Article Figures & Data
Figures
- FIGURE 1
Histogram of weekly counts of 9vHPV vaccinations administered in the VSD population from the week starting on October 4, 2015, through the week starting on October 1, 2017, by age and sex.
- FIGURE 2
Distribution of days to onset of appendicitis in the 42-day risk window after administration of 9vHPV vaccine among boys 9 to 17 years old.
Tables
Medical Setting Postvaccination Risk Window, d First Episode in What Period? Primary Comparison Groupa Uncommon or rare adverse event Anaphylaxis ED, inpatient 0–2 First in 42 d Historic Appendicitis ED, inpatient 1–42 First in 42 d Historic Pancreatitis ED, inpatient 1–42 First ever Historic GBS Outpatient, ED, inpatient 1–42 First in 42 d Historic CIDP Outpatient, ED, inpatient 1–180 First ever Historic Seizure ED, inpatient 0–42 First in 42 d and first ever Concurrent Stroke ED, inpatient 0–42 First in 42 d Historic VTE Outpatient, ED, inpatient 1–42 First in 1 y Historic Common adverse event Allergic reactions Outpatient, ED, inpatient 0–2 for ED and inpatient,1–2 for outpatient First in 42 d Concurrent Injection site reactions Outpatient, ED, inpatient 1–6 First in 42 d Concurrent Nonspecific reactions Outpatient, ED, inpatient 0–6 First in 42 d Concurrent Syncope Outpatient, ED, inpatient Day 0 First in 2 d Concurrent ↵a Concurrent comparison group: visits during which comparator vaccines were administered, with analytic strata defined by age (in 1-y increments), site, sex, and week of the vaccination visit. Two historic comparison groups (2007–2014) were used: general VSD population and vaccinated VSD population, vaccinated with comparator vaccines.
- TABLE 2
Summary of Uncommon Adverse Events in Selected Subgroups Evaluated With Historical Comparison Groups Using MaxSPRT and CMaxSPRT
AE Type of SPRT Analysisa Subgroup, Sex, Age Group in y No. Observed Vaccinations No. Observed AE No. Comparator Vaccinations, Historical Period No. AEs in the Historical Period No. Expected AEs RR Test Statistic Critical Valueb Signal Anaphylaxis Maximized Male, 9–17 334 381 0 — — 0.9 0 0 2.7 No CMax Male, 9–17 334 381 0 1 053 642 2 — 0 0 2.6 No Appendicitis Maximized Male, 9–17 78 885 33 — — 25.6 1.3 0.97 3.5 No CMax Male, 9–17 78 885 33 1 053 642 312 — 1.4 1.6 3.8 No GBS Maximized Female, 18–26 128 645 0 — — 0.6 0 0 2.6 No CMax Female, 18–26 128 645 0 431 401 3 — 0 0 2.7 No Pancreatitis Maximized Male, 18–26 51 944 8 — — 2.6 3.1 3.7 2.9 Yes CMax Male, 18–26 51 944 8 349 966 29 — 1.9 1.1 3.4 No Seizures Maximized Female, 9–17 304 384 44 — — 115.2 0.4 0 3.8 No CMax Female, 9–17 304 384 44 698 263 105 — 1.0 0 3.7 No Stroke Maximized Female, 18–26 128 645 5 — — 4.9 1.0 0 2.9 No CMax Female, 18–26 128 645 5 431 401 11 — 1.5 0.3 2.9 No VTE Maximized Female, 18–26 128 645 8 — — 9.8 0.8 0 3.1 No CMax Female, 18–26 128 645 8 431 401 54 — 0.5 0 3.4 No Results were extracted from the final report (week starting October 1, 2017) for all events except for pancreatitis, which comes from the week when it first signaled (week 71). CIDP was not included because there were no events during the study period. AE, adverse event; CMax, conditional maximized; SPRT, sequential probability ratio test; —, not applicable.
↵a MaxSPRT: analyses were conducted in combination with the general VSD population historic comparison group (2007–2014). CMaxSPRT: analyses were conducted in combination with the historic VSD population vaccinated with comparator vaccines (2007–2014).
↵b Critical values are threshold values of the test statistic above, in which the null hypothesis would be rejected.
- TABLE 3
Summary of Common Adverse Events Using ESA in Subgroups Evaluated With the Concurrent Comparison Group
Adverse Event Subgroup, Sex, Age Group in y, 9vHPV Dose Week When First Signaled No. 9vHPV Vaccinations in Subgroup No. Total Casesa No. Exposed Casesa RR P Allergic reactionb Female, 9–17, ED or inpatient, any 82 242 726 33 26 2.7 .04 Female, 9–17, outpatient, any No signalc 242 726 86 60 0.8 .75 Female, 9–17, ED or inpatient, dose 1 94 109 896 26 17 2.8 .04 Female, 9–17, outpatient, dose 1 No signald 109 896 82 50 1.2 .28 Female, 18–26, outpatient, dose 2 86 33 118 38 15 1.9 .04 Female, 18–26, ED or inpatient, dose 2 No signale 33 118 8 1 0.4 .92 Appendicitisf Male, 9–17, dose 3 84 73 122 50 30 2.1 .03 Male, 9–17, any No signalg 271 679 103 81 1.5 .09 Male, 9–17, dose 1 No signalg 106 741 47 25 1.4 .23 Male, 9–17, dose 2 No signalg 91 156 47 26 1.5 .23 Injection site reaction Male, 9–17, dose 3 26 23 409 29 18 2.5 .03 Nonspecific reaction Male, 18–26, dose 3 25 4054 3 2 95.0 .04 Male, 18–26, dose 1 34 13 228 14 9 11.1 .04 Female, 18–26, dose 1 50 26 711 71 34 1.7 .03 Female, 18–26, any 105 128 806 215 126 1.3 .04 Syncope Female, 18–26, any 25 28 234 98 67 1.8 .007 Female, 18–26, dose 1 25 12 245 65 35 2.0 .004 Female, 18–26, dose 2 31 10 924 60 25 1.7 .04 Results were extracted from the report for the week when the adverse event first signaled. NS, no signal.
↵a Cases in a specific subgroup are only counted for analytic strata with ≥1 case (either exposed or not), ≥1 9vHPV vaccine, and ≥1 comparator vaccine, in which analytic strata are defined by age (in 1-y increments), site, sex, and week of the vaccination visit.
↵b Diagnoses were made in the ED or inpatient setting or in the outpatient setting.
↵c No signal was detected for this subgroup. Data were extracted from the report for the week when allergic reaction signaled for girls 9 to 17 y old with any dose in the ED or inpatient setting.
↵d No signal was detected for this subgroup. Data were extracted from the report for the week when allergic reaction signaled for girls 9 to 17 y old with dose 1 in the ED or inpatient setting.
↵e No signal was detected for this subgroup. Data were extracted from the report for the week when allergic reaction signaled for women 18 to 26 y old with dose 2 in the outpatient setting.
↵f Appendicitis was classified as an uncommon adverse event in this study, but a statistical signal was detected with ESA, and it is therefore included here.
↵g No signal was detected for this subgroup. Data were extracted from the report for the week when appendicitis signaled for boys 9 to 17 y old with dose 3.
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