Table 2

Trials with statistically inconsistent inferences between central and local assessments

TrialEndpointMaskTumour typeTherapy (experimental arm vs control arm)HR/OR and p value
Primary endpoint
NCT0001968248 ORRSingleMelanomaExp: gp100:209-217(210M)+Montanide ISA-51+interleukin 2Central: 2.86 (95% CI 1.05 to 7.82); p=0.03
Con: Interleukin 2Local: 2.33 (95% CI 0.98 to 5.56); p=0.05
NCT0047132866 Central PFSOpenGastrointestinal stromal tumourExp: NilotinibCentral: 0.90 (95% CI 0.65 to 1.26); p=0.56
Con: Best supportive care/BSC+imatinib/BSC+sunitinibLocal: 0.58 (95% CI 0.42 to 0.80); p<0.01
NCT0011229433 Central PFSOpenNon-small-cell lung cancerExp: Cetuximab+taxane (paclitaxel/docetaxel)+carboplatinCentral: 0.90 (95% CI 0.76 to 1.07); p=0.24
Con: Taxane (paclitaxel/docetaxel)+carboplatinLocal: 0.79 (95% CI 0.67 to 0.93); p<0.01
NCT0070332669 Local PFSDoubleBreast cancerExp: Ramucirumab+docetaxelCentral: 0.79 (95% CI 0.67 to 0.94); p<0.01
Con: Placebo+docetaxelLocal: 0.88 (95% CI 0.75 to 1.01); p=0.08
NCT0039109229 Local PFSOpenBreast cancerExp: Bevacizumab+docetaxel+trastuzumabCentral: 0.72 (95% CI 0.54 to 0.94); p=0.02
Con: Docetaxel+trastuzumabLocal: 0.82 (95% CI 0.65 to 1.02); p=0.08
NCT0049429987 Central TTPDoubleHepatocellular carcinomaExp: SorafenibCentral: 0.87 (95% CI 0.70 to 1.09); p=0.25
Con: PlaceboLocal: 0.79 (95% CI 0.62 to 1.00); p=0.049
NCT0100794212 Local PFSDoubleBreast cancerExp: Everolimus+trastuzumab+vinorelbineCentral: 0.88 (95% CI 0.71 to 1.07); p=NG
Con: Placebo+trastuzumab+vinorelbineLocal: 0.78 (95% CI 0.65 to 0.95); p<0.01
NCT0158464834 35 Local PFSDoubleMelanomaExp: Trametinib+dabrafenibCentral: 0.78 (95% CI 0.59 to 1.04); p=NG
Con: Placebo+dabrafenibLocal: 0.75 (95% CI 0.57 to 0.99); p=0.03
NCT0041206144 Central PFSDoubleNeuroendocrine tumourExp: Everolimus+octreotideCentral: 0.77 (95% CI 0.59 to 1.00); p=0.03*
Con: Placebo+octreotideLocal: 0.78 (95% CI 0.62 to 0.98); p=0.02*
NCT0005645976 Central PFSDoubleColorectal adenocarcinomaExp: Vatalanib+oxaliplatin+fluorouracil+leucovorinCentral: 0.88 (95% CI 0.74 to 1.03); p=0.12
Con: Placebo+oxaliplatin+fluorouracil+leucovorinLocal: 0.83 (95% CI 0.70 to 0.98); p=0.03
Secondary endpoint
NCT0039109229 ORROpenBreast cancerExp: Bevacizumab+docetaxel+trastuzumabCentral: 1.66 (95% CI 1.08 to 2.54); p=0.02
Con: Docetaxel+trastuzumabLocal: 1.25 (95% CI 0.82 to 1.92); p=0.30
NCT0011229433 ORROpenNon-small-cell lung cancerExp: Cetuximab+taxane(paclitaxel/docetaxel)+carboplatinCentral: 1.67 (95% CI 1.15 to 2.43); p=0.01
Con: Taxane(paclitaxel/docetaxel)+carboplatinLocal: 1.31 (95% CI 0.92 to 1.86); p=0.13
NCT0072094157 ORROpenRenal cell carcinomaExp: PazopanibCentral: 1.35 (95% CI 1.03 to 1.75); p=0.03
Con: SunitinibLocal: 1.23 (95% CI 0.95 to 1.59); p=0.11
NCT0103078379 ORROpenRenal cell carcinomaExp: TivozanibCentral: 1.62 (95% CI 1.10 to 2.39); p=0.01
Con: SorafenibLocal: 1.23 (95% CI 0.85 to 1.78); p=0.26
NCT0152358797 ORROpenNon-small-cell lung cancerExp: AfatinibCentral: 2.05 (95% CI 0.98 to 4.29); p=0.06
Con: ErlotinibLocal: 2.88 (95% CI 1.60 to 5.21); p<0.01
NCT01345682105 ORROpenHead and neck cancerExp: AfatinibCentral: 1.90 (95% CI 0.88 to 4.14); p=0.10
Con: MethotrexateLocal: 3.00 (95% CI 1.3–6.9); p=0.01
NCT00785785110 ORROpenGastrointestinal stromal tumourExp: NilotinibCentral: 0.71 (95% CI 0.52 to 0.96); p=0.03
Con: ImatinibLocal: 0.78 (95% CI 0.57 to 1.06); p=0.12
NCT0038872617 PFSOpenBreast cancerExp: EribulinCentral: 0.87 (95% CI 0.71 to 1.05); p=0.14
Con: Treatment of physician’s choice†Local: 0.76 (95% CI 0.64 to 0.90); p<0.01
NCT0044903368 PFSDoubleNon-small-cell lung cancerExp: Sorafenib+gemcitabine+cisplatinCentral: 0.96 (95% CI 0.77 to 1.21); p=0.37*
Con: Placebo+gemcitabine+cisplatinLocal: 0.83 (95% CI 0.71 to 0.97); p<0.01*
TTPCentral: 0.91 (95% CI 0.67 to 1.23); p=0.26*
Local: 0.73 (95% CI 0.60to 0.88); p<0.01*
  • *One side.

  • †Any single-agent chemotherapy or hormonal or biological treatment approved for the treatment of cancer.

  • BSC, best supportive care; central, central assessed; Con, control arm; Double, double blind; Exp, experimental arm; Local, local assessed; NG, not given; Open, open label; ORR, objective response rate; PFS, progression-free survival; Single, single blind; TTP, time to progression.