European Geriatric Medicine

, Volume 9, Issue 2, pp 191–199 | Cite as

The adverse drug reaction risk in older persons (ADRROP) prediction scale: derivation and prospective validation of an ADR risk assessment tool in older multi-morbid patients

  • Denis O’MahonyEmail author
  • Marie Noelle O’Connor
  • Joseph Eustace
  • Stephen Byrne
  • Mirko Petrovic
  • Paul Gallagher
Research Paper



Adverse drug reactions (ADRs) cause serious morbidity and mortality in multi-morbid older adults. Reliable ADR risk prediction would improve patient safety in this at-risk population. We aimed to derive and validate a new predictive tool for assessing ADR Risk in Older People (acronym ADRROP).


We combined four databases describing 2217 older people hospitalized with acute illness in order to determine risk factor variables significantly associated with ADRs. We identified the independent ADR risk factors from 1687 patients (derivation cohort) and used them to construct the ADRROP scale. We prospectively validated ADRROP using data from 530 patients (validation cohort). We applied area under the curve (AUC) analysis to test ADRROP’s ADR predictive power. We also compared ADRROP’s performance to the GerontoNet ADR risk scale.


Eight independent ADR risk factors were identified in the derivation patient cohort: female gender, age > 70 years, estimated GFR < 30 ml/min/1.73 m2, assistance required for ≥ 1 daily activity, ≥ 4 co-morbidities, liver disease, presence and number of STOPP criteria-defined potentially inappropriate medications, and ≥ 1 fall in the previous year. The ADRROP predictive scale constructed from these combined variables ranged from 0 to 27. The derivation cohort AUC value was 0.623 (95% CI 0.598–0.665); the validation cohort AUC was 0.592 (95% CI 0.532–0.652). Applying the GerontoNet ADR risk scale to the combined cohorts yielded an AUC of 0.566 (95% CI 0.537–0.596).

Conclusions and relevance

Neither ADRROP nor the GerontoNet ADR risk scale predicted ADRs to a high level in hospitalized older people with multi-morbidity.


Adverse drug reactions (ADRs) Prevention Risk prediction Multi-morbidity Older people Polypharmacy 



This research was supported by the SENATOR Project, funded by the European Commission under the Seventh Framework Programme (Grant Number 305930) and the Health Research Board of Ireland (Grant Number HRA_HSR/2010/14). The assistance of Dr. Darren Dahly, PhD, of the University College Cork Clinical Research Facility with the statistical analysis of the data is gratefully acknowledged.

Compliance with ethical standards

Conflict of interest

None of the authors reports a conflict of interest in relation to this manuscript.

Ethical approval

Each of the 4 studies whose data constituted the database for the present study received approval from the Cork University Hospitals research ethics committee.

Informed consent

Each of the 4 ethically approved studies collected data on the basis of written informed consent from patients or their next-of-kin.


  1. 1.
    Kongkaew C, Noyce PR, Ashcroft DM (2008) Hospital admissions associated with adverse drug reactions: a systematic review of prospective observational studies. Ann Pharmacother 42(7):1017–1025CrossRefPubMedGoogle Scholar
  2. 2.
    Al Hamid A, Ghaleb M, Aljadhey H, Aslanpour Z (2014) A systematic review of hospitalization resulting from medicine-related problems in adult patients. Br J Clin Pharmacol 78(2):202–217CrossRefPubMedGoogle Scholar
  3. 3.
    Rehan HS, Chopra D, Kakkar AK (2009) Physician’s guide to pharmacovigilance: terminology and causality assessment. Eur J Intern Med 20(1):3–8CrossRefPubMedGoogle Scholar
  4. 4.
    Gurwitz JH, Field TS, Harrold LR, Rothschild J, Debellis K, Seger AC, Cadoret C, Fish LS, Garber L, Kelleher M, Bates DW (2003) Incidence and preventability of adverse drug events among older persons in the ambulatory setting. JAMA 289(9):1107–1116CrossRefPubMedGoogle Scholar
  5. 5.
    Hamilton H, Gallagher P, Ryan C, Byrne S, O’Mahony D (2011) Potentially inappropriate medications defined by STOPP criteria and the risk of adverse drug events in older hospitalized patients. Arch Intern Med 171(11):1013–1019CrossRefPubMedGoogle Scholar
  6. 6.
    Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, Farrar K, Park BK, Breckenridge AM (2004) Adverse drug reactions as cause of admission to hospital: prospective analysis of 18820 patients. Br Med J 329(7456):15–19CrossRefGoogle Scholar
  7. 7.
    Scott I, Jayathissa S (2010) Quality of drug prescribing in older patients: is there a problem and can we improve it? Intern Med J 40(1):7–18CrossRefPubMedGoogle Scholar
  8. 8.
    Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, Laffel G, Sweitzer BJ, Shea BF, Hallisey R et al (1995) Incidence of adverse drug events and potential adverse drug events. Implications for prevention. ADE Prevention Study Group. JAMA 274(1):29–34CrossRefPubMedGoogle Scholar
  9. 9.
    Leendertse AJ, Egberts AC, Stoker LJ, van den Bemt PM, HARM Study Group (2008) Frequency of and risk factors for preventable medication-related hospital admissions in the Netherlands. Arch Intern Med 168(17):1890–1896PubMedGoogle Scholar
  10. 10.
    Taché SV, Sönnichsen A, Ashcroft DM (2011) Prevalence of adverse drug events in ambulatory care: a systematic review. Ann Pharmacother 45(7–8):977–989CrossRefPubMedGoogle Scholar
  11. 11.
    Petrovic M, van der Cammen T, Onder G (2012) Adverse drug reactions in older people: detection and prevention. Drugs Aging 29(6):453–462CrossRefPubMedGoogle Scholar
  12. 12.
    O’Connor MN, Gallagher P, Byrne S, O’Mahony D (2012) Adverse drug reactions in older patients during hospitalisation: are they predictable? Age Ageing 41(6):771–776CrossRefPubMedGoogle Scholar
  13. 13.
    Lattanzio F, Laino I, Pedone C, Corica F, Maltese G, Salerno G, Garasto S, Corsonello A, Incalzi RA, PharmacosurVeillance in the elderly Care (PVC) Study Group (2012) Geriatric conditions and adverse drug reactions in elderly hospitalized patients. J Am Med Dir Assoc 13(2):96–99CrossRefPubMedGoogle Scholar
  14. 14.
    Tangiisuran B, Davies JG, Wright JE, Rajkumar C (2012) Adverse drug reactions in a population of hospitalized very elderly patients. Drugs Aging 29(8):669–679PubMedGoogle Scholar
  15. 15.
    Patel TK, Patel PB (2016) Incidence of adverse drug reactions in Indian hospitals: a systematic review of prospective studies. Curr Drug Saf 11(2):128–136CrossRefPubMedGoogle Scholar
  16. 16.
    Harugeri A, Parthasarathi G, Ramesh M, Guido S, Basavanagowdappa H (2011) Frequency and nature of adverse drug reactions in elderly in-patients of two Indian medical college hospitals. J Postgrad Med 57(3):189–195CrossRefPubMedGoogle Scholar
  17. 17.
    Passarelli MC, Jacob-Filho W, Figueras A (2005) Adverse drug reactions in an elderly hospitalised population: inappropriate prescription is a leading cause. Drugs Aging 22(9):767–777CrossRefPubMedGoogle Scholar
  18. 18.
    Dormann H, Sonst A, Müller F, Vogler R, Patapovas A, Pfistermeister B, Plank-Kiegele B, Kirchner M, Hartmann N, Bürkle T, Maas R (2013) Adverse drug events in older patients admitted as an emergency: the role of potentially inappropriate medication in elderly people (PRISCUS). Dtsch Arztebl Int 110(13):213–219PubMedPubMedCentralGoogle Scholar
  19. 19.
    Tosato M, Landi F, Martone AM, Cherubini A, Corsonello A, Volpato S, Bernabei R, Onder G, Investigators of the CRIME Study (2014) Potentially inappropriate drug use among hospitalised older adults: results from the CRIME study. Age Ageing 43(6):767–773CrossRefPubMedGoogle Scholar
  20. 20.
    Corsonello A, Pedone C, Corica F, Mussi C, Carbonin P, Antonelli Incalzi R, Gruppo Italiano di Farmacovigilanza nell’Anziano (GIFA) Investigators (2005) Concealed renal insufficiency and adverse drug reactions in elderly hospitalized patients. Arch Intern Med 165(7):790–795CrossRefPubMedGoogle Scholar
  21. 21.
    Helldén A, Bergman U, von Euler M, Hentschke M, Odar-Cederlöf I, Ohlén G (2009) Adverse drug reactions and impaired renal function in elderly patients admitted to the emergency department: a retrospective study. Drugs Aging 26(7):595–606CrossRefPubMedGoogle Scholar
  22. 22.
    Zhang M, Holman CD, Price SD, Sanfilippo FM, Preen DB, Bulsara MK (2009) Comorbidity and repeat admission to hospital for adverse drug reactions in older adults: retrospective cohort study. Br Med J 338:a2752CrossRefGoogle Scholar
  23. 23.
    McLachlan AJ, Pont LG (2012) Drug metabolism in older people—a key consideration in achieving optimal outcomes with medicines. J Gerontol A 67(2):175–180CrossRefGoogle Scholar
  24. 24.
    Budnitz DS, Lovegrove MC, Shehab N, Richards CL (2011) Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med 365(21):2002–2012CrossRefPubMedGoogle Scholar
  25. 25.
    Onder G, Pedone C, Landi F, Cesari M, Della Vedova C, Bernabei R, Gambassi G (2002) Adverse drug reactions as cause of hospital admissions: results from the Italian Group of Pharmacoepidemiology in the Elderly (GIFA). J Am Geriatr Soc 50(12):1962–1968CrossRefPubMedGoogle Scholar
  26. 26.
    Stevenson JM, Williams JL, Burnham TG, Prevost AT, Schiff R, Erskine SD, Davies JG (2014) Predicting adverse drug reactions in older adults; a systematic review of the risk prediction models. Clin Investig Aging 9:1581–1593Google Scholar
  27. 27.
    McElnay JC, McCallion CR, Al-Deagi F, Scott MG (1997) Development of a risk model for adverse drug events in the elderly. Clin Drug Investig 13:47–55CrossRefGoogle Scholar
  28. 28.
    Tangiisuran B, Scutt G, Stevenson J, Wright J, Onder G, Petrovic M, van der Cammen TJ, Rajkumar C, Davies G (2014) Development and validation of a risk model for predicting adverse drug reactions in older people during hospital stay: Brighton Adverse Drug Reactions Risk (BADRI) model. PLoS ONE 9(10):e111254CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Onder G, Petrovic M, Tangiisuran B, Meinardi MC, Markito-Notenboom WP, Somers A, Rajkumar C, Bernabei R, van der Cammen TJ (2010) Development and validation of a score to assess risk of adverse drug reactions among in-hospital patients 65 years or older: the GerontoNet ADR risk score. Arch Intern Med 170(13):1142–1148CrossRefPubMedGoogle Scholar
  30. 30.
    Trivalle C, Burlaud A, Ducimetriere P, The IMEPAG Group 1 (2011) Risk factors for adverse drug events in hospitalised elderly patients: a geriatric score. Eur Geriatr Med 2:284–289CrossRefGoogle Scholar
  31. 31.
    Schneider EL, Campese VM (2010) Adverse drug responses: an increasing threat to the well-being of older patients: comment on “Development and validation of a score to assess risk of adverse drug reactions among in-hospital patients 65 years or older”. Arch Intern Med 170(13):1148–1149CrossRefPubMedGoogle Scholar
  32. 32.
    World Health Organization technical report series, No. 498, p 9. Accessed 2 Nov 2017
  33. 33.
  34. 34.
    O’Sullivan D, O’Mahony D, O’Connor MN, Gallagher P, Gallagher J, Cullinan S, O’Sullivan R, Eustace J, Byrne S (2016) Prevention of adverse drug reactions in hospitalised older patients using a software-supported structured pharmacist intervention: a cluster randomised controlled trial. Drugs Aging 33(1):63–73CrossRefPubMedGoogle Scholar
  35. 35.
    O’Connor MN, O’Sullivan D, Gallagher PF, Eustace J, Byrne S, O’Mahony D (2016) Prevention of hospital-acquired adverse drug reactions in older people using screening tool of older persons’ prescriptions and screening tool to alert to right treatment criteria: a cluster randomized controlled trial. J Am Geriatr Soc 64(8):1558–1566CrossRefPubMedGoogle Scholar
  36. 36.
    Cunningham G, Dodd TR, Grant DJ, McMurdo ME, Richards RM (1997) Drug-related problems in elderly patients admitted to Tayside hospitals, methods for prevention and subsequent reassessment. Age Ageing 26(5):375–382CrossRefPubMedGoogle Scholar
  37. 37.
    Boeker EB, Ram K, Klopotowska JE, de Boer M, Creus MT, de Andrés AL, Sakuma M, Morimoto T, Boermeester MA, Dijkgraaf MG (2015) An individual patient data meta-analysis on factors associated with adverse drug events in surgical and non-surgical inpatients. Br J Clin Pharmacol 79(4):548–557CrossRefPubMedGoogle Scholar
  38. 38.
    O’Mahony D (2017) Optimizing pharmacotherapy for older patients. In: Michel J-P, Lynn Beattie B, Martin FC, Walston JD (eds) Oxford textbook of geriatric medicine, 3rd edn. Oxford University Press, Oxford, p 183–88Google Scholar
  39. 39.
    Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E, Domecq C, Greenblatt DJ (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30(2):239–245CrossRefPubMedGoogle Scholar
  40. 40. accessed on November 2, 2017
  41. 41.
    Alhawassi TM, Krass I, Bajorek BV, Pont LG (2014) A systematic review of the prevalence and risk factors for adverse drug reactions in the elderly in the acute care setting. Clin Interv Aging 9:2079–2086PubMedPubMedCentralGoogle Scholar

Copyright information

© European Geriatric Medicine Society 2018

Authors and Affiliations

  1. 1.Department of Medicine (Geriatrics), University College CorkCork University HospitalCorkIreland
  2. 2.Clinical Research FacilityUniversity College CorkCorkIreland
  3. 3.School of PharmacyUniversity College CorkCorkIreland
  4. 4.Department of Internal Medicine (Geriatrics)Ghent UniversityGhentBelgium

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