Key Message

• Hormone therapy may be prescribed to support individuals identifying as transgender, nonbinary, and gender-nonconforming who would like to align their bodies or appearance with their gender identity.
  For individuals seeking feminizing hormone therapy (FHT), estrogen is an established treatment.
  Various administration routes (ways to take estrogen) are available for FHT with estrogen, including oral (taken as a pill) and transdermal (absorbed through the skin). However, the comparative clinical efficacy, effectiveness, and safety of transdermal and oral administration routes are unclear.
• Decision-makers are interested in whether transdermal estrogen therapy should be considered for public reimbursement (funding) as a first treatment option (first-line option), as an alternative to oral estrogen therapy, in the context of gender-affirming care.
• We evaluated the evidence of the clinical efficacy, effectiveness, safety, and cost-effectiveness (value from a human or health system perspective) of transdermal versus oral estrogen in gender-affirming care using a rapid review approach.
• We searched for evidence-based guidelines on the use of transdermal or oral estrogen in gender-affirming care.
• We identified 1 systematic review, 3 primary studies, and 4 evidence-based guidelines relevant to this review. No relevant health technology assessment (HTA) reports or cost-effectiveness studies were identified.
• The systematic review reported no preidentified clinical efficacy or effectiveness outcomes and did not formally compare the safety of transdermal estrogen to oral estrogen, which limits any related conclusions regarding the safety of these products in the context of gender-affirming care.
• The primary studies suggest that transdermal estrogen therapy may have lower cardiometabolic risks (conditions that affect the heart and metabolism, such as heart attack, obesity, and diabetes), have similar effects on bone health, and have similar feminizing effects (breast development, changes in body fat composition) compared to oral therapy. However, important patient outcomes such as quality of life and adverse effects remain unexamined.
• Current guidelines, largely based on expert opinion, recommend transdermal estrogen therapy for patients older than either 40 or 45 years or those with a higher cardiovascular risk, starting at a lower dose and gradually increasing as necessary.
• Both transdermal and oral formulations appear safe, but it is unclear if transdermal estrogen offers the same or greater benefits in gender-affirming care.
• Those making reimbursement decisions may consider individual risk for venous thromboembolism (VTE) (blood clots in the veins) or other harms that have been identified by those who are concerned about the risks associated with oral therapy.

Key Message

• Hormone therapy may be prescribed to support individuals experiencing symptoms of menopause due to a decline in estrogen in the body. Menopausal symptoms may vary in frequency and intensity, and commonly include vasomotor symptoms (VMS) (often referred to as hot flashes or night sweats), sleep disruption, and mood changes, and may include impacts to bone or heart health and overall quality of life.
• For individuals seeking support managing these symptoms, menopausal hormone therapy (MHT) with estrogen (or a combination of estrogen and progesterone) is an established treatment.
• Various routes of administration (ways to take estrogen) are available for MHT with estrogen, including oral (taken as a pill) or transdermal (absorbed through the skin), but the comparative clinical efficacy, effectiveness, and safety of these administration routes are unclear.
• Decision-makers are interested in whether transdermal estrogen should be considered for public reimbursement (funding) as a first treatment option (first-line option), as an alternative to oral estrogen for MHT.
• We evaluated the evidence of the clinical efficacy, effectiveness, safety, and cost-effectiveness (value from a human or health system perspective) of transdermal versus oral estrogen in MHT using a rapid review approach.
• We searched for evidence-based guidelines on the use of transdermal or oral estrogen in MHT.
• We identified 7 systematic reviews, 4 primary studies, and 3 clinical practice guidelines relevant to this review. No relevant health technology assessment (HTA) reports or cost-effectiveness studies were identified.
• The included studies suggest that transdermal estrogen may reduce VMS, improve sleep, and have a lower risk of blood clots compared to oral estrogen. Both transdermal and oral MHT may improve bone health and have similar safety risk profiles for breast and gynecological cancers. Furthermore, transdermal MHT may be a safer choice for those at risk of developing blood clots; however, there are inconsistent results related to the risk of heart disease and stroke.
• The included studies suggest oral MHT is more effective at improving cholesterol levels but may raise triglyceride levels. In contrast, transdermal MHT has mixed effects on cholesterol levels, though it also raises triglyceride levels.
  Guideline recommendations consider transdermal MHT over oral MHT for addressing specific individual concerns related to sexual well-being and reducing risk for gallstones, blood clots, stroke, and heart disease.
• There is limited evidence comparing transdermal and oral MHT, particularly for managing VMS, health-related quality of life, and sleep quality. However, some studies suggest transdermal MHT may have a lower risk of venous thromboembolism (VTE) (blood clots in the veins).
• Given these safety considerations, policymakers may consider reimbursement for transdermal MHT, but additional research is needed to inform consideration for efficacy and cost-effectiveness.
   

Key Message

What Is the Issue?

Immune checkpoint inhibitor–based therapies, especially dual immune checkpoint inhibitor regimens, are now frequently used as initial treatments for advanced or metastatic renal cell carcinoma (RCC).

Cabozantinib has shown promise in RCC; however, cabozantinib is currently funded in the second-line setting for adult patients with advanced or metastatic RCC who have previously received other vascular endothelial growth factor (VEGF)-targeted therapy, limiting its availability in some second-line scenarios.

There is a need to understand the clinical effectiveness of cabozantinib when used after the failure of first-line immune checkpoint inhibitor (ICI) regimens.

What Did We Do?

To inform decisions about the use of cabozantinib for adults with advanced or metastatic RCC who have previously received ICIs in the first line, we sought to identify and summarize related evidence regarding the clinical effectiveness of second-line treatment with cabozantinib compared with sunitinib, axitinib, and pazopanib.

We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2020.

One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included publication, and summarized the findings.

What Did We Find?

One systematic review that included 2 small retrospective observational studies provided evidence for the research question.

Limited retrospective evidence suggests that second-line treatment with cabozantinib may be associated with numerically longer progression-free survival (PFS) compared to sunitinib and axitinib, but shorter PFS compared to pazopanib.

Cabozantinib may also have a potentially higher objective response rate (ORR) compared to sunitinib, axitinib, and pazopanib.

One small retrospective study indicated that cabozantinib had the numerically lowest rate of treatment discontinuation due to toxicity compared to sunitinib, pazopanib, and axitinib.

No studies reporting adverse event rates, overall survival (OS), or quality of life were identified.

What Does It Mean?

Decision-makers should consider the limited quantity and quality of the current evidence available for this patient population. Due to very low confidence in the body of evidence (small sample size, retrospective design, lack of statistical analyses), decision-makers choosing among second-line interventions cabozantinib, sunitinib, axitinib, and pazopanib should consider factors such as clinician expertise and/or patients' values and preferences.

Higher-quality research (with larger sample sizes, appropriate statistical tests, and transparent reporting) is needed to better inform decision-making, such as robust clinical trials or well-planned prospective observational studies focusing on second-line therapy with tyrosine kinase inhibitors (TKIs) such as cabozantinib.

Key Message

What Is the Issue?

Used to administer medications, nutrition, blood products, and other fluids, IV infusion therapy is an important part of clinical care across various health care settings.

Multiple types of venous access devices are available for IV therapy, including peripheral and central devices. Selecting the most appropriate venous access device is essential for ensuring patient safety and comfort.

Midline catheters, a type of peripheral venous access device, are increasingly used as an alternative to other peripheral catheters and central venous access devices. However, variations in clinical practice and uncertainty regarding their optimal use create challenges for clinicians and policy-makers in standardizing care.

What Did We Do?

• We prepared this Rapid Review to summarize and critically appraise the available studies on the clinical effectiveness of midline catheters compared to other vascular access devices to support decision-making about the use of midline catheters for administering IV infusion therapy. We also sought to identify evidence-based guidelines regarding the use of midline catheters for administering IV infusion therapy.
• We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2020. Two reviewers screened articles for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings.

What Did We Find?

• We found 8 systematic reviews (SRs) that evaluated the clinical effectiveness of midline catheters compared to peripherally inserted central catheters (PICCs) (7 SRs) and central venous catheters (1 SR) for administrating IV infusion therapy, as well as 5 evidence-based guidelines that provide recommendations on the appropriate indications for midline catheter use.
• Compared to PICCs, midline catheters may be associated with higher rates of total complications, catheter-related venous thromboembolism, catheter leakage, treatment discontinuation or premature catheter removals, infiltration, and shorter mean catheter dwell times. Midline catheters were also associated with lower rates of catheter-related bloodstream infection. None of the included SRs detected statistically significant differences between midline catheters and PICCs for phlebitis, catheter occlusion, catheter displacement, or mortality.
• Compared to central venous catheters, midline catheters were associated with lower rates of total complications, catheter-related thrombosis, catheter-related infections, and catheter blockage. They also had longer mean catheter dwell times. The SR that examined this comparison did not find significant differences in phlebitis, catheter leakage, or catheter displacement.
• Although some SRs reported statistically significant differences between midline catheters and other venous access devices, these findings were inconsistent across the included studies. Not all SRs detected statistically significant between-group differences for each of these outcomes.
• The quality of the SRs described in this Rapid Review, as well as the quality of primary studies included in the SRs, was limited. Most of the clinical evidence summarized in this review is from low-to-moderate quality nonrandomized studies that may be influenced by selection bias, confounding bias, and performance bias.
• We did not find any studies on the clinical effectiveness of midline catheters versus other peripheral venous access devices for administering IV infusion therapy that met our selection criteria for this review.
• Evidence-based guidelines based mostly on low-quality evidence or expert opinion recommend considering midline catheters as an option in various clinical scenarios, including for children and adults who need longer-term peripheral venous access (e.g., up to 4 weeks). Guidelines also recommend avoiding the use of midline catheters for administering continuous vesicant therapy, parenteral nutrition, or solutions with extremes of pH or osmolarity and for patients with a history of thrombosis, hypercoagulability, decreased venous flow to the extremities, end-stage renal disease requiring vein preservation, or with planned or existing arteriovenous fistula or arteriovenous graft.

What Does This Mean?

• Health care professionals and decision-makers can use this evidence to inform decisions around the appropriate use of midline catheters for administering IV infusion therapy.
• Current evidence-based guidelines support the use of midline catheters in certain clinical scenarios after consideration for the type and anticipated duration of therapy and individual patient needs.
• Further high-quality research from robustly conducted studies with improved reporting is needed to confirm the clinical effectiveness of midline catheters versus other vascular access devices.