Strengths and limitations
In contrast to the majority of trials in AOM research, the current study focused on pain management. By applying few exclusion criteria and with median age and reported symptom durations being similar with previous childhood AOM studies in primary care,46 the study managed to capture a sample of children with AOM closely mimicking everyday practice. The intervention at trial was tailored to GPs and parents, and developed by a multidisciplinary team to include an online training module, an interactive session, an information leaflet, and analgesic prescription.18 Both parentreported outcomes as well as medical records data were collected, which allowed the authors to capture a broad range of subjective and objective outcomes, use a patient-relevant primary outcome, and had few missing data. Information on the severity and duration of the child’s AOM symptoms at baseline allowed the authors to adjust for any differences in illness-severity between groups.
This study shows that an educational intervention, based on accepted clinical practice guidelines, is not necessarily beneficial for the patient, even if the intervention proves effective in changing clinician (prescribing) behaviour. As such, this study highlights the importance of careful evaluation of any intervention before considering introduction, and of carefully assessing the benefits and harms of medicines already widely used in everyday practice.
Despite not reaching the a priori defined sample size due to slower-than-anticipated recruitment, the authors believe that this study is sufficiently powered to draw meaningful conclusions. The target sample size was substantially inflated to account for the cluster design, whereas the random intercept for GP practice was found to be close to zero in this trial. The robustness of the findings was confirmed in the sensitivity analyses, in which missing baseline and outcome data were imputed, but also in the observation that the effect estimates for the primary outcome and associated 95% CIs excluded a difference considered clinically relevant.
The possibility cannot be entirely excluded that this trial might have been subject to post-randomisation differential recruitment, a phenomenon that is sometimes observed in cluster RCTs.47 Indeed, more children have been recruited to the control than the intervention group, and the baseline table suggests slight differences between treatment groups. However, no difference was observed between the crude and adjusted analyses, suggesting that this phenomenon did not substantially impact the findings.
Comparison with existing literature
Although children in the intervention group received paracetamol more regularly, for more days, and at a slightly higher dosage than those in the control group, overall dosing of analgesics was lower than recommended in the intervention and in the clinical practice guidelines.4 The same observation was made in trials focusing on effectiveness of antibiotics in children with AOM, in which the role and use of analgesics was discussed with parents as part of the protocol.36,40,48 This poses the question whether higher dosing of paracetamol by parents is achievable at all. Future qualitative research may unravel reasons and mechanisms for parents’ reluctance to give their children paracetamol in age- or weight-appropriate dosages.
Ibuprofen, when added to paracetamol if pain control was insufficient, had no effect on symptom control; this adds to the current limited, very low quality, evidence failing to detect a benefit of combined use of paracetamol and ibuprofen over paracetamol or ibuprofen alone, with regards to AOM symptoms.6
The increase in reconsultations with subsequent antibiotic prescriptions in the intervention group is remarkable. It may well be due to more extensive safetynetting advice in the intervention group. In contrast to the current Dutch guidelines,4 which advise reassessment if the child’s condition worsens or if pain and/or fever do not improve after 3 days, the information leaflet advised reconsultation if the child did not recover despite treatment, if the ear pain worsened, or if the ear pain had not resolved after 3 days. Hence, the leaflet may have increased the probability of reconsultation in the intervention group.
Alternatively, parents in the intervention group may also have been more likely to report higher ear pain scores than those in the control group (thereby obscuring an actual decline) leading to more reconsultation, as a result of the very nature of the intervention, which focuses on managing ear pain. The qualitative work with GPs in the intervention group confirmed that they did put an increased focus on treating symptoms with analgesics rather than treating the infection with antibiotics.49 Conversely, such an approach might be expected to reduce pain scores due to a placebo effect by recommending greater use and benefit of analgesics.
Arguably, parents from the intervention group may have been more inclined to reconsult their GP when symptoms persisted despite the increase in analgesics use (‘perceived treatment failure’), or owing to children in the intervention group receiving fewer immediate antibiotic prescriptions. The latter, however, is less likely, given the lack of evidence for an effect of immediate antibiotics on symptoms at days 3–7,50 and Dutch parents generally accepting analgesics as stand-alone therapy in AOM.51
Finally, higher reconsultation rates and subsequent antibiotic prescriptions may have been due to an increased use of ibuprofen. In a post-hoc analysis, children who used ibuprofen were compared with those who did not; children who used ibuprofen had higher pain scores, were more likely to reconsult the GP for AOM-related complaints, and received more antibiotic prescriptions, independent from initial pain scores and treatment allocation. In recent years, evidence is mounting that the use of NSAIDs may be harmful, not just due to the well-known gastric and renal side effects, but due to direct harm on the progression of disease. Limited trial evidence, as well as observational studies, suggest that NSAID use in children and adults with respiratory infections and UTIs leads to a longer duration of symptoms,10,11,13 an increase in repeat GP consultations,9 and a higher risk of complications.9,11,13–17 These adverse effects are proposed to be mediated by impaired neutrophil function.52,53 It should, however, be noted that this study’s findings should be interpreted with caution, since confounding by indication cannot be excluded and causality cannot be inferred from the data.
