Table 2.

Summary of evidence considered for drug-listing recommendations^a

Drug/indication	CDR assessment	PBAC assessment	NICE assessment
Rivaroxaban/venous thromboembolism	Clinical comparator Direct – Enoxaparin (5 RCTs) Indirect/MTC (none)	Clinical comparator Direct – Enoxaparin (3 RCTs) Indirect/MTC (none)	Clinical comparator Direct – Enoxaparin (4 RCTs) Indirect/MTC – Mixed-treatment comparison with dabigatran vs enoxaparin (3 RCTs)
Tenofovir/hepatitis B	Clinical comparator Direct – Adefovir (2 RCTs) Indirect/MTC (none)	Clinical comparator Directb – Adefovir (2 RCTs) – Tenofovir + emtricitabine (1 RCT) Indirect/MTC – Entecavir vs adefovir (1 RCT) – Entecavir vs lamivudine (1 RCT)	Clinical comparator Direct – Adefovir (2 RCTs) Indirect/MTC – Mixed-treatment meta-analysis comparison vs placebo, adefovir, entecavir, lamivudine, and telbivudine (23 RCTs)
Ustekinumab/ psoriasis	Clinical comparator Direct – Placebo (2 RCTs) – Etanercept (1 open-label assessor-blinded RCT) Indirect/MTC (none)	Clinical comparator Direct – Placebo (2 RCTs) – Etanercept (1 open-label assessor-blinded RCT) Indirect/MTC – Adalimumab vs placebo (3 RCTs) – Etanercept vs placebo (4 RCTs) – Infliximab vs placebo (4 RCTs)	Clinical comparator Direct – Placebo (2 RCTs) – Etanercept (1 open-label assessor-blinded RCT) Indirect/MTC Mixed-treatment meta-analysis, including – Adalimumab vs placebo (3 RCTs) – Etanercept vs placebo (5 RCTs) – Infliximab vs placebo (4 RCTs) – Efalizumab vs placebo (5 RCTs)
Varenicline/smoking cessation	Clinical comparator Direct – Bupropion and placebo (8 RCTs with placebo, 3 including a bupropion arm) Indirect/MTC (none)	Clinical comparator Direct – Bupropion and placebo (2 RCTs with placebo and bupropion arms) Indirect/MTC (none)	Clinical comparator Direct – Bupropion and placebo (3 RCTs with placebo, 2 including a bupropion arm) – Nicotine replacement (1 open-label study) Indirect/MTC – Meta-analysis of 70 nicotine replacement, 12 bupropion, and 4 varenicline trials against control/placebo
Abatacept/ rheumatoid arthritis	Clinical comparator Direct – Placebo and infliximab (5 RCTs with placebo, 1 including an infliximab arm) Indirect/MTC (none)	Clinical comparators Direct – Infliximab (+MTX) and placebo (+MTX or biologics/DMARDs) (4 RCTs vs placebo, including 3 RCTs with abatacept + MTX vs placebo + MTX, 1 including an infliximab + MTX arm, 1 with abatacept + DMARDs/biologics vs placebo + DMARDs/ biologics) Indirect/MTC – Infliximab + MTX vs placebo + MTX (1 RCT)	Clinical comparators Directc – Infliximab + MTX and placebo + MTX (4 RCTs with abatacept + MTX vs placebo + MTX, including 1 with an infliximab + MTX arm) Indirect/MTC Mixed-treatment comparison including – Infliximab + MTX vs placebo + MTX (1 RCT) – Rituximab + MTX vs placebo + MTX (1 RCT) – Adalimumab + MTX vs placebo + MTX (2 RCTs) – Certolizumab + MTX vs placebo + MTX (2 RCTs) – Etanercept + MTX vs placebo + MTX (2 RCTs) – Golimumab + MTX vs placebo + MTX (1 RCT)
Adalimumab/ psoriasis	Clinical comparators Direct – MTX and placebo (3 RCTs with placebo, 1 including an MTX arm) Indirect/MTC (none)	Clinical comparators Direct – MTX and placebo (3 RCTs with placebo, 1 including an MTX arm) Indirect/MTC – Efalizumab vs placebo (5 RCTs) – Infliximab vs placebo (4 RCTs)	Clinical comparators Direct – MTX and placebo (3 RCTs with placebo, 1 including an MTX arm) Indirect/MTC Mixed-treatment comparison, including – Efalizumab vs placebo (5 RCTs) – Infliximab vs placebo (4 RCTs) – Etanercept vs placebo (4 RCTs) – Cyclosporine vs placebo (1 RCT) – MTX vs cyclosporine (1 RCT)
Dabigatran/venous thromboembolism	Clinical comparators Direct – Placebo (1 RCT) – Enoxaparin (3 RCTs)d Indirect/MTC (none)	Clinical comparator Direct – Enoxaparin (4 RCTs) Indirect/MTC – Rivaroxaban vs enoxaparin (8 RCTs)	Clinical comparators Direct – Enoxaparin (3 RCTs) Indirect/MTC – Fondaparinux and low-molecular-weight heparin (using previously published mixed-treatment comparison meta-analysis)
Natalizumab/ multiple sclerosis	Clinical comparator Directe – Placebo (1 RCT) Indirect/MTC (none)	Clinical comparators Direct – Placebo (1 RCT) Indirect/MTC – Beta-interferon vs placebo (3 RCTs) – Glatiramer acetate vs placebo (1 RCT)	Clinical comparators Direct – Placebo (3 RCTs) Indirect/MTC – Beta-interferon vs placebo (3 RCTs) – Glatiramer acetate vs placebo (2 RCTs)
Telbivudine/hepatitis B	Clinical comparator Direct – Lamivudine (4 RCTs) Indirect/MTC (none)	Clinical comparators Direct – Lamivudine (2 RCTs and 1 pooled unweighted subgroup analysis of one of these 2 RCTs) Indirect/MTC – Entecavir vs lamivudine (2 RCTs)	Clinical comparator Direct – Lamivudine + placebo (1 RCT with telbivudine + placebo vs lamivudine + placebo) Indirect/MTC (none)f

Notes:

^aShaded boxes denote recommendations to reject reimbursement;

^bone trial omitted here was considered for tenofovir vs adefovir for treatment in HIV/hepatitis B coinfected patients;

^cthe manufacturer submitted data for six RCTs vs placebo, but NICE indicated that only one of these reflected the licensed indication for abatacept;

^dthree phase III RCTs against enoxaparin were submitted, but CDR discounted two of these, because the dosing of enoxaparin comparator in these trials (40 mg twice per day) was different from that approved by the Health Canada marketing authorization (30 mg twice per day);

^eCDR mentioned that it had considered using one additional RCT comparing natalizumab plus beta-interferon versus beta-interferon monotherapy, but chose not to include the trial in the analysis because natalizumab’s marketing authorization is for use as a monotherapy only;

^fthe same indirect RCTs as PBAC (entecavir vs lamivudine) were mentioned in the manufacturer submission, but there was insufficient detail and analysis for the NICE Evidence Review Group to consider.

Abbreviations: CDR, Common Drug Review; MTC, mixed-treatment comparison; NICE, National Institute for Health and Clinical Excellence; PBAC, Pharmaceutical Benefits Advisory Committee; RCT, randomized controlled trial.