Canada’s Drug Agency | Drugs, Health Technologies and Systems.

The Cost-Effectiveness and Budget Impact of Remdesivir for Outpatient Treatment of COVID-19

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This report aims to estimate the impacts of providing remdesivir as an outpatient treatment for COVID-19 in Canada on health system costs and health outcomes.

The analyses presented in this report were conducted using 2022 data, which represented a year of the pandemic when a large proportion of the population in Canada was infected with COVID-19.

Last Updated : March 11, 2025

The Cost-Effectiveness and Budget Impact of Remdesivir for Inpatient Treatment of COVID-19

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This report aims to estimate the impacts of providing remdesivir as an inpatient treatment for COVID-19 in Canada on health system costs and health outcomes.

The analyses presented in this report were conducted using 2022 data, which represented a year of the pandemic when a large proportion of the population in Canada was infected with COVID-19.

Last Updated : March 11, 2025

The Cost-Effectiveness and Budget Impact of Tocilizumab for COVID-19

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This report aims to estimate the impacts of providing tocilizumab as a treatment for COVID-19 in Canada on health system costs and health outcomes.

The analyses presented in this report were conducted using 2022 data, which represented a year of the pandemic when a large proportion of the population in Canada was infected with COVID-19.
 

Last Updated : March 11, 2025

Lenvatinib for the Treatment of Hepatocellular Carcinoma After Liver Transplant

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Question(s)

  1. What is the clinical effectiveness and safety of lenvatinib for the first-line treatment of patients with unresectable HCC recurrence after liver transplant?

Key Message


What Is the Issue?

  • Liver transplant is 1 of the main curative therapies for liver cancer; however, hepatocellular carcinoma (HCC) recurrence presents in 10% to 20% of patients after liver transplant.
  • Lenvatinib, an oral multikinase inhibitor drug, was approved for use in Canada as a first-line standard therapy for unresectable HCC, based on a pivotal trial that excluded patients who underwent a prior liver transplant.
  • Data were scarce on the efficacy and safety of lenvatinib for treatment of HCC recurrence in patients who received a liver transplant, and were limited to a few case series and case reports.

What Did We Do?

  • We identified and summarized the literature on the evidence of the clinical effectiveness and safety of lenvatinib for the first-line treatment of patients with unresectable HCC recurrence after liver transplant.
  • We searched key resources, including journal citation databases and conducted a focused internet search for relevant evidence published since 2019. One reviewer screened citations for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings.

What Did We Find?

  • We identified a multinational, multicentre, retrospective, single-arm chart review study evaluating the efficacy and safety of lenvatinib in patients with HCC recurrence after liver transplant. Lenvatinib was primarily used as a first-line treatment for most patients (n = 42; 93.3%) and as a second-line treatment for 3 patients (6.7%).
  • The single-arm chart review study showed lenvatinib treatment had an overall response rate (ORR) of 20.0%, a median overall survival of 14.5 months, and a median progression-free survival (PFS) of 7.6 months. These findings were similar to those randomized to lenvatinib in the pivotal phase III REFLECT trial, which excluded patients who had a prior liver transplant.

What Does This Mean?

  • The findings of this report suggest that lenvatinib has a potential role as a first-line treatment of patients with HCC recurrence after liver transplant.
  • As the current evidence is limited to a retrospective single-arm chart review study, which had several limitations (e.g., lack of sample size calculation, noncomparative, and retrospective design), further investigations are needed to establish the clinical efficacy and safety of lenvatinib as a first-line treatment for unresectable HCC recurrence after liver transplant.
     

Last Updated : October 2, 2024

The Cost-Effectiveness and Budget Impact of Nirmatrelvir-Ritonavir for COVID-19

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This report aims to estimate the impacts of providing nirmatrelvir-ritonavir as an outpatient treatment for COVID-19 in Canada on health system costs and health outcomes.

The analyses presented in this report were conducted using 2022 data, which represented a year of the pandemic when a large proportion of the population was infected with COVID-19
 

Last Updated : March 11, 2025

Review of Guidelines on Second-Line Therapy for Patients With Relapsing-Remitting Multiple Sclerosis: A 2024 Update

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Question(s)

  1. What are the evidence-based guidelines regarding switching to a second-line therapy in patients with relapsing-remitting multiple sclerosis?

Key Message

What Is the Issue?

  • Multiple sclerosis is a chronic autoimmune disorder that causes damage to central nervous system cells. Relapsing-remitting multiple sclerosis is characterized by relapses (episodes of new or worsening symptoms) followed by periods of partial or complete recovery (remission).
  • First-line therapies for multiple sclerosis include interferons, glatiramer acetate, dimethyl fumarate, and teriflunomide. Second-line therapies include natalizumab, alemtuzumab, and fingolimod.
  • The considerations for switching from a first-line to a second-line therapy for patients with relapsing-remitting multiple sclerosis are unclear.

What Did We Do?

  • To inform decisions around switching patients with relapsing-remitting multiple sclerosis from a first-line to a second-line therapy, we sought to identify and summarize recommendations from evidence-based guidelines.
  • We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2019. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included guidelines, and narratively summarized the findings.

What Did We Find?

  • We identified 2 evidence-based guidelines that included recommendations around switching from a first-line to a second-line therapy in patients with relapsing-remitting multiple sclerosis.
  • One guideline from Spain classified therapies as moderate-efficacy (interferons, glatiramer acetate, dimethyl fumarate, and teriflunomide) and high-efficacy (fingolimod, cladribine, ocrelizumab, natalizumab, and alemtuzumab). The guideline recommends that patients switch from a moderate-efficacy disease-modifying therapy to a high-efficacy disease-modifying therapy for a variety of reasons including suboptimal response, adverse events, comorbidities, pregnancy plans, confirmed progression of disability, and tolerability issues. The guideline also included several recommendations specific to switching to natalizumab as well as washout periods when switching from a moderate-efficacy therapy.
  • One guideline from France included recommendations regarding washout periods for switching from a first-line therapy. The guideline recommends that when switching from a first-line therapy, a second-line therapy or an induction therapy could be started without a washout period if the patient has normal biological results. The guideline also recommends validating the indication, timing, and washout period of a switch to a second-line therapy or induction therapy with a multiple sclerosis expert centre or in a multidisciplinary consensus meeting. The guideline also included specific considerations for washout periods for dimethyl fumarate and teriflunomide.

What Does It Mean?

  • The considerations for switching from a first-line to a second-line therapy in patients with relapsing-remitting multiple sclerosis — including the timing of a switch, choice of second-line therapy, and washout periods — depend on treatment response, individual patient characteristics, and the specific first-line therapy being used.
  • Additional evidence-based guidelines that use comprehensive methods for identifying evidence and include clear links between identified evidence and recommendations will help to reduce uncertainty around considerations for switching from first-line to second-line therapies in patients with relapsing-remitting multiple sclerosis.

Last Updated : September 17, 2024

Methoxyflurane Inhalation as an Analgesic for Minor Gynecological, Ambulatory, or Emergency Procedures

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Question(s)

  1. What is the clinical effectiveness and safety of methoxyflurane inhalation for the treatment of pain during minor gynecological procedures?
  2. What is the clinical effectiveness and safety of methoxyflurane inhalation for the treatment of pain during minor ambulatory or emergency procedures?
  3. What is the cost-effectiveness of methoxyflurane inhalation for the treatment of pain during minor gynecological procedures?
  4. What is the cost-effectiveness of methoxyflurane inhalation for the treatment of pain during minor ambulatory or emergency procedures?

Key Message

What Is the Issue

  • Patients presenting to outpatient clinics or emergency departments often undergo procedures that cause pain.
  • Procedural sedation and analgesia for pain management requires a trained person to administer sedative agents and manage any drug related complications during and after the procedures.
  • Inhaled methoxyflurane (Penthrox) was approved in Canada in 2022 for short-term relief of moderate to severe acute pain associated with trauma or interventional medical procedures in conscious adult patients.
  • Unlike conventional sedation, patients can self-administer and titrate the amount of methoxyflurane by inhaling through a 3 mL device of 99.9% methoxyflurane, which provides continuous analgesia for 25 to 30 minutes.
  • Decision-makers are interested in understanding the use of inhaled methoxyflurane for analgesia in minor gynecological procedures or for use in ambulatory or emergency care settings.

What Did We Do

  • We identified and summarized literature on the clinical effectiveness and safety of methoxyflurane compared to placebo or other analgesics in minor medical and surgical procedures. We also searched for economic evaluations of the cost-effectiveness of methoxyflurane to manage pain during minor procedures.
  • We searched peer-reviewed and grey literature sources published between January 1, 2012, and July 3, 2024. One reviewer screened citations for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings.

What Did We Find

  • We identified 1 systematic review, 1 randomized controlled trial, 1 prospective cohort study, and 2 retrospective chart review studies that provided evidence on the efficacy and safety of methoxyflurane during various minor medical procedures, including cancer-related procedures (i.e., colonoscopy, transrectal ultrasonography-guided prostate biopsy, bone marrow biopsy, and solid organ biopsy) and other minor procedures (i.e., portacath insertion, portacath removal, and reduction of acute shoulder dislocation and acute elbow dislocation). Methoxyflurane Inhalation as an Analgesic for Minor Medical Procedures 2
  • Collective evidence from the few studies available for each type of procedure shows that methoxyflurane is an effective analgesic that, compared with sedation, shortens the duration of both the procedure and recovery without impacting procedural success.
  • Methoxyflurane at the analgesic dose appears to be safe — that is, not associated with kidney or liver toxicity and resulting in fewer cardiorespiratory complications or severe adverse events — despite being more likely to cause drowsiness and dizziness compared with placebo or conventional sedation.
  • We did not find any studies on the clinical efficacy and safety or cost-effectiveness of methoxyflurane inhalation for the treatment of pain for minor gynecological procedures.
  • We did not find any studies on cost-effectiveness of methoxyflurane inhalation for the treatment of pain for minor ambulatory or emergency procedures.

What Does This Mean

  • The limited studies available suggested that patient-controlled analgesia with methoxyflurane is feasible and safe for use during various ambulatory and emergency procedures.
  • The benefits of methoxyflurane in terms of reducing procedural and recovery time may facilitate workflow and shorten waiting lists in ambulatory and emergency care settings.
  • More studies are needed to provide stronger evidence on the efficacy and safety of methoxyflurane during medical and surgical procedures.

Last Updated : September 11, 2024

Drug Shortages and Patient Harms

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This report is linked to an expert panel on drug shortages in Canada. The objective of this report is to summarize the evidence on patient outcomes associated with supply chain disruptions of pharmaceuticals and vaccines.  

Last Updated : September 9, 2024