Table 1.
Characteristics of randomized controlled trials included in the NMA
| Trial | Primary publication | ClinicalTrials.gov identifier | Treatment 1 | Treatment 2 | Treatment 3 | Blinding | Phase | Multicenter | Region |
|---|---|---|---|---|---|---|---|---|---|
| Trials included in final NMAs | |||||||||
| ECOG 1697 [22] | Agarwala et al. (2017) | NCT00003641 | IFN alfa-2b (high-dose) | Observation | NA | Open-label | III | Yes | Australia, Canada, South Africa, USA |
| Scottish study [23] | Cameron et al. (2001) | NA | IFN alfa-2b (low-dose) | Observation | NA | Open-label | NR | Yes | Scotland |
| WHO Melanoma Programme Trial 16 [24] | Cascinelli et al. (2001) | NA | IFN alfa-2b (low-dose) | Observation | NA | Open-label | NR | Yes | Italy |
| EORTC 18071 [25] | Eggermont et al. (2015) | NCT00636168 | Ipilimumab | Placebo | NA | Double-blind | III | Yes | Australia, Austria, Belgium, Canada, Czech Republic, Denmark, Finland, France, Germany, Italy, Netherlands, Norway, Poland, Russia, Spain, Sweden, Switzerland, United Kingdom, USA |
| EORTC 18952 [26] | Eggermont et al. (2005) | NA | IFN alfa-2b (high-dose/ 13 months) | IFN alfa-2b (low-dose/ 25 months) | Observation | Open-label | III | Yes | Austria, Belgium, Bulgaria, Croatia, Estonia, Finland, France, Germany, Hungary, Israel, Italy, Poland, Portugal, Russia, Serbia and Montenegro, Slovakia, Spain, Sweden, Switzerland, Netherlands, Turkey, United Kingdom |
| EORTC 18991 [27] | Eggermont et al. (2008) | NCT00006249 | PEG IFN alfa-2b | Observation | NA | Open-label | III | Yes | Australia, Belgium, Bulgaria, Croatia, Czech Republic, Estonia, France, Germany, Israel, Italy, Netherlands, Poland, Portugal, Slovenia, Spain, Switzerland, Turkey, United Kingdom |
| KEYNOTE-054 [28, 29] | Eggermont et al. (2018) | NCT02362594 | Pembrolizumab | Placebo | NA | Double-blind | III | Yes | Australia, Belgium, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, Netherlands, New Zealand, Norway, Poland, Portugal, Russian Federation, Serbia, Spain, Sweden, Switzerland, United Kingdom, USA |
| S0008 [30] | Flaherty et al. (2014) | NCT00006237 | IFN alfa-2b (high-dose) | Other chemotherapy | NA | Open-label | III | Yes | Australia, USA |
| Garbe 2008 (DeCOG) [31] | Garbe et al. (2008) | NA | IFN alfa-2a (low-dose) | IFN alfa-2a + dacarbazine | Observation | Open-label | III | Yes | Germany, Switzerland |
| AIM HIGH Study [32] | Hancock et al. (2004) | NA | IFN alfa-2a (low-dose) | Observation | NA | Open-label | III | Yes | United Kingdom |
| Nordic IFN Trial [33] | Hansson et al. (2011) | NCT01259934 | IFN alfa-2b (1 year) | IFN alfa-2b (2 years) | Observation | Open-label | III | Yes | Denmark, Finland, Norway, Sweden |
| Kim et al. 2009 [34] | – | NA | Cisplatin, vinblastine, dacarbazine, IFN alfa-2b, interleukin-2 | IFN alfa-2b (high-dose) | IFN alfa-2b (low-dose) | Open-label | III | NR | USA |
| ECOG 1690 [35] | Kirkwood et al. (2000) | NA | IFN alfa-2b (low-dose) | IFN alfa-2b (high-dose) | Observation | Open-label | III | Yes | USA |
| ECOG 1684 [10] | Kirkwood et al. (1996) | NA | IFN alfa-2b (high-dose) | Observation | NA | Open-label | III | Yes | USA |
| EORTC 18871 [36] | Kleeberg et al. (2004) | NA | rIFN alfa-2b | Observation | NA | Open-label | III | Yes | Austria, Belgium, Czech Republic, Estonia, France, Germany, Great Britain, Greece, Israel, Poland, Spain, Switzerland, Yugoslavia |
| COMBI-AD [7, 37] | Long et al. (2017) | NCT01682083 | Dabrafenib + trametinib | Placebo | NA | Double-blind | III | Yes | Argentina, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Denmark, France, Germany, Greece, Israel, Italy, Japan, Netherlands, New Zealand, Norway, Poland, Russia, Spain, Sweden, Switzerland, Taiwan, United Kingdom, USA |
| Stadler et al. (2006) [38] | – | NA | Dacarbazine + natural human IFN alfa | Observation | NA | Open-label | NR | Yes | Germany |
| E1609 [39] | Tarhini et al. (2017) | NCT01274338 | Ipilimumab (high-dose) | Ipilimumab (low-dose) | IFN alfa-2b (high-dose) | Open-label | III | Yes | Canada, USA |
| CheckMate 238 [15, 40] | Weber et al. (2017) | NA | Nivolumab | Ipilimumab | NA | Double-blind | III | Yes | Argentina, Australia, Austria, Belgium, Canada, Czech Republic, Finland, France, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Netherlands, Norway, Poland, Romania, South Africa, Spain, Sweden, Switzerland, Taiwan, United Kingdom, USA |
| Trials excluded from final NMAs | |||||||||
| Eigentler et al. 2016 (DeCOG) [41] | Eigentler et al. (2016) | NCT00204529 | PEG IFN alfa-2a | IFN alfa-2a (low-dose) | NA | Open-label | III | Yes | Austria, Germany |
| EADO study [42] | Grob et al. (2013) | NCT00221702 | PEG IFN alfa-2b | IFN alfa-2b (low-dose) | NA | Open-label | III | Yes | Austria, France, Germany |
| Lian et al. (2013) [43] | – | NA | IFN alfa-2b (high-dose) | Chemotherapy | Observation | NR | II | No | China |
| Sunbelt Melanoma Trial [44] | McMasters et al. (2016) | NA | IFN alfa-2b (high-dose) | Observation | NA | Open-label | III | Yes | Canada, USA |
| MM-ADJ-5 [45] | Mohr et al. (2015) | NCT00226408 | IFN alfa-2b (high-dose) | IFN alfa-2b (intermittent high-dose) | NA | Open-label | III | Yes | Austria, Germany, Greece, Switzerland |
| Tobin et al. (2018) [46] | – | NCT02403778 | Ipilimumab | Ipilimumab plus ATRA | NA | Open-label | II | No | USA |
| Wang et al. (2015) [47] | – | NA | IFN alfa-2b (high-dose) | Observation | NA | Open-label | II | No | China |
ATRA all-trans retinoic acid, IFN interferon, NA not applicable, NMA network meta-analysis, NR not reported, PEG pegylated, rIFN recombinant IFN