4. Dropouts.
| Dropouts (all included studies) |
LZV versus placebo The pooled data from the studies that compared zoster vaccine and placebo showed no differences in reasons for dropout (Analysis 1.5): for any reason (RR 0.99, 95% CI 0.91 to 1.08) (Analysis 1.5.1) (Mills 2010; Oxman 2005; Vermeulen 2012); discontinued due to vaccine‐related adverse events (RR 5.05, 95% CI 0.25 to 103.88) (Analysis 1.5.2) (Mills 2010; Vermeulen 2012); for clinical AE (RR 1.34, 95% CI 0.72 to 2.52) (Analysis 1.5.3) (Murray 2011; Vermeulen 2012); for physician decision (RR 0.20, 95% CI 0.01 to 4.17) (Analysis 1.5.4) (Murray 2011); for withdrawal of consent (RR 0.95, 95% CI 0.54 to 1.68) (Analysis 1.5.5) (Murray 2011; NCT00886613; Oxman 2005; Vermeulen 2012); for loss to follow‐up (RR 1.27, 95% CI 0.96 to 1.69) (Analysis 1.5.6) (Hata 2016; Murray 2011; NCT00886613; Oxman 2005; Vermeulen 2012); and for protocol deviation (RR 1.49, 95% CI 0.27 to 8.37) (Analysis 1.5.7) (Murray 2011; Vermeulen 2012). In Mills 2010, Oxman 2005, and Vermeulen 2012, consent was withdrawn after the intervention. In Murray 2011, some participants apparently withdrew consent after randomisation, but the exact number that withdrew consent after the intervention is not stated. The pooled data from the studies that compared zoster vaccine versus placebo showed no differences in reasons for participants with no follow‐up (RR 1.05, 95% CI 0.74 to 1.48) (Analysis 1.6) (Mills 2010; Murray 2011; Oxman 2005). High‐potency versus low‐potency zoster vaccine: there were no differences between groups (Tyring 2007). Refrigerated versus frozen zoster vaccine: there were no differences between groups (Gilderman 2008). LZV IM route versus LZV SC route: there were no withdrawals due to adverse events in either group (Diez‐Domingo 2015). LZV intradermal route versus LZV SC route: there were no significant differences between full‐dose intradermal versus full‐dose SC; 1/3 dose intradermal versus full‐dose SC; 1/10 dose intradermal versus full‐dose SC; 1/27 dose intradermal versus full‐dose SC; 1/3 dose intradermal versus 1/3 dose SC. There were no dropouts for full‐dose intradermal versus 1/3 dose SC; 1/10 dose intradermal versus 1/3 dose SC; and 1/27 dose intradermal versus 1/3 dose SC (Beals 2016). 2 doses of a zoster vaccine versus a single dose and 2 doses given at different intervals: there were no differences between groups for participant withdrawals due to adverse events (Vesikari 2013). LZV AMP versus LZV: there were no differences between groups (NCT01505647). LZV + IIV4 concomitant administration versus LZV + IIV4 sequential administration: for this comparison there were no significant differences for dropouts between groups (Levin 2018) In all the comparisons of Chlibek 2013, there were no differences in dropouts between the groups. Similarly, in all the comparisons of Chlibek 2014, there were no differences in dropouts between the groups.. RZV versus placebo:Cunningham 2016 and Lal 2015 described 4 reasons for dropout: did not receive vaccine according to protocol (Analysis 2.4.1); received wrong vaccine (Analysis 2.4.2); had diagnosis of HZ less than 30 days after dose 2 (Analysis 2.4.3); and did not receive second dose (Analysis 2.4.4). There were no differences between groups for the first 2 outcomes. The third outcome had an RR of 0.32 (95% CI 0.14 to 0.71) but no RD. For the fourth outcome, the vaccine group had a higher dropout rate than the placebo group: RR 1.25, 95% CI 1.13 to 1.39; RD 0.01, 95% CI 0.01 to 0.01; NNTH 100, 95% 100.0 to 100.0. RZV IM route versus RZV SC route: there was no difference in participant withdrawal between groups (Vink 2017). RZV + TDaPV co‐administration group versus RZV + TDaPV not co‐administration group: there was no difference in dropouts between groups (NCT02052596). Co‐administration RZV + IIV4 versus not co‐administration group RZV + IIV4: there was no difference between groups for dropouts (Schwarz 2017). |
AE: adverse event or adverse experiences AMP: Alternative Manufacturing Process AS01: liposome‐based adjuvant system containing the immunoenhancers 3‐O‐desacyl‐4′‐monophosphoryl lipid A (MPL) and the saponin QS‐21 (Quillaja saponaria Molina, fraction 21) Adjuvanted gE/AS01B: 50 μg purified gE with adjuvant B (1 mg dioleoyl phosphatidylcholine, 250 μg cholesterol, 50 μg MPL, and 50 μg QS‐21) Adjuvanted gE/AS01E: 50 μg purified gE with adjuvant E (500 μg dioleoyl phosphatidylcholine, 125 μg cholesterol, 25 μg MPL, and 25 μg QS‐21) AS01B: adjuvant B composed of 1 mg dioleoyl phosphatidylcholine, 250 μg cholesterol, 50 μg MPL, and 50 μg QS‐21 AS01E: adjuvant E composed of 500 μg dioleoyl phosphatidylcholine, 125 μg cholesterol, 25 μg MPL, and 25 μg QS‐21 Elderly or older adults: aged ≥ 60 years old Frozen: ‐15 °C or colder gE: recombinant subunit VZV composed of glycoprotein E gE/saline: unadjuvanted gE HZ: herpes zoster ID: identification IIV4: inactivated quadrivalent influenza vaccines IM: intramuscular LZV or ZV: live zoster vaccine (live attenuated Oka varicella zoster virus vaccine) MPL: immunoenhancer 3‐O‐desacyl‐4′‐monophosphoryl lipid A NNTB: number needed to treat for an additional beneficial outcome NNTH: number needed to treat for an additional harmful outcome pneumo‐23 vaccine: 23–valent pneumococcal polysaccharide vaccine QS‐21: immunoenhancer saponin Quillaja saponaria Molina, fraction 21 Refrigerated: 2 °C to 8 °C RR: risk ratio RZV: adjuvanted recombinant zoster vaccine (contains 50 µg of recombinant VZV glycoprotein E, and the liposome‐based AS01B adjuvant system contains 50 µg of 3‐O‐desacyl‐4′‐monophosphoryl lipid A (MPL) and 50 µg of Quillaja saponaria Molina, fraction 21 (QS21)) SAEs: serious adverse events SC: subcutaneously or subcutaneous TDaPV: tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine VZV: varicella zoster virus