Summary of findings for the main comparison. Comparison between needles with different lengths but with the same gauge.
| 25 G 25 mm needles compared with 25 G 16 mm needles for vaccination procedures | ||||||
|
Patient or population: infants aged approximately 2 to 6 months undergoing vaccination in the anterolateral thigh with a DTwP‐Hib vaccine Intervention: 25 G 25 mm needles; injection technique ‐ skin stretched flat between thumb and forefinger and needle inserted at a 90° angle to skin (WHO injection technique) and up to the needle hub in healthy infants Comparison: 25 G 16 mm needles; injection technique ‐ same as above | ||||||
| Outcomes (1 to 7) | Probable outcome with 25 G 16 mm needles* | Probable outcome with 25 G 25 mm needles (95% CI) | Relative effect (95% CI) | No. of participants (studies) | Quality of the evidence (GRADE) | Comments |
| 1. Incidence of diphtheria, tetanus, pertussis, Haemophilus influenzae type b (Hib) (not measured) | ‐ | ‐ | ‐ | ‐ | ‐ | Not measured |
| 2a. Adequate immune response (seroprotection) against diphtheria (surrogate outcome)2 | 1000 per 1000 | 1000 per 1000 (990 to 1000)** |
RR 1.00 (0.99 to 1.01) |
312 (1 study) | ⊕⊕⊕⊝ Moderate3 | ‐ |
| 2b. Adequate immune response (seroprotection) against tetanus (surrogate outcome)2 | 1000 per 1000 | 1000 per 1000 (990 to 1000)** |
RR 1.00 (0.99 to 1.01) |
390 (1 study) | ⊕⊕⊕⊝ Moderate3 | ‐ |
| 2c. Adequate immune response (seroprotection) against pertussis (not measured)2 | ‐ | ‐ | ‐ | ‐ | ‐ | Not measured |
| 2d. Adequate immune response (seroprotection) against Haemophilus influenzae type b disease (surrogate outcome)2 | 804 per 1000 | 885 per 1000 (812 to 965) |
RR 1.10 (1.01 to 1.2) |
400 (1 study) | ⊕⊕⊕⊝ Moderate3 | ‐ |
| 3. Pain (not measured) | ‐ | ‐ | ‐ | ‐ | ‐ | Not measured |
| 4a. Procedural crying (during and immediately after the vaccination procedure) (not measured) | ‐ | ‐ | ‐ | ‐ | ‐ | Not measured |
| 4b. Persistent inconsolable crying4 | 9 per 1000 |
22 per 1000 (4 to 114) |
RR 2.49 (0.49 to 12.7) |
447 (1 study) |
⊕⊝⊝⊝ Very low5,6,7 |
‐ |
| 5. Severe local reaction8 | 40 per 1000 |
2 per 1000 (0 to 36) |
RR 0.05 (0 to 0.89) |
447 (1 study) |
⊕⊕⊕⊝ Moderate7,9 |
NNTB*** 25 (95% CI 15 to 100) |
| 6. Non‐severe local reaction10 | 560 per 1000 |
359 per 1000 (291 to 443) |
RR 0.64 (0.52 to 0.79)11 |
447 (1 study) |
⊕⊕⊕⊝ Moderate12,13 |
NNTB**** 5 (95% CI 4 to 10) |
| 7. Fever14 | 179 per 1000 |
258 per 1000 (179 to 369) |
RR 1.44 (1.01 to 2.06) |
447 (1 study) |
⊕⊝⊝⊝ Very low5,7,12 |
‐ |
| *The basis for the assumed risk (i.e. the probable outcome with 25 G 16 mm needles) and the corresponding risk (ie the probable outcome with 25 G 25 mm needles) is provided in footnote 1. **Due to bounding the upper limit of the confidence interval for the absolute effect does not match exactly the upper limit of the confidence interval for the relative effect. ***NNTB = the expected number of infants who would need to be vaccinated with the 25 mm rather than the 16 mm needle for 1 additional infant to avoid a severe local reaction event. ****NNTB = the expected number of infants who would need to be vaccinated with the 25 mm rather than the 16 mm needle for 1 additional infant to avoid a non‐severe local reaction event. CI: confidence interval; DTwP‐Hib vaccine: a combination vaccine containing diphtheria, tetanus, whole‐cell pertussis, and Haemophilus influenzae type b vaccine antigen components; RR: risk ratio; WHO: World Health Organization. | ||||||
| GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | ||||||
Please see the Data collection and analysis section of the review for comprehensive details regarding the methods we used to assess the quality of evidence for outcomes included in 'Summary of findings' tables. See the Effects of interventions section of the review for a full explanation of the rationale for our judgements regarding the quality of evidence for each outcome.
1Only one trial provided data for the comparison between 25 G 25 mm and 25 G 16 mm needles (Diggle 2006). The assumed and corresponding risks for all outcomes are based on the event rates in the needle size groups in this trial. In Diggle 2006, a DTwP‐Hib vaccine and a meningitis C conjugate (MenC) vaccine were concurrently administered in the right (DTwP‐Hib) and left (MenC) anterolateral thighs of infants aged 2 months (first vaccine dose), 3 months (second dose), and 4 months (third dose). The MenC vaccine was administered in a schedule (time between vaccine doses) that is no longer recommended, and the results pertaining to the effects of needle size on the immunogenicity and reactogenicity of this vaccine are not presented in this 'Summary of findings' table or in the Abstract or Plain language summary for this Cochrane Review (the results are, however, presented in the Effects of interventions section). 2The term 'seroprotection' refers to antibody titre levels above a predefined threshold level that correlates with protection from disease (after completion of a series of 3 doses of a DTwP‐Hib vaccine). The threshold levels used in this review were: diphtheria antitoxin levels ≥ 0.01 IU/mL; tetanus antitoxin levels ≥ 0.01 IU/mL; Hib antibody titre levels ≥ 1.0 μg/mL. There is no well‐established immune correlate or surrogate of protection against pertussis. 3We downgraded the quality of evidence by one level for indirectness due to the use of a substitute (surrogate) seroprotection endpoint in place of the patient‐important outcome of interest. Although the seroprotection endpoints were reported in only one trial, thus precluding an evaluation of the consistency or inconsistency of results across trials, we did not downgrade the quality of evidence. We considered the consistency of the results of the seroprotection analyses reported in the trial and the results of the analyses of the ratios of the antibody/antitoxin geometric mean concentrations (GMCs) between the needle size groups. The GMC ratios (25 mm versus 16 mm) were: diphtheria: 1.05 (95% CI 0.85 to 1.29); tetanus: 0.97 (95% CI 0.81 to 1.17); Hib: 1.35 (95% CI 1.02 to 1.79). (NOTE: a ratio > 1.0 indicates a higher antibody level (better immune response) after vaccination with the 25 mm compared with the 16 mm needle.) 4This term refers to a persistent inconsolable crying event lasting for ≥ 4 hours. The data presented in the table relate to persistent inconsolable crying recorded at any time point (6 hours, day 1, day 2, or day 3) after concurrent administration of any dose (first, second, or third) of a DTwP‐Hib vaccine and a MenC vaccine. 5We downgraded the quality of evidence by one level due to imprecision, taking into account the width of the 95% confidence interval accompanying the effect estimate. 6We downgraded the quality of evidence by one level for indirectness. The definition of persistent inconsolable crying (≥ 4 hours' duration) used in the trial differed from the case definition specified in the protocol for our review (≥ 3 hours' duration). The reported effect size may have differed if the latter definition had been used in the trial, and we considered that this uncertainty merited downgrading the quality of evidence. 7We downgraded the quality of evidence by one level as this outcome was reported in only one trial, thus precluding any evaluation of the consistency or inconsistency of results across trials. 8'Severe local reaction' refers to redness and swelling covering more than two‐thirds of the anterolateral thigh after the first dose of a DTwP‐Hib vaccine. 9Although blinding of outcome assessment was incomplete, we did not downgrade the quality of evidence for risk of bias. We considered that the clinical severity of the reaction reduced the level of subjectivity in outcome assessment. 10'Non‐severe local reaction' refers to any redness, swelling, tenderness, or hardness (i.e. a composite outcome) at the injection site on the day after the first dose of a DTwP‐Hib vaccine. 11Similar effect sizes were observed in the trial after the second and third doses of the DTwP‐Hib vaccine (second dose RR 0.67, 95% CI 0.54 to 0.83; third dose RR 0.65, 95% CI 0.52 to 0.80). The corresponding NNTBs were 6 (95% CI 4 to 12) for the second dose and 5 (95% CI 4 to 10) for the third dose. 12We downgraded the quality of evidence by one level due to incomplete blinding of outcome assessment and the resultant uncertainty over the potential for bias. 13Although this outcome was reported in only one trial, thus precluding an evaluation of the consistency or inconsistency of results across trials, we did not downgrade the quality of evidence, taking into account the consistency of the effect sizes after the first, second, and third doses of the DTwP‐Hib vaccine (see footnote 11). 14The data presented in the table relate to fever (temperature ≥ 38 °C) experienced at any time point (6 hours, day 1, day 2, or day 3) after concurrent administration of any dose (first, second, or third) of a DTwP‐Hib vaccine and a MenC vaccine.