Summary of findings 2. Comparison between needles with different gauges but with the same length.

25 G 25 mm needles compared with 23 G 25 mm needles for vaccination procedures
Patient or population: infants aged approximately 2 to 6 months undergoing vaccination in the anterolateral thigh with a DTwP combination 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: 23 G 25 mm needles; injection technique ‐ same as above
Outcomes (1 to 7)	Probable outcome with 23 G 25 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)	311 (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)	402 (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	856 per 1000	881 per 1000 (822 to 950)	RR 1.03 (0.96 to 1.11)	414 (1 study)	⊕⊕⊕⊝ Moderate3	‐
3. Pain: 0 to 10 on MBPS 0 = no pain; 10 = worst possible pain4	Mean net pain score 5.9 points	Mean net pain score 0.7 points higher (0.39 higher to 1.01 higher)	N/A	320 (1 study)	⊕⊕⊝⊝ Low5,6	Differences between groups of less than 1 point may not be clinically relevant.
4a. Procedural crying (during and immediately after the vaccination procedure)	Mean crying time 37 seconds	Mean crying time 8 seconds longer (3 longer to 13 longer)	N/A	320 (1 study)	⊕⊕⊕⊝ Moderate7	‐
4b. Persistent inconsolable crying8	17 per 1000	22 per 1000 (6 to 82)	RR 1.31 (0.36 to 4.8)	459 (1 study)	⊕⊝⊝⊝ Very low7,9,10	‐
5. Severe local reaction11	Estimates not available, but risk very low; see footnote 12		See footnote 12	559 (2 studies)12	⊕⊕⊕⊕ High12	Only 1 severe local reaction event was recorded in the 23 G 25 mm group in 1 trial.
6. Non‐severe local reaction13	387 per 1000	356 per 1000 (283 to 453)	RR 0.92 (0.73 to 1.17)14	459 (1 study)	⊕⊕⊝⊝ low9,15,16	‐
7. Fever	See footnote 17	See footnote 17	See footnote 17	561 (2 studies)	⊕⊝⊝⊝ Very low9,15,17	‐
*The basis for the assumed risk (i.e. the probable outcome with 23 G 25 mm needles) and the corresponding risk (i.e. 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. CI: confidence interval; DTwP vaccine: a combination vaccine containing diphtheria, tetanus, and whole‐cell pertussis vaccine antigen components. The vaccine may be combined with other antigen components including Haemophilus influenzae type b (DTwP‐Hib vaccine) and hepatitis B (DTwP‐Hib‐Hep B vaccine); MBPS: Modified Behavioural Pain Scale; N/A: not applicable; 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 for a full explanation of the rationale for our judgements regarding the quality of evidence for each outcome.

¹Two trials contributed data to this comparison (Diggle 2006; Pathak 2007). The assumed and corresponding risks for the immune response outcomes, persistent inconsolable crying, and non‐severe local reactions are based on the event rates in the needle size groups in the Diggle 2006 trial. The entries in the table for pain and procedural crying are based on the results of the Pathak 2007 trial. The entries for severe local reactions and fever are based on the results from both trials.

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).

In Pathak 2007, the first, second, or third dose of 1) a DTwP vaccine or 2) a DTwP‐Hib vaccine or 3) a DTwP‐Hib‐Hep B vaccine was administered to infants aged up to 6 months.
 ²The term 'seroprotection' refers to antibody titre levels above a predefined threshold 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; and 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 gauge groups. The GMC ratios (25 G versus 23 G) were: diphtheria: 0.93 (95% CI 0.76 to 1.14); tetanus: 0.96 (95% CI 0.80 to 1.15); and Hib: 1.29 (95% CI 0.98 to 1.69). (NOTE: a ratio > 1.0 indicates a higher antibody level (better immune response) after vaccination with the 25 G compared with the 23 G needle.)
 ⁴The net pain score on the MBPS = postvaccination MBPS score minus prevaccination (baseline) MBPS score. Pain was also assessed in the trial using a visual analogue scale (see footnote 6). We have highlighted the MBPS pain score in the table because this pain scale was initially developed for use with infants during medical procedures such as vaccinations.
 ⁵We downgraded the quality of evidence by one level due to uncertainty over the potential for detection bias.
 ⁶In the trial, pain was also assessed by a researcher and by parents using a visual analogue scale (VAS) (0 to 100, 0 = no pain; 100 = worst possible pain). In the 25 G group the researcher‐assessed mean pain scores were 7.3 points higher (3.6 higher to 11 higher), and the parental‐assessed mean pain scores were 1.6 points higher (4 points lower to 7 points higher) compared with the 23 G group. Differences of less than 10 points on the 100‐millimetre VAS may not be clinically important. We downgraded the quality of evidence by one level for inconsistency taking into consideration the difference between the results of the parental and researcher pain assessments using the VAS and the reporting of procedural pain in only one trial, thus precluding any evaluation of the consistency or inconsistency of results across trials.
 ⁷We downgraded the quality of evidence by one level because this outcome was reported in only one trial, thus precluding any evaluation of the consistency or inconsistency of results across trials.
 ⁸This term refers to a persistent inconsolable crying event lasting for ≥ 4 hours. The data presented in the table are based on the results of a single included trial (Diggle 2006), and 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.
 ⁹We downgraded the quality of evidence by one level for imprecision taking into account the width of the confidence interval(s) around the effect estimate(s).
 ¹⁰We downgraded the quality evidence by one level for indirectness as the definition of persistent inconsolable crying (≥ 4 hours' duration) used in the trial that reported this outcome differed from the definition specified in the protocol for our review (≥ 3 hours' duration). The reported effect size in the trial 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.
 ¹¹'Severe local reaction' refers to redness and swelling covering more than two‐thirds of the anterolateral thigh.
 ¹²In Diggle 2006, only one severe local reaction occurred in the 23 G group (1/235) and 0 were reported in the 25 G group (0/224). In Pathak 2007, no severe local reactions were reported in either the 23 G (0/47) or the 25 G group (0/53). As there was only one severe local reaction event, our judgement about the quality of evidence was based on the absolute rather than the relative effect. The high quality rating reflects the fact that a severe local reaction did not occur in 558 out of the 559 participants analysed for reactogenicity in the needle groups in the two trials. Although 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.
 ¹³'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.
 ¹⁴Similar effect sizes were observed in Diggle 2006 after the second and third doses of the DTwP‐Hib vaccine (second dose RR 0.89, 95% CI 0.70, 1.12; third dose RR 0.84, 95% CI 0.66 to 1.06).
 ¹⁵We downgraded the quality of evidence by one level due to incomplete blinding of outcome assessment and the resultant uncertainty over the potential for bias.
 ¹⁶Although 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 14).
 ¹⁷We downgraded the quality of evidence for inconsistency taking into account the variation between the results of the two trials and our inability to definitively explain the reason(s) for this heterogeneity. In Diggle 2006, fever incidence was higher in the group of infants vaccinated with the 25 G needle (26%) versus the 23 G needle (20%) (RR 1.28, 95% CI 0.91 to 1.79). In Pathak 2007, fever incidence on the day after vaccination was lower in the group vaccinated with the 25 G needle (62%) versus the 23 G needle (78%) (RR 0.79, 95% CI 0.61 to 1.02). The confidence intervals accompanying the effect estimates in both trials did not rule out the absence of any difference between the needle size groups. The rates of fever were substantially higher in both needle gauge groups in Pathak 2007 compared with Diggle 2006. The reason for the difference between the results of the two trials is unclear, but it may be due to differences in the definitions of fever used in the two trials, in study populations, in the vaccines administered, or in the risk of bias between the trials. See footnote 1 for details of the vaccines administered in the two trials.