Comparison of Prescription Drug Costs in the United States and the United Kingdom, Part 4: Antibiotics in Young Children Hershel Jick,1,* Andrew Wilson,2 and Douglas Chamberlin1 1
Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, Lexington, Massachusetts; 2The Heller School for Social Policy and Management, Brandeis University, Waltham, Massachusetts
OBJECTIVES To compare the usage and cost of antibiotics in the United States and United Kingdom in children younger than 10 years. METHODS A follow up of some 160,000 young children enrolled in U.S. private health insurance companies and an equal number in general practices in the United Kingdom in 2009, based on two prospectively designed and documented electronic medical databases. MAIN RESULTS Percentage of young children in each country prescribed an antibiotic together with the estimated total annual cost. PRINCIPAL CONCLUSIONS In the United States, ~75% of privately insured children were prescribed one or more antibiotics compared with an estimated 50% in the United Kingdom. The annual cost was more than five times higher in the United States compared with the United Kingdom The usage and cost of antibiotics in young privately insured children is far higher in the United States than in the United Kingdom, where the government pays the cost of prescription drugs. KEY WORDS drug costs, antibiotics, children, United States, United Kingdom. (Pharmacotherapy 2014;34(4):324–329) doi: 10.1002/phar.1387
The cost of prescription drugs is a major element in the debate on health care costs that has continued for more than a decade in United States.1, 2 Prompted by an increased emphasis on this issue surrounding the presidential campaign of 2008, we constructed a large integrated electronic medical database that became the source of comprehensive, transparent, and accurate estimates of prescription drug usage and costs for people with private health insurance in the United States. To place the findings in a defined, quantitative, broader context, we com*Author for correspondence: Hershel Jick, Boston Collaborative Drug Surveillance Program, Boston University School of Medicine,11 Muzzey Street, Lexington, MA 02421; e-mail: [email protected]. Ó 2013 American College of Clinical Pharmacy
pared the U.S. results with those in a closely similar group of people in the United Kingdom, where the costs of prescription drugs are paid by the government.3–6 Initially, we identified more than 1 million people younger than 65 years registered in more than 300 general practices in the United Kingdom and matched each one at random to a person from the United States enrolled in a large private insurance company database according to year of birth, sex, and calendar time for years 2004–2006.3–6 The two data sets were merged into a single computer file structure that allows for rapid access. We recently updated the information to include 2007–2010.7 In this article we compare the use and cost of oral antibiotics in children younger than 10 years in both the United States and the United Kingdom in 2009.
DRUG COSTS FOR ANTIBIOTICS IN CHILDREN Jick et al Methods U.S. Data Source The U.S. prescription data were derived from the Truven Health MarketScan Research Databases (Ann Arbor, MI). The database contains comprehensive medical information contributed by large self-insured employers distributed throughout the United States, as well as a smaller number of health insurance plans.3–7 It includes longitudinal data from 1995 for more than 100 million people younger than 65 years including family members of employees. Demographic data are recorded, along with information about paid claims for drugs, medical services (with diagnoses), and procedures. Each drug claim includes information on the specific entity dispensed (coded using the National Drug Code), the date of dispensing, the quantity dispensed, and the intended duration. Most importantly, it also provides the payment for each dispensed supply of medication separately. Insurance company costs are regularly negotiated directly with drug companies. The data resource has previously been used to conduct large targeted drug safety research,8, 9 as well as drug and health care utilization studies.10, 11 U.K. Data Source The U.K prescription data were derived from the General Practice Research Database (GPRD) constructed in 1990. The recorded information has been repeatedly validated and found to be of high quality and completeness for research purposes.12–14 The GPRD contains continuous medical information derived from general practice (GP) outpatient office electronic records on more than 3 million people annually enrolled in more than 300 general practices throughout the United Kingdom. Participating practices were initially selected to reflect the age, gender, and geographic distribution of the U.K. population. The GPs use computers with identical software in their routine practice and have been trained to record demographic data, prescription drugs, and medical diagnoses in a standard format. All prescriptions (initially coded using Multilex codes) are generated electronically, and the details of each prescription are automatically recorded into the patient record. The drugs are then mapped onto a unique drug code constructed in 1966 and updated annually as necessary. This unique data resource has been used extensively for drug and
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vaccine utilization and safety research.15–19 For the current study, we included only general practices that were enrolled in the GPRD prior to 1996. Study Design We initially identified and estimated the number of children 9 years or younger who were prescribed at least one or more drugs in 2009 in both the United States and the United Kingdom. Rates of prescribed antibiotics were calculated by dividing the number of children who received at least one prescription for an oral liquid formulation antibiotic by the total number of children active in each database in 2009 excluding ophthalmic and aural preparations. Similarly, we estimated the rate of use of each antibiotic (prescribed to at least 1% of children) separately. We also estimated the average duration and cost of each prescription from a random sample of users directly from the original electronic record in the United States.3–7 In the United Kingdom, the duration and cost of each prescription were derived from the electronic medical record and based on the 2009 Prescription Cost Analysis reported by the National Health Service5–7 and converted to dollars (1 USD = 0.66 BP). Total annual cost for each antibiotic was estimated by multiplying the dollar cost per prescription by the number dispensed. Results An estimated population of ~160,000 children 0–9 years of age were enrolled and identified in each country in 2009. In the United States, an estimated 120,000 children (75%) received at least one prescription for an antibiotic. By contrast, in the United Kingdom, an estimated 80,000 children (50%) were prescribed at least one antibiotic. In each country, an estimated 10% of children were prescribed two or more antibiotic preparations in 2009. Table 1 shows the estimated number and percentage of children who were prescribed each antibiotic. Amoxicillin was the most commonly prescribed antibiotic in both countries. In the United States, an estimated 43% of children were prescribed amoxicillin at least once in 2009. The next most commonly prescribed antibiotics were azithromycin (26%) and amoxicillin/clavulanate (19%). In the United Kingdom, 34% of the children were prescribed amoxicillin. The next most commonly prescribed antibiotics were pen-
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Table 1. Estimated number of antibiotic users by drug and country in 2009, United States and United Kingdoma United States (No. of users, %)
Antibiotic Amoxicillin Azithromycin Amoxicillin/Clavulanate Cephalexin Trimethoprim/Sulfa Erythromycin
66,200 41,000 32,000 9500 8000 2400
(42) (26) (20) (6) (5) (1)
United Kingdom (No. of users, %)
Antibiotic Amoxicillin Pen-V Flucloxacillin Amoxicillin/Clavulanate Erythromycin Trimethoprim Clarithromycin
56,000 13,000 12,500 4800 3900 2800 2400
(34) (9) (8) (3) (2) (1) (2)
aBase population=160,000 children.
icillin V (8%) and flucloxacillin (8%). Amoxicillin/clavulanate was prescribed for only 3% of children. The estimated average duration and cost per prescription are shown by country in Table 2. In the United States, antibiotics were regularly prescribed for 9–11 days, except for azithromycin, which was regularly prescribed for only 5 days. The cost/prescription varied from a low of $1.17 for trimethoprim/sulfa to a high of $35.86 for amoxicillin/clavulanate. In the United Kingdom, antibiotics were regularly prescribed for only 6– 7 days. The cost/prescription varied from a low of $2.17 for trimethoprim and penicillin V to a high of $19.59 for clarithromycin. Table 3 shows the total number of prescriptions dispensed together with the estimated aver-
Table 3. Estimated average annual cost per child and total cost, United States and United Kingdom Antibiotic United States Amoxicillin/Clavulanate Erythromycin Azithromycin Cephalexin Amoxicillin Trimethoprim/Sulfa Total United Kingdom Clarithromycin Amoxicillin/Clavulanate Flucloxacillin Amoxicillin Erythromycin Pen-V Trimethoprim Total
Annual cost per child
Total annual cost
$39.45 $28.10 $21.30 $8.73 $3.70 $1.17
$1,177,000 $42,000 $781,000 $82,000 $432,000 $11,000 $2,525,000
$19.18 $6.81 $6.36 $4.05 $3.84 $2.48 $2.17
$40,000 $31,000 $73,000 $277,000 $12,000 $32,000 $11,000 $477,000
age annual cost for each antibiotic by country in 2009. In the United States, the highest annual costs were for amoxicillin/clavulanate ($1.18 million) and azithromycin ($781,000). The total annual cost was an estimated $2.5 million. In the United Kingdom, the highest annual cost was for amoxicillin ($277,000), and the total annual cost was estimated to be $477,000. Discussion The implementation of the Affordable Care Act (ACA) has led to renewed attention and debate on U.S. health care costs.20, 21 This has resulted in an increase in media articles based primarily on personal anecdotes that describe
Table 2. Total number of prescriptions Antibiotic
No. of prescriptions
(a) Average duration and cost/Rx, United States Amoxicillin 114,000 Azithromycin 37,000 Amoxicillin/Clavulanate 28,000 Cephalexin 9600 Trimethoprim/Sulfa 11,000 Erythromycin 4500 (b) Average duration and cost/Rx, United Kingdom Amoxicillin 68,500 Pen-V 13,100 Flucloxacillin 11,500 Trimethoprim 5000 Amoxicillin/Clavulanate 4600 Erythromycin 3200 Clarithromycin 2100 a
Average duration, days
Average cost/Rx
11 5 11 9 9 10
$2.64a $21.30 $35.86 $8.73 $1.17 $28.10
6 6 6 6 6 5 7
$2.66 $2.17 $6.36 $2.17 $6.05 $3.20 $9.59
Obtained locally at little cost in about 60% of patients. The prescription is recorded by insurer, but no additional payment ($0) is added.
DRUG COSTS FOR ANTIBIOTICS IN CHILDREN Jick et al striking differences in medical costs within the United States and in comparison with other countries.22–24 Many of the anecdotal reports have related to medical procedures (e.g., joint replacement, colonoscopy, and heart surgery), together with large discrepancies in costs related to hospitalization itself. In the absence of carefully documented formal studies, reliable estimates of the extent and nature of the differences in cost will remain uncertain and controversial. Prescriptions drugs are also a major contributor to the differential costs of health care. Unlike most medical procedures that are likely to be limited in time, individual drugs are often prescribed on a chronic basis, and expenditures can accumulate for decades. Extensive electronic medical records have for many years provided a useful source for estimating the costs of prescription drugs. However, a reliable comparison of relative costs within or between countries requires large continuous standardized generalizable recording systems of data that take into account age, sex, calendar time, and geography among other often necessary variables.3–7 Unlike the variability in factors related to the cost of medical procedures and hospitalizations, prescription drugs have the unique advantage in that they are typically produced by a single or relatively few international pharmaceutical companies. Furthermore, a particular drug has the same or closely similar chemical structure wherever it is produced. In the current article we provide an estimate of the relative expenditure for antibiotics in young children, comparing private insurance companies in the United States with those expended by the universal health care program in the United Kingdom. As was the case in three prior studies, the annual costs in the United States, estimated to be more than $2.4 million, were dramatically higher than those in the United Kingdom, estimated to be less than $0.48 million.3–7 Although all of the antibiotics were available in generic formulation in both countries, the percentage of children prescribed an antibiotic was far higher in the United States. The particular antibiotics commonly prescribed in the United States were regularly more costly and regularly prescribed for longer durations. The annual expenditure for amoxicillin/clavulanate pediatric prescriptions in the United States ($1.17 million) was more than twice as high as the total cost for antibiotics in the United Kingdom. Azithromycin, rarely prescribed in the
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United Kingdom, was also far more costly ($781,000) in the United States. Critical to the interpretation of the results of formal observational studies that compare drug usage and cost between countries over and beyond the need for accurate and stable information sources, is the necessity of adjusting for important population differences that bias the findings. The indication and specificity vary widely according to age, calendar time, geography, cultural differences in medical practice, and sometimes gender.3–7 In the absence of careful adjustment for these variables, comparison and interpretation of results becomes speculative. The design and implementation of the current study have a number of important strengths. The accuracy, completeness, and stability of the data sources over time have been repeatedly confirmed in both countries.3–19 The age and sex distributions of the base populations are identical and readily accounted for in an analysis of results.3 The sources and geographic distributions are broadly reflective of each general medical community. The information is derived from real-time standardized data entry. The sources are transparent and can be readily reviewed for validity by independent investigators. This cost study also has some limitations. The results apply only to young children in whom liquid formulations are routinely prescribed and the number of particular antibiotics prescribed is limited. In adults, antibiotic pills or capsules are routinely prescribed, and the overall prevalence of use is far lower than it is in children. Furthermore, more antibiotic preparations are prescribed for adults than for children.3 In addition, the results apply only to 2009. Insofar as new antibiotics are marketed or older ones become available in generic formulation, costs can differ from year to year.3–7 For the United Kingdom, the results apply to the entire population insured by a government universal health plan. In the United States, the results apply to only those who are enrolled with private health insurance companies. This difference may itself introduce related subtle prescribing biases. At the same time, the study provides a carefully designed and documented body of data that allows for a uniquely reliable estimation of the relative costs of prescription drugs expended by the U.K. National Health Service compared with expenditures by private health insurance companies in the United States. According to the U.S. Census Bureau, most people in the United States younger than 65
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years (roughly 180 million) have been enrolled annually with private health insurance companies over the last decade. The current study encompasses a representative sample of about 1.3 million (0.7%) of whom 160,000 were 9 years or younger in 2009. The recorded cost per prescription is applied by insurance companies and becomes a part of the health care cost estimate. For most of the remaining population—government employees, the military, veterans, the elderly, and other groups—health care costs for prescription drugs are at least partly paid by the government. The remainder of the population is uninsured. Detailed reliable estimates of drug costs paid by the governments could provide a useful basis for further insight into the nature of the remarkable difference in prescription drug costs between the United States and the United Kingdom. The expanded mandate of the ACA began on October 1, 2013, as millions of Americans began enrolling in private insurances plans through the health insurance exchanges. If properly applied, the subsequent impact on private insurance prescription drug costs can be evaluated and followed in real time, utilizing reliable comprehensive existing electronic resources that could provide a sound well-defined basis for policy decisions.7 Conclusion The 2009 costs of antibiotics covered by U.S. private insurance companies in children younger than 10 years were estimated to be more than five times higher than the costs in the United Kingdom covered by a government universal health plan. Reliable electronic resources continue to be available to provide comprehensive inexpensive and reliable estimates of private insurance prescription drug costs over time if properly constructed. The future effect of the ACA on drug costs in the United States is yet to be determined. Acknowledgments This manuscript received no outside funding. All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. None of the material in this manuscript has been previously published, and none of this material is under consideration or has been accepted for publication elsewhere.
References 1. Aldana SG. Financial impact of health promotion programs: a comprehensive review of the literature. Am J Health Promot 2001;15:296–320. 2. Bodenheimer T. High costs rising health care part 1: seeking an explanation. Ann Intern Med 2005;142:847–54. 3. Parkin L, Hagberg KW, Jick H. Comprehensive comparison of drug prescribing in the United States and United Kingdom. Pharmacotherapy 2011;31:623–9. 4. Jick H, Wilson A, Wiggins P, Chamberlin DP. Comparison of prescription drug costs in the United States and the United Kingdom, part 1: statins. Pharmacotherapy 2012;32:1–6. 5. Jick H, Wilson A, Wiggins P, Chamberlin DP. Comparison of prescription drug costs in the United States and the United Kingdom, part 2: proton pump inhibitors. Pharmacotherapy 2012;32:489–92. 6. Jick H, Wilson A, Wiggins P, Chamberlin DP. Comparison of prescription drug costs in the United States and the United Kingdom, part 3: methylphenidate. Pharmacotherapy 2012;32:970–3. 7. Jick H, Wilson A. The cost of prescription drugs: a comparison of two countries. Editorial. Pharmacotherapy 2012;32:967–9. 8. Jick SS, Hagberg KW, Kaye JA, Jick H. Postmenopausal estrogen-containing hormone therapy and the risk of breast cancer. Obstet Gynecol 2009;113:74–80. 9. Jick SS, Hagberg KW, Hernandez RK, Kaye JA. Postmarketing study of Ortho Evra and levonorgestrel oral contraceptives containing hormonal contraceptives with 30 mcg of ethinyl estradiol in relation to nonfatal venous thromboembolism. Contraception 2010;81:16–21. 10. Boulet SL, Molinari N-A, Grosse SD, Honcin MA, Correa-Villase~ nor A. Health care expenditures for infants and young children with Down syndrome in privately insured population. J Pediatr 2008;153:241–6. 11. Zhou F, Kyaw HM, Shefer A, Winston CA, Nuorti JP. Health care utilization for pneumonia in young children after routine pneumococcal conjugate vaccine use in the United States. Arch Pediatr Adolesc Med 2007;161:1162–8. 12. Jick H, Jick SS, Derby LE. Validation of information recorded on general practitioner-based computerized data resource in the United Kingdom. BMJ 1991;302:766–9. 13. Garcia Rodriguez LA, Perez Gutthann S. Use of the U.K. general practice research database for Pharmacoepidemiology. Br J Clin Pharmacol 1998;45:419–25. 14. Jick SS, Kaye JA, Vasilakis-Scaramoza C, et al. Validity of the general practice research database. Pharmacotherapy 2008;23:686–9. 15. Kaye JA, Melero-Montes MM, Jick H. Mumps, measles and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis. BMJ 2001;322:460–3. 16. Jick H, Chamberlin DP, Hagberg KW. The origin and spread of a mumps epidemic: United Kingdom, 2003–2006. Epidemiology 2009;20:656–61. 17. Ackers R, Murray MI, Besag FMC, Wong ICK. Prioritizing children’s medicines for research: a pharmaco-epidemiological study of antiepileptic drugs. Br J Clin Pharmacol 2007;63:689– 97. 18. Murray ML, de Vries CS, Wong ICK. A drug utilization study of antidepressants in children and adolescents using the general practice research database. Arch Dis Child 2004;89:1098– 102. 19. Viner RM, Hsia Y, Neubert A, Wong ICK. Rise in antiobesity drug prescribing for children and adolescents in the U.K.: a population-based study. Br J Clin Pharmacol 2009;68:844–51. 20. Emanuel EJ. Where are the health care cost savings? JAMA 2012;307:39–40. 21. Brook RH. Two years and counting: how will the effects of the Affordable Care Act be monitored? JAMA 2012;307:41–2. 22. Brill S. Bitter pill: why medical bills are killing us. Time magazine. March 4, 2013. Available from http://content.time.
DRUG COSTS FOR ANTIBIOTICS IN CHILDREN Jick et al com/time/magazine/article/0,9171,2136864,00.html#ixzz2drEq KOfB. 23. Rosenthal E. In need of a new hip, but priced out of the U.S. New York Times. August 3, 2013. Available from http:// www.nytimes.com/2013/08/04/health/for-medical-tourists-simplemath.html?pagewanted=all&_r=0.
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24. Bernstein N. How to charge $546 for six liters of saltwater. New York Times. August 25, 2013. Available from http://www.nytimes.com/2013/08/27/health/exploring-salines-secret-costs.html? pagewanted=all.
Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, Lexington, Massachusetts; 2The Heller School for Social Policy and Management, Brandeis University, Waltham, Massachusetts
OBJECTIVES To compare the usage and cost of antibiotics in the United States and United Kingdom in children younger than 10 years. METHODS A follow up of some 160,000 young children enrolled in U.S. private health insurance companies and an equal number in general practices in the United Kingdom in 2009, based on two prospectively designed and documented electronic medical databases. MAIN RESULTS Percentage of young children in each country prescribed an antibiotic together with the estimated total annual cost. PRINCIPAL CONCLUSIONS In the United States, ~75% of privately insured children were prescribed one or more antibiotics compared with an estimated 50% in the United Kingdom. The annual cost was more than five times higher in the United States compared with the United Kingdom The usage and cost of antibiotics in young privately insured children is far higher in the United States than in the United Kingdom, where the government pays the cost of prescription drugs. KEY WORDS drug costs, antibiotics, children, United States, United Kingdom. (Pharmacotherapy 2014;34(4):324–329) doi: 10.1002/phar.1387
The cost of prescription drugs is a major element in the debate on health care costs that has continued for more than a decade in United States.1, 2 Prompted by an increased emphasis on this issue surrounding the presidential campaign of 2008, we constructed a large integrated electronic medical database that became the source of comprehensive, transparent, and accurate estimates of prescription drug usage and costs for people with private health insurance in the United States. To place the findings in a defined, quantitative, broader context, we com*Author for correspondence: Hershel Jick, Boston Collaborative Drug Surveillance Program, Boston University School of Medicine,11 Muzzey Street, Lexington, MA 02421; e-mail: [email protected]. Ó 2013 American College of Clinical Pharmacy
pared the U.S. results with those in a closely similar group of people in the United Kingdom, where the costs of prescription drugs are paid by the government.3–6 Initially, we identified more than 1 million people younger than 65 years registered in more than 300 general practices in the United Kingdom and matched each one at random to a person from the United States enrolled in a large private insurance company database according to year of birth, sex, and calendar time for years 2004–2006.3–6 The two data sets were merged into a single computer file structure that allows for rapid access. We recently updated the information to include 2007–2010.7 In this article we compare the use and cost of oral antibiotics in children younger than 10 years in both the United States and the United Kingdom in 2009.
DRUG COSTS FOR ANTIBIOTICS IN CHILDREN Jick et al Methods U.S. Data Source The U.S. prescription data were derived from the Truven Health MarketScan Research Databases (Ann Arbor, MI). The database contains comprehensive medical information contributed by large self-insured employers distributed throughout the United States, as well as a smaller number of health insurance plans.3–7 It includes longitudinal data from 1995 for more than 100 million people younger than 65 years including family members of employees. Demographic data are recorded, along with information about paid claims for drugs, medical services (with diagnoses), and procedures. Each drug claim includes information on the specific entity dispensed (coded using the National Drug Code), the date of dispensing, the quantity dispensed, and the intended duration. Most importantly, it also provides the payment for each dispensed supply of medication separately. Insurance company costs are regularly negotiated directly with drug companies. The data resource has previously been used to conduct large targeted drug safety research,8, 9 as well as drug and health care utilization studies.10, 11 U.K. Data Source The U.K prescription data were derived from the General Practice Research Database (GPRD) constructed in 1990. The recorded information has been repeatedly validated and found to be of high quality and completeness for research purposes.12–14 The GPRD contains continuous medical information derived from general practice (GP) outpatient office electronic records on more than 3 million people annually enrolled in more than 300 general practices throughout the United Kingdom. Participating practices were initially selected to reflect the age, gender, and geographic distribution of the U.K. population. The GPs use computers with identical software in their routine practice and have been trained to record demographic data, prescription drugs, and medical diagnoses in a standard format. All prescriptions (initially coded using Multilex codes) are generated electronically, and the details of each prescription are automatically recorded into the patient record. The drugs are then mapped onto a unique drug code constructed in 1966 and updated annually as necessary. This unique data resource has been used extensively for drug and
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vaccine utilization and safety research.15–19 For the current study, we included only general practices that were enrolled in the GPRD prior to 1996. Study Design We initially identified and estimated the number of children 9 years or younger who were prescribed at least one or more drugs in 2009 in both the United States and the United Kingdom. Rates of prescribed antibiotics were calculated by dividing the number of children who received at least one prescription for an oral liquid formulation antibiotic by the total number of children active in each database in 2009 excluding ophthalmic and aural preparations. Similarly, we estimated the rate of use of each antibiotic (prescribed to at least 1% of children) separately. We also estimated the average duration and cost of each prescription from a random sample of users directly from the original electronic record in the United States.3–7 In the United Kingdom, the duration and cost of each prescription were derived from the electronic medical record and based on the 2009 Prescription Cost Analysis reported by the National Health Service5–7 and converted to dollars (1 USD = 0.66 BP). Total annual cost for each antibiotic was estimated by multiplying the dollar cost per prescription by the number dispensed. Results An estimated population of ~160,000 children 0–9 years of age were enrolled and identified in each country in 2009. In the United States, an estimated 120,000 children (75%) received at least one prescription for an antibiotic. By contrast, in the United Kingdom, an estimated 80,000 children (50%) were prescribed at least one antibiotic. In each country, an estimated 10% of children were prescribed two or more antibiotic preparations in 2009. Table 1 shows the estimated number and percentage of children who were prescribed each antibiotic. Amoxicillin was the most commonly prescribed antibiotic in both countries. In the United States, an estimated 43% of children were prescribed amoxicillin at least once in 2009. The next most commonly prescribed antibiotics were azithromycin (26%) and amoxicillin/clavulanate (19%). In the United Kingdom, 34% of the children were prescribed amoxicillin. The next most commonly prescribed antibiotics were pen-
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Table 1. Estimated number of antibiotic users by drug and country in 2009, United States and United Kingdoma United States (No. of users, %)
Antibiotic Amoxicillin Azithromycin Amoxicillin/Clavulanate Cephalexin Trimethoprim/Sulfa Erythromycin
66,200 41,000 32,000 9500 8000 2400
(42) (26) (20) (6) (5) (1)
United Kingdom (No. of users, %)
Antibiotic Amoxicillin Pen-V Flucloxacillin Amoxicillin/Clavulanate Erythromycin Trimethoprim Clarithromycin
56,000 13,000 12,500 4800 3900 2800 2400
(34) (9) (8) (3) (2) (1) (2)
aBase population=160,000 children.
icillin V (8%) and flucloxacillin (8%). Amoxicillin/clavulanate was prescribed for only 3% of children. The estimated average duration and cost per prescription are shown by country in Table 2. In the United States, antibiotics were regularly prescribed for 9–11 days, except for azithromycin, which was regularly prescribed for only 5 days. The cost/prescription varied from a low of $1.17 for trimethoprim/sulfa to a high of $35.86 for amoxicillin/clavulanate. In the United Kingdom, antibiotics were regularly prescribed for only 6– 7 days. The cost/prescription varied from a low of $2.17 for trimethoprim and penicillin V to a high of $19.59 for clarithromycin. Table 3 shows the total number of prescriptions dispensed together with the estimated aver-
Table 3. Estimated average annual cost per child and total cost, United States and United Kingdom Antibiotic United States Amoxicillin/Clavulanate Erythromycin Azithromycin Cephalexin Amoxicillin Trimethoprim/Sulfa Total United Kingdom Clarithromycin Amoxicillin/Clavulanate Flucloxacillin Amoxicillin Erythromycin Pen-V Trimethoprim Total
Annual cost per child
Total annual cost
$39.45 $28.10 $21.30 $8.73 $3.70 $1.17
$1,177,000 $42,000 $781,000 $82,000 $432,000 $11,000 $2,525,000
$19.18 $6.81 $6.36 $4.05 $3.84 $2.48 $2.17
$40,000 $31,000 $73,000 $277,000 $12,000 $32,000 $11,000 $477,000
age annual cost for each antibiotic by country in 2009. In the United States, the highest annual costs were for amoxicillin/clavulanate ($1.18 million) and azithromycin ($781,000). The total annual cost was an estimated $2.5 million. In the United Kingdom, the highest annual cost was for amoxicillin ($277,000), and the total annual cost was estimated to be $477,000. Discussion The implementation of the Affordable Care Act (ACA) has led to renewed attention and debate on U.S. health care costs.20, 21 This has resulted in an increase in media articles based primarily on personal anecdotes that describe
Table 2. Total number of prescriptions Antibiotic
No. of prescriptions
(a) Average duration and cost/Rx, United States Amoxicillin 114,000 Azithromycin 37,000 Amoxicillin/Clavulanate 28,000 Cephalexin 9600 Trimethoprim/Sulfa 11,000 Erythromycin 4500 (b) Average duration and cost/Rx, United Kingdom Amoxicillin 68,500 Pen-V 13,100 Flucloxacillin 11,500 Trimethoprim 5000 Amoxicillin/Clavulanate 4600 Erythromycin 3200 Clarithromycin 2100 a
Average duration, days
Average cost/Rx
11 5 11 9 9 10
$2.64a $21.30 $35.86 $8.73 $1.17 $28.10
6 6 6 6 6 5 7
$2.66 $2.17 $6.36 $2.17 $6.05 $3.20 $9.59
Obtained locally at little cost in about 60% of patients. The prescription is recorded by insurer, but no additional payment ($0) is added.
DRUG COSTS FOR ANTIBIOTICS IN CHILDREN Jick et al striking differences in medical costs within the United States and in comparison with other countries.22–24 Many of the anecdotal reports have related to medical procedures (e.g., joint replacement, colonoscopy, and heart surgery), together with large discrepancies in costs related to hospitalization itself. In the absence of carefully documented formal studies, reliable estimates of the extent and nature of the differences in cost will remain uncertain and controversial. Prescriptions drugs are also a major contributor to the differential costs of health care. Unlike most medical procedures that are likely to be limited in time, individual drugs are often prescribed on a chronic basis, and expenditures can accumulate for decades. Extensive electronic medical records have for many years provided a useful source for estimating the costs of prescription drugs. However, a reliable comparison of relative costs within or between countries requires large continuous standardized generalizable recording systems of data that take into account age, sex, calendar time, and geography among other often necessary variables.3–7 Unlike the variability in factors related to the cost of medical procedures and hospitalizations, prescription drugs have the unique advantage in that they are typically produced by a single or relatively few international pharmaceutical companies. Furthermore, a particular drug has the same or closely similar chemical structure wherever it is produced. In the current article we provide an estimate of the relative expenditure for antibiotics in young children, comparing private insurance companies in the United States with those expended by the universal health care program in the United Kingdom. As was the case in three prior studies, the annual costs in the United States, estimated to be more than $2.4 million, were dramatically higher than those in the United Kingdom, estimated to be less than $0.48 million.3–7 Although all of the antibiotics were available in generic formulation in both countries, the percentage of children prescribed an antibiotic was far higher in the United States. The particular antibiotics commonly prescribed in the United States were regularly more costly and regularly prescribed for longer durations. The annual expenditure for amoxicillin/clavulanate pediatric prescriptions in the United States ($1.17 million) was more than twice as high as the total cost for antibiotics in the United Kingdom. Azithromycin, rarely prescribed in the
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United Kingdom, was also far more costly ($781,000) in the United States. Critical to the interpretation of the results of formal observational studies that compare drug usage and cost between countries over and beyond the need for accurate and stable information sources, is the necessity of adjusting for important population differences that bias the findings. The indication and specificity vary widely according to age, calendar time, geography, cultural differences in medical practice, and sometimes gender.3–7 In the absence of careful adjustment for these variables, comparison and interpretation of results becomes speculative. The design and implementation of the current study have a number of important strengths. The accuracy, completeness, and stability of the data sources over time have been repeatedly confirmed in both countries.3–19 The age and sex distributions of the base populations are identical and readily accounted for in an analysis of results.3 The sources and geographic distributions are broadly reflective of each general medical community. The information is derived from real-time standardized data entry. The sources are transparent and can be readily reviewed for validity by independent investigators. This cost study also has some limitations. The results apply only to young children in whom liquid formulations are routinely prescribed and the number of particular antibiotics prescribed is limited. In adults, antibiotic pills or capsules are routinely prescribed, and the overall prevalence of use is far lower than it is in children. Furthermore, more antibiotic preparations are prescribed for adults than for children.3 In addition, the results apply only to 2009. Insofar as new antibiotics are marketed or older ones become available in generic formulation, costs can differ from year to year.3–7 For the United Kingdom, the results apply to the entire population insured by a government universal health plan. In the United States, the results apply to only those who are enrolled with private health insurance companies. This difference may itself introduce related subtle prescribing biases. At the same time, the study provides a carefully designed and documented body of data that allows for a uniquely reliable estimation of the relative costs of prescription drugs expended by the U.K. National Health Service compared with expenditures by private health insurance companies in the United States. According to the U.S. Census Bureau, most people in the United States younger than 65
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years (roughly 180 million) have been enrolled annually with private health insurance companies over the last decade. The current study encompasses a representative sample of about 1.3 million (0.7%) of whom 160,000 were 9 years or younger in 2009. The recorded cost per prescription is applied by insurance companies and becomes a part of the health care cost estimate. For most of the remaining population—government employees, the military, veterans, the elderly, and other groups—health care costs for prescription drugs are at least partly paid by the government. The remainder of the population is uninsured. Detailed reliable estimates of drug costs paid by the governments could provide a useful basis for further insight into the nature of the remarkable difference in prescription drug costs between the United States and the United Kingdom. The expanded mandate of the ACA began on October 1, 2013, as millions of Americans began enrolling in private insurances plans through the health insurance exchanges. If properly applied, the subsequent impact on private insurance prescription drug costs can be evaluated and followed in real time, utilizing reliable comprehensive existing electronic resources that could provide a sound well-defined basis for policy decisions.7 Conclusion The 2009 costs of antibiotics covered by U.S. private insurance companies in children younger than 10 years were estimated to be more than five times higher than the costs in the United Kingdom covered by a government universal health plan. Reliable electronic resources continue to be available to provide comprehensive inexpensive and reliable estimates of private insurance prescription drug costs over time if properly constructed. The future effect of the ACA on drug costs in the United States is yet to be determined. Acknowledgments This manuscript received no outside funding. All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. None of the material in this manuscript has been previously published, and none of this material is under consideration or has been accepted for publication elsewhere.
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