We agree with Dr. Tenser’s comments about stable MS patients and we cannot support with evidence the clinical decisions about therapy made on the basis of unvalidated surrogates. This is highlighted when therapies carry significant risk. Dialogue with patients should reflect what is known and not what is hoped for, unless this is explicitly stated.
The strong attraction of MRI both visually and conceptually has to be complemented by the hard work of showing that change in an MRI measure independently correlates with the key outcome of unremitting disability. If it is not independent and not related to the key outcome, the cost and time spent by patients for MRI cannot be justified. Furthermore, demonstrating correlation is not enough and it is required that treatment-related suppression of that MRI change translates into suppression of this key outcome. We have previously assessed the clinical trial utilization of disability measures and have similar reservations.
The key outcomes are surely the prevention of or delay in onset of progressive disease and the slowing of its progress when it occurs. Progressive disability, often in the absence of relapses, dwarfs any other outcome in importance and this should be the target of surrogate validation and treatment alike. This formidable and as yet undefeated foe is what patients and physicians most dread.
Disclosures: Prof Ebers received funding from Roche for participation in a meeting and from UCB Pharma for consulting, has received grant support from Bayer Schering Pharma for a natural history study and prepared 4 medico-legal reports. Dr. Daumer, Scientific Director of the Sylvia Lawry Centre for Multiple Sclerosis Research e.V. and Managing Director of Trium Analysis Online GmbH serves on the Editorial Board of MedNous,holds patents Patent 10 2007 044 705.3-35., German patent and trade mark office 307 19 449.3/09. The Sylvia Lawry Centre received honoraria for interviews of Dr. Daumer with Propagate Pharma Limited, Deerfield Research LLC, is Medical Advisor of the German Multiple Sclerosis Society, serves as consultant for the following commercial entities Hoffmann-La Roche, Biopartners, Novartis, EISAI Limited, Böhringer-Ingelheim; received research grants from the following gonvernmental entities Federal Ministry of Education and Research, Mayo Clinic Rochester, European Union (for SLC and Trium) Grant No 215820, European Union (for SLC) Grant No 223865, Federal Ministry of Economics and Technology. Grant No KF0564001KF7, University of Oxford, Technical University of Munich, Hertie Foundation and others Grant No 1.01.1/07/015, Bavarian Research Foundation, National Multiple Sclerosis Society (NMSS), Porticus Foundation Grant No 900.50578, European Union Grant No LSHM-CT-2006-03759, University of Rochester, Medical Center, European Union Grant No LSHM-CT-2004-503485.
We agree with Dr. Tenser’s comments about stable MS patients and we cannot support with evidence the clinical decisions about therapy made on the basis of unvalidated surrogates. This is highlighted when therapies carry significant risk. Dialogue with patients should reflect what is known and not what is hoped for, unless this is explicitly stated.
The strong attraction of MRI both visually and conceptually has to be complemented by the hard work of showing that change in an MRI measure independently correlates with the key outcome of unremitting disability. If it is not independent and not related to the key outcome, the cost and time spent by patients for MRI cannot be justified. Furthermore, demonstrating correlation is not enough and it is required that treatment-related suppression of that MRI change translates into suppression of this key outcome. We have previously assessed the clinical trial utilization of disability measures and have similar reservations.
The key outcomes are surely the prevention of or delay in onset of progressive disease and the slowing of its progress when it occurs. Progressive disability, often in the absence of relapses, dwarfs any other outcome in importance and this should be the target of surrogate validation and treatment alike. This formidable and as yet undefeated foe is what patients and physicians most dread.
Disclosures: Prof Ebers received funding from Roche for participation in a meeting and from UCB Pharma for consulting, has received grant support from Bayer Schering Pharma for a natural history study and prepared 4 medico-legal reports. Dr. Daumer, Scientific Director of the Sylvia Lawry Centre for Multiple Sclerosis Research e.V. and Managing Director of Trium Analysis Online GmbH serves on the Editorial Board of MedNous,holds patents Patent 10 2007 044 705.3-35., German patent and trade mark office 307 19 449.3/09. The Sylvia Lawry Centre received honoraria for interviews of Dr. Daumer with Propagate Pharma Limited, Deerfield Research LLC, is Medical Advisor of the German Multiple Sclerosis Society, serves as consultant for the following commercial entities Hoffmann-La Roche, Biopartners, Novartis, EISAI Limited, Böhringer-Ingelheim; received research grants from the following gonvernmental entities Federal Ministry of Education and Research, Mayo Clinic Rochester, European Union (for SLC and Trium) Grant No 215820, European Union (for SLC) Grant No 223865, Federal Ministry of Economics and Technology. Grant No KF0564001KF7, University of Oxford, Technical University of Munich, Hertie Foundation and others Grant No 1.01.1/07/015, Bavarian Research Foundation, National Multiple Sclerosis Society (NMSS), Porticus Foundation Grant No 900.50578, European Union Grant No LSHM-CT-2006-03759, University of Rochester, Medical Center, European Union Grant No LSHM-CT-2004-503485.