Vaccine preparation time, errors, satisfaction, and preference of prefilled syringes versus RSV vaccines requiring reconstitution: randomized, time and motion study

Figures & data

Figure 1. Study design.

Abbreviations: HCPs, healthcare providers; PFS, prefilled syringe; Vaccine A, ready-to-use PFS; Vaccine B, VRR1 (vial with a lyophilized vaccine and vial with an adjuvant suspension); Vaccine C, VRR2 (vial with lyophilized vaccine and a prefilled syringe with sterile water diluent); VRR, vaccine requiring reconstitution; VRR1, VRR with vial with a lyophilized vaccine and vial with an adjuvant suspension; VRR2, VRR with vial with lyophilized vaccine and a prefilled syringe with sterile water diluent.

Figure 2. STROBE flow chart.

Table 1. Participant demographics, overall and by randomization sequence.

	Overall, N = 63	Sequence ABC, N = 21	Sequence BCA, N = 21	Sequence CAB, N = 21
Age (years), mean (SD)	41.9 (10.7)	41.5 (11.0)	44.2 (10.8)	39.9 (10.5)
Male, n (%)	20 (31.7)	7 (33.3)	6 (28.6)	7 (33.3)
Occupation, n (%)
Pharmacist	38 (60.3)	14 (66.7)	13 (61.9)	11 (52.4)
Nurse	22 (34.9)	6 (28.6)	8 (38.1)	8 (38.1)
Pharmacy technician	3 (4.8)	1 (4.8)	0 (0.0)	2 (9.5)
Practice, n (%)^a
Urban	47 (74.6)	14 (66.7)	16 (76.2)	17 (81.0)
Suburban	21 (33.3)	6 (28.6)	8 (38.1)	7 (33.3)
Rural	5 (7.9)	2 (9.5)	0 (0.0)	3 (14.3)
Practice setting, n (%)^a
Retail pharmacy	36 (57.1)	14 (66.7)	12 (57.1)	10 (47.6)
Hospital	27 (42.9)	4 (19.0)	12 (57.1)	11 (52.4)
Academic institution	8 (12.7)	3 (14.3)	2 (9.5)	3 (14.3)
Clinical pharmacy	5 (7.9)	0 (0.0)	2 (9.5)	3 (14.3)
Other	11 (17.5)	4 (19.0)	1 (4.8)	6 (28.6)
Years experience, n (%)
1–10 years	25 (39.7)	9 (42.9)	6 (28.6)	10 (47.6)
11–20 years	21 (33.3)	7 (33.3)	8 (38.1)	6 (28.6)
21–30 years	9 (14.3)	2 (9.5)	4 (19.0)	3 (14.3)
31–40 years	4 (6.3)	1 (4.8)	2 (9.5)	1 (4.8)
>40 years	4 (6.3)	2 (9.5)	1 (4.8)	1 (4.8)
Average number of vaccines administered in a typical month, n (%)
1–10 vaccines	25 (39.7)	7 (33.3)	11 (52.4)	7 (33.3)
11–20 vaccines	8 (12.7)	4 (19.0)	0 (0.0)	4 (19.0)
21–30 vaccines	13 (20.6)	4 (19.0)	4 (19.0)	5 (23.8)
31–40 vaccines	5 (7.9)	0 (0.0)	2 (9.5)	3 (14.3)
>40 vaccines	12 (19.0)	6 (28.6)	4 (19.0)	2 (9.5)
Years administering vaccines, n (%)
1.5–3 years	8 (12.7)	2 (9.5)	2 (9.5)	4 (19.0)
>3–5 years	10 (15.9)	4 (19.0)	2 (9.5)	4 (19.0)
>5–10 years	13 (20.6)	4 (19.0)	4 (19.0)	5 (23.8)
>10 years	32 (50.8)	11 (52.4)	13 (61.9)	8 (38.1)
Training, n (%)^a
Vaccine preparation	61 (96.8)	19 (90.5)	21 (100.0)	21 (100.0)
VRR preparation	60 (95.2)	18 (85.7)	21 (100.0)	21 (100.0)
PFS preparation	53 (84.1)	16 (76.2)	17 (81.0)	20 (95.2)
Experience, n (%)^a
Administering VRR	60 (95.2)	19 (90.5)	20 (95.2)	21 (100.0)
Administering PFS	58 (92.1)	19 (90.5)	18 (85.7)	21 (100.0)

Abbreviations: A, ready-to-use PFS; B, VRR1 (vial with a lyophilized vaccine and vial with an adjuvant suspension); C, VRR2 (vial with lyophilized vaccine and a prefilled syringe with sterile water diluent); PFS, prefilled syringe; SD, standard deviation; VRR, vaccine requiring reconstitution.

^aThe sum of the percentages of individual categories may exceed 100% because multiple selection was allowed for this question.

Table 2. Vaccine preparation time, by vaccine and for pooled VRRs, with comparison.

	PFS	VRR1	PFS vs. VRR1^a^,^b	VRR2^c	PFS vs. VRR2^a^,^b	pVRRs^c	PFS vs. pVRR^a
Time for vaccine preparation (seconds)
N	63	63	–	62	–	125	–
Observed mean (SD)	43.5 (23.8)	185.3 (57.1)	–	147.2 (56.9)	–	166.4 (59.9)	–
Median (Q1, Q3)	38 (29, 53)	177 (155, 210)	–	137 (114, 160)	–	157 (128, 197)	–
Min, Max	15, 132	93, 405	–	64, 343	–	64, 405	–
Missing	0	0	–	1	–	1	–
Comparison of vaccine preparation time^d
N	63	63	–	62	–	125	–
LS Mean (95% CI)	43.5 (31.3–55.7)	185.3 (173.1–197.5)	–	147.1 (134.9–159.4)	–	166.2 (155.9–176.5)	–
LS Mean Difference (95% CI)	–	–	−141.8 (−156.8–−126.7)	–	−103.6 (−118.7– −88.5)	–	−122.7 (−134.2–−111.2)
p-value	–	–	<.0001	–	<.0001	–	<.0001

Abbreviations: CI, confidence interval; LS, least squares; PFS, ready-to-use prefilled syringe; pVRRs, pooled VRRs; Q1, first quartile; Q3, third quartile; SD, standard deviation; VRR, vaccine requiring reconstitution; VRR1, VRR with vial with a lyophilized vaccine and vial with an adjuvant suspension; VRR2, VRR with vial with lyophilized vaccine and a prefilled syringe with sterile water diluent; vs, versus.

^a Reference.

^b p-value and confidence intervals based on Dunnett multiple comparison adjustment.

^c One participant was unable to participate due to the malfunctioning of a vaccine kit vial adapter.

^d Estimates and p-values are derived from the LMM, with sequence and vaccine type as fixed effects, and site and subject as random effects.

Table 3. Vaccine preparation errors, by vaccine and for pooled VRRs.

Errors	PFS, N = 63	VRR1, N = 63	VRR2, N = 63	pVRR, N = 126
Total errors, mean (SD)	3.5 (1.1)	4.0 (1.5)	3.8 (1.5)	3.9 (1.5)
Total quality control errors, mean (SD)	1.6 (0.9)	2.3 (0.7)	1.8 (0.6)	2.0 (0.5)
Missed checking expiration date of vaccine kit/vials	29 (46.0)	26 (41.3)	51 (81.0)	77 (61.1)
Missed checking expiration date of syringe	–	59 (93.7)	–	59 (46.8)
Missed checking expiration date of needle	57 (90.5)	59 (93.7)	60 (95.2)	119 (94.4)
Missed visual inspection	15 (23.8)	0 (0)	2 (3.2)	2 (1.6)
Total handling errors, mean (SD)	0.9 (0.7)	1.1 (0.9)	1.0 (0.8)	1.0 (0.7)
Drop any part of vaccine	31 (49.2)	26 (41.3)	30 (47.6)	56 (44.4)
Lack of gloves	–	10 (15.9)	–	10 (7.9)
Selected needle of inappropriate size for intramuscular injection	0 (0)	13 (20.6)	11 (17.5)	24 (19.0)
Selected syringe of inappropriate size for aspiring vial contents	23 (36.5)	20 (31.7)	19 (30.2)	39 (31.0)
Total asepsis fault, mean (SD)	0.0 (0.0)	0.0 (0.1)	0.0 (0.0)	0.0 (0.1)
Finger(s) touched vial rubber cap after removal of protective plastic cap	0 (0)	0 (0)	0 (0)	0 (0)
Finger(s) touched top of syringe after removal of protective plastic cap	0 (0)	0 (0)	0 (0)	0 (0.0)
Finger(s) touched sterile part of needle	0 (0)	1 (1.6)	0 (0)	1 (0.8)
Needle stick	0 (0)	0 (0)	0 (0)	0 (0.0)
Total user technique errors, mean (SD)	1.0 (0.4)	0.6 (0.7)	1.0 (1.1)	0.8 (0.8)
Mixing error (vigorous shaking, not swirling, shaking PFS)	1 (1.6)	12 (19.0)	9 (14.3)	21 (16.7)
Dilution occurred	1 (1.6)	–	–	–
Tip cap removal when PFS not upright/removed abruptly/pulled while twisting	59 (93.7)	–	–	–
Purge of syringe at any stage	0 (0)	–	0 (0)	0 (0.0)
Lack of cleansing of vial rubber stopper	–	1 (1.6)	1 (1.6)	2 (1.6)
Vial content (adjuvant/reconstituted vaccine) not fully aspired into syringe	–	1 (1.6)	–	1 (0.8)
Missed reconstitution of vaccine	–	0 (0)	1 (1.6)	1 (0.8)
Reconstitution of vaccine using more than one needle (unless damaged/contaminated)	–	14 (22.2)	5 (7.9)	19 (15.1)
Spillage or leakage at any stage	1 (1.6)	7 (11.1)	2 (3.2)	9 (7.1)
Attachment of vial adapter at wrong angle	–	–	20 (31.7)	20 (15.9)
Syringe held at any part but the Luer lock adapter at any stage	–	–	17 (27.0)	17 (13.5)
Removal of syringe from vial before complete withdrawal after reconstitution	–	–	4 (6.3)	4 (3.2)
Vial not completely inverted during withdrawal	–	–	3 (4.8)	3 (2.4)
Plunger rod pulled out of syringe during withdrawal	–	–	0 (0)	0 (0.0)
Other	1 (1.6)	3 (4.8)	4 (6.3)	7 (5.6)
Missing	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)

Abbreviations: PFS, ready-to-use prefilled syringe; SD, standard deviation; pVRR, polled VRRs; VRR, vaccine requiring reconstitution; VRR1, VRR with vial with a lyophilized vaccine and vial with an adjuvant suspension; VRR2, VRR with vial with lyophilized vaccine and a prefilled syringe with sterile water diluent.

Note: Based on Poisson Generalized Linear Mixed Models comparing preparation errors, with sequence and vaccine type as fixed effects, and site and subject as random effects, incidence rate ratio (95% CI; p-value): PFS vs VRR1 [0.87 (0.72–1.04; p = .1197)]; PFS vs VRR2 [0.92 (0.76–1.10; p = .3559)]; PFS vs pVRR [0.89 (0.76–1.05; p = .1571)].

Figure 3. Participant satisfaction ratings for (a) ease of preparation, (b) time of preparation, and (c) overall satisfaction with vaccine preparation.

Abbreviations: PFS, ready-to-use prefilled syringe; VRR, vaccine requiring reconstitution; VRR1, VRR with vial with a lyophilized vaccine and vial with an adjuvant suspension; VRR2, VRR with vial with lyophilized vaccine and a prefilled syringe with sterile water diluent.

Table 4. Comparison of participant satisfaction with vaccine preparation procedures.

	Odds Ratios (95% CI)^a	p-value^a
Satisfaction with Ease of Use
PFS vs. VRR1	18.41 (7.70–43.99)	<.0001
PFS vs. VRR2	10.61 (4.61–24.37)	<.0001
PFS vs. pVRR	13.97 (6.37–30.66)	<.0001
Satisfaction with Preparation Time
PFS vs. VRR1	34.60 (12.85–93.16)	<.0001
PFS vs. VRR2	20.16 (7.78–52.20)	<.0001
PFS vs. pVRR	26.41 (10.60–65.82)	<.0001
Overall Satisfaction
PFS vs. VRR1	19.93 (8.32–47.72)	<.0001
PFS vs. VRR2	10.87 (4.72–25.06)	<.0001
PFS vs. pVRR	14.72 (6.68–32.41)	<.0001

Abbreviations: CI, confidence interval; PFS, ready-to-use prefilled syringe; pVRR, pooled VRRs; VRR, vaccine requiring reconstitution; VRR1, VRR with vial with a lyophilized vaccine and vial with an adjuvant suspension; VRR2, VRR with vial with lyophilized vaccine and a prefilled syringe with sterile water diluent; vs, versus.

^a Derived from a mixed-effects ordered logit regression model, with sequence and vaccine type as fixed effects, and site and subject as random effects.

Figure 4. Participant preference for vaccine preparations.

Abbreviations: PFS, ready-to-use prefilled syringe; VRR, vaccine requiring reconstitution; VRR1, VRR with vial with a lyophilized vaccine and vial with an adjuvant suspension; VRR2, VRR with vial with lyophilized vaccine and a prefilled syringe with sterile water diluent.

Data availability statement

All data generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.