Vaccination errors reported to the Vaccine Adverse Event Reporting System, (VAERS) United States, 2000–2013

Vaccine 33 (2015) 3171–3178

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Vaccination errors reported to the Vaccine Adverse Event Reporting System, (VAERS) United States, 2000–2013 Beth F. Hibbs ∗ , Pedro L. Moro, Paige Lewis, Elaine R. Miller, Tom T. Shimabukuro Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), 1600 Clifton Road, MS D-26 Atlanta, GA, USA

a r t i c l e

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Article history: Received 25 February 2015 Received in revised form 30 April 2015 Accepted 4 May 2015 Available online 14 May 2015 Keywords: Medication errors Vaccination Medical errors Errors Patient safety Vaccine safety

a b s t r a c t Importance: Vaccination errors are preventable events. Errors can have impacts including inadequate immunological protection, possible injury, cost, inconvenience, and reduced confidence in the healthcare delivery system. Objectives: To describe vaccination error reports submitted to the Vaccine Adverse Event Reporting System (VAERS) and identify opportunities for prevention. Methods: We conducted descriptive analyses using data from VAERS, the U.S. spontaneous surveillance system for adverse events following immunization. The VAERS database was searched from 2000 through 2013 for U.S. reports describing vaccination errors and reports were categorized into 11 error groups. We analyzed numbers and types of vaccination error reports, vaccines involved, reporting trends over time, and descriptions of errors for selected reports. Results: We identified 20,585 vaccination error reports documenting 21,843 errors. Annual reports increased from 10 in 2000 to 4324 in 2013. The most common error group was “Inappropriate Schedule” (5947; 27%); human papillomavirus (quadrivalent) (1516) and rotavirus (880) vaccines were most frequently involved. “Storage and Dispensing” errors (4983; 23%) included mostly expired vaccine administered (2746) and incorrect storage of vaccine (2202). “Wrong Vaccine Administered” errors (3372; 15%) included mix-ups between vaccines with similar antigens such as varicella/herpes zoster (shingles), DTaP/Tdap, and pneumococcal conjugate/polysaccharide. For error reports with an adverse health event (5204; 25% of total), 92% were classified as non-serious. We also identified 936 vaccination error clusters (i.e., same error, multiple patients, in a common setting) involving over 6141 patients. The most common error in clusters was incorrect storage of vaccine (582 clusters and more than 1715 patients). Conclusions: Vaccination error reports to VAERS have increased substantially. Contributing factors might include changes in reporting practices, increasing complexity of the immunization schedule, availability of products with similar sounding names or acronyms, and increased attention to storage and temperature lapses. Prevention strategies should be considered. Published by Elsevier Ltd.

Medication errors are an important preventable public health problem. The Institute of Medicine (IOM) report To Err Is Human: Building a Safer Health System (IOM, 2000) identified medication errors as the most common type of error in health care [1]. In 2007, the IOM Committee on Identifying and Preventing Medication Errors issued a report on medication errors [2]. Relatively few studies in the U.S. have focused specifically on vaccination errors. Those studies have found: that commonly reported errors involved wrong vaccine or improper dosing; adverse health outcomes were uncommon [3]; that about10–35% of young children had at least

∗ Corresponding author. Tel.: +1 404 639 8776; fax: +1 404 639 8834. E-mail address: [email protected] (B.F. Hibbs). http://dx.doi.org/10.1016/j.vaccine.2015.05.006 0264-410X/Published by Elsevier Ltd.

1 invalid dose administered [4,5]; and that a voluntary, team approach was effective in improving error reporting [6]. Several other studies have reported on specific vaccination errors including: extra immunization [7,8]; improper spacing of vaccine doses [9]; improper route [10,11]; expired vaccine [12]; improper storage [13] wrong drug administered [14]; and contraindication errors [15]. Other publications have highlighted possible contributors to errors, such as names and abbreviations which can soundalike and packaging that can look alike [16,17]. A review in the US Vaccine Adverse Event Reporting System (VAERS) for the period 1994–2001 identified 49 vaccination error reports, of which 42 (86%) also reported an adverse health event (AHE) [18]. In 2001–2002, 26 additional vaccination errors were identified; information on health outcomes was not included [19].

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The most frequently reported error in both reviews was wrong vaccine administered. Another VAERS review focusing on influenza vaccination in children from 1990 to 2006 found 201 reports of vaccination errors; 94% did not report any AHE [20]. Since 2000, the US immunization schedule has grown larger and more complex as new vaccines became available and recommendations expanded [21–23]. Vaccination errors, like other medical errors are preventable events. In this review we describe vaccination errors reported to VAERS from 2000 to 2013. 1. Methods VAERS is the US national spontaneous surveillance system for adverse events following US licensed vaccines, jointly administered by the Centers for Disease Control and Prevention (CDC) and the US Food and Drug Administration (FDA) [24]. The primary purpose of VAERS is to detect possible vaccine safety problems that might require further evaluation [25,26]. VAERS accepts all reports, including reports of vaccination errors, regardless of whether an AHE is documented. Guidance for reporting is available on the VAERS website [27]. Signs and symptoms of adverse events are coded using Medical Dictionary for Regulatory Affairs (MedDRA) terms; MedDRA terms are not medically confirmed diagnoses [28]. VAERS is a routine surveillance program conducted as a public health function and does not meet the definition of research; thus, it is not subject to Institutional Review Board review and informed consent requirements. We defined a vaccination error as a preventable event that might reflect incorrect use and/or potentially result in patient harm. We searched the VAERS database for US reports received from January 1, 2000 through December 31, 2013, with MedDRA terms describing vaccination errors (Appendix A). An individual VAERS report may contain more than 1 MedDRA term depending on symptoms reported; each error reported was counted in the error group totals. We used statistical package software SAS version 9.2 (SAS Institute Inc., Cary, NC) for analyses. 1.1. Vaccination error reports by type and reporting trends over time We categorized reports into 11 vaccination error groups, based on MedDRA error terms and groups created by the authors. Groups were created by grouping similar MedDRA terms describing the error and a sample of reports were reviewed to assure MedDRA term consistency with a specified group. Each report in an error group contained at least 1 of the corresponding MedDRA vaccination error terms associated with that group (Appendix A). A single report may be associated with 1 or more error groups, depending on assigned MedDRA terms. Single reports documenting multiple patients were counted as 1 report. We analyzed error groups by patient age and vaccines administered, and by year to identify trends in overall error reporting and in specific error groups over time. A 5% simple random sample of the top 3 error groups was performed using SAS. Each report sample was reviewed to characterize specific errors. 1.2. Vaccination error reports where an adverse health event (AHE) was reported We analyzed vaccination error reports with an AHE by error group, patient age and vaccines administered. A physician reviewed all serious reports and medical records when available and classified the AHE into body system categories as previously described [29].

Fig. 1. Vaccination error reports to VAERS, 2000–2013. * Based on the Code of Federal Regulations a report is classified as serious if 1 of the following is reported: death, life-threatening illness, hospitalization or prolongation of hospitalization or permanent disability. Clinical review of the 407 serious reports indicated that injection site reactions and systemic symptoms (e.g., fever) were most common (103; 25%), followed by musculoskeletal (e.g., pain in extremity) (52; 13%) and neurological (e.g., headache) (50; 12%) AHEs.

1.3. Reports involving vaccine contraindications We conducted clinical reviews of all vaccine “Contraindication” reports and examined all reports with MedDRA terms for maternal exposure or drug exposure during pregnancy to determine factors associated with this error. 1.4. Vaccination error clusters We defined a vaccination error cluster as an incident involving more than 1 patient affected by the same error, in a distinct setting and/or involving the same vaccine provider(s). Using key word search techniques in SAS, we identified a subset of reports suggestive of vaccination error clusters. Cluster reports included multiple individual VAERS reports for the cluster incident or a single cluster report documenting multiple patients affected. We reviewed reports to confirm the existence of a cluster, documented the number of patients involved, and described the cluster incidents by vaccines administered and error group. Clusters were counted as a single incident regardless of number of persons involved or reports submitted. 2. Results From January 1, 2000 through December 31, 2013, VAERS received a total of 311,185 U.S. reports, with 20,585 (7%) containing MedDRA term(s) for vaccination errors (Fig. 1). Seventy-five percent of VAERS error reports did not include any description of an AHE. Vaccination error reports increased during the study period, from 10 reports (<1% of all VAERS reports) in 2000, to 4324 (15% of VAERS reports) in 2013 (Fig. 2). Manufacturers submitted 64%

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Fig. 2. Vaccination error reports∗ and their percent† of all reports by year, VAERS, 2000–2013. * 20,585 total vaccination error primary U.S. reports 2000–2013. vaccination error reports among all primary U.S. VAERS reports by year. 311,185 total primary U.S.VAERS reports 2000–2013.

of vaccination errors reports, vaccine providers 21%, patients and parents 2%, and others (e.g. state health departments, registries) submitted 13% of reports. 2.1. Vaccination error reports by error group Of the 20,585 error reports, there were 21,843 total vaccination errors reported and categorized into 11 error groups (Table 1), most common were “Inappropriate Schedule” (5947; 27%), “Storage and Dispensing” (4983; 23%) and “Wrong Vaccine” (3372; 15%). The most common vaccines for “Inappropriate Schedule” reports and “Wrong Vaccine” errors are listed in (Table 2). In the 0–18 year old age group, (53%) of “Inappropriate Schedule” errors involved children 0–1 years old. A review of a 5% random sample (297), “Inappropriate Schedule” indicated the most common error was timing of the second Table 1 Vaccination errors categorized into 11 error groups* , VAERS, 2000–2013. Vaccination error groups Inappropriate schedule Storage and dispensing Wrong vaccine General error Incorrect dose Administration errors Accidental Product quality Contraindication Equipment Product labeling/packaging Total errors†

N (% total errors) 5947 (27) 4983 (23) 3372 (15) 2526 (12) 2002 (9) 1951 (9) 373 (2) 239 (1) 215 (1) 205 (1) 30 (<1) 21,843

An individual report may be associated with more than1 vaccination error or error group depending on assigned Medical Dictionary for Regulatory Activities (MedDRA) terms. * See Appendix A for details on vaccination error groups. † Total reports with errors = 20,585.

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†

Percent of

and third doses of human papillomavirus (quadrivalent) vaccine (HPV4), documented in 84 of the 297 (28%) random sample reports. Thirty reported delays between the first and second dose of HPV4 (median 577 days, range 179–2067 days). In 21 reports the third HPV4 dose was given prior to the minimum 12 week interval after the second dose. The next most common vaccine schedule error involved timing of pentavalent rotavirus vaccine (RV5), which was documented in 32 (11%) of the random sample reports. RV5 errors included giving the first dose beyond the “do not initiate after 15 weeks of age” prescribing information (21) and administering RV5 beyond the 32 week cut off (6). “Wrong Vaccine” was the third most commonly reported error. A review of a 5% random sample (169) of “Wrong Vaccine” error reports indicated that the most frequent of these errors involved vaccines with the same antigens given to different age groups, generally vaccines with similar names or acronyms, including: varicella/herpes zoster (shingles) (38), diphtheria, tetanus and acellular pertussis (DTaP)/tetanus toxoid, diphtheria and acellular pertussis (Tdap) (18), different trivalent inactivated influenza vaccine formulations with different age indications (10), pneumococcal conjugate/polysaccharide (7), and hepatitis A/hepatitis B (7). In 6 reports, a vaccine was mistakenly administered intradermally instead of tuberculin purified protein derivative (PPD). Five of these reports described large, painful injection site reactions. Possible sound alike (to PPD) vaccines were mistakenly administered in most of these reports: pneumococcal polysaccharide (PPV) (3), HPV4 (1), and tetanus-diphtheria (Td) (1), however reasons for the error occurrence were not specified in the reports. The second most common group error, “Storage and Dispensing” reports (4983) included two main categories: administration of expired vaccine (2746; 55%) and incorrectly stored vaccine (2202; 44%). In 96% of these reports there was no AHE. The most common expired vaccines were seasonal live attenuated influenza (LAIV) (978; 36%), herpes zoster (shingles) (332; 12%), and measles, mumps, and rubella (MMR) (216; 8%). In a review of a 5% random sample (110) of reports involving incorrect storage, most (97;

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Table 2 Inappropriate Schedule and Wrong Vaccine errors by age* and the most commonly involved vaccines, VAERS, 2000–2013. Inappropriate schedule

0–18 years old† (3385)

N (%)

19 years and older (1293)

N (%)

332 (26) 168 (13) 145 (11) 126 (10) 116 (9) 102 (8)

All ages (5947)

N (%)

Human papillomavirus (quadrivalent)

1516 (26)

Rotavirus (pentavalent)

767 (23)

Rotavirus (pentavalent) Trivalent inactivated influenza Hepatitis A DTaP¶ Varicella

880 (15) 670 (11) 494 (8) 488 (8) 435 (7)

Trivalent inactivated influenza DTaP Human papillomavirus (quadrivalent) Pneumococcal conjugate (7-valent) Hepatits A

541 (16) 392 (12) 391 (12) 390 (12) 389 (12)

Human papillomavirus (quadrivalent) Herpes zoster (shingles) Live attenuated H1N1influenza Tdap Trivalent live attenuated influenza Pneumococcal polysaccharide

0–18 years old (1981)

N (%)

19 years and older (891)

N (%)

Herpes zoster (shingles) DTaP Hepatitis A Varicella Tdap Inactivated poliovirus

345 (17) 338 (17) 311 (16) 295 (15) 284 (14) 239 (12)

Varicella DTaP Herpes zoster (shingles) Tdap Trivalent inactivated influenza Human papillomavirus (quadrivalent)

255 (29) 138 (16) 118 (13) 92 (10) 80 (9) 68 (8)

Wrong vaccine All ages (3372)

N (%)

Varicella vaccine Herpes zoster (shingles) DTaP Tdap** Hepatits A Trivalent inactivated influenza

810 (24) 597 (18) 500 (15) 384 (11) 372 (11) 314 (9)

*

Age not specified in 1269 (21%) “Inappropriate Schedule” reports. “Inappropriate Schedule” errors in the 0–18 years old age group involving children aged 0–1 years old (1801.53%). Age not specified in 500 (15%) “Wrong Vaccine” reports. ¶ DTaP: diphtheria, tetanus toxoids, and acellular pertussis vaccine. ** Tdap: tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine, adsorbed. †

88%) described vaccines kept outside of proper storage temperatures, with 53 reports of vaccines being exposed to temperatures below the recommended storage temperature. Refrigerator/freezer not holding proper temperatures was described in 72/97 reports. Patients receiving vaccine stored at incorrect temperatures were documented in almost all reports (95). 2.2. Vaccination error reports where an adverse health event (AHE) was also reported Of the 20,585 total vaccination error reports, 5204 (25%) also reported an AHE; 92% were non-serious (Fig. 1). The most common AHEs for all reports (not mutually exclusive) included injection site erythema (680; 13%), injection site pain (593; 11%) and pyrexia (569; 11%). More AHEs were reported in adults aged 19 years and older (2527) than in children aged 0–18 years (1877); in 800 (15%) reports, age was unknown or unavailable. The “Administration Errors” group (Table 1) had the highest percent of AHEs for its group (1176 of 1951 error reports; 60%); most commonly involving inactivated influenza vaccine (IIV3) (420) and HPV4 (163) vaccines. 2.3. Reports involving vaccine contraindication errors Of the 215 reports in the “Contraindication” error group (Table 1), 120 (56%) included coding terms for drug exposure during pregnancy. The remaining 95 reports included contraindications such as administering: LAIV to persons with asthma; live vaccines to persons with immunodeficiency conditions; vaccines to persons with a history of an allergic reaction to a vaccine component. In 37 of the 95 (39%) reports, an AHE was documented. Of the pregnancy-related reports, 111/120 (93%) involved live attenuated influenza vaccines, either LAIV or live attenuated monovalent pandemic H1N1 influenza vaccine (LAMV). AHEs were described in 18 (15%) of these reports; 7 were pregnancy related: spontaneous abortion (6) and vaginal bleeding (1). 2.4. Reports of vaccination error clusters We identified 936 independent vaccination error clusters out of 1501 reports, involving at least 6141 patients. Clusters ranged in

size from 2 to 501 patients (median 5). 110 clusters involved 10 or more patients affected by the same error. In 586 cluster reports, the number of patients involved was stated as “several” or “unknown” on the VAERS report and specific numbers could not be determined. Clusters related to the “Storage and Dispensing” error group accounted for 678/936 (72%) clusters; incorrect product storage (582 clusters and more than 1715 patients) and expired vaccine administered (96 clusters and more than 1340 patients) were most common. For clusters involving expired vaccine administered, the most common vaccines were live attenuated influenza vaccines, LAIV or LAMV (45 clusters involving at least 990 patients). One report described 500 children vaccinated at a local health department who received expired LAMV; no AHEs were reported. “Inappropriate Schedule” (N = 106 clusters and affecting at least 275 patients) was the next most common error group followed by “Wrong Vaccine” (N = 58 clusters affecting at least 1087 patients). 2.5. Reporting trends over time Vaccination error reports to VAERS increased over time with just 10 reports in 2000, to 4324 in 2013. From 2003 to 2004, 2006 to 2007, and 2011 to 2012, the number of error reports more than doubled compared to the previous year (Fig. 2). Prior to 2007 “General Error” was the most common vaccination error group. In 2004, 453 (62%) error reports involved a new IIV3 vaccine that was approved for persons 4 years of age and older. A review of a 5% random sample (23) of these reports coded as “General Error” revealed that the most common error was IIV3 given at an inappropriate age, to children under 4 years old (10), error reports for this specific IIV3 decreased after 2004 (197 in 2005 and 12 in 2006). “Inappropriate Schedule” (926) and “Wrong Vaccine”(755) errors constituted the increase in 2007; “Storage–Dispensing” (1439) and “Inappropriate Schedule” (794) error reports were most common among the increased reports in 2012–2013 (Fig. 3). 3. Discussion Vaccination error reports submitted to VAERS increased markedly, both in number and as a percent of all VAERS reports, during 2000–2013. Factors that might contribute to this temporal trend include: increases in the size and complexity of the

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2,500 2,000

Reports

Error Group Inappropriate Schedule

1,500

Storage/Dispensing Wrong Vaccine

1,000

General Error* Incorrect Dose

500

Administration Errors

0

Year Fig. 3. Vaccination error reports by the top 6 Error Groups, by year, VAERS, 2000–2013. * In 2007 VAERS transitioned from using Coding Symbols for a Thesaurus of Adverse Reaction Terms (COSTART) to MedDRA. MedDRA has many more options for vaccination error terms. This change likely resulted in a decrease in use of the “General Error” coding term.

immunization schedule over time [21], with more opportunity for vaccination errors; increased awareness of medical errors [2]; stimulated reporting to VAERS [30–32] and other unrecognized factors. In 2004, a large increase in vaccination error reports involved a specific new influenza vaccine, which had a more narrow age indication compared to other IIV3s in use at that time. From 2006 to 2007 vaccination error reporting increased sharply, going from 634 (4% of total reports) to 2168 (8%). VAERS coding changed in 2007, this change increased the number of codes used to describe errors and may have led to an increase in the count of errors but it is unlikely it would have been responsible for the large increase in reports observed. The coding change likely resulted in a decrease in use of the “General Error” coding terms (Fig. 3). Reports in 2007 commonly involved “Inappropriate Schedule” and “Wrong Vaccine” errors with several new vaccines (herpes zoster (shingles), rotavirus, and HPV4) and a new recommendation was made for a second dose of varicella vaccine in children [33]. In 2007, the IOM also published its report on medication errors [2] which may also have raised awareness of errors and stimulated reporting to VAERS. In 2012, an Office of the Inspector General report [34] might have stimulated increased reporting of vaccine storage errors to VAERS. More than half (64%) of error reports came from vaccine manufacturers compared to 23% of VAERS reports overall. Specific reasons for this reporting difference are unclear. Reporters may: want to discuss the error; seek guidance on how to handle an error; have a prevention idea they wish to communicate. They may also be unaware or unwilling to report errors to VAERS; or believe reporting to a manufacturer is more direct or confidential than reporting to VAERS. Medication errors have been associated with a low incidence of AHEs in various settings [35–37]. In VAERS between 2000 and 2013, 25% of vaccination error reports documented an AHE. Of the error reports with an AHE, the percentage of serious versus non-serious reports and the most common symptoms (i.e., injection site reactions, fever and other mild, self-limited systemic conditions) were similar to VAERS reports in general [38]. In a relatively large percentage of “Administration Errors” reports (60%), an AHE was also reported. These errors may include improper site, incorrect route, and wrong technique [10,11]. For all errors, “Inappropriate Schedule” errors were the most commonly reported. More than half of “Inappropriate Schedule” errors involved children aged 0–18 years old, with the majority of these in children 0–1 years old. There are

11 vaccine antigens given to children between ages 0–1 years in a highly structured, age-dependent schedule [39], and the opportunity for “Inappropriate Schedule” errors are numerous. Although the majority of these error reports involved children 0–1 years old, the single most common schedule problem reported involved HPV4 vaccine, possibly reflecting the challenges of administering a 3-dose vaccine series to an adolescent. Although schedule errors are not frequently associated with AHEs, vaccine doses given at less than minimum spacing intervals might result in a reduced immune response and require revaccination. Delayed doses may result in delayed or lack of protection/false sense of protection from vaccine preventable diseases [40]. “Storage and Dispensing” errors involved administration of vaccine that had expired or was stored outside of recommended temperature ranges. Administration of expired vaccine due to the short shelf life of LAIV has been previously described [12]. Reports of vaccines being exposed to low temperatures reinforce the need to identify and improve technology or equipment to address persistent temperature control problems [34]. A vaccine storage and handling tool kit discussing best practice strategies is available at http://www.cdc.gov/vaccines/recs/storage/toolkit/ Similar to previous VAERS reviews [18,19], “Wrong Vaccine” errors were also commonly reported. Many of these errors involved vaccines with similar antigen types approved for different age groups, or vaccines and injectable products with similar sounding names or acronyms. Clinical settings that serve both children and adults might be at increased risk for “Wrong Vaccine” errors related to age. Examples include mix-ups between varicella and herpes zoster (shingles), pneumococcal conjugate and polysaccharide vaccines, and DTaP and Tdap. Wrong drug errors in administration of HPV4 rather than tuberculin (PPD) products had not been previously reported; tetanus-containing vaccines, hepatitis B, IIV3 have been known to have been administered instead of PPD in previous observations [41]. Our findings are consistent with those of others who found that wrong vaccine errors may be more common among look-alike and sound-alike vaccines such as the tetanus-containing vaccines (Td, Tdap, DTaP and DT) [16,42]. 4. Limitations VAERS data should be interpreted with caution. Limitations include reporting bias (e.g., underreporting and stimulated reporting), variability in reporting patterns and practices among

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different types of reporters, secular changes in reporting practices, and inconsistent data quality and completeness, and a general inability to assess cause and effect. Vaccination errors described in this report were voluntarily reported to VAERS, and likely represent a small fraction of true vaccination errors. The VAERS form is not designed specifically for vaccination errors and is used to report a variety of adverse events following vaccination. Errors that are recognized, but where no AHE is experienced, might be less likely to be reported and many errors with no AHE might go completely unnoticed. VAERS does not collect information on vaccine doses administered, so rates cannot be calculated. Some error reports might not be true vaccination errors (e.g., off label use, patient delays in immunization, misclassified as “Inappropriate Schedule” errors). The VAERS database might include coding errors and coding inconsistencies which are not readily identifiable in automated analysis. Changes in coding systems and coding practices complicate our ability to draw historical comparisons to earlier years. 5. Conclusions Prevention of medical errors has been a prominent topic in US healthcare since the IOM brought the issue to the forefront [1,2]. The Institute for Safe Medication Practices [43], the National Coordinating Council for Medication Error Reduction and Prevention [44], and professional organizations such as the American Society of Health-System Pharmacists [45], and the American Academy of Pediatrics [46] have highlighted strategies for medication errors prevention. Vaccination errors that might result in patient harm and reduced immunity are an emerging area of vaccine safety surveillance and research. Potential strategies for reducing vaccination errors include: (1) education and training for providers and patients on vaccine timing and spacing, especially for vaccines with complex schedules; (2) training on proper administration technique; (3) improved monitoring of vaccine storage temperatures; (4) increase awareness of and establishment of procedures to monitor the relatively short expiration of live attenuated influenza vaccine; (5) improvements in differentiating vaccines and other products with similar sounding names and acronyms; and (6) implementation and enforcement of procedures to properly screen for vaccines contraindicated for an individuals, such as live vaccines in pregnant women. Although vaccination errors frequently do not cause AHEs, some do and they are preventable. Errors do have an impact in terms of additional costs, possible effect on immunological protection, patient/parent inconvenience, and loss of confidence in the healthcare delivery system. Even in reports in which no AHE followed the error, medical attention was often sought and some patients were revaccinated to better assure immunity. While education and enforcement of protocols and standards of practice can be helpful strategies, passive engineered interventions [47] (e.g. naming, labeling, packaging) [17,48] designed to decrease human error might be the most effective means to prevent many vaccination errors. Participating organizations Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Division of Healthcare Quality Promotion, Immunization Safety Office.

Funding/support The study was supported by the Centers for Disease Control and Prevention (CDC). This study had no external sponsors.

Role of the sponsors The CDC is responsible for vaccine safety surveillance activities, the data collection, management, interpretation, review and approval of this manuscript. Disclaimer The findings and conclusions in this article are those of the authors and do not necessarily represent those of CDC. Presentations An abstract of this research has been accepted to the Preventive Medicine Conference held, Feb 25–28, 2015. Condensation We describe reports of vaccination errors submitted to the U.S. Vaccine Adverse Event Reporting System from 2000 to 2013. Conflict of interest statement Conflict of interest none. No authors have a conflict of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript. Acknowledgements We thank Karen R. Broder, MD; CDC, Immunization Safety Office for her advice on the study methods and helpful comments. Cindy M. Weinbaum MD MPH, CDC Division of Health Care Quality Promotion for her review and editorial assistance. Appendix A. Vaccination error groups with corresponding Medical Dictionary for Regulatory Activities (MedDRA) preferred terms. Vaccination error group*

MedDRA preferred terms† ,

1. Accidental

Accidental exposure Accidental exposure to product Accidental needle stick

2. Administration errors

Drug administered at inappropriate site Drug administration error Incorrect drug dosage form administered Incorrect drug administration duration Incorrect route of drug administration Multiple use of single-use product Wrong technique in drug usage process

3. Contraindication

Contraindication to vaccination Documented hypersensitivity to administered drug Labelled drug-drug interaction medication error

4. Equipment

Injury associated with device Medical device complication Needle issue Syringe issue

5. General error

Medication error Vaccination error

6. Inappropriate schedule

Inappropriate schedule of drug administration Drug administered to patient of inappropriate age

7. Incorrect dose

Accidental overdose Drug dose omission Extra dose administered Incorrect dose administered Multiple drug overdose Overdose Underdose

B.F. Hibbs et al. / Vaccine 33 (2015) 3171–3178 Vaccination error group*

MedDRA preferred terms† ,

8. Product quality

Product contamination Product contamination microbial Product contamination physical Product quality issue Product quality control issue Product sterility lacking

9. Product labeling/packaging

Drug name confusion Drug label confusion Product label confusion Product name confusion Product container issue Product label issue Product label on wrong product Product outer packaging issue Product packaging issue Product packaging confusion

10. Storage/dispensing

Drug dispensing error Expired drug administered Incorrect product storage Incorrect storage of drug Poor quality drug administered product expiration date issue product reconstitution issue

11. Wrong vaccine

Drug dispensed to wrong patient Wrong drug administered

*

Vaccination error groups were created by authors. One MedDRA preferred term ‘Drug exposure during pregnancy’ was not included in the error groups when a review of these records revealed the vast majority did not fit our definition of a vaccination error in that the exposure occurred when neither the patient or provider was aware of the pregnancy. § MedDRA error codes are extensive, only MedDRA error codes found in VAERS data are included in this list. †

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