetes management. A modified stepped wedge controlled trial design will be used to evaluate the model. During the baseline phase, the CC will work with local healthcare workers to identify patients with type-2 diabetes and register them into the CARE platform, but not make any management recommendations. During the intervention phase, the CC will work with local healthcare workers to proactively manage patients with type-2 diabetes, including monitoring and recall of patients, relaying clinical information and coordinating care, facilitated through the shared use of the CARE platform. The RE-AIM framework will provide a comprehensive assessment of the model. The primary outcome measure will be a 10% improvement in any one of A1c, BP, or cholesterol over the baseline values. Secondary endpoints will address other diabetes care indicators including: the proportion of clinical measures completed in accordance with guidelines (e.g., foot and eye examination, receipt of vaccinations, smoking cessation counseling); the number of patients registered in CARE; and the proportion of patients linked to a health services provider. The cost-effectiveness of RADAR specific to these communities will be assessed. Concurrent qualitative assessments will provide contextual information, such as the quality/usability of the CARE platform and the impact/satisfaction with the model. DISCUSSION: RADAR combines innovative technology with personalized support to deliver organized diabetes care in remote First Nations communities in Alberta. By improving the ability of First Nations to systematically identify and track diabetes patients and share information seamlessly an overall improvement in the quality of clinical care of First Nations people living with type-2 diabetes on reserve is anticipated. TRIAL REGISTRATION: ISRCTN study ID ISRCTN14359671 , retrospectively registered October 7, 2016.

The Interplay Between Continuity of Care, Multimorbidity, and Adverse Events in Patients With Diabetes.

OBJECTIVES: To evaluate the impact of continuity of care and multimorbidity on health outcomes in patients with diabetes. RESEARCH DESIGN: Using a US claims database of insured patients, we identified those with incident diabetes between 2004 and 2008 and followed them until death, disenrollment, or December 31, 2010. Continuity of care was defined using Breslau's Usual Provider of Continuity (UPC; proportion of visits to the usual or predominant provider within 2 y of diabetes diagnosis). Multivariable logistic regression was used to determine the association between UPC in the first 2 years after diabetes diagnosis and subsequent 1-year composite primary outcome of all-cause hospitalization or death in year 3 in patients with/without multimorbidity. RESULTS: Of the 285,231 patients with incident diabetes, 74% had multimorbidity; their average age was 53 years (SD=10.5) and 49% were female. A total of 77,270 (27%) individuals had a mean UPC≥75% in the first 2 years. During year 3 of follow-up, 33,632 (12%) patients died or were hospitalized for any cause. Greater continuity of care (UPC≥75%) was associated with reduced risk of subsequent death or hospitalization [7.2% vs. 13.5%; adjusted odds ratio (aOR)=0.72; 95% CI, 0.70-0.75]. Although multimorbidity was independently associated with an increased risk of our primary composite endpoint (13.4% vs. 7.2%; aOR=1.26; 95% CI, 1.21-1.30), the association between greater continuity and better outcomes was similar in those with multimorbidity (aOR=0.71; 95% CI, 0.69-0.71) as in those without (aOR=0.75; 95% CI, 0.71-0.80). CONCLUSIONS: In patients with incident diabetes, greater continuity of care is associated with improved outcomes, irrespective of whether or not they have multimorbidity.

Changes in thiazolidinedione use and outcomes following removal of a prior-authorization policy: controlled time-series analysis.

OBJECTIVE: The aim of this study was to assess the impact of removing prior-authorization restrictions on the use of thiazolidinediones (TZDs) and outcomes. METHODS: In a controlled interrupted time-series analysis, whereby new users of antidiabetic agents over 65 years of age in adjacent Canadian provinces with different TZD-related policies [Alberta (n = 16,653) and Saskatchewan (n = 6682)] were followed from January 2001 to December 2006. Prior authorization for TZDs was removed in Alberta (intervention province) in December 2003 (rosiglitazone) and February 2004 (pioglitazone); no policy changes occurred in Saskatchewan (control province). Adjusted differences in percent change between intervention and control provinces were used to estimate policy-attributable effects (PAE) on TZD use within 30 days and 1 year and patient outcomes (composite of all-cause mortality or hospitalization for acute coronary events or heart failure) within 1 year. RESULTS: Mean age was 75 years, 51% were female, and 206,055 antidiabetic prescriptions were dispensed during follow-up. TZD use within 30 days among new users of antidiabetic agents increased almost >10% in Alberta compared with Saskatchewan controls immediately following the policy change: PAE = 9.4%, 95% confidence interval, 7.3%-11.6%. Other less expensive antidiabetic drug use decreased to exactly the same extent, suggesting TZD substitution. Compared with the controls, in Alberta there were no changes in the primary (clinical) composite outcome at 1 year (PAE = 0.31%, 95% confidence interval, -2.8% to +3.4%). CONCLUSIONS: The removal of a prior-authorization policy for TZDs was associated with an immediate increase in TZD use but did not impact patient outcomes. In this case, the policy removal shifted drug use to a more expensive drug with less certain clinical benefit.

Review of models used in economic analyses of new oral treatments for type 2 diabetes mellitus.

BACKGROUND: Economic models are considered to be important, as they help evaluate the long-term impact of diabetes treatment. To date, it appears that no article has reviewed and critically appraised the cost-effectiveness models developed to evaluate new oral treatments [glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors] for type 2 diabetes mellitus (T2DM). OBJECTIVES: This study aimed to provide insight into the utilization of cost-effectiveness modelling methods. The focus of our study was aimed at the applicability of these models, particularly around the major assumptions related to the clinical parameters (glycated haemoglobin [A1c], systolic blood pressure [SBP], lipids and weight) used in the models, and subsequent clinical outcomes. METHODS: MEDLINE and EMBASE were searched from 1 January 2004 to 14 February 2013 in order to identify published cost-effectiveness evaluations for the treatment of T2DM by new oral treatments (GLP-1 receptor agonists and DPP-4 inhibitors). Once identified, the articles were reviewed and grouped together according to the type of model. The following data were captured for each study: comparators; country; evaluation and key cost drivers; time horizon; perspective; discounting rates; currency/year; cost-effectiveness threshold, sensitivity analysis; and cost-effectiveness analysis curves. RESULTS: A total of 15 studies were identified in our review. Nearly all of the models utilized a health care payer perspective and provided a lifetime horizon. The CORE Diabetes Model, UK Prospective Diabetes Study (UKPDS) Outcomes Model, Cardiff Diabetes Model, Centers for Disease Control and Prevention (CDC) Diabetes Cost-Effectiveness Group Model and Diabetes Mellitus Model were cited. With the exception of two studies, all of the studies made significant assumptions surrounding the impact of GLP-1 receptor agonists or DPP-4 inhibitors on clinical parameters and subsequent short- and long-term outcomes. Moreover, often the differences in the clinical parameters were relatively small (e.g. 1 or 2 mmHg in blood pressure) and would not be considered by many as clinically important. Yet, the impact of these small clinical changes often resulted in large lifetime changes in health outcomes in the models. In particular, many studies assumed that changes in weight associated with the therapies would equate to improved outcomes, despite limited evidence for this assumption. Although the new oral treatments were regarded as cost effective in most studies based upon the studies reviewed, the validity of these projections, particularly for the longer time frames, is questionable. Indeed, although most of these studies have been conducted in the last 5 years, recent trial evidence has already questioned the validity of most of these studies. CONCLUSION: It is clear that a number of changes are required in the evaluation of diabetes therapies. First and foremost, the basic models need to be updated to include contemporary important clinical trial data assessing hard clinical outcomes in patients with diabetes. Second, there should be less emphasis on 40-year or lifetime costs and consequences of the therapies and a greater focus on short-term (5-year) and intermediate-term (10-year) outcomes. Practice is continually evolving, and the probability that these models would provide any valid predictions beyond 10 years is remote. Third, all modellers should immediately remove the basic assumption that small clinically inconsequential changes in A1c, SBP, lipids and weight result in major clinical improvements in patients. Future models should aim to include all relevant treatment outcomes, whether these relate to effects on underlying diabetes and its complications or to short- or long-term side effects of treatment. We need to explore why cost-saving interventions could benefit further from adding patient characteristics, which may be able to better predict the use of lower-cost alternatives. Moreover, the vast array of different clinical, cost and utility data used in the different models reviewed makes it apparent that a uniform methodology should be developed for diabetes economic models. In this manner, future models could be run using the same data, which would allow for more acceptable comparability between studies.

Evaluating the introduction of a computerized prior-authorization system on the completeness of drug exposure data.

PURPOSE: Administrative databases that only capture records for benefit-approved prescriptions may underestimate exposure because they do not capture non-benefit prescriptions. Using a natural experiment, we illustrate the impact of automating a prior-authorization policy on the completeness of drug exposure. METHODS: Using Saskatchewan (Canada) databases, weekly counts of benefit-approved and total prescription records in 2006 for new users of antidiabetic agents were examined across four categories: thiazolidinediones (TZDs), metformin, glyburide, and insulin. On July 1, 2006, Saskatchewan's public drug plan implemented an automated, online-adjudicated, prior-authorization process for TZDs; previously, prior approval was paper based. No such policy changes occurred for other drugs. We estimated the effect of this policy change on drug exposure using interrupted time-series analyses. RESULTS: We examined 223 552 prescription records: 19% were for TZDs, 48% for metformin, 20% for glyburide, and 13% for insulin. Prior to automation, there were, on average, 571 benefit-approved TZD records per week; however, the number of benefit-approved TZD records increased immediately after the automated process was introduced by 240 prescriptions per week (95% CI 200-280, p < 0.001). The average proportion of TZD benefit-approved records was 73% before and increased to 93% immediately following policy change (20% absolute change, 95% CI 18.7-20.4%). No changes were observed for metformin, glyburide, or insulin (p > 0.1 for all). CONCLUSIONS: Automating prior authorization for TZDs immediately increased the proportion of captured TZD records, suggesting in our study that one-fifth of TZD exposure was previously misclassified. If replicable, this indicates that even subtle changes in reimbursement policy may affect the validity of drug exposure data.

The association between market availability and adherence to antihypertensive medications: an observational study.

BACKGROUND: High adherence to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reported in observational studies has frequently been attributed to improved tolerability. However, these agents are also relatively new to the market compared to other antihypertensive medications. We aimed to determine if an association exists between adherence and market availability of a specific antihypertensive agent. METHODS: This retrospective cohort study used administrative data from Saskatchewan, Canada. Subjects were ≥40 years of age and received a new antihypertensive medication between 1994 and 2002. The primary outcome was the proportion of subjects achieving optimal adherence (≥80%) at 1 year, stratified by antihypertensive medication class and the year of availability. Adherence was measured using the cumulative mean gap ratio. RESULTS: A total of 36,214 subjects met the inclusion criteria. Optimal adherence was observed in 4987 of 8623 (57.8%) subjects receiving ACEIs and 1013 of 1600 (63.3%) subjects receiving ARBs, but adherence appeared inconsistent when examined within each antihypertensive class. A pattern of increasing mean adherence was observed according to availability in the ACEI subgroup (Spearman r = 0.82; P = 0.007) but not the ARB subgroup (Spearman r = 0.41; P = 0.49). However, the association between availability and optimal adherence converged when ARB and ACEI users were combined (Spearman r = 0.85, P < 0.001). CONCLUSIONS: Optimal adherence with ACEIs and ARBs compared to other antihypertensive agents may be associated with their relative availability. To what extent optimal adherence is also associated with improved tolerability, as currently believed, remains to be determined.

Restrictive drug coverage policies can induce substantial drug exposure misclassification in pharmacoepidemiologic studies.

BACKGROUND: Drugs reimbursed through a single-party payer such as health maintenance organizations or provincial governments are generally captured in administrative data if they have full-benefit status on that payer's formulary. However, drugs subject to restrictive drug coverage policies are often not fully captured if patients receive these drugs through mechanisms other than the single-payer formulary. OBJECTIVE: The goal of this study was to estimate the association between restrictive drug coverage and drug exposure misclassification across the Canadian provinces of Manitoba and Saskatchewan, which provide universal coverage for formulary-approved drugs to all citizens regardless of age or socioeconomic status. METHODS: Monthly dispensations were compared for 75 drugs between 2005 and 2008 from Canada's National Prescription Drug Utilization System database, which captures provincial drug formulary claims only, versus the IMS Brogan CompuScript Database, which captures all drug dispensations irrespective of formulary status. The association between restrictive drug coverage and drug exposure misclassification was measured using generalized estimating equations and multivariable adjustment. RESULTS: On average, 84% of monthly retail drug dispensations were captured by provincial claims data: 100% of monthly dispensations were captured for drugs with full-benefit status but only 61% of dispensations for drugs with restrictive drug coverage (adjusted risk ratio = 0.65 [95% confidence interval, 0.56-0.75]). The direction and magnitude of the potential misclassification bias between full-benefit and restricted policy drugs were consistent across all drug classes examined: acid-reducing drugs (97% vs 66%), analgesics (89% vs 64%), central nervous system drugs (103% vs 61%), cardiovascular drugs (100% vs 57%), diabetes drugs (98% vs 61%), osteoporosis drugs (96% vs 57%), and respiratory drugs (112% vs 60%). CONCLUSIONS: Drugs subject to restrictive coverage policies are substantially under-captured in administrative databases, leading to potential drug exposure misclassification in pharmacoepidemiologic studies relying on administrative databases. Pharmacoepidemiologic studies should clearly describe whether evaluated drugs are available as full benefits or subject to restrictive coverage policies and the potential impact on their results.