Comparative benefits and harms of individual opioids for chronic non-cancer pain: a systematic review and network meta-analysis of randomised trials.

BACKGROUND: Most systematic reviews of opioids for chronic pain have pooled treatment effects across individual opioids under the assumption they provide similar benefits and harms. We examined the comparative effects of individual opioids for chronic non-cancer pain through a network meta-analysis of randomised controlled trials. METHODS: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials to March 2021 for studies that enrolled patients with chronic non-cancer pain, randomised them to receive different opioids, or opioids vs placebo, and followed them for at least 4 weeks. Certainty of evidence was evaluated using the GRADE approach. RESULTS: We identified 82 eligible trials (22 619 participants) that evaluated 14 opioids. Compared with placebo, several opioids showed superiority to others for analgesia and improvement in physical function; however, when restricted to pooled-effect estimates supported by moderate certainty evidence, no differences between opioids were evident. Among opioids with moderate certainty evidence, all increased the risk of gastrointestinal adverse events compared with placebo, although no opioids were more harmful than others. Low to very low certainty evidence suggests that extended-release vs immediate-release opioids may provide similar benefits for pain relief and physical functioning, and gastrointestinal harms. CONCLUSIONS: Our findings support the pooling of effect estimates across different types and formulations of opioids to inform effectiveness for chronic non-cancer pain.

Evaluation of the cost and medical resource use outcomes associated with nasal glucagon versus injectable glucagon for treatment of severe hypoglycemia in people with diabetes in Canada: a modeling analysis.

OBJECTIVES: Treatments for severe hypoglycemia aim to restore blood glucose through successful administration of rescue therapy, and choosing the most effective and cost-effective option will improve outcomes for patients and may reduce costs for healthcare payers. The present analysis aimed to compare costs and use of medical services with nasal glucagon and injectable glucagon in people with type 1 and 2 diabetes in Canada when used to treat severe hypoglycemic events when impaired consciousness precludes treatment with oral carbohydrates using an economic model, based on differences in the frequency of successful administration of the two interventions. METHODS: A decision tree model was prepared in Microsoft Excel to project outcomes with nasal glucagon and injectable glucagon. The model structure reflected real-world decision-making and treatment outcomes, based on Canada-specific sources. The model captured the use of glucagon, emergency medical services (EMS), emergency room, inpatient stay, and follow-up care. Costs were accounted for in 2019 Canadian dollars (CAD). RESULTS: Nasal glucagon was associated with reduced use of all medical services compared with injectable glucagon. EMS call outs were projected to be reduced by 45%, emergency room treatments by 52%, and inpatient stays by 13%. Use of nasal glucagon was associated with reduced direct, indirect, and combined costs of CAD 1,249, CAD 460, and CAD 1,709 per severe hypoglycemic event, respectively, due to avoided EMS call outs and hospital costs, resulting from a higher proportion of successful administrations. CONCLUSIONS: When a patient with type 1 or type 2 diabetes is being treated for a severe hypoglycemic event when impaired consciousness precludes treatment with oral carbohydrate, use of nasal glucagon was projected to be dominant versus injectable glucagon in Canada reducing costs and use of medical services.

A cost-utility analysis of dulaglutide versus insulin glargine as third-line therapy for Type 2 diabetes in Canada.

AIM: The prevalence of Type 2 diabetes in Canada is estimated to be 7.6% and rising. Given the substantial economic burden associated with Type 2 diabetes treatment, optimizing healthcare expenditure is extremely important. In the present analysis, we evaluated the cost-effectiveness of dulaglutide 1.5 mg, a once-weekly glucagon-like peptide 1 agonist as third-line therapy relative to insulin glargine from the perspective of a Canadian healthcare payer. METHODS: A patient-level cost-utility model of Type 2 diabetes was developed to capture seven microvascular and macrovascular complications and severe and nonsevere hypoglycemia. Cohort characteristics and the relative efficacy of dulaglutide 1.5 mg and insulin glargine were derived from the AWARD-2 head-to-head trial, which was identified by systematic literature review. Cost data were derived from Canadian sources and expressed in 2016 Canadian dollars (CAD), and future cost and quality-adjusted life expectancy (QALE) estimates were discounted at 1.5% per annum. One-way and probabilistic sensitivity analyses were conducted. RESULTS: Based on the AWARD-2 trial, relative to insulin glargine, dulaglutide 1.5 mg was projected to increase QALE by 0.38 quality-adjusted life years and increase costs by CAD 19,773, resulting in an incremental cost-effectiveness ratio of CAD 52,580 per quality-adjusted life year gained. CONCLUSION: A computer simulation analysis showed that dulaglutide 1.5 mg would likely be cost-effective relative to insulin glargine in patients with Type 2 diabetes inadequately controlled on metformin and sulfonylurea in Canada.

The Cost of Unintended Pregnancies in Canada: Estimating Direct Cost, Role of Imperfect Adherence, and the Potential Impact of Increased Use of Long-Acting Reversible Contraceptives.

OBJECTIVE: Unintended pregnancies (UPs) are associated with a significant cost burden, but the full cost burden in Canada is not known. The objectives of this study were to quantify the direct cost of UPs in Canada, the proportion of cost attributable to UPs and imperfect contraceptive adherence and the potential cost savings with increased uptake of long-acting reversible contraceptives (LARCs). METHODS: A cost model was constructed to estimate the annual number and direct costs of UP in women aged 18 to 44 years. Adherence-associated UP rates were estimated using perfect- and typical-use contraceptive failure rates. Change in annual number of UPs and impact on cost burden were projected in three scenarios of increased LARC usage. One-way sensitivity analyses were conducted to assess the impact of key variables on scenarios of increased LARC use. RESULTS: There are more than 180 700 UPs annually in Canada. The associated direct cost was over $320 million. Fifty-eight percent (58%) of UPs occurred in women aged 20 to 29 years at an annual cost of $175 million; 82% of this cost ($143 million) was attributable to contraceptive non-adherence. Increased LARC uptake produced cost savings of over $34 million in all three switching scenarios; the largest savings ($35 million) occurred when 10% of oral contraceptive users switched to LARCs. The minimum duration of LARC usage required before cost savings was realized was 12 months. CONCLUSION: The cost of UPs in Canada is significant and much of it can be attributed to imperfect contraceptive adherence. Increased LARC uptake may reduce contraceptive non-adherence, thereby reducing rates of UP and generating significant cost savings, particularly in women aged 20 to 29.

Objectif : Les grossesses non planifiées (GNP) sont associées à un fardeau financier considérable; au Canada, l'ampleur de ce fardeau demeure inconnue. Cette étude avait pour objectif de quantifier les coûts directs des GNP au Canada, la proportion des coûts liés aux GNP attribuables à une observance imparfaite du schéma posologique contraceptif et les économies potentielles associées à un accroissement de l'utilisation de modes de contraception réversible à action prolongée (CRAP). Méthodes : Un modèle de coût a été conçu pour estimer le nombre annuel de GNP et leurs coûts directs chez les femmes âgées de 18 à 44 ans. Les taux de GNP associés à l'observance ont été estimés au moyen des taux d'échec de la contraception en utilisation parfaite et en utilisation typique. Les modifications du nombre annuel de GNP et les effets sur le fardeau financier ont été projetés dans le cadre de trois scénarios prévoyant un accroissement du recours aux modes de CRAP. Des analyses simples de la variance en matière de sensibilité ont été menées pour évaluer les effets de variables clés sur les scénarios prévoyant un accroissement du recours aux modes de CRAP. Résultats : On compte plus de 180 700 GNP chaque année au Canada. Les coûts directs qui leur sont associés sont de plus de 320 millions de dollars. Cinquante-huit pour cent (58 %) des GNP se sont manifestées chez des femmes de 20 à 29 ans, ce qui représente un coût annuel de 175 millions de dollars; 82 % de ce coût (143 millions de dollars) étaient attribuables à la non-observance du schéma posologique contraceptif. L'accroissement du recours aux modes de CRAP a généré des économies de plus de 34 millions de dollars dans le cadre des trois scénarios de transition envisagés; les économies les plus importantes (35 millions de dollars) ont été constatées dans le cadre du scénario prévoyant que 10 % des utilisatrices de contraceptifs oraux adopteraient un mode de CRAP. La durée minimale d'utilisation d'un mode de CRAP nécessaire pour l'obtention d'économies était de 12 mois. Conclusion : Au Canada, le coût des GNP est considérable; de plus, une bonne partie de ce coût est attribuable à une observance imparfaite du schéma posologique contraceptif. L'accroissement du recours aux modes de CRAP pourrait mener à une baisse du taux de non-observance du schéma posologique contraceptif, ce qui entraînerait une baisse des taux de GNP et générerait des économies considérables, particulièrement chez les femmes de 20 à 29 ans.

Impact of estradiol valerate/dienogest on work productivity and activities of daily living in women with heavy menstrual bleeding.

OBJECTIVES: To quantify the change in work productivity and activities of daily living in North American women with heavy menstrual bleeding (HMB) treated with estradiol valerate/dienogest (E2V/DNG; Qlaira(®)/Natazia(®)) compared to placebo. METHODS: Women in the United States and Canada, aged 20-53 years with an objective diagnosis of HMB and no recognizable anatomical pathology, were treated with E2V/DNG or placebo for seven cycles (196 days). Main outcome measures included work productivity (i.e., productivity while at work) and activities of daily living measured using a modified Work Productivity and Activity Impairment Questionnaire (mWPAI) on a Likert scale from 0 to 10 (higher values denote higher impairment levels). RESULTS: In both countries, significant improvement was observed between baseline and end of treatment in work productivity and activities of daily living impairment. The improvements in work productivity and activities of daily living with E2V/DNG treatment relative to placebo ranged from 37.2% to 39.2% across both countries. Monthly gains due to E2V/DNG treatment (net of placebo improvement) associated with improvement in work productivity were estimated to be US$80.2 and Can$70.8 (US$58.5) and those associated with improvement in activities of daily living were estimated to be US$84.9 and Can$73.5 (US$60.7). CONCLUSIONS: E2V/DNG was shown to have a consistent positive impact on work productivity and activities of daily living in U.S. and Canadian women with HMB. In addition, these improvements in work productivity and activities of daily living were associated with a reduction in HMB-related monetary burden compared to the placebo group.

Economic burden of surgically confirmed endometriosis in Canada.

OBJECTIVE: To estimate the societal economic burden of illness caused by surgically confirmed endometriosis in Canada in 2009, including direct health care costs, lost productivity, and lost leisure time costs. METHODS: Using a cross-sectional design, direct health care resource use data were obtained from nine family physicians and nine gynaecologists from across Canada, who were experienced in the treatment of women with surgically confirmed endometriosis. Data on alternative treatments and health care providers, as well as work absenteeism, lost leisure time, and caregiver time were obtained from a convenience sample of 27 women with endometriosis treated at two gynaecology clinics in Alberta and Quebec. Unit costs were assigned to resource use items for treatment-seeking patients, and total costs for each resource use item were aggregated to estimate the societal costs of endometriosis in Canada in 2009, across all prevalent cases of surgically confirmed endometriosis. RESULTS: The estimated mean annual societal cost of endometriosis was $5,200 per patient (95% CI $3,700 to $7,100), with lost productivity and lost leisure time costs accounting for 78%. Extrapolating these figures yields an estimated total annual cost to Canadian society of $1.8 billion (95% CI $1.3 billion to $2.4 billion) attributable to surgically confirmed endometriosis in Canada. CONCLUSION: For some women, surgically confirmed endometriosis has a substantial negative impact that can result in suffering to the individual and her family, and lead to substantial productivity losses. Understanding the interplay between direct costs, lost productivity, and quality of life is critical for accurately identifying and evaluating effective treatments for this condition.