Guideline authors' response: Rehabilitation in multiple sclerosis: Commentary on the recent AAN systematic review
Jodie K.Haselkorn, MD, MPH, MS Center of Excellence West, US Veterans Health Administration, University of Washington, Seattle, WAguidelines@aan.com
Christina Hughes, MD; Alex Rae-Grant, MD; Lily Jung Henson, MD,MMM; Christopher T. Bever, MD,MBA; Albert C. Lo, MD,PhD; Theodore R. Brown, MD,MPH; George H. Kraft, MD,MS; Gary Gronseth, MD; Melissa J. Armstrong, MD,MSc; Pushpa Narayanaswami, MBBS,DM
We thank Sutliff et al.1 for their commentary on our systematic review (SR), "Rehabilitation in Multiple Sclerosis."2 We would like to make several points in response. Firstly, contrary to their comment that our panel2 "lacked specialist diversity," the panel included MS experts, rehabilitation experts, non-MS neurologists and guideline methodologists. Furthermore, the National Multiple Sclerosis Society was part of the process.2 Physical and occupational therapists, speech/language therapists and exercise physiologists were not included; this reflects the guideline development process at the time. Nevertheless, this was a SR,2 not a clinical practice guideline (CPG). An SR makes conclusions based on available evidence, whereas CPGs make practice recommendations. The CPG process lends itself to expert formal consensus; the SR does not. The conclusions of our SR2 would have been the same even with the inclusion of other experts because they are based on the AAN risk of bias assessment of each study and not expert opinion.
Secondly, we have highlighted methodologic limitations of the rehabilitation literature in our recommendations for future research.2 We do not deem it appropriate to blame the risk of bias assessment for failure to identify high-level studies in our SR.2 Instead of setting a lower bar for the quality of studies and accepting weaker evidence to inform practice, the field of rehabilitation should be challenged to improve the science and obtain high-quality evidence. Thirdly, we recognize the lag between the search in 2013 and the SR2 published in 2015, which is a common issue for most SRs/CPGs due to the time it takes to develop them. Despite this, based on the quality of studies identified in the previous 2 searches,2 the likelihood of finding high-quality evidence to drive recommendations was low.
Fourthly, Sutliff et al.1 provide a table of studies that were "not included" in our SR.2 This is inaccurate. Because of word count limitations, only studies that drove conclusions were discussed in the executive summary.2 At least 5 of these "excluded studies"3-7 are included in the full SR online.2 Hebert et al.8 was excluded because vestibular rehabilitation was not within the scope of our SR.2 Several others9 were published after our SR2 or were narrative reviews.10 Finally, Sutliff et al.1 raise a concern regarding reimbursement due to misinterpretation of this review. We emphasize that this is an SR2 without practice recommendations.
We solicited comments on our SR2 twice from the AAN MS section and responded to all comments, many of which were brought up by Sutliff et al.1 (table e-1 available online in full-length response). A process to engage the SR authors and the AAN Guideline Development, Dissemination and Implementation subcommittee leadership prior to publication of their commentary1 would have conclusively clarified several of the concerns from Sutliff et al. CPGs/SRs are reviewed every 3 years to evaluate new literature that will change the published conclusions/recommendations. When this process is undertaken for the MS Rehabilitation SR,2 newer AAN guideline development methodology will be utilized to include perspectives from specialty societies, patients, other healthcare professionals and public comments.
Disclosures: J. Haselkorn is a full-time employee of the US Department of Veterans Affairs and has received funding for travel from the Paralyzed Veterans of America Summit and the Consortium of Multiple Sclerosis Centers (CMSC). C. Hughes received funding from TEVA Neuroscience for the MS Scholars Conference. A. Rae-Grant has received royalties from multiple books published by Demos Publishing and Wolters Kluwer on multiple sclerosis and neurology, and assists in editing neurology chapters for an online textbook of medicine for Dynamed. L. Henson serves on advisory boards for Biogen, Genzyme, Novartis, and sanofi-aventis; has received funding for travel from Genzyme; has received financial compensation for work on speakers' bureaus for Biogen, Genzyme, Novartis, Pfizer, Serono, and Teva; and has received research support from Biogen, Genzyme, the NIH, Novartis, Opexa Therapeutics, and sanofi-aventis. C. Bever received funding for travel from the American Academy of Neurology (AAN), Americas Committee on Research and Treatment of Multiple Sclerosis, the CMSC, and the University of Maryland; and has received research support from the US Department of Veterans Affairs and the National Multiple Sclerosis Society (NMSS). His spouse has received travel support from Johns Hopkins University, royalties from publishing from Elsevier and Johns Hopkins University Press, and honoraria from Harvard University and New York University. A. Lo has received honoraria from Acorda Therapeutics; funding for travel and honoraria from the Shepherd Center in Atlanta, GA; and research support from the US Department of Veterans Affairs, Harvard University, and St. Francis Hospital in Hartford, CT. T. Brown serves on the clinical advisory committee of the NMSS; has received compensation for serving on the scientific advisory boards of Acorda and Teva, and on the editorial board of the International Journal of MS Care; has received honoraria from and served on speakers' bureaus for Acorda, Genzyme, Pfizer, and Teva; and has received research support from Astellas, Biogen, Gallen, and Teva. G. Kraft serves on the advisory board for Acorda Therapeutics, has received funding for travel to Acorda Axon Council meetings, is a consulting editor for Physical Medicine and Rehabilitation Clinics of North America, has received royalties from publishing from Demos, has received honoraria from multiple academic and professional organizations for lecturing, has served on a speakers' bureau for Acorda, and has received research support from the National Institute on Disability and Rehabilitation Research. G. Gronseth serves as an associate editor for Neurology and as an editorial advisory board member of Neurology Now, and receives compensation from the AAN for work as the chief evidence-based medicine methodologist. M. Armstrong serves on the Level of Evidence Review Team for Neurology (not compensated financially), serves as an evidence-based methodologist for the AAN, and receives research funding from Abbott as a study subinvestigator. P. Narayanaswami is a member of the Level of Evidence Review Team for Neurology; has received honoraria from the American Association of Neuromuscular & Electrodiagnostic Medicine; has prepared expert medical reports for Advance Medical; has reviewed grant proposals for Boston Clinical Research Institute; is a member of the Pharmacy and Therapeutics Committee, Blue Cross Blue Shield MA; has received research support from the Agency for Healthcare Research and Quality and from MERZ Pharmaceuticals, USA; and has provided expert testimony for Hollingsworth LLP on behalf of General Electric and Milton, Leach, Whitman, D'Andrea & Eslinger. Go to Neurology.org for full disclosures.
References
1. Sutliff MH, Bennett SE, Bobryk P, et al. Rehabilitation in multiple sclerosis: Commentary on the recent AAN systematic review. Neurol Clin Pract 2016;6:475-479.
2. Haselkorn JK, Hughes C, Rae-Grant A, et al. Summary of comprehensive systematic review: Rehabilitation in multiple sclerosis. Neurology 2015;85:1896-1903.
3. Schulz K-H, Gold SM, Witte J, et al. Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis. J Neurol Sci 2004;225(1-2):11-18. doi:10.1016/j.jns.2004.06.009.
4. Cattaneo D, Jonsdottir J, Zocchi M, Regola A. Effects of balance exercises on people with multiple sclerosis: a pilot study. Clin Rehabil 2007;21:771-781. doi:10.1177/0269215507077602.
5. Dettmers C, Sulzmann M, Ruchay-Plossl A, Gutler R, Vieten M. Endurance exercise improves walking distance in MS patients with fatigue. Acta Neurol Scand 2009;120(4):251-257. doi:10.1111/j.1600-0404.2008.01152.x.
6. Petajan JH, Gappmaier E, White AT, Spencer MK, Mino L, Hicks RW. Impact of aerobic training on fitness and quality of life in multiple sclerosis. Ann Neurol 1996;39(4):432-441. doi:10.1002/ana.410390405.
7. Solari A, Filippini G, Gasco P, et al. Physical rehabilitation has a positive effect on disability in multiple sclerosis patients. Neurology 1999;52:57-62.
8. Hebert JR, Corboy JR, Manago MM, Schenkman M. Effects of vestibular rehabilitation on multiple sclerosis-related fatigue and upright postural control: a randomized controlled trial. Phys Ther 2011;91(8):1166-1183. doi:10.2522/ptj.20100399.
9. Chruzander C, Gottberg K, Ytterberg C, et al. A single-group pilot feasibility study of cognitive behavioural therapy in people with multiple sclerosis with depressive symptoms. Disabil Rehabil 2016;38(24):2383-91. doi:10.3109/09638288.2015.1130179. Epub 2016 Jan 10.
10. Motl RW, Sandroff BM. Benefits of Exercise Training in Multiple Sclerosis. Curr Neurol Neurosci Rep 2015;15(9):62. doi:10.1007/s11910-015-0585-6.
We thank Sutliff et al.1 for their commentary on our systematic review (SR), "Rehabilitation in Multiple Sclerosis."2 We would like to make several points in response. Firstly, contrary to their comment that our panel2 "lacked specialist diversity," the panel included MS experts, rehabilitation experts, non-MS neurologists and guideline methodologists. Furthermore, the National Multiple Sclerosis Society was part of the process.2 Physical and occupational therapists, speech/language therapists and exercise physiologists were not included; this reflects the guideline development process at the time. Nevertheless, this was a SR,2 not a clinical practice guideline (CPG). An SR makes conclusions based on available evidence, whereas CPGs make practice recommendations. The CPG process lends itself to expert formal consensus; the SR does not. The conclusions of our SR2 would have been the same even with the inclusion of other experts because they are based on the AAN risk of bias assessment of each study and not expert opinion.
Secondly, we have highlighted methodologic limitations of the rehabilitation literature in our recommendations for future research.2 We do not deem it appropriate to blame the risk of bias assessment for failure to identify high-level studies in our SR.2 Instead of setting a lower bar for the quality of studies and accepting weaker evidence to inform practice, the field of rehabilitation should be challenged to improve the science and obtain high-quality evidence. Thirdly, we recognize the lag between the search in 2013 and the SR2 published in 2015, which is a common issue for most SRs/CPGs due to the time it takes to develop them. Despite this, based on the quality of studies identified in the previous 2 searches,2 the likelihood of finding high-quality evidence to drive recommendations was low.
Fourthly, Sutliff et al.1 provide a table of studies that were "not included" in our SR.2 This is inaccurate. Because of word count limitations, only studies that drove conclusions were discussed in the executive summary.2 At least 5 of these "excluded studies"3-7 are included in the full SR online.2 Hebert et al.8 was excluded because vestibular rehabilitation was not within the scope of our SR.2 Several others9 were published after our SR2 or were narrative reviews.10 Finally, Sutliff et al.1 raise a concern regarding reimbursement due to misinterpretation of this review. We emphasize that this is an SR2 without practice recommendations.
We solicited comments on our SR2 twice from the AAN MS section and responded to all comments, many of which were brought up by Sutliff et al.1 (table e-1 available online in full-length response). A process to engage the SR authors and the AAN Guideline Development, Dissemination and Implementation subcommittee leadership prior to publication of their commentary1 would have conclusively clarified several of the concerns from Sutliff et al. CPGs/SRs are reviewed every 3 years to evaluate new literature that will change the published conclusions/recommendations. When this process is undertaken for the MS Rehabilitation SR,2 newer AAN guideline development methodology will be utilized to include perspectives from specialty societies, patients, other healthcare professionals and public comments.
Disclosures: J. Haselkorn is a full-time employee of the US Department of Veterans Affairs and has received funding for travel from the Paralyzed Veterans of America Summit and the Consortium of Multiple Sclerosis Centers (CMSC). C. Hughes received funding from TEVA Neuroscience for the MS Scholars Conference. A. Rae-Grant has received royalties from multiple books published by Demos Publishing and Wolters Kluwer on multiple sclerosis and neurology, and assists in editing neurology chapters for an online textbook of medicine for Dynamed. L. Henson serves on advisory boards for Biogen, Genzyme, Novartis, and sanofi-aventis; has received funding for travel from Genzyme; has received financial compensation for work on speakers' bureaus for Biogen, Genzyme, Novartis, Pfizer, Serono, and Teva; and has received research support from Biogen, Genzyme, the NIH, Novartis, Opexa Therapeutics, and sanofi-aventis. C. Bever received funding for travel from the American Academy of Neurology (AAN), Americas Committee on Research and Treatment of Multiple Sclerosis, the CMSC, and the University of Maryland; and has received research support from the US Department of Veterans Affairs and the National Multiple Sclerosis Society (NMSS). His spouse has received travel support from Johns Hopkins University, royalties from publishing from Elsevier and Johns Hopkins University Press, and honoraria from Harvard University and New York University. A. Lo has received honoraria from Acorda Therapeutics; funding for travel and honoraria from the Shepherd Center in Atlanta, GA; and research support from the US Department of Veterans Affairs, Harvard University, and St. Francis Hospital in Hartford, CT. T. Brown serves on the clinical advisory committee of the NMSS; has received compensation for serving on the scientific advisory boards of Acorda and Teva, and on the editorial board of the International Journal of MS Care; has received honoraria from and served on speakers' bureaus for Acorda, Genzyme, Pfizer, and Teva; and has received research support from Astellas, Biogen, Gallen, and Teva. G. Kraft serves on the advisory board for Acorda Therapeutics, has received funding for travel to Acorda Axon Council meetings, is a consulting editor for Physical Medicine and Rehabilitation Clinics of North America, has received royalties from publishing from Demos, has received honoraria from multiple academic and professional organizations for lecturing, has served on a speakers' bureau for Acorda, and has received research support from the National Institute on Disability and Rehabilitation Research. G. Gronseth serves as an associate editor for Neurology and as an editorial advisory board member of Neurology Now, and receives compensation from the AAN for work as the chief evidence-based medicine methodologist. M. Armstrong serves on the Level of Evidence Review Team for Neurology (not compensated financially), serves as an evidence-based methodologist for the AAN, and receives research funding from Abbott as a study subinvestigator. P. Narayanaswami is a member of the Level of Evidence Review Team for Neurology; has received honoraria from the American Association of Neuromuscular & Electrodiagnostic Medicine; has prepared expert medical reports for Advance Medical; has reviewed grant proposals for Boston Clinical Research Institute; is a member of the Pharmacy and Therapeutics Committee, Blue Cross Blue Shield MA; has received research support from the Agency for Healthcare Research and Quality and from MERZ Pharmaceuticals, USA; and has provided expert testimony for Hollingsworth LLP on behalf of General Electric and Milton, Leach, Whitman, D'Andrea & Eslinger. Go to Neurology.org for full disclosures.
References
1. Sutliff MH, Bennett SE, Bobryk P, et al. Rehabilitation in multiple sclerosis: Commentary on the recent AAN systematic review. Neurol Clin Pract 2016;6:475-479.
2. Haselkorn JK, Hughes C, Rae-Grant A, et al. Summary of comprehensive systematic review: Rehabilitation in multiple sclerosis. Neurology 2015;85:1896-1903.
3. Schulz K-H, Gold SM, Witte J, et al. Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis. J Neurol Sci 2004;225(1-2):11-18. doi:10.1016/j.jns.2004.06.009.
4. Cattaneo D, Jonsdottir J, Zocchi M, Regola A. Effects of balance exercises on people with multiple sclerosis: a pilot study. Clin Rehabil 2007;21:771-781. doi:10.1177/0269215507077602.
5. Dettmers C, Sulzmann M, Ruchay-Plossl A, Gutler R, Vieten M. Endurance exercise improves walking distance in MS patients with fatigue. Acta Neurol Scand 2009;120(4):251-257. doi:10.1111/j.1600-0404.2008.01152.x.
6. Petajan JH, Gappmaier E, White AT, Spencer MK, Mino L, Hicks RW. Impact of aerobic training on fitness and quality of life in multiple sclerosis. Ann Neurol 1996;39(4):432-441. doi:10.1002/ana.410390405.
7. Solari A, Filippini G, Gasco P, et al. Physical rehabilitation has a positive effect on disability in multiple sclerosis patients. Neurology 1999;52:57-62.
8. Hebert JR, Corboy JR, Manago MM, Schenkman M. Effects of vestibular rehabilitation on multiple sclerosis-related fatigue and upright postural control: a randomized controlled trial. Phys Ther 2011;91(8):1166-1183. doi:10.2522/ptj.20100399.
9. Chruzander C, Gottberg K, Ytterberg C, et al. A single-group pilot feasibility study of cognitive behavioural therapy in people with multiple sclerosis with depressive symptoms. Disabil Rehabil 2016;38(24):2383-91. doi:10.3109/09638288.2015.1130179. Epub 2016 Jan 10.
10. Motl RW, Sandroff BM. Benefits of Exercise Training in Multiple Sclerosis. Curr Neurol Neurosci Rep 2015;15(9):62. doi:10.1007/s11910-015-0585-6.