A Canadian Simulation Model for Major Depressive Disorder: Study Protocol.

BACKGROUND: Major depressive disorder (MDD) is a common, often recurrent condition and a significant driver of healthcare costs. People with MDD often receive pharmacological therapy as the first-line treatment, but the majority of people require more than one medication trial to find one that relieves symptoms without causing intolerable side effects. There is an acute need for more effective interventions to improve patients' remission and quality of life and reduce the condition's economic burden on the healthcare system. Pharmacogenomic (PGx) testing could deliver these objectives, using genomic information to guide prescribing decisions. With an already complex and multifaceted care pathway for MDD, future evaluations of new treatment options require a flexible analytic infrastructure encompassing the entire care pathway. Individual-level simulation models are ideally suited for this purpose. We sought to develop an economic simulation model to assess the effectiveness and cost effectiveness of PGx testing for individuals with major depression. Additionally, the model serves as an analytic infrastructure, simulating the entire patient pathway for those with MDD. METHODS AND ANALYSIS: Key stakeholders, including patient partners, clinical experts, researchers, and modelers, designed and developed a discrete-time microsimulation model of the clinical pathways of adults with MDD in British Columbia (BC), including all publicly-funded treatment options and multiple treatment steps. The Simulation Model of Major Depression (SiMMDep) was coded with a modular approach to enhance flexibility. The model was populated using multiple original data analyses conducted with BC administrative data, a systematic review, and an expert panel. The model accommodates newly diagnosed and prevalent adult patients with MDD in BC, with and without PGx-guided treatment. SiMMDep comprises over 1500 parameters in eight modules: entry cohort, demographics, disease progression, treatment, adverse events, hospitalization, costs and quality-adjusted life-years (payoff), and mortality. The model predicts health outcomes and estimates costs from a health system perspective. In addition, the model can incorporate interactive decision nodes to address different implementation strategies for PGx testing (or other interventions) along the clinical pathway. We conducted various forms of model validation (face, internal, and cross-validity) to ensure the correct functioning and expected results of SiMMDep. CONCLUSION: SiMMDep is Canada's first medication-specific, discrete-time microsimulation model for the treatment of MDD. With patient partner collaboration guiding its development, it incorporates realistic care journeys. SiMMDep synthesizes existing information and incorporates provincially-specific data to predict the benefits and costs associated with PGx testing. These predictions estimate the effectiveness, cost-effectiveness, resource utilization, and health gains of PGx testing compared with the current standard of care. However, the flexible analytic infrastructure can be adapted to support other policy questions and facilitate the rapid synthesis of new data for a broader search for efficiency improvements in the clinical field of depression.

Cost-effectiveness of pharmacogenomic-guided treatment for major depression.

BACKGROUND: Pharmacogenomic testing to identify variations in genes that influence metabolism of antidepressant medications can enhance efficacy and reduce adverse effects of pharmacotherapy for major depressive disorder. We sought to establish the cost-effectiveness of implementing pharmacogenomic testing to guide prescription of antidepressants. METHODS: We developed a discrete-time microsimulation model of care pathways for major depressive disorder in British Columbia, Canada, to evaluate the effectiveness and cost-effectiveness of pharmacogenomic testing from the public payer's perspective over 20 years. The model included unique patient characteristics (e.g., metabolizer phenotypes) and used estimates derived from systematic reviews, analyses of administrative data (2015-2020) and expert judgment. We estimated incremental costs, life-years and quality-adjusted life-years (QALYs) for a representative cohort of patients with major depressive disorder in BC. RESULTS: Pharmacogenomic testing, if implemented in BC for adult patients with moderate-severe major depressive disorder, was predicted to save the health system $956 million ($4926 per patient) and bring health gains of 0.064 life-years and 0.381 QALYs per patient (12 436 life-years and 74 023 QALYs overall over 20 yr). These savings were mainly driven by slowing or avoiding the transition to refractory (treatment-resistant) depression. Pharmacogenomic-guided care was associated with 37% fewer patients with refractory depression over 20 years. Sensitivity analyses estimated that costs of pharmacogenomic testing would be offset within about 2 years of implementation. INTERPRETATION: Pharmacogenomic testing to guide antidepressant use was estimated to yield population health gains while substantially reducing health system costs. These findings suggest that pharmacogenomic testing offers health systems an opportunity for a major value-promoting investment.

Barriers and facilitators influencing the management of academic detailing programs: A descriptive analysis of four programs.

BACKGROUND: Educating prescribers is a key strategy to reduce inappropriate prescribing in selection, dose, type, timing, and duration. Academic detailing (AD) is a form of continuing medical education to educate prescribers. AD programs have been established in Canada, Australia, the United States, and other countries. Each program operates uniquely to reflect its local context and resources. It remains unclear how AD programs in universal health care systems differ from each other in their program components and experiences. OBJECTIVES: To compare AD programs focusing on components of resources, activities, and services and to identify factors influencing program efficiency during the processes of program management, topic development, and service delivery among the selected Canadian and international AD programs. METHODS: We adopted a process evaluation methodology with semistructured interviews and documents. We selected 4 well-established AD programs through an iterative discussion with the BC Ministry of Health: three provincial AD programs in the Canadian provinces of British Columbia, Ontario, and Saskatchewan, and an Australian program based in the State of South Australia. We invited one leader from each program to attend a 1-hour teleconferencing interview. RESULTS: The 4 programs shared similarities of public government funding while differed in their operation models (centralized vs. decentralized), employment of detailers (part-time vs. full-time; hired by AD programs vs. hired by partnered multidisciplinary primary care teams) and staff who developed topics (detailers vs. nondetailers). The most common barriers were funding and reaching new participants, followed by team connection, detailer training resources, summarizing skills, and AD session scheduling. The most common facilitators were participant retention, participant recruitment through partnership, and easy access sessions. CONCLUSION: AD programs can potentially guide a prescriber's choice of drug. A program's operation can be impacted by its access to resources and participants, activities, and service design.

Assessing value in health care: using an interpretive classification system to understand existing practices based on a systematic review.

BACKGROUND: Implementing adequate strategies to assess the value of health services plays a central role in the effort to deal with the financial pressures faced by health care systems worldwide. This study aimed to understand which approaches to value assessment have been used in developed countries. METHODS: We conducted a rapid review and a gray literature search to identify value assessment frameworks. A two-stage screening process was utilized to identify existing approaches and cluster similar frameworks. In addition, we developed an interpretive classification system to make sense of existing approaches. RESULTS: One thousand one hundred seventy-six references were identified and 38 papers were selected for full-review. Among these 38 articles, 22 distinct approaches to assess value of health care interventions were identified and classified according to four points: 1) use of single or multiple considerations to base value estimates; 2) use of disease-specific or generic criteria; 3) reliance on process-based or outcomes-based consideration; and 4) type of input and evidence considered. CONCLUSIONS: The contextual nature of value assessment in health care becomes evident with the diversity of existing approaches. Despite the predominance of cases relying on the Incremental cost-effectiveness ratio as the measure of value, this approach has not been sufficient to meet the needs of decision-makers. The use of multiple criteria has become more and more important, as well as the consideration of patient-reported measures. Considerations of costs are not always explicit and consistent.

Uterine Artery Embolization and Surgical Methods for the Treatment of Symptomatic Uterine Leiomyomas: A Systemic Review and Meta-analysis Followed by Indirect Treatment Comparison.

PURPOSE: There is significant discussion and uncertainty about the optimal management of symptomatic uterine leiomyomas (SULs). Nonsurgical procedures such as uterine artery embolization (UAE) have been developed. The goal of this study was to conduct a meta-analysis and an indirect treatment comparison to examine the comparative efficacy and safety of the surgical procedures to treat SULs compared with UAE. METHODS: MEDLINE, EMBASE, Lilacs, and the Cochrane Central Register of Controlled Trials databases were searched from inception to February 2016. Ten randomized controlled trials comparing UAE versus hysterectomy, myomectomy, and laparoscopic occlusion of the uterine arteries in patients with SUL published in a peer-reviewed journal were included. Two reviewers independently selected studies, assessed quality, and extracted data. Discrepancies were resolved through consensus. FINDINGS: Data from 986 patients submitted to UEA (n = 527) or surgery (n = 459) were analyzed. UAE had a lower risk of major complications (risk ratio [RR], 0.45 [95% CI, 0.22-0.95]; P = 0.04)and a higher risk of minor complications (RR, 1.65 [95% CI, 1.32-2.06]; P < 0.00001); UAE had a higher risk of re-intervention up to 2 years (RR, 3.74 [95% CI, 1.76-7.96]; P = 0.0006) and up to 5 years (RR, 5.01 [95% CI, 1.37-18.39]; P = 0.02); UAE had a similar risk of follicle-stimulating hormone levels >40 IU/L after 6 months (RR, 1.76 [95% CI, 0.24-12.95]; P = 0.58)and of recommending the procedure to another patient up to 5 years after treatment (RR, 1.00 [95% CI, 0.87-1.14]; P = 0.94). The indirect comparison between myomectomy and hysterectomy found that the 2 procedures were similar in the studied outcomes. IMPLICATIONS: Compared with surgery, UAE had lower rates of major complications with an increased risk of re-intervention up to 2 and 5 years after the first procedure. UAE compared with surgery had a similar risk of ovarian failure and similar recommendation of the procedure to another patient. However, the number of trials was limited, and there was a high risk of bias in at least 2 domains. None of the trials blinded the participants and personnel or the outcome assessment. PROSPERO identifier: CRD42015026319.

A Systematic Review of Health Economics Simulation Models of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Many decision-analytic models with varying structures have been developed to inform resource allocation in chronic obstructive pulmonary disease (COPD). OBJECTIVES: To review COPD models for their adherence to the best practice modeling recommendations and their assumptions regarding important aspects of the natural history of COPD. METHODS: A systematic search of English articles reporting on the development or application of a decision-analytic model in COPD was performed in MEDLINE, Embase, and citations within reviewed articles. Studies were summarized and evaluated on the basis of their adherence to the Consolidated Health Economic Evaluation Reporting Standards. They were also evaluated for the underlying assumptions about disease progression, heterogeneity, comorbidity, and treatment effects. RESULTS: Forty-nine models of COPD were included. Decision trees and Markov models were the most popular techniques (43 studies). Quality of reporting and adherence to the guidelines were generally high, especially in more recent publications. Disease progression was modeled through clinical staging in most studies. Although most studies (n = 43) had incorporated some aspects of COPD heterogeneity, only 8 reported the results across subgroups. Only 2 evaluations explicitly considered the impact of comorbidities. Treatment effect had been mostly modeled (20) as both reduction in exacerbation rate and improvement in lung function. CONCLUSIONS: Many COPD models have been developed, generally with similar structural elements. COPD is highly heterogeneous, and comorbid conditions play an important role in its burden. These important aspects, however, have not been adequately addressed in most of the published models.

Pediatric Palliative Care Program versus Usual Care and Healthcare Resource Utilization in British Columbia: A Matched-Pairs Cohort Study.

BACKGROUND: Evidence on the impact of pediatric palliative care programs (PPCP) on resource utilization is scarce and requires broader measures to include utilization beyond the hospital setting. OBJECTIVE: This research aims to provide a Canadian comparative analysis between children in a PPCP with those under usual care, including hospice use to inpatient resource use measurement. METHODS: We conducted a retrospective matched-pairs (disease and age at death) cohort comparison of children who died in hospice versus hospital (never enrolled in a PPCP), from 2008 to 2012. Utilization was retrieved from administrative databases and chart review. The main outcomes were number of admissions and length of stay (LOS). RESULTS: Eleven pairs were found. PPCP users were more likely to have advanced directives (100% vs. 27%). After controlling for disease and age, we found no significant difference in number of admissions; however, PPCP users had an increase in admissions post-referral compared to pre-referral (median 3.08 admissions), driven by the need for critical care. We did not find a significant difference in LOS, but observed longer admissions among PPCP users pre- (1.91 days/month) and post-referral (3.66 days/month) compared to usual care. Over 60% of inpatient utilization shifted to the hospice post-referral. DISCUSSION: The terminal pediatric population referred to PPCP may systematically differ from those under usual care even before enrollment, presenting with higher inpatient utilization in critical care nearing death. A significant portion of inpatient utilization shifted to the hospice, with implications for resource reallocation and enhancements in PPCP referrals.

Effect of pediatric palliative care programs on health care resource utilization and costs among children with life-threatening conditions: a systematic review of comparative studies.

BACKGROUND: Pediatric palliative care is a relatively new and evolving field, and the cost of pediatric palliative care programs is unclear. We conducted a systematic review to compare inpatient health care utilization and costs among children with life-threatening conditions who have accessed a pediatric palliative care program and those who have not. METHODS: We searched MEDLINE, Embase, CINAHL and LILACS databases from January 2000 to July 2013, as well as the grey literature, for experimental or observational studies that compared pediatric palliative care programs with usual care. Outcomes of interest included hospital admissions, length of stay and health care costs. RESULTS: Of the 5193 records identified, we reviewed 109 in full and included 11 in our study. The overall quality of the studies was moderate to low. We observed mixed results for all outcomes. Compared with patients receiving usual care, fewer patients in the palliative care group had hospital admissions and fewer of those with cancer had planned hospital admissions. In contrast, no effects were observed regarding the overall number of hospital, emergency or outpatient admissions. Conflicting results were observed with regards to critical care utilization. Studies showed a trend toward shorter lengths of stay in hospital in the palliative care group. However, a single study that also considered inpatient time in hospice facilities found an increase in total length of stay, which showed a shift in the setting of health care utilization. We observed no conclusive trend in the effects on cost. INTERPRETATION: Evidence suggests that pediatric palliative care programs may result in a shift of utilization to other health care settings beyond hospital care. These settings should be considered when measuring resource utilization and costs.