The Journal of Frailty & Aging

, Volume 7, Issue 3, pp 150–154 | Cite as

Designing Drug Trials for Frailty: ICFSR Task Force 2018

  • Marco Pahor
  • S.B. Kritchevsky
  • D.L. Waters
  • D.T. Villareal
  • J. Morley
  • J.M. Hare
  • B. Vellas
  • The ICFSR Task Force
Special Article


To reduce disability and dependence in older adults, frailty may represent an appropriate target for intervention. While preventing frailty through lifestyle interventions may be the optimal public health approach for many population groups, pharmacological approaches will likely be needed for individuals who meet frailty criteria or who have comorbid conditions that contribute to and complicate the frailty syndrome, and for those who are not compliant with lifestyle interventions. Barriers to successful development of drug treatments for frailty include variability in how the frailty syndrome is defined, lack of agreement on the best diagnostic tools and outcome measures, and the paucity of sensitive, reliable, and validated biomarkers. The International Conference on Frailty and Sarcopenia Research Task Force met in Miami, Florida, on February 28, 2018, to consider the status of treatments under development for frailty and discuss potential strategies for advancing the field. They concluded that at the present time, there may be a more productive regulatory pathway for adjuvant treatments or trials targeting specific functional outcomes such as gait speed. They also expressed optimism that several studies currently underway may provide the insight needed to advance drug development for frailty.

Key words

Sarcopenia frailty gait speed short physical performance battery clinical trials 


  1. 1.
    Cesari M, Prince M, Thiyagarajan JA, De. Carvalho IA, Bernabei R, Chan P, et al. Frailty: An Emerging Public Health Priority. J Am Med Dir Assoc. 2016;17(3):188–92.CrossRefPubMedGoogle Scholar
  2. 2.
    Worl. Health Organization. World Report on Ageing and Health. Luxembourg. 2015.Google Scholar
  3. 3.
    Le. Cossec C, Perrine AL, Beltzer N, Fuhrman C, Carcaillon-Bentata L. Pre-Frailty, Frailty, and Multimorbidity: Prevalences and Associated Characteristics from Two French National Surveys. J Nutr Health Aging. 2016;20(8):860–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–62.CrossRefPubMedGoogle Scholar
  5. 5.
    Rodriguez-Manas L, Feart C, Mann G, Vina J, Chatterji S, Chodzko-Zajko W, et al. Searching for an Operational Definition of Frailty: A Delphi Method Based Consensus Statement. The Frailty Operative Definition-Consensus Conference Project. J Gerontol A Biol Sci Med Sci. 2013;68(1):62–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Vellas B, Cestac P, Moley JE. Implementing frailty into clinical practice: we cannot wait. J Nutr Health Aging. 2012;16(7):599–600.CrossRefPubMedGoogle Scholar
  7. 7.
    Vina J, Tarazona-Santabalbina FJ, Perez-Ros P, Martinez-Arnau FM, Borras C, Olaso-Gonzalez G, et al. Biology of frailty: Modulation of ageing genes and its importance to prevent age-associated loss of function. Mol Aspects Med. 2016;50:88–108.CrossRefPubMedGoogle Scholar
  8. 8.
    Silva RB, Aldoradin-Cabeza H, Eslick GD, Phu S, Duque G. The Effect of Physical Exercise on Frail Older Persons: A Systematic Review. J Frailty Aging. 2017;6(2):91–6.PubMedGoogle Scholar
  9. 9.
    Guigoz Y. Frailty and Nutrition: What We Have Learned from Research and Clinical Practice on the Mini Nutritional Assessment. J Frailty Aging. 2012;1(2):52–5.PubMedGoogle Scholar
  10. 10.
    Goisser S, Guyonnet S, Volkert D. The Role of Nutrition in Frailty: An Overview. J Frailty Aging. 2016;5(2):74–7.PubMedGoogle Scholar
  11. 11.
    Morley JE, Vellas B, van. Kan GA, Anker SD, Bauer JM, Bernabei R, et al. Frailty consensus: a call to action. J Am Med Dir Assoc. 2013;14(6):392–7.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Fielding RA, Travison TG, Kirn DR, Koochek A, Reid KF, von. Berens A, et al. Effect of structured physical activity and nutritional supplementation on physical function in mobility-limited older adults: Results from the VIVE2 randomized trial. J Nutr Health Aging. 2017;in press.Google Scholar
  13. 13.
    Bonnefoy M, Berrut G, Lesourd B, Ferry M, Gilbert T, Guerin O, et al. Frailty and nutrition: searching for evidence. J Nutr Health Aging. 2015;19(3):250–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Fougere B, Mazzuco S, Spagnolo P, Guyonnet S, Vellas B, Cesari M, et al. Association between the Mediterranean-style Dietary Pattern Score and Physical Performance: Results from TRELONG Study. J Nutr Health Aging. 2016;20(4):415–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Lopez J, Campa A, Lewis JE, Huffman FG, Liuzzi JP, Li T, et al. Assessing the relationship between vitamin D status and impairments in cognitive and physical performance in older adults using a dual task physical performance test. J Prev Alz Dis. 2017;4(1):29–36.Google Scholar
  16. 16.
    Fitschen PJ, Wilson GJ, Wilson JM, Wilund KR. Efficacy of beta-hydroxy-betamethylbutyrate supplementation in elderly and clinical populations. Nutrition. 2013;29(1):29–36.CrossRefPubMedGoogle Scholar
  17. 17.
    Herr M, Robine JM, Pinot J, Arvieu JJ, Ankri J. Polypharmacy and frailty: prevalence, relationship, and impact on mortality in a French sample of 2350 old people. Pharmacoepidemiol Drug Saf. 2015;24(6):637–46.CrossRefPubMedGoogle Scholar
  18. 18.
    Gutierrez-Valencia M, Izquierdo M, Cesari M, Casas-Herrero A, Inzitari M, Martinez-Velilla N. The relationship between frailty and polypharmacy in older people: A systematic review. Br J Clin Pharmacol. 2018.Google Scholar
  19. 19.
    Rosted E, Schultz M, Sanders S. Frailty and polypharmacy in elderly patients are associated with a high readmission risk. Dan Med J. 2016;63(9).Google Scholar
  20. 20.
    Muscedere J, Kim P, Aitken P, Gaucher M, Osborn R, Farrell B, et al. Proceedings of the Canadian Frailty Network Summit: Medication Optimization for Frail Older Canadians, Toronto, Monday April 24, 2017. Can Geriatr J. 2017;20(4):253–63.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Pahor M, Guralnik JM, Ambrosius WT, Blair S, Bonds DE, Church TS, et al. Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE study randomized clinical trial. JAMA. 2014;311(23):2387–96.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Cesari M, Vellas B, Hsu FC, Newman AB, Doss H, King AC, et al. A physical activity intervention to treat the frailty syndrome in older persons-results from the LIFE-P study. J Gerontol A Biol Sci Med Sci. 2015;70(2):216–22.CrossRefPubMedGoogle Scholar
  23. 23.
    Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–56.CrossRefPubMedGoogle Scholar
  24. 24.
    Trombetti A, Hars M, Hsu FC, Reid KF, Church TS, Gill TM, et al. Effect of Physical Activity on Frailty: Secondary Analysis of a Randomized Controlled Trial. Annals of internal medicine. 2018;168(5):309–16.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Vellas B, Sourdet S. Prevention of Frailty in Aging. J Frailty Aging. 2017;6(4):174–7.PubMedGoogle Scholar
  26. 26.
    Cesari M, Fielding R, Benichou O, Bernabei R, Bhasin S, Guralnik JM, et al. Pharmacological Interventions in Frailty and Sarcopenia: Report by the International Conference on Frailty and Sarcopenia Research Task Force. J Frailty Aging. 2015;4(3):114–20.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Bergman H, Hogan D, Karunananthan S. Frailty: A clinically relevant concept? Canadian J of Geriatrics. 2008;11(3):124–8.Google Scholar
  28. 28.
    Rockwood K, Mitnitski A. Frailty defined by deficit accumulation and geriatric medicine defined by frailty. Clin Geriatr Med. 2011;27(1):17–26.CrossRefPubMedGoogle Scholar
  29. 29.
    Buta BJ, Walston JD, Godino JG, Park M, Kalyani RR, Xue QL, et al. Frailty assessment instruments: Systematic characterization of the uses and contexts of highly-cited instruments. Ageing Res Rev. 2016;26:53–61.CrossRefPubMedGoogle Scholar
  30. 30.
    Marzetti E, Calvani R, Landi F, Hoogendijk EO, Fougere B, Vellas B, et al. Innovative Medicines Initiative: The SPRINTT Project. J Frailty Aging. 2015;4(4):207–8.PubMedCentralPubMedGoogle Scholar
  31. 31.
    Manini TM, Anton SD, Beavers DP, Cauley JA, Espeland MA, Fielding RA, et al. ENabling Reduction of Low-grade Inflammation in SEniors Pilot Study: Concept, Rationale, and Design. J Am Geriatr Soc. 2017.Google Scholar
  32. 32.
    Leng SX, Xue QL, Tian J, Walston JD, Fried LP. Inflammation and frailty in older women. J Am Geriatr Soc. 2007;55(6):864–71.CrossRefPubMedGoogle Scholar
  33. 33.
    Karantalis V, Hare JM. Use of mesenchymal stem cells for therapy of cardiac disease. Circ Res. 2015;116(8):1413–30.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Golpanian S, El-Khorazaty J, Mendizabal A, DiFede DL, Suncion VY, Karantalis V, et al. Effect of aging on human mesenchymal stem cell therapy in ischemic cardiomyopathy patients. J Am Coll Cardiol. 2015;65(2):125–32.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Golpanian S, DiFede DL, Khan A, Schulman IH, Landin AM, Tompkins BA, et al. Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty. J Gerontol A Biol Sci Med Sci. 2017.Google Scholar
  36. 36.
    Golpanian S, DiFede DL, Pujol MV, Lowery MH, Levis-Dusseau S, Goldstein BJ, et al. Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty. Oncotarget. 2016;7(11):11899–912.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Tompkins BA, DiFede DL, Khan A, Landin AM, Schulman IH, Pujol MV, et al. Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase IIRandomized, Double-Blind, Placebo-Controlled Clinical Trial. J Gerontol A Biol Sci Med Sci. 2017;72(11):1513–22.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Sanders JL, Boudreau RM, Penninx BW, Simonsick EM, Kritchevsky SB, Satterfield S, et al. Association of a Modified Physiologic Index with mortality and incident disability: the Health, Aging, and Body Composition study. J Gerontol A Biol Sci Med Sci. 2012;67(12):1439–46.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Odden MC, Peralta CA, Haan MN, Covinsky KE. Rethinking the association of high blood pressure with mortality in elderly adults: the impact of frailty. Arch Intern Med. 2012;172(15):1162–8.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194–217.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Hsu FC, Kritchevsky SB, Liu Y, Kanaya A, Newman AB, Perry SE, et al. Association between inflammatory components and physical function in the health, aging, and body composition study: a principal component analysis approach. J Gerontol A Biol Sci Med Sci. 2009;64(5):581–9.CrossRefPubMedGoogle Scholar
  42. 42.
    Kelaiditi E, Cesari M, Canevelli M, van. Kan GA, Ousset PJ, Gillette-Guyonnet S, et al. Cognitive frailty: rational and definition from an (I. A. N. A. /I. A. G. G. ) international consensus group. J Nutr Health Aging. 2013;17(9):726–34.CrossRefPubMedGoogle Scholar

Copyright information

© Serdi and Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Marco Pahor
    • 1
  • S.B. Kritchevsky
    • 2
  • D.L. Waters
    • 3
  • D.T. Villareal
    • 4
  • J. Morley
    • 5
  • J.M. Hare
    • 6
  • B. Vellas
    • 7
    • 8
    • 9
  • The ICFSR Task Force
  1. 1.University of Florida Institute on AgingGainesvilleUSA
  2. 2.Sticht Center for Healthy Aging and Alzheimer’s Prevention.Wake Forest School of Medicine.Winston-SalemUSA
  3. 3.University of OtagoDunedin School of MedicineDunedinNew Zealand
  4. 4.Baylor College of Medicine and Michael E DeBakey VA Medical CenterHoustonUSA
  5. 5.Division of Geriatrics, St. LouisUniversity Medical SchoolSt. LouisUSA
  6. 6.Interdisciplinary Stem Cell InstituteUniversity of Miami Miller School of MedicineMiamiUSA
  7. 7.UMR1027 InsermToulouseFrance
  8. 8.University of Toulouse IIIToulouseFrance
  9. 9.Gérontopôle ToulouseToulouse University HospitalToulouseFrance

Personalised recommendations