Defining Patient Centric Drug Product Design and Its Impact on Improving Safety and Effectiveness

  • Sven Stegemann
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 26)


Drug therapy is being recognized as the most preferred intervention in the cure or management of acute and chronic diseases. Progress in medical and pharmaceutical sciences coupled with the increasing life expectancy in aging societies has constantly increased the sophistication of the drug products as well as the complexity of the patients and their therapeutic regimen. Despite the fact that acute and chronic diseases can be treated with several drugs very effectively, poor adherence and medication errors often lead to poor therapeutic outcomes. Patient centricity has been identified as the way forward to improve the therapeutic outcomes by including the patient in a variety of different ways in drug product development and the therapy process. This review focus on the critical patient–product interface taking into account the increasing complexity of the micro- and macro-ergonomic context of the drug product and its use within therapeutic schemes and regimen of the patient. A definition for “patient centric drug product design” is proposed and the impact on drug product safety and effectiveness is discussed.


Patient centricity Patient centric design adherence medication Errors effectiveness 


  1. 1.
    Carnes BC, Witten TM. How long must humans live? J Gerontol A Biol Sci Med Sci. 2014;69(8):965–70.PubMedCrossRefGoogle Scholar
  2. 2.
    Eichler KA, Breckenridge A, Flamion B, Gustafsson LL, Leufkens H, Rowland M, Schneider CK, Bloechl-Daum B. Bridging the efficacy-effectiveness gap: a regulators perspective on addressing the variability of drug response. Nature Rev Drug Disc. 2011;10:495–506.CrossRefGoogle Scholar
  3. 3.
    Kassam R, Collins JB, Berkowitz J. Comparison of patients expectations and experiences at traditional pharmacies and pharmacies offering enhanced advanced pharmacy practice experiences. Am J Pharm Educ. 2010;74(5):90.Google Scholar
  4. 4.
    Sarasohn J. The wisdom of patients: healthcare meets online social media. California Healthcare Foundation. 2008.
  5. 5.
    van Herck P, De Smedt D, Annemans L, Remmen R, Rosenthal MB, Sermeus W. Systematic review: effects, design choices, and context of pay-for-performance in health care. BMC Health Serv Rev. 2010;10:247.CrossRefGoogle Scholar
  6. 6.
    Watson JD, Crick FHC. Molecular structure of nucleic acids. Nature. 1953;171:737–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Pina AS, Hussain A, Roque AC. A historical overview of drug discovery. Methods Mol Biol. 2009;575:3.Google Scholar
  8. 8.
  9. 9.
    Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Del Rev. 1997;23:3–25.CrossRefGoogle Scholar
  10. 10.
    Lipinski CA. Solubility in water and DSMO: issues and potential solutions. In: Borchardt RT, Kerns EH, Lipinski CA, Thakkur DR, Wand B, editors. Pharmaceutical profiling in drug discovery for lead selection. AAPS Press; 2004.Google Scholar
  11. 11.
    Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Meth. 2000;44:235–49.CrossRefGoogle Scholar
  12. 12.
    International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921.CrossRefGoogle Scholar
  13. 13.
    International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature 2004;431:931–45.Google Scholar
  14. 14.
    Goh K-I, Cusick ME, Valle D, Childs B, Vidal M, Barabasi A-L. The human disease network. PNAS. 2007;104(21):8685–90.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Barabasi A-L, Gulbahce N, Loscalzo J. Network medicine: a network-based approach to human disease. Nature. 2011;12:56–68.Google Scholar
  16. 16.
    Dewey FE, Grove ME, Pan C, et al. Clinical interpretation and implication of whole-genome sequencing. JAMA. 2014;311(10):1035–44.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Mullard A. 2010 FDA drug approvals. Nature Rev Drug Disc. 2011;10:82–5.CrossRefGoogle Scholar
  18. 18.
    Walsh G. Biopharmaceutical benchmark 2010. Nature Biotechnol. 2010;28(9):917–26.CrossRefGoogle Scholar
  19. 19.
    Crommelin DJA, Storm G, Verrijk R, de Leede L, Jiskoot W, Hennink WE. Shifting paradigms: biopharmaceuticals versus low molecular weight. Int J Pharm. 2003;266(1–2):3–16.PubMedCrossRefGoogle Scholar
  20. 20.
    Daugherty AL, Mrsny RJ. Formulation and delivery issues for monoclonal antibody therapeutics. Adv Drug Del Rev. 2006;58(5–6):686–706.CrossRefGoogle Scholar
  21. 21.
    FDA Guidance to industry. Clinical pharmacology data support a demonstration of biosimilarity to a reference product. Biosimilars. 2014.Google Scholar
  22. 22.
    Novartis. FDA accepts Sandoz application for biosimilar of filgrastim. 2014.
  23. 23.
    Weise M, Bielsky MC, De Smet K, Ehmann F, Ekman N, Giezen TJ, Gravanis I, Heim HK, Heinonen E, Ho K, Moreau A, Narayanan G, Kruse NA, Reichmann G, Thorpe R, van Aerts L, Vleminckx C, Wadhwa M, Schneider CK. Biosimilars: what clinicians should know. Blood. 2012;120(26):5111–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Schellekens H, Stegemann S, Weinstein V, de Vlieger JSB, Flühmann B, Mühlenbach S, Gasper R, Shah VP, Crommelin DJA. How to regulate nonbiological complex drugs (NBCD) and their follow-on versions: points to consider. AAPS J. 2014;16(1):15–21.PubMedCrossRefGoogle Scholar
  25. 25.
    Lehmann HE, Ban TA. The history of psychopharmacology of schizophrenia. Can J Psychiatry. 1997;42:152–62.PubMedCrossRefGoogle Scholar
  26. 26.
    Moser M. Historical perspective on the management of hypertension. Am J Med. 1986;80(5, Suppl 2):1–8.Google Scholar
  27. 27.
    Snow V, Barry P, Fihn SD, Gibbons RJ, Owens DK, Williams SV, Mottur-Pilson C, Weiss KB. Primary care management of chronic stable angina and asymptomatic suspected or known coronary artery disease: a clinical practice guideline from the American college of physicians. Ann Intern Med. 2004;141:562–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Williams B, Poulter NR, Brown MJ, Davis M, McInnes GT, Potter JE, Sever PS, McG Thom S. Guidelines for management of hypertension: Report of the fourth working party of the British hypertension society 2004—BHS IV. J Human Hyperten. 2004;18:139–85.CrossRefGoogle Scholar
  29. 29.
    AGS Choosing Wisely Workgroup. American Geriatrics Society identifies five things that healthcare providers and patients should question. J Am Geriatr Soc. 2013;61:612–34.CrossRefGoogle Scholar
  30. 30.
    Eichelbaum M, Ingelman-Sundberg M, Ewans WE. Pharmacogenomics and individualized drug therapy. Ann Rev Med. 2006;57:119–37.PubMedCrossRefGoogle Scholar
  31. 31.
    Annas GJ, Sherman E. 23andMe and the FDA. N Engl J Med. 2013;370(11):985–9.CrossRefGoogle Scholar
  32. 32.
    Collins FS, Hamburg MA. First FDA authorization for next-generation sequencer. N Engl J Med. 2013;369(25):2369–71.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Lesko LJ. Personalized medicine: elusive dream or imminent reality? Clin Pharmacol Ther. 2007;81(6):807–16.PubMedCrossRefGoogle Scholar
  34. 34.
    Bates S. Progress towards personalized medicines. Drug Discov Today. 2010;15(3/4):115–20.PubMedCrossRefGoogle Scholar
  35. 35.
    Cherubini A, Del Signore S, Ouslander J, Semla T, Michel J-P. Fighting against age discrimination in clinical trials. JAGS. 2010;58:1791–6.CrossRefGoogle Scholar
  36. 36.
    Cerreta F, Eichler H-G, Rasi G. Drug policy for an aging population—The European Medicines Agency’s geriatric medicines strategy. N Engl J Med. 2012;367(21):1972–4.PubMedCrossRefGoogle Scholar
  37. 37.
    Beard K. Drugs in the elderly—more good than harm? Expert Opin Drug Saf. 2007;6(3):229–31.PubMedCrossRefGoogle Scholar
  38. 38.
    Beckett N, Peters R, Tuomilehto J, Swift C, Sever P, Potter J, McCormack T, Forette F, Gil-Extremera B, Dumitrascu D, Staessen JA, Thijs L, Fletcher A. Immediate and late benefits of treating very elderly people with hypertension: results from active treatment extension to hypertension in the very elderly randomized controlled trial. Br Med J. 2012;344:d7541.CrossRefGoogle Scholar
  39. 39.
    Campanelli, et al. American Geriatrics Society updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2012;60(4):616–31.PubMedCentralCrossRefGoogle Scholar
  40. 40.
    Holt S, Schmiedl S, Thürmann PA. Potentiell inadäquate Medikation für ältere Menschen: Die PRISCUS-Liste. Dtsch Arztebl Int. 2010;107(31–32):543–51.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Gallagher P, Ryan C, Byrne S, Kennedy J, O’Mahony D. STOPP (screening tool of older persons prescriptions) and START (screening tool to alert doctors to right treatment). Consensus validation. Int J Clin Pharmacol Ther. 2008;46(2):72–83.PubMedCrossRefGoogle Scholar
  42. 42.
    Kuijpers MA, van Marum RJ, Egberts ACG, Jansen PAF. Relationship between polypharmacy and underprescribing. Br J Clin Pharmacol. 2007;65(1):130–3.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Holmes HM. Rational prescribing for patients with a reduced life expectancy. Clin Pharmacol Ther. 2009;85(1):103–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Cruz-Jentoft AJ, Boland B, Rexach L. Drug Therapy optimization at the end of life. Drugs Aging. 2012;29(6):511–21.PubMedCrossRefGoogle Scholar
  45. 45.
    Rabow MW. Chemotherapy near the end of life. A difficult decision with potentially unexpected implications. Br Med J. 2014;348:g1529.Google Scholar
  46. 46.
    ICH E11. Clinical investigation of medicinal products in the pediatric population, 20 Jul 2000.Google Scholar
  47. 47.
    Zisowsky J, Krause A, Dingemanse J. Drug development for pediatric populations: regulatory aspects. Pharmaceutics. 2010;2:364–88.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    EMA Reflection paper: Formulations of choice for the pediatric population. EMEA/CHMP/PEG/194810/2005, 28 Jul 2006.Google Scholar
  49. 49.
    EMA Guidelines on pharmaceutical development of medicines for pediatric use. EMA/CHMP/QWP/805880/2012 Rev. 2, 1 Aug 2013.Google Scholar
  50. 50.
    ICH E7. Studies in support of special populations: geriatrics. 1993.
  51. 51.
    ICH E7. E 7 Studies in support of special populations: geriatrics. Questions and answers. 2010.
  52. 52.
    EMA Geriatric Medicines Strategy. EMA/CHMP/137793/2011, 17 Feb 2011.Google Scholar
  53. 53.
    EMA Concept paper on the need for a reflection paper on quality aspects of medicines for older people. EMA/165974/2013, 20 Mar 2013.Google Scholar
  54. 54.
    Wax PM. Elixirs, diluents, and the passage of the 1938 Federal Food, Drug and Cosmetic Act. Ann Intern Med. 1995;122(6):456–61.PubMedCrossRefGoogle Scholar
  55. 55.
    Tyrer JH, Eadie MJ, Sutherland JM, Hooper WD. Outbreak of anticonvulsant intoxication in an Australian city. Br Med J. 1970;4(730):271–3.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Skelly JP. A history of biopharmaceutics in food and drug adminisration 1968–1993. AAPS J. 2010;12(1):44–50.PubMedCrossRefGoogle Scholar
  57. 57.
    Mastan S, Latha TB, Ajay S. The basic regulatory considerations and prospects for conducting bioavailability/bioequivalence (BA/BE) studies—an overview. J Comp Eff Res. 2011;1:1–25.Google Scholar
  58. 58.
    Florence AT. A short history of controlled drug release and an introduction. In: Wilson C, Crowley P, editors. Controlled release in oral delivery. Berlin: Springer; 2011.Google Scholar
  59. 59.
    Hoffman AS. The origins and evolution of “controlled” drug delivery systems. J Controlled Release. 2008;132:153–63.CrossRefGoogle Scholar
  60. 60.
    Lesar TS. Prescribing errors involving medication dosage forms. J Gen Intern Med. 2002;17:579–87.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Barber ND, Alldred DP, Raynor DK, Dickinson R, Garfield S, Jesson B, Lim R, Savage I, Standage C, Buckle P, Carpenter J, Franklin B, Woloshynowych M, Zermansky AG. Qual Saf Health Care. 2009;18:341–6.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    van Vliet MJ, Schuurmans MJ, Grypdonck MHF, Duijnstee MSH. Improper intake of medication by elders—insight on contributing factors: a review of the literature. Res Theory Nurs Pract. 2006;20(1):79–93.PubMedCrossRefGoogle Scholar
  63. 63.
    EMA. Reflection paper: Formulations of choice for the pediatric population. 2006. EMEA/CHMP/PEG/194810/2005.Google Scholar
  64. 64.
    Ernst TB, Elder DP, Martini LG, Roberts M, Ford JL. Developing paediatric medicines: identifying the needs and recognizing the challenges. J Pharm Pharmacol. 2007;59:1043–55.CrossRefGoogle Scholar
  65. 65.
    Cram A, Breitkreutz J, Desset-Brèthes S, Nunn T, Tuleu C. Challenges of developing palatable oral paediatric formulations. Int J Pharm. 2009;365:1–3.PubMedCrossRefGoogle Scholar
  66. 66.
    Strickley RG, Iwata Q, Wu S, Dahl TC. Pediatric drugs—a review of commercially available oral formulations. J Pharm Sci. 2007;97(5):1731–74.CrossRefGoogle Scholar
  67. 67.
    Spomer N, Klingmann V, Stoltenberg I, Lerch C, Meissner T, Breitkreutz J. Acceptance of uncoated mini-tablets in young children results from a prospective exploratory cross-over study. Arch Dis Child. 2012;97:283–6.PubMedCrossRefGoogle Scholar
  68. 68.
    Klingmann V, Spomer N, Lerch C, Stoltenberg I, Frömke C, Bosse HM, Breitkreutz J, Meissner T. Favorable acceptance of mini-tablets compared with syrup: a randomized controlled trial in infants and preschool children. J Pediatr. 2013;163(6):1728–32.PubMedCrossRefGoogle Scholar
  69. 69.
    Alldred DP, Standage C, Fletcher O, Savage I, Carpenter J, Barber N, Raynr DK. The influence of formulation and medicine delivery system on medication errors in care homes for older people. BMJ Qual Saf. 2011;20:397–401.PubMedCrossRefGoogle Scholar
  70. 70.
    Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology—drug disposition, action, and therapy in infant and children. N Engl J Med. 2003;349(12):1157–67.PubMedCrossRefGoogle Scholar
  71. 71.
    Baudisch A. Birds do it, bees do it, we do it: contributions of theoretical modeling to understand the shape of aging across the tree of life. Gerontology. 2012;58:481–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Gerstof D, Smith J, Baltes PB. A systemic-wholistic approach to differential aging: longitudinal findings from the Berlin aging study. Psychol Aging. 2006;21(4):645–63.CrossRefGoogle Scholar
  73. 73.
    Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev. 2009;41(2):67–76.PubMedCrossRefGoogle Scholar
  74. 74.
    Lassiter J, Bennett WM, Olyaei AJ. Drug dosing in elderly patients with chronic kidney disease. Clin Geriatr Med. 2013;29(3):657–705.PubMedCrossRefGoogle Scholar
  75. 75.
    Becker ML, Visser LE, van Gelder T, Hofman A, Stricker BHCh. Increasing exposure to drug-drug interactions between 1992–2005 in people aged ≥ 55 years. Drugs Aging. 2008;25(2):145–52.PubMedCrossRefGoogle Scholar
  76. 76.
    Tulner LR, Frankfort SV, Gijsen GJRT, van Campen JPCM, Koks CHW, Beijnen JH. Drug-drug interactions in a geriatric outpatient cohort. Drugs Aging. 2008;25(4):343–55.PubMedCrossRefGoogle Scholar
  77. 77.
    Shah RR. Development and use in the elderly: search for the right dose and dosing regimen. Br J Clin Pharacol. 2004;58(5):452–69.CrossRefGoogle Scholar
  78. 78.
    State of American well-being 2013 state, community, and congressional district analysis. 2014.
  79. 79.
    Maas I, Borchelt M, Mayer KU. Kohortenschicksale der Berliner Alten. In: Linderberger U, Smith J, Mayer KU, Baltes PB, editors. Die Berliner Altersstudie. Berlin: Akademie Verlag; 2010.Google Scholar
  80. 80.
    Steinhagen-Thiessen E, Schmader KE, Borchelt M. Disziplinspezifische Befunde, Morbidität, Medikation und Funktionalität im Alter. In: Linderberger U, Smith J, Mayer KU, Baltes PB, editors. Die Berliner Altersstudie. Berlin: Akademie Verlag; 2010.Google Scholar
  81. 81.
    Nobili A, Garattini S, Mannucci PM. Multiple disease and polypharmacy in the elderly: challenges for the internist of the third millennium. J Comorbid. 2011;1:28–44.CrossRefGoogle Scholar
  82. 82.
    Weuve J, Hebert LE, Scherr PA, Evans DA. Death in the United States among persons with Alzheimer’s disease (2010–2050). Alzheimers Dement. 2014;10(2):e40–6.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Yancik R. Cancer burden in the aged—an epidemiologic and demographic overview. Cancer. 1997;80:1273–83.PubMedCrossRefGoogle Scholar
  84. 84.
    Lindley RI. Drug trials for older people. J Gerontol A Biol Sci Med Sci. 2012;67A(2):152–7.CrossRefGoogle Scholar
  85. 85.
    Boyd CM, Fortin M. Future of multimorbidity research: how should understanding of multimorbidity in form health system design? Public Health Rev. 2010;32(2):451–74.Google Scholar
  86. 86.
    Hajjar ER, Cafiero AC, Hanlon JT. Polypharmacy in elderly patients. Am J Geriatr Pharmacother. 2007;5:345–51.Google Scholar
  87. 87.
    Marengoni A, Rizzuto D, Wang H-X, Winblad B, Fratiglioni L. Patterns of chronic multimorbidity in the elderly population. JAGS. 2009;57:225–30.CrossRefGoogle Scholar
  88. 88.
    Nobili A, Marengoni A, Tettamanti M, Salerno F, Pasina L, Franchi C, Iorio A, Marcucci M, Carrao S, Licata G, Mannucci PM. Association between clusters and diseases and polypharmacy in hospitalized elderly patients: results from the REPOSI study. Eur J Intern Med. 2011;22:597–602.PubMedCrossRefGoogle Scholar
  89. 89.
    Brunetti L, Suh D-C. Medication errors: scope and prevention strategies. J Hospit Admin. 2012;1(2):54–63.Google Scholar
  90. 90.
    Haw C, Stubbs J, Dickens G. An observational study of medication administration errors in old-age psychiatric patients. Int J Qual Health Care. 2007;19(4):210–6.Google Scholar
  91. 91.
    Lesar TS. Medication errors related to dosage formulation issues. Medscape Pharm. 2001;2(2).Google Scholar
  92. 92.
    Rasmussen J. Skills, rules and knowledge; signals, signs and symbols, and other distinctions in human performance models. IEEE Trans Syst Man Cybern, SMC-W. 1983;3:257–66.Google Scholar
  93. 93.
    Stegemann S, Gosch M, Breitkreutz J. Swallowing dysfunction and dysphagia as an unrecognized challenge for oral drug therapy. Int J Pharm. 2012;430:197–206.PubMedCrossRefGoogle Scholar
  94. 94.
    Best BM, Capparelli EV, Diep H, Rossie SS, Farrell MJ, Williams E, Lee G, van den Anker J, Rakhmanina N. Pharmacokinetics of lopinavir/ritonavir crushed versus whole tablets in children. J Acquir Immune Defic Syndr. 2011;58(4):385–91.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Kelly J, Eggleton A, Wright D. An analysis of two incidents of medicine administration to a patient with dysphagia. J Clin Nurs. 2010;20:146–55.PubMedCrossRefGoogle Scholar
  96. 96.
    Jones J. Misread labels as a cause of medication errors. Am J Nurs. 2014;114(3):11.PubMedCrossRefGoogle Scholar
  97. 97.
    Kutner M, Greenberg E, JinY, Paulsen C. The Health Literacy of America’s Adults: results from the 2003 National Assessment of Adult Literacy (NCES 2006–483). U.S. Department of Education. Washington, DC: National Center for Education Statistics; Centers for Disease Control and Prevention. Improving Health Literacy for Older Adults: Expert Panel Report 2009. 2006. Atlanta: U.S. Department of Health and Human Services; 2009.Google Scholar
  98. 98.
    Doyle G, Cafferkey K, Fullam J. The European health literacy survey: results from Ireland. HLS.EU. 2012.Google Scholar
  99. 99.
    Sundar RP, Becker MW, Bello NM, Bix L. Quantifying age-related differences in information processing behaviors when viewing prescription drug labels. PLoS ONE. 2012;7(6):e38819.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Ramaiah KD, Kumar KNV, Ramu K. Knowledge and beliefs about transmission, prevention and control of lymphatic filariasis in rural areas of South India. Trop Med Int Health. 1996;1(4):433–8.PubMedCrossRefGoogle Scholar
  101. 101.
    Pound P, Britten N, Morgan M, Yardley L, Pope C, Daker-White G, Campell R. Resisting medicines: a synthesis of qualitative studies of medicine taking. Soc Sci Med. 2005;61:133–55.PubMedCrossRefGoogle Scholar
  102. 102.
    Belcher VN, Fried TR, Agostini JV, Tinetti E. Views of older adults on patient participation in medication-related decision making. J Gen Intern Med. 2006;21:298–303.Google Scholar
  103. 103.
    Sorensen L, Stokes JA, Purdie DM, Woodward M, Roberts MS. Medication management at home: medication related risk factors associated with poor health outcomes. Age Ageing. 2005;34:626–32.PubMedCrossRefGoogle Scholar
  104. 104.
    Thompson S, Stewart K. Prescription medication use practices among non-institutionalized older persons. Int J Pharm Pract. 2001;9:141–51.CrossRefGoogle Scholar
  105. 105.
    Scherder E, Dekker W, Eggermont L. Higher-level hand motoric function in aging and (preclinical) dementia: Its relationship with (instrumental) activities of daily life: a mini-review. Gerontology. 2008;54:333–41.PubMedCrossRefGoogle Scholar
  106. 106.
    Carmeli E, Patish H, Coleman R. The aging hand. J Gerontol Med Sci. 2003;58A:146–52.CrossRefGoogle Scholar
  107. 107.
    Poole JL, Santhanam DD, Latham AL. Hand impairment and activity limitations in four chronic diseases. J Hand Ther. 2013;26(3) 323–6.Google Scholar
  108. 108.
    Klaver CCW, Wolfs RCW, Vingerling JR, Hofman A, de Jong PTWM. Age-specific prevalence and causes of blindness and visual impairment in an older population. Arch Ophthalmol. 1998;116:653–8.PubMedCrossRefGoogle Scholar
  109. 109.
    Eye disease prevalence research group. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004;122:546–72.CrossRefGoogle Scholar
  110. 110.
    Evans BJW, Rowlans G. Correctable visual impairment in older adults a major unmet need. Ophthal Physiol Opt. 2004;24:161–80.CrossRefGoogle Scholar
  111. 111.
    Agrawal Y, Platz EA, Niparko JK. Prevalence of hearing loss and differences by demographic characteristics among US adults. Arch Intern Med. 2008;168(14):22–1530.CrossRefGoogle Scholar
  112. 112.
    Cevera TC, Solar MJ, Dasi C, Ruiz JC. Speech recognition and working memory capacity in young-elderly listeners: effects of hearing sensitivity. Can J Exp Psychol. 2009;63(3):216–26.CrossRefGoogle Scholar
  113. 113.
    Gates GA, Mills JH. Presbycusis. Lancet. 2005;366:1111–20.PubMedCrossRefGoogle Scholar
  114. 114.
    Carayon P. Human factors and ergonomics in health care and patient safety. In: Carayon P, editor. Human factors and ergonomics in health care and patient safety. Boca Raton, London, New York: CRC Press; 2012.Google Scholar
  115. 115.
    Kohn LT, Corrigan JM, Donaldson MS. To Err is human: building a safer health system. Washington, DC: National Academy Press; 1999.Google Scholar
  116. 116.
    Ward J, Buckle P, Clarkson PJ. Designing packaging to support the safe use of medicines at home. Appl Ergonomics. 2010;41:682–94.CrossRefGoogle Scholar
  117. 117.
    Biron AD, Loiselle CG, Lavoie-Tremblay M. Work interruptions and their contribution to medication administration errors: an evidence review. Worldviews Evid-Based Nurs. 2009;6(2):70–86.PubMedCrossRefGoogle Scholar
  118. 118.
    Mira JJ, Martinez-Jimeno Orozco-Beltran D, Iglesias-Alonso F, Lorenzo S, Nuno R, Perez P, Toro N, Perez-Jover V, Gil-Guillen V. What older complex chronic patients need to know about their everyday medication for safe drug use. Expert Opin Drug Saf. 2014;13(6):713–21.PubMedGoogle Scholar
  119. 119.
    FDA. Draft guidance for industry—applying human factors and usability engineering to optimize medical device design, 22 Jun 2011.Google Scholar
  120. 120.
    Hughes B. Evolving R&D in emerging markets. Nature Rev Drug Discov. 2010;9:417–20.CrossRefGoogle Scholar
  121. 121.
    Baratta F, Germano A, Bursa P. Diffusion of counterfeit drugs in developing countries and stability of galenics under different conditions of temperature and relative humidity. Croat Med J. 2012;53:173–84.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    WHO. Progress on sanitation and drinking-water—2014 update. WHO Report: NLM classification: WA 670. 2014. ISBN 978 92 4 150724 0.Google Scholar
  123. 123.
    Vermeire E, Hearnshaw H, Van Royen P, Denekens J. Patient adherence to treatment: three decades of research. A comprehensive review. J Clin Pharm Ther. 2001;26:331–42.PubMedCrossRefGoogle Scholar
  124. 124.
    Cushing A, Metcalfe R. Optimizing medicines management: from compliance to concordance. Ther Clin Risk Manag. 2007;3:1047–58.PubMedPubMedCentralGoogle Scholar
  125. 125.
    McGraw C, Drennan V. Older people and medication management: from compliance to concordance. Rev Clin Gerontol. 2004;14:145–53.CrossRefGoogle Scholar
  126. 126.
    Sabate E. Adherence to long-term therapies: evidence for action. Geneva: World Health Organization; 2003. Available from:
  127. 127.
    Williams A, Manias E, Walker R. Interventions to improve medication adherence in people with multiple chronic conditions: a systematic review. J Adv Nurs. 2008;63(2):132–43.PubMedCrossRefGoogle Scholar
  128. 128.
    Peterson AM, Takiya L, Finley R. Meta-analysis of trials of interventions to improve medication adherence. Am J Health Syst Pharm. 2003;60:657–65.PubMedGoogle Scholar
  129. 129.
    Viswanathan M, Golin CE, Jones CD, Ashok M, Blalock SJ, Wines RCM, Coker-Schwimmer EJL, Rosen DL, Sista P, Lohr KN. Interventions to improve adherence to self-administered medications for chronic diseases in the United States. Ann Intern Med. 2012;157(11):785–95.PubMedCrossRefGoogle Scholar
  130. 130.
    Olaniyan JO, Ghaleb M, Dhillon S, Robinson P. Safety of medication use in primary care. Int J Pharm Pract. 2014.Google Scholar
  131. 131.
    Stegemann S, Baeyens J-P, Cerreta F, Chanie E, Löfgren A, Maio M, Schreier G, Thesing-Bleck E. Adherence measurement systems and technology for oral medications in older patient populations. Eur Geriat Med. 2012;3:254–60.CrossRefGoogle Scholar
  132. 132.
    Strachan I, Greener M. Medication-related swallowing difficulties may be more common than we realize. Pharm Pract. 2005;6:411–4.Google Scholar
  133. 133.
    Beckman AGK, Parker MG, Thorslund M. Can elderly people take their medicine? Patient Educ Couns. 2005;59:186–91.PubMedCrossRefGoogle Scholar
  134. 134.
    Donaghy A, Wright D. Standardizing risk assessment to reduce unintended non-compliance in aged patients pre-discharge. Int J Pharm Pract. 2003;11(Suppl):R51.Google Scholar
  135. 135.
    Stegemann S, Gosch M, Breitkreutz J. Swallowing dysfunction and dysphagia is an unrecognized challenge for oral drug therapy. Int J Pharm. 2012;430:197–206.PubMedCrossRefGoogle Scholar
  136. 136.
    EMA. Medication-errors workshop. Workshop report; EMA/144458/2013. 2013.
  137. 137.
  138. 138.
    EMA. Guideline on good pharmacovigilance practices (GVP) Module IV—Pharmacovigilance audits. EMA/220828/2012. 2012.
  139. 139.
    EMA. Guideline on good pharmacovigilance practices (GVP) Module VI—Management and reporting of adverse drug reactions to medicinal products. 2012.
  140. 140.
    EMA. Position paper on potential medication errors in the context of benefit-risk balance and risk minimization measures. EMA/CHMP/277591/2013. 2013.
  141. 141.
    FDA. Guidance for Industry: Safety considerations for product design to minimize medication errors. UCM331810. 2012.
  142. 142.
    Szczepura A, Wild D, Nelson S. Medication administration errors for older people in long-term resitential care. BMC Geriat. 2011;11:82.CrossRefGoogle Scholar
  143. 143.
    Lövborg H, Holmlund M, Hägg S. Medication errors related to transdermal opioid patches: lessons from a regional incident reporting system. BMC Pharmacol Toxicol. 2014;15:31.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    US Safety briefs. Fentanyl patches fatalities linked to bystander apathy. We all have a role in prevention. J Pharm Pract Res. 2013;43(4):300–01.Google Scholar
  145. 145.
    Lampert A, Seiberth J, Haefeli WE, Seidling HM. A systematic review of medication administration errors with transdermal patches. Expert Opin Drug Saf. 2014;12:1–14.Google Scholar
  146. 146.
    Imaizumi H, Yamauchi M, Namiki A, Takahashi H, Hatakeyama K. Obstructive ileus caused by a swallowed foreign body (a “press-through” package) and preexisting adhesion. Am J Emerg Med. 1997;15(1):52–3.PubMedCrossRefGoogle Scholar
  147. 147.
    Domen H, Ohara M, Noguchi M, Nakanishi Y, Komuro K, Iwashiro N, Ishizaka M. Anadvertent ingestion of a press through package causing perforation of the small intestine within incisional hernia and panperitonitis. Case Rep Gastroenterl. 2011;5:391–5.CrossRefGoogle Scholar
  148. 148.
    Bosmans JML, Spinhoven MJ, Deckers FP, Pouillon MMJ, Parizel PM. Accidental ingestion of a press-through package: an underestimated cause of serious iatrogenic disease in the elderly? J Am Geriatr Soc. 2006;54(9):1467–8.PubMedCrossRefGoogle Scholar
  149. 149.
    Fahimi F, Ariapanah P, Faizi M, Shafaghi B, Nambar R, Ardakani MT. Errors in preparation and administration of intravenous medications in the intensive care unit of a teaching hospital: An observational study. Austr Crit Care. 2008;21(2):110–6.CrossRefGoogle Scholar
  150. 150.
    Wirtz V, Taxis K, Barber ND. An observational study of intravenous medication errors in the United Kingdom and in Germany. Pharm World Sci. 2003;25(3):104–11.PubMedCrossRefGoogle Scholar
  151. 151.
    Bloch-Teitelbaum A, Lüde S, Rauber-Lüthy C, Kupferschmidt H, Russmann S, Kullak-Ublick GA, Ceschi A. Medication wrong route administration: a poisons center-based study. Expert Opin Drug Saf. 2013;12(2):145–52.PubMedCrossRefGoogle Scholar
  152. 152.
    Aronson JK. Medication errors: what they are, how they happen, and how to avoid them. Q J Med. 2009;102:513–21.CrossRefGoogle Scholar
  153. 153.
    Michaels AD, Spinler SA, Leeper B, Ohman EM, Alexander KP, Newby LK, Ay H, Gibler WB. Medication errors in acute cardiovascular and stroke patients: a scientific statement from the American Heart Association. Circulation. 2010;121:1664–82.PubMedCrossRefGoogle Scholar
  154. 154.
    Grosset KA, Reid JL, Grosset DG. Medicine-taking behavior: implications of suboptimal compliance in Parkinson’s disease. Mov Disord. 2005;20(11):1397–404.PubMedCrossRefGoogle Scholar
  155. 155.
    Manias E, Beanland C, Riley R, Baker L. Self-administration of medication in hospital: patients’ perspective. J Adv Nurs. 2004;46(2):194–203.PubMedCrossRefGoogle Scholar
  156. 156.
    Choudhry NK, Fischer MA, Avorn J, Liberman JN, Schneeweiss S, Pakes J, Brennan TA, Shrank WH. The implication of therapeutic complexity on adherence to cardiovascular medications. Arch Intern Med. 2011;171(9):814–22.PubMedGoogle Scholar
  157. 157.
    Mansur N, Weiss A, Beloosesky Y. Relationship of in-hospital modifications of elderly patients to postdischarge medications, adherence, and mortality. Ann Pharmacother. 2008;42:783–9.PubMedCrossRefGoogle Scholar
  158. 158.
    Steeman E, Moos P, Milisen K, De Bal N, De Geest S, De Froidmont C, Tellier V, Gosset C, Abraham I. Implementation of discharge management for geriatric patients at risk for readmission and institutionalization. Int J Qual Health Care. 2006;18(5):352–8.PubMedCrossRefGoogle Scholar
  159. 159.
    Scott IA. Preventing the rebound: improving care transition in hospital discharge process. Austr Health Rev. 2010;34:445–51.CrossRefGoogle Scholar
  160. 160.
    Keers RN, Williams SD, Cooke J, Ashcroft DM. Causes of medication administration errors in hospitals: a systematic review of quantitative and qualitative evidence. Drug Saf. 2013;36(11):1045–67.PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    Ching JM, Long C, Williams BL, Blackmore CC. Using lean to improve medication administration safety: in search of the “perfect dose”. Jt Comm J Qual Patient Saf. 2013;39(5):195–204.PubMedCrossRefGoogle Scholar
  162. 162.
    Messina R, Becker R, van Riet-Nales DA, Stegemann S. Results from a preliminary review of scientific evidence for appropriateness of preparations, dosage forms and other product design elements for older adult patients. Int J Pharm. 2015;478:822–8.PubMedCrossRefGoogle Scholar
  163. 163.
    Mishel MH. Perceived uncertainty and stress of illness. Res Nurs Health. 1984;4:163–71.CrossRefGoogle Scholar
  164. 164.
    Herbert TB, Cohen S. Stress and illness. Encycl Hum Behav. 1994;4:325–32.Google Scholar
  165. 165.
    Steptoe A. Invited review: the links between stress and illness. J Psychosomatic Res. 1991;35(6):633–44.CrossRefGoogle Scholar
  166. 166.
    Atkins PA, Finnegan TP, Ogle SJ, Shenfield GM. Functional ability of patients to manage medication packaging: a survey of geriatric inpatients. Age Ageing. 1994;23:113–6.CrossRefGoogle Scholar
  167. 167.
    Beckman AGK, Parker MG, Thorslund M. Can elderly people take their medicine? Patient Edu Counsel. 2005;59:186–91.CrossRefGoogle Scholar
  168. 168.
    Doggrell Sheila. Adherence to medicines in the older-aged with chronic conditions: does an intervention concerning adherence by an allied health professional help? Drugs Aging. 2010;27(3):239–54.PubMedCrossRefGoogle Scholar
  169. 169.
    Mitchell AJ, Selmes T. Why don’t patients take their medicine? Reasons and solutions in psychiatry. Adv Psychiat Treatment. 2007;13:336–46.CrossRefGoogle Scholar
  170. 170.
    Swanlund SL, Scherk KA, Metcalfe SA, Jesek-Hale SR. Keys to successful self-management of medications. Nurs Sci Quartely. 2008;21(3):238–46.CrossRefGoogle Scholar
  171. 171.
    Nicolas A, Eickhoff C, Griese N, Schulz M. Drug-related problems in prescribed medicines in Germany at the time of dispensing. Int J Clin Pharm. 2013;35(3):476–82.PubMedCrossRefGoogle Scholar
  172. 172.
    Kesselheim AS, Bykov K, Avron J, Tong A, Doherty M, Choudhry NK. Burden of changes in pill appearance for patients receiving generic cardiovascular medications after myocardial infarction. Ann Intern Med. 2014;161:96–103.PubMedCrossRefGoogle Scholar
  173. 173.
    FDA. Guidance for Industry Size, shape, and other physical attributes of generic tablets and capsules. 2013.Google Scholar
  174. 174.
    Greene JA, Kesselheim AS. Why do the same drugs look dofferent? Pills, trade dress and public health. N Engl J Med. 2011;365:83–9.PubMedCrossRefGoogle Scholar
  175. 175.
    Hellier E, Tucker M, Kenny N, Rowntree A, Edworthy J. Merits of using color and shape differentiation to improve the speed and accuracy of drug strength identification on over-the-counter medicines by laypeople. J Patient Saf. 2010;6:158–64.PubMedCrossRefGoogle Scholar
  176. 176.
    Stegemann S. Colored capsules—a contribution to drug product safety. Pharm Ind. 2005;67(9):1088–95.Google Scholar
  177. 177.
    FDA. Draft Guidance for Industry and Food and Drug Administration staff. Applying human factors and usability engineering to optimize medical device design. 2011.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2016

Authors and Affiliations

  1. 1.Graz University of TechnologyGrazAustria
  2. 2.CapsugelBornemBelgium

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