ANNEX 5RESEARCH AGENDA

The Guidelines Development Group established a research agenda in March 2010 while assessing the available evidence for pharmacological interventions as part of the process of developing recommendations. Having identified several research gaps, the GDG also discussed priorities for further investigation.

The list below ranks, in order of priority, the broad areas of research needed. This list aims to guide the scientific community in contributing to key research on pharmacological interventions for the management of persisting pain in children with medical illness. The outcomes measured in clinical studies comparing different pharmacological interventions should include both positive (efficacy, quality of life) and negative (incidence/prevalence and severity of adverse effects) outcomes.

First group of priorities

• Assessment of two-step treatment strategy.
• Research on alternative strong opioids to morphine (comparative trials of opioids in terms of effectiveness, side-effects and feasibility of use).
• Research on intermediate potency opioid analgesics (e.g. tramadol).
• Long-term safety data concerning first-step medicines (ibuprofen/paracetamol).

Second group of priorities (neuropathic pain)

• Antidepressants, specifically tricyclic antidepressants and selective serotonin reuptake inhibitors and newer antidepressants of the class of serotonin and norepinephrine reuptake inhibitors for persisting neuropathic pain in children.
• Gabapentin for persisting neuropathic pain in children.
• Ketamine as an adjuvant to opioids for refractory neuropathic pain in paediatric patients with longterm medical illness.

Third group of priorities

• Randomized controlled trials of the administration of opioids as an alternative to the oral route (including RCTs comparing subcutaneous and intravenous routes).

Fourth group of priorities

• Update Cochrane reviews on opioid switching, including paediatric data, if available.
• Randomized controlled trials on opioid switching and research on dose conversion in different age groups.
• Randomized controlled trials on short-acting opioids for breakthrough pain in children.

Other areas for research and development

• Research and psychometric validation of observational behaviour measurement tools for persisting pain settings (neonates, infants, preverbal and impaired children).
• Prospective clinical trials to investigate opioid rotation policies and their efficacy in preventing side-effects or opioid tolerance and dose escalation.
• Development of divisible, dispersible, oral solid-dosage forms of paracetamol and ibuprofen.
• Research into appropriate formulations for the extemporaneous preparation of oral liquid morphine. Dissemination of available evidence on the preparation of stable extemporaneous formulations.
• Child-appropriate oral solid dosage forms of opioid analgesics.
• Research on dose conversion of opioid analgesics in different age groups.