Abstract
Background:
California Senate Bill 277 (SB277) eliminated non-medical immunization exemptions. Since its introduction on February 19, 2015, the rate of medical exemptions in the state has increased. Filing a report to Vaccine Adverse Event Reporting System (VAERS) may be perceived as helpful in applying for a medical exemption. Our objective was to describe trends in reporting to VAERS from California coincident with introduction of SB277.
Methods:
This was a retrospective study of Californian children <18 years for whom a VAERS report was submitted between June 1, 2011 and July 31, 2018. VAERS is a national, passive, vaccine safety surveillance program co-managed by CDC and FDA. The main outcomes were the proportion of VAERS reports submitted by parents (versus other reporter types), time from immunization to VAERS report (reporting time), and adverse event type. We also performed spatial analysis, mapping reports pre- and post-mandate by county.
Results:
We identified 6,703 VAERS reports from California during the study period. The proportion of reports received from parents increased after implementation of SB277, from 14% to 23%. The median reporting time by parents increased from 9 days in 2013-2014 to 31 days in 2016-2017. After the introduction of SB277, we observed an increase in reports describing behavioral and developmental symptoms among reports submitted >6 months after immunization.
Conclusions:
These recent changes in reporting patterns coincident with the introduction of SB277 may indicate that more parents are using VAERS to assist in applying for a medical exemption for their child.
Keywords: Vaccine Policy, Adverse Event Reporting, Vaccine Exemption
Introduction
Medical exemption from immunization of school-aged children is permitted by all states. Some states also permit non-medical exemptions on religious or philosophical grounds. Non-medical exemptions were eliminated in California on July 1, 2016, with the implementation of Senate Bill 277 (SB277).1 The bill, first introduced on February 19, 2015, requires every child to be vaccinated or have a medical exemption on file before entering a new grade span (defined as birth to preschool, kindergarten to grade 6, and grades 7 to 12). Since the implementation of SB277, the proportion of kindergarteners who received all required vaccines has increased.2 However, the rate of medical exemptions has also increased from 0.2% in 2015-2016 to 0.7% in 2017-2018.2,3 The language of SB277 allows physicians to grant medical exemptions for reasons other than an established contraindication. The largest increases in medical exemptions occurred in regions that previously had high levels of personal-belief exemptions, suggesting that parents may be seeking medical exemptions to replace previous personal-belief exemptions.3
The Vaccine Adverse Event Reporting System (VAERS) is a national passive program for monitoring adverse events (AEs) following immunization and is co-managed by the Centers for Disease Control and Prevention (CDC) and U.S. Food and Drug Administration.4 VAERS primarily functions as an early warning system to detect signals and generate hypotheses about potential AEs following introduction of new vaccines and changes in existing vaccine recommendations. As a passive surveillance system, VAERS has several limitations, including underreporting, variability in report quality and completeness, the inability to determine causality, and lack of an appropriate denominator and, consequently, inability to measure statistical significance.4 VAERS accepts reports from any source—medical professionals, manufacturers, and the public—without and, as a result, is directly influenced by the perceptions of those reporters. Our objective was to examine trends in VAERS reporting from California associated with implementation of SB277.
Materials and Methods
VAERS reports may be submitted by healthcare providers, vaccinees or parents, vaccine manufacturers, and others.4 The report includes vaccinee and reporter information, vaccine administration information, and a description of the symptoms and outcome of the AE that are coded using the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms (PTs).5
The study population included children (<18 years of age at time of report) living in California, identified by vaccinee zip code. We restricted our study to only reports received from June 1, 2011 through July 31, 2018, using data as of December 31, 2018. For analysis, we subdivided into three periods based on when SB277 was announced and later went into effect: pre-SB277 (June 1, 2011 through February 18, 2015), inter-period (February 19, 2015 through June 30, 2016), and post-SB277 (July 1, 2016 through July 31, 2018). Reports were also grouped by school year, defined as June 1 to May 31 of the following year.
We analyzed reports by study period, describing vaccinee characteristics, reporter type, and interval from immunization date to report submission date (reporting time). We performed spatial analysis utilizing geographic information system (GIS) (R, Version 3.3.2), mapping pre- and post-mandate reports by county. In addition, we reviewed the top 25 MedDRA PTs for each study period stratified by reporter type and time from immunization to report submission date (≤6 months, >6 months). One report may contain more than one PT. VAERS reports are classified as “serious” based on Code of Federal Regulations Title 21 Section 600.80 if any of the following are reported: hospitalization, prolongation of hospitalization, life-threatening illness, permanent disability, or death.6 Recovery, a subjective variable, was also evaluated at the time of report.
We ran a second search with the same indices for the state of Texas. This state was chosen as a reference because it has a comparable population size but allows personal belief exemptions.
Results
We identified 6,703 VAERS reports (Table 1) from California for children <18 years of age, received June 1, 2011 through July 31, 2018. Of these, 3,652 (54%) were received pre-SB277, 1,402 (21%) during the inter-period, and 1,649 (25%) post-SB277. VAERS received the most reports during the 2015-2016 school year (n=1,096), followed by 2013-2014 (n=1,038), and 2011-2012 (n=1,033) (Table 2). Although the greatest proportion of reports during this study was from providers (54.35%), the proportion of parent reports began to increase in 2014-2015, peaking in 2016-2017 at 26.33%. Of note, 57 children had multiple reports of separate AEs following immunization.
Table 1.
Characteristics of California reports to Vaccine Adverse Event Reporting System for children <18 years, 2011-2018
| Pre-SB277 (2011-2015) |
Inter-period (2015-2016) |
Post-SB277 (2016-2018) |
Total | |
|---|---|---|---|---|
| No. (%) | No. (%) | No. (%) | No. (%) | |
| Sex | ||||
| Female | 1721 (47.12) | 541 (38.59) | 777 (47.12) | 3039 (45.34) |
| Male | 1723 (47.18) | 611 (43.58) | 834 (50.58) | 3168 (47.26) |
| Unknown | 208 (5.70) | 250 (17.83) | 38 (2.30) | 496 (7.40) |
| Age Group, years | ||||
| 4-6 | 685 (18.76) | 268 (19.12) | 356 (21.59) | 1309 (19.53) |
| 12-13 | 346 (9.47) | 126 (8.99) | 151 (9.16) | 623 (9.29) |
| Not Mandatorya | 2621 (71.77) | 1008 (71.90) | 1142 (69.25) | 4771 (71.18) |
| Reporter | ||||
| Parent/Patient | 494 (13.53) | 267 (19.04) | 373 (22.62) | 1134 (16.92) |
| Provider | 2096 (57.39) | 561 (40.01) | 986 (59.79) | 3643 (54.35) |
| Manufacturer | 428 (11.72) | 355 (25.32) | 108 (6.55) | 891 (13.29) |
| Other | 634 (17.36) | 219 (15.62) | 182 (11.04) | 1035 (15.44) |
| Outcome Statusb | ||||
| Non-serious | 3386 (92.72) | 1302 (92.87) | 1505 (91.27) | 6193 (92.39) |
| Emergency Room/Doctor Visit | 1104 (30.23) | 380 (27.10) | 698 (42.33) | 2182 (32.55) |
| Serious | 266 (7.28) | 102 (6.96) | 142 (8.95) | 510 (7.61) |
| Hospitalized | 211 (5.78) | 61 (4.35) | 86 (5.22) | 358 (5.34) |
| Prolonged Hospitalization | 19 (0.52) | 5 (0.36) | 2 (0.12) | 26 (0.39) |
| Permanent Disability | 33 (0.90) | 31 (2.21) | 40 (2.43) | 104 (1.55) |
| Life Threatening Illness | 67 (1.83) | 30 (2.14) | 37 (2.24) | 134 (2.00) |
| Death | 19 (0.52) | 6 (0.43) | 7 (0.42) | 32 (0.48) |
| Recovered | ||||
| Yes | 1873 (51.29) | 609 (43.44) | 748 (45.36) | 3230 (48.19) |
| No | 311 (8.52) | 149 (10.63) | 292 (17.71) | 752 (11.22) |
| Unknown | 1301 (35.62) | 578 (41.23) | 482 (29.23) | 2361 (35.22) |
| Missing | 167 (4.57) | 66 (4.71) | 127 (7.70) | 360 (5.37) |
| Total | 3652 | 1402 | 1649 | 6703 |
California Senate Bill 277 requires every child to be vaccinated or have a medical exemption on file prior to entering a new grade span (defined as birth to preschool, kindergarten to grade 6, and grades 7 to 12).
Reports may have more than one outcome.
Table 2.
Annual Vaccine Adverse Event Reporting System reports in California, by reporter type and school year, 2011-2018
| School Year | Parent/Patient No. (%) |
Provider No. (%) |
Manufacturer No. (%) |
Other No. (%) |
Total |
|---|---|---|---|---|---|
| 2011-2012 | 138 (13.36) | 576 (55.76) | 88 (8.52) | 231 (22.36) | 1033 |
| 2012-2013 | 117 (14.74) | 488 (61.46) | 60 (7.56) | 129 (16.25) | 794 |
| 2013-2014 | 119 (11.46) | 706 (68.02) | 62 (5.97) | 151 (14.55) | 1038 |
| 2014-2015 | 170 (16.77) | 442 (43.59) | 232 (22.88) | 170 (16.77) | 1014 |
| 2015-2016 | 196 (17.88) | 405 (36.95) | 337 (30.75) | 158 (14.42) | 1096 |
| 2016-2017 | 213 (26.33) | 419 (51.79) | 45 (5.56) | 132 (16.32) | 809 |
| 2017-2018 | 181 (19.70) | 607 (66.05) | 67 (7.29) | 64 (6.96) | 919 |
| All | 1134 (16.92) | 3643 (54.35) | 891 (13.29) | 1035 (15.44) | 6703 |
The distribution of sex and age was comparable for each time period, although the proportion of reports missing sex was approximately three times greater during the inter-period compared to pre-SB277. The proportion of reports reporting permanent disability doubled after the introduction of SB277 (from 0.90% to 2.21%); however, overall serious reports were reported with relative consistency throughout (7-9%). During the study period, we observed an increase in reports that stated the vaccinee had not recovered at the time of follow-up, from 9% pre-SB277 to 18% post-SB277.
Using GIS software, we mapped the vaccinee zip code for 6,547 reports (98%). Most counties did not have a significant change in reporting following the introduction of SB277 (Figure 1). The greatest increase in the average number of reports per year was in Contra Costa County, a county adjacent to San Francisco. San Diego County saw the greatest decrease in VAERS reporting.
Figure 1.
Change in Vaccine Averse Event Reporting System (VAERS) reporting after introduction of SB277, by county in California 2011-2018. VAERS reports were mapped by vaccinee zip code. Average annual reports were evaluated before and after the introduction of Senate Bill 277 (February 19, 2015).
The proportion of reports received from parents increased over time: 14% pre-SB277, 19% inter-period, and 23% post-SB277. After the introduction of SB277 (pre-SB277 to inter-period), the proportion of reports received from manufacturers increased from 12% to 25%, while reports from providers decreased from 57% to 40%. Due to the trends we observed for reporter type, our remaining analysis focused on parent reports. The median reporting time of a parent report began to increase with the 2014-2015 school year and peaked in 2016-2017. In contrast, in Texas no increase in reporting time was evident until 2016-2017 and even so, the change was moderate (Figure 2).
Figure 2.
Time from immunization to submission of Vaccine Averse Event Reporting System report by parents, California and Texas, 2011-218. The median interval from immunization date to report submission date (reporting time) for Vaccine Averse Event Reporting System (VAERS) reports submitted by parents living in California and Texas by school year.
Among VAERS reports submitted by parents, we examined the top 25 PTs by study period and time to report (Table 3). After the introduction of SB277, we observed an increase in behavioral and developmental PTs (abnormal behavior, anxiety, autism, developmental delay, autism spectrum disorder, speech developmental disorder, aggression, and aphasia). However, this trend was only observed for reports submitted >6 months after immunization.
Table 3.
Top 25 preferred terms (PTs) in California parental VAERS reports by time to report, 2011-2018
| 2011-2015 (pre-SB277) ≤6 months (N=419) |
2015-2016 (inter-period) ≤6 months (N=179) |
2016-2018 (post-SB277) ≤6 months (N=265) |
|||
|---|---|---|---|---|---|
| PT | No. (%) | PT | No. (%) | PT | No. (%) |
| Pyrexia | 168 (40.09) | Pyrexia | 77 (43.01) | Pyrexia | 99 (37.36) |
| Vomiting | 62 (14.80) | Vomiting | 28 (15.64) | Vomiting | 42 (15.85) |
| Injection site erythema | 53 (12.65) | Rash | 22 (12.29) | Injection site erythema | 39 (14.72) |
| Injection site swelling | 51 (12.17) | Crying | 20 (11.17) | Crying | 37 (13.96) |
| Irritability | 49 (11.69) | Irritability | 17 (9.50) | Irritability | 37 (13.96) |
| Rash | 45 (10.74) | Pain | 17 (9.50) | Fatigue | 33 (12.45) |
| Crying | 43 (10.26) | Decreased appetite | 16 (8.94) | Rash | 32 (12.08) |
| Headache | 41 (9.79) | Fatigue | 16 (8.94) | Decreased appetite | 30 (11.32) |
| Pain | 40 (9.55) | Headache | 15 (8.38) | Injection site swelling | 30 (11.32) |
| Urticaria | 38 (9.07) | Urticaria | 14 (7.82) | Headache | 28 (10.57) |
| Fatigue | 36 (8.59) | Injection site erythema | 13 (7.26) | Pain | 26 (9.81) |
| Decreased appetite | 32 (7.64) | Injection site pain | 13 (7.26) | Urticaria | 26 (9.81) |
| Lethargy | 30 (7.16) | Rash erythematous | 13 (7.26) | Dizziness | 25 (9.43) |
| Diarrhoea | 29 (6.92) | Erythema | 12 (6.70) | Injection site pain | 23 (8.68) |
| Dizziness | 29 (6.92) | Injection site swelling | 12 (6.70) | Injection site warmth | 23 (8.68) |
| Rash generalised | 29 (6.92) | Pruritus | 11 (6.15) | Lethargy | 20 (7.55) |
| Convulsion | 27 (6.44) | Dizziness | 10 (5.59) | Diarrhoea | 19 (7.17) |
| Injection site pain | 27 (6.44) | Lethargy | 10 (5.59) | Dyspnoea | 19 (7.17) |
| Nausea | 27 (6.44) | Cough | 9 (5.03) | Erythema | 18 (6.79) |
| Injection site warmth | 26 (6.21) | Diarrhoea | 9 (5.03) | Nausea | 18 (6.79) |
| Asthenia | 24 (5.73) | Insomnia | 9 (5.03) | Pain in extremity | 16 (6.04) |
| Erythema | 24 (5.73) | Nausea | 9 (5.03) | Rash generalised | 16 (6.04) |
| Cough | 23 (5.49) | Screaming | 9 (5.03) | Seizure | 16 (6.04) |
| Pruritus | 23 (5.49) | Seizure | 9 (5.03) | Abdominal pain upper | 15 (5.66) |
| Pain in extremity | 22 (5.25) | Pain in extremity | 8 (4.47) | Unresponsive to stimuli | 15 (5.66) |
|
2011-2015 (pre-SB277) >6 months (N=75) |
2015-2016 (inter-period) >6 months (N=88) |
2016-2018 (post-SB277) >6 months (N=108) |
|||
| Pyrexia | 27 (36.00) | Pyrexia | 40 (45.45) | Pyrexia | 44 (40.74) |
| Vomiting | 15 (20.00) | Crying | 22 (25.00) | Crying | 17 (15.74) |
| Lethargy | 13 (17.33) | Irritability | 15 (17.05) | Rash | 15 (13.89) |
| Rash | 10 (13.33) | Abnormal behaviour | 14 (15.91) | Diarrhoea | 14 (12.96) |
| Cough | 9 (12.00) | Seizure | 13 (14.77) | Vomiting | 14 (12.96) |
| Fatigue | 9 (12.00) | Tremor | 13 (14.77) | Cough | 13 (12.04) |
| Urticaria | 9 (12.00) | Screaming | 12 (13.64) | Abnormal behaviour | 12 (11.11) |
| Crying | 8 (10.66) | Vomiting | 12 (13.64) | Urticaria | 12 (11.11) |
| Decreased appetite | 8 (10.66) | Fatigue | 10 (11.36) | Irritability | 11 (10.19) |
| Diet refusal | 8 (10.66) | Anxiety | 9 (10.23) | Lethargy | 11 (10.19) |
| Screaming | 8 (10.66) | Autism | 9 (10.23) | Developmental delay | 10 (9.26) |
| White blood cell count increased | 8 (10.66) | Cough | 9 (10.23) | Autism spectrum disorder | 9 (8.33) |
| Asthenia | 7 (9.33) | Developmental delay | 9 (10.23) | Decreased appetite | 9 (8.33) |
| Convulsion | 7 (9.33) | Rash | 9 (10.23) | Eczema | 9 (8.33) |
| Lymphocyte percentage increased | 7 (9.33) | Staring | 9 (10.23) | Headache | 9 (8.33) |
| Neutrophil percentage decreased | 7 (9.33) | Decreased appetite | 8 (9.09) | Screaming | 9 (8.33) |
| Diarrhoea | 6 (8.00) | Diarrhoea | 8 (9.09) | Speech disorder developmental | 9 (8.33) |
| Dyskinesia | 6 (8.00) | Fall | 8 (9.09) | Aggression | 8 (7.41) |
| Headache | 6 (8.00) | Hypotonia | 8 (9.09) | Aphasia | 8 (7.41) |
| Injection site erythema | 6 (8.00) | Headache | 7 (7.95) | Fatigue | 8 (7.41) |
| Injection site swelling | 6 (8.00) | Malaise | 7 (7.95) | Pain | 8 (7.41) |
| Muscular weakness | 6 (8.00) | Nasopharyngitis | 7 (7.95) | Seizure | 8 (7.41) |
| Pain | 6 (8.00) | Pain | 7 (7.95) | Constipation | 7 (6.48) |
| Pain in extremity | 6 (8.00) | Sensory disturbance | 7 (7.95) | Decreased eye contact | 7 (6.48) |
| Blood test | 5 (6.67) | Eczema | 7 (7.95) | Erythema | 7 (6.48) |
Discussion
We observed several changes in reporting trends to VAERS following routine childhood vaccines after the introduction of SB277 in California. These included more reports of permanent disability, a greater proportion of parent reports, and an alteration in the type of reports submitted by parents. The increased proportion of parent reports following the introduction of SB277 along with the increased reporting time suggests that parents are more often reporting perceived AEs from the past. A number of PTs reported by parents are not known to be causally associated with any vaccine.7 Interestingly, the proportion of reports by manufacturers also increased after the introduction of SB277. There are a number of possibilities for this change, one being that manufacturers also accept reports from any source and have experienced a similar change in reporting trends.
VAERS reports do not collect information that indicate the reporter’s intent for submission. However, there are websites targeted to vaccine-hesitant parents that include VAERS reports among sources of documentation for medical exemption.8 A VAERS report alone may not provide sufficient information to support a medical exemption. This highlights the importance of follow-up by physicians, local and county public health authorities, and school district administrative personnel, to ensure that children have a valid reason for a medical exemption.
Among its limitations, VAERS accepts all reports regardless of perceived clinical importance. MedDRA coders then categorize a report as serious if any of the following are reported: hospitalization, prolongation of hospitalization, life-threatening illness, permanent disability, or death. Although associated medical records are requested for those reports considered serious, they are not required for confirmation. As an example, a report submitted by a parent that cites permanent disability, whether perceived or diagnosed, would be considered serious.
Our analysis demonstrates that VAERS reporting can be impacted by vaccine policy change. Importantly, for our analysis we also could not determine the intent behind filing an individual VAERS report. Although the primary function of VAERS is to serve as a system to detect signals of potential AEs, in the face of changing vaccine policy it is important to consider that a signal can be influenced by reporters themselves.
Conclusions
Changes in reporting patterns coincident with the passage of SB277 may indicate that some parents are using VAERS to assist in applying for a medical exemption.
Acknowledgments
Funding sources
Dr. Hause was supported by Award Number T32AI074492 from the National Institute of Allergy and Infectious Diseases. Dr. Omer’s effort on this study was supported by grant R01AI125405 from the National Institutes of Health. CDC participation was supported solely by the CDC and no external funding was secured.
Conflicts of Interest and Source of Funding: The authors have indicated they have no potential conflicts of interest to disclose. Dr. Hause was supported by the National Institute of Allergy and Infectious Diseases, award number T32AI074492. Dr. Omer was supported by that National Institutes of Health, grant number R01AI125405. CDC participation was supported solely by the CDC and no external funding was secured.
Footnotes
Conflicts of interest
No potential conflicts of interest were reported by the authors
Publisher's Disclaimer: Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, or the Centers for Disease Control and Prevention (CDC). Use of trade names and commercial sources is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention, or the U.S. Department of Health and Human Services.
References
- 1.Educational and Child Care Facility Immunization Requirements. California State Congress; 2015:120325–120380. [Google Scholar]
- 2.Mohanty S, Buttenheim AM, Joyce CM, Howa AC, Salmon D, Omer SB. Experiences With Medical Exemptions After a Change in Vaccine Exemption Policy in California. Pediatrics. 2018;142(5):e20181051. doi: 10.1542/peds.2018-1051 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Delamater PL, Leslie TF, Yang YT. Change in Medical Exemptions From Immunization in California After Elimination of Personal Belief Exemptions. JAMA. 2017;318(9):863–864. doi: 10.1001/jama.2017.9242 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Shimabukuro TT, Nguyen M, Martin D, DeStefano F. Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS). Vaccine. 2015;33(36):4398–4405. doi: 10.1016/j.vaccine.2015.07.035 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Medical Dictionary for Regulatory Activities. https://www.meddra.org/how-to-use/support-documentation. Published 2019. Accessed May 7, 2019.
- 6.Postmarketing Reporting of Adverse Experiences. Food and Drug Administration; 2018. [Google Scholar]
- 7.Adverse Effects of Vaccines. Washington, D.C: National Academies Press; 2012. doi: 10.17226/13164 [DOI] [PubMed] [Google Scholar]
- 8.South Park Doctor. Avilable at: http://www.southparkdoctor.com. Accessed June 6, 2019.