Abstract
Although most commonly used drugs cause adverse effects, some of them with potentially serious consequences, relatively little is known about their economic impact. The purpose of this review is to summarise information describing the cost of treatment of drug-induced adverse effects as an additional cost of pharmaceutical treatment. The focus of this study was limited to the overall economic impact of drug-related morbidity and to the economic analysis of a single class of drugs with different safety profiles.
Several studies carried out in the US have investigated adverse drug effects experienced by hospitalised patients and their impact on hospital costs. Patients who developed adverse effects were hospitalised an average of 1.2–3.8 days longer than patients who did not, with additional hospital costs of $US2284–5640 per patient (2000 values). Other research studies in different countries have quantified the incidence and economic consequences of adverse drug effects that occur in the ambulatory setting and that generate hospital admission and emergency department visits. They have shown that preventable adverse effects constitute between 43.3% and 80% of all adverse outcomes leading to emergency visits and hospital admissions, and disproportionately increase healthcare costs. Finally, a recent estimation revealed that in the US the cost of problems linked to drug use in the ambulatory setting exceeded $US177 billion in the year 2000.
NSAIDs constitute a widely used class of drugs and they are one of the leading drug classes in causing adverse effects. The acquisition costs of the drugs, as well as the costs for prevention and treatment of adverse effects, determine their cost-effectiveness ratio. Depending on the incidence and severity of adverse effects, the cost per adverse effect avoided ranges from $US215 to $US35 459 (2000 values). According to the contingent valuation methodology, willingness to pay to avoid or reduce the incidence of adverse effects is an indicator of the value individuals associate with the impact of such effects on their well-being. Individuals are willing to pay annually an average of $US240 and $US350, respectively, to avoid vomiting and gastrointestinal distress induced by NSAIDs.
Although the results of the different studies reviewed are not strictly comparable because of differences in the severity of adverse effects, the perspective of the analysis, the cost data included and the cost component considered, the data show that, apart from the implications for health, a substantial quantity of resources are used to treat adverse effects.
Similar content being viewed by others
References
Griffin MR. Epidemiology of nonsteroidal anti-inflammatory drug-associated gastrointestinal injury. Am J Med 1998; 104 (3A): 23–9
Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998 Apr 15; 279 (15): 1200–5
Kohn LT, Corrigan JM, Donaldson MS, editors. To err is human: building a safer health system. Washington, DC: National Academy Press, 1999
Bates DW, Spell N, Cullen DJ, et al., for the Adverse Drug Events Study Group. The costs of adverse drug events in hospitalised patients. JAMA 1997 Jan 22; 277 (4): 307–11
Johnson JA, Bootman JL. Drug-related morbidity and mortality: a cost-of-illness model. Arch Intern Med 1995 Oct 9; 155: 1949–56
Classen DC, Pestotnik SL, Evans RS, et al. Adverse drug events in hospitalised patients: excess length of stay, extra costs, and attributable mortality. JAMA 1997 Jan 22; 277 (4): 301–6
Col NC, Fanale JE, Kronholm P. The role of medication noncompliance and adverse drug reactions in hospitalizations of the elderly. Arch Intern Med 1990 Apr; 150: 841–5
Pouvourville G. Evaluating the real cost of NSAID therapy; ‘shadow costs’ relating to the treatment of gastrointestinal side effects. Br J Med Economics 1992; 5: 45–50
Prince BS, Goetz CM, Rihn TL, et al. Drug-related emergency department visits and hospital admissions. Am J Hosp Pharm 1992 Jul; 49 (7): 1696–700
Lin SH, Lin SH. A survey on drug-related hospitalization in a community teaching hospital. Int J Clin Pharmacol 1993; 31 (2): 66–9
Evans RS, Classen DC, Stevens LE, et al. Using a hospital information system to assess the effects of adverse drug events. In: Safran C, editor. The Seventeenth Annual Symposium on Computer Applications in Medical Care. New York: McGrawHill Inc, 1994: 161–5
Lapeyre-Mestre M, Gary J, Machelard-Roumagnac M. Incidence and cost of adverse drug reactions in a French cancer institute. Eur J Clin Pharmacol 1997; 53: 19–22
Major S, Badr S, Bahlawan L, et al. Drug-related hospitalization at a tertiary teaching center in Lebanon: incidence, associations, and relation to self-medicating behavior. Clin Pharmacol Ther 1998; 64 (4): 450–61
Moore N, Lecointre D, Noblet C, et al. Frequency and cost of serious adverse drug reactions in a department of general medicine. Br J Clin Pharmacol 1998; 45: 301–8
Moore R. Phillips C. Cost of NSAID adverse effects to the UK National Health Service. J Drug Assess 1999; 2: 207–17
Hawkins C, Hanks G. The gastroduodenal toxicity of nonsteroidal anti-inflammatory drugs: a review of the literature. J Pain Symptom Manage 2000; 20 (2): 140–51
Hunsche E, Chancellor J, Bruce N. The burden of arthritis and nonsteroidal anti-inflammatory treatment: a European literature review. Pharmacoeconomics 2001; 19 Suppl. 1: 1–15
Jones R. Nonsteroidal anti-inflammatory drug prescribing: past, present and future. Am J Med 2001; 110: 4s-7s
Soto J. Evaluatión económica del diclofenaco/misoprostol frente a rofecoxib en el tratamiento de la artrosis. Aten Farm 2001; 3: 30–7
Thomas EJ, Studdert DM, Newhouse JP, et al. Costs of medical injuries in Utah and Colorado. Inquiry 1999 Fall; 36: 255–64
Otero MJ, Domínguez-Gil A, Bajo AA, et al. Characteristics associated with ability to prevent adverse drug reactions in hospitalised patients: a comment. Pharmacotherapy 1999; 19 (10): 1185–7
Van den Bemt PMLA, Egberts TCG, Jong-van den Berg LTW, et al. Drug-related problems in hospitalised patients. Drug Saf 2000 Apr; 22 (4): 321–33
Leape LL, Kabcenell A, Berwick DM, et al. Reducing adverse drug events. Boston: Institute for Healthcare Improvement, 1998
Bates DW, Boyle DL, Vander Vliet MB, et al. Relationship between medication errors and adverse drug events. J Gen Intern Med 1995; 10: 199–205
Otero MJ, Domínguez-Gil A. Acontecimientos adversos por medicamentos: una patología emergente. Farm Hosp 2000; 24 (4): 258–66
World Health Organization. International drug monitoring: the role of the hospital. Geneva, Switzerland: World Health Organization; 1966. Report No. 425
Hepler CD, Strand LM. Opportunities and responsibilities in pharmaceutical care. Am J Hosp Pharm 1990 Mar; 47: 533–43
Avorn J. Putting adverse drug events into perspective. JAMA 1997 Jan 22; 277 (4): 341–2
Bates DW, Cullen D, Laird N, et al. Incidence of adverse drug events and potential adverse drug events: implications for prevention. JAMA 1995 Jul 5; 274 (1): 29–34
Cullen DJ, Sweitzer BJ, Bates DW, et al. Preventable adverse drug events in hospitalised patients: a comparative study of intensive care and general units. Crit Care Med 1997; 25: 1289–97
Sub D-C, Woodall BS, Shin S-K, et al. Clinical and economic impact of adverse drug reactions in hospitalised patients. Ann Pharmacother 2000 Dec; 34: 1373–9
Senst BL, Achusim LE, Genest RP, et al. Practical approach to determining costs and frequency of adverse drug events in a health care network. Am J Health Syst Pharm 2001 Jun 15; 58: 1126–32
Schneider PJ, Gift MG, Lee Y-P, et al. Cost of medication-related problems at a university hospital. Am J Health Syst Pharm 1995 Nov; 52: 2415–8
Stoukides CA, D’Agostino PR, Kaufman MB. Adverse drug reaction surveillance in an emergency room. Am J Hosp Pharm 1993 Apr; 50: 712–4
Dartnell JGA, Anderson RP, Chohan V, et al. Hospitalisation for adverse events related to drug therapy: Incidence, avoidability and costs. Med J Aust 1995 Jun 3; 164: 659–62
Dennehy CE, Kishi DT, Louie C. Drug-related illness in emergency department patients. Am J Health Syst Pharm 1996 Jun; 53: 1422–6
Otero López MJ, Bajo Bajo A, Maderuelo Fernández JA, et al. Evitabilidad de los acontecimientos adversos inducidos per medicamentos detectados en un Servicio de Urgencias. Rev Clin Esp 1999; 199: 796–805
Bajo Bajo AA. Acontecimientos adversos per medicamentos detectados en un servicio de urgencias: características de preventión y repercusión económica [thesis]. Spain: Universidad de Salamanca, 1999
Tafreshi MJ, Melby MJ, Kaback KR, et al. Medication-related visits to the emergency department: a prospective study. Ann Pharmacother 1999 Dee; 33: 1252–7
Moore N, Briffaut C, Noblet C, et al. Indirect drug-related costs. Lancet 1995 Mar 4; 345: 588–9
Lagnaoui R, Moore N, Fach J, et al. Adverse drug reactions in a department of systemic diseases-oriented internal medicine: prevalence, incidence, direct cost and avoidability. Eur J Clin Pharmacol 2000; 55: 181–6
Detournay B, Fagnani F, Pouyanne P, et al. Coût des hospitalisations pour effet indésirable médicamenteux. Therapie 2000; 55: 137–9
Pouyanne P, Haramburu F, Imbs JL, et al. Admissions to hospital caused by adverse drug reactions: cross sectional incidence study. BMJ 2000 Apr 15; 320: 1036
Johnson JA, Bootman JL. Drug-related morbidity and mortality and the economic impact of pharmaceutical care. Am J Health Syst Pharm 1997 Mar 1; 54: 554–8
Ernst FR, Grizzle AJ. Drug related morbidity and mortality: updating the cost-of-illness model. J Am Pharm Assoc 2001; 41 (2): 192–9
Bootman JL, Harrison DL, Cox E. The health care cost of drug-related morbidity and mortality in nursing facilities. Arch Intern Med 1997 Oct 13; 157: 2089–96
Alliance for Aging Research. When medicine hurts instead of helps: preventing medication problems in older persons. Washington, DC: The Alliance for Aging Research, 1998
Bloor K, Maynard A. Is there scope for improving the cost-effective prescribing of nonsteroidal anti-inflammatory drugs? Pharmacoeconomics 1996 Jun; 9 (6: 484–96
Johnson RE, Honnbbrook MC, Hooker RS, et al. Analysis of the costs of NSAID-associated gastropathy: experience in a US Health Maintenance Organisation. Pharmacoeconomics 1997 Jul; 12 (1): 76–88
Lanas A. Impacto económico de los efectos secundarios gastrointestinales asociados a anti-inflamatorios no esteroideos en el Servicio Nacional de Salud. Med Clin (Bare) 2000; 114: 46–53
Chevat C, Peña B, Maiwenn JA, et al. Healthcare resource utilisation and costs of treating NSAID-associated gastrointestinal toxicity: a multinational perspective. Pharmacoeconomics 2001; 19 Suppl. 1: 17–32
McIntosh E. The cost of rheumatoid arthritis. Br J Rheumatol 1996; 35 (8): 781–90
Bloom BS. Direct medical costs of disease and gastrointestinal side effects during treatment for arthritis. Am J Med 1988 Feb 22; 84 Suppl. 2A: 20–4
Smalley WE, Griffin MR, Fought RL, et al. Excess costs from gastrointestinal disease associated with nonsteroidal anti-inflammatory drugs. J Gen Intern Med 1996; 11: 461–9
Otero MJ, Bajo A, Martín R, et al. Gastrointestinal complications related to drug use: preventability and cost. IPA 2000 May 15; 37 (9): 791
Alonso P, Otero MJ, Maderuelo JA, et al. Análisis del coste de la hemorragia digestiva alta per anti-inflamatorios no esteroideos y salicilatos. Rev Clin Esp 2000; 200 Suppl. 1: 87
Bentkover JD, Baker A, Kaplan H. Nabumetone in elderly patients with osteoarthritis: economic benefits versus ibuprofen alone or ibuprofen plus misoprostol. Pharmacoeconomics 1994; 5 (4): 335–42
McCabe CJ, Akehurst RL, Kirsch J, et al. Choice of NSAID and management strategy in rheumatoid arthritis and osteoarthritis: the impact on cost and outcomes in the UK. Pharmacoeconomics 1998; 14 (2): 191–9
Akehurst RL, Backhouse M, Emery P, et al. Nabumetone compared with ibuprofen and a weighted NSAID combination; an economic evaluation. J Drug Assess 1998; 1: 81–99
Simon LS, Weaver AL, Graham DY, et al. Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial. JAMA 1999 Nov 24; 282 (20): 1921–8
Lagman MJ, Jensen DM, Watson DJ, et al. Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs. JAMA 1999 Nov 24; 282 (20): 1929–33
Hawkey CJ, Karrasch JA, Szczpanski L, et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal anti-inflammatory drugs. N Engl J Med 1998; 338: 727–34
Peterson WL, Cryer B. Cox-l-sparing NSAIDs: is the enthusiasm justified? JAMA 1999; 282 (20): 1961–3
Motheral BR, Bataoei JR. A strategy for evaluating the novel COX-2 inhibitors versus NSAIDs for arthritis. Formulary 1999; 34: 855–63
Zabinski RA, Burke TA, Johnson J, et al. An economic model for determining the costs and consequences of using various treatment alternatives for the management of arthritis in Canada. Pharmacoeconomics 2001; 19 (S1): 49–58
Chancellor JV, Hunsche E, de Cruz E, et al. Economic evaluation of celecoxib, a new cyclo-oxygenase 2 specific inhibitor in Switzerland. Pharmacoeconomics 2001; 19 (S1): 59–71
Canadian Coordinating Office for Health Technology Assessment. Guidelines for economic evaluations of pharmaceuticals: Canada. 2nd ed. Ottawa: CCOHTA, 1997
Stucki G, Johannesson M, Liang MIL Is misoprostol cost-effective in the prevention of non-steroidal anti-inflammatory drug-induced gastropathy in patients with chronic arthritis? Arch Intern Med 1994; 154: 2020–5
O’Brien BJ, Novosel S, Torrance G, et al. Assessing the economic value of a new antidepressant: a willingness to pay approach. Pharmacoeconomics 1995; 8 (1): 34–45
Rodríguez-Monguió R. From cost utility to cost benefit analysis in health policy decision-making [thesis]. Barcelona: Universidad de Barcelona, 2001
Agency for Healthcare Research and Quality. Making health care safer: a critical analysis of patient safety practices. AHRQ publication 01-E058. Rockville (MD): Agency for Healthcare Research and Quality, 2001 Jul
Wynne MA, Campbell M. Pharmacoeconomics of nonsteroidal anti-inflammatory drugs (NSAIDs). Pharmacoeconomics 1994; 3 (2): 107–23
Burke TA, Zanbinski RA, Pettit D, et al. A framework for evaluating the clinical consequences of initial therapy with NSAIDs, NSAIDs plus gastroprotective agents, or celecoxib in the treatment of arthritis. Pharmacoeconomics 2001; 19 (S1): 33–47
Acknowledgements
The authors would like to thank the helpful comments and suggestions from two anonymous referees. None of the authors received any funding related to the content of this manuscript, nor are they aware of any potential conflicts of interest related to the contents of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Rodríguez-Monguió, R., Otero, M.J. & Rovira, J. Assessing the Economic Impact of Adverse Drug Effects. Pharmacoeconomics 21, 623–650 (2003). https://doi.org/10.2165/00019053-200321090-00002
Published:
Issue Date:
DOI: https://doi.org/10.2165/00019053-200321090-00002