Summary of findings for the main comparison. Pilocarpine compared to no treatment/placebo for preventing salivary gland dysfunction following radiotherapy.
| Pilocarpine compared to no treatment/placebo for preventing salivary gland dysfunction following radiotherapy | ||||||
| Patient or population: patients receiving radiotherapy on its own or in addition to chemotherapy to the head and neck region Intervention: pilocarpine Comparison: no treatment/placebo | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | Number of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Risk with no treatment/placebo | Risk with pilocarpine | |||||
| Xerostomia ‐ Up to and including 6 months postRT Studies used different ways of measuring the outcome and therefore we combined the studies using SMD |
‐ | SMD 0.35 lower (1.04 lower to 0.33 higher) | ‐ | 126 (2 RCTs) | ⊕⊝⊝⊝ VERY LOW1 | Insufficient evidence of a difference at this time point and also at the end of RT and 3 months postRT 1 of the 2 studies in this assessment showed inconsistent results when using an alternative way of measuring this outcome at the 6‐month time point. 2 further studies showed insufficient evidence of a difference, 1 at the end of RT and the other at 3 months postRT |
| Salivary flow rate (unstimulated) ‐ Up to and including 3 months postRT Studies used different ways of measuring the outcome and therefore we combined the studies using SMD |
‐ | MD 0.06 lower (0.23 lower to 0.11 higher) | ‐ | 24 (1 RCT) | ⊕⊝⊝⊝ VERY LOW2 | Insufficient evidence of a difference at this time point and also at the end of RT Same results for stimulated salivary flow rates at end of RT, and 3, 6 and 12 months postRT Same results for a further study at the end of RT and 3 months postRT looking at whether or not stimulated and unstimulated salivary flow was > 0 g |
| Overall survival ‐ Up to and including 6 months postRT | 724 per 1000 | 775 per 1000 (579 to 1000) | RR 1.07 (0.80 to 1.43) | 60 (1 RCT) | ⊕⊝⊝⊝ VERY LOW3 | Insufficient evidence of a difference |
| Quality of life ‐ Up to and including 6 months postRT McMaster University Head and Neck Questionnaire (HNRQ). Score 1‐7, lower score = poorer quality of life |
Control group mean was 5.3 | MD 0.20 higher (0.19 lower to 0.59 higher) | ‐ | 90 (1 RCT) | ⊕⊝⊝⊝ VERY LOW3 | Insufficient evidence of a difference at this time point and also at the end of RT and 3 months postRT |
| Adverse effects | Insufficient evidence of a difference between groups for any reported adverse event, apart from for sweating where data from 5 studies showed an increased risk associated with pilocarpine (RR 2.98, 95% CI 1.43 to 6.22; P = 0.004; I2 = 0%; 389 participants; ⊕⊕⊝⊝ LOW4) | |||||
| *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI) CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio; SMD: standardised mean difference; RT: radiotherapy | ||||||
| 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 the 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 | ||||||
1Downgraded by 1 level for risk of bias, 1 level for imprecision (small sample size and 95% CIs include both possibility of benefit and harm), and 1 level for inconsistency (I2 = 68%). 2Downgraded by 1 level for risk of bias, and 2 levels for imprecision (single study with 12 participants per group and 95% CIs include both possibility of benefit and harm). 3Downgraded by 1 level for risk of bias, and 2 levels for imprecision (single study and 95% CIs include both possibility of benefit and harm). 4Downgraded by 1 level for risk of bias, and 1 level for imprecision (very wide 95% CIs).